Impact of Pheochromocytoma or Paraganglioma on Bone Metabolism: A Systemic Review and Meta-analysis.

INTRODUCTION: Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap. METHODS: Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP). RESULTS: Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2 = 0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2 = 0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); p = 0.01; I2 = 1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery. CONCLUSION: Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.

Glucagon-Like Peptide-1 Receptor Agonists in Post-bariatric Surgery Patients: A Systematic Review and Meta-analysis.

BACKGROUND: A significant number of patients face the issue of weight gain (WG) or inadequate weight loss (IWL) post-bariatric surgery for obesity. Several studies have been published evaluating the role of glucagon-like peptide-1 receptor agonists (GLP1RA) for weight loss post-bariatric surgery. However, no systematic review and meta-analysis (SRM) till date has evaluated the efficacy, safety and tolerability of GLP1RA in this clinical scenario. Hence, this SRM aimed to address this knowledge gap. METHODS: Databases were searched for randomized controlled trials (RCTs), case-control, cohort and observational studies involving use of GLP1RA in the intervention arm post-bariatric surgery. Primary outcome was weight loss post at least 3 months of therapy. Secondary outcomes were evaluation of body composition parameters, total adverse events (TAEs) and severe adverse events (SAEs). RESULTS: From initially screened 1759 articles, 8 studies (557 individuals) were analysed. Compared to placebo, patients receiving liraglutide had significantly greater weight loss after 6-month therapy [MD - 6.0 kg (95% CI, - 8.66 to - 3.33); P < 0.001; I2 = 79%]. Compared to liraglutide, semaglutide had significantly greater percent reduction in body weight after 6-month [MD - 2.57% (95% CI, - 3.91 to - 1.23); P < 0.001; I2 = 0%] and 12-month [MD - 4.15% (95% CI, - 6.96 to - 1.34); P = 0.004] therapy. In study by Murvelashvili et al. (2023), after 12-month therapy, semaglutide had significantly higher rates of achieving > 15% [OR 2.15 (95% CI, 1.07-4.33); P = 0.03; n = 207] and > 10% [OR 2.10 (95% CI, 1.19-3.71); P = 0.01; n = 207] weight loss. A significant decrease in fat mass [MD - 4.78 kg (95% CI, - 7.11 to - 2.45); P < 0.001], lean mass [MD - 3.01 kg (95% CI, - 4.80 to - 1.22); P = 0.001] and whole-body bone mineral density [MD - 0.02 kg/m2 (95% CI, - 0.04 to - 0.00); P = 0.03] was noted with liraglutide. CONCLUSION: Current data is encouraging regarding use of GLP1RAs for managing WG or IWL post-bariatric surgery. Deterioration of bone health and muscle mass remains a concern needing further evaluation. TRIAL REGISTRATION: The predefined protocol has been registered in PROSPERO having registration number of CRD42023473991.

Hyperprolactinemia Due to Prolactinoma has an Adverse Impact on Bone Health with Predominant Impact on Trabecular Bone: A Systematic Review and Meta-Analysis.

BACKGROUND: No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for studies having patients with hyperprolactinemia due to prolactinoma and the other being a matched control group. The primary outcome was to evaluate the differences in BMD Z-scores at different sites. The secondary outcomes of this study were to evaluate the alterations in bone mineral density, bone mineral content and the occurrence of fragility fractures. RESULTS: Data from 4 studies involving 437 individuals was analysed to find out the impact of prolactinoma on bone mineral metabolism. Individuals with prolactinoma had significantly lower Z scores at the lumbar spine [MD -1.08 (95 % CI: -1.57 - -0.59); P < 0.0001; I2 = 54 % (moderate heterogeneity)] but not at the femur neck [MD -1.31 (95 % CI: -3.07 - 0.45); P = 0.15; I2 = 98 % (high heterogeneity)] as compared to controls. Trabecular thickness of the radius [MD -0.01 (95 % CI: -0.02 - -0.00); P = 0.0006], tibia [MD -0.01 (95 % CI: -0.02 - -0.00); P=0.03] and cortical thickness of the radius [MD -0.01 (95 % CI: -0.19 - -0.00); P = 0.04] was significantly lower in patients with prolactinoma as compared to controls. The occurrence of fractures was significantly higher in patients with prolactinoma as compared to controls [OR 3.21 (95 % CI: 1.64 - 6.26); P = 0.0006] Conclusion: Bone mass is adversely affected in patients with hyperprolactinemia due to prolactinoma with predominant effects on the trabecular bone.

