Clinicoradiological Parameters and Biochemical and Molecular Alterations Predicting Remission and Recurrence After Surgical Treatment of Corticotroph Adenomas-Cushing Disease.

OBJECTIVE: Endonasal endoscopic transsphenoidal surgery (TSS) and resection of pituitary adenomas are considered the gold standard treatment for Cushing disease (CD). Even with various recent advances in management, disease persistence and recurrence are common in these patients. The remission rate in the global population after surgery has been reported to vary widely from 64% to 93%. This study aims to determine the various clinical, biochemical, radiological, and histological factors that correlate with persistence and recurrence in patients with CD. This study also aims to understand the clinicopathological significance of EGFR-MAPK, NF-κB, and SHH pathway activation and to study the protein expression of activation markers of these pathways (i.e., c-Fos, c-Jun, GLI-1, pMEK, NR4A1, and p44) in functioning corticotroph pituitary adenomas. METHODS: From January 2009 to September 2022, the clinical data of 167 patients who underwent surgical treatment (n = 174 surgeries) for CD with a median follow-up of 8.1 years (range, 1-13.29 years) were ambispectively analyzed. The preoperative clinical, biochemical, and radiological features, operative findings, postoperative clinical and biochemical data, and histopathological and molecular profiles were retrieved from the electronic medical records. The patients were followed up to assess their remission status. RESULTS: Among the 174 surgeries performed, 140 were primary surgeries, 22 were revision surgeries, 24 surgeries were for pediatric patients, and 12 surgeries were for patients with Nelson syndrome. In the primary surgery cohort, 74.3% were female, and the average age was 28.73 ± 10.15 years. Of the primary surgery cohort, 75% of the patients experienced remission compared with 47.4% after revision surgery. The remission rate for the pediatric patients was 55.5%. The postoperative day 1 plasma cortisol (P < 0.001; area under the curve, 0.8894; range, 0.8087-0.9701) and adrenocorticotropic hormone (P < 0.001; area under the curve, 0.9; range, 0.7386-1) levels were seen to be strong independent predictors of remission in the primary surgery cohort. The remission rate after endoscopic TSS was greater than that after microscopic TSS in patients undergoing primary surgery (81.08% vs. 57.14%; P = 0.008). The presence of adenoma on histopathological examination (HPE) was also a strong predictor of disease remission (P = 0.020). On stratifying by surgical approach and HPE, microscopically operated patients without histopathological evidence of adenoma had significantly higher odds of nonremission (odds ratio, 38.1; 95% confidence interval, 4.2-348.3) compared with endoscopically operated patients with adenoma found on HPE. A lower immunoreactivity score for NR4A1 was found to correlate with higher remission rates (P = 0.074). However, none of the molecular markers studied (i.e., c-Fos, c-Jun, GLI-1, pMEK, and p44) showed a significant correlation with the preoperative cortisol values. CONCLUSIONS: The remission rate after primary surgery is higher than that after revision surgery and is lower for pediatric patients than for adults. The postoperative day 1 plasma cortisol and adrenocorticotropic hormone levels are strong independent predictors of remission in the primary surgery cohort. An endoscopic approach with histopathological evidence of adenoma is associated with a higher remission rate; thus, endoscopy should be the approach of choice for these patients with the goal of identification of an adenoma on HPE.

Role of 18Fluorocholine Positron Emission Tomography/Computed Tomography in the Localization of Culprit Lesions in Patients of Persistent/Recurrent Primary Hyperparathyroidism: A Prospective Study in COVID Times.

Introduction: Recurrent/persistent primary hyperparathyroidism in patients who have undergone previous parathyroidectomy is a challenging condition. Imaging is important for localizing the parathyroid adenoma for re-exploration and 18F-Fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) seems ideal for this purpose. Aim: This prospective study attempted to ascertain the utility of 18F-FCH PET/CT as an investigation in preoperative localization of abnormal parathyroid tissue in recurrent/persistent primary hyperparathyroidism while comparing it with 99mTc-Sestamibi dual-phase scintigraphy with early single-photon emission CT (SPECT)/CT and neck ultrasonography (USG). Methods: Twenty patients with biochemical features of recurrent/persistent primary hyperparathyroidism were enrolled into this study. They underwent neck USG, 99mTc-Sestamibi dual-phase scintigraphy with early SPECT/CT and 18F-FCH PET/CT for localization of parathyroid lesions. Six patients underwent surgical resection of the detected lesions, 3 were awaiting surgery, and 11 were managed conservatively. One patient died due to COVID. Results: The calculated positive predictive values on a per-lesion basis of neck USG, 99mTc-sestamibi scintigraphy and early SPECT/CT and 18F-FCH PET/CT in the cohort of the 5 operated patients were 75% (3/4), 71.4% (5/7), and 71.4% (5/7), respectively. On a per-patient basis, the lesion detection rate was 100% for 99mTc-sestamibi scan and FCH PET (5/5) and 80% on neck USG (4/5). Conclusion: 18F-FCH PET/CT is a highly accurate imaging modality for the detection of parathyroid lesions in patients with recurrent/persistent primary hyperparathyroidism.

