Introduction: Thyrotropinomas are rare pituitary adenomas, representing 2% of pituitary tumors. T... more Introduction: Thyrotropinomas are rare pituitary adenomas, representing 2% of pituitary tumors. They are characterized by autonomous secretion of thyrotropin (TSH) and elevated levels of peripheral hormones. A third can secrete other hormones, including growth hormone (GH). We present the case of a patient with hypersecretion TSH and GH with clinical manifestations. Clinical case: 44-year-old woman with a history of palpitations and weight loss of 8 kilos of 3 months of evolution, as well as decreased visual acuity and headache. Physical exam: tachycardia, fine tremor, prognathism, thickening of the lips, increase in the base of the nose, hands and feet. TSH; 8.8mU / L (0.4-4), FT4: 35.59pg / ml (8-17), GH: 3.93 (less than 1.88), IGF-1: 716ng / ml (101-267), ANTI TPO negative, FSH, LH, Estradiol, Prolactin, Cortisol in range. Thyroid profile is repeated: TSH: 12.92mIU / ml (0.34-4.94); FT4 and T3 high. Campimetry: left temporal hemianopia Pituitary MRI: a heterogeneous 51x42x47mm Tu...
The patient is a 54-year-old male with type 2 diabetic treated with insulin who presented with a ... more The patient is a 54-year-old male with type 2 diabetic treated with insulin who presented with a two-week history of fever nausea and vomiting. He subsequently developed seizure episodes with changes in mental status prompting a visit to the emergency room. Upon admission the patient was hypotensive and lethargic. After an initial improvement, he developed polyuria (14-15 liters per day) in the context of eunatremia and specific gravity of 1010. His initial evaluation revealed a serum a.m. cortisol of 1.2 mcg/dL (6.2 to 19.4), low free T4 of 0.64 Ng/dl) 0.9-1.7) and secondary hypogonadism with a total testosterone of less than 2.5 ng/dL (181-772). Hormonal replacement was initiated. MRI of the brain revealed heterogeneous sellar lesion measuring 2.1 x 2.0 x 2.0 cm with peripheral enhancement following contrast administration and deviation of the pituitary stalk to the right. The lesion invaded the left cavernous sinus (Knosp III) and abutted the optic chiasm. He underwent an unevent...
Pituitary stalk interruption syndrome presenting as primary amenorrhea. The pituitary stalk inter... more Pituitary stalk interruption syndrome presenting as primary amenorrhea. The pituitary stalk interruption syndrome is a rare congenital defect that is characterized by the absence or thinning of the pituitary stalk, an absent or ectopic posterior pituitary lobe, and hypoplasia or aplasia of the anterior lobe. The clinical presentation is variable. It is usually diagnosed in the neonatal period due to the clinical manifestations that arise as a consequence of hormonal deficiencies. However some patients are diagnosed at a latter stage in life. Growth hormone deficiency it is observed in virtually all patients and can be associated to other anterior pituitary hormonal deficiencies. There is a high frequency of associated extra-pituitary malformations including those involving the central nervous system and the craniofacial structures. We report the case of a 19-year-old woman with primary amenorrhea, lack of secondary sexual characteristics, short stature, low body mass index due to hy...
INTRODUCTION: Morsier Syndrome is a rare congenital malformation, characterized by hypoplasia / a... more INTRODUCTION: Morsier Syndrome is a rare congenital malformation, characterized by hypoplasia / aplasia of the septum pellucidum and hypoplasia / aplasia of the optic nerves, in addition to pituitary and hypothalamic hormonal deficiencies. Klinefelter Syndrome is a sexual chromosomal genetic alteration, a frequent cause of male hypogonadism, The association of Morsier syndrome and Klinefelter is described below. CLINICAL CASE We report he case of a 12 year-old boy with psychomotor retardation and nystagumsho presented at 14 months of age with growth hormone deficiency (low weight and height,) and diabetes insipuidus with hypernatremia of of 159 mEq and low urinary density (less than 1,005). MRI showed an absence of septum pellucidum, thick right frontal cortical dysplasia with asymmetric appearance of the grooves, small optic chiasma, hypoplastic pitutary gland (3 mm height), compatible with Morsier syndrome. The physical examination draws attention to tall stature, and long lower l...
Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are associated with similar type 2 d... more Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are associated with similar type 2 diabetes mellitus (T2DM) resolution rates for morbidly obese subjects. However, the mechanisms underlying the resolution of T2DM after SG have not been clarified to date. This study aimed to compare the early changes in gastrointestinal hormones involved in insulin and glucagon secretion in morbidly obese T2DM subjects undergoing SG or RYGBP. This prospective study investigated 12 subjects with T2DM who had undergone SG (n = 6) or RYGBP (n = 6). Five body mass index (BMI)-matched obese non-diabetic subjects and five BMI-matched obese diabetic subjects served as control subjects. Glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and GLP-2 were determined after a standardized mixed liquid meal before surgery and 6 weeks afterward. After 6 weeks, five of the six subjects in each surgical group presented with T2DM remission, although the area under the curve (AUC)0–120 of glucose was greater than that of the non-diabetic control subjects (P < 0.01). Postsurgically, the indices of insulin and glucagon secretion were comparable between the two surgical groups. The AUC0–120 of GLP-1 (P < 0.05) and GLP-2 (P < 0.05) was significantly and comparably enlarged after SG and RYGB. The postsurgical GIP response was significantly associated with the glucagon response throughout the meal test (ρ = 0.747; P < 0.01). The data show that in a cohort of morbidly obese T2DM subjects, SG and RYGBP are associated with an early improvement in glucose tolerance, similar changes in insulin and glucagon secretion, and a similar GLP-1, GIP, and GLP-2 response to a standardized mixed liquid meal.
The objective of this study was to evaluate the association between the metabolic syndrome (MS) a... more The objective of this study was to evaluate the association between the metabolic syndrome (MS) and vitamin D [25(OH)D] or parathyroid hormone (PTH) levels in severely obese subjects. Cross-sectional study in 298 severely obese patients [body mass index (BMI) 46.7 +/- 5.3 kg/m2; women/men, 70.4/29.6%; age 42.9 +/- 10.6 years]. Logistic and stepwise regression models were fit to estimate the odds for the MS (revised ATPIII criteria) and each of its individual components across quartiles of 25(OH)D and PTH after adjusting for age (years), gender, BMI, %FM, and season of blood sample collection. Insufficient 25(OH)D and elevated PTH plasma levels were encountered, respectively, in 64.3 and 47.4% of the studied subjects. The prevalence of MS was 79.5%. In the unadjusted analysis, those in the highest quartile of 25(OH)D were less likely to present the MS [0.42 (95% CI 0.19-0.96)], hyperglycemia [0.47, (0.24-0.92)], high triglycerides [0.48 (0.25-0.95)], low HDL-cholesterol [1.51 (0.76-2.98)], and high blood pressure [0.35 (0.16-0.77)]. Nonetheless, these odds ratios lost significance after adjustment for age, gender, BMI, fat mass, and season. Backward stepwise regression analysis showed that only male gender [2.66 (1.16-6.10)] and age [1.07 (1.03-1.10)] were predictive variables for the MS. We did not find an association between the PTH quartiles and the MS or its individual components. Our data are consistent with previous reports on the high prevalence of alterations in calcium metabolism in severely obese subjects. However, our data do not support an independent contribution of 25(OH)D or PTH in the pathogenesis of the MS in severely obese subjects.