Semaglutide and cancer: A systematic review and meta-analysis.

BACKGROUND: French national health care insurance system database has suggested 1-3 years use of glucagon like peptide-1 receptor agonists (GLP1RA) (exenatide, liraglutide and dulaglutide) may be linked with increased occurrence of thyroid cancer. Similar data on semaglutide is not-available. Hence, we undertook this systematic review to look at the safety of semaglutide focussing on different cancers. METHODS: Databases were searched for randomized controlled trials (RCTs) and real-world studies involving patients receiving semaglutide in the intervention-arm. Primary outcome was to evaluate the occurrence of pancreatic and thyroid cancers. Secondary outcomes were to the evaluate occurrence of any other malignancies or severe adverse-events. RESULTS: Data from 37 RCTs and 19 real-world studies having 16,839 patients in placebo-control group, 16,550 patients in active-control group and 13,330 patients in real-world studies were analysed. Compared to placebo, occurrence of pancreatic cancer [OR 0.25 (95%CI: 0.03-2.24); P = 0.21], thyroid cancer [OR 2.04 (95%CI: 0.33-12.61); P = 0.44; I2 = 0%] and all neoplasms (benign, malignant and otherwise unspecified) [OR 0.95 (95%CI:0.62-1.45); P = 0.82; I2 = 0%] was similar in the semaglutide group. Compared to active controls, occurrence of pancreatic cancer [OR 0.40 (95%CI:0.09-1.87); P = 0.26; I2 = 0%], thyroid cancer [OR 1.19 (95%CI:0.15-9.66); P = 0.87; I2 = 0%] and all neoplasms (benign, malignant and otherwise unspecified) [OR 0.91 (95% CI: 0.44-1.89); P = 0.79; I2 = 0%] were similar in the semaglutide group. Real-world data analysis revealed single case each of pancreatic cancer and B-cell lymphoma. CONCLUSION: Semaglutide use in RCTs and real-world studies was not associated with an increased risk of any types of cancer, and this conclusion is supported by a high grade of evidence.

Impact of semaglutide on biochemical and radiologic measures of metabolic-dysfunction associated fatty liver disease across the spectrum of glycaemia: A meta-analysis.

BACKGROUND AND AIMS: No meta-analysis has analysed efficacy and safety of semaglutide in metabolic-dysfunction associated fatty-liver disease (MAFLD). METHODS: Electronic databases were searched for RCTs involving people with MAFLD and/or type-2 diabetes (T2DM) receiving semaglutide. Primary outcome was to evaluate changes in alanine aminotransferase (ALT). Secondary outcomes were to evaluate alterations in other measures of NAFLD, glycaemia, lipids and adverse-events. RESULTS: Data from 4 RCTs (2115 patients) was analysed. A greater lowering with injectable semaglutide 0.4mg/0.5 mg once weekly was seen with regards to ALT [MD -3.89U/L (95%CI: -5.41 to -2.36); P < 0.01; I2 = 0%; 2050 patients], liver stiffness (fibroscan®) [MD -3.19 kPa (95%CI: -3.26 to -3.12); P < 0.01; 162 patients], steatosis [MD -13.40 dB/m (95%CI: 20.56 to -6.24); P < 0.01; 162 patients], triglycerides [MD -21.43 mg/dl (95% CI: 41.63 to -1.23); P = 0.04; I2 = 99%; 2050 patients], total cholesterol [MD -5.53 mg/dl (95% CI: -8.45 to -2.61); P < 0.01; I2 = 0%; 1888 patients], LDL-cholesterol [MD -3.55 mg/dl (95% CI: -5.87 to -1.23); P < 0.01; I2 = 0%; 1888 patients], percent-weight [MD -8.99% (95%CI: -14.64 to -3.34); P = 0.002; I2 = 100%; 2115 patient] and HbA1c [MD -0.77% (95%CI: 1.10 to -0.45); P = 0.002; I2 = 100%; 2115 patients]. Number of patients inadequate to comment on histopathologic measures of MAFLD. Occurrence of treatment-emergent adverse-events [RR 2.31 (95% CI: 0.76-7.06); P = 0.14; I2 = 82%] and severe adverse events [RR 1.07 (95%CI: 0.69-1.65); P = 0.77; I2 = 33%] were comparable. Adverse-events leading to trial discontinuation [RR 2.37 (95% CI: 1.33-4.22); P = 0.003; I2 = 24%], diarrhea [RR 2.05 (95%CI: 1.17-3.60); P = 0.01; I2 = 66%], nausea [RR 4.98 (95%CI: 3.23-7.67); P < 0.001; I2 = 0%] and vomiting [RR 3.90 (95%CI: 1.75-8.68); P < 0.01; I2 = 54%] were higher with semaglutide. CONCLUSION: This meta-analysis provides reassuring data on efficacy of low dose semaglutide injections in improving ALT and certain radiologic features in MAFLD. Current conclusions are limited by small number of patients evaluated. Urgent need remains for larger studies focussing on liver biopsy.