Comparison of Neck Ultrasonography, Dual Phase 99mTc-Sestamibi with early SPECT-CT & 18F-Fluorocholine PET-CT as First Line Imaging in Patients with Primary Hyperparathyroidism.

Introduction: Successful surgical treatment for primary hyperparathyroidism requires accurate localization of abnormal parathyroid tissue in terms of location and number. Imaging is important for localizing the parathyroid adenoma, and there has been significant interest in 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) for this purpose. Aim: This study attempted to ascertain the utility of 18F-FCH PET/CT as a first-line investigation in preoperative localization of abnormal parathyroid tissue in primary hyperparathyroidism, in comparison with 99mTc-sestamibi dual-phase scintigraphy with early single-photon emission computed tomography (SPECT)/CT and neck ultrasonography. Materials and Methods: Fifty-five patients with biochemical features of primary hyperparathyroidism were enrolled in this study. They underwent neck ultrasonography, 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT, and 18F-FCH PET/CT for localization of parathyroid lesions. Thirty-three patients underwent surgical resection of the detected lesions. For two patients, clinical and biochemical follow-up was used as a gold standard. Results: A total of 40 lesions were resected in the 33 patients who underwent surgery. A further two lesions were localized in two patients with clinical and biochemical follow-up as the gold standard. Of these 42 lesions, 41 were detected in preoperative imaging and 1 lesion was noted intraoperatively and resected. 41/42 lesions were detected by 18F-FCH PET/CT (detection rate: 97.6%), 33/42 by 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT (detection rate: 78.5%), and 30/42 by neck ultrasonography (detection rate: 71.4%). Conclusion: Detection rates on 18F-FCH PET/CT were superior to both 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT and neck ultrasonography in preoperative localization of parathyroid lesions in patients with primary hyperparathyroidism.

68Ga-DOTANOC PET/CT for Screening and Surveillance of Von Hippel-Lindau (VHL) disease.

Purpose: Hereditary tumor syndrome Von Hippel-Lindau (VHL) disease is characterized by various benign and malignant tumors that are known to express somatostatin receptors (SSTR). We evaluated the role of 68Ga-DOTANOC PET/CT scan in patients with positive germline mutation of the VHL gene, presented initially or on follow-up, for the detection of recurrent or synchronous/metachronous lesions. Methods: Fourteen patients (8 males; 6 females) with mean age 30 ± 9.86 years were retrospectively analyzed, were tested positive for VHL on gene dosage analysis, and underwent 68 Ga-DOTANOC PET/CT scan for disease evaluation. The number and site of lesions were determined. The tracer uptake was analyzed semi-quantitatively by calculating the maximum standardized uptake values (SUVmax) of lesion. Results: Four of the 14 patients underwent scan for initial diagnosis as baseline, 6 patients for post-therapy disease status, and 4 patients for initial diagnosis as well as follow-up evaluation of the disease. A total of 67 lesions were detected in 14 patients. The sites of lesions were cerebellar/vertebral/spinal (17; mean SUVmax = 7.85); pancreatic neuroendocrine tumor (NET) (11; mean SUVmax = 20.64); retina (3; mean SUVmax = 10.46); pheochromocytoma (10; mean SUVmax = 16.32); paragangliomas (3; mean SUVmax = 10.65); pancreatic cyst (9; mean SUVmax = 2.54); and renal cyst (8; mean SUVmax = 1.56) and miscellaneous lesions constituted 6 lesions. Conclusion: Our results show that 68 Ga-DOTANOC PET/CT may be a useful modality for screening and follow-up of associated tumors in patients with germline gene mutation for VHL. It can be used as a one-stop imaging modality for VHL patients and may substitute for separate radiological investigations, making it more convenient for patients in terms of time and cost.

