Third-Generation Thyrotropin Receptor Antibody (TRAb) assay for predicting neonatal thyroid dysfunction in pregnant women with Graves' disease.

PURPOSE: The aim is to validate the third generation Thyrotropin receptor antibody (TRAb) assay for predicting neonatal thyroid dysfunction and adverse pregnancy outcomes in pregnant women with Graves' disease. METHODS: This prospective cohort study was conducted in TRAb positive pregnant women with Graves' disease and their off springs. The primary outcome was to assess different forms of neonatal thyroid dysfunction in relation to maternal and neonatal TRAb levels. The secondary outcome was to predict adverse pregnancy outcomes by using maternal TRAb levels. Serum T3, FT4, TSH, TRAb levels were measured using electrochemiluminescence immunoassay. RESULTS: 51 pregnant women were included. Five women had adverse pregnancy outcomes, TRAb levels of > 19.06 IU/L (10.9 times the upper limit of normal (ULN)) predicted adverse pregnancy outcomes with 100% sensitivity and 93.5% specificity. Among the 46 successful live births, 13 (28.3%) had neonatal thyroid dysfunction. Out of 13 neonates, 7 (32%) had neonatal thyrotoxicosis, 4 (18%) had primary hypothyroidism, and 2 (9%) had central hypothyroidism. Third trimester maternal TRAb levels of > 7.99 IU/L (4.6 times the ULN)and day three neonatal TRAb levels of > 5.03 IU/L (2.9 times the ULN), predicted the neonatal thyrotoxicosis with 100% sensitivity and 97.4% specificity. CONCLUSION: Very high maternal third generation TRAb levels strongly predicted the adverse pregnancy outcomes and neonatal thyroid dysfunction in pregnant women with Graves' disease. Neonatal thyroid function test along with the TRAb levels strongly correlated with different forms of neonatal thyroid dysfunction and is very useful in avoiding inadvertent treatment to neonates.

Clinico-radiological correlation of pituitary stalk interruption syndrome in children with growth hormone deficiency.

PURPOSE: To analyze the clinical, hormonal, and radiological characteristics of Pituitary stalk interruption syndrome (PSIS) in children with growth hormone deficiency (GHD). METHODS: This is a prospective cross-sectional study, conducted over a period of three years in a short stature clinic of tertiary care referral hospital. 57 severe short stature children with proven GHD were included in the study. RESULTS: Among 57 children with GHD, 14 (24%) were diagnosed as PSIS. The mean age at diagnosis was 11.8 ± 2.6years. The male to female ratio was 2.5:1. Nine (64%) children had multiple pituitary hormone deficiency (MPHD) and 5 (36%) had isolated growth hormone deficiency (IGHD). In spite of absent or ectopic posterior pituitary (EPP)in Magnetic Resonance Imaging (MRI) of PSIS cohorts, only one had Arginine vasopressin (AVP) deficiency. EPP was seen near median eminence in 6 (44%), elsewhere in 4 (28%), and absent in 4 (28%)children. The height gain following growth hormone therapy was better in PSIS cohorts as compared to non-PSIS. CONCLUSION: Male gender, breech presentation, external congenital anomalies like cryptorchidism, midline defects and nystagmus were more common in children with PSIS. MPHD were more frequently seen in PSIS whereas IGHD in non-PSIS cohort. AVP deficiency is very rare in PSIS despite of absent or ectopic posterior pituitary in MRI. High index of clinical suspicion in all severe short stature may lead to early diagnosis and prompt initiation of growth hormone treatment for better outcome.

A randomized controlled trial comparing myoinositol with metformin versus metformin monotherapy in polycystic ovary syndrome.

