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KEY CONCEPTS
Glucocorticoid secretion from the adrenal cortex is stimulated by adrenocorticotropic hormone (ACTH) or corticotropin that is released from the anterior pituitary in response to the hypothalamic-mediated release of corticotropin-releasing hormone (CRH).
To ensure the proper treatment of Cushing syndrome, diagnostic procedures should (1) establish the presence of hypercortisolism and (2) discover the underlying etiology of the disease.
The rationale for treating Cushing syndrome is to reduce the morbidity and mortality resulting from disorders such as diabetes mellitus, cardiovascular disease, and electrolyte abnormalities.
The treatment of choice for both ACTH-dependent and ACTH-independent Cushing syndrome is surgery. Pharmacologic agents are reserved for adjunctive therapy, refractory cases, or inoperable disease.
Pharmacologic agents that may be used to manage the patient with Cushing syndrome include steroidogenesis inhibitors, adrenolytic agents, neuromodulators of ACTH release, and glucocorticoid-receptor blocking agents.
Spironolactone, a competitive aldosterone-receptor antagonist, is the drug of choice in bilateral adrenal hyperplasia (BAH)–dependent hyperaldosteronism.
Addison’s disease (primary adrenal insufficiency) is a state of deficiency in cortisol, aldosterone, and various androgens due to the loss of function in all regions of the adrenal cortex.
Secondary adrenal insufficiency usually results from exogenous steroid use, leading to hypothalamic–pituitary–adrenal (HPA)–axis suppression followed by a decrease in ACTH release, and low levels of androgens and cortisol.
Virilism results from the excessive secretion of androgens from the adrenal gland and often manifests as hirsutism in females.
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Patient Care Process for Cushing Syndrome
Collect
Patient characteristics (eg, age, sex, pregnant)
Patient medical history (personal and family)
Social history (eg, tobacco/ethanol use)
Iatrogenic causes of Cushing syndrome: current medications including corticosteroids (all routes, past and present), medroxyprogesterone acetate, megestrol acetate, gamma-hydroxybutyic acid, CYP3A4 inhibitors and inducers
Objective data
Blood pressure, heart rate, body mass index
Test for hypercortisolism: 24-hour UFC, midnight plasma cortisol, late-night salivary cortisol, or low-dose dexamethasone suppression test
Follow-up diagnostic tests to differentiate etiologies (see Fig. 93-4)
Assess
Presence of Cushing syndrome complications:
Metabolic: impaired glucose metabolism, dyslipidemia
Cardiovascular: hypertension, vascular damage, thrombosis, hypokalemia
Immunologic: bacterial, fungal, and viral infections; rebound autoimmunity Musculoskeletal: osteopenia/osteoporosis, myopathy
Neuropsychiatric: depression, anxiety, bipolar disorder
Reproductive: decreased libido, hypogonadism (men), menstrual irregularity (women)
Dermatologic: hirsutism, alopecia, hyperhidrosis
Physical exam: Peripheral obesity, fat accumulation (Buffalo Hump), rounded face (moon face), striae, ecchymosis, hyperpigmentation, acanthosis nigricans, acne, and thin skin
Current medications that may contribute to or worsen Cushing syndrome.
Results of follow-up diagnostic testing for etiology (see Fig. 93-4, and Tables 93-2 and 93-3)
Ability/willingness to pursue surgical/chemotherapeutic (if indicated) versus medical management
Plan*
Ensure proper administration of necessary corticosteroid therapy; discontinue unnecessary corticosteroid therapy, with taper if HPA axis integrity is suspect
Nondrug options for endogenous Cushing syndrome, depending on etiology: surgery, chemotherapy, irradiation, postoperative steroid replacement (see Table 93-4)
Steroid replacement regimens postoperatively for patients with adrenal adenomas (see Table 93-7)
Medical management when surgery is not possible or against patient wishes (see Tables 93-5 and 93-6 for ...