64-year-old woman • hot flashes, facial flushing,
excessive sweating, and palpitations • daily
headaches • history of hypertension • Dx?

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doi:doi: 10.12788/jfp.0605

Case Reports

64-year-old woman • hot flashes, facial flushing, excessive sweating, and palpitations • daily headaches • history of hypertension • Dx?

J Fam Pract. 2023 June;72(5):222-224 | doi: 10.12788/jfp.0605

By

Nicole O. Vietor, MD

Andrew J. Spiro, MD

Mohamed K. M. Shakir, MD

Mitchell Harrison, MD

Robert C. Vietor, MD

Thanh D. Hoang, DO

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► Hot flashes, facial flushing, excessive sweating, and palpitations
► Daily headaches
► History of hypertension

References

1. Carey RM, Calhoun DA, Bakris GL, et al. Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association. Hypertension. 2018;72:e53-e90. doi: 10.1161/HYP.0000000000000084

2. Young WF Jr. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. J Intern Med. 2019;285:126-148. doi: 10.1111/joim.12831

3. Young WF Jr, Calhoun DA, Lenders JWM, et al. Screening for endocrine hypertension: an Endocrine Society Scientific Statement. Endocr Rev. 2017;38:103-122. doi: 10.1210/er.2017-00054

4. Lenders JWM, Pacak K, Walther MM, et al. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002;287:1427-1434. doi: 10.1001/jama.287.11.1427

5. Lenders JW, Duh Q-Y, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99:1915-1942. doi: 10.1210/jc.2014-1498

6. Kimura N, Takayanagi R, Takizawa N, et al. Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma. Endocr Relat Cancer. 2014;21:405-414. doi: 10.1530/ERC-13-0494

7. Thompson LDR. Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. Am J Surg Pathol. 2002;26:551-566. doi: 10.1097/00000478-200205000-00002

8. Vaidya A, Hamrahian A, Bancos I, et al. The evaluation of incidentally discovered adrenal masses. Endocr Pract. 2019;25:178-192. doi: 10.4158/DSCR-2018-0565

9. Young WF Jr. Conventional imaging in adrenocortical carcinoma: update and perspectives. Horm Cancer. 2011;2:341-347. doi: 10.1007/s12672-011-0089-z

10. Neumann HPH, Young WF Jr, Eng C. Pheochromocytoma and paraganglioma. N Engl J Med. 2019;381:552-565. doi: 10.1056/NEJMra1806651

11. Iñiguez-Ariza NM, Kohlenberg JD, Delivanis DA, et al. Clinical, biochemical, and radiological characteristics of a single-center retrospective cohort of 705 large adrenal tumors. Mayo Clin Proc Innov Qual Outcomes. 2017;2:30-39. doi: 10.1016/j.mayocpiqo.2017.11.002

12. Marty M, Gaye D, Perez P, et al. Diagnostic accuracy of computed tomography to identify adenomas among adrenal incidentalomas in an endocrinological population. Eur J Endocrinol. 2018;178:439-446. doi: 10.1530/EJE-17-1056

13. Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab. 2007;92:4069-4079. doi: 10.1210/jc.2007-1720

THE CASE

A 64-year-old woman sought care after having hot flashes, facial flushing, excessive sweating, palpitations, and daily headaches for 1 month. She had a history of hypertension that was well controlled with hydrochlorothiazide 25 mg/d but over the previous month, it had become more difficult to control. Her blood pressure remained elevated to 150/100 mm Hg despite the addition of lisinopril 40 mg/d and amlodipine 10 mg/d, indicating resistant hypertension. She had no family history of hypertension, diabetes, or obesity or any other pertinent medical or surgical history. Physical examination was negative for weight gain, stretch marks, or muscle weakness.

Laboratory tests revealed a normal serum aldosterone-renin ratio, renal function, and thyroid function; however, she had elevated levels of normetanephrine (2429 pg/mL; normal range, 0-145 pg/mL) and metanephrine (143 pg/mL; normal range, 0-62 pg/mL). Computed tomography (CT) revealed an 8.6-cm complex, hemorrhagic, necrotic left adrenal mass with attenuation of 33.1 Hounsfield units (HU) (FIGURE 1). Magnetic resonance imaging (MRI) demonstrated a T2 hyperintense left adrenal mass. An evaluation for Cushing syndrome was negative, and positron emission tomography (PET)/CT with gallium-68 dotatate was ordered. It showed intense radiotracer uptake in the left adrenal gland, with a maximum standardized uptake value of 70.1 (FIGURE 2).

THE DIAGNOSIS

After appropriate preparation with alpha blockade (phenoxybenzamine 20 mg twice daily for 7 days) and fluid resuscitation (normal saline run over 12 hours preoperatively), the patient underwent successful open surgical resection of the adrenal mass, during which her blood pressure was controlled with a nitroprusside infusion and boluses of esmolol and labetalol. Pathology results showed cells in a nested pattern with round to oval nuclei in a vascular background. There was no necrosis, increased mitotic figures, capsular invasion, or increased cellularity. Chromogranin immunohistochemical staining was positive. Given her resistant hypertension, clinical symptoms, and pathology results, the patient was given a diagnosis of pheochromocytoma.

DISCUSSION

Resistant hypertension is defined as blood pressure that is elevated above goal despite the use of 3 maximally titrated antihypertensive agents from different classes or that is well controlled with at least 4 antihypertensive medications.¹ The prevalence of resistant hypertension is 12% to 18% in adults being treated for hypertension.¹ Patients with resistant hypertension have a higher risk for cardiovascular events and death, are more likely to have a secondary cause of hypertension, and may benefit from special diagnostic testing or treatment approaches to control their blood pressure.¹

There are many causes of resistant hypertension; primary aldosteronism is the most common cause (prevalence as high as 20%).² Given the increased risk for cardiovascular/cerebrovascular disease, all patients with resistant hypertension should be screened for this condition.² Other causes of resistant hypertension include renal parenchymal disease, renal artery stenosis, coarctation of the aorta, thyroid dysfunction, Cushing syndrome, paraganglioma, and as seen in our case, pheochromocytoma. Although pheochromocytoma is a rare cause of resistant hypertension (0.01%-4%),¹ it is associated with high rates of morbidity and mortality if left untreated and may be inherited, making it an essential diagnosis to consider in all patients with resistant hypertension.^1,3

Common symptoms of pheochromocytoma are hypertension (paroxysmal or sustained), headaches, palpitations, pallor, and piloerection (or cold sweats).¹ Patients with pheochromocytoma typically exhibit metanephrine levels that are more than 4 times the upper limit of normal.⁴ Therefore, measurement of plasma free metanephrines or urinary fractionated metanephrines is recommended.⁵ Elevated metanephrine levels also are caused by obesity, obstructive sleep apnea, and certain medications and should be ruled out.⁵

All pheochromocytomas are potentially malignant. Despite the existence of pathologic scoring systems^6,7and radiographic features that suggest malignancy,^8,9 no single risk-stratification tool is recommended in the current literature.¹⁰ Ultimately, the only way to confirm malignancy is to see metastases where chromaffin tissue is not normally found on imaging.¹⁰

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