1. Diagnosis is pheochromocytoma. You can not tell histologically whether a pheochromocytoma is benign or malignant. Demonstration of metastases is the only way to diagnose malignancy.

2. Clinical tests that can make the diagnosis of pheochromocytoma prior to surgery include urinary catecholamines and metabolites, metanephrine and VMA (vanillylmandelic acid), or plasma catecholamines.

3. If the same type of neoplasm arose outside of the adrenal gland it would be called a paraganglioma.

4. Clinical features might include hypertension (especially labile type). Sudden release of catecholamines may precipitate congestive heart failure, pulmonary edema, myocardial infarction, ventricular fibrillation, cerebral hemorrhage or death. However, pheochromocytomas are rare tumors, and therefore most hypertension is not caused by pheochromocytomas.

5. Rule of ten: 10% bilateral, 10% metastasize, 10% are familial.

6. Origin is neural crest.

1. Diagnosis is ganglioneuroma. It is benign.

2. Origin is neural crest.

3. A ganglioneuroma is a benign tumor of neural crest origin that is completely differentiated. (Older children and young adults).

A neuroblastoma is an undifferentiated or malignant tumor of neural crest origin found in children, 80% under the age of 5 years. (>90% secrete catecholamines, primarily norepinephrine).

A tumor of neural crest origin that is intermediate in differentiation between neuroblastoma and ganglioneuroma are called ganglioneuroblastoma.

A neuroblastoma is composed of dense sheets of small, round to fusiform cells with hyperchromatic nuclei and scanty cytoplasm and frequent mitoses. Homer-Wright rosettes, rim of dark tumor cells in a circumferential arrangement around a central pale fibrillar core. Pseudo rosettes with tumor cells arranged around small vessels are also present.

A ganglioneuroma is well encapsulated and histologically has mature ganglion cells associated with scanty spindle cells in a loose and abundant stroma.

A ganglioneuroblastoma has combination of these patterns having ganglions and immature cells.

Both pheochromocytoma and paraganglioma have cells resembling the chromaffin cells of the adrenal medullar arranged in a zellballen pattern (nests of tumor cells surrounded by a delicate highly vascular network) and usually the cells have abundant finely granular eosinophilic cytoplasm and round nuclei with prominent nucleoli.

The neuroblastoma and ganglioneuroma show differentiation towards neuroblasts or neurons of the sympathetic ganglia. These tumors resemble immature neurons (neuroblastoma) or mature peripheral neurons or ganglion cells (ganglioneuroma). They do not show the same zellballen pattern seen with pheochromocytomas or paragangliomas even though these tumors are also of neural crest origin.

1. The hypercalcemia is more likely caused by primary hyperparathyroidism since, in addition to her elevated parathyroid hormone, the serum calcium was significantly elevated and there was increased urinary excretion of calcium and the serum phosphorus was decreased. In secondary hyperparathyroidism the increase in PTH is in response to a low serum calcium (so there would be low serum calcium and high PTH). Hypercalcemia can also be caused by malignancies either by bony mets or by secretion of a PTH like substance.

2. Diagnosis is parathyroid adenoma since by history the other three glands were normal. In hyperplasia all of the glands would be enlarged although not necessarily to the same degree.

3. Adenomas. 80% of cases of hyperparathyroidism are caused by a single adenoma. Only 15% are caused by hyperplasia. The others are caused by multiple adenomas or carcinomas.

4. In differentiating hyperplasia from adenomas, all glands would be enlarged and be more cellular with less fat than normal. In adenomas at least one gland should be of normal size and cellularity (for age and weight).

5. Carcinoma involves one gland, may be adherent to adjacent structures, has a thick fibrous capsule and thick fibrous bands often with capsular or vascular invasion, and more often has a trabecular growth pattern with increased mitotic figures.

6. Secondary hyperparathyroidism is caused by compensatory secretion of PTH in response to decreased blood calcium levels. it is most often caused by chronic renal insufficiency. other causes include vitamin D deficiency, intestinal malabsorption syndromes, Fanconi's syndrome and RTA.

