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We report the rare occurrence of an opticochiasmatic glioblastoma multiforme 6 years following conventional radiotherapy for Cushing's disease. This article highlights the risks of collateral damage to the optic apparatus when irradiating the sellar region.

Introduction: We report a case of acute adrenal insufficiency (AAI) in a patient with antiphospholipid syndrome (APS). Case Report: A 44-year-old female patient presented to us with acute abdominal pain associated with recurrent vomiting and giddiness. On examination, her blood pressure was 80/50 mm Hg. Systemic examination was normal. Further evaluation revealed hypocortisolemia with elevated plasma adrenocorticotropin hormone indicative of primary adrenal insufficiency. Her abdominal computed tomography scan showed features of evolving bilateral adrenal infarction. Etiological work-up revealed prolonged activated thromboplastin time, which didn't correct with normal plasma, her anti-cardiolipin antibody and lupus anticoagulant were also positive. She was diagnosed to have APS with adrenal insufficiency and she was started on intravenous steroids and heparin infusion. Conclusion: AAI due to the APS can present with acute abdominal pain followed by hypotension. A high index of suspicion is needed to make the correct diagnosis and to initiate appropriate treatment.

Primary hyperparathyroidism (PHP) with pheochromocytoma and neurofibromatosis type 1 is a rare clinical association. We present a case of PHP and pheochromocytoma occurring in a 33-year-old male with familial cutaneous neurofibromatosis.

We report the results of a prospective randomized controlled trial, which looked at the incidence of postoperative diabetes insipidus (DI) following the use of three different hydrocortisone protocols, and the results of a study, on the incidence of DI and cortisol response in patients not given hydrocortisone. In study 1, 114 patients with pituitary macroadenoma were randomized into three groups: conventional dose (inj. hydrocortisone 100 mg IV 6-hourly for 3 days); intermediate dose (inj. hydrocortisone 100 mg IV 6-hourly on day 1, 100 mg IV 8-hourly on day 2, and 100 mg IV 12-hourly on day 3); low dose protocol (inj. hydrocortisone 25 mg IV 6-hourly on day 1, 25 mg IV 8-hourly on day 2 and 25 mg IV 12-hourly on day 3). Radical excision was achieved in 92 patients. The incidence of DI with the conventional dose was 52%, intermediate dose, 36% and low dose, 24% (p = 0.025). Study 2 included 16 consecutive patients with Hardy's grade A & B pituitary adenoma. These patients were randomized to receive (Group I) or not receive (Group II) hydrocortisone. Patients in Group II demonstrated normal cortisol response intraoperatively and no patient developed features of hypocortisolism; the incidence of DI in this group was 14%. The low dose hydrocortisone protocol reduced the incidence of DI by 46% when compared with the conventional dose hydrocortisone protocol. In patients with grade A and B tumour with normal preoperative cortisol levels, the use of perioperative hydrocortisone can be avoided.

Cardiac dextroposition is the horizontal displacement of the heart into the right hemithorax. We present a case with an unusual cause of cardiac dextroposition. A 75-year-old, morbidly obese woman on regular follow-up for diabetes, hypertension, and ischemic heart disease presented with complaints of a persistent cough. Her chest X-ray showed elevation of the left dome of the diaphragm and shift of the mediastinum to the right which was a new finding as compared to her previous chest X-ray taken in April 2012. Subsequent radiological examination revealed the presence of a well-defined, fat-containing mass in the left hypochondrium displacing the stomach, spleen, and transverse colon downward. She was taken up for laparotomy, and a 2 kg well-circumscribed intraperitoneal tumor was excised from the left hypochondrium. The biopsy showed a well-differentiated liposarcoma. New-onset cardiac dextroposition is usually secondary to pathology in the lungs or the pleura or the diaphragm. An intra-abdominal tumor causing cardiac dextroposition has not been reported so far.

To describe outcomes and complications in patients undergoing transsphenoidal surgery for acromegaly using the 2010 consensus criteria for biochemical remission.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 was1 ng/ml or the nadir GH was0.4 ng/ml following oral glucose suppression at last follow-up.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 level40 ng/ml, adenoma size20mm 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.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.

