I am passionate about improving patient outcomes, by developing health care technology software and apps to help providers in making the best decisions based upon the up to date available medical evidence.
Capsaicin, the spicy component of hot chili peppers activates the TRPV1 pain receptors, and cause... more Capsaicin, the spicy component of hot chili peppers activates the TRPV1 pain receptors, and causes rapid desensitization. Capsaicin also ameliorates cisplatin-induced nephrotoxicity. Cisplatin, a commonly used anti-neoplastic agent for solid tumors causes significant hearing loss, nephrotoxicity and peripheral neuropathy. Upregulation of cochlear TRPV1 expression is related to cisplatin-mediated ototoxicity. Here we report that direct TRPV1 activation by localized trans-tympanic (TT) or oral administration of capsaicin (TRPV1 agonist) prevents cisplatin ototoxicity by sustained increased activation of pro-survival transcription factor signal transducer and activator of transcription (STAT3) in the Wistar rat. Cisplatin treatment produced prolonged activation of pro-apoptotic Ser 727 p-STAT1 and suppressed Tyr 705-p-STAT3 for up to 72 h in the rat cochlea. Our data indicate that capsaicin causes a transient STAT1 activation via TRPV1 activation, responsible for the previously reported temporary threshold shift. Additionally, we found that capsaicin increased cannabinoid receptor (CB2) in the cochlea, which leads to pro-survival Tyr 705-p-STAT3 activation. This tilts the delicate balance of p-STAT3/ p-STAT1 towards survival. Furthermore, capsaicin mediated protection is lost when CB2 antagonist AM630 is administered prior to capsaicin treatment. In conclusion, capsaicin otoprotection appears to be mediated by activation of CB2 receptors in the cochlea which are coupled to both STAT1 and STAT3 activation. Capsaicin is the spicy component of hot chili peppers of the genus Capsicum which activates the TRPV1 pain receptors. Capsaicin is a dietary nutraceutical used in cooking spicy Asian food. Absorption of oral capsaicin has been determined to be 94% in the Wistar rat model 1,2. Capsaicin produces rapid desensitization of TRPV1 receptors which contributes to its use in the treatment of pain in diseases such as arthritis and peripheral neurop-athy associated with diabetes 3-6. Capsaicin is known to possess anti-inflammatory 7 and anticancer properties 8-10. Capsaicin has also been shown to ameliorate cisplatin-induced nephrotoxicity 11,12. Cisplatin chemotherapy is associated with significant hearing loss, nephrotoxicity and peripheral neuropathy. We have previously implicated increased TRPV1 expression in the cochlea in cisplatin-mediated ototoxicity 13. Other groups have also shown expression and function of TRPV1 in the cochlea 14-16. Several studies have implicated TRPV1 in mediating entry of cisplatin and aminoglycosides into auditory hair cells 13,16,17. Local administration of capsaicin by trans-tympanic injection produced temporary hearing loss 18 which was associated with transient activation of signal transducer and activator of transcription 1 (STAT1) 19. In contrast, cisplatin produced prolonged activation of Ser 727 p-STAT1 lasting up to at least 72 h in the rat cochlea following drug administration. Knockdown of STAT1 by siRNA reduced cisplatin ototoxicity 19 , implicating this pathway in cisplatin and possibly TRPV1-mediated
Objective: Rare disease Background: Sarcoidosis is a systemic disease that can affect any organ, ... more Objective: Rare disease Background: Sarcoidosis is a systemic disease that can affect any organ, including the liver. It is manifested by the presence of non-caseating granulomas within involved organs, most commonly the pulmonary, lymphatic, and hepatic system. Unlike pulmonary or lymphatic involvement, hepatic involvement is usually asymptomatic and it is un-derdiagnosed. Here, we report a case of a patient with a history of pulmonary sarcoidosis who developed he-patic sarcoidosis. Case Report: 68-year-old female with pulmonary sarcoidosis with a 2-week history of severe abdominal pain and epigas-tric tenderness presented to our center. Abdominal magnetic resonance imaging (MRI) demonstrated mild he-patic fibrosis and cirrhosis. A thorough workup was performed including a liver biopsy which showed chronic non-necrotizing granulomas consistent with sarcoidosis. She was started on prednisone and subsequently improved. The patient was symptom-free on follow-up 1 month later. Conclusions: The majority of patients with hepatic sarcoidosis are usually asymptomatic, with only 5–30% presenting with abdominal pain, jaundice, nausea, vomiting, and hepatosplenomegaly. In rare cases, hepatic sarcoidosis can lead to cholestasis, portal hypertension, cirrhosis, or Budd-Chiari syndrome. Treatment with steroids is the mainstay of therapy; however, in severe cases, patients may require liver transplantation. This case report demonstrates that hepatic sarcoidosis is a serious condition, and if not treated, can lead to portal hypertension and cirrhosis. In patients with sarcoidosis, early detection and longitudinal follow-up is important in preventing overt liver failure. 1212 Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] [Web of Science by Clarivate] This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Influenza A associated with rhabdomyolysis has become more commonly recognized in recent years. I... more Influenza A associated with rhabdomyolysis has become more commonly recognized in recent years. It requires prompt recognition and treatment in order to prevent heme pigment-induced acute kidney injury. Here we report a 50-year-old female without a significant past medical history who presented with a one-week history of fevers, chills, fatigue, and generalized body aches. She was on no prior medication. Laboratory studies were significant for leukocytosis and elevated creatinine kinase up to a peak of 28,216 IU/L. Rapid influenza antigen testing was positive for influenza A virus. The patient was diagnosed with influenza A-induced rhabdomyolysis. According to our literature review, we are the first to report a case of influenza A-induced rhabdomyolysis in the 2017-2018 flu season. This case highlights the importance of considering rhabdomyolysis as a manifestation of an influenza infection.
Acute pericarditis as a presenting sign of adrenal insufficiency is rarely reported. We present a... more Acute pericarditis as a presenting sign of adrenal insufficiency is rarely reported. We present a rare case that highlights pericarditis as a clinical presentation of secondary adrenal insufficiency later complicated by cardiac tamponade. A 44-year-old lady who presented to the hospital with a one-day history of pleuritic chest pain and shortness of breath. In the emergency room, she had a blood pressure of 70/35 mmHg. Laboratory evaluation revealed white blood cell count of 16.08 k/cumm with neutrophilia, normal renal function and elevated troponin (0.321 ng/mL, normal 0.000-0.028). An electrocardiogram (EKG) showed sinus tachycardia, low voltage, PR suppression and ST changes consistent with acute pericarditis. Echocardiogram showed small pericardial effusion without tamponade physiology. Infectious workup was negative; she was thought to have acute adrenal insufficiency likely secondary to viral pericarditis. We treated the patient with high dose nonsteroidal anti-inflammatory drugs (NSAIDS) and hydrocortisone. Three weeks later, she presented to emergency room with complaints of persistent nausea, vomiting, chills, weakness. Her blood pressure was 49/23 mmHg. Random serum cortisol level was <1.2 mcg/dl (normal A.M. specimens 3.7-19.4 mcg/dl). Echocardiogram showed loculated pericardial fluid adjacent to the right ventricle with echocardiographic evidence of tamponade. Emergent pericardiocentesis yielded 250 ml of straw color fluid. Blood pressure improved after the procedure. The patient was initially started on IV stress dose steroids, but following clinical stabilization, hydrocortisone was switched to a physiological dose of 15 mg in am and 10 mg in pm. Although the mechanism of pericarditis in adrenal failure is unknown, this clinical presentation may help early diagnosis of adrenal failure and pericarditis. Early recognition and prompt treatment of this rare presentation are critical to prevent morbidity and mortality.
Icodextrin is a colloid osmotic agent used in some peritoneal dialysates. It is absorbed into the... more Icodextrin is a colloid osmotic agent used in some peritoneal dialysates. It is absorbed into the systemic circulation and hydrolyzed to maltose, a disaccharide that causes factitiously elevated capillary blood glucose (CBG) measurements by point-of-care (POC)
meters utilizing glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) and glucose-dye-oxidoreductase (GDO) based re
-actions to detect glucose. We report a recent case of icodextrin-related factitious hyperglycemia leading to iatrogenic hypoglyce-mia, brain injury, and death
ABSTRACT
Duodenal switch surgery causes malabsorption through biliopancreatic diversion that byp... more ABSTRACT
Duodenal switch surgery causes malabsorption through biliopancreatic diversion that bypasses the duodenum and proximal jejunum (Fig 1). Hypovitaminosis D and hypocalcemia may result and lead to secondary hyperparathyroidism (SHPT). Little is published regarding refractory SHPT in obese patients managed by bariatric surgery. We present a case of SHPT refractory to vitamin D repletion that responded favorably to treatment with the calcimimetic agent cinacalcet. Though cinacalcet is used to manage SHPT due to chronic kidney disease, we are unaware of any reports documenting cinacalcet as therapy for SHPT caused by bariatric surgery.
Journal of general internal medicine. 2008 Mar; 23, supplement 2(0884-8734): 39.
LEARNING OBJECTIVES: 1) To recognize symptoms of ectopic ACTH
syndrome. 2) To understand pathoph... more LEARNING OBJECTIVES: 1) To recognize symptoms of ectopic ACTH
syndrome. 2) To understand pathophysiology and treatment of ectopic
ACTH syndrome
CASE: A 56 year old Caucasian male with a history of Type 2 diabetes
and hypertension was admitted to the hospital for poorly controlled
blood glucose, high blood pressure, pedal edema and severe lemia. He was known to have localised prostate cancer which was
diagnosed 1 year ago. Significant physical findings included blood
pressure of 170/100 mm Hg, pitting pedal edema and proximal
muscle weakness. His admission investigations revealed glucose of
425 mg/dl, potassium 2.7 mmol/L and bicarbonate 30 mmol/L.
Prostate specific antigen (PSA) was elevated at 11.6 ng/ml (nanogram/
milliliter) and recurrence of prostate cancer was suspected. Computed
tomography of abdomen and chest showed wide spread metastasis
to liver, lung and osteoblastic lesions in lumbar spine. Biopsy
of the liver lesions revealed undifferentiated small cell carcinoma.
Immunohistochemical stains for prostate cocktail (PSA/Prostate acid
phospatase) and chromogranin, a marker for neuroendocrine tumor
were negative. Further work up revealed severely elevated morning
cortisol of 72 ug/dL (4–24 ug/dl) and 24 hour urinary cortisol of
1872 ug/24 hrs (3.5–40 ug/24 hr). ACTH level was high at 501 pg/ml
(0–46 pg/mL).With this constellation of findings, a diagnosis of
ectopic ACTH secretion from metastatic small cell cancer was made.
