Approach to the Patient with Subclinical Cushing’s Syndrome

Abstract

: A growing number of patients with adrenal incidentalomas and subclinical Cushing’s syndrome (SCS) led to a growing number of different guidelines, diagnostic and treatment recommendations. Excess cortisol secretion in patients with SCS is associated with a number of comorbidities, such as hypertension, dyslipidemia, type 2 diabetes mellitus and obesity, which in long-term increase mortality of these patients. Subtle cortisol secretion effects also bone health, quality of life and cause depression, but due to the unapparent clinical features, patients with SCS are often in risk between over and under treatment. The aim of this narrative review was to summarize the latest recommendations on the approach to the patient with subclinical Cushing’s syndrome.

The Entity of Connshing Syndrome: Primary Aldosteronism with Autonomous Cortisol Secretion

“…Adrenal tumours display a highly heterogeneous profile with respect to molecular and pathological/immunohistochemistry profile, as well as genetic background, and this field has recently seen spectacular progress [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 ].…”

“…Traditionally, PA is associated with an adrenal tumour, bilateral adrenal hyperplasia, adrenal cortex carcinoma and ectopic aldosterone production, but benign adrenal sources are described as aldosteronona (solitary tumour), aldosterone-producing nodule or multiple micronodules (non-classical type), respective bilateral adrenal disease; for instance, unilateral PA may underline a unilateral single or multiple aldosterone-producing adenoma or an aldosterone-producing cell cluster [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 127 , 128 , 129 , 130 , 131 , 135 , 136 ].…”

“…On the other hand, adrenal Cushing syndrome relates either to benign adenomas or bilateral adrenal lesions (bilateral macronodular or micronodular adrenal cortical diseases), or to adrenocortical carcinoma [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. In terms of clinical expression, there may be an overt clinical presentation or a (traditionally) so-called subclinical Cushing syndrome, a term underlying autonomous cortisol secretion (ACS) or possible ACS [ 12 ].…”

“…The medical and social burden of clinically manifested Cushing syndrome and to a lesser extent of mild hypercortisolism—despite not having the global epidemiological impact of PA—is caused by multi-organ morbidity and mortality due to HBP, diabetes mellitus, thromboembolism, obesity, myopathy, osteoporosis, infections, depression and neurocognitive impairment, etc. [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Subclinical Cushing syndrome (which is the type of cortisol excess most associated with PA in Connshing syndrome) is generally identified in 5–50% (roughly, one-third) of adrenal incidentalomas, depending on endocrine tests used in order to confirm the cortisol over production [ 22 ].…”

Severe infection including disseminated herpes zoster triggered by subclinical Cushing’s disease: a case report

“…SCD is defined by ACTH-induced mild hypercortisolism without typical physical features of CD including moon face, central obesity, buffalo hump, purple striae, thin skin, easy bruising, and proximal myopathy [3]. Even when clinical signs of overt hypercortisolism are not present, mild hypercortisolism is associated with metabolic changes such as hypertension, type 2 diabetes mellitus, dyslipidemia, and obesity, resulting in increased risk of mortality [4,5]. Infection is one of the major complications related to mortality in the patients with CD [6], while no detailed reports on the risk of infection in the patients with SCD are available.…”