Phaeochromocytomas may be discovered incidentally when patients present with hypertensive crisis during general anaesthesia. A 49-year-old man underwent thyroidectomy 25 years ago and was diagnosed to have spindle cell carcinoma of the thyroid. He presented with recent onset of hoarseness of voice and was found to have a vocal cord nodule. He developed a hypertensive crisis during surgery. He was subsequently evaluated and found to have bilateral phaeochromocytoma. Further evaluation revealed a RET proto-oncogene mutation at codon 634 consistent with multiple endocrine neoplasia (MEN)-2A.

Background & objectives: Plasma and urinary metanephrines are used as screening tests for the diagnosis of phaeochromocytoma. The recommended cut-off levels are not standardized. This study was conducted to identify a cut-off level for 24 h urinary fractionated metanephrines viz. metanephrine (uMN) and normetanephrine (uNMN) using enzyme immunoassay for the diagnosis of phaeochromocytoma. Methods: Consecutive patients suspected to have phaeochromocytoma were included in the study. uMN and uNMN in 24 h urinary sample were measured using a commercial ELISA kit. Results: Overall, 72 patients were included over a period of 18 months. Twenty patients had histopathologically confirmed phaeochromocytoma and in 52 patients phaeochromocytoma was ruled out. Using the upper limit of normal stated by the assay manufacturer as the cut-off, uMN >350 μg/day had a low sensitivity and uNMN >600 μg/day had a poor specificity. By increasing the cut-off value of uNMN to twice the upper limit, specificity increased significantly without much loss in sensitivity. Combining uMN and uNMN using a cut-off twice the upper limit improved the diagnostic performance - sensitivity (95%); specificity (92.3%); positive predictive value (PPV - 82.6%); negative predictive value (NPV - 98%). In subsets of patients with a variable pretest probability for phaeochromocytoma, the PPV correlates well with the occurred of these tumors decreased, while the NPV remained at 100 per cent. Interpretation & conclusions: ELISA is a simple and reliable method for measuring uMN and uNMN. The test has a good NPV and can be used as an initial screening test for ruling out phaeochromocytoma. Each hospital will have to define the cut-off value for the assay being used, choosing a proper control population.

A number of imaging modalities have been used in the preoperative localization of insulinomas. Computed tomography (CT) is the most commonly employed modality. Endoscopic ultrasound (EUS) allows the transducer to be placed in close proximity to the pancreas, thereby yielding higher quality images, which facilitates accurate localization, minimally invasive surgery, and a lower occurrence of residual tumors, all of which contribute to a better clinical outcome.We analyzed the hospital records of all adult patients (age18 years) diagnosed with insulinoma between October 2004 and September 2010. The diagnosis was based on the clinical practice guidelines of the American Endocrine Society. We compared the sensitivities of EUS and multidetector computed tomography (MDCT) in lesion.Eighteen patients were seen over a period of 6 years, and all underwent EUS. MDCT scans were carried out in 17 patients. EUS had greater sensitivity (89%) in localizing insulinomas compared to CT (69%). In this series, the lesions that were missed on CT but picked up on EUS were smaller (12 mm, P.001). Lesions that were near mesenteric vessels and those located in the head of the pancreas were more likely to be missed on CT.EUS has a greater sensitivity in identifying and localizing insulinomas. As availability increases, EUS should be part of a preoperative insulinoma workup.

Mutation in VHL gene causes the von Hippel-Lindau (VHL) disease, a dominantly inherited familial cancer syndrome. The VHL mutation pattern includes point mutations, small deletions and large deletions. While most mutations can be identified during sequencing, large deletions often remain unnoticed in initial mutational screening. We evaluated the utility of a previously described real-time quantitative PCR (RQ-PCR) using SYBR Green for detection of larger deletions in the VHL gene and normalized the data using two reference genes with a normal copy number i.e., ZNF80 (3q13.31) and GPR15 (3q12.1). DNA sequencing was also done on all cases included in the study. SJNB-6 cell line demonstrating distal 3p loss was used as a positive control for deletion. Out of 21 individual cases included of VHL disease, 2 cases were found with partial deletion by RQ-PCR, with an exon 1 deletion, while PCR–sequencing identified 5 cases with base pair substitution and 1 with splice site variant which were not picked up by RQ-PCR. RQ-PCR proved to be fast, accurate and sensitive for identifying large deletions and can be incorporated into the routine work-up for detection of large deletions in VHL disease.

