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A 49-year-old woman with membranous nephropathy was referred to our hospital during the tapering of oral prednisolone, because of suspicion of primary adrenal insufficiency based on a plasma ACTH level of 399.1 pg/mL in the Elecsys assay and a serum cortisol level of 3.1 μg/dL. A rapid ACTH stimulation test revealed a suboptimal response, whereas a prolonged ACTH simulation test showed a sufficient increase in her urinary free cortisol. Also, big ACTH was not detected by gel exclusion chromatography. Therefore, we speculated that ACTH levels were falsely elevated due to some interference substances. Pretreatment of her plasma with either polyethylene glycol precipitation or a heterophilic blocking tube substantially reduced her ACTH values. When either the Immulite ACTH II or the TOSOH II ACTH was tried instead of the Elecsys ACTH, her plasma ACTH values turned out to be lower and appropriate for her clinical status. These results indicated that heterophilic antibodies interfered only with the Elecsys ACTH assay presumably by bridging the capture and tracer antibodies. To our knowledge, this is the first case in which the Elecsys ACTH assay yielded falsely elevated results. Regardless of the measurement system used, if there is a discordance between assay results and clinical findings, it should be considered to adopt additional procedures and/or another assay.

血中ACTH高値を示し, クリプトコッカス髄膜炎, 皮膚クリプトコッカス症を併発した肺小細胞癌の一例を報告した. 患者は58歳の男性で, 湿性咳噺と呼吸困難を主訴に入院し, 気管支鏡検査で肺小細胞癌と診断された. 全身の皮膚の著明な色素沈着や低カリウム血症を伴う代謝性アルカローシスがあり, 血中ACTHは異常高値を示した. 経過中にクリプトコッカス髄膜炎および皮膚クリプトコッカス症を併発し, 全経過21日で死亡した.

A case of bilateral isolated adrenal coccidioidomycosis in a previously healthy and immunocompetent 43-year-old Caucasian male is presented. He had never travelled to a coccidioidomycosis endemic area. Subclinical adrenal dysfunction was found with elevated plasma ACTH and mineralocorticosteroid and androgen pathway abnormalities. The implement of the fungal infection on adrenal function, and the diagnosis and management of adrenal coccidioidomycosis are discussed.

Effects of acute cold exposure (10 degrees C for 60 min) on the concentrations of adrenocorticotropin (ACTH) and zinc in plasma were investigated in seven healthy male students. There were no significant changes in total zinc, albumin-bound zinc, and alpha 2-macroglobulin-bound zinc concentrations throughout the experimental period. On the other hand, ACTH concentration increased markedly during cold exposure. In addition, a statistically significant inverse relationship existed between the changes in ACTH and albumin-bound zinc values during the experiment. These results suggest that acute cold exposure produces elevated plasma ACTH levels, with resulting zinc redistribution in the human body.

Diurnal rhythms of plasma ACTH and plasma corticosterone concentrations were studied in intact rats at 1, 3, 5, and 7 weeks of age and in bilaterally adrenalectomized adult rats 1, 3, 5, and 7 weeks after transplantation of the neonatal (day 1) adrenal to the anterior chamber of the eye. Whereas there was no difference in adrenal weight or plasma corticosterone concentration between intact and transplanted rats during adrenal development, the plasma ACTH concentration was significantly increased in transplanted rats relative to that in intact rats throughout development. A diurnal rhythm of plasma corticosterone concentration was observed in transplanted rats 5 and 7 weeks after transplantation; however, the onset of the rhythmicity was delayed relative to that of intact rats, who displayed rhythmicity at 3, 5, and 7 weeks of age. Elevated plasma ACTH concentrations in chronically cannulated transplanted rats exhibited diurnal variation in parallel with plasma corticosterone concentrations. Adult rats bearing adult adrenal transplants under the kidney capsule for 5 weeks had plasma ACTH concentrations in the evening that were not different from those in unilaterally adrenalectomized, sham-transplanted rats. In contrast, adult rats bearing neonatal adrenal transplants under the kidney capsule for 5 weeks had increased plasma ACTH concentrations in the evening. Thus, the increased plasma ACTH concentration after adrenal transplantation is dependent on the age of the transplant and not on the site of transplantation. The finding of elevated plasma ACTH concentration associated with normal plasma corticosterone concentration suggests that adrenal responsiveness to ACTH is decreased after transplantation of the neonatal adrenal to the adult rat.

SUMMARY In order to define nyctohemeral plasma ACTH secretory patterns, frequent plasma ACTH samples were obtained in seven patients with untreated Cushing's disease (i.e. pituitary-dependent Cushing's syndrome), five Cushing's patients treated by bilateral adrenalectomy, four of whom had Nelson's syndrome, and one patient with 21-hydroxylase deficiency (congenital adrenal hyperplasia). A nyctohemeral rhythm of plasma ACTH concentration was apparent in the one patient with the adrenogenital syndrome but not in those with Nelson's syndrome or Cushing's disease. The effect of graded doses of dexamethasone, 2, 8 or 32 mg per 24 h period, on plasma ACTH concentrations was studied in patients with untreated or treated Cushing's disease or Nelson's syndrome. In all of these hypercorticotrophic states, the mean plasma ACTH concentration was not significantly affected by the smallest dose of dexamethasone, was partially suppressed by the intermediate dose, and further suppressed by the largest dose. In contrast, the patient with congenital adrenal hyperplasia and elevated plasma ACTH concentrations showed complete suppression of plasma ACTH levels following the smallest dose of dexamethasone. These findings indicate that there is resistance to ACTH suppression by dexamethasone in all stages of Cushing's disease and suggest that negative feedback of glucocorticoids may be involved in the pathogenesis of this disease.

Plasma ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, subjected to treatment with either a median eminence extract with corticotropin releasing factor (CRF) activity or to ether exposure. 'CRF' injection elevated plasma ACTH levels on all days tested. Ether exposure elevated ACTH levels on days 14 and 21, but not on days 1 or 7. These results indicate: (1) that there is no diminution of responsiveness of the pituitary to direct stimulation by CRF as a function of age, and (2) that the mediators of the stress response above the level of the pituitary are not functionally mature until approximately day 14. Correlations with previous studies also indicate that there is a delay in the return of adrenal responsiveness until some time after these mediators attain maturity.

THE ASSOCIATION OF Cushing's syndrome and carcinoma of the lung has occurred with sufficient frequency to suggest more than a coincidental relationship. The idea that the tumor might, in some manner, stimulate the pituitary to secrete ACTH has been suggested by the finding of elevated plasma ACTH levels in several patients. 1,2 However, this finding is also consistent with the concept that the neoplasm itself secretes a corticotropic substance that acts directly on the adrenal glands. The following case is that of a patient with fulminating Cushing's syndrome and an oat cell carcinoma of the lung. Endocrinologic studies performed during life, postmortem bioassay of the tissue obtained from the anterior pituitary, and the neoplasm for corticotropic activity, form the basis of this report. Report of a Case A 49-yr-old male entered the Boston Veterans Administration Hospital on June 16, 1961, with the chief complaint of swelling of the face