SPECIFIC SYNDROMES ASSOCIATED WITH OBESITY

Cushing's syndrome
Although obese patients commonly have central obesity, hypertension, and glucose intolerance, they lack
other specific stigmata of Cushing's syndrome (Chap. 342). Nonetheless, a potential diagnosis of Cushing's
syndrome is often entertained. Cortisol production and urinary metabolites (17OH steroids) may be
increased in simple obesity. Unlike in Cushing's syndrome, however, cortisol levels in blood and urine in the
basal state and in response to corticotropin-releasing hormone (CRH) or ACTH are normal; the overnight 1-
mg dexamethasone suppression test is normal in 90%, with the remainder being normal on a standard 2-
day low-dose dexamethasone suppression test. Obesity may be associated with excessive local reactivation

of cortisol in fat by 11 -hydroxysteroid dehydrogenase 1, an enzyme that converts inactive cortisone to
cortisol.
Hypothyroidism
The possibility of hypothyroidism should be considered, but it is an uncommon cause of obesity;
hypothyroidism is easily ruled out by measuring thyroid-stimulating hormone (TSH). Much of the weight gain
that occurs in hypothyroidism is due to myxedema (Chap. 341).
Insulinoma

Patients with insulinoma often gain weight as a result of overeating to avoid hypoglycemic symptoms (Chap.
345). The increased substrate plus high insulin levels promote energy storage in fat. This can be marked in
some individuals but is modest in most.
Craniopharyngioma and other disorders involving the hypothalamus
Whether through tumors, trauma, or inflammation, hypothalamic dysfunction of systems controlling satiety,
hunger, and energy expenditure can cause varying degrees of obesity (Chap. 339). It is uncommon to
identify a discrete anatomic basis for these disorders. Subtle hypothalamic dysfunction is probably a more
common cause of obesity than can be documented using currently available imaging techniques. Growth
hormone (GH), which exerts lipolytic activity, is diminished in obesity and is increased with weight loss.
Despite low GH levels, insulin-like growth factor (IGF)-I (somatomedin) production is normal, suggesting that
GH suppression is a compensatory response to increased nutritional supply.