Endocrine Abstracts

Introduction: Cyclooxygenase-2 (COX-2), an inducible enzyme in prostaglandin synthesis, plays a major role in the pathogenesis of sporadic colorectal carcinoma (CRC). COX-2 inhibitors reduce the mortality from sporadic CRC. Acromegaly is associated with an increased risk of CRC, with a preponderance of right sided disease, but COX-2 protein is reduced or absent in acromegalic normal and malignant colonic mucosa. The mechanisms responsible for this are unknown.Aims: (i) To ...

Background: Acromegalics are at increased risk of developing colorectal neoplasia with an increase of right-sided disease. Several genes are implicated in colorectal neoplasia including components of the GH/IGF-1 axis. It is unclear whether regional variations in neoplasia are explained by variations in local expression of these genes. Aims: To compare the expression of the components of the GH/IGF-1 axis and other putative genes between the left and right colon of patients wi...

Background: Patients with acromegaly have an increased risk of colorectal neoplasia. In non-acromegalic subjects, carcinomas develop from dysplastic tubular adenomas and colonoscopic removal of these reduces the subsequent incidence of carcinoma. The frequency of such screening in acromegaly is controversial and it is uncertain which patients should be considered to be at particular increased risk. Methods: We reviewed the incidence of new colonic lesions amongst our large coh...

Background: We have previously demonstrated colonic expression of the endogenous GH secretagogue, ghrelin, but not the GHS-R, and that ghrelin exerts proliferative effects on colonic epithelial cells. However, whether these are specific to ghrelin, or which genes are affected in response is uncertain.Aims: Determine the specificity of the proliferative effects of ghrelin on colonic epithelial cells, and effects on mRNA levels of the cancer associated ge...

Background: Human toxicity of bisphenol-A (BPA), a weak estrogenic environmental endocrine disruptor widely used in plastics, babybottles, cans and dental sealants, is under investigation. Human pharmacokinetics involves a rapid inactivation by hepatic glucuronyl- or sulfoconjugation and renal clearance. Fetal or perinatal exposure in rodents is associated with programmed adult reproductive diseases. Human epidemiological studies remain scarce especially concerning testicular ...

Activating mutations of the RET proto-oncogene, encoding a tyrosine kinase receptor, are associated with inherited syndromes, MEN2A and MEN2B, and with both familial and sporadic medullary thyroid cancer (MTC). Single base-pair missense mutations in the extracellular cysteine-rich domain are responsible for the majority of MEN2A and familial MTC (FMTC) cases. Rarely, somatic deletions and germline duplications of variable segments of the gene have been reported in spora...

Diazoxide is an agonist of ATP sensitive K+ (KATP) channels in beta-cells and is used in the treatment of hyperinsulinism caused by insulinomas or Hyperinsulinism in Infancy (HI). The responsiveness of patients to diazoxide is highly variable and complicated by side-effects which include hypertension and hypertrichosis. The aim of this study was to examine the actions of a novel benzothiadiazine-derivative, BPDZ-154, on beta-cell KATP channels and insulin release. W...

Cortisol metabolism is modulated by inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1) during GH replacement (Weaver et al, Clin Endocrinol, 1994, 41, 639; Gelding et al, Clin Endocrinol, 1998, 48, 153) and in active acromegaly (Moore et al, J Clin Endocrinol Metab, 1999, 84, 4172). 11 beta HSD1 activity is also influenced by both fat mass and insulin. To determine the relative contribution of GH/IGF-I to alteration in cortisol metabolism we have examined...

Grave’s disease is an autoimmune mediated thyrotoxicosis which accounts for 50–80% of cases of hyperthyroidism. In addition to non-thyroid organ involvement, presence of thyroid stimulating hormone receptor antibodies (TRAb) or increased uptake on a nuclear scan are diagnostic. Ultrasound typically shows a diffuse enlargement of the thyroid with increased vascularity, but up to 23% of patients are known to have thyroid nodules. Thyroid nodules carry a 4–6% risk ...

Functional hypothalamic amenorrhoea (FHA) is an endocrine disorder secondary to a deficiency of pulsatile gonadatrophin-releasing hormone (GnRH) secretion. It is not related to hypothalamus-pituitary organic lesions, endocrine or systemic disease. The clinical profile is dependant on the degree of GnRH suppression – it can range from an inadequate luteal phase to hypothalamic amenorrhoea. The incidence of FHA ranges from 15% to 48% of the secondary amenorrheas. We present...