Hypertension Associated With Rhabdomyolysis

Abstract

Primary aldosteronism accompanied by hypokalemia is a cause of secondary hypertension. Diagnosis of primary aldosteronism has increased dramatically in recent years with the wider availability of aldosterone and plasma renin activity measurements. The authors present the case of a patient with resistant hypertension and severe hypokalemia that evaded diagnosis until complications from hypokalemia occurred.

A 36‐year‐old woman was referred to our department with the diagnosis of myopathy. The patient had been hypertensive since the age of 30, with poor blood pressure control despite treatment with a combination of atenolol 50 mg and chlorthalidone 25 mg. She reported episodes of muscular weakness for the past 2 years. During previous hospitalizations, hypokalemia was found (K, <3.2 mEq/L) but never further investigated despite the fact that she reported severe muscle weakness in both arms and legs. At the initial workup, increased creatine kinase (CK) (2860 IU), increased aspartate aminotransferase (60 IU), and severe hypokalemia (2.2 mEq/L) were found. She was referred to our department with the provisional diagnosis of myopathy.

On presentation, the patient was afebrile and appeared well. Blood pressure was 152/108 mm Hg. She reported diffuse myalgias and paresthesias. Her physical examination was unremarkable, apart from extreme muscular weakness, especially of the arms, rendering elevation above the shoulder level almost impossible. No muscle tenderness, edema, or rash was detected. Drop of the right foot was also noted. The patient was not on any medication known to cause increased CK (such as 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors or cyclosporine) and no alcohol or laxative abuse was reported.

Biochemical values at admission were serum K, 2.1 mEq/L; CK, 2635 IU/L (normal, 170 IU/L); aspartate aminotransferase, 110 IU/L (normal, 35 IU/L); and serum creatinine, 1.3 mg/dL. Metabolic alkalosis was found, with a pH of 7.56; HCO₃, 37 mmol/L; O₂ saturation, 98% PO₂, 98 mm Hg, and PCO₂, 44 mm Hg. The 24‐hour urine K was 45 mEq. The patient's urine was positive for myoglobin. On the admission electrocardiogram, sinus rhythm with U waves was observed (Figure 1). The chest x‐ray showed cardiomegaly, and the 2‐dimensional Doppler echocardiogram revealed left ventricular hypertrophy.

Figure 1.

Patient electrocardiogram on admission, with U waves.

Intravenous (IV) potassium supplementation was followed by correction of hypokalemia and reversal of muscular weakness despite the continuing rise of CK to the level of 11,000 IU on the fourth day. After 10 days, muscular strength and CK levels had returned to normal. Conduction studies and electromyography were performed after the correction of hypokalemia and reported as normal.

Control of hypokalemia was difficult, with serum K remaining at the levels of 3.2–3.5 mEq/L despite the discontinuation of diuretics and the administration of potassium. The coexistence of hypertension, hypokalemia with hyperkaliuria, and metabolic alkalosis raised the possibility of primary aldosteronism. This was considered the most likely diagnosis.

Aldosterone levels were 17.4 pg/dL (normal, <15 pg/dL) and the plasma renin activity (PRA) value was below the detection limit of our method (0.2 ng AI/mL/h) with the patient in the supine position. Suppression tests with the IV administration of 2 L of 0.9% NaCl in 4 hours after 4 days of fludrocortisone 1 mg qid were performed. PRA levels remained undetectable, while aldosterone levels were 20.6 and 21 pg/dL respectively, showing no suppression and confirming the diagnosis of primary aldosteronism.

Adrenal computerized tomography revealed a tumor, 2 × 3 cm, of the right adrenal (Figure 2). After the administration of spironolactone at an initial dose of 400 mg daily, serum potassium (4.6 mEq/L) and blood pressure (114/86 mm Hg) were controlled, and the dose was tapered to 50 mg/d in 4 weeks. The patient refused to undergo further investigation with the possibility of surgical removal because her symptoms resolved with spironolactone and her general condition improved dramatically. The patient remains on treatment with spironolactone 25 mg/d.

Figure 2.

Adrenal computed tomographic scan. Arrow indicates 2 × 3‐cm tumor of the right adrenal gland.

DISCUSSION

Although rhabdomyolysis is defined as the dissolution of the muscle cell membrane, the term is generally used to include a clinical and laboratory syndrome resulting from muscle injury and release of potentially toxic substances into the circulation. Myoglobinuria is also frequently included in the definition. ¹ Hypokalemia is a recognized but relatively rare cause of rhabdomyolysis. In certain cases, the role of hypokalemia may be obscured by the fact that during rhabdomyolysis intracellular potassium is released and, if renal failure coexists, serum potassium levels are falsely elevated. Potassium is the major intracellular cation (150 mEq/L) and is critical for the activity of specific enzymes, muscle cell contraction, blood flow during exercise, and structural integrity. Hypokalemia may cause rhabdomyolysis by 3 mechanisms: (1) inadequate vasodilation of arterioles and capillaries that perfuse exercising muscle, (2) suppression of synthesis and storage of glycogen, and (3) deranged ion transport across the cell membrane. ¹

There are rare reports of cases of hyperaldosteronism complicated by hypokalemia and rhabdomyolysis.2, 3, 4, 5 Diuretic administration for blood pressure control may exacerbate hypokalemia.6, 7 Rhabdomyolysis is rarely complicated by acute renal failure.6, 8

Primary aldosteronism is a secondary cause of hypertension that classically features hypokalemia, metabolic alkalosis, and excessive urinary potassium excretion. There is a normokalemic form of the disease.9, 10 While primary aldosteronism is considered a rare disease, the wider application of measurements of aldosterone and PRA in recent years has suggested that it is probably a more common cause of secondary hypertension than previously considered. ¹¹ From our series of 148 patients with primary aldosteronism, hypokalemia was found in 41% of patients. Very low levels of serum potassium (<3 mEq/L) were found in the minority (6.7%) of our patients. One patient presented with quadriplegia; none presented with rhabdomyolysis. ¹²

Although the diagnosis of primary aldosteronism is more often pursued in patients with resistant hypertension even without the presence of hypokalemia, patients with the findings of hypertension and hypokalemia may still evade diagnosis. This delay in diagnosis may result in some of the complications of hypokalemia, eg, arrhythmias, renal disease, and long‐term disability due to muscular weakness. Although primary aldosteronism is rare, it should always be considered when arterial hypertension is associated with hypokalemia, even if the latter is considered to be the consequence of potassium depletion from diuretic therapy.