Subclinical Cushing's Syndrome

Abstract

Subclinical Cushing's syndrome (CS) is attracting increasing interest since the serendipitous discovery of an adrenal mass has become a rather frequent event owing to the routine use of sophisticated radiologic techniques. Cortical adenoma is the most frequent type of adrenal incidentaloma accounting for approximately 50% of cases in surgical series and even greater shares in medical series. Incidentally discovered adrenal adenomas may secrete cortisol in an autonomous manner that is not fully restrained by pituitary feedback, in 5 to 20% of cases depending on study protocols and diagnostic criteria. The criteria for qualifying subclinical cortisol excess are controversial and presently there is no consensus on a gold standard for the diagnosis of this condition. An increased frequency of hypertension, central obesity, impaired glucose tolerance, diabetes and hyperlipemia has been described in patients with subclinical CS; however, there is still no clear demonstration of the long-term complications of this condition whose management remains largely empirical. Either adrenalectomy or careful observation associated with treatment of the metabolic syndrome have been suggested as treatment options. RESUMO Síndrome de Cushing Subclínica.A síndrome de Cushing subclínica (SCS) tem atraído interesse cada vez maior desde que a descoberta casual de uma massa adrenal se tornou um evento freqüente devido ao emprego rotineiro de técnicas sofisticadas de imagem. O adenoma cortical é o tipo mais freqüente de incidentaloma adrenal, correspondendo a cerca de 50% dos casos em séries cirúrgicas e até mais do que isso em séries médicas. Adenomas adrenais descobertos incidentalmente podem secretar cortisol de maneira autônoma ou não controlada totalmente pelo feedback hipofisário, em 5 a 20% dos casos, dependendo do protocolo de estudo e dos critérios diagnósticos. Os critérios para qualificar um excesso subclínico de cortisol são controversos e atualmente não existe consenso a respeito de "padrão ouro" para o diagnóstico dessa condição. Em pacientes com SCS, tem sido descrita uma freqüência elevada de hipertensão, obesidade central, intolerância à glicose, diabetes e hiperlipemia; entretanto, ainda não existe uma evidente demonstração de complicações a longo prazo dessa condição, cujo manejo permanece amplamente empírico. Tanto a adrenalectomia como a observação cuidadosa, associada com o tratamento da síndrome metabólica, têm sido sugeridos como opções terapêuticas.

The limited role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism in patients with adrenal incidentaloma

“…The delayed diagnosis of SH could impact negatively on morbidity and the identification of patients with SH may suggest in some of them the need of adrenalectomy, which has been shown to ameliorate cardiovascular risk profile of these patients (30,31).…”

KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas [Rapid Communication]

“…Among patients with adrenocortical adenomas, those with no typical symptoms of Cushing's syndrome (CS) such as moon face, buffalo hump etc. but showing the autonomous secretion of cortisol have been identified as having preclinical (or subclinical) Cushing's syndrome [20,21]. Although the concept of preclinical (or subclinical) CS is not universally accepted [14], Spath et al recently reported that we should consider an APA with co-secretion of cortisol if a patient has 1) PA and an adenoma that is larger than 2.5 cm, 2) cortisol that is non-suppressible with overnight low-dose dexamethasone, or 3) grossly elevated serum levels of hybrid steroids, such as 18-OH-F [22].…”

Post-surgical hypocortisolism after removal of an adrenal incidentaloma: is it predictable by an accurate endocrinological work-up before surgery?

“…However, in about 5-30% of patients, endocrine work-up reveals abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis function, in keeping with a subtle cortisol hypersecretion, defined as 'subclinical Cushing's syndrome' or 'subclinical hypercortisolism' (SH) (7,8). The true SH prevalence is unknown, due to the lack of widely accepted biochemical criteria for defining this condition (7)(8)(9)(10)(11).…”