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. 2024 Aug 10;64(6):871–879. doi: 10.2169/internalmedicine.3629-24

Primary Aldosteronism and Hypokalemia-induced Rhabdomyolysis in a Patient with Aldosterone-producing Adenoma: A Case Report and Literature Review

Nobumasa Ohara 1, Takashi Tani 2, Kenshi Terajima 2, Tetsutaro Ozawa 3, Yuichiro Yoneoka 4, Hiroki Shimada 5, Yasuhiro Nakamura 5, Go Hasegawa 6, Tsutomu Nishiyama 7
PMCID: PMC11986306  PMID: 39135257

Abstract

Many cases of primary aldosteronism (PA) in patients who developed hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for aldosterone-producing adenoma (APA) have been reported; however, the immunohistopathological and molecular features remain unknown. We herein report the case of a 28-year-old woman with PA who presented with hypokalemia-induced rhabdomyolysis and underwent adrenalectomy for unilateral APA. An immunohistochemical analysis revealed that most adenoma cells were positive for steroidogenic enzymes, including CYP11B2. A genetic analysis revealed a somatic mutation in the KCNJ5. These findings suggest a strong aldosterone production capacity in our patient's adenoma, which was presumably related to her severe hyperaldosteronism and the resultant hypokalemia-induced rhabdomyolysis.

Keywords: adrenalectomy, aldosterone-producing adenoma, hypertension, immunohistochemistry, KCNJ5, rhabdomyolysis

Introduction

Rhabdomyolysis (RM) is a potentially life-threatening syndrome caused by skeletal muscle injury, with the leakage of toxic cellular contents into the systemic circulation (1). It manifests as muscle weakness, myalgia, and vomiting with or without acute kidney injury. A characteristic biochemical finding in patients with RM is a high serum creatine phosphokinase (CPK) level (2). RM can be caused by direct muscle injury as well as by a wide variety of medical factors, such as electrolyte imbalance.

Primary aldosteronism (PA) is an endocrine disorder characterized by autonomous hypersecretion of the mineralocorticoid aldosterone from adrenocortical lesions (3,4). The major subtypes of PA include unilateral aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism. PA can develop at any age and it is the most common cause of secondary hypertension. Hypokalemia occurs in some patients, particularly in those with APA (5). Hypokalemia in patients with PA is usually mild and asymptomatic, but it can become severe and lead to acute life-threatening conditions, such as hypokalemia-induced RM (6-36).

Although hypokalemia-induced RM may occur in any subtype of PA (10,11,13,14), most reported cases have occurred in patients with unilateral APA (6,8,9,12,15-36); many of them were treated by the surgical removal of the APA (16-36). However, little is known about the immunohistopathological and molecular features of APA and the relationship between these features and hypokalemia-induced RM in such patients.

We herein describe the case of a patient with PA who presented with hypokalemia-induced RM. The patient underwent adrenalectomy for unilateral APA, and a detailed immunohistochemical investigation of the resected APA and a genetic analysis of somatic mutations in the KCNJ5 gene (3) were conducted.

Measurement of plasma aldosterone concentration (PAC)

PAC in this case was measured using a conventional radioimmunoassay with the SPAC-S Aldosterone kit (Fujirebio, Tokyo, Japan) (4,37).

Case Report

A 28-year-old Japanese woman presented with difficulty walking after a 3-day history of muscle weakness in the extremities. The patient's family history was unremarkable. The patient followed a traditional Japanese diet. She had never smoked cigarettes or drunk alcohol. She had no medical history, except for childhood asthma. She had no history of trauma, did not engage in excessive exercise, and was not taking any medications. She had no diarrhea, vomiting, or dietary potassium restriction. A medical check-up performed in August 2015 revealed no abnormalities, and her blood pressure (BP) was normal. The patient was healthy until 3 days before admission, when she developed weakness in her arms and legs. The muscle weakness gradually worsened until she experienced difficulty in walking. She was transported by ambulance to Uonuma Kikan Hospital in January 2016.

Physical examination revealed that the patient's height, weight, and body temperature were 153 cm, 48 kg (body mass index: 20.5 kg/m2), and 37.3°C, respectively. Her BP and pulse rate were 153/107 mmHg and 83 beats/min, respectively. She had no heart murmurs, chest rales, abdominal tenderness, or peripheral edema. Her trunk muscle strength was normal, but the proximal and distal muscle strengths of her extremities were low (2/5 and 3/5, respectively, on manual muscle testing). She had no muscle atrophy, but exhibited mild tenderness and exercise-induced pain in her limb muscles. She exhibited no cushingoid features, such as a round face, thin skin, or easy bruising.

