The aims of the present systematic review were to: (1) assess the role of 18F-fluorocholine (FCH)... more The aims of the present systematic review were to: (1) assess the role of 18F-fluorocholine (FCH) positron emission tomography (PET) with computed tomography (CT) and PET with magnetic resonance imaging (MRI) in patients with biochemically known hyperparathyroidism; (2) compare the diagnostic performance of FCH PET/CT or PET/MRI with conventional morphological and functional imaging. A literature search until December 2019 was performed in the PubMed, Scopus and Web of Science databases, using the terms “choline” AND “PET” AND “hyperparathyroidism”. The search was conducted with and without the addition of filters (e.g., language: English only; type of article: original article; subjects: humans only) and selecting only articles published in the last 5 years. Twenty-three articles and 1112 patients were considered. Different FCH PET/CT acquisition protocols were adopted across the studies, using dynamic, early or delayed scans. FCH PET/CT proved more accurate than ultrasonography (U...
Untreated hypercortisolism is a fatal state, causing functional disability. Even after successful... more Untreated hypercortisolism is a fatal state, causing functional disability. Even after successful treatment, clinical recovery is slower than the biochemical one, but data about clinical results, well-being and working capacity after surgery are scarce. This retrospective study aimed at evaluating the long-term outcome of patients after adrenalectomy for ACTH-independent hypercortisolism by the analysis of the clinical results, the survival and the subjective well-being status after surgery. Clinical data in 50 patients suffering from ACTH-independent hypercortisolism and treated between 1980 and 2000 by unilateral adrenalectomy were recorded. At a mean follow-up of 134 months, 3 patients were dead. All the surviving patients were asked to self estimate the physical and psychological recovery after surgery. After surgery, 100% of patients were biochemically cured. A clinical recovery was observed in most cases: obesity in 59.6% and hypertension in 57.5%. Bone mass density (BMD) significantly improved (+20%). The long-term mortality rate did not differ from normal population. Subjectively, a full recovery was confirmed by 95.6% of the surviving patients; it was correlated with the subjective feeling of physical recovery (95.6%) and regained working ability (93.3%). Despite of biochemical and clinical cure, no subjective improvement of the psychological conditions was observed in 26.7% of cases. At long-term follow-up, most objective symptoms of Cushing's syndrome (CS) disappear; subjective health and working ability are often regained, but a psychological impairment could persist in spite of a successful treatment.
Somatostatin is a widely distributed polypeptide that modulates endocrine and exocrine secretion,... more Somatostatin is a widely distributed polypeptide that modulates endocrine and exocrine secretion, cell proliferation, and apoptosis by 5 somatostatin receptors (SSTR1-5). The inhibitory effects of somatostatin on tumor growth may be the result of its suppressing the synthesis and/or secretion of growth factors and growth-promoting hormones. Very little information is available on the effect of somatostatin analogs on adrenal tumors, so we examined SSTR expression in adrenocortical tumors and studied the effect of a somatostatin analog (SOM230) on hormone secretion and cell viability in adrenal cells. SSTR expression was analyzed by real-time PCR in 13 adrenocortical carcinomas (ACC), 24 aldosterone-producing adenomas (APA), 11 cortisol-producing adenomas (CPA), and 7 normal adrenals (NA), and verified by immunohistochemistry (IHC) in 14 samples. The effect of SOM230 on cortisol or aldosterone secretion in H295R and primary cell cultures was determined by radioimmunoassay, and its effect on viability in H295R and SW13 using the MTT test. SSTR1 and SSTR2 mRNA was expressed in 100% of adrenal tumors. Compared to NA, ACC revealed an increase in almost all SSTR, while only some APA over-expressed SSTR3 and SSTR1. CPA expressed SSTR similar to NA. IHC confirmed the mRNA expression data. At nanomolar concentrations, SOM230 inhibited hormone secretion in primary adrenal cultures and H295R cells, but had no evident effect on cell viability. The evidence of SSTR over-expression (particularly in ACC) and of hormone secretion being inhibited by SOM230 suggests a potential therapeutic role for this broad-spectrum somatostatin analog in adrenal tumors.