Management protocol and surgical techniques for MRI-Negative Cushing's disease: a series of 6 cases.

Up to 40% of Cushing's disease (CD) patients show no evidence of an adenoma on dynamic contrast-enhanced MRI. Inferior petrosal sinus sampling (IPSS) remains the gold standard for diagnosis in these patients. Remission rates in MRI-Negative CD are far less at 50%-71%, compared with patients in whom an adenoma is identified on MRI. Endoscopic endonasal transsphenoidal surgery is the surgical approach of choice in these cases. Various adjuncts can be used to localize an adenoma. In this video, the authors highlight their additional usage of pituitary perfusion MRI for identification of the adenoma. They present their stepwise management algorithm and surgical techniques for sellar and suprasellar exploration in 6 cases of MRI-Negative CD operated on by the senior author (A.S.). The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2318.

Impact of Fluoro-Choline PET/CT in Reduction in Failed Parathyroid Localization in Primary Hyperparathyroidism.

INTRODUCTION: Accurate localization of the pathological parathyroid gland is a prerequisite for minimally invasive surgical management of hyperparathyroidism (HPT). Poor imaging or discordance in odd situations like ectopic adenomas, parathyroid hyperplasia, syndromic HPT results in localization dilemma thus causing failed parathyroidectomy. We studied the impact of Fluoro-Choline (FCH) PET/CT imaging in reduction in localization failure of parathyroid adenoma. MATERIALS AND METHODS: We did a retrospective observational study (2018-2021) of HPT among which 97 patients underwent focused parathyroidectomy (FP). All patients had undergone ultrasound imaging and 99mTc-sestaMIBI scan with early SPECT/CT (MIBI). When this preliminary imaging was doubtful or negative or multiple lesions were expected, FCH PET/CT was performed. We compared the localization accuracy of MIBI scan and FCH PET/CT with surgical outcomes as reference standard. RESULTS: MIBI scan showed overall lesion detection rate (LDR) of 88.65% in localization of pathological parathyroid gland in 97 patients. The addition of FCH PET/CT improved the overall lesion detection to 97.9%. The overall possible localization failure was reduced from 11.34 to 2.06% with the addition of FCH PET/CT (p < 0.05). Out of 97 patients of FP, 87 patients showed features of parathyroid adenoma. Single hyperplastic gland was seen in 7 patients, lipoadenoma was seen in 1 patient and 1 patient had features suggestive of parathyroiditis on histopathology. FCH PET/CT was a useful adjunct and showed significant reduction in localization failure of parathyroid adenoma.

Transcriptional modulation of inflammation, and aging in Indian obese adults following a 12-week yoga-based lifestyle intervention: A randomized controlled trial.

Introduction: Obesity is one of the major global problems in today's world, both in children, and the adult age group. Current evidence suggests obesity alters the expression of various genes related to oxidative stress, inflammation, and aging. In recent times complementary therapy like yoga-based lifestyle intervention (YBLI) is used as an adjunct therapy to modern medicine. This study examines the efficacy of 12 weeks of yoga-based lifestyle intervention with standard care (SC) on the expression of genes related to oxidative stress, inflammation, and aging in obese adults. Methods: This was a two-arm parallel randomized control trial implemented at Integral Health Clinic (IHC), an outpatient facility that regularly conducted YBLI programs for the prevention of lifestyle diseases like obesity and diabetes in the Department of Physiology, All India Institute of Medical Sciences (AIIMS), New Delhi. Blood samples at baseline and weeks 2,4, and 12 were collected from 72 adults (male n = 21; female n = 51) of age 20-45 years with a body-mass index (BMI) of 25-35 kg/m2 who were randomized to receive either a 12-week SC (n = 36) or YBLI (n = 36). SC included recommendations for the management of obesity as per Indian guidelines including a low-calorie individualized diet and physical activity. Asana (physical postures), pranayama (breathing exercises), and meditation were all part of the YBLI. Primary outcomes were relative fold change in the expression of genes associated with oxidative stress [Nuclear factor-kappa B (NF-Kappa B)], inflammation [Tumor necrosis factor-α (TNFα), interleukin-6 (IL-6)], and aging [human telomerase reverse transcriptase (TERT)] in peripheral blood mononuclear cells between the two groups at week-12. Results: There were no significant changes in fold change of TERT, IL-6, and NF-kappa B between the groups at week 12. The relative fold change of TERT was significantly greater in the YBLI group (p = <0.0001) vs the SC group at 2 weeks. The relative fold change of TNF α was significantly lower at week 12 in YBLI though the change was not continuous and reliable. Within both groups, TERT expression was significantly increased at week 2 though the change was greater in the YBLI group (p < 0.0001). TNF α gene expression was significantly lower at weeks 2 and 4, compared to baseline level, in the SC group but it increased at week 12. Conclusion: The results while did not confirm our hypothesis, are important to share with the scientific society, to be able to improve prospective study designs and find optimal time/intervention/biological marker settings for this highly important scientific field. The results are suggestive of a positive impact of YBLI and SC on the fold change of aging-related TERT gene in obesity, though the benefit was not evident till week 12. However, the results should be evaluated with caution and in light of other published studies. To better understand the positive effects of YBLI on oxidative stress, inflammation, and aging-related gene expression in obesity, larger studies are recommended.