Expert opinion on the preoperative medical optimization of adults with diabetes undergoing metabolic surgery.

Diabetes mellitus (DM) and obesity are interrelated in a complex manner, and their coexistence predisposes patients to a plethora of medical problems. Metabolic surgery has evolved as a promising therapeutic option for both conditions. It is recommended that patients, particularly those of Asian origin, maintain a lower body mass index threshold in the presence of uncontrolled DM. However, several comorbidities often accompany these chronic diseases and need to be addressed for successful surgical outcome. Laparoscopic Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) are the most commonly used bariatric procedures worldwide. The bariatric benefits of RYGB and LSG are similar, but emerging evidence indicates that RYGB is more effective than LSG in improving glycemic control and induces higher rates of long-term DM remission. Several scoring systems have been formulated that are utilized to predict the chances of remission. A glycemic target of glycated hemoglobin < 7% is a reasonable goal before surgery. Cardiovascular, pulmonary, gastrointestinal, hepatic, renal, endocrine, nutritional, and psychological optimization of surgical candidates improves perioperative and long-term outcomes. Various guidelines for preoperative care of individuals with obesity have been formulated, but very few specifically focus on the concerns arising from the presence of concomitant DM. It is hoped that this statement will lead to the standardization of presurgical management of individuals with DM undergoing metabolic surgery.

Prevalence of Macroprolactinemia in People Detected to Have Hyperprolactinemia.

Background Macroprolactinemia is an analytic laboma encountered as a part of prolactin assay. No data are available on the burden of macroprolactinemia in Indians. This study aimed to determine the prevalence and predictors of macroprolactinemia among people with hyperprolactinemia. Methods Consecutive patients detected to have serum prolactin > 18 ng/mL as per the upper reference limit were further screened for macroprolactin by post-polyethylene-glycol (PEG)-precipitation test. Macroprolactinemia was defined as post-PEG recovery of prolactin < 40%. Results The four most common underlying etiologies for the testing of hyperprolactinemia were polycystic ovary syndrome ( n = 402; 32.71%), pituitary adenomas ( n = 318; 25.87%), drug-induced hyperprolactinemia ( n = 224; 18.23%), and infertility ( n = 126; 10.25%). A total of 1,229 patients (male:female = 191:1038) having mean age 30.46 ± 10.14 years had hyperprolactinemia, of which 168 (13.7%) were diagnosed to have macroprolactinemia. Macroprolactinemia was significantly higher in females than males (15.03 vs. 6.28%; p < 0.001). Age quartile-based analysis revealed no difference in occurrence of macroprolactinemia. Only 34 patients (2.76%) with macroprolactinemia (< 40% recovery of prolactin post-PEG precipitation) had raised prolactin levels after recovery. These patients primarily had underlying pituitary pathology. Conclusion Macroprolactinemia is not uncommon in people being tested for hyperprolactinemia. We should not hesitate to screen for macroprolactinemia in patients who have incidentally been detected to have hyperprolactinemia.

Anticancer Medications and Sodium Dysmetabolism.