Background: Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic ... more Background: Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic features were redefined with the 2022 WHO classification. A total of 24 Italian institutions designed this multicenter study to specify PC incidence, describe its clinical, functional, and imaging characteristics and improve its differentiation from the atypical parathyroid tumour (APT). Methods: All relevant information was collected about PC and APT patients treated between 2009 and 2021. Results: Among 8361 parathyroidectomies, 351 patients (mean age 59.0 ± 14.5; F = 210, 59.8%) were divided into the APT (n = 226, 2.8%) and PC group (n = 125, 1.5%). PC showed significantly higher rates (p < 0.05) of bone involvement, abdominal, and neurological symptoms than APT (48.8% vs. 35.0%, 17.6% vs. 7.1%, 13.6% vs. 5.3%, respectively). Ultrasound (US) diameter >3 cm (30.9% vs. 19.3%, p = 0.049) was significantly more common in the PC. A significantly higher frequency of local recurrences ...
Liu and colleagues1 investigated the long-term clinical results of unilateral laparoscopic adrena... more Liu and colleagues1 investigated the long-term clinical results of unilateral laparoscopic adrenalectomy (LA) and a renal artery denervation (LA-RDN) performed from the adventitia in selected patients with resistant hypertension (RH) caused by unilateral aldosteroneproducing adenoma (APA). By this complex procedure, they claimed to have achieved sustained lowering of blood pressure (BP) and resolution of RH at three years follow up with LA-RDN. Moreover, owing to the lack of any periprocedural complications in their hands, they suggested that this procedurewould be safe. However, in our view, their studywas affected by several issues that question the validity of these conclusions. First, the authors stated that they used the American Heart Association definition of RH2 as the main inclusion criteria. However, from the mean number of drugs ± SD (3.57 ± .69 and 3.39 ± .50 in the LARDN and control group, respectively, shown in Table 3), it can be calculated that the 95%CI were 2.19–4.95 and 2.39–4.39, indicating that in both groups, they enrolled patients thatwere on less than three antihypertensive drugs/day. Hence, the fact that not all patients of theirs had RH, indicates an obvious inclusion bias that is relevant for their conclusions. Moreover, it should be noted that the authors reported neither the defined daily dose (DDD), nor the duration of the hypertension and the concurrence of hypertension-mediated organ damage, all factors which could influence the primary endpoint of their study, besides the patients’ outcome.Theauthors claimed the superiorityof LA-RDNover LA alone based on a decrease in the number of anti-hypertensivemedications. However, they should have reported the concomitant changes in DDD, since patients can require less drugs but higher doses of each drug to control their high BP values. Second, the authors stated that their definition of cure and remission of RH differed from that of the PASO study.3 For this reason, it would be important to describe in detail what definition of clinical cure, improvement and failure, they used what were the biochemical
Background: The prognosis of pheochromocytoma and sympathetic paraganglioma (PHEO/sPGL) is diffic... more Background: The prognosis of pheochromocytoma and sympathetic paraganglioma (PHEO/sPGL) is difficult to predict at the time of diagnosis and long-term follow-up data are scarce, especially for apparently benign and sporadic variants. The aim of the study was to analyze the long-term outcomes in PHEO/sPGL patients. Methods: A monocentric series of 170 patients who underwent surgery for PHEO/sPGL was analyzed. Results: The study cohort included 91 female and 79 males with a median age of 48 years (range 6–83). The majority of PHEO/sPGL cases were considered apparently benign at the time of diagnosis; evident malignant behavior was found in 5% of cases. The overall 10-year risk of recurrence was 13%, but it rose up to 33% at 30 years. The risk of new tumor recurrence was higher in patients with hereditary tumors, but the risk was still significant in patients with apparently sporadic variants (20-year risk: 38% vs. 6.5%, respectively; p < 0.0001). The risk of metastatic recurrence w...