He received chemotherapy with Cisplatin and CPT-11[Irinotecan] and
was started on Ketoconazole for suppressing the synthesis of glucocorticoids.
However this resulted in QT prolongation on follow up electrocardiogram,
so Ketoconazole was discontinued. Therapy with
Octreotide 100 micrograms three times a day was started. In 5 days,
ACTH decreased by 23 percent and 24 urinary cortisol decreased by 73
percent. Patient was switched to long acting Octreotide 20 mg once a
month. His muscle strength improved significantly. He had better
glycemic and blood pressure control and potassium level normalized.
After 2 months on Octreotide therapy ACTH was 11 pg/ml and 24 hour
urine Cortisol was within the normal range
DISCUSSION: Cushing’s syndrome caused by ectopic production of
ACTH should be considered in all patients with a malignancy,
associated with peripheral edema, hypertension, raised blood glucose
and hypokalemic alkalosis. This patient had all these typical
manifestations. In patients with ectopic ACTH syndrome due to
aggressive small cell cancers, onset of Cushing’s syndrome can be
rapid and this can explain absence of classic manifestations such as
fat deposition in clavicular fossa and interscapular area. These
patients have extreme hypercortisolemia which causes, marked salt
retention (contributing to edema and hypertension), increased glucuneogenesis
(producing glucose intolerance), and hypokalemic alkalosis
(causing profound muscle weakness). Surgical excision or debulking of
the tumor is the definitive therapy of ectopic ACTH syndrome. Medical
therapy with adrenal enzyme inhibitors, such as Aminoglutethimide,
Ketoconazole or Metyrapone can be used to reduce cortisol production.
Octreotide, a long-acting analogue of somatostatin can be
effective in suppressing ACTH levels. The long acting analog of
Octreotide (Sandostatin LAR) given once monthly is effective and
preferred once efficacy of Octreotide is documented (This is an off
label use of Octreotide).
We completed a prospective study with historical controls to evaluate the
impact of a pocket ins... more We completed a prospective study with historical controls to evaluate the
impact of a pocket insulin dosing guide on diabetes management practices
of SIU School of Medicine resident physicians. Patients and controls were
well matched with the exception of gender. During the study, basal/bolus
insulin (BBI) orders increased nearly five-fold, and overall BBI orders
increased six-fold compared to the historical control period before the
insulin dosing guide. A significant decrease in sliding scale insulin (SSI)
occurred during the study and in comparison to the historical control
period. In February 2011, when BBI was ordered more than SSI, mean
capillary blood glucose (CBG) and percent CBG measurements 70-140
mg/dL were significantly improved without an increase in hypoglycemia
(CBG < 70 mg/dL). The pocket insulin dosing guide significantly increased
utilization of BBI, decreased SSI orders, and improved hospital glycemic
control for patients with Type 2 diabetes.
Background. Heterozygous inactivating mutations of the calcium-sensing receptor (CaSR) are the mo... more Background. Heterozygous inactivating mutations of the calcium-sensing receptor (CaSR) are the most common cause of familial hypocalciuric hypocalcemia (FHH). Patients typically have mild, asymptomatic hypercalcemia with normal to modestly elevated parathyroid hormone (PTH) level, 24 hour urine calcium < 200 mg, and a calcium/creatinine clearance ratio (CCCR) < 0.01. We present a case of familial hypercalcemia with CaSR gene mutation and phenotypic features of primary hyperparathyroidism (PHPT).
Case. A 27 year old female was referred for evaluation of persistent hypercalcemia. The patient was incidentally discovered to be hypercalcemic approximately six years before referral. Nine serum calcium measurements ranged from 10.8-11.6 mg/dL (8.5-10.4) from initial discovery of hypercalcemia through end of metabolic evaluation. PTH level on diagnosis of hypercalcemia was 27 pg/mL (12-88), and three additional measurements ranged from 37-50 pg/mL. Three measurements of 25-hydroxyvitamin D level ranged from 22-31 ng/mL. Initial 24 hour urine calcium was 132 mg, though urine creatinine was not measured to allow calculation of CCCR. The patient’s father (deceased), daughter, and a niece had been diagnosed with hypercalcemia, prompting sequencing of the CaSR gene that revealed a heterozygous sequence variant (c.2657G>C) in exon seven predicting a R886P substitution in the receptor. Another 24 hour urine collection yielded a calcium of 272 mg, and CCCR was equivocal (0.016). A DXA scan obtained before referral and following traumatic right hand fracture was notable for marginal Z-scores of the distal third of the radius (-1.7), left femoral neck (-1.9), and left total hip (-1.8). Three serum phosphate levels were low or marginal (2.3-2.6 mg/dL, 2.5-4.5). Approximately 15 months after referral, the patient experienced right nephrolithiasis. No parathyroid adenomas were identified on sestamibi parathyroid scintigraphy. Unfortunately, the patient was lost to follow up.
Conclusion. CaSR mutation positive hypercalcemia may present with biochemical and clinical manifestations that are atypical for FHH. For example, the F881L mutation has been linked to hypercalciuria and nephrolithiasis that benefitted from parathyroidectomy. The R886P mutation found in our patient maps near F881L, and the proband in the initial R886P kindred presented with an elevated PTH level, 24 hour urine calcium > 200 mg, and CCCR > 0.02. However, no PHPT phenotype was described in this kindred. PHPT may also co-occur with CaSR mutations; in a German series of 139 PHPT patients, four had co-existing features of FHH and confirmatory CaSR mutations. Case reports of concurrent FHH and PHPT have also been published, though in our patient parathyroid imaging failed to clearly identify an adenoma. This case demonstrates that familial CaSR mutation positive hypercalcemia may not have the benign course typical of FHH.
Background: MEN1 is a rare autosomal dominant disorder characterized by tumors of parathyroid, an... more Background: MEN1 is a rare autosomal dominant disorder characterized by tumors of parathyroid, anterior pituitary and pancreatic islet cells. Pituitary adenomas in MEN1 can be aggressive and invade surrounding structures including the skull base. However, acute bacterial meningitis in patients with untreated pituitary macroadenomas is an exceptional finding reported in only a few cases.
Capsaicin, the spicy component of hot chili peppers activates the TRPV1 pain receptors, and cause... more Capsaicin, the spicy component of hot chili peppers activates the TRPV1 pain receptors, and causes rapid desensitization. Capsaicin also ameliorates cisplatin-induced nephrotoxicity. Cisplatin, a commonly used anti-neoplastic agent for solid tumors causes significant hearing loss, nephrotoxicity and peripheral neuropathy. Upregulation of cochlear TRPV1 expression is related to cisplatin-mediated ototoxicity. Here we report that direct TRPV1 activation by localized trans-tympanic (TT) or oral administration of capsaicin (TRPV1 agonist) prevents cisplatin ototoxicity by sustained increased activation of pro-survival transcription factor signal transducer and activator of transcription (STAT3) in the Wistar rat. Cisplatin treatment produced prolonged activation of pro-apoptotic Ser 727 p-STAT1 and suppressed Tyr 705-p-STAT3 for up to 72 h in the rat cochlea. Our data indicate that capsaicin causes a transient STAT1 activation via TRPV1 activation, responsible for the previously reported temporary threshold shift. Additionally, we found that capsaicin increased cannabinoid receptor (CB2) in the cochlea, which leads to pro-survival Tyr 705-p-STAT3 activation. This tilts the delicate balance of p-STAT3/ p-STAT1 towards survival. Furthermore, capsaicin mediated protection is lost when CB2 antagonist AM630 is administered prior to capsaicin treatment. In conclusion, capsaicin otoprotection appears to be mediated by activation of CB2 receptors in the cochlea which are coupled to both STAT1 and STAT3 activation. Capsaicin is the spicy component of hot chili peppers of the genus Capsicum which activates the TRPV1 pain receptors. Capsaicin is a dietary nutraceutical used in cooking spicy Asian food. Absorption of oral capsaicin has been determined to be 94% in the Wistar rat model 1,2. Capsaicin produces rapid desensitization of TRPV1 receptors which contributes to its use in the treatment of pain in diseases such as arthritis and peripheral neurop-athy associated with diabetes 3-6. Capsaicin is known to possess anti-inflammatory 7 and anticancer properties 8-10. Capsaicin has also been shown to ameliorate cisplatin-induced nephrotoxicity 11,12. Cisplatin chemotherapy is associated with significant hearing loss, nephrotoxicity and peripheral neuropathy. We have previously implicated increased TRPV1 expression in the cochlea in cisplatin-mediated ototoxicity 13. Other groups have also shown expression and function of TRPV1 in the cochlea 14-16. Several studies have implicated TRPV1 in mediating entry of cisplatin and aminoglycosides into auditory hair cells 13,16,17. Local administration of capsaicin by trans-tympanic injection produced temporary hearing loss 18 which was associated with transient activation of signal transducer and activator of transcription 1 (STAT1) 19. In contrast, cisplatin produced prolonged activation of Ser 727 p-STAT1 lasting up to at least 72 h in the rat cochlea following drug administration. Knockdown of STAT1 by siRNA reduced cisplatin ototoxicity 19 , implicating this pathway in cisplatin and possibly TRPV1-mediated
Objective: Rare disease Background: Sarcoidosis is a systemic disease that can affect any organ, ... more Objective: Rare disease Background: Sarcoidosis is a systemic disease that can affect any organ, including the liver. It is manifested by the presence of non-caseating granulomas within involved organs, most commonly the pulmonary, lymphatic, and hepatic system. Unlike pulmonary or lymphatic involvement, hepatic involvement is usually asymptomatic and it is un-derdiagnosed. Here, we report a case of a patient with a history of pulmonary sarcoidosis who developed he-patic sarcoidosis. Case Report: 68-year-old female with pulmonary sarcoidosis with a 2-week history of severe abdominal pain and epigas-tric tenderness presented to our center. Abdominal magnetic resonance imaging (MRI) demonstrated mild he-patic fibrosis and cirrhosis. A thorough workup was performed including a liver biopsy which showed chronic non-necrotizing granulomas consistent with sarcoidosis. She was started on prednisone and subsequently improved. The patient was symptom-free on follow-up 1 month later. Conclusions: The majority of patients with hepatic sarcoidosis are usually asymptomatic, with only 5–30% presenting with abdominal pain, jaundice, nausea, vomiting, and hepatosplenomegaly. In rare cases, hepatic sarcoidosis can lead to cholestasis, portal hypertension, cirrhosis, or Budd-Chiari syndrome. Treatment with steroids is the mainstay of therapy; however, in severe cases, patients may require liver transplantation. This case report demonstrates that hepatic sarcoidosis is a serious condition, and if not treated, can lead to portal hypertension and cirrhosis. In patients with sarcoidosis, early detection and longitudinal follow-up is important in preventing overt liver failure. 1212 Indexed in: [PMC] [PubMed] [Emerging Sources Citation Index (ESCI)] [Web of Science by Clarivate] This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Influenza A associated with rhabdomyolysis has become more commonly recognized in recent years. I... more Influenza A associated with rhabdomyolysis has become more commonly recognized in recent years. It requires prompt recognition and treatment in order to prevent heme pigment-induced acute kidney injury. Here we report a 50-year-old female without a significant past medical history who presented with a one-week history of fevers, chills, fatigue, and generalized body aches. She was on no prior medication. Laboratory studies were significant for leukocytosis and elevated creatinine kinase up to a peak of 28,216 IU/L. Rapid influenza antigen testing was positive for influenza A virus. The patient was diagnosed with influenza A-induced rhabdomyolysis. According to our literature review, we are the first to report a case of influenza A-induced rhabdomyolysis in the 2017-2018 flu season. This case highlights the importance of considering rhabdomyolysis as a manifestation of an influenza infection.
