USP8, USP48, and BRAF mutations differ in their genotype-phenotype correlation in Asian Indian patients with Cushing's disease.

PURPOSE: To estimate the prevalence of USP8, USP48, and BRAF mutations in patients with Cushing's disease (CD) from the Indian subcontinent, and determine their genotype-phenotype correlation. METHODS: We prospectively recruited 46 patients with CD who underwent surgery between September 2015 and July 2019 at our institute. Fresh frozen tumour tissue was obtained in all patients. Using Sanger sequencing, the presence of somatic USP8 mutations was documented and the frequency of USP48 and BRAF mutations in USP8 wild-type corticotroph adenomas was determined. Clinical, hormonal, and surgical data were then compared between USP8-, USP48- and BRAF-variant carriers and patients with wild-type tumours. RESULTS: Signature USP8 mutations were detected in 17 (37%) patients. Of the 29 USP8 wild-type adenomas, 4 (13.8%) harboured USP48 mutations, one of them being a splice-site mutation that has previously not been described. BRAF mutations were not found in any of the 29 patients. Corticotroph adenomas with USP8 mutations had a higher incidence of Crooke's hyaline change than wild-type tumours (70.6 vs. 37.9%, p = 0.032). Adenomas with USP48 mutations had a higher rate of cavernous sinus invasion than their wild-type counterparts (50 vs. 4%, p = 0.042). No other significant phenotypic difference could be established between mutant and wild-type tumours. CONCLUSIONS: The prevalence of USP8 mutations in our series of patients with CD was 37%. The prevalence of USP48 mutations in USP8 wild-type adenomas was 13.8%, including a novel splice-site mutation. BRAF mutations were not found in any USP8 wild-type tumour. USP8-mutants showed significantly more Crooke's hyaline change and USP48-mutants were more likely to demonstrate cavernous sinus invasion.

Allele-specific PCR and Next-generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India.

Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India. Through these investigations, 88.7% of the subjects with 21 hydroxylase deficiency were positive for eight CYP21A2 mutations with ASPCR. The targeted NGS assay was sensitive to pick up all the mutations identified by ASPCR. Utilizing NGS in subjects negative for ASPCR, five study subjects were homozygous positive for other CYP21A2 variants: one with a novel c.1274G>T, three with c.1451G>C and one with c.143A>G variant. One subject was compound heterozygous for c.955C>T and c.1042G>A variants identified using ASPCR and NGS. One subject suspected for a Simple Virilizing (SV) 21 hydroxylase deficiency was positive for a CYP19A1:c.1142A>T variant. CYP11B1 variants (c.1201-1G>A, c.1200+1del, c.412C>T, c.1024C>T, c.1012dup, c.623G>A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. The overall mutation positivity was 97.2%. Our results suggest that ASPCR followed by targeted NGS is a cost-effective and comprehensive strategy for screening common CYP21A2 mutations and the CAH panel of genes in a clinical setting.

Clinical Profile and Mutations Associated with Multiple Endocrine Neoplasia-Type1 (MEN1) and Their First-Degree Relatives at Risk of Developing MEN1: A Prospective Study.

Multiple Endocrine Neoplasia type-1 (MEN1) is an autosomal dominant disorder with a combined occurrence of tumours of parathyroid glands, pancreatic islets, and anterior pituitary. About 90% of these patients carry mutations in the MEN1 gene, though the spectrum is not well defined in India. Forty clinically suspected cases of MEN1 were enrolled prospectively over six years; 32 patients (23 index-cases and nine affected relatives) with≥2 classical endocrine tumours of MEN1 were considered definite, and eight were categorised as 'MEN1-like'. Details of their clinical presentation, treatment and mutational analysis including MEN1 gene, 3' and 5' untranslated regions (UTR) of MEN1, CDKN1B, and CaSR genes were collated. Asymptomatic first-degree relatives were also screened. Among the 32 definite MEN1 patients, all had primary hyperparathyroidism, 22 (68.7%) had gastroentero-pancreatic neuroendocrine tumours, and 21 (66%) had pituitary adenoma. Of the 23 definite index-cases, 13 (56.5%) carried mutations in the MEN1 gene. Five of nine affected first-degree relatives (55.5%), and four of 10 asymptomatic relatives (40%) also had MEN1 mutations. Seven of 10 MEN1 mutation-negative definite index-cases harboured p.V109G polymorphism in the CDKN1B gene. All eight MEN1-like cases were negative for mutations and large deletions in MEN1, mutations in 3' and 5' UTR of MEN1, CaSR and CDKN1B genes. The study has helped to clearly document the pattern of mutations among Indian MEN1 patients. However, the absence of MEN1 mutation in ~44% of cases and the presence of p.V109G polymorphism in CDKN1B gene raise the question whether such polymorphisms could independently contribute to pathogenesis.

