Endocrine Abstracts

Introduction: Testicular germ cell tumours are the most frequent cancer of young men. Epidemiological and clinical data have suggested that fetal or perinatal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, EEDs (like bisphenol A (BPA) are often weak ligands for classical nuclear estrogen receptors.Using a human seminoma cell line (JKT-1), devoid of ERα...

The calcium-sensing receptor (CaSR) belongs to family C of G-protein coupled receptors (GPCRs) that bind glutamate, GABA, taste molecules and pheromones. Loss-of-function mutations of the CASR gene located on chromosome 3q21–24, cause familial benign hypocalciuric hypercalcaemia type 1 (FBHH1). The genes causing FBHH2 and FBHH3, whose chromosomal locations are on 19p and 19q13.3, respectively, remain unknown. FBHH3, sometimes called the Oklahoma variant (FBHHO...

Progressive osseous heteroplasia (POH, MIM 166350) is a rare autosomal dominant disorder characterised by extensive dermal ossification during childhood, followed by widespread heterotopic ossification of skeletal muscle and deep connective tissue. Recently, genetic basis was found to be common with Albright’s hereditary osteodystrophy (AHO) (Shore et al., 2002): paternally inherited inactivating mutations of the GNAS1 gene were found. GNAS1 is the ge...

By including the synthetic glucocorticoid (GC), dexamethasone, in the maternal drinking water on gestational days 16–19 (0.5 μg/ml) or days 1–7 after birth (1.0 μg/ml), we have recently demonstrated (McArthur et al. J. Neuroendocrinol. 17: 475) that perinatal exposure of rat pups to GCs increased dopaminergic (DA) cell numbers in the adult ventral tegmental area (VTA) at −5.1 to −5.4 mm relative to Bregma (level I). In order to investig...

By direct measurement of muscle sympathetic nerve activity (MSNA) we previously demonstrated a markedly decreased adrenergic tone in newly diagnosed acromegalic patients. The present study was aimed at confirming this finding in a larger group of patients and establishing the pathophysiological role of insulin resistance, GH and IGF1 levels, circulating leptin and extracellular water (ECW) in this abnormality.Study design: Fifteen de novo patients...

The Thyrotropin receptor (TSHR) is known as the important key-player for regulation of thyroid growth and function. As a G-protein coupled receptor (GPCR) TSHR predominantly activates the Gs/adenylyl cyclase and the Gq/11 phospholipase C signaling pathways, that finally regulate thyroid hormone production. Aberrant thyroid hormone production can be caused by activating TSHR mutations in case of toxic thyroid nodules or non-autoimmune hyperthyroidism or via inactivating mutatio...

Case: A 44-year-old lady was diagnosed with Acromegaly (IGF-1 of 1315 ng/ml, prolactin 498 mu/l). She was also thyrotoxic clinically and biochemically with T4 29 pmol/l (normal 9-26), total T3 3.24 nmol/l (normal 0.9–2.2) but high TSH of 3.50 mu/l (normal 0.35–3.5). Further work-up with TRH testing and α-subunit measurement confirmed a TSHoma. Pituitary MRI scan showed a macroadenoma displacing optic chiasm and extending into cavernous sinu...

The pharmacology and function of G protein-coupled receptors (GPCRs) is frequently studied following expression of a single receptor in heterologous cell lines. However, many GPCRs are co-expressed. We wished to investigate how expression of pairs of receptors might modulate their function. Using a Human Embryonic Kidney 293 cell line in which the CB1 cannabinoid receptor was expressed constitutively and in which varying levels of expression of the orexin-1 receptor could be i...

Although amyloid deposition can cause a goitre thyrotoxicosis secondary to amyloidosis is rare. We report a case of fatal systemic amyloidosis presenting as thyrotoxicosis.A 62-year-old previously healthy male presented with heat intolerance, weight loss and tremor. On examination he had moderate sized firm goitre and mild dysthyroid eye disease. Biochemistry confirmed thyrotoxicosis; serum free T4 47 pmol/l (normal 10–25) freeT3 14.4 pmol/l (normal...

We present a case of 55 years old obese man with type 2 diabetes of 13 years duration, seen in diabetes clinic. His HbA1c had been 8–10% for about 7 years despite being on maximum doses of sulphonylurea and metformin.It was decided to start him on 30/70 mixed insulin and Metformin was continued. His HbA1c did not improve despite aggressive insulin titration. His injections became painful as insulin doses increased and resistance was noted on injecti...