Acute pericarditis as a presenting sign of adrenal insufficiency is rarely reported. We present a... more Acute pericarditis as a presenting sign of adrenal insufficiency is rarely reported. We present a rare case that highlights pericarditis as a clinical presentation of secondary adrenal insufficiency later complicated by cardiac tamponade. A 44-year-old lady who presented to the hospital with a one-day history of pleuritic chest pain and shortness of breath. In the emergency room, she had a blood pressure of 70/35 mmHg. Laboratory evaluation revealed white blood cell count of 16.08 k/cumm with neutrophilia, normal renal function and elevated troponin (0.321 ng/mL, normal 0.000-0.028). An electrocardiogram (EKG) showed sinus tachycardia, low voltage, PR suppression and ST changes consistent with acute pericarditis. Echocardiogram showed small pericardial effusion without tamponade physiology. Infectious workup was negative; she was thought to have acute adrenal insufficiency likely secondary to viral pericarditis. We treated the patient with high dose nonsteroidal anti-inflammatory drugs (NSAIDS) and hydrocortisone. Three weeks later, she presented to emergency room with complaints of persistent nausea, vomiting, chills, weakness. Her blood pressure was 49/23 mmHg. Random serum cortisol level was <1.2 mcg/dl (normal A.M. specimens 3.7-19.4 mcg/dl). Echocardiogram showed loculated pericardial fluid adjacent to the right ventricle with echocardiographic evidence of tamponade. Emergent pericardiocentesis yielded 250 ml of straw color fluid. Blood pressure improved after the procedure. The patient was initially started on IV stress dose steroids, but following clinical stabilization, hydrocortisone was switched to a physiological dose of 15 mg in am and 10 mg in pm. Although the mechanism of pericarditis in adrenal failure is unknown, this clinical presentation may help early diagnosis of adrenal failure and pericarditis. Early recognition and prompt treatment of this rare presentation are critical to prevent morbidity and mortality.
Icodextrin is a colloid osmotic agent used in some peritoneal dialysates. It is absorbed into the... more Icodextrin is a colloid osmotic agent used in some peritoneal dialysates. It is absorbed into the systemic circulation and hydrolyzed to maltose, a disaccharide that causes factitiously elevated capillary blood glucose (CBG) measurements by point-of-care (POC)
meters utilizing glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) and glucose-dye-oxidoreductase (GDO) based re
-actions to detect glucose. We report a recent case of icodextrin-related factitious hyperglycemia leading to iatrogenic hypoglyce-mia, brain injury, and death
ABSTRACT
Duodenal switch surgery causes malabsorption through biliopancreatic diversion that byp... more ABSTRACT
Duodenal switch surgery causes malabsorption through biliopancreatic diversion that bypasses the duodenum and proximal jejunum (Fig 1). Hypovitaminosis D and hypocalcemia may result and lead to secondary hyperparathyroidism (SHPT). Little is published regarding refractory SHPT in obese patients managed by bariatric surgery. We present a case of SHPT refractory to vitamin D repletion that responded favorably to treatment with the calcimimetic agent cinacalcet. Though cinacalcet is used to manage SHPT due to chronic kidney disease, we are unaware of any reports documenting cinacalcet as therapy for SHPT caused by bariatric surgery.
Journal of general internal medicine. 2008 Mar; 23, supplement 2(0884-8734): 39.
LEARNING OBJECTIVES: 1) To recognize symptoms of ectopic ACTH
syndrome. 2) To understand pathoph... more LEARNING OBJECTIVES: 1) To recognize symptoms of ectopic ACTH
syndrome. 2) To understand pathophysiology and treatment of ectopic
ACTH syndrome
CASE: A 56 year old Caucasian male with a history of Type 2 diabetes
and hypertension was admitted to the hospital for poorly controlled
blood glucose, high blood pressure, pedal edema and severe lemia. He was known to have localised prostate cancer which was
diagnosed 1 year ago. Significant physical findings included blood
pressure of 170/100 mm Hg, pitting pedal edema and proximal
muscle weakness. His admission investigations revealed glucose of
425 mg/dl, potassium 2.7 mmol/L and bicarbonate 30 mmol/L.
Prostate specific antigen (PSA) was elevated at 11.6 ng/ml (nanogram/
milliliter) and recurrence of prostate cancer was suspected. Computed
tomography of abdomen and chest showed wide spread metastasis
to liver, lung and osteoblastic lesions in lumbar spine. Biopsy
of the liver lesions revealed undifferentiated small cell carcinoma.
Immunohistochemical stains for prostate cocktail (PSA/Prostate acid
phospatase) and chromogranin, a marker for neuroendocrine tumor
were negative. Further work up revealed severely elevated morning
cortisol of 72 ug/dL (4–24 ug/dl) and 24 hour urinary cortisol of
1872 ug/24 hrs (3.5–40 ug/24 hr). ACTH level was high at 501 pg/ml
(0–46 pg/mL).With this constellation of findings, a diagnosis of
ectopic ACTH secretion from metastatic small cell cancer was made.
He received chemotherapy with Cisplatin and CPT-11[Irinotecan] and
was started on Ketoconazole for suppressing the synthesis of glucocorticoids.
However this resulted in QT prolongation on follow up electrocardiogram,
so Ketoconazole was discontinued. Therapy with
Octreotide 100 micrograms three times a day was started. In 5 days,
ACTH decreased by 23 percent and 24 urinary cortisol decreased by 73
percent. Patient was switched to long acting Octreotide 20 mg once a
month. His muscle strength improved significantly. He had better
glycemic and blood pressure control and potassium level normalized.
After 2 months on Octreotide therapy ACTH was 11 pg/ml and 24 hour
urine Cortisol was within the normal range
DISCUSSION: Cushing’s syndrome caused by ectopic production of
ACTH should be considered in all patients with a malignancy,
associated with peripheral edema, hypertension, raised blood glucose
and hypokalemic alkalosis. This patient had all these typical
manifestations. In patients with ectopic ACTH syndrome due to
aggressive small cell cancers, onset of Cushing’s syndrome can be
rapid and this can explain absence of classic manifestations such as
fat deposition in clavicular fossa and interscapular area. These
patients have extreme hypercortisolemia which causes, marked salt
retention (contributing to edema and hypertension), increased glucuneogenesis
(producing glucose intolerance), and hypokalemic alkalosis
(causing profound muscle weakness). Surgical excision or debulking of
the tumor is the definitive therapy of ectopic ACTH syndrome. Medical
therapy with adrenal enzyme inhibitors, such as Aminoglutethimide,
Ketoconazole or Metyrapone can be used to reduce cortisol production.
Octreotide, a long-acting analogue of somatostatin can be
effective in suppressing ACTH levels. The long acting analog of
Octreotide (Sandostatin LAR) given once monthly is effective and
preferred once efficacy of Octreotide is documented (This is an off
label use of Octreotide).
We completed a prospective study with historical controls to evaluate the
impact of a pocket ins... more We completed a prospective study with historical controls to evaluate the
impact of a pocket insulin dosing guide on diabetes management practices
of SIU School of Medicine resident physicians. Patients and controls were
well matched with the exception of gender. During the study, basal/bolus
insulin (BBI) orders increased nearly five-fold, and overall BBI orders
increased six-fold compared to the historical control period before the
insulin dosing guide. A significant decrease in sliding scale insulin (SSI)
occurred during the study and in comparison to the historical control
period. In February 2011, when BBI was ordered more than SSI, mean
capillary blood glucose (CBG) and percent CBG measurements 70-140
mg/dL were significantly improved without an increase in hypoglycemia
(CBG < 70 mg/dL). The pocket insulin dosing guide significantly increased
utilization of BBI, decreased SSI orders, and improved hospital glycemic
control for patients with Type 2 diabetes.
Background. Heterozygous inactivating mutations of the calcium-sensing receptor (CaSR) are the mo... more Background. Heterozygous inactivating mutations of the calcium-sensing receptor (CaSR) are the most common cause of familial hypocalciuric hypocalcemia (FHH). Patients typically have mild, asymptomatic hypercalcemia with normal to modestly elevated parathyroid hormone (PTH) level, 24 hour urine calcium < 200 mg, and a calcium/creatinine clearance ratio (CCCR) < 0.01. We present a case of familial hypercalcemia with CaSR gene mutation and phenotypic features of primary hyperparathyroidism (PHPT).
Case. A 27 year old female was referred for evaluation of persistent hypercalcemia. The patient was incidentally discovered to be hypercalcemic approximately six years before referral. Nine serum calcium measurements ranged from 10.8-11.6 mg/dL (8.5-10.4) from initial discovery of hypercalcemia through end of metabolic evaluation. PTH level on diagnosis of hypercalcemia was 27 pg/mL (12-88), and three additional measurements ranged from 37-50 pg/mL. Three measurements of 25-hydroxyvitamin D level ranged from 22-31 ng/mL. Initial 24 hour urine calcium was 132 mg, though urine creatinine was not measured to allow calculation of CCCR. The patient’s father (deceased), daughter, and a niece had been diagnosed with hypercalcemia, prompting sequencing of the CaSR gene that revealed a heterozygous sequence variant (c.2657G>C) in exon seven predicting a R886P substitution in the receptor. Another 24 hour urine collection yielded a calcium of 272 mg, and CCCR was equivocal (0.016). A DXA scan obtained before referral and following traumatic right hand fracture was notable for marginal Z-scores of the distal third of the radius (-1.7), left femoral neck (-1.9), and left total hip (-1.8). Three serum phosphate levels were low or marginal (2.3-2.6 mg/dL, 2.5-4.5). Approximately 15 months after referral, the patient experienced right nephrolithiasis. No parathyroid adenomas were identified on sestamibi parathyroid scintigraphy. Unfortunately, the patient was lost to follow up.
