Endocrine Abstracts

Central obesity and increased visceral adipose tissue (VAT) are key factors contributing to metabolic dysfunction in PCOS. We therefore hypothesized that there would be alterations in the morphology and function of adipocytes from visceral fat depots. The female offspring of pregnant sheep treated biweekly with either 100 mg of testosterone propionate (TP) or vehicle control (C) from day 62–102 of gestation develop a clinically realistic PCOS-like condition. They develop ...

Women with Polycystic Ovary Syndrome (PCOS) are at increased risk of developing insulin resistance, obesity and dyslipidemia, however obesity per se does not explain the higher incidence of insulin resistance in PCOS women when compared to the general population. Altered adipose tissue morphology and function may be a central factor contributing to metabolic disturbances in PCOS. Using a clinically realistic ovine model of PCOS we reported hyperinsulinaemia and early ...

Exposure of pregnant sheep to increased concentrations of testosterone during midgestation results in a PCOS-like condition in the female offspring that includes increased hepatic IGF1. The aim of this study was to investigate the molecular pathophysiology of this increase. We studied 11-month-old female offspring whose mother had been treated with testosterone propionate (TP: 100 mg) in oil (n=8), or oil control (n=4) twice weekly from day 62 to 102 gestatio...

In patients with diabetes an isolated ‘sausage toe’ is suggestive of underlying osteomyelitis. Neuropathic (Charcot) arthropathy, devastating complication of diabetes, normally presents in the midfoot and can be precipitated by surgery or minor trauma.We report a 62-year-old man with a 2-year history of well controlled type 2 diabetes (HbA1c 56 mmol/mol), with no micro or macro vascular complications, referred to diabetic podiatrist with a hot,...

Background: The potential for a healthy life is programmed by in utero development. Fetal development is impacted by perturbed hormonal signalling, with lifelong consequences. Polycystic Ovary Syndrome (PCOS), affecting over 10% of women, is an important condition linked to an altered prenatal endocrine environment. Women with PCOS have increased androgen concentrations, including during pregnancy. Increased prenatal androgen exposure is associated with a PCOS-phenoty...

Within target cells, cortisol-cortisone inter-conversion is catalysed by both a NADP(H)-dependent, bidirectional type 1 11β-hydroxysteroid dehydrogenase (11βHSD1) enzyme and by a NAD+-dependent, unidirectional type 2 11βHSD (11βHSD2) isoenzyme. Since several published studies have reported altered glucocorticoid metabolism in polycystic ovary syndrome (PCOS), the current study assessed whether prenatal exposure of lambs to testosterone propionate...

Thyrotoxicosis is characterised by increased osteoclast activity. Thyroid hormone receptor alpha (TRα) is the predominant TR-isoform in bone and mice lacking TRα have skeletal hypothyroidism with impaired osteoclastic bone resorption. By contrast, mice lacking TRβ have skeletal hyperthyroidism and increased bone resorption. Thus, we hypothesized that T3 acts via TRα to stimulate osteoclastogenesis. Osteoclasts were differentiated in vitro ...

The type 3 deiodinase enzyme (D3) inactivates T3 and prevents activation of T4 to protect the fetus from premature exposure to thyroid hormones. Rapidly falling levels of D3 activity and rising levels of T3 at birth initiate the onset of cell differentiation and organ maturation during the post-natal period. Congenital hypothyroidism causes delayed ossification with reduced bone mineral deposition and short stature. We hypothesize that increase...

Similar to thyroid hormones, the calcineurin/NFAT pathway regulates bone mass via its actions in osteoblasts and by indirect effects on osteoclast function. Calcineurin is a calcium- and calmodulin-activated phosphatase that dephosphorylates the transcription factor NFAT enabling its translocation to the nucleus. RCAN2 is an inhibitor of calcineurin that is stimulated by T3 in brain, heart and skeletal muscle although its expression in bone has not been studied. Thu...

MEN2B is the most aggressive form of MEN2. Consequently, the new American Thyroid Association guidelines recommend prophylactic thyroidectomy early in the first year of life. Ninety-seven percentage of MEN2B cases result from a germline methionine to threonine mutation at codon 918 (M918T) of the RET proto-oncogene. In addition, an exceedingly rare alanine to phenylalanine mutation at codon 883 (A883F) has been reported in 4 unrelated adults. In each case metastatic MTC and th...