Preclinical Cushing’s Syndrome: Report of Four Cases and Analysis of Steroid Contents in Adenomas

Abstract

We report 4 cases of preclinical Cushing’s syndrome (PCS) that were discovered incidentally by computed tomography (CT) as adrenal incidentalomas. Routine endocrine examinations revealed a suppressed plasma ACTH level. A final diagnosis was made by means of precise endocrine assessments and adrenal scintigraphy with radiolabelled iodocholesterol. Although endocrine data varied, the positive accumulation of radioisotope in the adrenal tumor, with nonvisualization of the contralateral side, was observed in all cases. Endocrine studies and analyses of steroid contents in tumors by HPLC suggested that subtypes or heterogenous forms of this disease entity may exist. One type shows small tumors with relatively elevated cortisol production, and a disturbed diurnal rhythm and suppression of plasma cortisol with dexamethasone (DXM). The other type showed large tumors with weak-to-average cortisol production, and the diurnal rhythm of cortisol was preserved.

Preclinical Cushing’s syndrome: Report of seven cases and a review of the literature

“…This supplement therapy was not given to case 4, because a moderate response of 11‐deoxycortisol to metyrapone was identified. 9 Regarding case 6, who was given hydrocortisone for 4 months, the supplement was maintained because of his complaint (general malaise) without definite biochemical evidence of adrenal insufficiency. Plasma ACTH levels rapidly recovered, within 3 weeks in six of the seven cases.…”

“…Four of these cases, cases 1–4, have been reported previously. 9 The other three cases were recently discovered. Cushing’s stigmata such as buffalo hump and central obesity were not seen, but simple obesity was seen in cases 2, 3 and 7.…”

“…Adrenal adenomas which show autonomous cortisol secretion without specific endocrine symptoms have been described as subclinical or preclinical Cushing’s syndrome (PCS). The clinical endocrine data and pathophysiology of subtle hypercortisolism have been discussed in many reports, 3–9 but the diagnostic parameters of PCS have varied. In the present study, the endocrine data of seven Japanese patients were examined and the diagnostic parameters of PCS, the risk of adrenal insufficiency after adrenalectomy and surgical indications were reviewed and discussed.…”

The Analysis of Steroidogenic Activity in Non-Hyperfunctioning Adrenocortical Adenoma.

“…Although F content in case 10 was greater than in case 9 despite rather reduced P450c17a activity, it may be accounted for by increased P450c21 activity supporting F production in the adenoma in case 10. As several differences were observed between two cases of PCS, that is, age, tumor volume, response of plasma F to ACTH stimulation and P450c21 activity, it was considered that the entity of PCS is heterogeneous, and several subtypes which produce various amounts of F may exist [12]. As a result of the present study, the steroidogenic activity in NHFA was considered to be similar to that in normal control adrenals.…”

Aldosterone-Producing Adrenal Cortical Cancer: A Case Report and Analysis of Steroidogenic Enzymes in the Tumor.

“…A suppressed plasma ACTH level was frequently observed in cases with benign adenomas causing Cushing's syndrome or preclinical Cushing's syndrome even if the production of cortisol was not excessive [13]. For this reason, some differences in sensitivity to ACTH may exist between adrenal cancers and benign adenomas.…”