Endocrine activity of the “silent” adrenocortical adenoma is uncovered by response to corticotropin-releasing hormone

Abstract

The purpose of this study was to ascertain whether the pituitary-adrenal responses to human corticotropin-releasing hormone (hCRH) in "non-functioning" adrenocortical adenoma would uncover a functional activity in these adrenal nodules. Eleven patients with incidentally discovered "silent" adrenocortical adenoma and eleven controls were studied. The initial clinical and laboratory examination, including an overnight 1 mg dexamethasone suppression test, revealed no abnormalities in any of the subjects. IR-ACTH and serum steroids (F, S, P, 17OHP, 18OHB, and aldosterone) were normal in both controls and patients. After pulse IV injection of 100 micrograms hCRH, the cortisol response was significantly exaggerated (P = 0.01). Stimulated plasma ACTH levels were, however, significantly lower in patients than in controls (P = 0.01), indicating counter-feedback regulation of cortisol. The peak cortisol/peak ACTH ratio (Fmax/ACTHmax) in the patients was significantly elevated (26.8 +/- 4.37 nmol/ng vs. 14.6 +/- 2.16 nmol/ng, P = 0.02). Two further patients with incidentally discovered "pre-Cushing's" adrenocortical adenoma displayed an even higher ratio (43.5 and 45.5 nmol/ng). In established Cushing's syndrome due to an autonomous adrenocortical adenoma, suppression of ACTH and of the ACTH response to hCRH occurs with a very high basal cortisol/basal ACTH ratio. Our findings suggest some functional activity even in clinically "silent" adrenocortical adenoma. Response to hCRH uncovers a continuous spectrum between adrenocortical adenoma, "pre-Cushing's", and Cushing's syndrome.

Long-term morphological and hormonal follow-up in a single unit on 115 patients with adrenal incidentalomas

“…Barzon et al (1999), in the most comprehensive study to date, reported that though the risk of malignancy was very low even in the case of an increment in mass size, the large incidentalomas should be carefully followed-up due to the elevated probability of hyperfunction which, in their study, occurred in two out of 75 patients studied. Other authors have similarly reported the development of overt hypersecretion of the mass over time and even occasional malignant transformation of adrenal incidentalomas (Hensen et al, 1990;Jockenhovel et al, 1992). In contrast, no shift toward malignancy or functional hyperactivity was observed in several other studies (Osella et al, 1994;Barry et al, 1998;Terzolo et al, 1998;Rossi et al, 2000;Siren et al, 2000;Grossrubatscher et al, 2001).…”

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 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.…”

“…Hypertension (>160/ 95 mmHg), obesity (>120% of ideal weight), and noninsulin dependent diabetes mellitus (NIDDM) were not considered to be specific symptoms for Cushing's syndrome because they were frequently found in patients with adrenal incidentaloma [19]; 2) incidentally discovered adrenal mass; 3) normal serum cortisol levels (5-20 ug/dl) in the morning; 4) impaired suppressibility of plasma cortisol (not less than 5 jig/dl) caused by 1 mg dexamethasone administration; 5) lack of normal diurnal rhythm of serum cortisol (cortisol level over 5 ug/dl even at night); 6) unilateral uptake of 1311-6 f3-iodomethy-19-norcholest-5(10)-en-3f3-ol (1311-NCL) into the adrenal mass. Twenty-one patients served as the controls.…”