Data on the effectiveness of sleeve gastrectomy in improving or resolving type 2 diabetes mellitu... more Data on the effectiveness of sleeve gastrectomy in improving or resolving type 2 diabetes mellitus (T2DM) and the metabolic syndrome (MS) are scarce. A twelve-month prospective study on the changes in glucose homeostasis and the MS in 91 severely obese T2DM subjects undergoing laparoscopic SG (SG; n = 39) or laparoscopic Roux-en-Y gastric bypass (GBP; n = 52), matched for DM duration, type of DM treatment, and glycemic control was conducted. At 12 months after surgery, subjects undergoing SG and GBP lost a similar amount of weight (%EBL: SG: 63.00 +/- 2.89%, BPG: 66.06 +/- 2.34%; p = 0.413). On that evaluation, T2DM had resolved, respectively, in 33 out of 39 (84.6%) and 44 out of 52 (84.6%) subjects after SG and GBP (p = 0.618). The rate of resolution of the MS (SG: 62.2%, BPG: 67.3%; p = 0.392) was also comparable. A shorter DM duration (p < 0.05), a DM treatment not including pharmacological agents (p < 0.05), and a better glycemic control (p < 0.05), were significantly associated with T2DM resolution in both surgical groups. Weight loss was not associated with T2DM resolution after SG or GBP, but was associated with resolution of the MS following the two surgical procedures (p < 0.05). Our data show that at 12 months after surgery, SG is as effective as GBP in inducing remission of T2DM and the MS. Furthermore, our data suggest that SG and GBP represent a successful an integrated strategy for the management of the different cardiovascular risk components of the MS in subjects with T2DM.
The metabolic syndrome (MS), a cluster of metabolic abnormalities with insulin resistance as its ... more The metabolic syndrome (MS), a cluster of metabolic abnormalities with insulin resistance as its central component, is increasing in prevalence and is associated with an increased risk of cardiovascular disease and Type 2 diabetes mellitus (T2DM). Current evidence supports an aggressive intervention approach that comprises lifestyle modification in conjunction with drug treatment of the MS components. Healthier eating and regular exercise greatly reduce waistline and body mass index, lower blood pressure and improve lipid profile. Lifestyle modification has been proven to prevent T2DM development. Nevertheless, appropriate treatment of MS components often requires pharmacologic intervention with insulin-sensitizing agents, such as metformin and thiazolidinediones, while statins and fibrates, or angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the first-line lipid-modifying or antihypertensive drugs. Only severely obese patients require specific drug treatments. Very often, drug combinations will be necessary to manage multiple risk factors. As we progress in the understanding of the pathophysiology of the MS, new targets for therapies will probably be identified and new treatments will prove to be even more efficacious than those currently available for the management of this life-threatening condition.
Few randomized studies have focused on the optimal management of non-ICU patients with type 2 dia... more Few randomized studies have focused on the optimal management of non-ICU patients with type 2 diabetes in Latin America. We compared the safety and efficacy of a basal bolus regimen with analogs and human insulins in general medicine patients admitted to a University Hospital in Asuncion, Paraguay. In a prospective, open-label trial, we randomized 134 non-surgical patients with blood glucose (BG) between 140-400 mg/dL to a basal bolus regimen with glargine once daily and glulisine before meals (n=66) or NPH twice daily and regular insulin before meals (n=68). Major outcomes included differences in daily BG levels and frequency of hypoglycemic events between treatment groups. There were no differences in the mean daily BG (157±37 mg/dL vs. 158±44 mg/dL, p=0.9) or in the number of BG readings within target <140 mg/dl before meals (76% vs. 74%) between the glargine/glulisine and NPH/regular regimens. The mean insulin dose in the glargine/glulisine was 0.76±0.3 U/kg/day (glargine 22±9 U/day, glulisine 31±12 U/day) was no different to NPH/regular (0.75±0.3 U/kg/day [NPH 28±12 U/d, regular 23±9 U/day]). The overall prevalence of hypoglycemia (<70 mg/dl) was similar between patients treated with NPH/regular and glargine/glulisine (38% vs. 35%, p=0.68), but more patients treated with human insulin had severe (<40 mg/dL) hypoglycemia (7.6% vs. 25%, p=0.08). There were no differences in length of hospital stay or mortality between groups. Basal bolus regimen with insulin analogs resulted in equivalent glycemic control and frequency of hypoglycemia compared to treatment with human insulin in hospitalized patients with diabetes.
