Patients with pituitary ACTH-dependent disease (i.e., Cushing disease) usually have a history of disease that begins 2 to 3 years before a definitive diagnosis is made. In milder cases, symptoms may be present for 5 to 10 years. Earliest symptoms include weight gain, progressive changes in physical appearance, hypertension, and glucose intolerance. Patients may have been treated for these conditions with weight-reduction diets, antihypertensive drugs, and oral hypoglycemic agents. The
response to diet is frequently unsuccessful. Those who do not experience actual weight gain notice redistribution of adipose tissue resulting in changes in appearance, with facial rounding, increased central adiposity, and thinning of upper and lower extremities.

After 2 to 3 years of mild symptoms, additional symptoms or increased severity of the initial symptoms draw patients to the attention of the physician. Patients relate the appearance of striae, easy bruising, and increased body hair growth; irregular menses or amenorrhea may be present in women or gynecomastia in men. Proximal muscle weakness and atrophy are common, and some patients exhibit manifestations of a steroid myopathy. Other manifestations include peripheral edema, back pain, and loss of height if patients have developed severe osteoporosis and compression fractures of the vertebrae (Fig. 75-6A).