Evidence for a Thyrotropin Inhibitory Effect of Histamine in Man

Abstract

Because of certain side effects of cimetidine therapy which may be hormonally mediated (e.g. gynecomastia), there has been recent interest in the possible endocrine effects of this H2 histamine receptor-blocking agent used in the treatment of peptic ulcer disease. Accordingly, the effect of chronic cimetidine therapy on anterior pituitary function was examined in 12 adult men with mild peptic ulcer disease. TRH and insulin-hypolycemic stimulation tests were performed by standard methods. Serum for TSH and PRL RIA was obtained after TRH; serum for GH, cortisol, and PRL RIA was obtained after insulin-induced hypoglycemia. In addition, serum for LH, FSH, testosterone, and PRL was obtained every 4 h for 24 h. After these baseline studies, 300 mg cimetidine were administered orally 4 times a day for 4--8 weeks and the studies were repeated as before. Chronic treatment with cimetidine caused a significant increase in the peak TSH response to TRH at 30 min (mean peak TSH value before cimetidine, 7.0 microU/ml; after cimetidine, 10.2 microU/ml; P less than 0.05) as well as a significant increase in the TSH area under the curve. There was no statistically significant effect of cimetidine on basal TSH or basal or stimulated PRL secretion. Cimetidine had no effect on the GH, PRL, or cortisol response to insulin-induced hypolycemia or the 24-h secretion of LH, FSH, testosterone, or PRL.

Neurotransmitter Control of Thyrotropin Secretion

“…Not much more is known about the histaminergic system. In humans, cimetidine, the blocker of the H> histaminic receptors had no effect on either basal or stimulated TSH levels when giv en acutely [21,53,132], while chronic treatment seemed to increase the response to TRH [72]. Feeding histidine defi cient diets to rats to decrease histamine concentration and thus the histaminergic neurotransmission in the brain did not alter TSH levels [47].…”

The effects of ranitidine on pituitary‐thyroid function.

“…The hypothalamic median eminence contains histamine (May et al, 1979) and histamine H2-receptor antagonists modify pituitary hormone secretion. Intravenous cimetidine stimulates prolactin secretion (Carlson & Ippoliti, 1977), but most studies suggest prolonged oral treatment is without effect (Barber & Hoare, 1979;Van Thiel et al, 1979).…”

“…Intravenous cimetidine stimulates prolactin secretion (Carlson & Ippoliti, 1977), but most studies suggest prolonged oral treatment is without effect (Barber & Hoare, 1979;Van Thiel et al, 1979). Whether cimetidine influences TSH secretion and circulating thyroid hormone concentrations is unclear (May et al, 1979;Valk et al, 1981;Knigge et al, 1982). Intravenous ranitidine also stimulates prolactin secretion (Knigge et al, 1981) but prolonged oral use does not (Pasquali et al, 1981).…”

Effect of a Short-Term Oral Administration of Cimetidine and Ranitidine on the Basal and Thyrotropin-Releasing Hormone-Stimulated Serum Concentrations of Prolactin, Thyrotropin and Thyroid Hormones in Healthy Volunteers

“…The effect of an oral dose is more con troversial. Some studies have not reported any effect of cimetidine on PRL levels [May et al, 1979;Nelis and Van de Meene, 1980a;Valk et al, 1981] but others described a slight stimulating effect [Delle Fave et al, 1977;Bohnet et al, 1978;Hugueset al, 1982]. It is of special interest to determine whether or not histamine H2-receptor antagonists en hance PRL secretion since hyperprolactin emia leads to major side effects such as infer tility and sexual dysfunction.…”