Therapeutic advances have revolutionised cancer treatment over the last two decades, but despite improved survival and outcomes, adverse effects to anticancer therapy such as dyselectrolytaemias do occur and need to be managed appropriately. This review explores essential aspects of sodium homeostasis in cancer with a focus on alterations arising from anticancer medications. Sodium and water balance are tightly regulated by close interplay of stimuli arising from hypothalamic osmoreceptors, arterial and atrial baroreceptors and the renal juxtaglomerular apparatus. This delicate balance can be disrupted by cancer itself, as well as the medications used to treat it. Some of the conventional chemotherapeutics, such as alkylating agents and platinum-based drugs, can cause hyponatraemia and, on rare occasions, hypernatraemia. Other conventional agents such as vinca alkaloids, as well as newer targeted cancer therapies including small molecule inhibitors and monoclonal antibodies, can cause hyponatraemia, usually as a result of inappropriate antidiuretic hormone secretion. Hyponatraemia can also sometimes occur secondarily to drug-induced hypocortisolism or salt-wasting syndromes. Another atypical but distinct mechanism for hyponatraemia is via pituitary dysfunction induced by immune checkpoint inhibitors. Hypernatraemia is uncommon and occasionally ensues as a result of drug-induced nephrogenic diabetes insipidus. Identification of the aetiology and appropriate management of these conditions, in addition to averting treatment-related problems, can be lifesaving in critical situations.

Vitamin D, Thyroid Autoimmunity and Cancer: An Interplay of Different Factors.

BACKGROUND AND AIMS: In spite of large volume of data linking Vitamin D with cardiovascular morbidity, autoimmunity, cancer, and virtually every organ system, Vitamin D and thyroid is a lesser-known aspect of Vitamin D in clinical practice. This article intends to highlight the current literature on the impact of Vitamin D status and supplementation on thyroid autoimmunity and cancer. METHODS: References for this review were identified through searches of PubMed for articles published to from 1950 to August 2019 using the terms "thyroid" [MeSH Terms] AND "Vitamin D" [MeSH Terms] OR "thyroid" [All Fields] AND "Vitamin D" [All Fields]. RESULTS: Significant inverse correlation was documented between anti-thyroid peroxidase antibody (TPOAb) and serum 25-hydroxy-Vitamin D (25OHD). TPOAb positivity is more prevalent in Vitamin D deficient individuals. A large volume of medical literature is available from observational studies linking Vitamin D with thyroid autoimmunity. Data from interventional studies documenting beneficial effects of Vitamin D on thyroid autoimmunity is also available, but lesser than that from observational studies. Short-term high dose oral Vitamin D supplementation reduces TPOAb titers. Certain Vitamin D receptor (VDR) gene polymorphism have been linked to increased occurrence of autoimmune thyroid disorders (AITD). Vitamin D deficiency, decreased circulating calcitriol has been linked to increased thyroid cancer. Certain VDR gene polymorphisms have been linked with increased as well as decreased occurrence of thyroid cancer. Data is scant on use of Vitamin D and its analogues for treating thyroid cancer. CONCLUSION: In spite of large volume of medical literature from observational studies linking Vitamin D with thyroid autoimmunity and cancer, meaningful concrete clinical data on impact of Vitamin D supplementation on hard clinical end points in these disorders is lacking, and should be the primary area of research in the next decade.

The diabetic knee.

Diabetes is a multisystemic and multifaceted syndrome, and its clinical impact is wide ranging and varied. The musculoskeletal complications of diabetes, too cover a broad spectrum of joints and presentations. Relatively less attention is paid, however, to the diabetic knee. This communication describes the bidirectional relationship between diabetes and the knee, and the potential influence this may have on therapy.

Ultrasound Elastography is a Useful Adjunct to Conventional Ultrasonography and Needle Aspiration in Preoperative Prediction of Malignancy in Thyroid Nodules: A Northern India Perspective.

INTRODUCTION: Data on ultrasound elastography (USE) are scant from India. This study aimed to compare the sensitivity and specificity of USE with thyroid ultrasonography (USG) and fine-needle aspiration (FNA) as preoperative predictor of malignancy, using postoperative histopathology as gold standard. MATERIALS AND METHODS: Consecutive patients with thyroid swelling/goiter underwent thyroid USG followed by USE. Patients with pure cystic nodules or eggshell calcification were excluded. Patients with nodules >10 mm with one or more high-risk USG features underwent FNA. Patients with no USG high-risk features, benign score on USE, and benign FNA were conservatively followed. All other patients underwent thyroidectomy. RESULTS: 246 consecutive patients underwent USG. Data from 97 patients (117 nodules) were analyzed. Median age of patients was 43 years with 85.4% females. All patients with USE score-1 had benign USG and FNA characteristics. Of 86 nodules having USE score-2, 18.6% nodules were hypoechoic and 16.28% had microcalcification. Hypoechogenicity and microcalcifications were observed in 66.67% nodules with USE score-3. All nodules with USE score-4 and 5 were hypoechoic and had microcalcifications. Histopathology was benign in 84 and malignant in 33 patients. Occurrence of malignancy in USE scores 1-5 was 0, 4.65, 100, 90.5, and 100%, respectively. All eight nodules with diagnosis of follicular adenoma had preoperative USE score-2. The sensitivity of preoperative USG, USE, and FNA in picking up malignancy was 66.67, 87.88, and 69.70%, respectively. Specificity of USG, USE, and FNA in detecting thyroid malignancy was 88.10, 100, and 97.6%, respectively. False positivity rates for USG, USE, and FNA in diagnosing thyroid malignancy was 11.9, 0, and 2.4%, respectively. The overall diagnostic accuracy of USG, USE, and FNA cytology in this study was 82.05, 96.58, and 89.74%, respectively. CONCLUSION: USE may be better than USG for preoperative detection of malignancy in thyroid nodules.

