Chapter 195: Cushing Syndrome

Patient Story

A 21-month-old girl is brought to the pediatrician for a routine physical examination. The mother notes that the child has recently gained an excessive amount of weight. Examination shows an obese toddler who has a blood pressure of 130/90 mm Hg. The linear growth is noted to be abnormal and her weight has jumped from the 50^th percentile at the last visit 6 months ago to above the 90^th percentile. The girl has hirsutism and acne on the forehead (Figure 195-1). Urinalysis shows glycosuria. The pediatrician is suspicious for hypercortisolism and refers the child to a pediatric endocrinologist. A dexamethasone suppression test reveals lack of suppression of cortisol, consistent with Cushing syndrome. A CT scan of the abdomen reveals an adrenal tumor, which is surgically resected and found to be an adrenal adenoma. The girl is maintained on glucocorticoid therapy and recovers.

Introduction

Cushing syndrome occurs as a result of cortisol or glucocorticoid excess from any cause. Excess plasma cortisol production in endogenous Cushing syndrome may be caused by either excess ACTH secretion from the pituitary gland (Cushing disease) or adrenal overproduction of plasma cortisol from adrenal tumors. Cushing syndrome can also be the result of exogenous administration of ACTH or glucocorticoids (iatrogenic).

Synonyms

Hypercortisolism.

Epidemiology

• Non-iatrogenic Cushing syndrome is rare in children.

• Children with lymphoproliferative disorders, nephrotic syndrome, and autoimmune disorders are at risk for developing exogenous Cushing syndrome.

• The incidence of Cushing syndrome is higher in obese patients with type 2 diabetes, occurring in 2 to 5 percent of these patients.¹

• Cushing syndrome is 2 to 3 times more common in girls than boys.

Etiology and Pathophysiology

• Cushing syndrome is most commonly caused by the administration of oral, parenteral, or topical glucocorticoids (exogenous or iatrogenic Cushing syndrome).

• In children over 7 years of age, true Cushing disease (hypersecretion of pituitary ACTH causing adrenal hyperplasia) is the most common cause of Cushing syndrome.²

• In infants and young children, Cushing syndrome is most often caused by a functioning adrenocortical tumor. Infants show signs of hypercortisolism along with signs of hypersecretion of other steroids such as androgens, estrogens, and aldosterone.^3–5

• ACTH-dependent Cushing syndrome may also result from ectopic production of ACTH, although this is uncommon in children. Ectopic ACTH secretion in children has been associated with islet cell carcinoma of the pancreas, neuroblastoma, hemangiopericytoma, Wilms tumor, and thymic carcinoid.⁶

Risk Factors

• Lymphoproliferative disorders.

• Nephrotic syndrome.

• Autoimmune disorders.

• Obesity and ...