Pheochromocytoma (Pheo) is a tumor derived from chromaffin cells. It can be studied using 18F-dih... more Pheochromocytoma (Pheo) is a tumor derived from chromaffin cells. It can be studied using 18F-dihydroxyphenylalanine (DOPA)—positron emission tomography (PET) due to its overexpression of L-type amino acid transporters (LAT1 and LAT2). The oncogenic pathways involved are still poorly understood. This study examined the relationship between 18F-DOPA-PET uptake and LAT1 expression, and we explored the role of miR-375 and putative target genes. A consecutive series of 58 Pheo patients were retrospectively analyzed, performing 18F-DOPA-PET in 32/58 patients. Real-time quantitative PCR was used to assess the expression of LAT1, LAT2, phenylethanolamine N-methyltransferase (PNMT), miR-375, and the major components of the Hippo and Wingless/Integrated pathways. Principal germline mutations associated with hereditary Pheo were also studied. Pheo tissues had significantly higher LAT1, LAT2, and PNMT mRNA levels than normal adrenal tissues. MiR-375 was strongly overexpressed. Yes-associated p...
The improper expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) and the G... more The improper expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) and the GIP/GIPR axis activation has been increasingly recognized in endocrine tumors, with a potential diagnostic and prognostic value. A high tumor-to-normal tissue ratio (T/N ratio) of GIPR was reported both in humans’ and in rats’ medullary thyroid cancer (MTC), suggesting a direct link between the neoplastic transformation and the mechanism of receptor overexpression. In this study, we evaluated the potential diagnostic and prognostic significance of GIPR expression in a large cohort of MTC patients by correlating GIPR mRNA steady-state levels to clinical phenotypes. The molecular effect of GIP/GIPR axis stimulation in MTC-derived cells was also determined. We detected GIPR expression in ~80% of tumor specimens, especially in sporadic, larger, advanced-stage cancers with higher Ki-67 values. GIPR stimulation induced cAMP elevation in MTC-derived cells and a small but significant fluctuation ...
Background: procalcitonin (proCt) was recently proposed as an alternative or in addition to calci... more Background: procalcitonin (proCt) was recently proposed as an alternative or in addition to calcitonin (Ct) in medullary thyroid cancer (MTC) diagnostics. Methods: serum basal Ct (bCt) and proCt (bproCt) levels were measured before surgery from a consecutive series of patients with (n=43) and without (n=75) MTC, retrospectively collected in Padua. Serum bproCt, bCt and stimulated proCt and Ct (sproCt and sCt) were measured in another consecutive series of 33 patients seen at three tertiary-level institutions underwent a calcium stimulation test prior to surgery, 20 of them with a final diagnosis of MTC, and 13 with non-MTC nodular disease. Results: median bproCt levels were higher in MTC than in non-MTC. A positive correlation was found for bproCt with bCt (P<0.01, R2=0.75), and with tumor size (P<0.01, R2=0.39). The cut-off for bproCt differentiating between MTC and non-MTC patients was >0.07 ng/ml (sensitivity: 85.7%, specificity: 98.9%, positive predictive value [PPV]: 9...
SommarioIl carcinoma paratiroideo è un tumore raro (1% dei casi di iperparatiroidismo primitivo) ... more SommarioIl carcinoma paratiroideo è un tumore raro (1% dei casi di iperparatiroidismo primitivo) e può presentarsi in modo sporadico o ereditario (nel quadro di HPT-JT Syndrome, associato a tumori mascellari). Il quadro clinico è generalmente caratterizzato da ipercalcemia grave, refrattaria al trattamento medico, severo coinvolgimento renale e osseo e, talvolta, dall’invasione delle strutture circostanti. La terapia chirurgica rappresenta il trattamento di scelta e prevede resezioni en-bloc allargate alle strutture adiacenti.