Various missense mutations in the VHL gene have been reported among patients with familial bilateral pheochromocytoma. However, the p.Arg82Leu mutation in the VHL gene described here among patients with familial bilateral pheochromocytoma, has never been reported previously in a germline configuration. Interestingly, long-term follow-up of these patients indicated that the mutation might have had little impact on the normal function of the VHL gene, since all of them have remained asymptomatic. We further attempted to correlate this information with the results obtained by in silico analysis of this mutation using SIFT, PhD-SNP SVM profile, MutPred, PolyPhen2, and SNPs&GO prediction tools. To gain, new mechanistic insight into the structural effect, we mapped the mutation on to 3D structure (PDB ID 1LM8). Further, we analyzed the structural level changes in time scale level with respect to native and mutant protein complexes by using 12 ns molecular dynamics simulation method. Though these methods predict the mutation to have a pathogenic potential, it remains to be seen if these patients will eventually develop symptomatic disease.

Objective To describe a family with hereditary paraganglioma due to a disease-causing mutation in the SDHD gene. Methods We present the clinical findings, diagnostic test results, treatment, and genetic test results in a family with hereditary paraganglioma. Results Three siblings with bilateral carotid body tumors presented at different time points and with varied clinical presentations. While the proband, a 20-year-old man, was not hypertensive and had normal urinary metanephrine and normetanephrine levels, his sister and brother had a more severe clinical picture, with hypertension in both and elevated normetanephrine levels in his brother (his brother had pheochromocytoma and 2 intra-abdominal paragangliomas). Mean age at presentation was 24 years. A 4-base pair frameshift mutation, c.337-340delGACT, was detected in exon 4 of the SDHD gene in all 3 patients. Conclusion This is the first report of the c.337340delGACT mutation being associated with hereditary paraganglioma; this report emphasizes the need to screen all at-risk first-degree relatives for the disease-causing SDHD mutation once it has been identified in an affected family member. (Endocr Pract. 2012;18:e106-e110)

We describe an endoscopic transsphenoidal excision of a GH-PRL-secreting pituitary adenoma and remodeling of frontotemporal fibrous dysplasia in a patient with McCune–Albright syndrome. Sphenoid dysplasia rendered transsphenoidal surgery challenging, but a study of the radiological anatomy and good surgical planning made this feasible. Medical therapy and radiation was required for persistent acromegaly after surgery.

Hyperthyroidism due to a thyroid stimulating hormone (TSH) pituitary adenoma is rare. We report a 29-year-old woman with thyrotoxicosis and elevated serum 3,5,3',5'-tetraiodothyronine and TSH levels that resolved after a transsphenoidal excision of the detected TSH pituitary adenoma. The diagnosis and management options in such patients are reviewed.

Hypokalaemic periodic paralysis constitutes a heterogeneous group of disorders that present with acute muscular weakness. In this analysis, we discuss the aetiological factors that appear to be more common in the Indian population.From 1995 to 2001, 31 patients presented with periodic paralysis (mean age 34.5 years, range 11-68 years). Of the 31 patients, 19 were men. The clinical and laboratory data of these patients were analysed. Patients were investigated for possible secondary causes of hypokalaemla.There were 13 patients (42%) with renal tubular acidosis, 13 with primary hyperaldosteronism (42%), 2 each with thyrotoxic periodic paralysis and sporadic periodic paralysis, and I with Gitelman syndrome. Of the 13 patients with renal tubular acidosis, 10 had proximal and 3 distal renal tubular acidosis. Three of these patients with renal tubular acidosis had Sjogren syndrome. The patients diagnosed to have renal tubular acidosis had significantly lower serum bicarbonate (18.7 [14.6] v. 29.6 [5.0] mEq/L; p0.05) and higher levels of chloride (107.5 [6.0] v. 99.5 [3.4] mEq/L; p0.05) compared with those who had primary hyperaldosteronism, although the potassium values were similar (2.4 [0.65] v. 2.26 [0.48] mEq/L; p = 0.43). All patients with primary hyperaldosteronism had hypertension at presentation and were proven to have adrenal adenomas.A significant number of patients in this study had secondary and potentially reversible causes of hypokalaemic periodic paralysis. The common causes were renal tubular acidosis and primary hyperaldosteronism. A detailed work-up for secondary causes should be undertaken in Indian patients with hypokalaemic periodic paralysis.