Laboratory examinations showed metabolic alkalosis (arterial pH: 7.502), low serum potassium (1.8 mEq/L), and high serum CPK level (3,908 IU/L) (Table 1). Electrocardiography revealed a normal sinus rhythm, but ST-segment flattening, U waves, and QT interval prolongation were present. The troponin test result was negative. The patient was diagnosed with hypokalemia-induced myopathy with RM and she was subsequently admitted to the hospital's neurology department.

Table 1.

Laboratory Findings upon Arrival in the Emergency Department (January 2017).

Hematology
Red blood cells 371×104 /μL (386-492)
Hemoglobin 10.4 g/dL (11.6-14.8)
Hematocrit 30.2 % (35.1-44.4)
White blood cells 4,500 /μL (3,300-8,600)
Platelets 25.3×104 /μL (15.8-34.8)
Blood chemistry
Aspartate aminotransferase 62 IU/L (13-30)
Alanine aminotransferase 35 IU/L (7-23)
Lactate dehydrogenase 398 IU/L (124-222)
Creatine phosphokinase 3,908 IU/L (41-153)
Blood urea nitrogen 6.0 mg/dL (8.0-18.4)
Creatinine 0.42 mg/dL (0.46-0.79)
Sodium 146 mEq/L (137-147)
Potassium 1.8 mEq/L (3.5-4.7)
Chloride 105 mEq/L (98-108)
Calcium 8.6 mg/dL (8.7-10.1)
Phosphorus 2.9 mg/dL (2.7-4.6)
Magnesium 2.05 mg/dL (1.7-2.3)
C-reactive protein 0.85 mg/dL (0-0.14)
Casual plasma glucose 92 mg/dL (70-109)
Glycated hemoglobin 5.0 % (4.6-6.2)
Thyroid-stimulating hormone 1.91 μIU/mL (0.50-5.00)
Free triiodothyronine 3.36 pg/mL (2.30-4.00)
Free thyroxine 1.38 ng/dL (0.90-1.70)
Antinuclear antibody <40 titer (<40)
Anti-Jo-1 antibody Negative
Arterial blood gas analysis (on room air)
pH 7.502 (7.35-7.45)
Bicarbonate 28.3 mmol/L (21-28)
Partial pressure of carbon dioxide 36.4 mmHg (32-48)
Partial pressure of oxygen 101 mmHg (83-108)
Urinalysis
Specific gravity 1.009 (1.005-1.020)
Glucose Negative
Protein Negative
Occult blood Positive
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Reference range for each parameter is shown in parentheses.

The patient received fluid therapy (normal saline, 1 L/day; potassium, 40 mEq) and oral potassium supplementation (20 mEq/day) to treat the severe hypokalemia and RM (Fig. 1). As a blood test performed on day 3 after admission showed a higher CPK level (18,639 IU/L), the saline infusion rate was increased to 2 L/day. On day 6 after admission, her potassium level was 3.0 mEq/L, and her CPK level decreased (3,025 IU/L). With improvements in hypokalemia and RM, the patient's muscle pain and weakness in the extremities gradually improved, and she thereafter became ambulatory. However, her BP remained high (＞140/90 mmHg).

Figure 1.

Figure 1.

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The patient’s clinical course during hospitalization. Blank columns indicate that the laboratory parameters were not determined. CPK: creatine phosphokinase, BP: blood pressure

The patient was diagnosed with hypertension (38) and a screening test for secondary hypertension was conducted. A morning blood test performed in the supine position showed a high PAC (84.3 ng/dL, reference range: 3.0-15.9 ng/dL) and low plasma renin activity (PRA) (0.1 ng/mL/h, reference range: 0.2-2.3 ng/mL/h), with a high PAC to PRA ratio (3, 4). The morning plasma levels of cortisol and adrenocorticotropic hormone were normal (14.2 μg/dL, reference range: 4.0-18.3 μg/dL and 21.5 pg/mL, reference range: 7.2-63.3 pg/mL, respectively), with a normal circadian rhythm. The overnight 1 mg dexamethasone suppression test showed a normal response (plasma cortisol the next morning: 1.3 μg/dL). Hypercortisolism and subclinical Cushing's syndrome were ruled out, and PA was suspected; thus, the patient was referred to the endocrinology and metabolism department of our hospital for further investigation and treatment on day 9 after admission.

