Genetic counseling may be proposed in families with a known disease causing mutation. Antenatal diagnosisĪntenatal or preimplantation diagnosis may be proposed in families with identified mutations and severe/incurable diseases (e.g. Suspicion of a genetic condition warrants a specialized multidisciplinary genetic consultation. Differential diagnosisĪfter excluding exogenous CS, the differential diagnosis includes pseudo-CS that regresses after resolution of the cause (alcoholism and depression). Normal 1st line tests should be repeated in patients with suspected cyclic hypercortisolism, or who show additional signs over time. Abnormal results should lead to testing for the cause of CS. Diagnostic methodsĭiagnosis of a hypercortisolemic state is based on recommended 1st line tests (at least two measurements of 24h urinary cortisol and late night salivary cortisol, and 1 mg overnight or 48h-2 mg dexamethasone suppression test) and 2nd line tests that should be performed by an endocrinologist (either one of the above or, in some cases, midnight serum cortisol measurement, serum cortisol cycle, dexamethasone-suppressed corticotropin-releasing hormone (Dex-CRH) test, desmopressin test or even CRH-test). CS may occur in rare genetic conditions such as multiple endocrine neoplasia type 1 (MEN 1), Carney complex (CNC), McCune-Albright syndrome (MAS), Li-Fraumeni syndrome (LFS) (see these terms) and familial isolated pituitary adenoma (FIPA). ACTH-independent CS is due to unilateral adrenocortical tumors, either benign (adrenocortical adenoma: 60%) or malignant (adrenocortical carcinoma: 40%) or to bilateral adrenocortical hyperplasia, including ACTH-independent macronodular adrenal hyperplasia (AIMAH) and primary pigmented nodular adrenocortical disease (PPNAD) (see these terms). ACTH-dependent CS is due to pituitary adenomas (80%) or to ectopic ACTH secretion (20%). Endogenous CS includes adrenocorticotropic hormone (ACTH) dependent CS (75-80%) and ACTH-independent CS (20-25%). EtiologyĮxogenous CS is due to anti-inflammatory steroid medications, ritonavir co-administration in HIV-infected patients or high-dose megestrol. Mild CS (termed subclinical or occult) is more common than previously thought and has been identified while investigating for diabetes, osteoporosis, hypertension or neuropsychological disturbances. Other less specific features include fatigue, high blood pressure, glucose intolerance, hypokalemia, acne, hirsutism, menstrual irregularity, diminished libido, erectile dysfunction, neuropsychological disturbances (including depression, emotional irritability, sleep disturbances, cognitive deficits), increased susceptibility to infections and urolithiasis. Typical clinical features are truncal and facial obesity, signs of hypercatabolism (thinned skin, purple striae, ecchymosis, bruising with no obvious trauma, proximal muscle weakness with amyotrophy, unexplained osteoporosis) and, in children, weight gain with decreasing growth velocity. Prevalence of endogenous CS is 1/26,000 and, in the EU, it has an annual incidence of 1/1,400,000-1/400,000, with a peak incidence at 25-40 years of age.
0 kommentar(er)