Atypical parathyroid adenoma: Severe manifestations in an adolescent girl.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a disease that is usually diagnosed in an asymptomatic state during routine biochemical screening. It generally manifests as a sporadic disease in post-menopausal women. However, in India and developing countries, we continue to see severe skeletal and renal manifestations of the disease. CASE REPORT: Herein, we describe the case of a 16-year-old adolescent girl who presented with severe manifestations of primary hyperparathyroidism. Biochemically, she had severe parathyroid hormone (PTH)-dependent hypercalcaemia with hypophosphataemia and vitamin D deficiency (serum total Ca - 18.5 mg/dl [8.5-10.5 mg/dl], serum PO4 - 1.9 mg/dl [2.5-4.5 mg/dl], serum ALP - 2015 IU/l [80-240 IU/l], serum 25[OH]D - 19.1 ng/ml [30-100 ng/ml] and serum iPTH > 5000 pg/ml [15-65 pg/ml]). Pre-operatively, she required management with saline diuresis, bisphosphonate, and calcitonin. After surgery, the patient had severe hungry bone syndrome (serum Ca - 4.1 mg/dl, serum PO4 - 2.1 mg/dl, serum ALP > 10,000 IU/l) that required treatment with calcium infusions for almost 3 months. Although the clinical and biochemical picture was suggestive of parathyroid carcinoma, histopathology revealed atypical parathyroid adenoma with low proliferative index. Atypical parathyroid adenoma is a term applied to a neoplasm with 'worrisome' features but not fulfilling the 'absolute histopathological criteria of malignancy'. CONCLUSIONS: Atypical parathyroid adenoma, a rare cause of PHPT, may be associated with severe manifestations. Although malignancy was not discerned in the immediate post-operative period, we plan to continue long-term follow-up of the patient to look for any signs of recurrence or development of parathyroid carcinoma.

Efficacy of myo-inositol and d-chiro-inositol combination on menstrual cycle regulation and improving insulin resistance in young women with polycystic ovary syndrome: A randomized open-label study.

OBJECTIVE: To compare the effect of myo-inositol and d-chiro-inositol in combination (MI + DCI) with combined hormonal contraceptive (CHC) on menstrual cycle regulation in young Indian women with polycystic ovary syndrome (PCOS). METHODS: Seventy young women with PCOS aged 15-24 years with delayed cycles were randomized into two groups and were treated for 6 months with MI + DCI (550 + 150 mg, 3.6:1 ratio) twice a day and CHC (ethinyl estradiol 20 µg + drospirenone 3 mg) once a day. RESULTS: Spontaneous menses resumed in 28 (84.85%) young women on MI + DCI, compared with withdrawal bleeding in 34 (100%) on CHC. The mean cycle length reduced with both MI + DCI (124.54 ± 8.08 to 57.75 ± 3.00 days, P < 0.001) and CHC (105.88 ± 7.96 to 30.53 ± 2.95 days, P < 0.001). Regular menstrual cycles were established in 9 (27.27%) young women with MI + DCI (P = 0.001) and 30 (88.23%) with CHC (P < 0.001). Three months after stopping the treatment, 24 young women (85.71%) on MI + DCI and 25 (73.53%) on CHC continued to have spontaneous cycles. Anti-Müllerian hormone decreased with both the drugs (P = 0.001), whereas luteinizing hormone (P = 0.001) and testosterone (P = 0.04) decreased with CHC and homeostatic model assessment of insulin resistance (P < 0.001) with MI + DCI. CONCLUSION: Myo-inositol and d-chiro-inositol in combination (3.6:1 ratio) are effective in regularizing menstrual cycles and improving insulin resistance. TRIAL REGISTRATION: Clinical Trials Registry of India (CTRI/2018/03/012643). http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=20969&EncHid=&userName=myo-inositol.

