Endocrine Abstracts

Introduction: Proinflammatory cytokines, for example interleukin-6, have been found to stimulate the HPA axis at all levels. In animal models glucocorticoids have been shown to suppress cytokines. There may therefore be a balanced interaction during stress when both are raised. For this reason, we investigated patients undergoing routine coronary artery bypass grafting on day 3 post-operatively (CABG) to examine the mechanisms for failure of suppression of the HPA axis in resp...

Nicotine has been reported to have detrimental effects on fibroblasts while androgen metabolites and oestradiol are potentially anabolic. The aim of this investigation is to study the effects of oestradiol and nicotine on androgen metabolism as an index of healing. Monolayer cultures of human gingival fibroblasts (Approved by the local Ethics Committee) were established in Eagle's MEM with 14C-testosterone / 14C-4-androstenedione (4-A) as substrates. (Nicotine (N:1,50 microgra...

The anti-convulsant phenytoin stimulates matrix synthesis in inflamed gingivae. Oestrogen and androgen metabolites have anabolic effects on target tissue. The aim of this investigation is to study the effects of phenytoin on androgen metabolism in human gingival fibroblasts in response to oestradiol and the anti-androgen finasteride (approved by the local Ethics Committee). Monolayer cultures of human gingival fibroblasts were established in Eagle's MEM with 14C-testosterone a...

Alkaline phosphatase (ALP) is an important enzyme in the turnover of connective tissue and bone matrix. In view of the anabolic effects of the physiologically active androgen metabolite 5alpha dihydrotestosterone (DHT), it was relevant to investigate the effects of ALP and its inhibitor levamisole (L) on androgen metabolism in oral periosteal fibroblasts. Four cell-lines of oral periosteal fibroblasts (approved by the local Ethics Committee)were incubated in duplicate in Eagle...

Phenytoin (Ph) causes gingival overgrowth in inflamed gingivae. Androgen metabolism could be influenced by alkaline phosphatase activity and inhibited by the alkaline phosphatase inhibitor levamisole (L). In view of the anabolic role of the androgen metabolite 5alpha dihydrotestosterone (DHT), the aim of this investigation is to study the effects of Ph, histamine (H) and the alkaline phosphatase inhibitor levamisole (L) on the metabolism of androgen substrates by human gingiva...

Measurement of urinary free cortisol (UFC) in overnight, early morning and 24h sample collections are often used to assess potential effects of inhaled or intranasal corticosteroids (ICS) on the HPA axis. In the present study the effects of single inhaled doses of fluticasone propionate (FP), Budesonide (Bud), Triamcinolone acetate (TAA)(molar equivalence; 1750, 1600 and 1600 micrograms respectively) and placebo on UFC excretion was investigated in 13 healthy male subjects. UF...

In human GL cells, 11beta-HSD catalyses the interconversion of cortisol (F) with its inert 11-ketosteroid metabolite, cortisone (E). Since GL cells synthesise prostaglandins (PGs), and PGs have been shown to modulate the expression and activity of the cloned 11beta-HSD enzymes, the objective of the present study was to establish whether locally synthesised PGs affected the net oxidation of F to E by 11beta-HSD in human GL cells recovered from the ovaries of women undergoing co...

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...

Primary hyperaldosteronism ('Conn's syndrome') may have a prevalence as high as 10% in hypertensive patients, and in some cases there may not be obvious hypokalaemia. Recently the use of a single aldosterone/ renin ('A/R') ratio has been advocated as a screening test for Conn's, and less influence by anti-hypertensive drug therapy has been claimed.We have established a cut-off for ambulant A/R ratios of 25 ng/mU using the DPC'Coat-a-Count' aldosterone method and the Nichols 'A...

Plasma and urine 18-hydroxycortisol ('18-OHF') measurements are helpful to discriminate primary hyperaldosteronism (Conn's syndrome) caused by adrenal hyperplasia (normal 18-OHF) from adrenal adenoma or glucocorticoid suppressible hyperaldosteronism ( raised 18-OHF). We have developed DELFIA time-resolved fluorescence assays for 18-OHF as a second-line biochemical investigation for patients with raised plasma aldosterone/ renin ratios. Following ether extraction, test samples ...

Background: The 250microgram synacthen test may give false negative responses, and will not allow easy discrimination between primary and secondary dysfunction. Furthermore, the use of synacthen is contra-indicated on the data sheet in certain common conditions such as asthma, and may not easily be interpreted in women taking oral oestrogen. Some patients with incipient adrenal failure may have elevated plasma ACTH, whilst passing the synacthen test. We have routinely measured...

We assessed whether the hypothalamic-pituitary-adrenal (HPA) axis is affected after withdrawal of oral steroids in patients who have been on steroids for at least ten years. Recent advances in treatment of patients with severe asthma with inhaled fluticasone propionate, and the use of steroid sparing drugs such as methotrexate has allowed the withdrawal of long term oral steroids in patients who otherwise had steroid dependant disease.We performed a 250 ...

Acute cortisol increase in man, whether from endogenous or exogenous sources, is associated with changes in cortisol:cortisone equilibrium. We have examined these during normal daily circadian rhythms and following treatment with hydrocortisone. Following local ethical committee approval, four adult volunteers (2 male) collected urine samples over 3 hour periods starting from midnight and over hourly periods between 0600 & 0900 to define the morning cortisol peak. They pro...