Introduction: Thyrotropinomas are rare pituitary adenomas, representing 2% of pituitary tumors. T... more Introduction: Thyrotropinomas are rare pituitary adenomas, representing 2% of pituitary tumors. They are characterized by autonomous secretion of thyrotropin (TSH) and elevated levels of peripheral hormones. A third can secrete other hormones, including growth hormone (GH). We present the case of a patient with hypersecretion TSH and GH with clinical manifestations. Clinical case: 44-year-old woman with a history of palpitations and weight loss of 8 kilos of 3 months of evolution, as well as decreased visual acuity and headache. Physical exam: tachycardia, fine tremor, prognathism, thickening of the lips, increase in the base of the nose, hands and feet. TSH; 8.8mU / L (0.4-4), FT4: 35.59pg / ml (8-17), GH: 3.93 (less than 1.88), IGF-1: 716ng / ml (101-267), ANTI TPO negative, FSH, LH, Estradiol, Prolactin, Cortisol in range. Thyroid profile is repeated: TSH: 12.92mIU / ml (0.34-4.94); FT4 and T3 high. Campimetry: left temporal hemianopia Pituitary MRI: a heterogeneous 51x42x47mm Tu...
The patient is a 54-year-old male with type 2 diabetic treated with insulin who presented with a ... more The patient is a 54-year-old male with type 2 diabetic treated with insulin who presented with a two-week history of fever nausea and vomiting. He subsequently developed seizure episodes with changes in mental status prompting a visit to the emergency room. Upon admission the patient was hypotensive and lethargic. After an initial improvement, he developed polyuria (14-15 liters per day) in the context of eunatremia and specific gravity of 1010. His initial evaluation revealed a serum a.m. cortisol of 1.2 mcg/dL (6.2 to 19.4), low free T4 of 0.64 Ng/dl) 0.9-1.7) and secondary hypogonadism with a total testosterone of less than 2.5 ng/dL (181-772). Hormonal replacement was initiated. MRI of the brain revealed heterogeneous sellar lesion measuring 2.1 x 2.0 x 2.0 cm with peripheral enhancement following contrast administration and deviation of the pituitary stalk to the right. The lesion invaded the left cavernous sinus (Knosp III) and abutted the optic chiasm. He underwent an unevent...
Pituitary stalk interruption syndrome presenting as primary amenorrhea. The pituitary stalk inter... more Pituitary stalk interruption syndrome presenting as primary amenorrhea. The pituitary stalk interruption syndrome is a rare congenital defect that is characterized by the absence or thinning of the pituitary stalk, an absent or ectopic posterior pituitary lobe, and hypoplasia or aplasia of the anterior lobe. The clinical presentation is variable. It is usually diagnosed in the neonatal period due to the clinical manifestations that arise as a consequence of hormonal deficiencies. However some patients are diagnosed at a latter stage in life. Growth hormone deficiency it is observed in virtually all patients and can be associated to other anterior pituitary hormonal deficiencies. There is a high frequency of associated extra-pituitary malformations including those involving the central nervous system and the craniofacial structures. We report the case of a 19-year-old woman with primary amenorrhea, lack of secondary sexual characteristics, short stature, low body mass index due to hy...
INTRODUCTION: Morsier Syndrome is a rare congenital malformation, characterized by hypoplasia / a... more INTRODUCTION: Morsier Syndrome is a rare congenital malformation, characterized by hypoplasia / aplasia of the septum pellucidum and hypoplasia / aplasia of the optic nerves, in addition to pituitary and hypothalamic hormonal deficiencies. Klinefelter Syndrome is a sexual chromosomal genetic alteration, a frequent cause of male hypogonadism, The association of Morsier syndrome and Klinefelter is described below. CLINICAL CASE We report he case of a 12 year-old boy with psychomotor retardation and nystagumsho presented at 14 months of age with growth hormone deficiency (low weight and height,) and diabetes insipuidus with hypernatremia of of 159 mEq and low urinary density (less than 1,005). MRI showed an absence of septum pellucidum, thick right frontal cortical dysplasia with asymmetric appearance of the grooves, small optic chiasma, hypoplastic pitutary gland (3 mm height), compatible with Morsier syndrome. The physical examination draws attention to tall stature, and long lower l...
Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are associated with similar type 2 d... more Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are associated with similar type 2 diabetes mellitus (T2DM) resolution rates for morbidly obese subjects. However, the mechanisms underlying the resolution of T2DM after SG have not been clarified to date. This study aimed to compare the early changes in gastrointestinal hormones involved in insulin and glucagon secretion in morbidly obese T2DM subjects undergoing SG or RYGBP. This prospective study investigated 12 subjects with T2DM who had undergone SG (n = 6) or RYGBP (n = 6). Five body mass index (BMI)-matched obese non-diabetic subjects and five BMI-matched obese diabetic subjects served as control subjects. Glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and GLP-2 were determined after a standardized mixed liquid meal before surgery and 6 weeks afterward. After 6 weeks, five of the six subjects in each surgical group presented with T2DM remission, although the area under the curve (AUC)0–120 of glucose was greater than that of the non-diabetic control subjects (P < 0.01). Postsurgically, the indices of insulin and glucagon secretion were comparable between the two surgical groups. The AUC0–120 of GLP-1 (P < 0.05) and GLP-2 (P < 0.05) was significantly and comparably enlarged after SG and RYGB. The postsurgical GIP response was significantly associated with the glucagon response throughout the meal test (ρ = 0.747; P < 0.01). The data show that in a cohort of morbidly obese T2DM subjects, SG and RYGBP are associated with an early improvement in glucose tolerance, similar changes in insulin and glucagon secretion, and a similar GLP-1, GIP, and GLP-2 response to a standardized mixed liquid meal.
The objective of this study was to evaluate the association between the metabolic syndrome (MS) a... more The objective of this study was to evaluate the association between the metabolic syndrome (MS) and vitamin D [25(OH)D] or parathyroid hormone (PTH) levels in severely obese subjects. Cross-sectional study in 298 severely obese patients [body mass index (BMI) 46.7 +/- 5.3 kg/m2; women/men, 70.4/29.6%; age 42.9 +/- 10.6 years]. Logistic and stepwise regression models were fit to estimate the odds for the MS (revised ATPIII criteria) and each of its individual components across quartiles of 25(OH)D and PTH after adjusting for age (years), gender, BMI, %FM, and season of blood sample collection. Insufficient 25(OH)D and elevated PTH plasma levels were encountered, respectively, in 64.3 and 47.4% of the studied subjects. The prevalence of MS was 79.5%. In the unadjusted analysis, those in the highest quartile of 25(OH)D were less likely to present the MS [0.42 (95% CI 0.19-0.96)], hyperglycemia [0.47, (0.24-0.92)], high triglycerides [0.48 (0.25-0.95)], low HDL-cholesterol [1.51 (0.76-2.98)], and high blood pressure [0.35 (0.16-0.77)]. Nonetheless, these odds ratios lost significance after adjustment for age, gender, BMI, fat mass, and season. Backward stepwise regression analysis showed that only male gender [2.66 (1.16-6.10)] and age [1.07 (1.03-1.10)] were predictive variables for the MS. We did not find an association between the PTH quartiles and the MS or its individual components. Our data are consistent with previous reports on the high prevalence of alterations in calcium metabolism in severely obese subjects. However, our data do not support an independent contribution of 25(OH)D or PTH in the pathogenesis of the MS in severely obese subjects.