Myoinositol versus metformin pretreatment in GnRH-antagonist cycle for women with PCOS undergoing IVF: a double-blinded randomized controlled study.

OBJECTIVE: To study the effects of myoinositol (Myo) in comparison to metformin (Met), in reducing the risk of OHSS and improving ART outcome in PCOS women undergoing IVF. DESIGN: Double-blinded randomized controlled trial (CTRI/2018/05/014196). SETTING: ART Clinic, AIIMS, New Delhi patients: 102 infertile PCOS women undergoing IVF cycles were enrolled after evaluating for eligibility and allotted as 50 in group 1 (Myo) and 52 in group 2 (Met) after randomization. INTERVENTIONS: Recruited patients received Myo 2 g twice daily (group 1) and Met 850 mg twice daily (group 2). Pre- and post-treatment clinical (menstrual pattern, BMI), hormonal profile (LH, FSH, testosterone, prolactin [PRL], and AMH), biochemical parameters (HOMA IR, fasting glucose, and insulin), ovarian with antral follicle count (AFC) and side effect profile were assessed. After 3 months of therapy, patients were recruited for IVF cycle by antagonist protocol was involving controlled ovarian stimulation, cycle monitoring, oocyte recovery, insemination of oocytes and follow up with fertilization, cleavage, transfer of good grade cleavage embryos, or blastocysts pregnancy outcomes and OHSS incidence and medications was continued until the day of OPU. MAIN OUTCOME MEASURES: Primary outcome was OHSS and clinical pregnancy rate including spontaneous, IVF, and cumulative pregnancy rate including FET. Secondary outcome was ART outcomes and the change in biochemistry and hormonal profile between groups and inter group after medications at 12 weeks. RESULTS: Incidence of OHSS (Myo 5 (10.0) (n = 50), Met 10 (20.0) (n = 50) p .07) was not statistically different between groups. Clinical pregnancy rate (Myo 18 (36.0) (n = 50), Met 9 (18.0) (n = 50) p .04) cumulative pregnancy rate including FET (Myo 16 (43.2) (n = 37) vs. Met 10) 22.7) (n = 44) p .05) and spontaneous conception (prior to IVF) Myo 13 (26.0) (n = 50), Met 6 (12.0) (n = 50) p .07) was significantly high in Myo group. No between group difference in ovarian stimulation outcomes including duration and dosage of gonadotropins, E2, P4 levels, number of follicles >14 mm on day of trigger. Number of oocytes retrieved and grade of maturity were similar between groups. Fertilization, cleavage and number of good grade embryos were significantly higher in Myo group. However, implantation rate and number of embryos for freezing were similar between groups. Myo had improvement in fasting insulin, HOMA, Sr.AMH, and SHBG suggesting decreased insulin resistance. CONCLUSIONS: Myo is equally beneficial as Met in reducing the risk of OHSS and has better ART outcome in PCOS women undergoing antagonist cycles.

Late effects in pediatric Hodgkin lymphoma survivors after uniform treatment with ABVD with or without radiotherapy.

PURPOSE: ABVD (doxorubicin, bleomycin,vinblastine, and dacarbazine) is not a standard regimen in children due to concerns regarding late effects. However, no studies have evaluated long-term toxicities of ABVD in children. METHODS: Total 154 pediatric Hodgkin lymphoma (HL) survivors uniformly treated with ABVD were clinically followed up as per institutional protocol. All participants were evaluated for cardiac, pulmonary, and thyroid function abnormalities by multigated acquisition scan (MUGA) scan, spirometry with diffusion capacity of lung for the uptake of carbon monoxide (DLCO), and thyroid profile test, respectively, at a single time point. Predictors of toxicity were also analyzed. RESULTS: The median duration of follow-up of the cohort was 10.3 years (6.04-16.8). No secondary malignant neoplasm (SMN) or symptomatic cardiac/pulmonary toxicities were detected. Nine patients (5.9%) had left ventricular ejection fraction (LVEF) <55%. Subclinical and overt hypothyroidism were observed in 78 (50.6%) and 16 (10.4%) survivors, respectively. Abnormal spirometry and reduced DLCO was observed in 43.2% and 42.0% survivors, respectively. Receiving neck radiation was significantly associated with thyroid dysfunction (odds ratio [OR] 16.04, p < .001); age ≥10 years predicted reduced DLCO (OR 4.12, p = .001). Sixty-three and 33 patients had one and two late adverse effects, respectively; receiving neck radiation predicted development of multiple late effects (proportional OR 4.72, p < 0.001). Cumulative dose of chemotherapy did not predict toxicity. CONCLUSIONS: Overall, ABVD appears safe in children at a relatively short follow-up. Long-term safety data are required before it can be adopted for treating pediatric HL patients. Children receiving neck radiation require close follow-up.