Obesity Indicators and Health-related Quality of Life - Insights from a Cohort of Morbidly Obese, Middle-aged South Indian Women.

OBJECTIVE: The global prevalence of obesity is increasing and has nearly doubled in the last decade, disproportionately impacting less-developed countries. The aim of this cross-sectional study was to analyse health-related quality of life (HRQOL) in morbidly obese women attending a bariatric clinic in India, and assess potential obesity indicators that can be utilised in under-resourced settings, to better understand HRQOL of individual patients. METHODS: Anthropometric measurements were collected, including waist circumference, hip circumference, waist-hip ratio, waist-height ratio and body mass index (BMI). HRQOL was assessed using an obesity-related quality-of-life questionnaire focused on the impact of obesity on physical distress, self-esteem, sexual life and work life. RESULTS: The average BMI of study participants was 39.6 kg/m2, with an average HRQOL of 40.2%. The strongest correlation was noted between BMI and HRQOL (R2=0.16). Exploratory analyses demonstrated that patients with higher BMI quartiles had lower scores for physical impact and psychosocial impact, and higher scores for sexual health, comfort with food, and experience with dieting compared to patients in lower quartiles. CONCLUSION: In South Indian, middle-aged, morbidly obese women, HRQOL is lower than average and is highly correlated with BMI, with different BMI levels having higher impacts in different subcategories, supporting the need for an individualised therapeutic focus for each patient.

Selective perioperative steroid supplementation protocol in patients undergoing endoscopic transsphenoidal surgery for pituitary adenomas.

BACKGROUND: There is no consensus regarding the use of perioperative steroids for transsphenoidal pituitary surgery. We audited the effectiveness and safety of our selective perioperative steroid supplementation protocol in patients with pituitary adenomas. METHODS: Two hundred ninety-seven patients underwent 306 endoscopic transsphenoidal surgeries for removal of their pituitary tumors. Steroids were given to those with an impaired hypothalamic-pituitary-adrenal (HPA) axis, age ≥ 60 years, clinical apoplexy, hyponatremia, or if the pituitary gland was not preserved at surgery. We excluded 111 patients in whom the integrity of the HPA axis could not be determined. We compared the incidence of early postoperative adrenal insufficiency and complications in 135 patients with intact HPA axes who underwent surgery without steroids (group A) with 60 patients who had compromised preoperative HPA axes and received perioperative steroids (group B). In addition, we audited the total number of protocol violations during this period. RESULTS: Five patients (3.7%) in group A developed postoperative hypocortisolemia. There was no significant difference in the incidence of cerebrospinal fluid leak, diabetes insipidus, or hyponatremia between both groups. There were protocol deviations in 47 (15.4%) patients. Twenty one of these patients did not receive perioperative steroids in violation of the protocol, of whom 4 (19%) developed postoperative hypocortisolemia. CONCLUSIONS: Our steroid sparing protocol was both safe and effective. The 15% incidence of protocol deviations is a reminder that the rigorous usage of checklists is mandatory for successful clinical practice.

Postoperative Hormonal Outcomes in Patients with Large and Giant Non-functioning Pituitary Adenomas.