The patient began oral amlodipine (5 mg/day) treatment for hypertension and continued oral potassium chloride at 32 mEq/day. The result of a captopril challenge test was positive (4); her PAC and PRA at 1.5 h after the oral administration of captopril (50 mg) were 95.0 ng/dL and 0.1 ng/mL/h, respectively. The result of a furosemide and upright posture test was also positive (4); when measured 2 h after receipt of intravenous furosemide (40 mg) and in an upright posture, her PRA remained suppressed (0.1 ng/mL/h). Abdominal computed tomography revealed a 2.4×1.7 cm low-density tumor in the left adrenal gland (Fig. 2). Therefore, the patient was diagnosed with PA and possibly unilateral APA.

Figure 2.

Figure 2.

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Abdominal computed tomography. (A) Plain computed tomography scan showing a 2.4×1.7 cm homogenous, low-density left adrenal tumor with a Hounsfield unit value of approximately +10 (arrow). (B) Contrast-enhanced computed tomography scan showing less enhancement in the left adrenal tumor (arrow).

As the patient's hypertension was sufficiently controlled, she was discharged 12 days after admission.

Two weeks after discharge, a blood test showed a normal CPK level (60 IU/L), but her serum potassium level remained mildly low (3.4 mEq/L). Thus, the dose of oral potassium chloride was increased to 40 mEq/day. Thereafter, her potassium level returned to the reference range.

Adrenal vein sampling in March 2016 indicated aldosterone hypersecretion from the left adrenal gland (Supplementary material). The lateralization index and contralateral ratio (4) after tetracosactide stimulation were markedly high (28.5) and low (0.12), respectively.

The patient underwent laparoscopic left adrenalectomy in July 2016. A histological analysis showed that the tumor was mostly composed of clear cells with a clear margin (Fig. 3A, B). The tumor met none of the nine parameters of the Weiss criteria (39). An immunohistochemical analysis revealed that most part of the tumor showed positive immunoreactivity for steroidogenic enzymes (40), including 3β-hydroxysteroid dehydrogenase (3β-HSD) type 2, CYP21A, CYP11B1, and CYP11B2 (Fig. 3C-F). These findings supported a diagnosis of APA with a high capacity to biosynthesize aldosterone (41-43).

Figure 3.

Figure 3.

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Histopathological findings in the resected left adrenal gland. (A, B) Hematoxylin and Eosin staining. (A) The tumor was mostly composed of clear cells with a clear margin. Nontumoral adrenal tissues were found adjacent to the tumor (*). (B) Extended image of the tumor (high-power field). (C-G) Immunohistochemical localization of steroidogenic enzymes within the tumor. Most of the tumor area showed positive immunoreactivity for (C) 3β-hydroxysteroid dehydrogenase (3β-HSD) type 2, (D) CYP21A, (E) CYP11B1, and (F) CYP11B2. (G) CYP17A1 expression was predominantly negative.

After obtaining written informed consent from the patient to perform molecular studies that had been approved by the ethics committee of the hospital, we conducted a genetic analysis of KCNJ5 using a tissue specimen extracted from the resected adenoma. A p.L168R mutation was identified (Fig. 4).

Figure 4.

Figure 4.

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Genetic analysis using Sanger sequencing of the KCNJ5 gene extracted from the resected left adrenal tumor. A p.L168R point mutation was detected. The arrow indicates heterozygous substitution of leucin by arginine.

The patient's hypertension, hypokalemia, and metabolic alkalosis resolved after surgery; thus, she discontinued the antihypertensive treatment and potassium supplementation. Blood chemistry tests in November 2016 reveled normal PAC (13.7 ng/dL) and PRA (1.8 ng/mL/h). Her office and home BP values were normal (120/78 and 116/68 mmHg, respectively).

The patient's clinical course has remained uneventful for more than 6 years.

Discussion

We conducted a PubMed search to identify articles reporting PA in patients who presented with hypokalemia-induced RM and underwent adrenalectomy for the treatment of unilateral APA, and we found 25 cases (16-36). The clinical characteristics of all 26 patients with PA (including the present case) are summarized in Table 2. There were 17 females and 9 males, with a median age of 44 years (range, 14-70 years). The patients presented with limb muscle weakness (often involving difficulty walking), RM, profound hypokalemia, and treated or untreated hypertension. The median serum concentrations of potassium and CPK were 1.8 (range, 1.2-3.1) mEq/L and 4,587 (range, 881-21,000) IU/L, respectively. The hypokalemia-induced RM was treated with adequate hydration and potassium supplementation. The patients were diagnosed with PA based on the biochemical abnormalities of suppressed PRA and high PAC, with a median concentration of 375 pg/mL (range, 153-226,000 pg/mL). Computed tomography or magnetic resonance imaging revealed a unilateral adrenal tumor with a median size of 2.0 cm (range, 1.1-3.3 cm). After adrenalectomy, hyperaldosteronism and hypokalemia resolved in all patients, and hypertension resolved or partially improved.