The Twin White Herrings: Salt and Sugar.

India has the dubious distinction of being a hotspot for both diabetes and hypertension. Increased salt and sugar consumption is believed to fuel these two epidemics. This review is an in-depth analysis of current medical literature on salt and sugar being the two white troublemakers of modern society. The PubMed, Medline, and Embase search for articles published in January 2018, using the terms "salt" [MeSH Terms] OR "sodium chloride" [All Fields] OR "sugar" [All Fields]. India is world's highest consumer of sugar with one of the highest salt consumption per day. Increased salt intake is associated with increased risk of hypertension, left ventricular hypertrophy and fibrosis, cardiovascular events, renal stones, proteinuria, and renal failure. Increased sugar intake is directly linked to increased risk of obesity, fatty liver disease, and metabolic syndrome. Also, increased sugar intake may be indirectly related to the increased risk of type 2 diabetes. Both salt and sugar intake is directly linked to increased systemic and hypothalamic inflammation, endothelial dysfunction, microangiopathy, cardiovascular remodelling, cancers, and death. High fructose corn is especially damaging. There is no safe limit of sugar consumption, as the human body can produce its own glucose. Being nature's gift to mankind, there is no harm in moderate consumption of salt and sugar, however, modest reduction in the consumption of both can substantially reduce the burden of non-communicable diseases. Public health interventions to facilitate this behavioural change must be instituted and encouraged.

18F-Fluorocholine-Positron Emission Tomography/Computerised Tomography is Useful in Localising 99mTc-Sesta-methoxyisobutylisonitrile-Negative Parathyroid Cyst Causing Normocalcemic Primary Hyperparathyroidism.

Parathyroid cysts are extremely rare and are rarely associated with primary hyperparathyroidism (PHPT), which are difficult to localise, as they are 99mTc-sesta-methoxyisobutylisonitrile (sestaMIBI) negative. We report for the first time the utility of 18F-fluorocholinepositron emission tomography/computerised tomography (PC-PET/CT) in localising parathyroid cyst causing normocalcemic PHPT. A 76-year-old lady with progressively worsening osteoporosis from 2014-2017 (in spite of annual zolendronic acid infusions, daily calcium and vitamin-D supplementation) with persistently normal serum calcium and vitamin D, but elevated parathyroid hormone, had normal sestaMIBI scans of the neck on multiple occasions. FC-PET/CT finally revealed soft tissue uptake, suggestive of right superior parathyroid adenoma/ hyperplasia. Surgical removal of the culprit lesion resulted in resolution of hyperparathyroidism, histopathologic evaluation of which revealed a cystic lesion lined by chief cell variant parathyroid cells without any nuclear atypia, capsular or vascular invasion. FC-PET/CT is useful in localising culprit parathyroid lesions, especially when they are sestaMIBI negative. PC-PET/CT is useful in localising parathyroid hyperplasia and ectopic parathyroids, which are frequently missed by sestaMIBI. There is an urgent need for comparative studies between sestaMIBI and FC-PET/CT in PHPT. We report for the first time the usefulness of FC-PET/CT in localising sestaMIBI-negative functional parathyroid cyst causing normocalcemic PHPT.

Presence, patterns & predictors of hypocortisolism in patients with HIV infection in India.

