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Abstract Pubertal disorders in the form of delayed puberty (DP) or precocious puberty (PP) can cause considerable anxiety to both children and parents. Since the clinical and biochemical signatures of self-limiting and permanent conditions overlap considerably, it can be hard to determine whether to offer reassurance or intervention. Researchers have thus long been searching for a robust test to indicate whether the process of endogenous puberty is underway and is likely to proceed to completion. Although existing tests are available, such as basal gonadotropins, gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone, and basal and human chorionic gonadotropin-stimulated testosterone, their diagnostic specificity is inadequate. Inhibin B, a glycoprotein hormone, is secreted by Sertoli cells in males and small antral follicles in females. Entry into puberty is characterized by a rise in inhibin B levels in both genders. For the past 2 decades, researchers have been studying the role of inhibin B in the differential diagnosis of DP and PP. Initial studies showed promising results for using inhibin B to distinguish between constitutional (or self-limited) DP and congenital hypogonadotropic hypogonadism. However, diverse population studies have revealed varying cutoffs, limiting the use of basal inhibin B (basal-iB) in routine clinical practice. Recently, the concept of stimulated inhibin B has been introduced, using either follicle-stimulating hormone (FSH) or GnRH-analogs. Both FSH- and GnRH-analog-stimulated inhibin B concentrations were found to be more reliable than basal levels for investigation of pubertal disorders. This review examines the current status of basal-iB in the differential diagnosis of DP and PP, addressing its main advantages and limitations, and shedding light on the role of stimulated inhibin B concentrations.

Thrombocytopenia as a precipitating factor for pituitary apoplexy (PA) is very rare event. There are only five reported cases of PA secondary to thrombocytopenia caused by underlying haematological malignancy. Herein, we report a case of 60-year-old male presenting with acute-onset headache, bilateral vision loss, and ptosis. Computed tomography and magnetic resonance imaging revealed findings indicative of pituitary adenoma with apoplexy. He was noted to have thrombocytopenia, and bone marrow evaluation revealed precursor B-lineage CALLA-positive acute lymphoblastic leukemia. Accordingly, he was started on dexamethasone and vincristine but succumbed to Acinetobacter baumanii-related hospital-acquired pneumonia two weeks after initiation of chemotherapy. We performed a literature search and found five cases of pituitary apoplexy secondary to haematological malignancy-related thrombocytopenia. The usual age of presentation was in the 6th to 7th decade, and there was slight male preponderance. The underlying pituitary adenoma was either nonfunctioning or a prolactinoma, and in majority, the apoplexy event occurred after the diagnosis of haematological malignancy. The platelet counts at the time of PA were less than 30 × 109/L in all, and the malignancy subtypes were acute or chronic myeloid leukemia and chronic lymphoid leukemia. The current case highlights the importance of careful evaluation for the cause of thrombocytopenia in a case of PA.

AimsWe studied mortality in individuals of diabetes with or without Charcot neuroarthropathy (CN).MethodsPeople attending diabetic foot care facility with CN of foot (Cohort 1) were prospectively evaluated. Details pertaining to the duration of diabetes, microvascular and macrovascular complications, foot ulcer, amputation and mortality outcomes were recorded and compared with those without foot complications (Cohort 2) by multivariate logistic regression.ResultsData for 260 individuals of diabetes with CN and 520 individuals without CN were analysed. Mean age at presentation with CN was 55.8 ± 9.1 years, and duration of diabetes was 12.9 ± 7.8 years. 39.8% individuals with CN had foot ulcer, and 15.3% had amputation. People with CN were younger (55 ± 9.1 vs. 59.9 ± 8.1 years, p < 0.001) and had higher prevalence of microvascular complications. A total of 39 (15%) individuals with CN and 50 (9.8%) (p = 0.03) individuals without CN died during median follow-up of 40(24–51) months. People with CN had 2.7 times (OR 2.72, 95% CI 1.4–5.2, p = 0.003) increased mortality risk when matched for potential confounders. Prevalent CAD and low eGFR predicted higher mortality in people with CN.ConclusionsPeople with Charcot neuroarthropathy have almost three times increased risk of mortality despite being younger at presentation.