OBJECTIVE AND AIMS: To study hormonal axis (HA) dysfunction pre-operatively and at three months after surgery in patients with large (>3 cms) (Hardy's grade C) and giant (>4 cms) nonfunctioning pituitary adenomas (NFPA). METHODS: One hundred thirty nine patients operated between 2006 and 2017, with 3 months post-operative hormonal evaluation, were included in this retrospective study. HA damage was categorized as 0 to 3 based on number of axes (thyrotroph, corticotroph and gonadotroph) that were affected. Risk factors studied for HA dysfunction before and after surgery included duration of symptoms, size of tumor, diabetes mellitus, hypertension and extent of resection. RESULTS: Preoperatively 45 (32.3%) had no axis involvement, 34 (24.4%), 36 (25.8%) and 24 (17.2%) had one, two and three axes involvement respectively. Thyrotroph axis was affected in most patients. Tumor volume had significant correlation with preoperative pituitary dysfunction (P < 0.000). Post-operatively HA function remained same in 100 (72%), improved in only 7 (5%) and worsened in 32 (23%) of the patients. Of the 3 HA, corticotroph function worsened in most patients. None of the patients who had dysfunction in all three axes had improvement after surgery. No significant risk factors were associated with post-operative pituitary function outcomes. Persistent diabetes insipidus was noted in six (4.3%) patients. CONCLUSION: Pre-operatively anterior pituitary dysfunction is noted in nearly two-thirds of patients with large and giant NFA. Tumor volume >15 cc had significant correlation with pre-operative panhypopituitarism. Post-operatively, pituitary function remains the same in nearly three quarters of the patients. No significant risk factors were found for post-operative hormonal outcomes.

Delayed Hyponatremia Following Surgery for Pituitary Adenomas: An Under-recognized Complication.

BACKGROUND: Delayed hyponatremia is a serious complication seen after pituitary surgery. We document the incidence, presentation, outcome and risk factors for this condition. MATERIALS AND METHODS: This was a retrospective study involving 222 patients operated for nonfunctioning pituitary macroadenomas between 2007-2016. Delayed hyponatremia was defined as serum sodium <135 mmol/L, occurring after the third post-operative day. Hyponatremia was categorized as mild (134-130 mmol/L), moderate (129-125 mmol/L) and severe (<125 mmol/L). All patients received intravenous (0.9%) saline, intravenous hydrocortisone and 12g oral salt over 24 hours. Patients with severe hyponatremia were given 3% saline. RESULTS: Fifty eight patients (26%) developed delayed hyponatremia; thirty (13.5%) had severe hyponatremia. Delayed hyponatremia usually (43.1%) occurred on the seventh post-operative day (range, 3-15 days). Most patients (81%) remained asymptomatic; 11 patients developed vomiting (5), seizures (3), lethargy (1), fever (1) and paralytic ileus (1). One patient developed status epilepticus. Patients who manifest symptoms had lower sodium levels as compared to those who did not have symptoms (mean 117.7 mmol/L vs. 123 mmol/L; P < 0.01). Male gender (P = 0.002) and intra-operative CSF leak (P = 0.003) were risk factors for developing delayed hyponatremia. Other factors like, age, pre-operative cortisol levels, extent of resection and post-operative diabetes insipidus did not correlate with the occurrence of delayed hyponatremia. Patients who maintained their mean serum sodium levels >138 mmol/L (day 1-day 3) were unlikely to develop delayed hyponatremia (sensitivity, 55.2% and specificity, 83.9%), positive predictive value, 63.2% [confidence interval (CI) 48, 76.7%] and negative predictive value, 78.8% (CI 70.6, 85.5%). In most patients (57%) hyponatremia was corrected within 48 hours (h). CONCLUSIONS: We recommend routine serum sodium testing on the seventh post-operative day for all patients undergoing pituitary surgery. Most patients remain asymptomatic and unless they are detected early they can go on to develop serious complications.

Paget's Disease of Bone: An Entity Still Exists in India.

BACKGROUND: Paget's disease of bone (PDB) is uncommonly reported from India. We attempted to study the clinical and imaging features and management of participants who presented with PDB. MATERIALS AND METHODS: In this retrospective study, clinical and imaging profile, biochemistry, and treatment outcomes of participants with PDB (n = 48) were obtained. RESULTS: The mean age was 60 ± 11.3 years and 35% were women. Twenty percent were asymptomatic. Many (87%) had polyostotic involvement. Sixty percent (n = 29) underwent treatment with zoledronic acid and rest with oral bisphosphonates, and all achieved remission. CONCLUSION: Most of the pagetic participants had polyostotic disease and one-fifth were asymptomatic. All participants had disease remission following treatment.

