Elevated IL-6 levels in a patient with pheochromocytoma.

Pheochromocytoma is a chromaffin cell-derived adrenal medullary tumour and usually presents with paroxysms of hypertension, palpitations, sweating and headache due to excessive catecholamine release. These tumours can also secrete a variety of bioactive neuropeptides and hormones other than catecholamines, resulting in unusual clinical manifestations. We report a female in her mid-30s who presented with fever, anaemia, thrombocytosis and markedly elevated inflammatory markers. The fever profile, including cultures, was negative. Contrast-enhanced CT of abdomen showed a large solid-cystic right adrenal lesion with elevated plasma-free normetanephrine levels suggestive of pheochromocytoma. The fever persisted despite empirical antibiotics and antipyretics. Interleukin-6 (IL-6) levels were elevated (41.2 pg/mL (3-4 pg/mL)). She was initiated on naproxen (NPX) at a dose of 250 mg two times per day. The patient responded to NPX, and after stabilisation, she underwent an adrenalectomy. There was a complete resolution of fever with normalisation of IL-6 levels postoperatively.

Steroidogenic acute regulatory protein (STAR) deficiency: Our experience and systematic review for phenotype-genotype correlation.

OBJECTIVE: Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. A systematic review of phenotype-genotype correlation and data on testicular histology in LCAH patients is unavailable. We aim to describe our experience and provide phenotype-genotype correlation. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective review of three genetically proven LCAH patients from our centre and per-patient data analysis from a systematic review of 292 probands. The phenotypic subgroups of 46,XY were Group A (typical female genitalia), Group B (atypical genitalia) and Group C (typical male genitalia). RESULTS: We report three new LCAH probands from India, all diagnosed post-infancy with preserved gonadal function and one novel variant. The systematic review reports 46,XY to 46,XX LCAH ratio of 1.1 (155:140). Patients with 46,XY LCAH in Group A were diagnosed in infancy (116/117) and had higher mineralocorticoid involvement than Group C (96.4% vs. 75%, p = 0.035), whereas Group C had preserved gonadal function. Hyperplastic adrenals are noted in ~60% of LCAH diagnosed with primary adrenal insufficiency in infancy. There was no report of gonadal germ cell cancer and rare reports of germ cell neoplasia in situ in adolescents, especially with intraabdominal gonads. Two-thirds of LCAH probands were East-Asian and 11/16 regional recurrent variants were from East Asia. There was minimal overlap between variants in Groups A (n = 55), B (n = 9) and C (n = 8). All nonsense and frameshift and most of the splice-site variants and deletion/insertions were present in Group A. CONCLUSIONS: We report three new cases of LCAH from India. We propose a phenotype-derived genotypic classification of reported STAR variants in 46,XY LCAH.

Comparative Study of Insulin Sensitivity and Resistance and Their Correlation with Androgens in Lean and Obese Women with Polycystic Ovary Syndrome.

There is a lack of consensus on the optimal screening strategy for insulin resistance (IR), particularly in lean women with polycystic ovary syndrome (PCOS). Therefore, we conducted a cross-sectional study in 80 women with PCOS (28 lean/52 obese) and 80 age- and body mass index (BMI)-matched controls. Using a 5-point 75-g oral glucose tolerance test (OGTT) (0, 30, 60, 90, 120 min), we examined glucose and insulin excursions, IR, insulin sensitivity, beta-cell function (ßF), and the effect of androgens on IR. Lean and obese women with PCOS had similar glucose but higher insulin (except fasting in lean women) and insulin AUC as compared to their respective controls (p < 0.05). Lean women with PCOS were equally insulin-resistant but more hyperinsulinemic than the obese controls (p < 0.05). Although ßF ([1st phase: 481.71 ± 263.53 vs. 430.56 ± 232.37], [2nd phase: 815.16 ± 447.12 vs. 752.66 ± 428.95]) was comparable in lean and obese women with PCOS, lean women had better insulin sensitivity (112.78 ± 66.26 vs. 75.49 ± 55.6) (p < 0.05). Dehydroepiandrosterone sulfate (DHEAS) and androstenedione decreased with increasing BMI in lean women, and this correlated with deteriorating insulin sensitivity and exaggerated hyperinsulinemia. In obese women with PCOS, sex hormone-binding globulin (SHBG) correlated negatively with BMI and hyperinsulinemia, and positively with insulin sensitivity. This data suggests that estimating only fasting insulin may miss IR in lean women with PCOS; hence, additional time points in OGTT will add value to screening for IR. DHEAS and androstenedione may have a beneficial effect on insulin sensitivity and may be used to screen IR in lean women, while SHBG can be used as a predictive marker for IR in obese women with PCOS.

Prevalence and predictors of abnormal glucose tolerance and its resolution in acromegaly: Single Centre retrospective study of 90 cases.