Impact of myoinositol with metformin and myoinositol alone in infertile PCOS women undergoing ovulation induction cycles - randomized controlled trial.

PURPOSE: To evaluate the benefits of myoinositol plus metformin versus myoinositol alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction cycles. MATERIALS AND METHODS: Total 116 infertile PCOS women were randomized: Group I (n = 57): metformin (1500 mg) plus myoinositol (4 g) per day; Group II (n=59): myoinositol 4 g per day. Subjects were advised to try for spontaneous conception. Those who did not conceive after three months were given three cycles of ovulation induction. Primary outcome was clinical pregnancy rate after 6 months. Secondary outcomes were improvement in metabolic and endocrine parameters, ongoing pregnancy, abortion and multiple pregnancy rate. RESULTS: Baseline demographic, metabolic and hormonal parameters were comparable in two groups. After 3 months of therapy, both study groups had comparable improvement in metabolic and hormonal parameters. After 6 months, clinical pregnancy rate was 42.0% in Group I and 45.5% Group II respectively (RR 0.92(95% CI:0.60-1.43) (p > .05). Side-effects (mainly gastrointestinal) were significantly higher in Group I than group II. CONCLUSIONS: Myoinositol (4 g) might be used alone as an insulin sensitizer to improve metabolic, hormonal and reproductive outcome in infertile PCOS women. Further studies with large numbers are warranted to confirm the role of myoinostiol as a sole insulin sensitizer.

Renal Tubular Acidosis Manifesting as Severe Metabolic Bone Disease.

Renal tubular acidosis (RTA) is a condition characterized by normal anion gap metabolic acidosis. Type 1 and type 2 RTA are the most common, and are caused by defective secretion of hydrogen ions and impaired absorption of bicarbonate, respectively. Long-standing uncorrected acidosis can lead to metabolic bone disease (MBD). Rickets and osteomalacia remain the commonest manifestations of uncorrected RTA. In addition, there can be a myriad of other skeletal manifestations like fractures, pseudofractures, secondary osteoporosis and even sclerotic bone disease. The postulated mechanism for bone involvement includes acidosis-mediated exaggerated osteoclastic bone resorption. Other contributory factors include abnormal renal handling of phosphate leading to hypophosphataemia in proximal RTA, and impaired vitamin D metabolism and action. In distal RTA, hypercalciuria and secondary hyperparathyroidism may play a key role for bone involvement. Recognizing the disease in its early course is important to prevent permanent sequelae of skeletal involvement. Most of these patients may, in fact, undergo orthopaedic interventions without primary correction of acidosis. We describe five cases who presented with MBD in varied forms. While evaluating the aetiology of MBD, they were diagnosed with RTA. Subsequently, we attempted to analyse the causes of RTA. Although the common causes were ruled out, genetic aetiology could not be ascertained due to resource constraints. RTA remains an important differential diagnosis of MBD. More awareness is required to diagnose the disease early and to treat it adequately. Our case series is an attempt to provide the clinical, biochemical and skeletal spectrum of RTA. In addition, we have attempted to provide algorithms for the approach and evaluation of RTA along with their varied causes.

Oncogenic osteomalacia due to phosphaturic mesenchymal tumour in the upper thoracic spine.