Psychiatric Burden in the Morbidly Obese in Multidisciplinary Bariatric Clinic in South India.

BACKGROUND: Obesity is a global epidemic. Bariatric surgery is being considered as the treatment of choice in morbid obesity. Psychiatric comorbidity affects outcomes in this population. There is a dearth of data on psychiatric profile of the morbidly obese from Indian subcontinent. We studied people with morbid obesity to estimate the psychiatric burden among them and to identify factors associated for developing psychiatric disorders. METHODOLOGY: This is a cross-sectional study done in a bariatric clinic of a tertiary care teaching hospital in South India. Sixty morbidly obese patients were evaluated by psychiatrists and data from medical records were collected and analyzed. Prevalence of psychiatric disorders was estimated. They were compared with patients without psychiatric disorders using appropriate statistical tests. RESULTS: Nearly 33.33% of the patients had a psychiatric disorder. Depression and dysthymia accounted for about half of those cases. The variables that were associated with psychiatric disorders were current suicidal ideation, past self-injurious behavior, perceived poor social support, and past psychiatric history. CONCLUSION: One-third of the morbidly obese patients having psychiatric disorder is suggestive of high comorbidity. Considering this active involvement of psychiatrists in bariatric clinic would be useful.

Re-operative Surgery for Pheochromocytoma-Paraganglioma: Analysis of 13 Cases from a Single Institution.

Re-operative adrenal surgery for recurrent pheochromocytoma/paraganglioma (PCC/PGL) is a therapeutic situation not commonly encountered. The recurrence rate of pheochromocytoma is estimated to be 6.1-16.5% of patients from published retrospective series; there are no reports from the Asian continent. A retrospective analysis of the departmental database was performed on patients who had undergone surgery for PCC/PGL from January 2004 to December 2014 at the Christian Medical College Hospital, Vellore, India. Among 99 patients identified during the study period, there were 14 recurrent tumours and 13 patients underwent re-operative surgery. We located eight recurrences on the right side, three on the left side and three in the midline. All 14 recurrences were functioning, and the biochemical analysis as well as imaging studies were positive in 13 of them. The mean duration to recurrence from the time of the primary surgery was 76.3 months (range 6-180 months). Of the 89 patients who underwent their first operation at our centre, 67.4% reported for follow-up for a mean period of 25 months (range 4-132 months). Four of these required re-operation with a recurrence rate of 4.5% (4/89). The open approach was used for all but one of the recurrent tumours. Recurrence following surgery for PCC/PGL is a rarely studied though significant problem. Right adrenal tumour recurrences were most common, and all these recurrences were in the retrocaval region; this typical phenomenon may be dubbed the 'right retrocaval trap'. The reason for this was presumably due to difficult access and inadequate exposure of this area in open and laparoscopic surgery, resulting in incomplete dissection.

Outcome of Treatment for Medullary Thyroid Carcinoma-a Single Centre Experience.

We conducted this study to evaluate the demography, clinical presentation, management and outcomes of medullary thyroid carcinoma (MTC) from the Indian context. This was a retrospective study of patients with MTC managed between January 2008 and December 2016. All pertinent data was collected and the results were analysed using STATA (v.13.1). MTC accounted for 90/2022 (4.45%) patients managed with thyroid cancer during the study period. The mean age of presentation was 40 years (range 14-70 years) with 47 males and 43 females. The most common presentation included goitre with cervical lymphadenopathy seen in 60 patients (66.7%). There were 11 patients (12.2%) with systemic metastasis at presentation. Rearranged during transfection (RET) testing was performed in 71 patients and was positive in 25 (35.2%). The mutations among these patients were seen in the following codons: 634 (12), 804 (8), 790 (3) and 618 (2). Persistent hypercalcitoninemia (calcitonin > 50 pg/ml) was observed in 62/80 (77.5%) patients. Forty patients underwent a meta-iodo-benzyl-guanidine (MIBG) scan in the postoperative period, 10 were positive. The mean duration of follow-up was 32 months and 10 patients defaulted from follow-up. Sixteen patients developed metastasis during the period of follow-up while eight patients expired. The mean survival was 85.75 months (95% CI 78.7-92.7). MTC accounted for 4.5% of thyroid carcinomas in this cohort among which 35% were hereditary. Persistent hypercalcitoninemia following surgery is seen in more than 70% of patients but this does not affect survival. RET screening should be performed for all patients with MTC as curative surgery can be offered for mutation positive offspring.