Conclusion. CaSR mutation positive hypercalcemia may present with biochemical and clinical manifestations that are atypical for FHH. For example, the F881L mutation has been linked to hypercalciuria and nephrolithiasis that benefitted from parathyroidectomy. The R886P mutation found in our patient maps near F881L, and the proband in the initial R886P kindred presented with an elevated PTH level, 24 hour urine calcium > 200 mg, and CCCR > 0.02. However, no PHPT phenotype was described in this kindred. PHPT may also co-occur with CaSR mutations; in a German series of 139 PHPT patients, four had co-existing features of FHH and confirmatory CaSR mutations. Case reports of concurrent FHH and PHPT have also been published, though in our patient parathyroid imaging failed to clearly identify an adenoma. This case demonstrates that familial CaSR mutation positive hypercalcemia may not have the benign course typical of FHH.
Background: MEN1 is a rare autosomal dominant disorder characterized by tumors of parathyroid, an... more Background: MEN1 is a rare autosomal dominant disorder characterized by tumors of parathyroid, anterior pituitary and pancreatic islet cells. Pituitary adenomas in MEN1 can be aggressive and invade surrounding structures including the skull base. However, acute bacterial meningitis in patients with untreated pituitary macroadenomas is an exceptional finding reported in only a few cases.
Case Presentation: A 72-year-old man presented to the
hospital with acute onset headache, diplopi... more Case Presentation: A 72-year-old man presented to the hospital with acute onset headache, diplopia, and vomiting. Examination was notable for hypertension and partial left third and sixth cranial nerve palsies. No stigmata of Cushing’s syndrome were observed. MRI revealed a 2.9 cm pituitary macroadenoma with acute hemorrhage extending into the left cavernous sinus. Evaluation of anterior pituitary function approximately 30 hr after admission revealed serum cortisol 56.4 μg/dL (8.7-22.4) and ACTH 337 pg/mL (7-69). TSH (0.92 mIU/L, 0.34-5.60), free T4 (1.0 ng/dL, 0.5-1.3), and IGF-1 (167 ng/mL, 36-215) were unremarkable, though prolactin level was low (1.0 ng/mL, 2.6-13.2). Over the next 4 d, serum cortisol ranged from 50-60 μg/dL, and 24 hr urine free cortisol was 1,883 μg (< 60). At hospital discharge 7 d after admission, cortisol (24.6 μg/dL) and ACTH (148 pg/mL) were falling, and at 15 d from admission early hypopituitarism had occurred [8 AM cortisol 5.7 μg/dL, ACTH 15 pg/mL, TSH 0.55 mIU/L, free T4 0.6 ng/dL, IGF-1 65 ng/mL, LH 2.2 mIU/ mL (1.2-8.6), testosterone 76 ng/dL (270-1070)]. The adenoma was resected 6 wk after initial presentation, and postoperative histology revealed neuroendocrine cells in a background of fibrosis and pigment-laden macrophages but no staining for ACTH. Discussion: Pituitary apoplexy usually occurs due to hemorrhage or infarction of an adenoma. Hypopituitarism often occurs either at time of presentation due to compromise of anterior pituitary blood flow or before the event due to mass effect of the adenoma. Secondary adrenal insufficiency is reported in approximately 70% of pituitary apoplexy cases, but significant hypercortisolemia is rare. Literature review identified only one published case of hypercortisolemia during apoplexy in the setting of Cushing’s disease. In this case, hemorrhage of a corticotroph adenoma is unlikely as corticotroph macroadenomas are rare, the patient had no symptoms or signs of Cushing’s syndrome, and no immunohistochemical staining for ACTH was detected on histological evaluation of the tumor. Elevations of ACTH and cortisol most likely reflect stress activation of the hypothalamic-pituitary-adrenal axis, with subsequent central hypogonadism and declines in other pituitary functions reflecting subacute onset of hypopituitarism. Conclusion: This case illustrates that pituitary apoplexy may provoke a stress glucocorticoid response if corticotrophs remain viable. There is little published to predict subsequent anterior pituitary function after hemorrhage when initial cortisol levels are elevated, though low prolactin level appears to have been a marker for eventual hypopituitarism as in more typical cases of apoplexy.
Case Presentation: A 59-year-old male was receiving induction
dosing of ipilimumab (Ipi), a human... more Case Presentation: A 59-year-old male was receiving induction dosing of ipilimumab (Ipi), a humanized monoclonal cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) antibody, for management of metastatic melanoma. Shortly after the fourth dose, he presented to his oncologist with subacute onset frontal headache and lethargy. MRI of the sella turcica failed to show pituitary metastases or enlargement indicative of hypophysitis. The patient was treated empirically with a 5 d methylprednisolone taper, and symptoms abated. However, headache and fatigue recurred, prompting two additional 5 d treatment courses in the 4 weeks between symptoms onset and endocrinology referral. Pituitary function was evaluated 2 weeks after the last dose of methylprednisolone and notable for 8 AM cortisol 0.4 μg/dL (6.2-19.4), ACTH < 5 pg/mL (0-46), free T4 0.70 ng/dL (0.93-1.70), and TSH 0.62 mIU/L (0.27-4.20). Prolactin was low (2.4 ng/mL, 4.0-15.2), but morning testosterone (331 ng/dL, 193-740) and LH level (4.5 mIU/mL, 1.7-8.6) were unremarkable. Partial Ipi-induced hypopituitarism was diagnosed, and the patient was started on hydrocortisone followed by levothyroxine one week later. Headache and fatigue completely resolved, and the patient started Ipi maintenance therapy. Discussion: CTLA-4 antibodies are checkpoint inhibitors that disrupt immune tolerance to antigens on tumor cells. However, immune-related adverse events may occur as a consequence of T-cell activation including hypophysitis. In a recently published retrospective review, hypophysitis occurred in 11% of Ipi treated patients, and male gender and advanced age were risk factors. Central hypothyroidism occurred in all patients, central hypogonadism was present in all cases where evaluation was performed, and central adrenal insufficiency occurred in half of patients. Mild to moderate pituitary enlargement was demonstrated on MRI in all cases in the series. Animal studies have found CTLA-4 expression on anterior pituitary cells, lymphocytic infiltration of the pituitary, and antipituitary antibodies after injection of CTLA-4 antibodies. Conclusion: Hypophysitis and varying degrees of hypopituitarism occur in approximately 10% of patients treated with Ipi. This case is unusual for two reasons: 1) no pituitary enlargement was apparent on MRI, and 2) gonadotrope function was preserved. Ipi-induced hypophysitis should be investigated promptly when patients develop provocative symptoms and appropriate hormone replacement started based on anterior pituitary function. This case illustrates that Ipi-induced hypophysitis can occur even in the absence of obvious pituitary enlargement.
Objective: Inhaled corticosteroids (ICS) are commonly
used for management of chronic obstructive ... more Objective: Inhaled corticosteroids (ICS) are commonly used for management of chronic obstructive pulmonary disease (COPD). CS are less likely to cause systemic side effects than oral corticosteroids because 80 to 90 percent of a dose is absorbed through the upper gastrointestinal tract and inactivated by first pass hepatic metabolism. Although there is variability between ICS preparations and different inter-individual susceptibilities, high doses of ICS may lead to biochemical evidence of hypothalamicpituitary-adrenal (HPA) axis suppression. Reports of clinical secondary adrenal insufficiency, however, are rare. We present a case of clinically apparent secondary adrenal insufficiency in a patient receiving high dose ICS for management of COPD. Case Presentation: An 86-year-old woman was admitted to hospital for near syncope. Several weeks prior to admission, she experienced dizziness and weakness after standing that resolved in a seated or supine position. The the patient denied falls, chest pain, dyspnea, palpitations, or weight loss. She reported full compliance with her medical regimen which included olmesartan, nifedipine, furosemide, and isosorbide mononitrate. Inhaled fluticasone (1,000 mcg daily) had been prescribed for two years to manage COPD. The patient denied treatment with oral or articular corticosteroids. Examination was unremarkable with the exception of orthostatic blood pressure and heart rate changes. Orthostasis resolved after blood pressure medications were held and isotonic fluid was administered. Two consecutive 8:00 AM cortisol levels were unequivocally low (0.9 mcg/dL), and simultaneous ACTH measured on the second morning was 10 pg/mL (ref range 0-64). Thirty minute stimulated cortisol during a 250 mcg Cosyntropin stimulation test was 7 mcg/dL. FSH was unequivocally elevated, and simultaneous measurements of TSH and free T4 were unremarkable. Secondary adrenal insufficiency due to high dose fluticasone was diagnosed. The patient remained normotensive off anti-hypertensive agents, and she was given a prescription for prednisone to take during acute illnesses. Discussion: Inhaled fluticasone has minimal effects on the HPA axis when prescribed at doses less than 500 mcg daily. Though data are limited, there is an apparent 5-10% risk of measurable HPA axis suppression at cumulative daily doses exceeding 500 mcg. Most cases appear to be subclinical, and the rate of clinical secondary adrenal insufficiency as unmasked by anti-hypertensive therapy in our patient is unknown. Conclusion: The HPA axis should be evaluated promptly in patients receiving high dose ICS and a clinical presentation suspicious for secondary adrenal insufficiency.