Bilateral macronodular adrenal hyperplasia (BMAH) is a relatively rare cause of Cushing's Syn... more Bilateral macronodular adrenal hyperplasia (BMAH) is a relatively rare cause of Cushing's Syndrome (CS). In recent years, growing evidence has shown that steroidogenesis is regulated by aberrant G-protein-coupled receptors (GPCRs) expression and their ligands, in a significant proportion of patients with BMAH. The screening of patients with overt or subclinical CS demonstrates the frequent expression of several GPCRs that opened the option to potential therapeutic applications. Thus, several studies have demonstrated that targeting the involved receptor with specific antagonists may result in a more or less effective control of cortisol excess. Bilateral adrenalectomy has traditionally been considered the treatment of choice for BMAH. However, unilateral adrenalectomy has been recently proposed as an alternative in selective patients to avoid the long-term necessity of gluco/mineralocorticoid replacement. Adrenal steroidogenesis inhibitors remain a valid option when medical treatment is needed due to high surgical risk.
Chen et al. [1] meta-analyzed the studies comparing radiofrequency ablation (RFA) with laparoscop... more Chen et al. [1] meta-analyzed the studies comparing radiofrequency ablation (RFA) with laparoscopic adrenalectomy (LA), which is currently held to be the gold standard for the surgical treatment of patients with primary aldosteronism (PA) due to unilateral aldosterone-producing adenoma (APA). They could include only five small non-randomized retrospective studies [2–6], and, moreover, their meta-analysis was affected by several methodological flaws and mistakes that, on the whole, question the validity of its results and the strength of its conclusions. First, prerequisites for including studies in a metaanalysis are a thorough check of their quality and exclusion of duplicated cases. The study by Chen et al. [1] fell short on both these items. They could not include any prospective randomized trial and the quality assessment score used by the Authors [7] revealed that all studies included are high quality, but the Newcastle–Ottawa score (NOS) is not appropriate as it is designed for cohort-studies and case–control studies. Moreover, of the five meta-analyzed studies two were by Liu et al. [3, 4] and included duplicated series of patients treated with RFA. Second, according to guidelines [8, 9], unilateral PA due to an aldosterone-producing adenoma should be diagnosed based on an adrenal vein sampling (AVS) showing lateralized aldosterone secretion. Oddly enough, the AVS was routinely performed in just one of the five meta-analyzed studies, [2] and therefore, the presence of unilateral and bilateral form of hyperaldosteronism could not be ascertained. Likely this worsened the outcome of adrenal ablation in both treatment groups thus blunting differences between RFA and LA. Third, on a biological plausibility ground, one cannot imagine any reasons why in lowering blood pressure (BP) a presumably total adrenal ablation achieved with RFA should surpass the certainly total adrenal ablation achieved with LA. Additionally, for the analysis of the BP outcome the Authors compared studies that reported the highest BP value measured [4] and studies that provided the mean BP values [2, 5, 6]. Moreover, the study by Liu et al. [4] considered the highest BP values at baseline and the mean BP values at follow-up, thus clearly overestimating the BP lowering effect of treatment and affecting the meta-analysis conclusions. By repeating the meta-analysis after exclusion of this study, it can be found that the reduction of systolic BP (SBP) and diastolic BP (DBP) was less different between the RFA group and the LA group. Fourth, while being limited methodologically by the fact that they rely on summary data and not on individual data, meta-analyses require a precise knowledge of the measures of spread of the variables to be meta-analyzed. Of note, in four of the five studies included in the meta-analysis, the standard deviation (SD) was not provided [2–5]. Regrettably, no information was provided on how the SDs were calculated for the mean change of key variables as SBP, DBP, and serum potassium levels (K+). Furthermore, in the four Donatella Schiavone and Viola Sanga are co-first authors and contributed equally to this work.