Abstract Background Clinicians have long been struggling to find an effective tool to predict onset of puberty. Objective To explore stimulability of inhibin B after exogenous FSH and its potential role for prediction of onset of puberty. Design and participants Study subjects were enrolled into “exploratory cohort” (n = 42) and “validation cohort” (n = 19). The exploratory cohort was further divided into group 1 (healthy children with spontaneous puberty [SP], n = 26) and group 2 (patients with hypogonadotropic hypogonadism [HH], n = 16). The validation cohort included children who presented with complaints of delayed puberty. Intervention and outcome Participants were subjected to FSH stimulation test and GnRH analogue stimulation test. Cutoffs derived from the exploratory cohort for basal and FSH stimulated inhibin B (FSH-iB) were applied on the validation cohort. Basal LH, GnRH analogue-stimulated LH, basal inhibin B, and FSH-iB were compared with clinical outcomes on a prospective follow-up for prediction of onset of puberty. Results There was statistically significant increment in inhibin B after exogenous FSH in group 1 (SP) in both male (188.8 pg/mL; P = 0.002) and female (1065 pg/mL; P = 0.023) subjects. The increment was not statistically significant in group 2 (HH) in both sexes. FSH-iB at a cutoff of 116.14 pg/mL in males and 116.50 pg/mL in females had 100% sensitivity and specificity for labelling entry into puberty. On application of these cutoffs on the validation cohort, FSH-iB had 100% positive predictive value, negative predictive value, and diagnostic accuracy for prediction of pubertal onset. Conclusion Inhibin B was stimulable in both male and female subjects. FSH-iB can be considered a novel and promising investigation for prediction of onset of puberty. Future studies are required for further validation.

Objective To evaluate the role of basal and follicle-stimulating hormone (FSH)-stimulated inhibin B in differentiating premature thelarche from gonadotropin-dependent precocious puberty (GDPP). Method This was a prospective interventional study. Basal and FSH-stimulated inhibin B levels were estimated in girls presenting with thelarche < 8 years age ( n = 10), healthy girls with normal pubertal development (pubertal control) ( n = 8) and healthy prepubertal girls (prepubertal control) ( n = 7). Girls with early puberty were classified as premature thelarche or GDPP based on GnRH agonist stimulation test. Results Median (IQR) basal inhibin B levels (pg/mL) in premature thelarche was 5.42 (2.91, 30.58) and FSH-stimulated inhibin B was 236.72 (111.53, 4431.73) ( P = 0.043). Median (IQR) basal inhibin B in GDPP was 64.11 (24.96, 792.45) pg/mL and FSH-stimulated inhibin B was 833.66 (500.11–1266.18) pg/mL ( P = 0.043). Basal inhibin B was discriminatory between GDPP and premature thelarche ( P = 0.032). Median (IQR) basal inhibin B in prepubertal and pubertal controls was 20.36 (9.61, 29.12) and 75.48 (58.55, 165.55) pg/mL, respectively. Conclusion Basal inhibin B is useful in differentiation of premature thelarche from GDPP while the role of FSH-stimulated inhibin B needs to be further explored in large sample size.

Purpose The current study aimed to report cases of McCune Albright syndrome (MAS) with growth hormone (GH) hyper secretion along with a systematic review of literature to elucidate challenges and intricacies in its diagnosis and management. Methods It was a single centre study carried out in individuals with MAS and autonomous GH secretion (AGHS). In addition, a systematic search of literature across three databases (PubMed, Scopus and EMBASE) was performed from inception until May 31, 2021 to identify cases of MAS with AGHS in the pediatric age group (<18 years). Results Three cases from authors centre and 42 cases identified from systematic literature review were analysed. Precocious puberty was the most common presenting endocrinopathy seen in 56.8% (25/44) cases, followed by hyperthyroidism (10/45), hypophosphatemia (4/45), and hypercortisolism (2/45). Cranio-facial fibrous dysplasia (CFFD) was seen in all while polyostotic fibrous dysplasia and Café au lait macule was seen in 40/45 (88.9%) and 35/45 (77.8%), respectively. Pituitary adenoma (58.3% microadenoma) was localized in 53.3% (24/45) cases on pituitary imaging. Biochemical and clinical remission of AGHS was achieved in 61.5% (24/45) cases with medical therapy. Conclusion Diagnosing AGHS in MAS is challenging because of concomitant presence of CFFD, non-GH endocrinopathies associated height spurt and elevated serum IGF-1. GH-GTT should be performed in presence of elevated growth velocity and serum IGF-1 (>1 X ULN) despite adequate control of non-GH endocrinopathies. Medical management can lead to disease control in substantial number of cases and often entails use of multiple agents.

