EFFECTS OF CIMETIDINE ON PITUITARY FUNCTION: ALTERATIONS IN HORMONE SECRETION PROFILES

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Abstract
Cimetidine, an H2-receptor antagonist, was given for 6 wk to 6 normal male volunteers to study the effects on pituitary, adrenal, thyroid and testicular hormone secretion. Patients were studied before (day 1) and after (day 42) cimetidine (300 mg 4 times daily) therapy, and 4 of the 6 were restudied after discontinuing cimetidine for 1 mo. (day 72). Basal TSH concentrations and responses to TRH administration as well as triiodothyronine radioimmunoassay and thyroxine resin uptakes did not change during or after cimetidine therapy. The diurnal rhythm of plasma cortisol and maximum cortisol response to insulin (0.15 .mu./kg) were similar on days 1 and 42, but urinary free cortisol excretion fell 31% (P < 0.01). Response of GH [growth hormone] to exercise, 100 g carbohydrate ingestion and insulin were unchanged, but mean nocturnal GH secretion decreased 33% (P < 0.025) on cimetidine, and returned to baseline on day 72. The 24-h plasma prolactin profile was unchanged as was the prolactin response to insulin and TRH stimulation. Plasma FSH was not altered, but mean LH [luteinizing hormone] concentrations decreased 20% on cimetidine and continued to decline (45% of day 1 levels) after discontinuation of cimetidine (P < 0.01). Spontaneous LH pulse amplitude declined slightly on day 42, but became significantly lower on day 72 (P < 0.01) while pulse frequency increased modestly on day 72 (P < 0.05). Peak LH responses to gonadotropin-releasing hormone were also reduced on cimetidine therapy (P < 0.02). Plasma testosterone concentrations did not change but plasma estradiol concentrations were 38% lower (P < 0.025) after cimetidine was discontinued. H2 histamine receptors are involved in the control of multiple hormone secretory patterns and blockade of these receptors by cimetidine alters hormone profiles. These changed patterns have to be considered in the interpretation of hormone measurements in patients receiving cimetidine therapy.