Porth's Essentials of Pathophysiology, 4e

789

Disorders of Endocrine Control of Growth and Metabolism

C h a p t e r 3 2

is the adrenal form, caused by a benign or malignant adrenal tumor. The third form is ectopic Cushing syn- drome, caused by a nonpituitary ACTH-secreting tumor. Certain extrapituitary malignant tumors such as small cell carcinoma of the lung may secrete ACTH or, rarely, CRH and produce Cushing syndrome. Cushing syn- drome also can result from long-term therapy with one of the potent pharmacologic preparations of glucocorti- coids; this form is called iatrogenic Cushing syndrome. The major manifestations of Cushing syndrome rep- resent an exaggeration of the many actions of cortisol. Altered fat metabolism causes a peculiar deposition of fat characterized by a protruding abdomen; subclavicu- lar fat pads or “buffalo hump” on the back; and a round, plethoric “moon face” (Fig. 32-16). There is muscle weakness, and the extremities are thin because of protein breakdown and muscle wasting. In advanced cases, the

skin over the forearms and legs becomes thin, having the appearance of parchment. Purple striae, or stretch marks, from stretching of the catabolically weakened skin and subcutaneous tissues are distributed over the breast, thighs, and abdomen. Osteoporosis may develop because of destruction of bone proteins and alterations in calcium metabolism, resulting in back pain, compres- sion fractures of the vertebrae, and rib fractures. As cal- cium is mobilized from bone, renal calculi may develop. Derangements in glucose metabolism are found in approximately 75% of patients, with clinically overt diabetes mellitus occurring in approximately 20%. The glucocorticoids possess mineralocorticoid properties; this causes hypokalemia as a result of excessive potas- sium excretion and hypertension resulting from sodium retention. Inflammatory and immune responses are inhibited, resulting in increased susceptibility to infec- tion. Cortisol increases gastric acid secretion, which may provoke gastric ulceration and bleeding. An accompany- ing increase in androgen levels causes hirsutism (facial hair), mild acne, and thinning of the hair, along with menstrual irregularities in women (Fig. 32-17). Excess levels of the glucocorticoids may give rise to extreme emotional lability, ranging from mild euphoria and absence of normal fatigue to grossly psychotic behavior. Diagnosis of Cushing syndrome depends on the find- ing of cortisol hypersecretion. 39,40,47,48 The determination of 24-hour excretion of cortisol in urine provides a reliable and practical index of cortisol secretions. One of the promi- nent features of Cushing syndrome is loss of the diurnal pattern of cortisol secretion. This is why late-night (between 11 pm and midnight) serum or salivary cortisol levels can be inappropriately elevated, aiding in the diagnosis of Cushing syndrome. The overnight dexamethasone suppression test is also used as a screening tool for Cushing syndrome.

Emotional disturbance

Fat pads (buffalo hump)

Moon facies

Cardiac hypertrophy (hypertension)

Thin, wrinkled skin

Pendulous abdomen

Poor wound healing

Abdominal striae

Amenorrhea

Osteoporosis

Ecchymosis

Muscle wasting and weakness

Purpura

FIGURE 32-17. Cushing syndrome. A woman who suffered from a pituitary adenoma that produced adrenocorticotropic hormone exhibits a moon face, buffalo hump, increased facial hair, and thinning of scalp hair (From: Merino MJ, Quezado M. The endocrine system. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2012:1073.)

FIGURE 32-16. Clinical features of Cushing syndrome.