Figure - available from: Pituitary
This content is subject to copyright. Terms and conditions apply.
Physiology and principles of testing for autonomous cortisol secretion. Approximately 5% of cortisol in serum is unbound, 10–15% is bound with low affinity to albumin, while the remaining is bound to CBG. The latter may be both a reservoir for cortisol and a modulator of cortisol release, by changes in cortisol binding affinity between a high- and a low-affinity conformation. Only unbound free cortisol is transferred into urine, mixed with other steroids and metabolites
Source publication
Diagnosis of Cushing’s syndrome (CS) is often delayed due to variable clinical features and its rarity. Simple and accurate screening tests are required to enhance screening for hypercortisolism. Both overnight 1 mg dexamethasone suppression test (DST) and urinary free cortisol (UFC) demonstrate high sensitivity and specificity for the diagnosis of...
Citations
... Screening for CS includes measuring salivary cortisol [2], urinary free cortisol and performing an overnight Dexamethasone suppression test [3], each with specific caveats. Excluding non-tumoral hypercortisolemia is also paramount in many patients [4]. ...
... Nevertheless, incomplete urine collection and impaired GFR may lead to false negative results. Therefore, confirmation by a repeated urinary free cortisol assay is suggested by the guidelines, even though intra-individual variations of cortisol excretion is an issue that should be taken into account when interpreting the results [1,2,16,31]. The 1 mg DST has shown a high sensitivity (99%) with a specificity of 91% for diagnosis of Cushing's syndrome [30]. ...
... The 1 mg DST has shown a high sensitivity (99%) with a specificity of 91% for diagnosis of Cushing's syndrome [30]. Given the high sensitivity at the cortisol cut off of 1.8 µg/dL, the 1 mg DST is appropriate for screening purposes, after having excluded potential sources of bias (incomplete or lack of ingestion of dexamethasone by the patient, changes in cortisol binding globulin or albumin, and drugs altering the CYP3A4 activity) [31]. Collection of LNSC is a simple and non-invasive test that can be performed at home by the patients, with sensitivity and specificity for the diagnosis of Cushing's syndrome > 90% [32]. ...
Purpose
Screening of Cushing Syndrome (CS) and Mild Autonomous Cortisol Secretion (MACS) in hypertensive patients is crucial for proper treatment. The aim of the study was to investigate screening and management of hypercortisolism among patients with hypertension in Italy.
Methods
A 10 item-questionnaire was delivered to referral centres of European and Italian Society of Hypertension (ESH and SIIA) in a nationwide survey. Data were analyzed according to type of centre (excellence vs non-excellence), geographical area, and medical specialty.
Results
Within 14 Italian regions, 82 centres (30% excellence, 78.790 patients during the last year, average 600 patients/year) participated to the survey. Internal medicine (44%) and cardiology (31%) were the most prevalent medical specialty. CS and MACS were diagnosed in 313 and 490 patients during the previous 5 years. The highest number of diagnoses was reported by internal medicine and excellence centres. Screening for hypercortisolism was reported by 77% in the presence of specific features of CS, 61% in resistant hypertension, and 38% in patients with adrenal mass. Among screening tests, the 24 h urinary free cortisol was the most used (66%), followed by morning cortisol and ACTH (54%), 1 mg-dexamethasone suppression test (49%), adrenal CT or MRI scans (12%), and late night salivary cortisol (11%). Awareness of referral centres with expertise in management of CS was reported by 67% of the participants, which reduced to 44% among non-excellence centres.
Conclusions
Current screening of hypercortisolism among hypertensive patients is unsatisfactory. Strategies tailored to different medical specialties and type of centres should be conceived.
Importance:
Cushing syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology. Although the most frequent cause of Cushing syndrome is exogenous steroid use, the estimated incidence of Cushing syndrome due to endogenous overproduction of cortisol ranges from 2 to 8 per million people annually. Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders.
Observations:
Cushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae and with metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs. Cushing disease, in which corticotropin excess is produced by a benign pituitary tumor, occurs in approximately 60% to 70% of patients with Cushing syndrome due to endogenous cortisol production. Evaluation of patients with possible Cushing syndrome begins with ruling out exogenous steroid use. Screening for elevated cortisol is performed with a 24-hour urinary free cortisol test or late-night salivary cortisol test or by evaluating whether cortisol is suppressed the morning after an evening dexamethasone dose. Plasma corticotropin levels can help distinguish between adrenal causes of hypercortisolism (suppressed corticotropin) and corticotropin-dependent forms of hypercortisolism (midnormal to elevated corticotropin levels). Pituitary magnetic resonance imaging, bilateral inferior petrosal sinus sampling, and adrenal or whole-body imaging can help identify tumor sources of hypercortisolism. Management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production followed by medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers. For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate.
Conclusions and relevance:
The incidence of Cushing syndrome due to endogenous overproduction of cortisol is 2 to 8 people per million annually. First-line therapy for Cushing syndrome due to endogenous overproduction of cortisol is surgery to remove the causative tumor. Many patients will require additional treatment with medications, radiation, or bilateral adrenalectomy.
