Cortisol Secretion by an Incidentally Discovered Nonfunctional Adrenal Adenoma*

Abstract

We describe a middle-aged man with late-onset multiple sclerosis and an incidentally discovered asymptomatic adrenal mass. He had no symptoms or signs of hypercortisolism. A 24-h profile revealed fluctuating serum cortisol values (between 15.1 and 4.7 micrograms/dl) and inappropriately low plasma ACTH values. Urinary cortisol excretion was 89 and 106 micrograms/day on two occasions. After a 4-h ACTH infusion, serum cortisol rose from 6.3 to 108 micrograms/dl. The serum dehydroepiandrosterone level, 33 ng/dl before ACTH stimulation, did not change. During dexamethasone administration, the lowest daily urinary cortisol excretion was 37 micrograms/day, and 17-ketosteroid excretion was 8 mg/day. The response to metyrapone showed a rise of serum 11-deoxycortisol to 25.6 micrograms/dl and of ACTH to 169.5 pg/ml. After removal of the tumor, most likely an adenoma, the circadian pattern of cortisol and ACTH was normal. During a 4-h ACTH infusion, the serum cortisol level rose from 10 to 27 micrograms/dl, and dehydroepiandrosterone rose from 62 to 90 ng/dl. During dexamethasone administration, daily urinary cortisol excretion decreased to 12 micrograms/day, and 17-ketosteroid excretion dropped to 3.9 mg/day. These data show that while the tumor appeared clinically to be nonfunctional, it was producing cortisol and possibly androgens autonomously, albeit at levels too low to cause complete suppression of the pituitary-adrenal axis.

Serum Levels of Dehydroepiandrosterone Sulfate in Patients with Asymptomatic Cortisol Producing Adrenal Adenoma: Comparison with Adrenal Cushing's Syndrome and Non-Functional Adrenal Tumor.

“…In some reports, serum levels of DHEA-S were low in the patients with ASCA [15,19,21,30,31]. But in these reports, DHEA-S levels were not fully discussed compared with age matched controls.…”

“…In all the patients with nonfunctional adrenal tumor, plasma ACTH and serum cortisol levels were normal and, furthermore, in three cases examined, ACTH and cortisol showed a normal response to CRH. The ACTH level in patients with ASCA was reported to be suppressed [12,15,[17][18][19][20][21], but in some other cases it was normal [13,20,21]. Thus the plasma ACTH levels varied among the patients with ASCA.…”

“…These so-called "adrenal incidentalomas" are usually asymptomatic and often classified as non-functional tumors, but in recent years there have been several case reports of asymptomatic cortisol producing adrenal adenoma (ASCA) which secretes cortisol without clinical evidence of Cushing's syndrome, the so-called "Pre-Cushing's syndrome" or "Preclinical Cushing's syndrome" [12][13][14][15][16][17][18][19][20][21]. Some cases with incidentaloma were reported to have had adrenocortical insufficiency after removal of the adrenal tumor [17,20].…”

“…Plasma ACTH in ASCA was reported to be lowered by cortisol hypersecretion [12,15,[17][18][19][20][21], and therefore a decrease in ACTH may lead to a DHEA-S decrease in ASCA.…”

Localization of Steroidogenic Enzymes in Adrenal Cortex and Its Disorders.

“…These lesions have been termed as "incidentaloma" or "non -functioning adrenocortical tumors" or "hormonally inactive adrenocortical tumors". Morphologically, these lesions cannot be differentiated from adrenocortical adenoma associated with Cushing's syndrome or primary aldosteronism [11,13,15,16]. Therefore, it is important to determine whether there are any differences of the patterns of the expression of steroidogenic enzymes between hormonally active and inactive adrenocortical neoplasms in order to obtain a better understanding of steroid metabolism in these incidentaloma.…”