7. The hyperparathyroidism led to increase excretion of calcium with secondary stone formation.

1. Tests would include morning and evening plasma cortisol levels (early there is a loss of the normal nocturnal decline in plasma cortisol levels), 24 hour urinary free cortisol, and dexamethasone suppression test. Dexamethasone, a steroid that has about 25 times more glucocorticoid potency than cortisol, suppresses pituitary ACTH (if given in adequate dose) and thus hypercorticolism but does not affect adrenal tumors. FYI "Low dose" dexamethasone is used to differentiate healthy individuals (which are suppressed) from those with Cushing's syndrome (which are not suppressed). "High dose" dexamethasone suppression test differentiates ACTH dependent (which are suppressed) from ACTH independent (which are not suppressed) forms of hypercortisolism.

2. The tumor is an adrenal cortical tumor.

3. Cushing's syndrome includes the clinical features of hypercortisolism from any cause. Cushing's syndrome is defined as ACTH-dependent (pituitary) adrenal hyperfunction. The most common cause of Cushing's's syndrome in the U.S. is iatrogenic, the chronic administration of corticosteroids in the treatment of immunologic and inflammatory disorders. The second most common etiology is praneoplastic effect of non-pituitary neoplasms such as bronchogenic carcinoma producing ACTH (small cell). The pituitary is 5 times more common as a cause of Cushing's's syndrome than adrenal neoplasm. Cushing's disease would show suppression of cortisol secretion by the dexamethasone suppression test and Cushing's syndrome resulting from an adrenal neoplasm would not show suppression.

4. Clinical features that may be present:

5. Addison's disease is primary chronic adrenal insufficiency. Failure of the adrenal glands to produce glucocorticoids, mineralocorticoids and androgen. Initially TB common cause. Now autoimmune adrenalitis accounts for 75% of cases.

Conn's syndrome: inappropriate secretion of aldosterone by an adrenal adenoma or hyperplastic adrenal gland producing hypertension and hypokalemia.

1. If the swelling was diffuse and not localized the differential would include diffuse nontoxic (simple goiter), multinodular goiter, and thyroiditis.

Adenomas are usually solitary discrete and < 4 cm nodules.

2. Hashimoto's thyroiditis.

3. Thyroid scan. Fine needle aspiration biopsy. Tests for autoimmune problems and antimicrosomal antibodies.

4. Surgery is not usually necessary in this disease.

5. The disease is an autoimmune inflammatory disorder.

It is thought that there may be a defect in suppressor T cell activity that allows persistence of sensitized clones of antithyroid lymphocytes allowing cytotoxic T cell attacks on follicular cells and allowing T helper cell participation in formation of autoantibodies such as those directed against the TSH receptor, thyroid microsomes, thyroglobulin, T3, T4 and follicular cell membranes.

6. Graves disease (and primary hypothyroidism) is also an autoimmune thyroid disorder.

1. Papillary carcinoma is the diagnosis.

Papillary architecture, and nuclear features including ground glass appearance, intranuclear pseudoinclusins, and longitudinal grooving.

2. It is the most frequent form of thyroid carcinoma.

3. It is indolent in its growth with 70-80% 10 year survival.

4. Extra-nodal extension, poorly differentiated histology, older age of patient, and long duration of disease are factors that worsen the prognosis.

1. Myxedema

2. It is more likely the result of goitrous hypothyroidism (or lack of thyroid tissue from surgical ablation etc) since the TSH is elevated and would be low if the underlying cause was suprathyroidal disorders such as hypopituitarism or hypothalamic lesions.

3. Not all patients with goiters are hypothyroid. Patients with diffuse nontoxic or simple goiters are hypothyroid. Patients with multinodular goiter may be nontoxic or be associated with thyrotoxicosis.

1. Grave's disease.

2. Multinodular goiter (may be nontoxic or hyperfunctioning) and toxic adenoma (only occasionally is an adenoma associated with hyperthyroidism) along with Graves disease make up 99% of cases of hyperthyroidism.

3. TSH would be decreased because antibodies cause stimulation for production of T3 and T4. The increased levels of thyroid hormones cause suppression of TSH.

4. The symmetrically enlarged thyroid would have hypertrophy and hyperplasia of the follicular epithelium (tall, columnar epithelium often forming papillae) with decreased colloid (often scalloped or "moth-eaten" where it abuts on the follicular epithelium).