The incidence of ovarian hyperstimulation syndrome is reduced with adjuvant metformin in PCOS patients at risk for severe ovarian hyperstimulation syndrome (153).
Cushing Syndrome The adrenal cortex produces three classes of steroid hormones: glucocorticoids, mineralocorticoids, and sex steroids (androgen and estrogen precursors). Hyperfunction of the adrenal gland can produce clinical signs of increased activity of any or all of these hormones. Increased glucocorticoid action results in nitrogen wasting and a catabolic state. This causes muscle weakness, osteoporosis, atrophy of the skin with striae, nonhealing ulcerations and ecchymoses, reduced immune resistance that increases the risk of bacterial and fungal infections, and glucose intolerance resulting from enhanced gluconeogenesis and antagonism to insulin action.
Although most patients with Cushing syndrome gain weight, some lose it. Obesity is typically central, with characteristic redistribution of fat over the clavicles around the neck and on the trunk, abdomen, and cheeks. Cortisol excess may lead to insomnia, mood disturbances, depression, and even overt psychosis. With overproduction of sex steroid precursors, women may exhibit hyperandrogenism (hirsutism, acne, oligomenorrhea or amenorrhea, thinning of scalp hair). Masculinization is rare, and its presence suggests an autonomous adrenal origin, most often an adrenal malignancy. With overproduction of mineralocorticoids, patients may manifest arterial hypertension and hypokalemic alkalosis. The associated ﬂuid retention may cause pedal edema (Table 31.7) (154).
Characteristic clinical laboratory findings associated with hypercortisolism are confined mainly to a complete blood count showing evidence of granulocytosis and reduced levels of lymphocytes and eosinophils. Increased urinary calcium secretion may be present.
Table 31.7 Overlapping Conditions and Clinical Features of Cushing Syndrome
Easy bruising Facial plethora Proximal myopathy (or proximal muscle weakness) Striae (especially if reddish purple and >1 cm wide) In children, weight gain with decreasing growth
Cushing syndrome features in the general population that are common and/or less discriminatory
Features are listed in random order. ∗Cushing’s syndrome is more likely if onset of the feature is at a younger age.
Causes The six recognized noniatrogenic causes of Cushing syndrome can be divided between those that are ACTH dependent and those that are ACTH independent (Table 31.8). The ACTH-dependent causes can result from ACTH secreted by pituitary adenomas or from an ectopic source. The hallmark of ACTH-dependent forms of Cushing syndrome is the presence of normal or high plasma ACTH concentrations with increased cortisol levels. The adrenal glands are hyperplastic bilaterally. Pituitary ACTH-secreting adenoma, or Cushing disease, is the most common cause of endogenous Cushing syndrome (154). These pituitary adenomas are usually microadenomas (<10 mm in diameter) that may be as small as 1 mm. They behave as though they are resistant, to a variable degree, to the feedback effect of cortisol. Like the normal gland, these tumors secrete ACTH in a pulsatile fashion; unlike the
Table 31.8 Causes of Cushing Syndrome
ACTH, adrenocorticotropic hormone; CRH, corticotropin-releasing hormone. ACTH-dependent Cushing syndrome may be caused by pituitary adenoma, basophil hyperplasia, nodular adrenal hyperplasia, or cyclic Cushing syndrome.