In healthy and non-pregnant adults with hypothyroidism, a thyroxine dose of approximately 1.6 μg/... more In healthy and non-pregnant adults with hypothyroidism, a thyroxine dose of approximately 1.6 μg/kg/d is usually adequate to ameliorate symptoms and restore biochemical euthyroidism. While dose requirements may be increased by factors that limit absorption (reduced gastric acidity), increase excretion (nephrotic syndrome), or accelerate metabolism (e.g. carbamazepine) of thyroxine, medical non-compliance is the most common etiology of treatment failure. We report a case in which pseudomalabsorption was clearly demonstrated by directly observed, weekly administration of thyroxine in the office. A 25 year-old woman was referred for evaluation of persistent clinical and biochemical hypothyroidism despite prescription of very high doses of thyroxine and liothyronine. Thyroidectomy had been performed to manage Graves' thyrotoxicosis and goiter with compressive symptoms. Despite reported compliance, the patient experienced several months of persistently elevated TSH, undetectable T4, and symptoms of hypothyroidism such as fatigue and constipation. Evaluation for celiac sprue was unrevealing. The patient was educated to take thyroxine with water and on an empty stomach remote from food and mineral supplements. When confronted with the possibility of non-compliance, she changed primary care providers. At time of consultation, she was reportedly taking Levoxyl™ brand thyroxine 600 μg daily and Cytomel™ brand liothyronine 25 μg daily. Examination was notable for a well-healed low neck incision and deep tendon reflex delay. TSH was 133 mIU/L (ref. range 0.40-4.00), and total T4 was undetectable. The patient's pharmacy confirmed that she had not been filling her prescriptions. Weekly administration of 616 μg of Synthroid™ brand thyroxine (seven 88 μg pills) in the office was offered as alternative therapy, and the patient agreed. After 4 weeks, TSH fell to 4.74 mIU/L, and she acknowledged improvement of hypothyroidism-related symptoms. Weekly and directly observed thyroxine therapy confirmed medical non-compliance as the etiology of persistent hypothyroidism in our patient's case and resulted in significant biochemical and clinical improvements. In direct comparisons, the biochemical and clinical effects of daily or weekly administration of equivalent thyroxine doses are indistinguishable. Supervised weekly administration of thyroxine should be considered to confirm pseudomalabsorption and circumvent non-compliance in treatment of hypothyroidism.
While isolated coronary artery spasm has been well described among the cardiovascular manifestati... more While isolated coronary artery spasm has been well described among the cardiovascular manifestations of hyperthyroidism, a diffuse coronary blood flow abnormality suggestive of diffuse coronary artery disease (CAD) has not been reported prior. We report the case of a patient with thyroid storm whose angiographic findings mimicked multiple vessel CAD. A 44-year-old previously healthy woman was admitted to the hospital with acute respiratory failure due to pulmonary edema that required mechanical ventilation. She had had 3 months of dyspnea, “hot flushes”, profound fatigue, accompanied by a 60-pound weight loss. On presentation she had sinus tachycardia 180 beats/min, blood pressure of 205/123 mm Hg, fever of 39.1 C, unremarkable electrocardiogram and troponin I 0.18 ng/ml (indeterminate range). Her physical exam showed goiter, signs of thyrotoxicosis and onycholysis of distal nail beds. Echocardiogram revealed mild global hypokinesis with depressed ejection fraction of 30-35% and cardiac catheterization was suggestive of severe CAD with multivessel 70% stenosis. Cardiac output was high at 12 L//min (normal range 2.5 to 4.0 L/min per m2) Thyroid function tests obtained prior to cardiac catheterization confirmed hyperthyroidism: TSH 0.02 IU/ml, thyroxine (T4) 26.3 mcg/dl (6.1-12.2), free T4 3.9 ng/dl (0.6-1.6), total T3 228 ng/dl (87-178), T3 uptake 52% (32-48). TBII 90% (<10) and TSI 135% (<130) were consistent with Graves' disease. Based on clinical criteria she was diagnosed with thyroid storm and treatment with high dose propylthiouracil, lithium, glucocorticoids and beta-blockers was initiated with rapid symptomatic improvement. Within four days her cardiac ejection fraction dramatically improved to normal (50-60%). After 3 months of thionamide therapy she became biochemically euthyroid and a repeat cardiac catheterization showed normal coronary anatomy. This case demonstrates the presence of severe coronary artery vasospasm with left ventricular LV dysfunction in a patient during thyroid storm and argues in favor of a cautious interpretation of any angiographic findings in this scenario. The rapid reversibility of both the LV dysfunction and the angiographic abnormalities suggests a role for temporary dysfunctional changes in coronary arteries, an important entity to be recognized in hyperthyroidism since this pathology can be ameliorated with treatment of the underlying thyroid disease, hence avoiding unnecessary surgical interventions.
Ono et al have recently reported normalization of hyperprolactinemia with restoration of ovulator... more Ono et al have recently reported normalization of hyperprolactinemia with restoration of ovulatory cycles in all (n=85) patients treated with high dose cabergoline. Eighty patients conceived a total of 95 reported pregnancies. We report a case of cabergoline resistance in a patient who failed to normalize prolactin and remained anovulatory despite cabergoline therapy at a dose of 10 mg/week. Case: Patient was diagnosed to have secondary amenorrhea at age 18. Two years later her serum prolactin (PRL) was reported elevated at 2000 ng/ml (normal 3-24), and brain MRI showed a pituitary macroadenoma (11 mm x 10 mm). She was treated with bromocriptine and soon switched to cabergoline at 2mg/week due to intolerance. Over the ensuing 17 months her pituitary tumor shrank to 4 x 7 mm, and PRL level fell to 120 ng/ml. She had several interruptions of medical therapy largely related to intermittent nonadherence. At age 26 she was on cabergoline 10 mgs/week for 16 months, and she remained hyperprolactinemic (range: 200 -230 ng/ml) with sporadic menses. Patient was unable to conceive despite trying actively for 2 years at which point gonadotrophin induction was contemplated. At age 28years, she conceived (twin pregnancy) with HCG/Follistim therapy. At conception her PRL was 256 ng/ml with only a small microadenoma on the MRI scan. At 7 weeks gestation cabergoline was discontinued; PRL rose to 414 ng/ml at 11 weeks of gestation. She remained well during pregnancy until 25 weeks gestation when emergency C-section was required for placental abruption. Following delivery only one infant survived. She breastfed this infant for 16 months and he remains well. Repeat pituitary MRI done 2 year postpartum showed small pituitary adenoma. She presently continues to be hyperprolactinemic (495 ng/ml) with persistent galactorrhea/amenorrhea despite tumor shrinkage. Discussion: This case is one of the very few reported cases where cabergoline dose of > 9 mg/week failed to resolve hyperprolactinema and anovulation. Furthermore, discordance persisted between the tumor size shrinkage and degree of hyperprolactinemia. Additionally, following initial robust decline in PRL level in response to cabergoline therapy, PRL levels did not rise to pre cabergoline range despite its discontinuation – possibly reflecting loss of tumor volume. Our case also highlights the efficacy of ovulation induction when dopamine agonist therapy has not been successful in cases with persistent hyperprolactinemia. Ono M et al. J Clin Endocrinol Metab 2010; 95(6):2672-2679. Nothing to Disclose: CKM, ER, SN, CF, KR, GS
Endocrine Reviews, Volume 34, Issue 4, August 2013-2014, 2014
Pseudohypoparathyroidism Type 1A (PHP1A) is caused by maternal inheritance of an inactivating GNA... more Pseudohypoparathyroidism Type 1A (PHP1A) is caused by maternal inheritance of an inactivating GNAS1 mutation that results in Albright’s Hereditary Osteodystrophy (short stature, brachydachtyly, subcutaneous ossifications, neurocognitive disorders) and resistance to multiple hormones, most notably resistance to parathyroid hormone (PTH) in the proximal tubule. Most families harbor unique mutations, and no genotype-phenotype correlations have been reported. We present a family with variable skeletal manifestations of this unusual disorder of hormone resistance.
Abstract:
Background:
Transient changes in thyroid hormone levels following surgical neck explo... more Abstract:
Background:
Transient changes in thyroid hormone levels following surgical neck exploration have been sporadically reported. This phenomenon is often overlooked due to its rarity. We report three cases encountered over the past decade.
Clinical Case 1:
A 45 year-old female underwent single parathyroidectomy. On POD#1, she complained of palpitations and heart rate increased to 116 BPM. Thyroid test results noted low-normal TSH [0.56 uIU/ml, n 0.5-4.8 uIU/ml] and elevated Total T4 (TT4) and Free T4 (FT4) [13.8 mcg/dL and 2.1 ng/dL, n TT4 4.5-12.0 mcg/dL and n FT4 0.9-1.5 ng/dL]. Pre-surgery and post-recovery thyroid function was normal with TSH 1.2 and 1.2 uIU/ml, TT4 10.2 and 9.4 mcg/dL and FT4 0.9 and 0.8 ng/dL.
Clinical Case 2:
A 65 year-old male underwent single parathyroidectomy without complications. Calcium levels stabilized without repletion. SBP increased to 180 mm Hg on POD#1 and he experienced palpitations, chest pressure and new-onset atrial fibrillation on POD#2. Thyroid test results noted suppressed TSH [0.42 uIU/ml] and elevated TT4 and FT4 [14.2 mcg/dL and 1.99 ng/dL]. Cardiac evaluation was unremarkable. Pre-surgery and post-recovery thyroid function was normal with TSH 0.92 and 0.98 uIU/ml, TT4 9.7 and 8.8 mcg/dL and FT4 1.1 and 0.9 ng/dL.
Clinical Case 3:
A 58 year-old female underwent neck exploration for presumed parathyroid mass and complained of fine tremors, hyperhidrosis and palpitations on POD#2. SBP was elevated to 174 mm Hg. Thyroid test results noted suppressed TSH [0.32 uIU/ml] and elevated TT4 and FT4 [14.2 mcg/dL and 2.2 ng/dL]. Pre-surgery and post-recovery results demonstrated normal thyroid function with TSH 2.1 and 2.4 uIU/ml, TT4 8.7 and 8.7 mcg/dL and FT4 0.75 and 0.75 ng/dL.
All three patients had no history of hyperthyroidism and were started on beta-blockers to control heart rate and moderately elevated blood pressure. Thyroid functions rapidly returned to baseline normal state without treatment.
Conclusion:
Clinical assessment is critical in decision to initiate treatment for apparent hyperthyroidism based on abnormal post-operative thyroid tests. When in doubt, testing of blood samples drawn within a week prior to surgery is advised. Hyperthyroxinemia may be encountered in a small percentage of cases following neck exploration for non-thyroid related reasons. Appreciation of transient hyperthyroxinemia would avoid unnecessary treatment risk of severe toxicities and committing patients to costly surveillance testing.
Nothing to Disclose: ER, NS, CM, SG, RK
Periodic paralysis (PP) is a muscle disorder caused by ion channel dysfunction and characterized ... more Periodic paralysis (PP) is a muscle disorder caused by ion channel dysfunction and characterized by episodes of muscle weakness. Most cases are autosomal dominant, though sporadic cases may occur as a rare complication of hyperthyroidism. We present a case of thyrotoxic PP and review the literature on this acquired form of PP.
Endocrinologists commonly see referrals for flushing and should be aware that the neurological sx... more Endocrinologists commonly see referrals for flushing and should be aware that the neurological sx associated with cerebral amyloid angiopathy(CAA )may include facial flushing. While small subclinical hemorrhages in CAA are common, small areas of hemorrhage may be associated with headache, seizure or focal neurological deficits as in this case. CAA more often manifests as spontaneous cerebral lobar bleeding in subcortical white matter.