Table 2.

Comparison of Our Case with Previously Reported Cases of Primary Aldosteronism in Patients Who Presented with Hypokalemia-induced Rhabdomyolysis and Underwent Adrenalectomy for Treatment of Unilateral APA.

Ref. Age (years) /sex Major symptoms BP (mmHg) Antihypertensive agents Blood test results Laterality and diameter (cm) of APA Outcome after adrenalectomy Comorbid disorders
pH Potassium (mEq/L) CPK (IU/L) Creatinine (mg/dL) Aldosterone (pg/mL) PRA (ng/mL/h)
(16) 55/M Acute difficulty walking N.D. N.D. N.D. 1.8 881 N.D. 333.3 0.12 Left (diameter, N.D.) N.D. Thyroid cancer
(17) 32/F Generalized muscle weakness, left calf pain, swelling 170/100 β-blocker, diuretic (thiazide) N.D. 2.0 10,000 N.D. 580 0.5 Right, 2.0 Improved (persistent hypertension) None
(18) 70/M Leg weakness, difficulty walking, retrosternal chest pain 155/85 CCB, β-blocker N.D. 1.8 1,017-2,799 2.1 1,172 0.02 Right, 2.0 Improved Hyperglycemia, lumbar plexopathy
(19) 44/F Fatigue, myalgia, proximal weakness 150/110 CCB N.D. 1.73 1,254 N.D. 460 0.3 Right, 2.2 Resolved None
(20) 55/M Limb muscle weakness 138/68 ARB, CCB, diuretic (thiazide) 7.54 1.4 15,760 0.83 266 <0.1 Left, 1.7 Improved (persistent slightly high BP) High alcohol intake
(21) 42/F Generalized weakness, muscle pain 166/108 None 7.536 1.3 21,000 0.9 966 Undetectable Right, 2.0 Improved (persistent hypertension) None
(22) 14/F Lower limb weakness, inability to walk 160/120 None N.D. 1.7 3,375 N.D. 295 <0.2 Right, 3.0 Resolved None
(23) 34/M Limb muscle weakness 144/86 ARB N.D. 3.1 1,048 N.D. 297 0.1 Left (diameter, N.D.) Resolved Myasthenia gravis
(24) 45/M Limb muscle pain, weakness 185/115 None N.D. 1.24 18,560 N.D. 199.8 0.04 Left, 1.2 Resolved None
(24) 36/F Limb muscle pain, weakness 165/105 None N.D. 1.85 6,954 N.D. 178.6 0.05 Right, 1.1 Resolved None
(24) 41/F Limb muscle pain, weakness 180/108 None N.D. 2.0 3,565 N.D. 184.1 0.12 Left, 2.0 Resolved None
(25) 43/F Limb muscle weakness 150/90 ARB N.D. 1.7 4,267 0.6 980 0.48 Right, 3.2 N.D. None
(26) 45/F Fatigue, limb pain 143/80 ACE-I, CCB 7.43 1.38 4,907 1.05 639.4 0.84 Left, 2.1 Resolved None
(26) 44/F Fatigue, limb pain N.D. N.D. 7.49 1.98 8,531 0.67 449.7 0.07 Left, 1.6 Resolved None
(27) 42/F Lower limb paralysis, muscle pain 160/100 ARB, CCB, β-blocker, diuretic (furosemide) 7.54 2.0 11,347 1.47 226,000 0.2 Right, 2.0 Resolved None
(28) 54/M Lower limb weakness 170/100 ARB, CCB, β-blocker, diuretic (thiazide) 7.46 2.0 2,982 N.D. 375 0.3 Right, 1.5 Resolved Sporadic inclusion body myositis
(29) 44/F Lower limb weakness, difficulty walking 130-140 /80-90 ACE-I, diuretic (indapamide) N.D. 1.53 2,373-17,291 N.D. 266 <0.1 Right, 1.8 Resolved Diarrhea
(30) 55/F Lower limb weakness, difficulty walking 144/90 ARB, β-blocker, diuretic (xipamide) N.D. 1.5 2,900 N.D. 209 (PRC 4 µIU/mL) Left, 2 Resolved History of papillary thyroid cancer
(31) 38/F Limb weakness 190/110 N.D. 7.46 1.9 1,015 0.67 199 (PRC 7.08 µIU/mL) Left, 1.7 Resolved None
(32) 42/F Limb weakness, difficulty walking 150/75 CCB N.D. 2.1 1,579 0.94 153.1 (PRC 1.3 ng/mL) Left, 1.8 Resolved None
(33) 53/M Limb weakness, tenderness 164/100 ARB, CCB, diuretic (thiazide) 7.51 2.1 15,930 1.15 388 <0.07 Left, 1.3 Improved (persistent hypertension) Diabetes mellitus, gouty arthritis
(33) 46/M Lower limb pain, weakness 217/136 ARB, diuretic (thiazide) 7.45 1.9 1,629 0.85 136 <0.07 Left, 1.5 Improved (persistent hypertension) None
(34) 48/F Inability to walk, lift the arms, myalgia 160/90 ARB, β-blocker 7.65 1.3 14,248 0.52 887 0.24 Right, 3.3 N.D. None
(35) 65/F Limb weakness, myalgia 120-138 /70-87 None 7.55 1.8 18,370 0.67 >1,000 0.66 Left, 2.6 Resolved None
(36) 68/M Lower limb weakness 183/101 MRAs, ACE-I, β-blocker N.D. 2.1 3,616 2.1 1,880 0.18 Right, 2.7 Improved (persistent hypertension) Type 2 diabetes mellitus, schizophrenia
Our case 28/F Limb weakness, difficulty walking 153/107 None 7.50 1.8 3,908-19,223 0.42 843 0.1 Left, 2.4 Resolved None
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ACE-I: angiotensin-converting enzyme inhibitor, APA: aldosterone-producing adenoma, ARB: angiotensin II receptor blocker, BP: blood pressure, CCB: calcium channel blocker, CPK: creatine phosphokinase, F: female, M: male, MRAs: mineralocorticoid receptor antagonists, N.D.: not described, PRC: plasma renin concentration

