Anders Dejgaard

THE ACUTE AND LONG TERM EFFECT OF THE H2‐RECEPTOR ANTAGONISTS CIMETIDINE AND RANITIDINE ON THE PITUITARY‐GONADAL AXIS IN MEN

We have investigated the effect on the human pituitary–gonadal axis of the H2‐receptor antagonists cimetidine 300 mg and ranitidine 50, 100, and 200 mg by i.v. bolus, or treatment for 6 months with either cimetidine (1000 mg/day for 1·5 months followed by 400 mg/day for 4·5 months) or ranitidine (200–400 mg/day for 1·5 months followed by 100–200 mg/day for 4·5 months). Administration of the H2‐antagonists (i.v.) to normal men did not cause any release of LH, FSH, or testosterone. Long‐term treatment with cimetidine of duodenal ulcer patients caused a significant rise in basal LH (6 weeks) and FSH secretion (11 weeks). Following reduction of the cimetidine dose LH and later FSH returned to pre‐treatment values. However, despite reduction of the cimetidine dose, the LH and FSH responses to LHRH stimulation were still significantly higher after 6 months of treatment compared with pre‐treatment responses. No changes were found in basal or in LHRH stimulated testosterone or dihydrotestosterone secretion. Treatment with the more potent H2‐antagonist ranitidine did not cause any change in basal or in LHRH stimulated LH and FSH secretion. The effects on LH and FSH secretion observed during cimetidine treatment might therefore be caused by other mechanisms than blockade of H2‐receptors. It is possible that cimetidine, having anti‐androgen properties, blocks pituitary or hypothalamic androgen receptors.

Modulation of Basal and LRH-Stimulated Gonadotrophin Secretion by Histamine in Normal Men

The effects of histamine (HA) and of HA in combination with H1- and H2-receptor antagonists on basal and LRH-receptor antagonists on basal and LRH-stimulated LH and FSH secretion were investigated in 10 normal men. HA enhanced the LH response to LRH (p less than 0.05), but had no effect on basal LH secretion. The enhancement of LRH-stimulated LH secretion was not observed when either an H1- (mepyramine) or an H2- (cimetidine) receptor antagonist was administered concomitantly with HA. Cimetidine administered alone had no effect on basal or LRH-stimulated LH secretion. HA had no effect on basal or LRH-stimulated FSH secretion. We conclude that the effect of HA on LRH-stimulated LH secretion is mediated through a combined stimulation of H1- and H2-receptors.

Veno-occlusive disease and peliosis of the liver after thorotrast administration

A case of veno-occlusive disease and peliosis of the liver without coexisting liver malignancy 35 years after thorotrast administration is presented. In the liver four main widely distributed lesions were found: Venoocclusive disease (VOD), peliosis, fibrosis and thorotrast deposits. Whether the VOD and the peliotic lesions are pathogenetically related or totally independent cannot be determined in the present case. However, the VOD and the peliosis are possibly related to the protracted alpha-emitting effect of thorotrast deposited in the liver parenchyma.

Plasma fibronectin concentrations in patients with liver diseases

Plasma, obtained just prior to diagnostic liver biopsy in 71 patients with various liver diseases, was examined by electroimmunoassay using immunoglobulin against human fibronectin and purified plasma fibronectin as standard. The plasma fibronectin concentration was not significantly different from age- and sex-matched healthy controls in patients with chronic persistent or chronic active hepatitis (n = 7), primary biliary cirrhosis (n = 8), alcoholic fatty liver (n = 9), alcoholic hepatitis (n = 10), and alcoholic cirrhosis (n = 16). Patients with acute viral hepatitis (type A (n = 2); type B (n = 7); type non A, non B (n = 1] had significantly (P less than 0.01) raised plasma fibronectin concentrations (median 506 mg/l (range 339-804] compared to controls (median 399 mg/l (range 304-462]. Morbidly obese patients with fatty liver (n = 11) had significantly (P less than 0.001) raised plasma fibronectin concentrations (median 610 mg/l (range 429-862] compared to controls (median 361 mg/l (range 303-419].

Plasma fibronectin concentrations in morbidly obese patients

Plasma fibronectin concentrations and liver morphology were investigated in 45 morbidly obese subjects (median overweight 88%) and in 42 normal weight controls, matched for sex and age. A significantly (P less than 0.01) raised plasma fibronectin concentration (median 464 mg/l, range 276-862 mg/l) was found in the obese subjects when compared with concentrations in the controls (median 348 mg/l, range 164-536 mg/l). Plasma fibronectin concentrations of the obese patients correlated significantly to their degree of overweight (r = 0.33, P less than 0.05) as well as to the degree of fatty change found in their liver biopsies (r = 0.33, P less than 0.05). Significantly (P less than 0.05) elevated plasma fibronectin concentrations even in obese subjects without hepatic fatty change indicate that liver fat accumulation is no prerequisite of the obesity-related elevation of plasma fibronectin. Raised plasma fibronectin concentration in obesity may more readily be explained by an increased fibronectin formation by lipocytes.

Plasma concentrations of pituitary and peripheral hormones during ranitidine treatment for two years in men with duodenal ulcer

SummaryThe effects of treatment for 2 years with the histamine H2-receptor antagonist ranitidine (100 or 200 mg b.d. for 6 weeks followed by 100 or 200 mg daily) on plasma concentrations of pituitary and peripheral hormones in ten men with duodenal ulcer have been investigated. Stimulation tests with TRH 200 µg i.v. and LHRH 100 µg i.v. were performed before, during (6 and 24 months), and at least 6 months after treatment.Basal and TRH-stimulated prolactin (PRL) secretion was marginally reduced after treatment for 6 months, but not for 24 months. The LH response to LHRH was slightly increased after treatment for 6 months and 24 months and after the end of treatment. The plasma concentrations of TSH, FSH, cortisol, androgenic hormones, and thyroid hormones did not change significantly during treatment. No adverse effects were reported during the observation period.The few, minor changes in pituitary hormone concentrations were all within the reference range. They may be related to ranitidine treatment, but are more likely to be due to age-dependent alterations in hormone secretion. It is concluded that long-term treatment with ranitidine does not cause major changes in circulating hormone concentrations.