Autonomy of Cortisol Secretion in Clinically Silent Adrenal Incidentaloma

Abstract

Recent progress in non-invasive imaging techniques have resulted in an increasing frequency of adrenal incidentaloma discovery. In addition, even clinically silent adrenal tumor has been suggested to possess a subtle production of adrenal hormones. The aim of the study was to ascertain the autonomy of cortisol production in clinically silent adrenocortical incidentaloma. We investigated the hypothalamic-pituitary-adrenal axis in 38 patients with adrenal incidentaloma. Basal plasma cortisol level was reproducibly within normal range in all the patients with adrenal incidentaloma, but was also normal in half of the Cushing's syndrome cases studied. Eighteen of 38 patients showed plasma cortisol above 3 microg/dl after 1 mg dexamethasone (Dex) and above 1 microg/dl after 8 mg Dex, respectively, and were defined as preclinical Cushing's syndrome. These patients were subjected to further evaluation of the autonomy of cortisol production. The incidence of positive findings indicating autonomy of cortisol secretion was as follows: suppressed basal plasma ACTH level in 44%, loss of normal diurnal rhythm in 79%, lack of ACTH response to CRF in 35%, decreased plasma DHEA-S level in 28%, significant laterality of 131I-adosterol uptake in 75%, atrophy of the contralateral side of the adrenal on CT scan in 6%, and histological atrophy of the adjacent adrenal cortex in 56%, respectively. The endocrine feature relevant to the hypothalamic-pituitary-adrenal axis varied from patient to patient, ranging from the non-functioning adrenal adenoma to Cushing's syndrome. In addition, the results of each test did not coincide with others in each patient. These results clearly demonstrated that the incidence of autonomy of cortisol production in the clinically silent adrenal incidentaloma is not infrequent, showing significant diversity. Systemic evaluation of the hypothalamic-pituitary-adrenal axis before adrenal surgery is warranted for an appropriate glucocorticoid replacement after adrenal surgery.

Atherosclerotic risk factors and complications in patients with non-functioning adrenal adenomas treated with or without adrenalectomy: a long-term follow-up study

“…The prevalence of subclinical Cushing's syndrome among patients with NFAAs depends on the criteria used to define it. The lack of a golden standard, however, makes the diagnosis of subclinical hypercortisolism uncertain (3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Discrepancies in Results of Low-and High-dose Dexamethasone Suppression Tests for Diagnosing Preclinical Cushing's Syndrome

“…The diagnostic criteria were established to provide reliable evaluation of PreCS by standardizing diagnostic methods between medical institutions, but problems have been reported concerning discrepancies and reproducibility of DST results, including at our medical center [5][6][7]. The present study was conducted to investigate these problems, including the validity of using the DST in diagnostic criteria.…”

Pros and cons of dexamethasone suppression test for screening of subclinical Cushing’s syndrome in patients with adrenal incidentalomas

“…Conversely, 1-mg dexamethasone is usually sufficient to suppress cortisol secretion by the non-adenomatous adrenal tissue that is driven by pituitary ACTH, while higher dexamethasone doses are not more effective (6,(26)(27)(28)(29)(30). As a matter of fact, the phenomenon of resistance to increasing doses of dexamethasone has been already observed in small groups of patients submitted to both tests (7,31,32). Spontaneous fluctuation of cortisol secretion over time, that has been demonstrated also in subclinical Cushing's syndrome (33), may contribute to the finding that cortisol was paradoxically higher after 8-mg than 1-mg DST.…”