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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.

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. 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. 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. 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.

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.

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.

Purpose Genotyping CYP21A2 gene is known to be extremely challenging and is not utilized as a first tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating extended panel of genes implicated in CAH. This study aims to establish a comprehensive genetic screening strategy for five genes in CAH. Methods Allele-Specific Polymerase Chain Reaction (ASPCR) for hotspot mutations in CYP21A2 gene followed by targeted Next-Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes were carried out to screen 72 clinically diagnosed CAH subjects from India. Results Utilizing ASPCR, 88.7% (n = 55/62) of the subjects suspected with 21 hydroxylase deficiency were positive for CYP21A2 hotspot mutations. Utilizing NGS, the ASPCR assay was found to highly sensitive and specific for screening these hotspot mutations. Additionally, through targeted NGS, six study subjects were 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/c.1042G > A variants identified using ASPCR and NGS. One subject suspected for a simple virilizing 21-hydroxylase deficiency was positive for a CYP19A1:c.1142A > T variant. CYP11B1 variants (c.1201-1G > A, c.1200 + 1delG, c.412C > T, c.1024C > T, c.1012dup, c.623G > A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. Conclusion With an overall mutation-positivity rate of 97.2% (140/144 alleles), ASPCR followed by a multigene targeted NGS assay has shown to be highly sensitive and specific as a cost-effective and comprehensive diagnostic tool for CAH in a clinical setting.

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).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.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 (P0.000). 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.Pre-operatively anterior pituitary dysfunction is noted in nearly two-thirds of patients with large and giant NFA. Tumor volume15 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.

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.

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.

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.

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.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).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.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.ACTH = adrenocorticotropic hormone CT = computed tomography DOTATATE =

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.

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.

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

Delayed hyponatremia is a serious complication seen after pituitary surgery. We document the incidence, presentation, outcome and risk factors for this condition.This was a retrospective study involving 222 patients operated for nonfunctioning pituitary macroadenomas between 2007-2016. Delayed hyponatremia was defined as serum sodium135 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.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; P0.01). 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 levels138 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).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.

Objective: To study the profile of Renal Tubular Acidosis (RTA) in Asian Indian patients with Primary Sjögren's Syndrome (pSS). Methods: The Electronic medical records of patients with a diagnosis of pSS seen between 2003 and 2010 at our tertiary care teaching hospital were screened for RTA. Clinical features, immunological profile, acid-base balance and electrolyte status, 25-hydroxyvitamin D (25(OH) D3) levels, histopathological changes in minor salivary gland biopsy samples and radiological findings were retrieved. RTA was diagnosed in cases of hyperchloremic metabolic acidosis with urinary pH values higher than 5.5. Those with known features suggestive of RTA including hypokalemic paralysis, hyperchloremia and nephrocalcinosis without acidosis were defined as incomplete RTA. Results: Of the 380 patients with clinically suspected pSS, 25 had RTA. The median age was 32 (18-60) years. Nineteen patients had complete RTA. Six had incomplete RTA. Only 10 patients (40%) had symptoms related to RTA at presentation. Sixteen patients (64%) had present or past history of hypokalemic paralysis. Pseudofractures were seen in 7 patients and an additional 2 had subclinical radiological osteomalacia. Majority of the patients (61.2%) had a normal 25(OH) D3 level. Those with osteomalacia had significantly lower serum phosphate, blood ph and higher alkaline phosphatase. Serum calcium and 25(OH) D3 levels were not significantly different between patients with osteomalacia and those without. Conclusion: Most patients were asymptomatic for RTA inspite of clinically overt and elicitable features. Skeletal manifestation was a common finding in patients with Sjögren and RTA, despite normal levels of 25 (OH) D3 in a majority.

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.

This study was performed to examine patient outcomes following pure endoscopic transsphenoidal surgery (ETS) for Cushing's disease (CD).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 to1.8 μg/dl after 1 mg dexamethasone on evaluation at least 3 months after surgery.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 for3 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 cortisol2 μg/dl in the 1st week after surgery was highly predictive of remission (p = 0.001).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.

