Endocrine Abstracts

Background: Thyroid disease is associated with BMI with hyperthyroidism causing weight loss and hypothyroidism leading to weight gain. However, the relation of body weight distribution to thyroid function in euthyroid individuals is unclear. This study assessed body composition in euthyroid women.Methods: Euthyroid women (n=1072) from the Osteoporosis and Ultrasound Study (OPUS), a population based cohort study recruited participants from 5 Europe...

The prevalence of primary hyperparathyroidism (PHPT) is increasing and the majority (over 85%) are now asymptomatic and remain untreated. In order to know whether or not they can be left safely without surgery, issues on disease progression need to be addressed. We aimed to update the natural history of PHPT, with a focus of serum calcium progression in mild untreated patients, selected from a large pre-defined cohort of PHPT in Tayside, Scotland. Possible predictors of progre...

GH and IGF1 play an important role in cardiac development and function. Conditions leading to abnormal GH levels are associated with cardiovascular disease. Although acromegaly is associated with hypertension, insulin resistance, diabetes type 2 and dislipemia, several studies ascribe the heart alterations displayed by these patients to the direct action of chronically elevated GH and IGF1 levels.Given that insulin acts as a growth factor to the heart an...

Introduction: One of the most promising potential targets for new treatments in Graves ophthalmopathy (GO) is the insulin-like growth factor 1 receptor (IGF1R). However, a significant impediment to the translational pathway in developing new treatments for GO is the lack of any animal or in vitro model.Aims: To characterise dysregulation of IGF1 pathway related gene expression in GO. To develop a new in vitro model for tissue expansion in G...

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoids thus amplifying their intracellular actions. 11β-HSD1 deficiency or inhibition, which improve metabolic syndrome and attenuate atherosclerosis in vulnerable rodent strains, is a target for drug development. However, 11β-HSD1 also converts 7-ketocholesterol (7KC) (which accumulates in fatty tissues), to the potentially more atherogenic, 7β-hydroxycholesterol. Whether a...

Congenital adrenal hyperplasia due to P450 oxidoreductase (POR) deficiency (ORD) results in disordered sex development (DSD) in individuals of both sexes. POR provides electrons to CYP17A1 thereby facilitating synthesis of the major androgen precursor dehydroepiandrosterone (DHEA). ORD disrupts this enzymatic step, resulting in deficient synthesis of 5α-dihydrotestosterone (DHT) via DHEA, readily explaining undervirilisation (46,XY DSD) in male ORD neonates. Female virili...

In humans, androgen synthesis crucially depends on the enzyme CYP17A1 expressed in adrenals and gonads. The 17,20 lyase activity of CYP17A1 catalyses the key step in human androgen biosynthesis, the conversion of 17-hydroxypregnenolone to the universal sex steroid precursor dehydroepiandrosterone (DHEA). For its catalytic activity, CYP17A1 requires electron transfer from P450 oxidoreductase (POR). Mutations in CYP17A1 and POR are known to disrupt human androgen s...

Objective: Hypothyroidism is common and predominantly managed in primary care. Symptoms are non-specific, with thyroid function tests (TFT) required for diagnosis. We sought to investigate current practice in levothyroxine prescribing in primary care.Methods: We studied the initiation of levothyroxine using the General Practice Research Database (GPRD), the world’s largest database of anonymised medical records. Individuals with i) thyroid cancer ii...