Endocrine Abstracts

Case: A 19-year-old British-Asian man presented with a two-year history of gynaecomastia. He had no other symptoms of hypogonadism. On examination, BMI was 28 kg/m2 and he had post-pubertal-sized testes (20 ml) with normal secondary sexual characteristics. Hypogonadism was confirmed by two morning fasting total testosterone levels of 4.7 and 5.2 (RR 9.2–31.6 nmol/l). Haemoglobin was normal (152 g/l) and serum oestradiol was <100 pmol/l. He had inappropriate...

Introduction: Thyroid cancer is one of the most common malignancies of the endocrine system and displays a variety of histological patterns. The understanding of the molecular pathogenesis and the identification of molecular markers which will be used for diagnosis and prognosis is of high clinical significance. The most common molecular alterations include BRAF and RAS point mutations and RET/PTC and PAX8/PPARγ rearrangements. The pres...

Introduction: Kallmann syndrome (KS) is a rare genetic disorder typically due to defective migration of olfactory-axons and GnRH-neurons. KS results in congenital hypogonadotrophic hypogonadism (CHH) typically associated with absent (anosmia) or reduced (microsmia) sense of smell. Unilateral hypoplastic/absent olfactory bulbs on MRI are reported, although disturbance in smell is usually bilateral. Here, we present an unusual case of KS with unilateral anosmia....

Clinical Endocrinology 2016 84 939–945. DOI: 10.1111/cen.12603...

Background: Hot flushes (HF) affect 70% of menopausal women and can be debilitating. Oestrogen administration is effective but not without risk. Neurokinin B signalling is increased in menopausal women, and is likely critical in the aetiology of their HF. We therefore hypothesised that a neurokinin 3 receptor (NK3R) antagonist could attenuate menopausal flushing.Design: This single-centre, phase 2, randomised, double-blind, placebo-controlled, crossover ...

Clinical Endocrinology 2016 84 939–945. DOI: 10.1111/cen.12603...

Background: Hot flushes (HF) affect 70% of menopausal women and can be debilitating. Oestrogen administration is effective but not without risk. Neurokinin B signalling is increased in menopausal women, and is likely critical in the aetiology of their HF. We therefore hypothesised that a neurokinin 3 receptor (NK3R) antagonist could attenuate menopausal flushing.Design: This single-centre, phase 2, randomised, double-blind, placebo-controlled, crossover ...

Introduction: Hypothalamic amenorrhoea (HA) is a condition characterised by reduced GnRH pulsatility and is a common cause of anovulatory subfertility. Kisspeptin is an endogenous neuropeptide that regulates hypothalamic GnRH function. Hypothalamic kisspeptin expression is reduced, and kisspeptin receptor expression is increased, in a rodent model of HA. The kisspeptin analogue MVT-602 has a 3-4-fold longer half-life than native kisspeptin-54 (t1/2 0.5 h). We invest...

Background: Hot flushes affect 70% of menopausal women, can be long-lasting, and often severely impact on physical, psychosocial, sexual, and overall wellbeing. Hormone replacement therapy is effective but not without risk. Neurokinin B is an important mediator of hot flushes in rodents and elevated hypothalamic expression occurs in menopausal women. Neurokinin B acts via the neurokinin 3 receptor. We therefore hypothesised that neurokinin 3 receptor antagonism could be a nove...

Background: Hypothalamic KNDy neurons have recently been identified as key regulators of reproductive function by releasing three neuropeptides namely kisspeptin, neurokinin B (NKB) and dynorphin. Animal studies show they interact to control pulsatile GnRH release, which is vital for fertility. In animals, kisspeptin stimulates, NKB modulates and the opioid dynorphin inhibits GnRH pulsatility. However, the interaction of these peptides has never been studied in humans. To inve...