Studies on Application of Metopirone (11-β-Hydroxylase Inhibitor) for the Diagnosis oF Pituitary and Adrenocortical Disorders

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1) The pituitary ACTH reserves were studied in five normal subjects, five patients with Cushing's syndrome and eight patients with hypothalamo-pituitary or adrenocortical disorders with the use of Metopirone. Three grams of Metopirone divided into 6 doses which were administered orally over a period of two or three days. Pituitary ACTH reserve was estimated by 24-hour urinary output of 17-OHCS.2) It was recognized that the increase of urinary 17-OHCS on the second therapeutic day with Metopirone was most useful for the determination of pituitary ACTH reserve.3) In 3 of 4 patients with Cushing's syndrome due to adrenocortical hyperplasia, a marked increase in urinary 17-OHCS was observed following Metopirone administration. In one patient with Cushing's syndrome due to adrenocortical adenoma, however, the increase of urinary 17-OHCS did not occur following Metopirone administration, while a normal response was found following ACTH administration.4) In 6 patients with hypothalamo-pituitary disorders, the increment of urinary 17-OHCS excretion was not observed during Metopirone administration, even though adrenocortical responsiveness to exogenous ACTH was not lost.5) Despite an impaired Metopirone response in each patient with chromophobe adenoma, with hematoma at the base of the brain or with craniopharyngioma, a significant increase in urinary 17-OHCS was observed during the procedure of craniotomy or pneumoventriculography. Concerning pituitary ACTH secretion, it is considered that there are quantitative and/or qualitative differences between the stress-mechanism and the feedback-mechanism.6) Not only in normal subjects but also in patients with normal pituitary reserve, it was observed that a normal diurnal rhythm of 6-hour urinary 17-OHCS excretion was found on the 2nd or 3rd therapeutic day with Metopirone. On the contrary, in patients with Cushing's syndrome and patients with hypothalamo-pituitary disorders, the normal diurnal rhythm was not found during Metopirone administration, even though normal rhythm was observed before Metopirone administration.7) During the administration of Metopirone, the decrease of urinary sodium and the increase of urinary potassium were observed in normal subjects and patients with Cushing's syndrome due to adrenocortical hyperplasia. On the other hand, in a patient with Cushing's syndrome due to adrenocortical adenoma, the increase of urinary sodium and the decrease of urinary potassium were observed. In a patient with primary aldosteronism, the urine potassium level fell during Metopirone administration as well.