OBJECTIVE: Insulin resistance and hyperinsulinemia plays an important role in pathogenesis of polycystic ovary syndrome (PCOS). Metformin, Myoinositol and d-chiro-inositol acts as insulin sensitizers and exerts a beneficial effects in PCOS. The objective is to compare the effect of metformin monotherapy versus a combination of metformin with Myoinositol and d-chiro-inositol in PCOS. DESIGN: This study is a randomized controlled trial conducted over a period of 6 months. All overweight and obese women with PCOS with the age group between 18 and 35 were included and randomized into two groups, 27 in the metformin monotherapy arm and 26 in the myoinositol combination arm. PATIENTS AND MEASUREMENTS: The variables assessed were duration of menstrual cycle, anthropometric parameters, modified Ferriman Gallwey score, global acne score, Fasting insulin, HOMA-IR, fasting lipid profile, serum testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, anti-Mullerian hormone, and pelvic ultrasound to assess ovarian volume, PCOS Questionnaire score. Changes in the parameters from baseline at the end of 6 months of treatment were assessed and compared between the groups. RESULTS: Menstrual cycle regularity improved in both groups with significantly greater improvement in the group receiving myoinositol-based therapy (p < .001). Pregnancy rate was equal in both the arms. There was a significant improvement in PCOSQ score in myoinositol-based therapy group (p < .001). However, there was no statistically significant difference in other hormonal, metabolic parameters between two groups in spite of symptomatic benefits. CONCLUSIONS: The addition of myoinositol to metformin exerts additional benefits in improving menstrual cycle regularity, and quality of life in women with PCOS.

Clinical Profile and Molecular Genetic Analysis of Prader - Willi Syndrome: A Single Center Experience.

Aim: The prevalence of childhood and adolescent obesity is increasing worldwide as well as in India. Prader--Willi syndrome (PWS) is one of the most common causes of syndromic obesity with varied clinical manifestations across different lifespan. Herewith, we describe clinical and molecular characteristics of eight PWS who were diagnosed in an obesity clinic of tertiary care hospital. Materials and Methods: Clinically suspected cases of PWS were screened between January 2014 and January 2022. Detailed history and clinical examination were done to look for typical features of PWS like characteristic facial appearance, short stature, obesity, hyperphagia, delayed puberty or hypogonadism, diabetes mellitus, developmental delay, cognitive dysfunction, learning disabilities or abnormal behavior. All were evaluated, with 75 g oral glucose tolerance tests (GTT), HbA1c, Free T4, TSH, LH, FSH, testosterone, and growth hormone level. Intelligent quotient (IQ) of each patient was assessed by a psychiatrist using Binet-Kamat test. Molecular confirmation of clinically suspected PWS was done by either Methylation-specific polymerase chain reaction (MS-PCR) or Fluorescence in situ Hybridization (FISH) methods. Results: Based on clinical and molecular characteristics, eight were diagnosed as PWS. Except one, all were male with characteristic facies, mean age of study cohort was 12 years and mean BMI of 44.58. Obesity, short stature, hyperphagia, hypotonia, and mild to moderate mental retardation were noted in entire (100%) PWS study population. All male PWS patients had cryptorchidism, which was bilateral in six patients and unilateral (right undescended testes) in one. Apart from obesity, short stature, other endocrine associations noted were diabetes mellitus in 50% and subclinical hypothyroidism in 37% of PWS. Molecular characteristics of PWS were confirmed by Methylation-specific PCR in seven and by FISH method in one. Conclusion: Prader-Willi syndrome should be kept in mind in case of childhood or adolescent obesity with short stature, hypotonia, cryptorchidism, and developmental delay or cognitive dysfunction. Judicious use of molecular diagnostic testing should be made in all clinically suspected cases. Early diagnosis and appropriate management of this complex disorder by a multidisciplinary team will improve the quality of life and treatment outcome.

Fahr's Disease and Hypoparathyroidism - A Missing Link.

Fahr's disease is an idiopathic basal ganglia calcification with autosomal dominant inheritance. Prior to diagnosing Fahr's disease based on computed tomography (CT) and/or magnetic resonance imaging (MRI) of the brain, one should rule out hypoparathyroidism (HP), and pseudohypoparathyroidism (PHP). Treatments of these conditions are entirely different. HP- and PHP-related hypocalcemia requires calcium, calcitriol, and vitamin D therapy in a long run to avoid recurrent seizures whereas Fahr's disease is treated with an antiepileptic alone.

