Compensatory increase in tsh secretion without effect on prolactin secretion in patients treated with aminoglutethimide

Richard J. Santen, Samuel A. Wells, Neal Cohn, Laurence M. Demers, Robert I. Misbin, Elwood L. Foltz

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35 Scopus citations


Administration of the adrenal steroid inhibitor, aminoglutethimide, in combination with hydrocortisone effectively lowered the levels of dehydroepiandrosterone - sulfate, androstenedione, estrone and estradiol in women with breast carcinoma. Since aminoglutethimide also exerts a blocking action on thyroxine synthesis, it was of interest to measure plasma TSH prospectively before and during chronic administration of this drug. In 35 patients who received aminoglutethimide, TSH secretion increased 2-fold over the first 16 weeks in response to an 18% fall in serum thyroxine. The levels of TSH then increased further over a chronic period of up to 48 weeks and as a result, thyroxine levels returned toward basal. The secretion of TSH and prolactin are interrelated in a variety of clinical circumstances. Because of this phenomenon, it appeared possible that prolactin might increase in parallel with TSH in patients receiving aminoglutethimide. The levels of prolactin measured acutely and chronically during the treatment period, however, did not increase. Furthermore, the responsiveness of prolactin to thyrotropin releasing hormone (TRH) during therapy was not exaggerated. These observed effects did not result from a direct inhibitory action of aminoglutethimide on prolactin secretion since 16 normal men, given either this drug or a placebo, responded similarly to TRH and chlorpromazine. No change in LH or FSH levels were observed during therapy. We conclude from the data reported that aminoglutethimide exerts a nearly uniform inhibitory effect on thyroxine synthesis. The compensatory TSH increments which resulted from lowered thyroxine were usually sufficient to counteract this blockade. Under the clinical circumstances of this study, the secretion of TSH and prolactin were not interrelated.

Original languageEnglish (US)
Pages (from-to)739-746
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number4
StatePublished - Oct 1977

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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