Paget's disease is a localized disorder of the skeleton characterized by increased osteoclastic activity. While the prevalence in the Western Population is 1-2%, the prevalence in India is not known. We studied the clinical profile, biochemical parameters, bone scans, therapeutic details and follow up data of patients with Paget's disease, attending the Endocrinology outpatient clinic in our institution.A retrospective review was done of the medical records of 51 patients seen in a tertiary referral centre in Southern India from 1995 to 2003. The data was analyzed using SPSS 9.0 software package.There were a total of 51 patients (41 male and 10 female). The mean age at presentation was 56 years and the mean duration of symptoms was 43 months. At least 6 months of follow-up was available in 31 patients and longer term (2 years) follow-up in 22 patients. The symptoms at presentation were bone pain in 65%, low backache in 37%, skeletal deformities in 33%, pathological fractures in 20%, neurogenic claudication in 4%, deafness and head enlargement in 7% and renal stones in 4% of subjects. Five patients (9.8%) were asymptomatic and were incidentally diagnosed during evaluation of an elevated alkaline phosphatase. The mean serum alkaline phosphatase (range and SD) at the time of presentation was 690 IU/L (91-3873 U/L, 698 U/L). There was no statistically significant difference in the serum alkaline phosphatase values between female and male patients (576 U/L versus 718 U/L). Polyostotic involvement was seen in 90.2% of the patients. The pattern of skeletal involvement was very similar to that described in the Western literature. Twenty patients were started on Calcitonin and of these, 13 patients were later changed over to bisphosphonates to induce remission. In all, thirty six subjects received Alendronate and of them, 31 received lower doses (10-20mg/day). All the treated patients showed a good clinical and biochemical improvement. Two patients with severe Pagetic involvement of the bone who also had neurologic symptoms (root pains in one and cauda equina lesion in the other) needed intravenous Pamidronate to obtain a rapid response in the initial phase of treatment.In our series, Paget's disease had a male predominance. The clinical presentation and the pattern of skeletal involvement was similar to the Western series. Serum alkaline phosphatase declined by 40% at 6 months of therapy and by 64% by one year of treatment in patients who were on lower doses of Alendronate (10-20 mg/day) in our series, which is similar to what has been described with conventional doses (40 mg per day) in the Western series.

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.

Background: Papillary thyroid microcarcinoma (PTMC) describes a focus of papillary thyroid cancer that is less than 1 cm in size. These tumors are frequently found on histopathological examination of thyroid specimens, operated upon for an indication other than suspected malignancy. Materials and Methods: From 2005 to 2012, 94 of 1300 thyroidectomy specimens in our institution were found to have PTMC. Of these, 77 were isolated PTMC while the others were associated with other differentiated cancers. We studied their clinicopathologic features, treatment and long-term outcome. Results: There were 18 men and 59 women (the male: female ratio was 1:3), their mean age was 44 ± 10.5 years (range: 18-72 years). Multinodular goiter was the most common indication for surgery. Malignancy was suspected in only 31.4% cases. The mean tumor size was 4.1 ± 2.3 mm. Nearly 17% cases had slightly larger tumors measuring >6 but

Introduction : Although,there are several tests available, not one of them fulfils the criteria of being an ideal screening test. Continuing the search for an ideal screening test, we explored the use of urine spot cortisol-creatinine ratio as a novel method of evaluating patients with Cushing′s syndrome. Method: A total of 35 subjects were studied and divided into 3 groups - 15 having cushings syndrome, 15 patients with obesity and 5 normal weight subjects. All patients with cushings syndrome were positive for the other screening tests. Results : The mean (standard deviation) of cortisol:creatinine ratio among the 3 groups (cushings, obese and control subjects) was 36.00(24.74), 7.01(2.73) and 3.49(2.68) respectively. Using the cutoff of 12.27 nano mol/ micro mol(based on data of normal subjects) for the urine cortisol creatinine ratio we get a sensitivity of 93.75% and a specificity of 100%. Also the positive and negative predictive value as calculated with this cutoff is 100% and 93.3% respectively. Conclusion: In this study we found that UCCR is similar in both Obese and Non Obese subjects who did not have cushings syndrome. UCCR is significantly elevated in individuals with Cushing′s syndrome as compared to those who do not have cushings syndrome. Also when a cut off of 12.27 nano mol/ micro mol was used this test had a higher sensitivity, however this test had a higher specificity at a cut off of 15.35.