Aims The aim of the study was to evaluate the prevalence and predictors of abnormal glucose tolerance (Diabetes + Prediabetes) and its resolution in Acromegaly. SETTINGS AND DESIGN: Retrospective observational study. METHODS AND MATERIAL: Ninety patients with acromegaly and followed up post operatively for 1 year were included. The study cohort was divided into two groups: Group A: abnormal glucose tolerance [AGT: Diabetes + prediabetes (n = 40)] and Group B: normal glucose tolerance (NGT) (n = 50).The impact of the following parameters: age, sex, Waist Circumference(WC), Body Mass Index (BMI), duration of acromegaly, Growth Hormone (GH) levels, Insulin like Growth Factor 1 (IGF1) levels, pituitary tumour size, hypertension, and family history of diabetes as predictors for diabetes were studied pre surgery and post-surgery at 3 months and 1 year affecting glycaemia. Unpaired t-test, chi-square test and binary logistic regression analysis were used for statistical analysis. RESULTS: The prevalence of AGT in our cohort was 44.44% (Diabetes 37.77%, prediabetes 6.66%).Patients with AGT were older (44.2 ± 12.21 years vs. 34.92 ± 11.62 years; p = 0.00040) and had higher WC (in cm) (91.35 ± 7.87 vs.87.12 ± 6.07; p = 0.005) than NGT. Hypertension and family history of diabetes were significantly more frequent in patients with AGT. GH and IGF1 levels were not significantly different between the groups. On binary logistic regression, Sex (p = 0.0105) (OR = 6.0985), waist circumference (p = 0.0023) (OR = 1.2276) and hypertension (p = 0.0236) (OR = 1.632) were found to be significant predictors of AGT in acromegaly. After surgery 42.5% and 62.5% patients became normoglycemic at 3 months and 1 year respectively. On binary logistic regression there were no predictors for achieving normoglycemia at 3 months or 1 year, however the delta change in GH, BMI and tumour size were significant. CONCLUSIONS: The prevalence of AGT was 44.44%. Female sex, WC and hypertension were found to be significant predictors of AGT in acromegaly. Post-surgery normoglycemia was achieved in 42.5% at 3 months and 62.5% at 1 year with no predictors for normalisation of AGT.

Unrecognized Primary Hypothyroidism As a Possible Cause of Hyperreactio Luteinalis.

Hyperreactio luteinalis (HRL) is characterised by benign enlargement of ovaries in pregnancy associated with hyperandrogenism. A 19-year-old primigravida presented with breathlessness, abdominal distension and vomiting in the thirteenth week of gestation. Abdominal examination revealed distension of abdomen disproportionate to the gestational age. Ultrasound was suggestive of bilaterally enlarged multicystic ovaries with a characteristic "spoke-wheel" pattern and a diagnosis of HRL was made. Laboratory investigations revealed primary hypothyroidism and elevated testosterone. She was initiated on levothyroxine therapy. Her respiratory distress worsened on the third day of admission for which she underwent emergency laparotomy with cyst aspiration. Thyroid function tests normalized within six weeks after the initiation of therapy and remained normal for the remainder of pregnancy. Serum testosterone levels returned to normal six weeks postpartum. The elevated thyroid-stimulating hormone levels could have contributed to development of HRL by cross-reacting with human chorionic gonadotropin and follicle-stimulating hormone receptors. Hyperandrogenism and ovarian enlargement regresses with levothyroxine therapy.

POU1F1 mutations in combined pituitary hormone deficiency: differing spectrum of mutations in a Western-Indian cohort and systematic analysis of world literature.

CONTEXT: POU1F1 mutations are prevalent in Indian CPHD cohorts. Genotype-phenotype correlation is not well-studied. AIM: To describe phenotypic and genotypic spectrum of POU1F1 mutations in our CPHD cohort and present systematic review as well as genotype-phenotype analysis of all mutation-positive cases reported in world literature. METHODS: Retrospective study of POU1F1 mutation-positive patients from a western-Indian center. PRISMA guidelines based pubmed search of published literature of all mutation-positive patients. RESULTS: Our cohort had 15 POU1F1 mutation-positive patients (9 index, 6 relatives). All had severe GH, TSH and prolactin deficiencies (GHD, TSHD and PD). TSHD was diagnosed earliest followed by GHD (median ages: TSHD-6 months, GHD-3 years), while PD was more variable. Two sisters had central precocious puberty at 7 years of age. Pubic hair was deficient in all post-pubertal patients (females: P1-P2, males: P3-P4). Splice-site/intronic/frameshift mutations were most common, while missense/nonsense mutations were less frequent (33%). Review of world literature yielded 114 patients (82 index patients) from 58 studies. GHD was present in all patients. TSHD was spared in 12.5% and PD in 4.4% patients. Missense/nonsense mutations accounted for 75% of spectrum. Phenotype-genotype analysis revealed higher mean peak-GH levels (1.1 vs 0.2 ng/ml, p = 0.008) and lower prevalence of anterior-pituitary hypoplasia (63.6% vs 86.3%, p = 0.03) in patients with heterozygous than homozygous and compound heterozygous mutations. CONCLUSIONS: We present largest series of POU1F1 mutation-positive patients. Precocious puberty and defective pubarche are lesser-appreciated phenotypic features. Our mutation spectrum is different from that of world literature. Patients with heterozygous mutations have milder phenotype.

Current Status of Diagnosis and Management of Functioning Pituitary Tumors: Part II.

Functioning pituitary tumors contribute to significant morbidity and mortality. Proper diagnostic approach and management is essential for optimal outcomes. Prolactinomas, the commonest of these, are the only tumors which can be managed medically. Acromegaly, apart from acral enlargement, can have multiple comorbidities like diabetes, hypertension, and obstructive sleep apnea. The primary treatment is surgical and it can be supplemented by radiotherapy and medications such as somatostatin analogs, growth hormone receptor blockers, or cabergoline. Thyrotropin-secreting tumors are rare and present with hyperthyroidism. Optimal preoperative management followed by surgical resection often leads to cure.