Normal adrenal gland thickness on computerized tomography in an Asian Indian adult population.

CONTEXT: The size and morphology of the adrenal glands are affected by several physiological and pathological conditions. Radiologists need to be aware of the normal thickness of adrenal gland to accurately assess patients with suspected adrenal pathology. However, there is limited data on the normal size of the adrenal glands. Moreover, this has not been studied in our population. AIMS: To study the normal thickness of adrenal gland on computerized tomography (CT) in Indian adult population. SETTINGS AND DESIGN: Retrospective study in a tertiary care hospital in Southern India. SUBJECTS AND METHODS: Our study included 586 adults who underwent a CT abdominal angiogram over 15 months, and excluding patients with clinical or imaging evidence of adrenal disease. The measurements made included: the maximum thickness of the body, medial and lateral limbs, measured perpendicular to the long axis. RESULTS: The median age was 51 (range: 18-85) years. The mean maximum thickness of the adrenal body, medial, and lateral limbs were 7.2 ± 1.8, 4.1 ± 1.1, and 4.3 ± 1.1 mm on the right side and 8.8 ± 1.9, 4.7 ± 1.1, and 4.9 ± 1.3 mm on the left. The cumulative thickness of the body and the limbs were 15.6 ± 3.7 mm and 18.4 ± 3.8 mm on the right and left sides, respectively. There was a statistically significant difference in all the measurements between the right and left adrenal glands (all P values = 0.000) and between men and women, being larger in men (P value <0.05). Among our patients 27% had at least one adrenal gland body measuring ≥10 mm in thickness. CONCLUSIONS: Our study has defined the normal range of adrenal gland thickness in an Asian Indian adult population, which may be used as a baseline reference for future research and as a reference for radiological reporting.

Presurgical Screening of Fine Needle Aspirates from Thyroid Nodules for BRAF Mutations: A Prospective Single Center Experience.

OBJECTIVE: Analysis of BRAF V600E mutation in thyroid fine needle aspirates (FNA) is an important adjunct to cytology, particularly among FNA placed in the "indeterminate category." However, such a prospective evaluation of FNA obtained from patients with thyroid nodules has been lacking from India. MATERIAL AND METHODS: FNA from 277 patients were prospectively evaluated for BRAF mutations by Sanger's sequencing. A subset of 30 samples was also analyzed by pyrosequencing using the PyroMark BRAF mutation kit. RESULTS: Overall, 27.2% of FNA samples were positive for mutations including 19 (35.8%) of the 53 histologically confirmed papillary thyroid carcinoma (PTC), 2 of the 25 follicular variants of PTC, and 1 anaplastic thyroid carcinoma. Only 1 (2.7%) of the 37 samples in the atypia of undetermined significance/follicular lesion of unknown significance category was BRAF positive. The sensitivity of cytology improved marginally from 67.1% to 68.3% when evaluated with BRAF. Further, a comparison of the clinicopathological characteristics of BRAF positive and negative PTCs showed a significant association (P = 0.05) between lymph node metastasis and BRAF positivity. CONCLUSION: BRAF positivity was lower than that reported from East Asia with the test being useful in confirming malignancies among the suspicious of malignancy and malignant categories.

ECTOPIC CUSHING SYNDROME: A 10-YEAR EXPERIENCE FROM A TERTIARY CARE CENTER IN SOUTHERN INDIA.

