Endocrine Abstracts

Introduction: Acromegaly links to cardiomyopathy and potential cardiac failure, if untreated. Mechanisms involved in acromegalic cardiomyopathy are incompletely understood. We investigated the effects of growth hormone (GH) excess and somatostatin receptor ligands (SRLs) on cardiac fibrosis using an acromegalic mouse model with pituitary-specific deletion of the Aip gene coding aryl hydrocarbon receptor interacting protein (AipFlox/Flox;Hesx1<su...

Background: Pituitary neuroendocrine tumours (PitNETs) have almost invariably benign histopathological characteristics but result in comorbidity and mortality. There has been interest in the composition of the PitNET immune microenvironment, particularly with the advent of immunotherapy-associated hypophysitis linked to PD-L1 and CTLA-4 checkpoint inhibitors. The innate immune cGAS-STING pathway is activated by DNA damage and DNA damage is a known feature of somatotrophinomas....

Context: Serum IGF-binding protein-3 (IGFBP-3) and molar IGF-I to IGFBP-3 ratio can aid the diagnosis of GH-related diseases. However, their clinical utility is limited by lack of validated reference intervals.Objectives: To establish age-, gender- and Tanner stage-specific reference intervals for IGFBP-3 and IGF-I to IGFBP-3 ratio for Indian ethnicity.Setting and Participants: We conducted a cross-sectional epidemiological study (...

Non-functioning pituitary adenomas (NFPAs) are the second most common subtype (15-43%) of all clinically presenting pituitary adenomas. Although the primary treatment of symptomatic NFPAs is surgery, gross total resection is achieved only in about 66% of the cases, and 20% of gross total resected tumours recur after 10 years. Despite recent advances in medical management of pituitary tumours, NFPAs remain the only subtype with no widely accepted pharmacological treatment. Expr...

Context: To diagnose and monitor GH-related disorders, serum IGF-I is a cornerstone, but Indian ethnicity based data, following consensus criteria for establishment of normative data are not available.Objectives: To generate normative IGF-I data for chronological age, bone age (BA) [Greulich & Pyle] and Tanner stage for both genders.Setting and Participants: We conducted a cross-sectional epidemiological study for children (age...

Context: Serum IGF-1 levels are of paramount importance for diagnosis and management of growth related disorders. The reference range of IGF- 1 should be ethnicity and Tanner specific. Indian data on the same is scarce and there is a need to develop the same.Objective: To develop age, sex and Tanner based normative reference range of serum IGF-1 level for Indian children and correlate the same with peri-pubertal hormonal parameters.<p class="abstext"...

Whilst several key genetic contributors to the phenotype of central precocious puberty (CPP) have been recognized, many familial cases remain without a clear genetic aetiology. Methyl-CpG-binding protein 2 (MECP2) is a chromatin-associated transcriptional regulator, which plays an essential role in neuronal maturation. It is encoded by the MECP2 gene, located at chromosome Xq28, which is highly expressed in brain tissues. Loss-of-function mutations in MECP2 are usually associa...

Introduction: Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene predispose to growth hormone (GH, 90% of patients) or prolactin (PRL)-secreting tumours, with negligible number of patients with other pituitary tumour types. Animal models of acromegaly are scarce and Aip models have controversial data. Therefore we have generated two pituitary-specific Aip knockout mouse models to study the consequences of loss of AIP p...

Introduction: Heterozygous mutations in the AIP gene are associated with young-onset pituitary adenomas while homozygous loss of AIP in animal models is lethal. As early diagnosis could lead to better outcomes, family members of AIP mutation-positive patients need follow up. The R304Q variant is commonly described as pathogenic based on clinical assessment. However, it is also present in the general population (minor-allele-frequency (MAF) 0.0007&#15...

Introduction: Approximately 25% of medullary thyroid cancer (MTC) cases arise in a familial setting, either as MEN2 or fMTC. While most of these are caused by mutations in the RET gene, a few families have unidentified mutations. Recently, a frameshift mutation in the ESR2 gene (coding oestrogen receptor beta) was found in a family with RET-negative fMTC associated with C-cell hyperplasia. In vitro, transfection of mutant ESR2 led t...