Cushing's syndrome from lesions of the adrenal gland: causes, diagnostic methods, and pathologic appearances. (<250 words)

Cushing's syndrome results from increased cortisol production. Adrenal causes include functioning neoplasms, with adrenal cortical adenomas more common than carcinomas. An adrenal adenoma is usually a discrete small yellow cortical nodule; an adrenal cortical carcinoma is much larger, more variegated in appearance, and often obliterates the normal architecture. In both cases, remaining adrenal tissue is compressed or atrophic. Less commonly, bilateral adrenal cortical hyperplasia occurs in which the cortex is thickened and nodular. Microscopically, all of these lesions show cells with clear to pink cytoplasm. There is some pleomorphism, even in benign neoplasms. Cortical carcinomas have more atypia, but metastases are the only reliable indicator for malignancy. Diagnosis of Cushing's syndrome is suggested by clinical features such as truncal obesity, moon facies, striae, hypertension, and glucose intolerance. Laboratory testing will reveal an increased cortisol with loss of diurnal variation along with decreased ACTH. Cushing's syndrome from adrenal neoplasms often shows lack of suppression of cortisol with the dexamethasone suppression test and a minimal increase in ACTH in response to administration of metyrapone.

Discuss etiologies for hypercalcemia. (<250 words)

Hypercalcemia is often discovered by routine serum chemistry, but signs and symptoms may include: constipation, cardiac arrhythmias, renal stones, pancreatitis, muscle weakness, nausea, hypertension, metastatic calcification of tissues, osteitis fibrosa cystica. Hypercalcemia can result from primary hyperparathyroidism with increased parathormone. This will cause the serum calcium to be increased and phosphate to be decreased. Usually, this is due to an adenoma from enlargement of one of the glands. Parathyroid hyperplasia typically causes enlargement of all of the glands. Adenoma and hyperplasia can be difficult to distinguish pathologically, so all of the glands should be identified at the time of surgery. Parathyroid carcinoma, which involves one gland and invades surrounding tissues, is uncommon but can lead to very high calcium levels. Parathyroid hyperplasia or adenoma can occur as part of multiple endocrine neoplasia syndromes.

Hypercalcemia from neoplasia outside of the parathyroid glands occurs about as often as primary hyperparathyroidism. Some malignancies, particularly lung and renal cancers, can secrete a parathormone-like substance which increases calcium, though the actual parathormone level will not be increased. Metastatic tumors to bone, as well as multiple myeloma, can cause lysis with release of calcium. In these conditions, the alkaline phosphatase is often greatly increased.

Less common causes of hypercalcemia include excess vitamin D, granulomatous disease such as sarcoidosis, drugs such as thiazide diuretics, and prolonged immobilization. In these cases, parathormone would not be increased. Though initially chronic renal failure with phosphate retention tends to cause hypocalcemia, late in the course secondary hyperparathyroidism can lead to hypercalcemia.