High molecular weight corticotropin measured with immunoradiometric assay in a patient with asymptomatic pituitary corticotropinoma

A 57-yr-old female with corticotropinoma showing no Cushingoid stigmata is reported. Basal plasma levels of ACTH measured with immunoradiometric assay and beta-endorphin were high, 12.6-15.9 pmol/l and 3.5 pmol/l, respectivel y. Plasma cortisol level and urinary free cortisol excretion were normal, 3 03-359 nmol/l and 171-226 nmol/day, respectively. Plasma ACTH markedly incr eased to 70.5 pmol/l with intravenous administration of 100 mu g CRH. Diurn al rhythm of plasma ACTH was seen, but its level in the night was still hig h. Plasma ACTH suppression with dexamethasone was insufficient. CRH stimula tion after dexamethasone suppression increased plasma ACTH level from 4.4 t o 13.7 pmol/l. Intravenous administration of 4 mu g desmopressin increased plasma ACTH from 15.6 to 19.6 pmol/l. Oral administration of 16 mg lepramid e insufficiently decreased plasma ACTH from 7.3 to 5.3 pmol/l. However, pla sma cortisol responses in these conditions were normal. Postoperative patho logical study revealed sub type 1 corticotropinoma immune histo chemically and electron-microscopically. Postoperative basal plasma ACTH decreased to 3.9 pmol/l, although plasma cortisol did not change. Diurnal rhythm and dex amethasone suppressibility of plasma ACTH became normal. Plasma sample was chromatographed on a Sephadex G-75 column. The elution profile showed two p eaks of ACTH, one of which was compatible with 1-39 ACTH and another with h igher molecular weight ACTH which was probably secreted from corticotropino ma. Anomaly in processing of proopiomelanocortin was suspected.