OBJECTIVE: Ectopic adrenocorticotropic hormone (ACTH) secretion is a less common cause of Cushing syndrome and is seen in 5 to 10% of cases with endogenous hypercortisolemia. We hereby describe our experience of patients with ectopic ACTH syndrome, who have been managed over the past 10 years at a tertiary care center in Southern India. METHODS: The inpatient and outpatient records of patients from 2006 to 2015 were retrospectively reviewed. The clinical features, clinical history, biochemical values, imaging features, including radiologic findings and positron emission tomography scans, management, details of follow-up, and outcomes, were documented. We compared the biochemical findings in these patients with 20 consecutive patients with Cushing disease (Cushing syndrome of pituitary origin). RESULTS: A total of 21 patients were studied. The median age at presentation was 34 years (range, 19 to 55 years). Seven patients had thymic carcinoid, 7 had bronchial carcinoid, 3 had lung malignancies, 2 had medullary carcinoma thyroid, 1 patient had a pancreatic neuroendocrine tumor, and 1 patient had an occult source of ACTH. The most common clinical features at presentation were muscle weakness (95%), hyperpigmentation (90%), facial puffiness (76%), easy bruising (61%), edema (57%), and striae (52%). Extensive acne was seen in a large number of patients (43%). Only 3 patients (14%) had central obesity. The median 8 am cortisol was 55.5 µg/dL (range, 3.8 to 131 µg/dL), median 8 am ACTH was 207 pg/mL (range, 31.1 to 703 pg/mL), and the median 24-hour urinary free cortisol was 2,484 µg (range, 248 to 25,438 µg). Basal cortisol and ACTH, as well as midnight cortisol and ACTH level, were markedly higher in patients with ectopic Cushing syndrome as compared to patients with Cushing disease. Twelve of 21 patients had developed life-threatening infections by follow-up. Nine patients had undergone surgical intervention to address the primary tumor. However, only 1 patient exhibited a complete cure on follow-up. CONCLUSION: In our series, ectopic Cushing syndrome was most commonly seen in association with intrathoracic tumors such as bronchial or thymic carcinoid. Hyperpigmentation and proximal myopathy were frequent, while central obesity was uncommon. Early and rapid control of hypercortisolemia was important in order to prevent life-threatening infections and metabolic complications. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CT = computed tomography DOTATATE = 68Ga-DOTA-Tyr3-octreotate ECS = ectopic Cushing syndrome FDG = fluorodeoxyglucose MTC = medullary thyroid cancer NET = neuroendocrine tumor PET = positron emission tomography.

Pure endoscopic transsphenoidal surgery for functional pituitary adenomas: outcomes with Cushing's disease.

BACKGROUND: This study was performed to examine patient outcomes following pure endoscopic transsphenoidal surgery (ETS) for Cushing's disease (CD). METHOD: We studied 64 consecutive patients who underwent 69 endoscopic transsphenoidal procedures. Radiological evaluation comprised detailed examination of preoperative magnetic resonance images (MRI), including positron emission tomography (PET) for select cases. Inferior petrosal sinus sampling (IPSS) was not performed for any patient. Remission was defined by the presence of hypocortisolemia with requirement for steroid replacement therapy or eucortisolemia with suppression to <1.8 µg/dl after 1 mg dexamethasone on evaluation at least 3 months after surgery. RESULTS: Preoperative MRI was abnormal in 87.5 % of cases and included 11 macroadenomas (17.2 %). PET was used to localize the adenoma in four cases. For microadenomas, operative procedures executed were as follows: selective adenomectomy (n = 15), enlarged adenomectomy (n = 21) and subtotal/hemihypophysectomy (n = 17). Overall, pathological confirmation of an adenoma was possible in 58 patients (90.6 %). Forty-nine patients (76.6 %) developed hypocortisolemia (<5 µg/dl) in the early postoperative period. Mean follow-up was 20 months (range 6-18 months). Remission was confirmed in 79.7 % of the 59 cases followed up for >3 months and was superior for microadenomas (86.4 %) versus macroadenomas (55.6 %) and equivocal MRI adenomas (66.7 %). Postoperative CSF rhinorrhea occurred in five patients, and new endocrine deficits were noted in 17.1 % patients. A nadir postoperative cortisol <2 µg/dl in the 1st week after surgery was highly predictive of remission (p = 0.001). CONCLUSION: ETS allows for enhanced intrasellar identification of adenomatous tissue, providing remission rates that are comparable to traditional microsurgery for CD. The best predictor of remission remains induction of profound hypocortisolemia in the early postoperative period.