The precipitating factors for hypokalemia-induced RM in patients with PA are not well known, but the clinical features in previous reports (6-36) included profound hypokalemia and severe hyperaldosteronism. Additionally, many patients were taking diuretics such as thiazide and furosemide to treat hypertension; such treatment may cause or exacerbate hypokalemia (6,8,9,13,14,17,20,27-30,33,44). Some patients had concurrent muscle disorders [e.g., mitochondrial disease (12), myasthenia gravis (23), and sporadic inclusion body myositis (28)], although the etiological link between these disorders and hypokalemia-induced RM was uncertain. In the present case, with the exception of profound hypokalemia, the patient had no concurrent muscle disorders or medical factors that could have caused RM, such as infection, intoxication, or trauma (1). She was not taking any diuretics and had no potassium-lowering disorders, such as vomiting or diarrhea (44). However, she exhibited severe hyperaldosteronism, as indicated by a markedly high PAC compared with the level in most cases of PA (45,46). These findings suggest that hyperaldosteronism was the principal cause of the hypokalemia-induced RM in our patient.

In previously reported cases of APA with hypokalemia-induced RM treated by adrenalectomy (Table 2), histological analysis of Hematoxylin and Eosin staining confirmed the morphology of adrenocortical adenoma (16-36). We also performed an immunohistochemical analysis of steroidogenic enzymes in the APA of our patient (Fig. 3). This analysis showed diffuse immunolocalization of enzymes involved in the aldosterone biosynthetic pathway, including 3β-HSD type 2, CYP21A, CYP11B1, and CYP11B2 (40). Because high CYP11B2 expression is possibly correlated with higher aldosterone biosynthesis (41,42), APA in our patient was suspected to exhibit a markedly high aldosterone production capacity. To the best of our knowledge, this is the first report to demonstrate the immunohistopathological features of APA with hypokalemia-induced RM. It is likely that the high aldosterone production capacity was closely related to severe hyperaldosteronism and the resultant hypokalemia-induced RM in our case.

