Jump to content

Case Detection of Cushing Syndrome in Adults

Recommended Posts

Case Detection of Cushing Syndrome in Adults

Endogenous Cushing syndrome (CS) or hypercortisolism is a rare condition with an incidence of 1 to 2.5 cases per 1 million persons per year in the United States. CS is associated with increased morbidity and death. The typical clinical features of hypercortisolism include:


?Central weight gain

?Easy bruising

?Facial plethora and rounding of the face (moon facies)

?Emotional lability


?Proximal muscle weakness

?Supraclavicular fullness

?Dorsocervical fat pad




?Osteopenia or osteoporosis

?Wide purple-red striae over the abdomen, inner thighs, and axilla

Dana Erickson, M.D., of the Division of Endocrinology, Diabetes, Metabolism, and Nutrition at Mayo Clinic notes: "When patients present with signs and symptoms consistent with CS, the clinician should first exclude exogenous corticosteroid use and then pursue biochemical testing.


"We frequently encounter patients with mild signs and symptoms that may be consistent with CS ? a presentation that overlaps with frequent problems seen in the general population, such as obesity, metabolic syndrome, depression, and menstrual irregularities. Therefore, it is important for us to have a good understanding of the diagnostic accuracy of the currently available tests for evaluation of hypercortisolism."


The 3 standard case detection tests for CS are:


?24-hour urinary free cortisol (UFC)

?Late-night salivary cortisol

?1-mg overnight dexamethasone suppression test (DST)

UFC measures cortisol that is not bound to cortisol-binding globulin and represents integrated adrenal cortisol secretion over 24 hours. Ravinder J. Singh, Ph.D., of the Department of Laboratory Medicine and Pathology at Mayo Clinic, explains: "Our laboratories use liquid chromatography ? tandem mass spectrometry (LC-MC/MS) ? for measurements of cortisol.


"To ensure accuracy, we confirm that the patient has completed an entire 24-hour urine collection (typically assessed with measurement of urinary creatinine), does not have excessive fluid intake (24-hour urine volumes more than 5 L can result in falsely elevated levels of cortisol excretion), and has normal renal function (renal failure can decrease urinary cortisol excretion)."


Dr. Erickson highlights: "It is important to note that 1 out of four 24-hour UFC measurements in the setting of true CS can be within normal limits. Thus, when the UFC result is normal but the clinical suspicion for CS is high, the 24-hour UFC measurements should be repeated several times (eg, weekly or monthly).


"CS is confirmed when the 24-hour UFC is more than 3-fold increased above the upper limit of the reference range. The test characteristics of 24-hour UFC include sensitivities of 76% to 100% and specificities of 95% to 98%. (The variation depends on patient population, reference range, and type of assays used.) The interpretation of urinary cortisol excretion should incorporate the degree of clinical suspicion for CS."



Mary L. Eastvold, assistant supervisor of the Mayo Clinic Endocrine Laboratory, holds a salivette used for collection of saliva for cortisol testing.

Late-night salivary cortisol, collected at 11 p.m. with a salivate-collecting device, is an attractive option for CS case detection because it assesses cortisol secretion at the physiologic nadir.


Dr. Singh explains: "At Mayo Medical Laboratories, we use LC-MC/MS to measure salivary cortisol. When the sample is obtained at 11:00 PM, the upper limit of the reference range is 100 ng/dL. Based on published studies, the salivary cortisol test characteristics include a sensitivity of 93% to 100% and a specificity of 85% to 100%. However, our preliminary data suggest that the true sensitivity may be lower than previously reported."


Another useful detection test is the 1-mg overnight DST, in which dexamethasone is administered between 11 p.m. and midnight and the serum cortisol concentration is measured between 8 and 9 a.m. the following morning. Normal suppression is defined as a serum cortisol concentration less than 1.8 mcg/dL (sensitivity, 95%; specificity, 80%).


Dr. Erickson explains: "If the diagnostic threshold is raised to 5 mcg/dL, the specificity increases to 95% but sensitivity declines. Interpretation of DST results can be confounded by medications that accelerate the metabolism of dexamethasone (eg, anticonvulsants) or medications that increase serum cortisol-binding globulin concentrations (eg, oral estrogens)."


What should the clinician do when the findings of the 24-hour UFC, late-night salivary cortisol, and 1-mg overnight DST are equivocal or inconclusive? Dr. Erickson answers: "When the findings from the 3 standard case detection tests are inconclusive, there are 2 options to consider:


?One option is to reassess 3 to 6 months later. If a patient has true CS, the signs and symptoms and the levels of cortisol secretory abnormalities should progress over time.

?Another option is to perform a combined corticotropin-releasing hormone?DST (CRH-DST). The basis for the CRH-DST is that tumorous corticotroph cells respond to CRH in the presence of dexamethasone, whereas normal corticotroph cells do not respond.

"Our experience with 51 patients (21 with CS and 30 without CS) showed that a 15-minute post-CRH serum cortisol concentration greater than 2.5 mcg/dL resulted in sensitivity and specificity of 90% each. In addition, a serum corticotropin concentration greater than 27 pg/mL at 15 minutes after CRH administration provided a sensitivity of 95% and a specificity of 97% for diagnosis of CS."


Dr. Erickson concludes: "We recommend that to establish a diagnosis of CS, at least 2 case detection tests should have abnormal results. However, sound clinical judgment should guide the interpretation of laboratory tests and in many instances, close follow-up of the patient and repeat testing are necessary to establish a firm diagnosis of CS before initiating further evaluation and treatment."



Link to comment
Share on other sites

It appears that their criteria for diagnosis is pretty strict. Wondering how many of us would have been diagnosed using their criteria? The use of CBG testing isn't mentioned in the article. Has anyone gone to Mayo Clinic and gotten diagnosed? What was the protocol that they used?

Link to comment
Share on other sites


This topic is now archived and is closed to further replies.

  • Create New...