Evaluation of a protocol-based treatment strategy for postoperative diabetes insipidus in craniopharyngioma.

BACKGROUND: Postoperative diabetes insipidus (DI) is a significant cause of morbidity in craniopharyngiomas (CP) and its effective management improves outcome. OBJECTIVE: The objective was to determine the efficacy of a treatment protocol in the management of early postoperative DI in CP. MATERIALS AND METHODS: The quality of postoperative DI control in a prospective cohort of 26 patients treated utilizing a strict protocol (Group 1) was compared with a retrospective cohort of 34 patients (Group 2) managed without a protocol. A 6-h urine output more than 4 ml/kg/h or serum sodium (Na+) more than 145 mEq/L was diagnosed as DI. The quality of DI control was assessed by determining the incidence of serum Na+ values above 150 mEq/L or below 130 mEq/L and the incidence of wide (>10 mEq/L) intra-day fluctuations of serum Na+ levels. RESULTS: The occurrence of high and low serum Na+ levels was significantly lower in Group 1(P = 0.032). The incidence of serum Na+ exceeding 150 mEq/L on postoperative days 2 and 3 was significantly higher in Group 2 as compared with those in Group 1 (25% vs. 7.6%, P = 0.0008). Hyponatremia was more frequent in Group 2 and tended to occur on postoperative days 6, 7, and 8 (14.2% vs. 3.2%; P = 0.004). The same patients who had hypernatremia in the early part of the week later developed hyponatremia. Although the incidence of wide intra-day fluctuations (>10 mEq/L) was higher in Group 2, it did not reach statistical significance. CONCLUSION: A strict protocol based management results in better control of postoperative DI in CP.

Endocrinological outcomes following endoscopic and microscopic transsphenoidal surgery in 113 patients with acromegaly.

BACKGROUND: To describe outcomes and complications in patients undergoing transsphenoidal surgery for acromegaly using the 2010 consensus criteria for biochemical remission. METHODS: Retrospective review of 113 treatment naïve patients who underwent transsphenoidal surgery with the endoscopic (n=66) and the endonasal microscopic technique (n=47). Cure was defined if the age and sex-adjusted IGF-1 level was normal and either the basal GH was <1 ng/ml or the nadir GH was <0.4 ng/ml following oral glucose suppression at last follow-up. RESULTS: The mean age at presentation was 38.1 ± 7.1 years and 86% of tumors were macroadenomas. Adenoma sizes averaged 21.1 ± 9.7 mm, but 56% of all tumors were ≥ 2 cm in size and 43.4% were invasive. Remission rates between endoscopic and microscopic transsphenoidal surgery did not differ significantly overall (28.8% versus 36.2%). On univariate analysis, a preoperative GH level <40 ng/ml, adenoma size <20mm and non-invasiveness were predictors of remission at follow-up. Although there were no statistically significant differences in remission rates between the endoscopic and microsurgical groups, surgically induced hypopituitarism was less frequent with the former. CONCLUSIONS: We report our surgical experience with predominantly large, invasive GH adenomas using the 2010 criteria for cure. Patients with smaller, non-invasive tumors with lower preoperative GH levels are most likely to achieve remission. Outcomes with either the microscopic or endoscopic approach do not differ significantly, although the rate of surgically induced hypopituitarism may be higher with the former. Transsphenoidal surgery remains the first line of treatment for patients with acromegaly, but invasive adenomas will frequently require adjuvant therapy.

RET mutations in a large indian family with medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a tumor arising from the para follicular (C) cells of the thyroid gland and can occur either sporadically or as part of an inherited syndrome. A proportion of these cases carry an autosomal dominant mutation in the RET (REarranged during Transfection) proto-oncogene. Screening for these mutations in the affected patients and the carriers "at risk" which includes the first-degree relatives is of utmost importance for early detection and prompt treatment including prophylactic thyroidectomy in cases that harbor these mutations. RESULTS: This report presents details of screening and subsequent follow-up of a large Indian family, where the index case was found to carry p. Cys634Ser mutation involving exon 11 of the RET gene. These data are of value considering the paucity of information within the region in context of screening large families affected by these mutations.