CUSHING SYNDROME AND DISEASE
Cushing syndrome designates any form of glucocorticoid excess; Cushing disease designates hypercortisolism from pituitary overproduction of corticotropin (ACTH). Other causes include adrenal adenoma, adrenal carcinoma, multinodular adrenal hyperplasias, and the ectopic ACTH syndrome. Iatrogenic Cushing syndrome results from administration of supraphysiologic quantities of glucocorticoids.
Early signs of glucocorticoid excess include increased appetite, weight gain, and growth arrest without delayed bone age. Chronic glucocorticoid excess in children results in typical Cushingoid facies, but the centripetal fat distribution characteristic of adult Cushing disease is seen only in long-standing disease. Mineralocorticoid excess is characterized by hypertension, but patients receiving low-sodium diets (eg, newborns) are not hypertensive, as mineralocorticoids increase blood pressure by retaining sodium and increasing intravascular volume. Moderate hypersecretion of adrenal androgens is characterized by mild signs of virilization; substantial hypersecretion of adrenal androgens is characterized by accelerated growth, increased bone age, increased muscle mass, acne, hirsutism, and deepening of the voice.
In adults and children > 7 years of age, the most common cause of Cushing syndrome is Cushing disease. About 25% of patients referred for Cushing disease are children, and many patients first diagnosed as adults experienced the onset of symptoms in childhood or adolescence; thus, pediatric Cushing disease is more common than generally recognized. Before puberty, boys are more frequently affected, the sex ratio is equal during adolescence, and women have a higher incidence in adulthood. Adrenal tumors cause most cases of Cushing syndrome in children < 7 years old (Table 528-1). The ectopic ACTH syndrome, where a malignancy “ectopically” produces proopiomelanocortin (POMC; the precursor to ACTH), is rare in children; associated tumors include neuroblastoma, pheochromocytoma, and pancreatic islet cell carcinomas. ACTH-independent multinodular adrenal hyperplasias are characterized by hypersecretion of cortisol and adrenal androgens.
TABLE 528-1ETIOLOGY OF CUSHING SYNDROME IN 60 INFANTS |Favorite Table|Download (.pdf) TABLE 528-1ETIOLOGY OF CUSHING SYNDROME IN 60 INFANTS
| ||Males ||Females |
|Adrenal tumors (n = 48) || || |
|Carcinoma ||5 ||20 |
|Adenoma ||4 ||16 |
|Not defined ||2 ||1 |
|Ectopic ACTH syndrome ||1 ||1 |
|Nodular adrenal hyperplasia ||1 ||4 |
|Undefined adrenal hyperplasia ||2 ||2 |
|ACTH-producing tumor ||1 ||0 |
|TOTAL ||16 ||44 |
CLINICAL FINDINGS AND DIAGNOSIS
Central obesity, “moon facies,” hirsutism, and facial flushing are seen in > 80% of adults with Cushing syndrome. Striae, hypertension, muscular weakness, back pain, “buffalo hump” fat distribution, psychological disturbances, acne, and easy bruising are seen in 35% to 80%, but these features of advanced Cushing disease can take 5 years to develop; hence, the classic “Cushingoid appearance” is not the initial picture in pediatric Cushing syndrome. The earliest, most reliable indicators of hypercortisolism in children are weight gain (> 90% of cases) and growth arrest (~85%) (Table 528-2); any overweight child who stops growing should be evaluated for Cushing syndrome. Glucocorticoids suppress growth by increasing hypothalamic somatostatin, suppressing growth ...