Clinical Profile of Addison's Disease in a Tertiary Care Institute, Southern India - The Changing Landscape.

Aims and Objectives: Clinical, biochemical, and radiological profiles of Addison's disease and to assess the various etiological spectrum of primary adrenal insufficiency (PAI) in adults. Materials and Methods: A retrospective cohort study was carried out in the Department of Endocrinology, Madurai Medical College, Madurai between January 2014 and January 2021 over a 7-year period. Inclusion Criteria: All the patients with clinical symptoms and or signs of suspected PAI, such as hyperpigmentation, weight loss, persistent nausea or vomiting, fatigue, and hypotension, were recruited. All suspected cases underwent measurement of 8-AM plasma ACTH and cortisol levels. In possible cases and equivocal cortisol levels, patients underwent Co-syntropin/ACTH stimulation test. To know the underlying etiology of PAI, 21-hydroxylase autoantibodies (21OHAb), thyroid function test, Anti TPO, calcium, parathyroid hormone (PTH), LH and FSH, CT of chest and abdomen, and sputum AFB based on the clinical pattern of involvement were performed. Exclusion Criteria: Patients with onset of PAI at infancy and childhood, secondary adrenal insufficiency or exogenous Cushing's syndrome, and central hypocortisolism, including Sheehan's syndrome, were excluded. Results: Thirty-six patients were diagnosed with PAI in this study; 19 (53%) were females and 17 were males (47%). The median age of diagnosis was 35 years. Patients were divided into acute presentation and subacute presentation. Twenty-six patients presented with acute presentation and ten were presented with progressive evolved symptoms. Non-tuberculous etiology was the predominant finding noted in our cohort study (87%, 31 out of 36 patients). The other causes of Addison disease included isolated auto-immune PAI, polyglandular autoimmune syndrome type 1 and II, APLA Syndrome, and adrenal metastasis. Conclusion: Non-tuberculous causes of PAI are the leading etiology in our retrospective study. Autoimmune PAI and Polyglandular autoimmune syndromes are increasingly being recognized as the cause of Addison's disease. PAI individuals require lifelong surveillance for possible development of coexisting autoimmune syndromes and need for glucocorticoid/mineralocorticoid therapy.

The Spectrum of CYP21A2 Gene Mutations from 16 Families of Congenital Adrenal Hyperplasia: Genotype-Phenotype Correlation.

Aim: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder of the adrenal steroidogenic pathway. The most common form of CAH is due to 21-hydroxylase deficiency resulting from mutations in CYP21A2 gene. The present study aimed to identify CYP21A2 common gene mutations, phenotype correlation, and to analyze the segregation pattern in CAH patients, parents, and siblings. Materials and Methods: Sixteen families having at least one classic CAH child in each family, a total of 58 subjects were recruited. The presence of six most common gene mutations, namely, Intron 2 (c.293-13A/C>G), c.844G>T (p.Val282Leu), c.1019G>A (p.Arg340His), c.92C>T (p.Pro31Leu), c.955C>T (p.Gln319*), and c.518T>A (p.Ile173Asn) in CYP21A2 gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using specific primers. Results: Out of 16 classic CAH females analyzed, salt-wasting (SW) form was present in 12 (75%) and simple virilizing form in four (25%) children. Isolated clitoromegaly was the most common clinical presentation followed by ambiguous genitalia. The most common mutation observed in CAH patient population was Intron 2 (c.293-13A/C>G) (100%) followed by p.Pro31Leu (98%), p.Gln319* (93%), p.Val282Leu (91.4%), and p.Ile173Asn (19%). Although p.Arg340His mutation was not observed in this study. Interestingly, Intron 2 (c.293-13A/C>G) homozygous was observed in 31.3% of the entire study cohort and p.Ile173Asn mutation was found to be associated with SW form. Conclusions: Our results suggested a high prevalence of CYP21A2 gene mutations among CAH patients and heterogeneous mutation spectrum in their families of south Indian cohort. The outcomes afford valuable evidence for premarital and prenatal screening as well as planning suitable programs to prevent the development of CAH in Indian population.