Somatic mutations in genes encoding ion channels, including KCNJ5, are often present in patients with APA and they are thought to be involved in the pathogenesis of the disease (3,43). Studies have shown that patients with APA who have KCNJ5 mutations are younger, more often female, have larger tumor sizes, more pronounced hyperaldosteronism (47), and higher CYP11B2 mRNA expression in APA tissue (48). In addition, Japanese patients with KCNJ5 mutations have lower serum potassium levels, possibly associated with a high salt intake (49). However, there is no information regarding somatic mutations in previously reported cases of APA with hypokalemia-induced RM (Table 2). In our patient, the presence of a KCNJ5 mutation in APA (Fig. 4) may have been associated with a higher aldosterone production capacity, severe hyperaldosteronism, and the resultant hypokalemia-induced RM.

Although the pathogenesis of hypokalemia-induced RM in patients with PA is still not fully understood, ischemic muscle injury is one possible mechanism (9,14,15,20,21,23,28,30,33,35). Potassium, a major intracellular cation, regulates the blood flow in skeletal muscle. When muscle cells contract, potassium ions are released into the extravascular spaces and mediate vasodilation, which increases muscle-specific blood flow to meet the energy demands (50,51). In PA, hyperaldosteronism causes hypokalemia and metabolic alkalosis by increasing the loss of potassium and hydrogen in the distal nephron in exchange for sodium reabsorption (5). At the same time, hyperaldosteronism and metabolic alkalosis promote the transcellular shift of potassium into muscle cells through the activation of sodium-potassium pumps (Na, K-ATPases), thereby decreasing extracellular potassium (46,52). Thus, in patients with PA and hypokalemia, the potassium concentration in the extravascular spaces may be insufficient to vasodilate arterioles and capillaries that perfuse exercising muscles, resulting in muscle ischemia and cell destruction. Hypokalemia may also promote muscle injury by suppressing glycogen biosynthesis and storage (51,53) and interrupting ion transport across the cell membrane (51,54).

In conclusion, we encountered a patient with PA who presented with hypokalemia-induced RM and underwent adrenalectomy for unilateral APA with a somatic mutation in KCNJ5. An immunohistochemical analysis of steroidogenic enzymes demonstrated a high aldosterone production capacity in APA, thus suggesting a close relationship between marked hyperaldosteronism and the resultant hypokalemia-induced RM. This case emphasizes the importance of biochemical testing for possible PA in patients with hypokalemia-induced RM, especially in patients with a high BP, regardless of their age.

The authors state that they have no Conflict of Interest (COI).

Supplementary Material

Supplementary Table 1. Results of adrenal vein sampling.

The selective index, calculated by dividing the cortisol concentration in the adrenal vein by that in the inferior vena cava, after administration of tetracosactide (0.25 mg) in the elbow vein was 18.0 for the right side and 22.0 for the left side. The lateralization index for the left side, calculated by dividing the aldosterone-to-cortisol concentration ratio (ACR) in the left adrenal vein by that in the right adrenal vein, before and after administration of tetracosactide in the elbow vein was 7.9 and 28.5, respectively. The contralateral ratio, calculated by dividing the ACR in the right adrenal vein by that in the inferior vena cava, before and after administration of tetracosactide was 0.36 and 0.12, respectively.

1349-7235-64-0871-s001.pdf (83.4KB, pdf)

Acknowledgments

The authors thank the clinical laboratory technicians at Uonuma Kikan Hospital for their technical support.