The aims of the present systematic review were to: (1) assess the role of 18F-fluorocholine (FCH)... more The aims of the present systematic review were to: (1) assess the role of 18F-fluorocholine (FCH) positron emission tomography (PET) with computed tomography (CT) and PET with magnetic resonance imaging (MRI) in patients with biochemically known hyperparathyroidism; (2) compare the diagnostic performance of FCH PET/CT or PET/MRI with conventional morphological and functional imaging. A literature search until December 2019 was performed in the PubMed, Scopus and Web of Science databases, using the terms “choline” AND “PET” AND “hyperparathyroidism”. The search was conducted with and without the addition of filters (e.g., language: English only; type of article: original article; subjects: humans only) and selecting only articles published in the last 5 years. Twenty-three articles and 1112 patients were considered. Different FCH PET/CT acquisition protocols were adopted across the studies, using dynamic, early or delayed scans. FCH PET/CT proved more accurate than ultrasonography (U...
Untreated hypercortisolism is a fatal state, causing functional disability. Even after successful... more Untreated hypercortisolism is a fatal state, causing functional disability. Even after successful treatment, clinical recovery is slower than the biochemical one, but data about clinical results, well-being and working capacity after surgery are scarce. This retrospective study aimed at evaluating the long-term outcome of patients after adrenalectomy for ACTH-independent hypercortisolism by the analysis of the clinical results, the survival and the subjective well-being status after surgery. Clinical data in 50 patients suffering from ACTH-independent hypercortisolism and treated between 1980 and 2000 by unilateral adrenalectomy were recorded. At a mean follow-up of 134 months, 3 patients were dead. All the surviving patients were asked to self estimate the physical and psychological recovery after surgery. After surgery, 100% of patients were biochemically cured. A clinical recovery was observed in most cases: obesity in 59.6% and hypertension in 57.5%. Bone mass density (BMD) significantly improved (+20%). The long-term mortality rate did not differ from normal population. Subjectively, a full recovery was confirmed by 95.6% of the surviving patients; it was correlated with the subjective feeling of physical recovery (95.6%) and regained working ability (93.3%). Despite of biochemical and clinical cure, no subjective improvement of the psychological conditions was observed in 26.7% of cases. At long-term follow-up, most objective symptoms of Cushing&#39;s syndrome (CS) disappear; subjective health and working ability are often regained, but a psychological impairment could persist in spite of a successful treatment.
Somatostatin is a widely distributed polypeptide that modulates endocrine and exocrine secretion,... more Somatostatin is a widely distributed polypeptide that modulates endocrine and exocrine secretion, cell proliferation, and apoptosis by 5 somatostatin receptors (SSTR1-5). The inhibitory effects of somatostatin on tumor growth may be the result of its suppressing the synthesis and/or secretion of growth factors and growth-promoting hormones. Very little information is available on the effect of somatostatin analogs on adrenal tumors, so we examined SSTR expression in adrenocortical tumors and studied the effect of a somatostatin analog (SOM230) on hormone secretion and cell viability in adrenal cells. SSTR expression was analyzed by real-time PCR in 13 adrenocortical carcinomas (ACC), 24 aldosterone-producing adenomas (APA), 11 cortisol-producing adenomas (CPA), and 7 normal adrenals (NA), and verified by immunohistochemistry (IHC) in 14 samples. The effect of SOM230 on cortisol or aldosterone secretion in H295R and primary cell cultures was determined by radioimmunoassay, and its effect on viability in H295R and SW13 using the MTT test. SSTR1 and SSTR2 mRNA was expressed in 100% of adrenal tumors. Compared to NA, ACC revealed an increase in almost all SSTR, while only some APA over-expressed SSTR3 and SSTR1. CPA expressed SSTR similar to NA. IHC confirmed the mRNA expression data. At nanomolar concentrations, SOM230 inhibited hormone secretion in primary adrenal cultures and H295R cells, but had no evident effect on cell viability. The evidence of SSTR over-expression (particularly in ACC) and of hormone secretion being inhibited by SOM230 suggests a potential therapeutic role for this broad-spectrum somatostatin analog in adrenal tumors.
