Pitfalls in the diagnosis and management of Cushing's syndrome

Abstract

<jats:p>Despite many recent advances, the management of patients with Cushing's disease continues to be challenging. Cushing's syndrome is a complex metabolic disorder that is a result of excess glucocorticoids. Excluding the exogenous causes, adrenocorticotropic hormone–secreting pituitary adenomas account for nearly 70% of all cases of Cushing's syndrome. The suspicion, diagnosis, and differential diagnosis require a logical systematic approach with attention paid to key details at each investigational step. A diagnosis of endogenous Cushing's syndrome is usually suspected in patients with clinical symptoms and confirmed by using multiple biochemical tests. Each of the biochemical tests used to establish the diagnosis has limitations that need to be considered for proper interpretation. Although some tests determine the total daily urinary excretion of cortisol, many others rely on measurements of serum cortisol at baseline and after stimulation (e.g., after corticotropin-releasing hormone) or suppression (e.g., dexamethasone) with agents that influence the hypothalamic-pituitary-adrenal axis. Other tests (e.g., measurements of late-night salivary cortisol concentration) rely on alterations in the diurnal rhythm of cortisol secretion. Because more than 90% of the cortisol in the circulation is protein bound, any alteration in the binding proteins (transcortin and albumin) will automatically influence the measured level and confound the interpretation of stimulation and suppression data, which are the basis for establishing the diagnosis of Cushing's syndrome. Although measuring late-night salivary cortisol seems to be an excellent initial test for hypercortisolism, it may be confounded by poor sampling methods and contamination. Measurements of 24-hour urinary free-cortisol excretion could be misleading in the presence of some pathological and physiological conditions. Dexamethasone suppression tests can be affected by illnesses that alter the absorption of the drug (e.g., malabsorption, celiac disease) and by the concurrent use of medications that interfere with its metabolism (e.g., inducers and inhibitors of the P450 enzyme system). In this review, the authors aim to review the pitfalls commonly encountered in the workup of patients suspected to have hypercortisolism. The optimal diagnosis and therapy for patients with Cushing's disease require the thorough and close coordination and involvement of all members of the management team.</jats:p>

Striae rubrae: Cushing’s syndrome

“…Interferences with ACTH assays cause a high variability, and falsely increased or decreased results have been reported (5,6). In addition to mentioned testes, also late-night salivary cortisol or free urinary cortisol are useful as screening tools as well as dexamethasone-CRH (corticotropin-releasing hormone) test for pathogenic tests (7,8).…”

A Stratified Approach for Cushing’s Syndrome Diagnosis

“…Likewise, somatostatin analogues could be combined with 68 Ga for PET, which would offer a better pharmacokinetic and visualisation profile. A recent systematic review comparing conventional imaging techniques with those of nuclear medicine in the determination of ectopic Cushing syndrome, shows an improvement in diagnostic sensitivity after applying nuclear medicine techniques when the identification of the tumour is challenging, and both 111 In-Pentetreotide Scintigraphy and FDG-PET were useful, while 68 Ga-SSTR-PET / CT offers the highest sensitivity but the high cost limit its use (Isidori, et al, 2015;Bansal, El Asmar, Selman, & Arafah, 2015).…”

Cushing's syndrome: a practical approach to diagnosis and differential diagnoses

“…Confounding factors such as poor acquisition techniques and contamination may interfere with diagnostic utility of this test 79. Sensitivity and specificity have recently been reported to be low in patients with SCS in a small series 80.…”