Determining the mutational status of susceptibility genes including RET, VHL, SDHx (SDHB, SDHC, SDHD) among patients with pheochromocytoma/paraganglioma (PCC/PGL) is gaining importance. These genes have not been systematically characterized among patients with PCC/PGL from India. The aim of the work was to screen the most frequently mutated genes among patients with PCC/PGL to determine the frequency and spectrum of mutations seen in this region. Fifty patients with PCC/PGL treated at our tertiary care hospital between January 2010 and June 2012 were screened for mutations in susceptibility genes using an algorithmic approach. Thirty-two percent (16/50) of patients were found to be positive for mutations including mutations among RET (n=4), VHL (n=6), SDHB (n=3), and SDHD (n=3) genes. None of these patients were positive for SDHC mutations. A significant association was found between young patients with bilateral tumors and VHL mutations (p=0.002). Two of the 3 patients with extra-adrenal SDHB associated tumors, had unique mutations, viz., c.436delT (exon 5) and c.788_857del (exon 8), one of which was malignant. High frequency of mutations seen among patients in this study emphasizes the need to consider mutational analysis among Indian patients with PCC/PGL.

AIMS We have analyzed the risk factors and the impact of external beam radiotherapy (EBRT) in reducing the locoregional recurrence of parathyroid carcinoma (PTC). METHODS Various parameters such as clinical presentation, intraoperative findings, surgical methods, and usage of parafibromin were analyzed. Selected endpoints were locoregional progression-free survival and overall survival. RESULTS Three patients had local recurrence. Two of them received EBRT after the first recurrence but continued to have local recurrence. One patient was lost to follow-up. Six patients with EBRT remain asymptomatic with a locoregional progression-free survival and overall survival of 42 months. The presence of a palpable nodule in the neck, serum calcium >14 mg/dL, and intraoperative substrap adhesion (OR=9.3, 95% confidence interval, 1.76-56.1; P

The aim of this study was to determine the factors influencing the use of a transcranial (TC) approach in pituitary adenomas and suggest a decision-making tree for the surgical strategy. The data for 23 (4.6 %) patients who underwent TC surgery from amongst 494 pituitary adenomas were retrospectively analyzed. Eight factors on magnetic resonance imaging (MRI) that could predict a difficult transsphenoidal (TS) surgery were noted. Adverse findings at TS surgery leading to a 2nd stage TC surgery were documented. Eighteen of the 23 cases were giant adenomas. Thirteen patients underwent TC surgery alone or as an initial approach when combined with TS while 10 underwent 2nd stage TC surgery following a TS approach. Most cases in the first group had 3 or more radiological factors in combination with a small sella. The 2nd group had higher sellar tumor volumes and fewer unfavourable radiological factors that led to the initial use of the TS approach. A hard, fibrous consistency or a significant residue obscured from the surgeon’s view, and difficulty in hemostasis were additional factors prompting the use of a TC approach. Tumor excision ≥90 % could be achieved in 13 cases (56.5 %). Post-operative RT was administered in 12 patients. There were 2 deaths (8.7 %) and the major morbidity rate was 43 %. Despite advances in endoscopic surgery the TC approach may be required in 5 % of cases. A study of the preoperative MRI for factors that predict difficulty with the TS approach might encourage the surgeon to consider a TC surgery either as an initial approach or combined with a TS surgery.

Neurofibromatosis type 1 is the most common phakomatoses and is inherited in autosomal dominant fashion with complete penetrance. Secondary hypertension is common in these patients due to various causes including adrenal tumors. Pheochromocytoma is a rare catecholamine producing tumor seen in 0.5% to 5% of patients with neurofibromatosis. The combination of pheochromocytoma with neurofibromatosis is rarely reported in the literature. We recently encountered an elderly lady with this combination who successfully underwent adrenalectomy. We report the case for the uncommon occurrence and to highlight the relevant literature review about pheochromocytoma in neurofibromatosis.

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.

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.

Snake venom can cause local tissue damage and lead to coagulopathy, shock, neurotoxicity and acute kidney injury. Hypopituitarism is a rare complication following snake bite. It has been described following Russell's viper bite from Burma and South India. Herein we describe a patient who presented with severe thyrotoxicosis and partial hypopituitarism following snake bite.

To report a case of primary amenorrhoea and to describe an approach to evaluation.Primary amenorrhoea can be due to diverse causes and needs detailed and astute evaluation. We report the case of a 17 years old individual born and brought up as a female, who was brought to us with primary amenorrhoea. Approach to such a patient with a review of available published literature is described.After detailed history, biochemical testing, imaging and karyotyping, we found that this patient had a XY karyotype with normal uterus, fallopian tubes and vagina, but streak gonads.Swyer syndrome (46,XY gonadal dysgenesis), a sex reversal disorder characterized by a phenotypic female with non-functional streak gonads, poorly developed secondary sexual characters, primary amenorrhoea and 46,XY karyotype was diagnosed. This patient was treated with gonadectomy and sex hormone replacement.