Oncogenic osteomalacia (OO) is an uncommon paraneoplastic syndrome occurring due to the presence of a tumour that oversecretes fibroblast growth factor-23, which impairs renal phosphate handling. In most cases, the tumour is a morphologically distinct entity called 'phosphaturic mesenchymal tumour' (PMT). Spinal tumours causing OO are exceedingly rare. A 55-year-old man presented with multiple bone pain and proximal muscle weakness in the lower limbs. The constellation of biochemical findings (hypophosphataemia, normocalcaemia, increased alkaline phosphatase, low-normal serum vitamin D and hyperphosphaturia) with radiographical rarefaction of the skeleton and pseudofractures led us to consider OO as a possibility. Functional imaging (68Ga DOTA-NOC positron emission tomography/CT scan) localised the tumour to the D2 vertebra. Complete surgical resection led to resolution of symptoms, improved ambulatory status, normalisation of biochemical parameters and healing of pseudofractures. PMT should be considered in the differential diagnosis of hypophosphataemic osteomalacia with hyperphosphaturia. Tumour localisation with functional imaging and complete surgical resection produces satisfactory outcome.

X-Linked Hypophosphatemic Rickets Manifesting as Sclerotic Bone Disease and Enthesopathy.

X-linked hypophosphatemic (XLH) rickets is a genetic disease caused due to the inactivation of the PHEX gene (phosphate regulating gene with homology to endopeptidase on the X chromosome). The usual presentation is with rickets and osteomalacia, and dental abscesses leading to premature loss of teeth. However, enthesopathy and sclerotic bone disease in XLH have also been reported in a few case reports. In this report, we describe the case of a 23-year-old female patient who presented to us with severe bone deformities, proximal myopathy, truncal weakness, and recent onset of pain and stiffness around the joints. She was diagnosed with XLH and was found to have severe enthesopathy along with heterotopic ossification.

46, XY complete gonadal dysgenesis with pubertal virilisation due to dysgerminoma/gonadoblastoma.

Complete gonadal dysgenesis (CGD) or Swyer syndrome is characterised by sexual infantilism in a phenotypic female with 46, XY karyotype. Patients with gonadal dysgenesis and Y-chromosome material are at a high risk of developing gonadoblastoma and dysgerminoma. A 16-year-old girl presented with progressive virilisation, poor breast development and primary amenorrhea. On evaluation, she was found to have male-range serum testosterone, large abdominopelvic mass lesion, elevated germ cell tumour markers and 46, XY karyotype. She underwent surgical excision of left gonadal mass and right streak gonad, histopathology of which revealed dysgerminoma and gonadoblastoma, respectively. A diagnosis of virilising germ cell tumour arising in the setting of 46, XY CGD was, therefore, made. This case highlights a rare presentation of 46, XY CGD and the need to consider early prophylactic gonadectomy in patients affected with this rare condition. The presence of dysgerminoma/gonadoblastoma should be suspected if a hitherto phenotypic female with CGD undergoes virilisation.

Management of Cushing's Disease: Changing Trend from Microscopic to Endoscopic Surgery.

BACKGROUND: Cushing's disease (CD) is a spectrum of clinical manifestations due to adrenocorticotropic hormone-secreting pituitary adenoma. Transsphenoidal adenomectomy remains the standard treatment. There has been a paradigm shift from microscopic to endoscopic transsphenoidal surgery in recent years. However, the efficacy of endoscopic transsphenoidal surgery has not been established. Therefore, it is of interest to determine the superiority of endoscopic transsphenoidal surgery, if any, over microscopic surgery. OBJECTIVE: To assess the efficacy of endoscopic endonasal transsphenoidal surgery for the treatment of CD and to determine the factors affecting remission. METHODS: Patients undergoing surgery for CD from 2009 to 2017 were analyzed retrospectively. Transsphenoidal resection was the preferred treatment, with recent trends in favor of the endonasal endoscopic skull base approach. Postoperative cortisol level of <2 µg/dL was taken as remission and value between 2 and 5 µg/dL as possible remission. RESULTS: In total, 104 patients operated primarily for CD were included for analysis; 47 patients underwent microscopic surgery, 55 endoscopic surgery, and 2 were operated transcranially. Remission was achieved in 76.47% of patients. In univariate analysis, factors significantly associated with remission were 1) type of surgery (P = 0.01); remission in endoscopy surgery (88.23%) is better than microscopy (56.6%); 2) postoperative day 1 morning cortisol (P = 0.004); and 3) postoperative day 1 morning ACTH (P = 0.015). In multivariate analysis, only postoperative day 1 cortisol was found to be significant predictor of remission (P = 0.02). CONCLUSIONS: Postoperative plasma cortisol level is a strong independent predictor of remission. Remission provided by endoscopy is significantly better than the microscopic approach.