Background: Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic ... more Background: Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic features were redefined with the 2022 WHO classification. A total of 24 Italian institutions designed this multicenter study to specify PC incidence, describe its clinical, functional, and imaging characteristics and improve its differentiation from the atypical parathyroid tumour (APT). Methods: All relevant information was collected about PC and APT patients treated between 2009 and 2021. Results: Among 8361 parathyroidectomies, 351 patients (mean age 59.0 ± 14.5; F = 210, 59.8%) were divided into the APT (n = 226, 2.8%) and PC group (n = 125, 1.5%). PC showed significantly higher rates (p < 0.05) of bone involvement, abdominal, and neurological symptoms than APT (48.8% vs. 35.0%, 17.6% vs. 7.1%, 13.6% vs. 5.3%, respectively). Ultrasound (US) diameter >3 cm (30.9% vs. 19.3%, p = 0.049) was significantly more common in the PC. A significantly higher frequency of local recurrences ...
Liu and colleagues1 investigated the long-term clinical results of unilateral laparoscopic adrena... more Liu and colleagues1 investigated the long-term clinical results of unilateral laparoscopic adrenalectomy (LA) and a renal artery denervation (LA-RDN) performed from the adventitia in selected patients with resistant hypertension (RH) caused by unilateral aldosteroneproducing adenoma (APA). By this complex procedure, they claimed to have achieved sustained lowering of blood pressure (BP) and resolution of RH at three years follow up with LA-RDN. Moreover, owing to the lack of any periprocedural complications in their hands, they suggested that this procedurewould be safe. However, in our view, their studywas affected by several issues that question the validity of these conclusions. First, the authors stated that they used the American Heart Association definition of RH2 as the main inclusion criteria. However, from the mean number of drugs ± SD (3.57 ± .69 and 3.39 ± .50 in the LARDN and control group, respectively, shown in Table 3), it can be calculated that the 95%CI were 2.19–4.95 and 2.39–4.39, indicating that in both groups, they enrolled patients thatwere on less than three antihypertensive drugs/day. Hence, the fact that not all patients of theirs had RH, indicates an obvious inclusion bias that is relevant for their conclusions. Moreover, it should be noted that the authors reported neither the defined daily dose (DDD), nor the duration of the hypertension and the concurrence of hypertension-mediated organ damage, all factors which could influence the primary endpoint of their study, besides the patients’ outcome.Theauthors claimed the superiorityof LA-RDNover LA alone based on a decrease in the number of anti-hypertensivemedications. However, they should have reported the concomitant changes in DDD, since patients can require less drugs but higher doses of each drug to control their high BP values. Second, the authors stated that their definition of cure and remission of RH differed from that of the PASO study.3 For this reason, it would be important to describe in detail what definition of clinical cure, improvement and failure, they used what were the biochemical
Background: The prognosis of pheochromocytoma and sympathetic paraganglioma (PHEO/sPGL) is diffic... more Background: The prognosis of pheochromocytoma and sympathetic paraganglioma (PHEO/sPGL) is difficult to predict at the time of diagnosis and long-term follow-up data are scarce, especially for apparently benign and sporadic variants. The aim of the study was to analyze the long-term outcomes in PHEO/sPGL patients. Methods: A monocentric series of 170 patients who underwent surgery for PHEO/sPGL was analyzed. Results: The study cohort included 91 female and 79 males with a median age of 48 years (range 6–83). The majority of PHEO/sPGL cases were considered apparently benign at the time of diagnosis; evident malignant behavior was found in 5% of cases. The overall 10-year risk of recurrence was 13%, but it rose up to 33% at 30 years. The risk of new tumor recurrence was higher in patients with hereditary tumors, but the risk was still significant in patients with apparently sporadic variants (20-year risk: 38% vs. 6.5%, respectively; p < 0.0001). The risk of metastatic recurrence w...