Primary hyperparathyroidism during pregnancy though uncommon, represents a preventable cause of f... more Primary hyperparathyroidism during pregnancy though uncommon, represents a preventable cause of fetal and maternal morbidity and mortality. In cases of severe gestational PHP, parathyroid surgery can be safely performed in the second trimester and is the most definitive treatment modality with optimal prognosis for both the mother and fetus.
Methods A prospective study with historical controls will be performed. All SIU resident physicia... more Methods A prospective study with historical controls will be performed. All SIU resident physicians will be provided with the SIU insulin dosing guide as an electronic application that can be downloaded to Apple iPhones and Android smart phones, which together account for well over 90% of all smartphone platforms. Study investigators will make presentations at residency didactic (noon) conferences on the topic of hospital diabetes management and utilization of the insulin dosing application. From July 2017-June 2017, diabetes management practices (i.e. BBI or other approaches) on the SIU resident medicine service will be monitored as the primary study endpoint, and capillary blood glucose measurements and hospital length of stay will be monitored as secondary endpoints. In addition to primary and secondary endpoints, patient charts will be reviewed for relevant demographic and clinical information including age, gender, type of diabetes, hemoglobin A1c (HbA1c) obtained prior to or during admission, and mode of pre-hospital diabetes treatment. A historical controls database will created using patients admitted to the SIU resident medicine service July 2016-June 2017 the year before the electronic insulin dosing application is introduced. Results for the two time periods will be compared using the same statistical methods as the pocket insulin dosing guide study (5). All patient data will be recorded and stored without unique identifiers on a password protected computer accessible only to study investigators and will be stored only until final data analysis is completed. There are no costs to study subjects or requirements for ongoing contact. Diabetes management decisions remain under the control of admitting house staff medicine teams and their attending physicians. Objectives 1. Increase utilization of BBI on the SIU resident covered medicine service at MMC. 2. Improve blood glucose control for diabetes patients admitted to the SIU medicine service at MMC. 3. Reinforce best hospital diabetes management practices for SIU internal medicine resident physicians. 4. Validate smart phones as a platform for clinical practice tools. Expected outcomes Based on experience with the pocket insulin dosing guide (5), it is anticipated that the electronic insulin dosing application will significantly increase utilization of BBI for patients with diabetes admitted to the SIU resident covered medicine service and improve blood sugar control compared to other management approaches. Hospital length of stay (LOS) will be included as a clinical endpoint of the study, though there was no change in LOS in the pocket insulin dosing guide study. It is also anticipated that SIU resident physicians will gain insight into initiating and adjusting insulin in the hospital and become more confident and proficient with diabetes management in this setting. Impact on patient care
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meters utilizing glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) and glucose-dye-oxidoreductase (GDO) based re
-actions to detect glucose. We report a recent case of icodextrin-related factitious hyperglycemia leading to iatrogenic hypoglyce-mia, brain injury, and death
Duodenal switch surgery causes malabsorption through biliopancreatic diversion that bypasses the duodenum and proximal jejunum (Fig 1). Hypovitaminosis D and hypocalcemia may result and lead to secondary hyperparathyroidism (SHPT). Little is published regarding refractory SHPT in obese patients managed by bariatric surgery. We present a case of SHPT refractory to vitamin D repletion that responded favorably to treatment with the calcimimetic agent cinacalcet. Though cinacalcet is used to manage SHPT due to chronic kidney disease, we are unaware of any reports documenting cinacalcet as therapy for SHPT caused by bariatric surgery.
syndrome. 2) To understand pathophysiology and treatment of ectopic
ACTH syndrome
CASE: A 56 year old Caucasian male with a history of Type 2 diabetes
and hypertension was admitted to the hospital for poorly controlled
blood glucose, high blood pressure, pedal edema and severe lemia. He was known to have localised prostate cancer which was
diagnosed 1 year ago. Significant physical findings included blood
pressure of 170/100 mm Hg, pitting pedal edema and proximal
muscle weakness. His admission investigations revealed glucose of
425 mg/dl, potassium 2.7 mmol/L and bicarbonate 30 mmol/L.
Prostate specific antigen (PSA) was elevated at 11.6 ng/ml (nanogram/
milliliter) and recurrence of prostate cancer was suspected. Computed
tomography of abdomen and chest showed wide spread metastasis
to liver, lung and osteoblastic lesions in lumbar spine. Biopsy
of the liver lesions revealed undifferentiated small cell carcinoma.
Immunohistochemical stains for prostate cocktail (PSA/Prostate acid
phospatase) and chromogranin, a marker for neuroendocrine tumor
were negative. Further work up revealed severely elevated morning
cortisol of 72 ug/dL (4–24 ug/dl) and 24 hour urinary cortisol of
1872 ug/24 hrs (3.5–40 ug/24 hr). ACTH level was high at 501 pg/ml
(0–46 pg/mL).With this constellation of findings, a diagnosis of
ectopic ACTH secretion from metastatic small cell cancer was made.
He received chemotherapy with Cisplatin and CPT-11[Irinotecan] and
was started on Ketoconazole for suppressing the synthesis of glucocorticoids.
However this resulted in QT prolongation on follow up electrocardiogram,
so Ketoconazole was discontinued. Therapy with
Octreotide 100 micrograms three times a day was started. In 5 days,
ACTH decreased by 23 percent and 24 urinary cortisol decreased by 73
percent. Patient was switched to long acting Octreotide 20 mg once a
month. His muscle strength improved significantly. He had better
glycemic and blood pressure control and potassium level normalized.
After 2 months on Octreotide therapy ACTH was 11 pg/ml and 24 hour
urine Cortisol was within the normal range
DISCUSSION: Cushing’s syndrome caused by ectopic production of
ACTH should be considered in all patients with a malignancy,
associated with peripheral edema, hypertension, raised blood glucose
and hypokalemic alkalosis. This patient had all these typical
manifestations. In patients with ectopic ACTH syndrome due to
aggressive small cell cancers, onset of Cushing’s syndrome can be
rapid and this can explain absence of classic manifestations such as
fat deposition in clavicular fossa and interscapular area. These
patients have extreme hypercortisolemia which causes, marked salt
retention (contributing to edema and hypertension), increased glucuneogenesis
(producing glucose intolerance), and hypokalemic alkalosis
(causing profound muscle weakness). Surgical excision or debulking of
the tumor is the definitive therapy of ectopic ACTH syndrome. Medical
therapy with adrenal enzyme inhibitors, such as Aminoglutethimide,
Ketoconazole or Metyrapone can be used to reduce cortisol production.
Octreotide, a long-acting analogue of somatostatin can be
effective in suppressing ACTH levels. The long acting analog of
Octreotide (Sandostatin LAR) given once monthly is effective and
preferred once efficacy of Octreotide is documented (This is an off
label use of Octreotide).
impact of a pocket insulin dosing guide on diabetes management practices
of SIU School of Medicine resident physicians. Patients and controls were
well matched with the exception of gender. During the study, basal/bolus
insulin (BBI) orders increased nearly five-fold, and overall BBI orders
increased six-fold compared to the historical control period before the
insulin dosing guide. A significant decrease in sliding scale insulin (SSI)
occurred during the study and in comparison to the historical control
period. In February 2011, when BBI was ordered more than SSI, mean
capillary blood glucose (CBG) and percent CBG measurements 70-140
mg/dL were significantly improved without an increase in hypoglycemia
(CBG < 70 mg/dL). The pocket insulin dosing guide significantly increased
utilization of BBI, decreased SSI orders, and improved hospital glycemic
control for patients with Type 2 diabetes.
Case. A 27 year old female was referred for evaluation of persistent hypercalcemia. The patient was incidentally discovered to be hypercalcemic approximately six years before referral. Nine serum calcium measurements ranged from 10.8-11.6 mg/dL (8.5-10.4) from initial discovery of hypercalcemia through end of metabolic evaluation. PTH level on diagnosis of hypercalcemia was 27 pg/mL (12-88), and three additional measurements ranged from 37-50 pg/mL. Three measurements of 25-hydroxyvitamin D level ranged from 22-31 ng/mL. Initial 24 hour urine calcium was 132 mg, though urine creatinine was not measured to allow calculation of CCCR. The patient’s father (deceased), daughter, and a niece had been diagnosed with hypercalcemia, prompting sequencing of the CaSR gene that revealed a heterozygous sequence variant (c.2657G>C) in exon seven predicting a R886P substitution in the receptor. Another 24 hour urine collection yielded a calcium of 272 mg, and CCCR was equivocal (0.016). A DXA scan obtained before referral and following traumatic right hand fracture was notable for marginal Z-scores of the distal third of the radius (-1.7), left femoral neck (-1.9), and left total hip (-1.8). Three serum phosphate levels were low or marginal (2.3-2.6 mg/dL, 2.5-4.5). Approximately 15 months after referral, the patient experienced right nephrolithiasis. No parathyroid adenomas were identified on sestamibi parathyroid scintigraphy. Unfortunately, the patient was lost to follow up.
Conclusion. CaSR mutation positive hypercalcemia may present with biochemical and clinical manifestations that are atypical for FHH. For example, the F881L mutation has been linked to hypercalciuria and nephrolithiasis that benefitted from parathyroidectomy. The R886P mutation found in our patient maps near F881L, and the proband in the initial R886P kindred presented with an elevated PTH level, 24 hour urine calcium > 200 mg, and CCCR > 0.02. However, no PHPT phenotype was described in this kindred. PHPT may also co-occur with CaSR mutations; in a German series of 139 PHPT patients, four had co-existing features of FHH and confirmatory CaSR mutations. Case reports of concurrent FHH and PHPT have also been published, though in our patient parathyroid imaging failed to clearly identify an adenoma. This case demonstrates that familial CaSR mutation positive hypercalcemia may not have the benign course typical of FHH.
meters utilizing glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) and glucose-dye-oxidoreductase (GDO) based re
-actions to detect glucose. We report a recent case of icodextrin-related factitious hyperglycemia leading to iatrogenic hypoglyce-mia, brain injury, and death
Duodenal switch surgery causes malabsorption through biliopancreatic diversion that bypasses the duodenum and proximal jejunum (Fig 1). Hypovitaminosis D and hypocalcemia may result and lead to secondary hyperparathyroidism (SHPT). Little is published regarding refractory SHPT in obese patients managed by bariatric surgery. We present a case of SHPT refractory to vitamin D repletion that responded favorably to treatment with the calcimimetic agent cinacalcet. Though cinacalcet is used to manage SHPT due to chronic kidney disease, we are unaware of any reports documenting cinacalcet as therapy for SHPT caused by bariatric surgery.
syndrome. 2) To understand pathophysiology and treatment of ectopic
ACTH syndrome
CASE: A 56 year old Caucasian male with a history of Type 2 diabetes
and hypertension was admitted to the hospital for poorly controlled
blood glucose, high blood pressure, pedal edema and severe lemia. He was known to have localised prostate cancer which was
diagnosed 1 year ago. Significant physical findings included blood
pressure of 170/100 mm Hg, pitting pedal edema and proximal
muscle weakness. His admission investigations revealed glucose of
425 mg/dl, potassium 2.7 mmol/L and bicarbonate 30 mmol/L.