BACKGROUND & OBJECTIVES: : Adrenal insufficiency (AI) is rarely diagnosed in patients with HIV infection, in spite of autopsy studies showing very high rates of adrenal involvement. This study was aimed to determine the presence, patterns and predictors of AI in patients with HIV infection. METHODS: : Consecutive HIV patients, 18-70 yr age, without any severe co-morbid state, having at least one-year follow up at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. RESULTS: : From initially screened 527 patients, 359 patients having good immune function were analyzed. Basal morning cortisol <6 µg/dl (<165 nmol/l; Group 1), 6-11 µg/dl (165-300 nmol/l; Group 2), 11-18 µg/dl (300-500 nmol/l; Group 3) and ≥18 µg/dl (500 nmol/l; Group 4) were observed in 13, 71, 199 and 76 patients, respectively. Adrenocorticotropic hormone (ACTH) stimulation test revealed 87 patients (24.23%) to have AI. AI in groups 1-4 was 100, 56.34, 17.09 and 0 per cent, respectively. AI patients were more likely to be females (P< 0.05), having longer disease duration (P< 0.05), immune reconstitution inflammatory syndrome, hyperkalaemia (P< 0.01), lower fasting glucose (P< 0.01), dehydroepiandrosterone sulphate (DHEAS) and vitamin D. Regression analysis revealed morning cortisol and DHEAS to be best predictors of AI (P=0.004 and 0.028, respectively). INTERPRETATION & CONCLUSIONS: : AI is a significant problem in HIV-infected individuals, observed in nearly a quarter of patients. Diagnosis warrants high index of suspicion and low threshold for screening, especially in those having low DHEAS and hyperkalaemia. Morning cortisol is a reasonable screening test, with ACTH stimulation warranted to confirm diagnosis, especially in patients with morning cortisol <11 µg/dl (300 nmol/l).

Phenotypic presentation of adolescents with overt primary hypothyroidism.

BACKGROUND: The phenotypic presentation of overt hypothyroidism during adolescence is less well characterized. The aim of the study was to study the phenotypic presentation of patients with overt hypothyroidism presenting during adolescence (age 9-18 years). METHODS: Records of adolescent patients with overt hypothyroidism (thyroid stimulating hormone [TSH]>10 mIU/L) were retrospectively analyzed for presenting complaints, height and pubertal status. RESULTS: A total of 67 patients (40 females and 37 males, average age 13.2+2.3 years) with a mean TSH of 241.3±336.6 mIU/L were included. The commonest presentation was short stature in 46.2% of patients followed by neck swelling (16.4%) and weight gain (11.9%). The mean height standard deviation score (SDS) was -2.5+2.11, 43% of patients had less than 3 SDS. The height age and bone age were around 3 years less than the chronological age. The bone age significantly correlated with the height age but not with TSH levels. Three patients referred from neurology with primary complaints of headache had pituitary hyperplasia and one presented with hypokalemic periodic paralysis. Seven had delayed puberty and one patient had early periods due to huge ovarian cysts. CONCLUSIONS: In the present study, severe short stature and uncommon phenotypic presentations were a consequence of long-standing severe untreated hypothyroidism.

Occult phosphaturic mesenchymal tumour of femur cortex causing oncogenic osteomalacia - diagnostic challenges and clinical outcomes.

BACKGROUND: Tumor induced osteomalacia (TIO) are extremely rare paraneoplastic syndrome with less than 300 reported cases. This report highlights the pitfalls and challenges in diagnosing and localizing TIO in patients with refractory and resistant osteomalacia. PATIENT AND METHODS: 41- year gentleman with 4-year history of musculoskeletal weakness and pathologic fractures presented in wheelchair bound incapacitated state of 1-year duration. Investigations were significant for severe hypophosphatemia, severe phosphaturia, normal serum calcium, reduced 1,25-dihydroxy vitamin-D, elevated ALP, elevated intact parathyroid hormone (iPTH), and pseudo-fractures involving pelvis and bilateral femur. Whole body MRI and 99mTc methylene diphosphonate bone-scan were also normal. Whole body FDG-PET scan involving all 4 limbs revealed a small FDG avid lesion at lateral border of lower end of left femur (SUV max 3.9), which was well characterized on 3-dimensional CT reconstruction. Plasma C-terminal fibroblast growth factor (FGF)-23 was 698 RU/ mL (normal < 150 RU/ml). Wide surgical excision of the tumor was done. Histopathology confirmed mesenchymal tumor of mixed connective tissue variant. Serum phosphorous normalized post-surgery day-1. High dose oral calcium and vitamin-D was continued. FGF-23 normalized post surgery (73RU/ml). Physical strength improved significantly and now he is able to walk independently. CONCLUSION: TIO is frequently confused with normocalcemic hyperparathyroidism and vitamin-D resistant rickets/osteomalacia, which increases patient morbidity. Imaging for tumor localization should involve whole body from head to tip of digits, cause these tumors are notoriously small and frequently involve digits of hands and legs. Complete surgical removal of the localized tumor is key to good clinical outcomes.