Pheochromocytoma (Pheo) is a tumor derived from chromaffin cells. It can be studied using 18F-dih... more Pheochromocytoma (Pheo) is a tumor derived from chromaffin cells. It can be studied using 18F-dihydroxyphenylalanine (DOPA)—positron emission tomography (PET) due to its overexpression of L-type amino acid transporters (LAT1 and LAT2). The oncogenic pathways involved are still poorly understood. This study examined the relationship between 18F-DOPA-PET uptake and LAT1 expression, and we explored the role of miR-375 and putative target genes. A consecutive series of 58 Pheo patients were retrospectively analyzed, performing 18F-DOPA-PET in 32/58 patients. Real-time quantitative PCR was used to assess the expression of LAT1, LAT2, phenylethanolamine N-methyltransferase (PNMT), miR-375, and the major components of the Hippo and Wingless/Integrated pathways. Principal germline mutations associated with hereditary Pheo were also studied. Pheo tissues had significantly higher LAT1, LAT2, and PNMT mRNA levels than normal adrenal tissues. MiR-375 was strongly overexpressed. Yes-associated p...
The improper expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) and the G... more The improper expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) and the GIP/GIPR axis activation has been increasingly recognized in endocrine tumors, with a potential diagnostic and prognostic value. A high tumor-to-normal tissue ratio (T/N ratio) of GIPR was reported both in humans’ and in rats’ medullary thyroid cancer (MTC), suggesting a direct link between the neoplastic transformation and the mechanism of receptor overexpression. In this study, we evaluated the potential diagnostic and prognostic significance of GIPR expression in a large cohort of MTC patients by correlating GIPR mRNA steady-state levels to clinical phenotypes. The molecular effect of GIP/GIPR axis stimulation in MTC-derived cells was also determined. We detected GIPR expression in ~80% of tumor specimens, especially in sporadic, larger, advanced-stage cancers with higher Ki-67 values. GIPR stimulation induced cAMP elevation in MTC-derived cells and a small but significant fluctuation ...
Background: procalcitonin (proCt) was recently proposed as an alternative or in addition to calci... more Background: procalcitonin (proCt) was recently proposed as an alternative or in addition to calcitonin (Ct) in medullary thyroid cancer (MTC) diagnostics. Methods: serum basal Ct (bCt) and proCt (bproCt) levels were measured before surgery from a consecutive series of patients with (n=43) and without (n=75) MTC, retrospectively collected in Padua. Serum bproCt, bCt and stimulated proCt and Ct (sproCt and sCt) were measured in another consecutive series of 33 patients seen at three tertiary-level institutions underwent a calcium stimulation test prior to surgery, 20 of them with a final diagnosis of MTC, and 13 with non-MTC nodular disease. Results: median bproCt levels were higher in MTC than in non-MTC. A positive correlation was found for bproCt with bCt (P<0.01, R2=0.75), and with tumor size (P<0.01, R2=0.39). The cut-off for bproCt differentiating between MTC and non-MTC patients was >0.07 ng/ml (sensitivity: 85.7%, specificity: 98.9%, positive predictive value [PPV]: 9...
SommarioIl carcinoma paratiroideo è un tumore raro (1% dei casi di iperparatiroidismo primitivo) ... more SommarioIl carcinoma paratiroideo è un tumore raro (1% dei casi di iperparatiroidismo primitivo) e può presentarsi in modo sporadico o ereditario (nel quadro di HPT-JT Syndrome, associato a tumori mascellari). Il quadro clinico è generalmente caratterizzato da ipercalcemia grave, refrattaria al trattamento medico, severo coinvolgimento renale e osseo e, talvolta, dall’invasione delle strutture circostanti. La terapia chirurgica rappresenta il trattamento di scelta e prevede resezioni en-bloc allargate alle strutture adiacenti.
