Here’s another USMLE® Step 2 CK Question of the Day! Today’s case involves a 31-year-old woman with recurrent episodes of headache, palpitations, and anxiety. Can you figure it out?
A 31-year-old woman comes to her physician for evaluation of recurrent episodes of headache, palpitations, and anxiety. She works as a lawyer and states her job has been stressful recently, and she has noticed that these episodes occur more frequently now. The patient had a prophylactic thyroidectomy at a young age due to an inherited genetic condition. Her temperature is 37.0°C (98.6°F), her pulse is 88/min, and her blood pressure is 128/80 mmHg. Physical examination reveals an arm span that exceeds the patient’s height. Examination of the oral cavity shows multiple small mucosal nodules at the tip of the tongue. Which of the following diagnostic studies would be most helpful in confirming the diagnosis in this patient?
A. 24-hour urinary metanephrines test
B. MRI of the brain
C. Midnight salivary cortisol
D. Serum calcium measurement
E. Serum gastrin measurement
Scroll down for the correct answer!
The correct answer to today’s USMLE® Step 2 CK Question is…
A. 24-hour urinary metanephrines test
Before we get to the Main Explanation, let’s see why the answer wasn’t B, C, D, or E. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
Today’s incorrect answers are…
B. MRI of the brain
Incorrect: MRI of the brain would be useful for visualizing an intracranial mass, such as a pituitary adenoma. Patients with multiple endocrine neoplasia (MEN) type 1, for example, are predisposed to developing pituitary masses. This patient with MEN 2B, however, is not likely to have an intracranial mass, nor would it explain her symptoms.
C. Midnight salivary cortisol
Incorrect: An elevated midnight salivary cortisol level may be present in patients with hypercortisolism, either due to a pituitary or adrenal mass. This patient with multiple endocrine neoplasia (MEN) type 2B, however, is not likely to have Cushing syndrome. Furthermore, hypercortisolism would not manifest with the intermittent episodes of headaches, palpitations, and anxiety experienced by this patient.
D. Serum calcium measurement
Incorrect: Serum calcium measurement would be useful for patients suspected of having hypercalcemia (e.g., nephrolithiasis, constipation, neuropsychiatric disturbances). Parathyroid hyperplasia, a common cause of hypercalcemia, is associated with MEN 1 and MEN 2A. This patient, however, has tongue neuromas and a Marfanoid body habitus (arm span exceeding height), which is more consistent with MEN 2B.
E. Serum gastrin measurement
Incorrect: Pancreatic neoplasms can be seen in multiple endocrine neoplasia (MEN) type 1. Gastrinomas, for example, can present with abdominal pain, diarrhea, and weight loss. However, a gastrinoma would not manifest with intermittent episodes of headaches, palpitations, and anxiety.
Main Explanation
This patient has a history of prophylactic thyroidectomy and a physical examination showing mucosal neuromas and a Marfanoid habitus. She likely has multiple endocrine neoplasia type 2B (MEN 2B).
MEN 2B is caused by a mutated RET proto-oncogene and can result in tumor formation within the thyroid and adrenal gland. Medullary thyroid cancer occurs in almost all patients, therefore warranting prophylactic removal when the syndrome is diagnosed. Adrenal gland neoplasms typically occur in the medulla in the form of pheochromocytomas. The sudden release of catecholamines from the adrenal tumor causes paroxysmal episodes characterized by sympathetic overactivation; hypertensive episodes associated with anxiety, tachycardia, palpitations, headache, diaphoresis (sweating), and tremors are common symptoms.
The diagnosis of pheochromocytoma is made based upon biochemical confirmation of catecholamine hypersecretion, followed by identifying the tumor with imaging studies. Initial biochemical tests involve checking the levels of two hormones, metanephrine, and normetanephrine, which are compounds produced from the degradation of catecholamines in the blood and urine. This laboratory evaluation can be done by either a plasma-free metanephrines test or a 24-hour urinary metanephrines test. Once a diagnosis of pheochromocytoma is confirmed, an ultrasound or a CT scan can be used to identify the tumor’s location.
Major Takeaway
Pheochromocytomas are neoplasms found within the adrenal medulla that autonomously secrete catecholamines. Therefore, diagnosis relies on biochemical confirmation of catecholamine hypersecretion (e.g., plasma metanephrines, 24-hour urine metanephrines test), followed by identifying the tumor’s location via imaging studies.
References
Farrugia, F.A., Martikos, G., Tzanetis, P., et al. (2017) Pheochromocytoma, diagnosis and treatment: Review of the literature. Endocrine Regulations. 51(3), 168-181. Doi: 10.1515/enr-2017-0018.
Kumar, V., Abbas, A.K., Aster, J.C., Perkins, J.A., Robbins, S.L. (2018) Robbins basic pathology (10th ed.). Philadelphia, PA: Elsevier. ISBN: 978-0-323-35317-5.
Mubarik, A., Aeddula, N.R. (2020) “Chromaffin cell cancer”. StatPearls [Internet]. Web Address: https://www.ncbi.nlm.nih.gov/books/NBK535360/.
Leave a Reply