Occurrence, patterns & predictors of hypogonadism in patients with HIV infection in India.

BACKGROUND & OBJECTIVES: Data on hypogonadism among human immunodeficiency virus (HIV)-infected Indians are not available. This study was aimed to evaluate the occurrence, pattern and predictors of hypogonadism in HIV-infected Indians. METHODS: Consecutive stable HIV-infected patients, 18-70 yr age, without any severe comorbid state, having at least one year follow up data at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. RESULTS: From initially screened 527 patients, 359 patients (225 males; 134 females), having disease duration of 61.44±39.42 months, 88.58 per cent on highly active antiretroviral therapy (HAART), 40.67 per cent having tuberculosis history and 89.69 per cent with vitamin D insufficiency were analyzed. Testosterone <300 ng/dl was documented in 39.11 per cent males. Primary, hypogonadotropic hypogonadism (HypoH) and compensated hypogonadism were observed in 7.56, 31.56 and 12.44 per cent males, respectively. Males with hypogonadism were significantly older (P=0.009), and had higher opportunistic infections (P<0.001) with longer disease duration (P=0.05). Menstrual abnormalities were observed in 40.3 per cent females, who were significantly older (P<0.001), had lower CD4 count (P=0.038) and higher tuberculosis history (P=0.005). Nearly 46.3, 16.2 and 13 per cent women with menstrual abnormalities were in peri-/post-menopausal state, premature ovarian insufficiency (POI) and HypoH, respectively. Age, CD4 count at diagnosis and 25(OH)D were best predictors of male hypogonadism. Age and CD4 count increment in first 6-12 months following HAART were the best predictors of POI. INTERPRETATION & CONCLUSIONS: Hypogonadism was observed to be a significant problem in HIV-infected men and women in India, affecting 39 and 29 per cent patients, respectively. HypoH was the most common form in males whereas ovarian failure being the most common cause in females.

Hyperprolactinemia in Children with Subclinical Hypothyroidism.

Prevalence of hyperprolactinemia in children with subclinical hypothyroidism (ScH) is not known. This study aimed to determine the occurrence and predictors of hyperprolactinemia in euthyroid children and in children with ScH and overt primary hypothyroidism (OPH). Serum prolactin levels were estimated in consecutive children <18 years of age undergoing thyroid function evaluation and diagnosed to have normal thyroid function, ScH, or OPH. Children with pituitary adenomas, secondary hypothyroidism, multiple pituitary hormone deficiency, comorbid states, and drug-induced hyperprolactinemia were excluded. From the initially screened 791 children, hormonal data from 602 children who fulfilled all criteria were analyzed. Seventy-one (11.79%) of these had ScH, and 33 (5.48%) had OPH. Occurrence of hyperprolactinemia was highest in the OPH group (51.51%), followed by ScH (30.98%) and euthyroid children (4.41%) (p<0.001). Median (25th-75th percentiles) levels for prolactin in euthyroid, ScH, and OPH children were 13.3 (9.4-17.95), 19.15 (15.97-30.12), and 28.86 (17.05-51.9) ng/mL, respectively (p<0.001). In children, prolactin levels were comparable in males and females. An age-related increase in serum prolactin was noted in euthyroid children, which was statistically significant in post-pubertal (16-18 years) children. Area under the curve for thyroid stimulating hormone (TSH) in predicting hyperprolactinemia in children was 0.758 (95% confidence interval: 0.673-0.829; p<0.001). TSH ≥4.00 mIU/L had a sensitivity of 69.4% and specificity of 77.6% in detecting hyperprolactinemia. Hyperprolactinemia is common in children with ScH and OPH. TSH ≥4.00 mIU/L has a good sensitivity and specificity in predicting hyperprolactinemia in children. More studies are needed to establish if hyperprolactinemia should be an indication for treating ScH in children.