Basal and FSH-stimulated Inhibin B in Precocious Puberty.

OBJECTIVE: To evaluate the role of basal and follicle-stimulating hormone (FSH)-stimulated inhibin B to differentiate 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 in premature thelarche was 5.42 (2.91, 30.58) pg/mL and FSH-stimulated inhibin B was 236.72 (111.53, 4431.73) pg/mL (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 prepubertal controls was 20.36 (9.61, 29.12) and 75.48 (58.55, 165.55) pg/mL, respectively. CONCLUSIONS: 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.

Autonomous growth hormone secretion due to McCune Albright syndrome in paediatric age group: an ominous triad.

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.

Pheochromocytoma in Pregnancy: A Syndromic Association.

Introduction: Pheochromocytoma 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. Methodology: Three primigravida were diagnosed before the 20th week of gestation when they presented with classical triad of pheochromocytoma. Results: Diagnosis 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. Conclusions: Pregnancy 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.

Four cases of Graves' disease following viral vector severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) vaccine.

Mass immunization has led to a decrease in the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) worldwide. At the same time, awareness regarding possible adverse effects of newly developed vaccines is critical. The present study was undertaken to report the cases of Graves' disease occurring after administration of viral vector vaccine (ChAdox1nCoV-19) and describe the clinical profile, response to treatment, and effect of administration of a second dose in patients developing Graves' disease. Four cases of Graves' disease after administration of the vaccine were noted. Two of these had a mild thyroid eye disease. Three cases were female and had a family/self-history of autoimmune disease. All cases responded well to treatment and became euthyroid within two to four months. Two patients exhibited worsening thyrotoxicosis after receiving a second dose of the vaccine. We propose that the temporal relationship between administration of the vaccine and the onset of symptoms establishes Graves' disease as an adverse event after the SARS-CoV-2 viral vector vaccine. Close follow-up is advisable in individuals developing Graves' disease after SARS-CoV-2 vaccination.

Spectrum of Endocrine Dysfunction and Association With Disease Severity in Patients With COVID-19: Insights From a Cross-Sectional, Observational Study.

Introduction: Evidence on new-onset endocrine dysfunction and identifying whether the degree of this dysfunction is associated with the severity of disease in patients with COVID-19 is scarce. Patients and Methods: Consecutive patients enrolled at PGIMER Chandigarh were stratified on the basis of disease severity as group I (moderate-to-severe disease including oxygen saturation <94% on room air or those with comorbidities) (n= 35) and group II (mild disease, with oxygen saturation >94% and without comorbidities) (n=49). Hypothalamo-pituitary-adrenal, thyroid, gonadal axes, and lactotroph function were evaluated. Inflammatory and cell-injury markers were also analysed. Results: Patients in group I had higher prevalence of hypocortisolism (38.5 vs 6.8%, p=0.012), lower ACTH (16.3 vs 32.1pg/ml, p=0.234) and DHEAS (86.29 vs 117.8µg/dl, p= 0.086) as compared to group II. Low T3 syndrome was a universal finding, irrespective of disease severity. Sick euthyroid syndrome (apart from low T3 syndrome) (80.9 vs 73.1%, p= 0.046) and atypical thyroiditis (low T3, high T4, low or normal TSH) (14.3 vs 2.4%, p= 0.046) were more frequent in group I than group II. Male hypogonadism was also more prevalent in group I (75.6% vs 20.6%, p=0.006) than group II, with higher prevalence of both secondary (56.8 vs 15.3%, p=0.006) and primary (18.8 vs 5.3%, p=0.006) hypogonadism. Hyperprolactinemia was observed in 42.4% of patients without significant difference between both groups. Conclusion: COVID-19 can involve multiple endocrine organs and axes, with a greater prevalence and degree of endocrine dysfunction in those with more severe disease.

FSH-stimulated Inhibin B (FSH-iB): A Novel Marker for the Accurate Prediction of Pubertal Outcome in Delayed Puberty.

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.

Acute Lymphoblastic Leukemia Presenting as Pituitary Apoplexy: A Case Report and Review of the Literature.

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.

Mortality in Asian Indians with Charcot's neuroarthropathy: a nested cohort prospective study.

AIMS: We studied mortality in individuals of diabetes with or without Charcot neuroarthropathy (CN). METHODS: People 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. RESULTS: Data 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. CONCLUSIONS: People with Charcot neuroarthropathy have almost three times increased risk of mortality despite being younger at presentation.