Pre-Clinical Cushing’s Syndrome: Report of Three Cases and Literature Review

Abstract

Pre-Cushing’s syndrome (PCS) is defined as an overproduction of cortisol by an adrenal adenoma, without physical changes on clinical examination. Three patients with PCS were recently diagnosed among 21 consecutive patients suffering from adrenal ‘incidentaloma’. All patients showed nonsuppression of serum and urinary cortisol following 2 and 8 mg of dexamethasone (DXM), and suppressed or normal baseline plasma ACTH. Unilateral uptake of radiolabelled iodocholesterol, which persisted after DXM, was uniformly present. The authors review 36 patients with PCS previously reported. This entity probably constitutes a transition from classic ‘nonfunctional’ adrenal adenoma to cortisol-producing adenoma. Uniform guidelines in the management of PCS cannot yet be given, but surgical intervention is usually required to prevent the development of long-term complications of subtle corticoid excess.

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

“…Our first major finding is that, in agreement with several reports (Reincke et al, 1992;Fernandez-Real et al, 1994;Osella et al, 1994;Mantero et al, 1997;Barzon et al, 1998;Terzolo et al, 1998;Mantero et al, 2000;Sworczak et al, 2001), patients with adrenal incidentalomas frequently show isolated subtle subclinical endocrine alterations. Several terms have been adopted to define these forms, on the basis of the hormone involved, such as pre-, subclinical or silent Cushing's syndrome, and preclinical hyperaldosteronism or pheochromocytoma, but the clinical significance of these abnormalities remains unknown.…”

Prevalence of Subclinical Cushing's Syndrome in 70 Patients with Adrenal Incidentaloma: Clinical, Biochemical and Surgical Outcomes

“…Previous studies reported an occurrence of SCS that ranged 5-20% [6][7][8][9][10][11][12][13][14][15][16][17]. Hensen et al found cortisolproducing adenomas in 6% of all incidentally detected adrenal tumors [6], whereas McLeod et al reported a 5% prevalence cortisol-producing tumors in 122 patients with adrenal incidentaloma [7].…”

“…Recent studies have reported increasing evidence that subtle cortisol production and abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are more frequent than previously thought. Depending on the diagnostic criteria and the study design used, SCS is found in 5% to 20% of patients with adrenal incidentaloma [6][7][8][9][10][11][12][13][14][15][16][17]. It is assumed that glucocorticoid production in these patients is insufficient to cause a clinically recognizible syndrome.…”

The value of dehydroepiandrosterone sulfate measurement in the differentiation between benign and malignant adrenal masses

“…Low dehydroepiandrosterone sulfate (DHEAS) levels are frequently observed in patients with adrenal incidentalomas even if the reason for this reduction remains to be fully clarified (7)(8)(9)(10). Conversely, high DHEAS levels are a marker of adrenal androgen excess that may herald the presence of an adrenal carcinoma (11).…”