References

  • 1.Zutt R, van der Kooi AJ, Linthorst GE, Wanders RJ, de Visser M. Rhabdomyolysis: review of the literature. Neuromuscul Disord 24: 651-659, 2014. [DOI] [PubMed] [Google Scholar]
  • 2.Stahl K, Rastelli E, Schoser B. A systematic review on the definition of rhabdomyolysis. Neurol 267: 877-882, 2020. [DOI] [PubMed] [Google Scholar]
  • 3.Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 101: 1889-1916, 2016. [DOI] [PubMed] [Google Scholar]
  • 4.Naruse M, Katabami T, Shibata H, et al. Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021. Endocr J 69: 327-359, 2022. [DOI] [PubMed] [Google Scholar]
  • 5.Gruber S, Beuschlein F. Hypokalemia and the prevalence of primary aldosteronism. Horm Metab Res 52: 347-356, 2020. [DOI] [PubMed] [Google Scholar]
  • 6.Dominic JA, Koch M, Guthrie GP Jr, Galla JH. Primary aldosteronism presenting as myoglobinuric acute renal failure. Arch Intern Med 138: 1433-1434, 1978. [PubMed] [Google Scholar]
  • 7.Schady W, Yuill GM. Myopathy and primary hyperaldosteronism. Neurology 31: 225-226, 1981. [DOI] [PubMed] [Google Scholar]
  • 8.Ozgür B, Kürsat S. Hypokalemic rhabdomyolysis aggravated by diuretics complicating Conn's syndrome without acute renal failure. Clin Nephrol 57: 89-91, 2002. [DOI] [PubMed] [Google Scholar]
  • 9.Petidis K, Douma S, Aslanidis S, Papaefthimiou P, Kartali N, Zamboulis C. Hypertension associated with rhabdomyolysis. J Clin Hypertens (Greenwich) 9: 60-62, 2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Kotsaftis P, Savopoulos C, Agapakis D, et al. Hypokalemia induced myopathy as first manifestation of primary hyperaldosteronism - an elderly patient with unilateral adrenal hyperplasia: a case report. Cases J 2: 6813, 2009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Tsai WT, Chen YL, Yang WS, Lin HD, Chien CC, Lin CL. Primary aldosteronism associated with severe hypokalemic rhabdomyolysis. Hormones (Athens) 11: 505-506, 2012. [DOI] [PubMed] [Google Scholar]
  • 12.Finsterer J, Lässer S. Severe hypokalemic paralysis as a manifestation of a mitochondrial disorder. Tohoku J Exp Med 231: 9-12, 2013. [DOI] [PubMed] [Google Scholar]
  • 13.Grifoni E, Fabbri A, Ciuti G, Matucci Cerinic M, Moggi Pignone A. Hypokalemia-induced rhabdomyolysis. Intern Emerg Med 9: 487-488, 2014. [DOI] [PubMed] [Google Scholar]
  • 14.Zavatto A, Concistrè A, Marinelli C, et al. Hypokalemic rhabdomyolysis: a rare manifestation of primary aldosteronism. Eur Rev Med Pharmacol Sci 19: 3910-3916, 2015. [PubMed] [Google Scholar]
  • 15.Dyrmishi B, Olldashi T, Rista E, Fureraj T, Ylli D, Ylli A. Severe hypokalemia induced rhabdomyolysis by primary hyperaldosteronism coexistent with recurrent bilateral renal calculi. Acta Endocrinol (Buchar) 13: 228-231, 2017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Atsumi T, Ishikawa S, Miyatake T, Yoshida M. Myopathy and primary aldosteronism: electronmicroscopic study. Neurology 29: 1348-1353, 1979. [DOI] [PubMed] [Google Scholar]
  • 17.Mahdyoon H, Mermiges DN, Wisgerhof M. Conn's syndrome with rhabdomyolysis mimicking deep vein thrombophlebitis. South Med J 83: 346-347, 1990. [DOI] [PubMed] [Google Scholar]
  • 18.Chow CP, Symonds CJ, Zochodne DW. Hyperglycemia, lumbar plexopathy and hypokalemic rhabdomyolysis complicating Conn's syndrome. Can J Neurol Sci 24: 67-69, 1997. [DOI] [PubMed] [Google Scholar]
  • 19.Kaşifoğlu T, Korkmaz C, Paşaoğlu O. Conn's syndrome (primary hyperaldosteronism) simulating polymyositis. Rheumatol Int 25: 133-134, 2005. [DOI] [PubMed] [Google Scholar]
  • 20.Goto A, Takahashi Y, Kishimoto M, et al. Primary aldosteronism associated with severe rhabdomyolysis due to profound hypokalemia. Intern Med 48: 219-223, 2009. [DOI] [PubMed] [Google Scholar]
  • 21.Martínez JJ, Oliveira CL, Meneses AL, et al. Rhabdomyolysis due to primary hyperaldosteronism. Endocrinol Nutr 56: 431-434, 2009. [DOI] [PubMed] [Google Scholar]
  • 22.Karagüzel G, Bahat E, Imamoğlu M, Ahmetoğlu A, Yildiz K, Okten A. An unusual case of an aldosterone-producing adrenocortical adenoma presenting with rhabdomyolysis. J Pediatr Endocrinol Metab 22: 1087-1090, 2009. [DOI] [PubMed] [Google Scholar]
  • 23.Yamashita S, Tsuchimochi W, Yonekawa T, et al. Myasthenia gravis complicated with primary aldosteronism and hypokalemic myopathy. Intern Med 48: 1465-1469, 2009. [DOI] [PubMed] [Google Scholar]