Data on the effectiveness of sleeve gastrectomy in improving or resolving type 2 diabetes mellitu... more Data on the effectiveness of sleeve gastrectomy in improving or resolving type 2 diabetes mellitus (T2DM) and the metabolic syndrome (MS) are scarce. A twelve-month prospective study on the changes in glucose homeostasis and the MS in 91 severely obese T2DM subjects undergoing laparoscopic SG (SG; n = 39) or laparoscopic Roux-en-Y gastric bypass (GBP; n = 52), matched for DM duration, type of DM treatment, and glycemic control was conducted. At 12 months after surgery, subjects undergoing SG and GBP lost a similar amount of weight (%EBL: SG: 63.00 +/- 2.89%, BPG: 66.06 +/- 2.34%; p = 0.413). On that evaluation, T2DM had resolved, respectively, in 33 out of 39 (84.6%) and 44 out of 52 (84.6%) subjects after SG and GBP (p = 0.618). The rate of resolution of the MS (SG: 62.2%, BPG: 67.3%; p = 0.392) was also comparable. A shorter DM duration (p < 0.05), a DM treatment not including pharmacological agents (p < 0.05), and a better glycemic control (p < 0.05), were significantly associated with T2DM resolution in both surgical groups. Weight loss was not associated with T2DM resolution after SG or GBP, but was associated with resolution of the MS following the two surgical procedures (p < 0.05). Our data show that at 12 months after surgery, SG is as effective as GBP in inducing remission of T2DM and the MS. Furthermore, our data suggest that SG and GBP represent a successful an integrated strategy for the management of the different cardiovascular risk components of the MS in subjects with T2DM.
The metabolic syndrome (MS), a cluster of metabolic abnormalities with insulin resistance as its ... more The metabolic syndrome (MS), a cluster of metabolic abnormalities with insulin resistance as its central component, is increasing in prevalence and is associated with an increased risk of cardiovascular disease and Type 2 diabetes mellitus (T2DM). Current evidence supports an aggressive intervention approach that comprises lifestyle modification in conjunction with drug treatment of the MS components. Healthier eating and regular exercise greatly reduce waistline and body mass index, lower blood pressure and improve lipid profile. Lifestyle modification has been proven to prevent T2DM development. Nevertheless, appropriate treatment of MS components often requires pharmacologic intervention with insulin-sensitizing agents, such as metformin and thiazolidinediones, while statins and fibrates, or angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the first-line lipid-modifying or antihypertensive drugs. Only severely obese patients require specific drug treatments. Very often, drug combinations will be necessary to manage multiple risk factors. As we progress in the understanding of the pathophysiology of the MS, new targets for therapies will probably be identified and new treatments will prove to be even more efficacious than those currently available for the management of this life-threatening condition.
Few randomized studies have focused on the optimal management of non-ICU patients with type 2 dia... more Few randomized studies have focused on the optimal management of non-ICU patients with type 2 diabetes in Latin America. We compared the safety and efficacy of a basal bolus regimen with analogs and human insulins in general medicine patients admitted to a University Hospital in Asuncion, Paraguay. In a prospective, open-label trial, we randomized 134 non-surgical patients with blood glucose (BG) between 140-400 mg/dL to a basal bolus regimen with glargine once daily and glulisine before meals (n=66) or NPH twice daily and regular insulin before meals (n=68). Major outcomes included differences in daily BG levels and frequency of hypoglycemic events between treatment groups. There were no differences in the mean daily BG (157±37 mg/dL vs. 158±44 mg/dL, p=0.9) or in the number of BG readings within target <140 mg/dl before meals (76% vs. 74%) between the glargine/glulisine and NPH/regular regimens. The mean insulin dose in the glargine/glulisine was 0.76±0.3 U/kg/day (glargine 22±9 U/day, glulisine 31±12 U/day) was no different to NPH/regular (0.75±0.3 U/kg/day [NPH 28±12 U/d, regular 23±9 U/day]). The overall prevalence of hypoglycemia (<70 mg/dl) was similar between patients treated with NPH/regular and glargine/glulisine (38% vs. 35%, p=0.68), but more patients treated with human insulin had severe (<40 mg/dL) hypoglycemia (7.6% vs. 25%, p=0.08). There were no differences in length of hospital stay or mortality between groups. Basal bolus regimen with insulin analogs resulted in equivalent glycemic control and frequency of hypoglycemia compared to treatment with human insulin in hospitalized patients with diabetes.
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