Prostate specific antigen (PSA) was elevated at 11.6 ng/ml (nanogram/
milliliter) and recurrence of prostate cancer was suspected. Computed
tomography of abdomen and chest showed wide spread metastasis
to liver, lung and osteoblastic lesions in lumbar spine. Biopsy
of the liver lesions revealed undifferentiated small cell carcinoma.
Immunohistochemical stains for prostate cocktail (PSA/Prostate acid
phospatase) and chromogranin, a marker for neuroendocrine tumor
were negative. Further work up revealed severely elevated morning
cortisol of 72 ug/dL (4–24 ug/dl) and 24 hour urinary cortisol of
1872 ug/24 hrs (3.5–40 ug/24 hr). ACTH level was high at 501 pg/ml
(0–46 pg/mL).With this constellation of findings, a diagnosis of
ectopic ACTH secretion from metastatic small cell cancer was made.
He received chemotherapy with Cisplatin and CPT-11[Irinotecan] and
was started on Ketoconazole for suppressing the synthesis of glucocorticoids.
However this resulted in QT prolongation on follow up electrocardiogram,
so Ketoconazole was discontinued. Therapy with
Octreotide 100 micrograms three times a day was started. In 5 days,
ACTH decreased by 23 percent and 24 urinary cortisol decreased by 73
percent. Patient was switched to long acting Octreotide 20 mg once a
month. His muscle strength improved significantly. He had better
glycemic and blood pressure control and potassium level normalized.
After 2 months on Octreotide therapy ACTH was 11 pg/ml and 24 hour
urine Cortisol was within the normal range
DISCUSSION: Cushing’s syndrome caused by ectopic production of
ACTH should be considered in all patients with a malignancy,
associated with peripheral edema, hypertension, raised blood glucose
and hypokalemic alkalosis. This patient had all these typical
manifestations. In patients with ectopic ACTH syndrome due to
aggressive small cell cancers, onset of Cushing’s syndrome can be
rapid and this can explain absence of classic manifestations such as
fat deposition in clavicular fossa and interscapular area. These
patients have extreme hypercortisolemia which causes, marked salt
retention (contributing to edema and hypertension), increased glucuneogenesis
(producing glucose intolerance), and hypokalemic alkalosis
(causing profound muscle weakness). Surgical excision or debulking of
the tumor is the definitive therapy of ectopic ACTH syndrome. Medical
therapy with adrenal enzyme inhibitors, such as Aminoglutethimide,
Ketoconazole or Metyrapone can be used to reduce cortisol production.
Octreotide, a long-acting analogue of somatostatin can be
effective in suppressing ACTH levels. The long acting analog of
Octreotide (Sandostatin LAR) given once monthly is effective and
preferred once efficacy of Octreotide is documented (This is an off
label use of Octreotide).
impact of a pocket insulin dosing guide on diabetes management practices
of SIU School of Medicine resident physicians. Patients and controls were
well matched with the exception of gender. During the study, basal/bolus
insulin (BBI) orders increased nearly five-fold, and overall BBI orders
increased six-fold compared to the historical control period before the
insulin dosing guide. A significant decrease in sliding scale insulin (SSI)
occurred during the study and in comparison to the historical control
period. In February 2011, when BBI was ordered more than SSI, mean
capillary blood glucose (CBG) and percent CBG measurements 70-140
mg/dL were significantly improved without an increase in hypoglycemia
(CBG < 70 mg/dL). The pocket insulin dosing guide significantly increased
utilization of BBI, decreased SSI orders, and improved hospital glycemic
control for patients with Type 2 diabetes.
Case. A 27 year old female was referred for evaluation of persistent hypercalcemia. The patient was incidentally discovered to be hypercalcemic approximately six years before referral. Nine serum calcium measurements ranged from 10.8-11.6 mg/dL (8.5-10.4) from initial discovery of hypercalcemia through end of metabolic evaluation. PTH level on diagnosis of hypercalcemia was 27 pg/mL (12-88), and three additional measurements ranged from 37-50 pg/mL. Three measurements of 25-hydroxyvitamin D level ranged from 22-31 ng/mL. Initial 24 hour urine calcium was 132 mg, though urine creatinine was not measured to allow calculation of CCCR. The patient’s father (deceased), daughter, and a niece had been diagnosed with hypercalcemia, prompting sequencing of the CaSR gene that revealed a heterozygous sequence variant (c.2657G>C) in exon seven predicting a R886P substitution in the receptor. Another 24 hour urine collection yielded a calcium of 272 mg, and CCCR was equivocal (0.016). A DXA scan obtained before referral and following traumatic right hand fracture was notable for marginal Z-scores of the distal third of the radius (-1.7), left femoral neck (-1.9), and left total hip (-1.8). Three serum phosphate levels were low or marginal (2.3-2.6 mg/dL, 2.5-4.5). Approximately 15 months after referral, the patient experienced right nephrolithiasis. No parathyroid adenomas were identified on sestamibi parathyroid scintigraphy. Unfortunately, the patient was lost to follow up.
Conclusion. CaSR mutation positive hypercalcemia may present with biochemical and clinical manifestations that are atypical for FHH. For example, the F881L mutation has been linked to hypercalciuria and nephrolithiasis that benefitted from parathyroidectomy. The R886P mutation found in our patient maps near F881L, and the proband in the initial R886P kindred presented with an elevated PTH level, 24 hour urine calcium > 200 mg, and CCCR > 0.02. However, no PHPT phenotype was described in this kindred. PHPT may also co-occur with CaSR mutations; in a German series of 139 PHPT patients, four had co-existing features of FHH and confirmatory CaSR mutations. Case reports of concurrent FHH and PHPT have also been published, though in our patient parathyroid imaging failed to clearly identify an adenoma. This case demonstrates that familial CaSR mutation positive hypercalcemia may not have the benign course typical of FHH.
hospital with acute onset headache, diplopia, and vomiting.
Examination was notable for hypertension and partial
left third and sixth cranial nerve palsies. No stigmata of
Cushing’s syndrome were observed. MRI revealed a 2.9 cm
pituitary macroadenoma with acute hemorrhage extending
into the left cavernous sinus. Evaluation of anterior
pituitary function approximately 30 hr after admission
revealed serum cortisol 56.4 μg/dL (8.7-22.4) and ACTH
337 pg/mL (7-69). TSH (0.92 mIU/L, 0.34-5.60), free T4
(1.0 ng/dL, 0.5-1.3), and IGF-1 (167 ng/mL, 36-215) were
unremarkable, though prolactin level was low (1.0 ng/mL,
2.6-13.2). Over the next 4 d, serum cortisol ranged from
50-60 μg/dL, and 24 hr urine free cortisol was 1,883 μg
(< 60). At hospital discharge 7 d after admission, cortisol
(24.6 μg/dL) and ACTH (148 pg/mL) were falling, and at
15 d from admission early hypopituitarism had occurred
[8 AM cortisol 5.7 μg/dL, ACTH 15 pg/mL, TSH 0.55
mIU/L, free T4 0.6 ng/dL, IGF-1 65 ng/mL, LH 2.2 mIU/
mL (1.2-8.6), testosterone 76 ng/dL (270-1070)]. The
adenoma was resected 6 wk after initial presentation, and
postoperative histology revealed neuroendocrine cells in
a background of fibrosis and pigment-laden macrophages
but no staining for ACTH.
Discussion: Pituitary apoplexy usually occurs due to
hemorrhage or infarction of an adenoma. Hypopituitarism
often occurs either at time of presentation due to
compromise of anterior pituitary blood flow or before the event due to mass effect of the adenoma. Secondary
adrenal insufficiency is reported in approximately
70% of pituitary apoplexy cases, but significant
hypercortisolemia is rare. Literature review identified
only one published case of hypercortisolemia during
apoplexy in the setting of Cushing’s disease. In this
case, hemorrhage of a corticotroph adenoma is unlikely
as corticotroph macroadenomas are rare, the patient had
no symptoms or signs of Cushing’s syndrome, and no
immunohistochemical staining for ACTH was detected
on histological evaluation of the tumor. Elevations of
ACTH and cortisol most likely reflect stress activation of
the hypothalamic-pituitary-adrenal axis, with subsequent
central hypogonadism and declines in other pituitary
functions reflecting subacute onset of hypopituitarism.
Conclusion: This case illustrates that pituitary apoplexy
may provoke a stress glucocorticoid response if corticotrophs
remain viable. There is little published to predict subsequent anterior pituitary function after hemorrhage when initial
cortisol levels are elevated, though low prolactin level
appears to have been a marker for eventual hypopituitarism
as in more typical cases of apoplexy.
dosing of ipilimumab (Ipi), a humanized monoclonal cytotoxic
T-lymphocyte associated antigen-4 (CTLA-4) antibody, for
management of metastatic melanoma. Shortly after the fourth
dose, he presented to his oncologist with subacute onset
frontal headache and lethargy. MRI of the sella turcica failed
to show pituitary metastases or enlargement indicative of
hypophysitis. The patient was treated empirically with a 5 d
methylprednisolone taper, and symptoms abated. However,
headache and fatigue recurred, prompting two additional 5
d treatment courses in the 4 weeks between symptoms onset
and endocrinology referral. Pituitary function was evaluated
2 weeks after the last dose of methylprednisolone and notable
for 8 AM cortisol 0.4 μg/dL (6.2-19.4), ACTH < 5 pg/mL
(0-46), free T4 0.70 ng/dL (0.93-1.70), and TSH 0.62 mIU/L
(0.27-4.20). Prolactin was low (2.4 ng/mL, 4.0-15.2), but
morning testosterone (331 ng/dL, 193-740) and LH level (4.5
mIU/mL, 1.7-8.6) were unremarkable. Partial Ipi-induced
hypopituitarism was diagnosed, and the patient was started
on hydrocortisone followed by levothyroxine one week later.
Headache and fatigue completely resolved, and the patient
started Ipi maintenance therapy.
Discussion: CTLA-4 antibodies are checkpoint inhibitors
that disrupt immune tolerance to antigens on tumor cells.
