Cushing's Awareness: Subclinical Cushing's

Subclinical Cushing's Disease/Syndrome has be a controversial diagnosis.  Only in the past decade has the term been used.  According to Pathophysiology and treatment of subclinical Cushing’s disease and pituitary silent corticotroph adenomas  “subclinical has been used in the pituitary. Subclinical Cushing’s disease is defined by ACTH-induced mild hypercortisolism without typical features of Cushing’s disease."  This places the cause of subclinical Cushing's with the pituitary.

The authors of Clinical Cushing’s syndrome: Current concepts and trends define subclinical Cushing's as coming from an adrenal incidentaloma.

Initial diagnostic evaluation of a patient with an adrenal incidentaloma aims to determine the functional status of the mass and the possibility of malignant disease. The vast majority of these lesions are benign nonhypersecreting cortical neoplasms. However, a significant percentage of cases present subclinical hormonal activity, mainly concerning glucocorticoid secretion.4-6 Subtle cortisol hypersecretion by adrenal incidentalomas is characterized by alterations of the hypothalamic-pituitary-adrenal (HPA) axis due to adrenal autonomy in the absence of the typical clinical phenotype of hypercortisolism, a disorder that has been defined as subclinical Cushing’s syndrome. (Underlining is mine.)

Late-Night Salivary Cortisol for Diagnosis of Overt and Subclinical Cushing’s Syndrome in Hospitalized and Ambulatory Patients also indicates subclinical as having a pituitary origin.   But Subclinical Cushing's syndrome also indicates an adrenal incidentaloma as the source.  It goes on to say, "Patients with subclinical Cushing's syndrome lack the classical stigmata of hypercortisolism but have a high prevalence of obesity, hypertension, and type 2 diabetes."  (I thought those were classical symptoms of Cushing's.)

Subclinical Cushing's Disease is considered to be an epidemic disease. It has a prevalence of 0·2–2 per cent in the adult population, alone.  (Systematic review of surgical treatment of subclinical Cushing's syndrome)  However, there is no definite criteria for diagnosing it.  Most use the dexamethasone suppression test as a frontline test, but the cut-off criteria for subclinical Cushing's have not been standardized.  Subclinical Cushing's is also sometimes called "mild" Cushing's by some.

The article,  High Prevalence of Normal Tests Assessing Hypercortisolism in Subjects with Mild and Episodic Cushing’s Syndrome Suggests that the Paradigm for Diagnosis and Exclusion of Cushing’s Syndrome Requires Multiple Testing, states:

We have recently described poor sensitivity of a single overnight dexamethasone test in detecting hypercortisolism in patients with mild or episodic Cushing’s syndrome [37]. Thus, our data suggest that current screening tests performed once are inadequate to detect or exclude hypercortisolism in patients with mild or episodic Cushing’s disease.

If there are such epidemic numbers of subclinical Cushing's, seems to me these learned folks need to get together and figure this out.