Hypertension Case 1

Hypertension Case 1

A 35-year-old man has hypertension, which has been difficult to control with medication. Periodically, he experiences periods when he develops intense symptoms including racing heart, Iightheadedness, flushing, diaphoresis, clammy skin, headache, and a sense of impending
doom. He has gone to the emergency department of a local hospital several times during these episodes, but by the time he is seen several
hours later, the symptoms have long passed, and nothing can be found on physical examination or serum chemistry studies.

Q1
The patient's physician orders a 24-hour urine to be collected, which is found to contain significantly elevated levels of vanillylmandelic acid.
This compound is a degradation product of which of the following?
/ A. Acetylcholine
/ B. Cholesterol
/ C. Epinephrine
/ D. Serotonin
/ E. Testosterone


Q2
Which of the following is the most likely diagnosis?
/ A. Leiomyosarcoma
/ B. Lymphoma
/ C. Neuroblastoma
/ D. Pheochromocytoma
/ E. Small cell carcinoma


Q3
The tumors producing this patient's symptoms are usually found in which of the following sites?
/ A. Adrenal gland
/ B. Pancreas
/ C. Salivary gland
/ D. Thymus
/ E. Thyroid gland


Q4
Roughly what percentage of this patient's tumor type behave in a malignant fashion?
/ A. 5-10%
/ B. 20-30%
/ C. 50-60%
/ D. 70-80%
/ E. 90-95%


Q5
This patient's lesion has been associated with which of the following thyroid disorders?
/ A. Follicular carcinoma
/ B. Graves disease
/ C. Hashimoto disease
/ D. Medullary carcinoma
/ E. Papillary carcinoma


Q6
This patient is scheduled for surgical removal of the tumor. Which of the following agents should be administered before the surgery?
/ A. Iodide
/ B. Lorazepam
/ C. Phenoxybenzamine
/ D. Propylthiouracil
/ E. Spironolactone


____________________________________________________________________

Hypertension Case 1 Answers

A1
The correct answer is C. Vanillylmandelic acid (VMA) is a degradation product of both epinephrine and norepinephrine. It is secreted into the urine, and 24 hour screening for this metabolite (often along with the dopamine degradation product homovanillic acid, HVA) is used to look for excessive catecholamine secretion. The half-lives of epinephrine, norepinephrine, and dopamine are all very short and consequently direct measurement in serum of these species only provides a clinical answer if a patient is having a hypertensive paroxysm at the time. Two enzymes in these degradative pathways of which you should be aware are catechol-O-methyl transferase (COMT: adds methyl groups to hydroxyl moieties) and monamine oxidase (MAO: removes amino groups, oxidizing the nearby carbon to an aldehyde).
Acetylcholine (choice A) is usually not measured in the clinical laboratory.
Cholesterol (choice B) is measured in serum, and is unrelated to this patient's disease.
Serotonin (choice D) is produced by carcinoid tumors, and can be measured directly in serum, or its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), can be measured in urine.
Testosterone (choice E) can be measured directly in serum, and its precursors and metabolites (including DHT, androstenedione, 3-alpha-androstenediol glucuronide, DHEA) can also be measured in serum.


A2
The correct answer is D. This patient most likely has a pheochromocytoma. Pheochromocytoma is a rare tumor that is often suspected and seldom found. (Its incidence on the USMLE is very much higher than its incidence in general practice.) The tumors can secrete catecholamines such as epinephrine, norepinephrine, and/or dopamine, and the urinary determination of metabolites (see previous question) is the most reliable method of specifically suggesting the diagnosis. The vast majority of patients with pheochromocytoma have either paroxysmal or persistent hypertension. Patients who have a strong paroxysmal character to the secretion may have episodes similar to those described in the question stem. Neuroblastoma (choice C) can also secrete catecholamines, but is a tumor of childhood.
Lymphomas (choice B) and leiomyosarcomas (choice A, malignant tumor of smooth muscle) do not secrete catecholamines.
Small cell carcinoma (choice E) is known for the large number of paraneoplastic syndromes it can produce, but does not usually secrete catecholamines and would be very unusual in a man this young


A3
The correct answer is A. Approximately 80% of pheochromocytomas are found in the adrenal medulla, with the remainder being found in a wide variety of other tissues derived from neural crest cells, including, among others, the paraganglia of the sympathetic chain, along the aorta, in the carotid body, in the genital urinary tract, and in the brain. The other sites listed in the choices are not particularly prone to develop pheochromocytoma.


A4
The correct answer is A. 5-10% of pheochromocytomas overall are malignant; the proportion of malignant cases is higher (30%) in the extra-adrenal pheochromocytomas. 10% (20% in children) of the adrenal tumors are bilateral. Pheochromocytomas typically weigh 50-200 grams (uncommonly up to several kilograms) and are composed of nests of chromaffin cells that often appear cytologically bizarre, even when the tumors do not metastasize. Surgical resection is the preferred treatment modality; alpha and beta blockers are used to block the effects of the excess catecholamines prior to and during surgery.


A5
The correct answer is D. Both pheochromocytoma and medullary carcinoma of the thyroid can occur as part of familial multiple endocrine neoplasia, types IIA (Sipple syndrome) and IIb (mucosal neuronal syndrome). The medullary carcinoma is derived from the parafollicular C cells that secrete calcitonin, rather than thyroxine. Pheochromocytoma also has associations with neurofibromatosis and von Hippel-Lindau syndrome.
Follicular carcinoma (choice A) and papillary carcinoma (choice E) of the thyroid are cancers of the thyroid follicular epithelium, and are not associated with pheochromocytoma.
Graves disease (choice B) and Hashimoto disease (choice C) are both autoimmune thyroid disorders with no association with pheochromocytoma.

A6
The correct answer is C. Phenoxybenzamine, a nonselective alpha-blocking agent related to the nitrogen mustards, is indicated for the treatment of pheochromocytoma. It binds covalently to both alpha-1 and alpha-2-adrenergic receptors. After this medication is injected, a few hours must elapse before actual blockade occurs. By blocking alpha-receptors, phenoxybenzamine prevents the constriction of peripheral blood vessels, producing a reflex tachycardia. The desired action in patients with pheochromocytoma is related to the "epinephrine reversal," seen in classic drug traces. In epinephrine reversal, unopposed epinephrine increases blood pressure. After administration of an alpha antagonist (e.g., phenoxybenzamine, phentolamine), subsequent epinephrine administration decreases blood pressure because of unopposed beta stimulation.
Iodide (choice A) inhibits the release and the biosynthesis of T4 and T3. Iodide decreases the size and vascularity of the thyroid gland, hence makes it the preoperative treatment of choice for Graves disease.
Benzodiazepines, such as lorazepam (choice B), potentiate the effects of gamma-aminobutyrate (GABA), and are used for sedation, hypnosis, muscle relaxation, and anxiolysis. Although these agents may help to calm the patient, they would not ameliorate the patient's condition.
Propylthiouracil (choice D) inhibits the synthesis of the thyroid hormones. This agent does not inactivate existing T4 and T3; however, it is able to inhibit the peripheral conversion of T4 to T3. It is indicated for long-term hyperthyroid therapy, which may lead to disease remission, as well as short-term treatment before thyroidectomy or radioactive iodine therapy.
Spironolactone (choice E) is indicated for the treatment of edematous states as well as the prophylaxis and treatment of hypokalemia. It is commonly combined with other non-potassium sparing diuretics to prevent the appearance of hypokalemia.