Just another sports physical, right? Wrong! Although this teenager said he felt fine lately, his pediatrician noted a significantly high blood pressure reading of 170/90 and requested that he return a few days later for close follow up. But before then, he joined a family member on a visit to a local ED, where the family member registered the adolescent for a quick blood pressure check. Again it was elevated at 170/90. So, a medical student and physician in the ED asked, have you had any recent, unusual symptoms? Well, yes, for the past few months he had been experiencing intermittent headaches, frequent episodes of heavy sweating and urination at night, heart palpitations and heat intolerance so severe he wore shorts in the winter. That was enough for the ED doc, who promptly began a thorough workup.
History also revealed hypertension among maternal relatives and family drug use. While his labs were benign, CT imaging picked up a right adrenal mass, triggering a transfer to Johns Hopkins Children’s Center pediatric intensive care unit (PICU). There, along with the PICU team, pediatric resident Kathryn Lemberg began to manage the patient’s hypertension while considering the differential diagnosis for this patient—including coarctation of the aorta, Cushing syndrome, glomerulonephritis, hyperthyroidism, and renal artery stenosis.
“In a pediatric patient with hypertension, renal problems always come to mind, but there was potentially a cardiac cause and we didn’t want to rule out a toxin or drug exposure,” says Lemberg. “Endocrine causes, like hyperthyroidism, were being considered, too.”
Pediatric nephrologist Cozumel Pruette agreed, citing the patient’s history, diaphoresis, headaches, nocturia and significant heat intolerance.
“I also considered renal artery stenosis, an underlying chronic kidney disease like glomerulonephritis, or a urologic disorder that could explain the urination frequency,” says Pruette. “Given his symptoms, I also thought of a pheochromocytoma. Often we have it on our list but we don’t necessarily move it toward the top.”
Pheochromocytoma, a benign tumor that develops in the cells in the center of the adrenals, are known to prompt these glands to release hormones that cause persistent or episodic high blood pressure which, if untreated, may result in severe or life-threatening damage to other body systems, especially the cardiovascular system. But these tumors are rare, especially in children—most patients are between 20 and 50. Some doubt was also raised in imaging, which showed internal calcifications uncharacteristic of a pheochromocytoma.
Indeed, pediatric radiology fellow Alexander Oshmyansky, in looking at the images from an outside hospital, first suspected an adrenal cortical carcinoma, a rare but aggressive cancer originating in the cortex of the adrenal gland.
“Pheos don’t often calcify centrally, although they are known to calcify peripherally,” says Oshmyansky. “What does give us a more definitive diagnosis is further imaging with MIBG scans.” MIBG (Meta-Iodo-Benzyl-Guanidine) is a type of nuclear imaging that uses a radioactive tracer to confirm the presence of a pheochromocytoma.
Confirmation of the diagnosis by biochemical testing should precede localization of the tumor, notes pediatric endocrinologist Janet Crane. In such cases she recommends 24-hour urine testing of catecholamines produced in the adrenal gland, as well as random plasma metanephrine testing. Indeed, in this patient both his urine and plasma catecholamines and metanephrines were quite elevated.
The diagnosis, adds Crane, raises another flag for pediatricians as 35 percent of pheochromocytomas are associated with a genetic disorder, commonly Von-Hippel Lindau syndrome (VHL), and multiple endocrine neoplasia type 2 (MEN2), which also needs to be evaluated. In this case, additional laboratory tests, imaging and experts were consulted.
MIBG imaging localized the tumor, opening the door for the treatment of choice, surgery. Resection of the tumor is straightforward but careful preoperative management is required to control blood pressure, correct fluid volume, and prevent intraoperative hypertensive crises. Surgical follow-up includes blood pressure management and annual plasma metanephrine testing. Lifelong follow-up is required for patients with an underlying genetic mutation.
What stands out in this case for Lemberg was the early attention by the pediatrician and the outside hospital ED staff, and the need for careful attention to blood pressure monitoring in the outpatient setting.
“The most interesting thing was the incidental finding on a sports physical exam and the subsequent workup at the outside ED that picked up a lot of the points that led to this patient getting more attention,” says Lemberg. “For myself, I came to appreciate the importance of checking blood pressures sufficiently with patients who haven’t been seen in a while. It’s important for our patients’ long-term health that we pick up on hypertension and then work to identify the cause and manage it appropriately.”