Diagnosis
History and physical
Comments
Pheochromocytoma
Episodic hyperadrenergic symptoms (5 P’s): pressure (hypertension), pain (headache), perspiration, palpitation, pallor
Associated with MEN 2, neurofibromatosis-1, and von Hippel-Lindau disease (VHL)
Carcinoid syndrome
Bronchospasm, diarrhea, flushing of skin, and right-sided heart disease; symptoms triggered by alcohol or emotional stress
Excess serotonin release, malignant proliferation of neuroendocrine cells, most commonly arise from the small bowel, need liver metastasis or extra-GI tumor for syndrome
Fibromuscular dysplasia
Severe hypertension in a young female
Renal artery has “string-of-beads” appearance due to medial thinning alternating with stenosis; also affects carotid, superior mesenteric, and external iliac arteries
Panic attack
Intense fear or feeling of impending doom, palpitations, perspiration, and hyperventilation
Associated with mitral valve prolapse
Hyperthyroidism
Anxiety, emotional lability, weakness, tremor, palpitations, heat intolerance, perspiration, and weight loss despite increased appetite
Decreased TSH, increased TH
Migraine
Pulsatile, unilateral headache, with nausea/vomiting; some associated with aura (photopsia, paresthesia, numbness)
Can mimic stroke
Coarctation of the aorta
Hypertension in the arms but not the legs, weak femoral and pedal pulses
Turner syndrome, aortic valve pathology
Insulinoma
Whipple’s triad: hypoglycemia, symptoms of hypoglycemia (tremulousness, palpitations, perspiration, and anxiety), and improvement after carbohydrate load
Tumor of pancreatic beta cells; MEN 1; 90 % benign
Drug induced
Combination of MAOI (monoamine oxidase inhibitors) with decongestants, sympathomimetics
Never give β-blockers to patients using cocaine (can lead to vasoconstrictive angina due to unopposed alpha-receptor stimulation)
Illicit drugs including phencyclidine (PCP), lysergic acid diethylamide (LSD), and cocaine
What Is the Most Likely Diagnosis?
In a patient with newly discovered hypertension coupled with reports of episodes where she experiences sweating, flushing, and palpitations lasting for a few minutes, the most likely diagnosis is a catecholamine surge secondary to pheochromocytoma. This is further supported by her biochemical workup confirming elevated urine metanephrine levels and a CT scan showing a mass in her right adrenal gland. Additionally, she has orthostatic hypotension and elevated hematocrit and serum glucose, all of which support the diagnosis.
History and Physical
What Is the Differential Diagnosis for Surgically Correctable Hypertension (HTN)?
Ninety-five percent of HTN cases are due to essential or primary HTN. It is important that the clinician be aware that 5 % are due to surgically correctable causes. These include pheochromocytoma, adrenal adenomas that produce cortisol or aldosterone, renal artery fibromuscular dysplasia, and aortic coarctation.
What Is the Classic Triad of Symptoms in Pheochromocytoma?
The symptoms of pheochromocytoma derive from the systemic effects of excess catecholamines (Table 10.1). The classic triad of symptoms includes headache, flushing, and palpitations. Though only a minority of patients have all three of these symptoms, 90 % have at least one. It is important to remember that these symptoms are nonspecific and may reflect a number of other underlying diagnoses.
Table 10.1
Effects of normal and excessive amounts of catecholamine
Receptor | Normal function | Excessive function |
|---|---|---|
α 1 | Smooth muscle contraction, gluconeogenesis, glycogenolysis | Hypertension, hyperglycemia |
α 2 | Smooth muscle contraction, platelet aggregation | Pallor |
β 1 | Chronotropic, inotropic, sweat glands | Tachycardia, sweating |
β 2 | Smooth muscle relaxation | Hypotension |
What Are the Other Symptoms of Pheochromocytoma?
The vast majority of patients with pheochromocytoma have either sustained or episodic hypertension, often resistant to standard medical therapy. Other symptoms include anxiety and impaired gastrointestinal motility. Cardiovascular sequelae consist of myocardial infarction, arrhythmias, stroke, and less commonly heart failure.
Watch Out
Hypertension associated with pheochromocytoma can be paroxysmal or can have fluctuations superimposed on constantly elevated blood pressure. This is dependent on whether catecholamines are released continuously or in shorter bursts.
Why Do Some Patients Have Orthostatic Hypotension?
Orthostatic hypotension may reflect a low intravascular volume. In addition, patients with pheochromocytoma have adrenergic receptors that are exposed to large amounts of catecholamine and can become desensitized over time. The normal baroreceptor reflex which causes vasoconstriction upon standing from a supine position may be compromised, resulting in orthostatic hypotension.
Can Patients with Pheochromocytoma Be Asymptomatic?
With the increasing use of CT scans, upwards of 25 % of patients are now diagnosed incidentally during imaging for unrelated disorders. About 5–10 % of incidentally discovered adrenal nodules are pheochromocytomas.
What Is the Average Age of Diagnosis? Is There a Gender Predisposition?
Patients are usually diagnosed at age 40–50 years. There is an equal incidence of cases in males and females.
What Is the “Rule of Tens” and Is It Still True?
The “rule of tens” regarding pheochromocytoma (10 % bilateral, 10 % extra-adrenal, 10 % familial, 10 % multifocal, 10 % malignant) was taught to generations of medical students. It was ultimately disproved in the year 2000 after a series of reports described novel germline mutations causing pheochromocytoma. We now recognize that 20–40 % of pheochromocytomas arise as a result of an underlying familial syndrome and that clear genotype-phenotype correlations exist (Table 10.2).
Table 10.2
Hereditary syndromes associated with pheochromocytoma
Syndrome | Gene mutation (function) | Clinical phenotype | Pheo characteristics | Riska (%) |
|---|---|---|---|---|
MEN 2A | RET (proto-oncogene) | Medullary thyroid cancer, primary hyperparathyroidism | Benign, bilateral or multicentric; intra-adrenal | 50 |
MEN 2B | RET (proto-oncogene) | Medullary thyroid cancer, marfanoid habitus, mucosal neuromas | Benign, bilateral or multicentric; intra-adrenal | 50 |
Neurofibromatosis (NF) type 1 (von Recklinghausen’s disease) | NF1 (negative regulator of ras oncogene pathway) | Neurofibromas, café au lait spots, Lisch nodules (benign iris hamartomas) | 15 % malignant; intra-adrenal | 1–5 |
von Hippel-Lindau (VHL) | VHL (tumor suppressor) | Retinal angioma, CNS hemangioblastoma, renal cell cancer, PNET, pancreatic and renal cysts | Benign, bilateral; younger age at diagnosis | 10–20 |
Pheo pheochromocytoma, PG paraganglioma, MEN multiple endocrine neoplasia, CNS central nervous system, PNET pancreatic neuroendocrine tumor
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