We describe a case of a young adult in whom sudden cardiac death due to ventricular fibrillation was the presenting manifestation of an adrenocortical carcinoma.The arrhythmia was precipitated by severe hypokalemia induced by the aldosterone-secreting tumor. Sudden death has not been previously described as a manifestation of this adrenal neoplasm. Unexplained persistent hypokalemia after resuscitated sudden death (especially when combined with hypertension) should prompt investigation for an underlying secondary hypertension, particularly adrenal pathology. Adrenocortical carcinoma should be considered in the differential diagnosis of unexplained sudden death associated with unexplained hypokalemia.
Various endocrine disorders, mainly those affecting the thyroid or adrenal glands, can lead to lethal cardiac arrhythmias including torsade de pointes and ventricular fibrillation (VF) through excess or insufficient hormone activity and electrolyte imbalance.1–3 Severe hypokalemia is frequent in most forms of adrenal tumor, but sudden death is a most unusual presentation of an adrenal tumor. We describe for the first time a case of an aldosterone-producing adrenocortical carcinoma presenting as VF due to severe hypokalemia.
A 31-year-old male patient was admitted to our intensive cardiac care unit (ICCU) after out-of-hospital cardiac arrest. The patient was married with no children and was taking no medications. Apart from smoking, there were no known coronary risk factors. There was no personal history of substance abuse and no family history of sudden death. A week prior to admission, the patient complained of new-onset ‘heartburn,’ which was treated by an antacid.
On the day of admission the patient collapsed without preceding signs during his morning prayers. Basic life support was not provided. Paramedics found him 15 minutes later in VF and administered defibrillation and advanced cardiac life support. Upon admission to the ICCU the patient experienced two more episodes of VF, which were successfully terminated by defibrillation. Physical examination upon admission was normal except for a blood pressure of 200/130mmHg. The admission electrocardiogram (ECG) was normal. Induced hypothermia was initiated using external cooling for 24 hours. Laboratory tests were unremarkable except for a potassium level of 2.3mmol/l. Echocardiography revealed preserved biventricular function, no left ventricular hypertrophy, and normal valvular function. The patient was extubated 48 hours after admission and was quickly ambulated. He remained neurologically intact except for mild amnesia. Coronary angiography revealed normal coronary arteries. The patient continued to demonstrate persistent hypokalemia and high blood pressure for a few days, both of which responded to treatment with an angiotensin-converting enzyme inhibitor and spironolactone.
Further history obtained from family members shortly after admission indicated that the patient had been admitted to another hospital one month earlier due to right flank pain, which was demonstrated to be the result of a retroperitoneal hematoma surrounding and obscuring the right kidney. The patient was discharged and ambulatory magnetic resonance imaging (MRI) was scheduled one month later to allow for resolution of the hematoma. The patient sustained his episode of sudden death before the MRI could be performed.
The working hypothesis of suspected hyper-aldosteronism was established by laboratory evaluation which demonstrated an aldosterone level of 47.9ng/dl (normal range 3–16ng/dl), a normal plasma renin activity (PRA) of 0.61ng/ml/1hr (normal range 0.2–0.8ng/ml/hr), and a correspondingly high aldosterone/PRA ratio of 77.7. The 24-hour urine metanephrine level was 243mcg/g (normal range 102–600mcg/g). An abdominal MRI scan revealed a large (4.1x4.7x5.8cm) solid tumor with surrounding hematoma in the right adrenal gland.
At surgery a large adrenal tumor was found that penetrated the inferior vena cava and the patient underwent right adrenalectomy. Histological examination revealed an aggressive adrenocortical carcinoma penetrating surrounding blood vessels. The patient was referred for oncological evaluation.