Bilateral macronodular adrenal hyperplasia (BMAH) is a relatively rare cause of Cushing's Syn... more Bilateral macronodular adrenal hyperplasia (BMAH) is a relatively rare cause of Cushing's Syndrome (CS). In recent years, growing evidence has shown that steroidogenesis is regulated by aberrant G-protein-coupled receptors (GPCRs) expression and their ligands, in a significant proportion of patients with BMAH. The screening of patients with overt or subclinical CS demonstrates the frequent expression of several GPCRs that opened the option to potential therapeutic applications. Thus, several studies have demonstrated that targeting the involved receptor with specific antagonists may result in a more or less effective control of cortisol excess. Bilateral adrenalectomy has traditionally been considered the treatment of choice for BMAH. However, unilateral adrenalectomy has been recently proposed as an alternative in selective patients to avoid the long-term necessity of gluco/mineralocorticoid replacement. Adrenal steroidogenesis inhibitors remain a valid option when medical treatment is needed due to high surgical risk.
Chen et al. [1] meta-analyzed the studies comparing radiofrequency ablation (RFA) with laparoscop... more Chen et al. [1] meta-analyzed the studies comparing radiofrequency ablation (RFA) with laparoscopic adrenalectomy (LA), which is currently held to be the gold standard for the surgical treatment of patients with primary aldosteronism (PA) due to unilateral aldosterone-producing adenoma (APA). They could include only five small non-randomized retrospective studies [2–6], and, moreover, their meta-analysis was affected by several methodological flaws and mistakes that, on the whole, question the validity of its results and the strength of its conclusions. First, prerequisites for including studies in a metaanalysis are a thorough check of their quality and exclusion of duplicated cases. The study by Chen et al. [1] fell short on both these items. They could not include any prospective randomized trial and the quality assessment score used by the Authors [7] revealed that all studies included are high quality, but the Newcastle–Ottawa score (NOS) is not appropriate as it is designed for cohort-studies and case–control studies. Moreover, of the five meta-analyzed studies two were by Liu et al. [3, 4] and included duplicated series of patients treated with RFA. Second, according to guidelines [8, 9], unilateral PA due to an aldosterone-producing adenoma should be diagnosed based on an adrenal vein sampling (AVS) showing lateralized aldosterone secretion. Oddly enough, the AVS was routinely performed in just one of the five meta-analyzed studies, [2] and therefore, the presence of unilateral and bilateral form of hyperaldosteronism could not be ascertained. Likely this worsened the outcome of adrenal ablation in both treatment groups thus blunting differences between RFA and LA. Third, on a biological plausibility ground, one cannot imagine any reasons why in lowering blood pressure (BP) a presumably total adrenal ablation achieved with RFA should surpass the certainly total adrenal ablation achieved with LA. Additionally, for the analysis of the BP outcome the Authors compared studies that reported the highest BP value measured [4] and studies that provided the mean BP values [2, 5, 6]. Moreover, the study by Liu et al. [4] considered the highest BP values at baseline and the mean BP values at follow-up, thus clearly overestimating the BP lowering effect of treatment and affecting the meta-analysis conclusions. By repeating the meta-analysis after exclusion of this study, it can be found that the reduction of systolic BP (SBP) and diastolic BP (DBP) was less different between the RFA group and the LA group. Fourth, while being limited methodologically by the fact that they rely on summary data and not on individual data, meta-analyses require a precise knowledge of the measures of spread of the variables to be meta-analyzed. Of note, in four of the five studies included in the meta-analysis, the standard deviation (SD) was not provided [2–5]. Regrettably, no information was provided on how the SDs were calculated for the mean change of key variables as SBP, DBP, and serum potassium levels (K+). Furthermore, in the four Donatella Schiavone and Viola Sanga are co-first authors and contributed equally to this work.
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