IntroductionPheochromocytoma during pregnancy is a rare cause of secondary hypertension with lethal consequences to both mother and fetus. As patients are young, the possibility of syndromic associations like MEN-2, VHL, NF-1, etc., needs to be considered. MethodologyThree primigravida were diagnosed before the 20th week of gestation when they presented with classical triad of pheochromocytoma.ResultsDiagnosis of pheochromocytoma was confirmed by 24 h urinary metanephrine/normetanephrine or epinephrine/norepinephrine levels. Non-contrast MRI abdomen could localize the tumor. One patient had medullary thyroid carcinoma with hyperparathyroidism, indicative of MEN-2A. Another patient had brain stem hemangioblastoma, pancreatic cysts and family history of spinal hemangioblastoma, so diagnosed to have Von Hippel-Lindau (VHL) syndrome. Whereas, the third patient had sporadic pheochromocytoma. Preoperatively, they required antihypertensive medications including prazosin and metoprolol. They underwent laparoscopic/open adrenalectomy between 19th and 21st week of gestation without complication. Histopathology in all the three patients revealed low-grade pheochromocytoma by pheochromocytoma of the adrenal gland scaled score. None required antihypertensive medications after surgery. All the three newborns were small for gestational age, while one neonate expired due to intra-cardiac rhabdomyoma. So, the timely evaluation and surgical intervention for pheochromocytoma avoid lethal consequences.ConclusionsPregnancy leads to unmasking of pheochromocytoma as it is physiological stress. The syndromic association is more frequent as the population is younger. A poor fetal outcome like IUGR can be explained by endovascular changes in uterine vessel or due to the associated manifestations of MEN-2A, VHL syndromes. Family members should be screened for associated syndromic feature.

Background: Predicting puberty is a clinical challenge. Available tests include basal gonadotropins, GnRH and GnRH analogue stimulation test, hCG stimulation test and basal inhibin B(INHB). Unlike GnRH and GnRH analogue stimulated LH, no study has investigated for possibility of rapidly releasable pool of inhibin B from gonads so far. Therefore, in quest of a better diagnostic test present study was undertaken to explore stimulability of inhibin B and if found stimulable, potential role of FSH stimulated inhibin B(FSH-INHB) as marker of entry into puberty. Methods: A total of forty-two subjects fulfilling eligibility criteria were enrolled into this prospective interventional study. Study cohort was divided into Cohort A (Healthy children in puberty; n=26) and Cohort B (Patients of hypogonadotropic hypogonadism; n=16). All participants were subjected to FSH stimulation test and GnRHa stimulation test as per study protocol. Data was analysed for male and female separately. Results: Mean delta change between INHB and FSH-INHB in cohort A (Male; n=18) was 188.8 pg/ml (p value-0.002) while in cohort B(Male; n=8) was 16.64 pg/ml (p value-0.076). Mean delta change in cohort A(Female; n=8) was 1065 pg/ml (p value- 0.023) while in cohort B (Female; n=8) was 9.8 pg/ml (p value-0.128). On ROC analysis, INHB of 68.88 pg/ml in male had 94.4 % sensitivity and 87.5% specificity while 51.47 pg/ml in female had 75% sensitivity and 100% specificity for entry into puberty. Cut off for FSH-INHB were 116.14 pg/ml and 116.50 pg/ml for male and female respectively (100% sensitivity/100% specificity). Conclusion: Inhibin B was stimulable in both male and female after entry into puberty, highlighting the presence of rapidly releasable pool in ovaries and testes. FSH stimulated inhibin B may emerge as promising tool for entry into puberty.