Sudden cardiac death is most commonly associated with ischemic heart disease, and VF is the most common underlying arrhythmia.1 All other forms of structural heart disease, as well as many electrical derangements, may also lead to VF and sudden death. Sudden cardiac death at this young age is very uncommon and is most frequently the result of hypertrophic cardiomyopathy, myocarditis, and conduction system abnormalities.4 Beyond 30 years of age, however, coronary artery disease becomes the leading cause of death (58% of cases), followed by myocarditis (11% of cases).5
The transmembrane potential difference depends on the transmembrane potassium gradient. Hypokalemia produces hyperpolarity, elevates the resting potential, accelerates depolarization, prolongs the QT interval, and increases automaticity. As a consequence, hypokalemia predisposes to ventricular arrhythmia and sudden cardiac death.6
Changes in potassium levels may occur following cardiac arrest but are usually transient, reflecting catecholamine surge, diuretics, and medications used during resuscitation. Unexplained persistent hypokalemia after successful resuscitation (especially when combined with hypertension) should prompt investigation for underlying secondary hypertension, particularly due to an adrenal pathology. These pathologies include primary aldosteronism, Cushing’s syndrome, adrenal adenoma, and pheochromocytoma.1–3 Hypokalemia, occasionally severe, is a well-known presenting symptom of primary hyperaldosteronism, but ventricular arrhythmias are a very unusual presenting manifestation of an adrenal tumour.7–10
Adrenocortical carcinoma, a rare aggressive tumor affecting one to two persons per 1,000,000, is hormonally inactive in 40% of cases but can secrete mineralocorticoids, corticosteroids, catecholamines, and other hormones.11–13 The clinical presentation varies from an asymptomatic accidental finding to symptoms secondary to a mass effect and hormonal imbalance. Causing severe hypokalemia by aldosterone or cortisol excess secretion renders the heart to arrhythmias. Specifically, ventricular arrhythmias have not been described as the presenting manifestation of adrenocortical carcinoma. Five-year survival depends on tumor staging and varies from 60% in stage 1 to 0% in stage 4. Complete surgical resection is the treatment of choice.
We conclude that adrenocortical carcinoma, by inducing hyperaldosteronism and hypokalemia, may cause ventricular fibrillation. Hypokalemia due to an adrenal tumor, including an adrenocortical carcinoma, should be considered in the differential diagnosis of unexplained sudden death, particularly when persistent, unexplained hypokalemia and hypertension are present.
- Zipes PD, Camm AJ, Borggrefe M, et al., ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society, Circulation, 2006;114:e385–e484.
- Scott BD, Friday KJ, Cushing’s syndrome presenting as sudden death, Am Heart J, 1988;115(2):487–8.
- Kazumasa S, Yukio M, Yuki M, et al., QT prolongation with torsade de pointes in pheochromocytoma, Am Heart J, 1992;124(1):235–9.
- Liberthson RR, Sudden death from cardiac causes in children and young adults, N Engl J Med, 1996;334(16):1039–44.
- Drory Y, Turetz Y, Hiss Y, et al., Sudden unexpected death in persons less than 40 years of age, Am J Cardiol, 1991;68(13):1388–92.
- Macdonald JE, Struthers AD, What is the optimal serum potassium level in cardiovascular patients?, J Am Coll Cardiol, 2004;43(2): 155–61.
- Abdo A, Bebb RA, Wilkins GE, Ventricular fibrillation: an extreme presentation of primary hyperaldosteronism, Can J Cardiol, 1999;15:347–8.
- Sade E, Oto A, Oto A, et al., Adrenal adenoma presenting with torsade de pointes—a case report, Angiology, 2002;53(4):471–4.
- Geist M, Dorian P, Davies T, et al., Hyperaldosteronism and sudden cardiac death, Am J Cardiol, 1996;78:605–6.
- Furukawa A, Komatsu R, et al., Primary aldosteronism with ventricular fibrillation: a case report, J Cardiol, 2007;50(1):77–82.
- Messer CK, Kirschenbaum A, New MI, et al., Concomitant secretion of glucocorticoid, androgens, and mineralocorticoid by an adrenocortical carcinoma: case report and review of literature, Endocr Pract, 2007;13(4):408–12.
- Van Ditzhuijsen CI, van de Weijer R, Haak HR, Adrenocortical carcinoma, Neth J Med, 2007;65(2):55–60.
- Allolio B, Fassnacht M, Clinical review: Adrenocortical carcinoma: clinical update, J Clin Endocrinol Metab, 2006;91(6):2027–37.