However, immune-related adverse events may occur as a
consequence of T-cell activation including hypophysitis.
In a recently published retrospective review, hypophysitis
occurred in 11% of Ipi treated patients, and male gender
and advanced age were risk factors. Central hypothyroidism
occurred in all patients, central hypogonadism was present
in all cases where evaluation was performed, and central
adrenal insufficiency occurred in half of patients. Mild to
moderate pituitary enlargement was demonstrated on MRI in
all cases in the series. Animal studies have found CTLA-4
expression on anterior pituitary cells, lymphocytic infiltration
of the pituitary, and antipituitary antibodies after injection of
CTLA-4 antibodies.
Conclusion: Hypophysitis and varying degrees of
hypopituitarism occur in approximately 10% of patients treated
with Ipi. This case is unusual for two reasons: 1) no pituitary
enlargement was apparent on MRI, and 2) gonadotrope
function was preserved. Ipi-induced hypophysitis should be
investigated promptly when patients develop provocative symptoms and appropriate hormone replacement started
based on anterior pituitary function. This case illustrates
that Ipi-induced hypophysitis can occur even in the
absence of obvious pituitary enlargement.
used for management of chronic obstructive pulmonary
disease (COPD). CS are less likely to cause systemic side
effects than oral corticosteroids because 80 to 90 percent
of a dose is absorbed through the upper gastrointestinal
tract and inactivated by first pass hepatic metabolism.
Although there is variability between ICS preparations
and different inter-individual susceptibilities, high doses
of ICS may lead to biochemical evidence of hypothalamicpituitary-adrenal
(HPA) axis suppression. Reports of
clinical secondary adrenal insufficiency, however, are
rare. We present a case of clinically apparent secondary
adrenal insufficiency in a patient receiving high dose ICS
for management of COPD.
Case Presentation: An 86-year-old woman was admitted
to hospital for near syncope. Several weeks prior to
admission, she experienced dizziness and weakness after
standing that resolved in a seated or supine position. The the patient denied falls, chest pain, dyspnea, palpitations,
or weight loss. She reported full compliance with her
medical regimen which included olmesartan, nifedipine,
furosemide, and isosorbide mononitrate. Inhaled fluticasone
(1,000 mcg daily) had been prescribed for two years to
manage COPD. The patient denied treatment with oral or
articular corticosteroids. Examination was unremarkable
with the exception of orthostatic blood pressure and heart
rate changes. Orthostasis resolved after blood pressure
medications were held and isotonic fluid was administered.
Two consecutive 8:00 AM cortisol levels were
unequivocally low (0.9 mcg/dL), and simultaneous ACTH
measured on the second morning was 10 pg/mL (ref range
0-64). Thirty minute stimulated cortisol during a 250 mcg
Cosyntropin stimulation test was 7 mcg/dL. FSH was
unequivocally elevated, and simultaneous measurements
of TSH and free T4 were unremarkable. Secondary adrenal
insufficiency due to high dose fluticasone was diagnosed.
The patient remained normotensive off anti-hypertensive
agents, and she was given a prescription for prednisone to
take during acute illnesses.
Discussion: Inhaled fluticasone has minimal effects on
the HPA axis when prescribed at doses less than 500 mcg
daily. Though data are limited, there is an apparent 5-10%
risk of measurable HPA axis suppression at cumulative
daily doses exceeding 500 mcg. Most cases appear to
be subclinical, and the rate of clinical secondary adrenal
insufficiency as unmasked by anti-hypertensive therapy in
our patient is unknown.
Conclusion: The HPA axis should be evaluated promptly in
patients receiving high dose ICS and a clinical presentation
suspicious for secondary adrenal insufficiency.
A 44-year-old previously healthy woman was admitted to the hospital with acute respiratory failure due to pulmonary edema that required mechanical ventilation. She had had 3 months of dyspnea, “hot flushes”, profound fatigue, accompanied by a 60-pound weight loss.
On presentation she had sinus tachycardia 180 beats/min, blood pressure of 205/123 mm Hg, fever of 39.1 C, unremarkable electrocardiogram and troponin I 0.18 ng/ml (indeterminate range). Her physical exam showed goiter, signs of thyrotoxicosis and onycholysis of distal nail beds. Echocardiogram revealed mild global hypokinesis with depressed ejection fraction of 30-35% and cardiac catheterization was suggestive of severe CAD with multivessel 70% stenosis. Cardiac output was high at 12 L//min (normal range 2.5 to 4.0 L/min per m2)
Thyroid function tests obtained prior to cardiac catheterization confirmed hyperthyroidism: TSH 0.02 IU/ml, thyroxine (T4) 26.3 mcg/dl (6.1-12.2), free T4 3.9 ng/dl (0.6-1.6), total T3 228 ng/dl (87-178), T3 uptake 52% (32-48). TBII 90% (<10) and TSI 135% (<130) were consistent with Graves' disease. Based on clinical criteria she was diagnosed with thyroid storm and treatment with high dose propylthiouracil, lithium, glucocorticoids and beta-blockers was initiated with rapid symptomatic improvement. Within four days her cardiac ejection fraction dramatically improved to normal (50-60%). After 3 months of thionamide therapy she became biochemically euthyroid and a repeat cardiac catheterization showed normal coronary anatomy.
This case demonstrates the presence of severe coronary artery vasospasm with left ventricular LV dysfunction in a patient during thyroid storm and argues in favor of a cautious interpretation of any angiographic findings in this scenario. The rapid reversibility of both the LV dysfunction and the angiographic abnormalities suggests a role for temporary dysfunctional changes in coronary arteries, an important entity to be recognized in hyperthyroidism since this pathology can be ameliorated with treatment of the underlying thyroid disease, hence avoiding unnecessary surgical interventions.
Case:
Patient was diagnosed to have secondary amenorrhea at age 18. Two years later her serum prolactin (PRL) was reported elevated at 2000 ng/ml (normal 3-24), and brain MRI showed a pituitary macroadenoma (11 mm x 10 mm). She was treated with bromocriptine and soon switched to cabergoline at 2mg/week due to intolerance. Over the ensuing 17 months her pituitary tumor shrank to 4 x 7 mm, and PRL level fell to 120 ng/ml. She had several interruptions of medical therapy largely related to intermittent nonadherence. At age 26 she was on cabergoline 10 mgs/week for 16 months, and she remained hyperprolactinemic (range: 200 -230 ng/ml) with sporadic menses. Patient was unable to conceive despite trying actively for 2 years at which point gonadotrophin induction was contemplated. At age 28years, she conceived (twin pregnancy) with HCG/Follistim therapy. At conception her PRL was 256 ng/ml with only a small microadenoma on the MRI scan. At 7 weeks gestation cabergoline was discontinued; PRL rose to 414 ng/ml at 11 weeks of gestation. She remained well during pregnancy until 25 weeks gestation when emergency C-section was required for placental abruption. Following delivery only one infant survived. She breastfed this infant for 16 months and he remains well. Repeat pituitary MRI done 2 year postpartum showed small pituitary adenoma. She presently continues to be hyperprolactinemic (495 ng/ml) with persistent galactorrhea/amenorrhea despite tumor shrinkage.
Discussion:
This case is one of the very few reported cases where cabergoline dose of > 9 mg/week failed to resolve hyperprolactinema and anovulation. Furthermore, discordance persisted between the tumor size shrinkage and degree of hyperprolactinemia. Additionally, following initial robust decline in PRL level in response to cabergoline therapy, PRL levels did not rise to pre cabergoline range despite its discontinuation – possibly reflecting loss of tumor volume. Our case also highlights the efficacy of ovulation induction when dopamine agonist therapy has not been successful in cases with persistent hyperprolactinemia.
Ono M et al. J Clin Endocrinol Metab 2010; 95(6):2672-2679.
Nothing to Disclose: CKM, ER, SN, CF, KR, GS
Background:
Transient changes in thyroid hormone levels following surgical neck exploration have been sporadically reported. This phenomenon is often overlooked due to its rarity. We report three cases encountered over the past decade.
Clinical Case 1:
A 45 year-old female underwent single parathyroidectomy. On POD#1, she complained of palpitations and heart rate increased to 116 BPM. Thyroid test results noted low-normal TSH [0.56 uIU/ml, n 0.5-4.8 uIU/ml] and elevated Total T4 (TT4) and Free T4 (FT4) [13.8 mcg/dL and 2.1 ng/dL, n TT4 4.5-12.0 mcg/dL and n FT4 0.9-1.5 ng/dL]. Pre-surgery and post-recovery thyroid function was normal with TSH 1.2 and 1.2 uIU/ml, TT4 10.2 and 9.4 mcg/dL and FT4 0.9 and 0.8 ng/dL.
Clinical Case 2:
A 65 year-old male underwent single parathyroidectomy without complications. Calcium levels stabilized without repletion. SBP increased to 180 mm Hg on POD#1 and he experienced palpitations, chest pressure and new-onset atrial fibrillation on POD#2. Thyroid test results noted suppressed TSH [0.42 uIU/ml] and elevated TT4 and FT4 [14.2 mcg/dL and 1.99 ng/dL]. Cardiac evaluation was unremarkable. Pre-surgery and post-recovery thyroid function was normal with TSH 0.92 and 0.98 uIU/ml, TT4 9.7 and 8.8 mcg/dL and FT4 1.1 and 0.9 ng/dL.
Clinical Case 3:
A 58 year-old female underwent neck exploration for presumed parathyroid mass and complained of fine tremors, hyperhidrosis and palpitations on POD#2. SBP was elevated to 174 mm Hg. Thyroid test results noted suppressed TSH [0.32 uIU/ml] and elevated TT4 and FT4 [14.2 mcg/dL and 2.2 ng/dL]. Pre-surgery and post-recovery results demonstrated normal thyroid function with TSH 2.1 and 2.4 uIU/ml, TT4 8.7 and 8.7 mcg/dL and FT4 0.75 and 0.75 ng/dL.
All three patients had no history of hyperthyroidism and were started on beta-blockers to control heart rate and moderately elevated blood pressure. Thyroid functions rapidly returned to baseline normal state without treatment.
Conclusion:
Clinical assessment is critical in decision to initiate treatment for apparent hyperthyroidism based on abnormal post-operative thyroid tests. When in doubt, testing of blood samples drawn within a week prior to surgery is advised. Hyperthyroxinemia may be encountered in a small percentage of cases following neck exploration for non-thyroid related reasons. Appreciation of transient hyperthyroxinemia would avoid unnecessary treatment risk of severe toxicities and committing patients to costly surveillance testing.
Nothing to Disclose: ER, NS, CM, SG, RK