  • 24.Tang YC, Wang SK, Yuan WL. Primary aldosteronism simulating polymyositis. J Rheumatol 38: 1529-1533, 2011. [DOI] [PubMed] [Google Scholar]
  • 25.Wen Z, Chuanwei L, Chunyu Z, Hui H, Weimin L. Rhabdomyolysis presenting with severe hypokalemia in hypertensive patients: a case series. BMC Res Notes 6: 155, 2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Olt S, Yaylaci S, Tatli L, Gunduz Y, Garip T, Tamer A. Hypokalemia-induced myopathy and massive creatine kinase elevation as first manifestation of Conn's syndrome. Niger Med J 54: 283-284, 2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Cooray MS, Bulugahapitiya US, Peiris DN. Rhabdomyolysis: a rare presentation of aldosterone-producing adenoma. Indian J Endocrinol Metab 17: S237-S239, 2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Lee JH, Kim E, Chon S. Hypokalemia-induced rhabdomyolysis by primary aldosteronism coexistent with sporadic inclusion body myositis. Ann Rehabil Med 39: 826-832, 2015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Wu C, Xin J, Xin M, et al. Hypokalemic myopathy in primary aldosteronism: a case report. Exp Ther Med 12: 4064-4066, 2016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Pecnik P, Müller P, Vrabel S, Windpessl M. Two cases of hypokalaemic rhabdomyolysis: same but different. BMJ Case Rep 2018: bcr2017223609, 2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Kollipara S, Ravindra S, Pai K, Shetty S. Quadriplegia and rhabdomyolysis as a presenting feature of Conn's syndrome. BMJ Case Rep 14: e234686, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Maung AC, Kerwen AK, Ching LP. Hypokalaemic rhabdomyolysis as initial presentation of primary aldosteronism. J R Coll Physicians Edinb 5: 149-152, 2021. [DOI] [PubMed] [Google Scholar]
  • 33.Chen CT, Wang YC, Lin CM. Hypokalemia-induced rhabdomyolysis caused by adrenal tumor-related primary aldosteronism: a report of 2 cases. Am J Case Rep 22: e929758, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Sirkeci O, Sirkeci EE, Kucukciloglu Y. Severe hypokalemia and rhabdomyolysis caused by Conn syndrome. Clin Ter 172: 407-409, 2021. [DOI] [PubMed] [Google Scholar]
  • 35.Han R, Jiang X. Hypokalemia-induced rhabdomyolysis as the first symptom of primary aldosteronism: a case report and literature review. Ann Palliat Med 11: 2778-2784, 2022. [DOI] [PubMed] [Google Scholar]
  • 36.Díaz-López EJ, Villar-Taibo R, Rodriguez-Carnero G, et al. Should we suspect primary aldosteronism in patients with hypokalaemic rhabdomyolysis? A systematic review. Front Endocrinol (Lausanne) 14: 1257078, 2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Nishikawa T, Omura M, Satoh F, et al.; Task Force Committee on Primary Aldosteronism; The Japan Endocrine Society . Guidelines for the diagnosis and treatment of primary aldosteronism - the Japan Endocrine Society 2009. Endocr J 58: 711-21, 2011. [DOI] [PubMed] [Google Scholar]
  • 38.Umemura S, Arima H, Arima S, et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019). Hypertens Res 42: 1235-1481, 2019. [DOI] [PubMed] [Google Scholar]
  • 39.Lau SK, Weiss LM. The Weiss system for evaluating adrenocortical neoplasms: 25 years later. Hum Pathol 40: 757-768, 2009. [DOI] [PubMed] [Google Scholar]
  • 40.Rege J, Turcu AF, Else T, Auchus RJ, Rainey WE. Steroid biomarkers in human adrenal disease. J Steroid Biochem Mol Biol 190: 273-280, 2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Sakuma I, Suematsu S, Matsuzawa Y, et al. Characterization of steroidogenic enzyme expression in aldosterone-producing adenoma: a comparison with various human adrenal tumors. Endocr J 60: 329-336, 2013. [DOI] [PubMed] [Google Scholar]
  • 42.Monticone S, Castellano I, Versace K, et al. Immunohistochemical, genetic and clinical characterization of sporadic aldosterone-producing adenomas. Mol Cell Endocrinol 411: 146-154, 2015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Mete O, Erickson LA, Juhlin CC, et al. Overview of the 2022 WHO classification of adrenal cortical tumors. Endocr Pathol 33: 155-196, 2022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Unwin RJ, Luft FC, Shirley DG. Pathophysiology and management of hypokalemia: a clinical perspective. Nat Rev Nephrol 7: 75-84, 2011. [DOI] [PubMed] [Google Scholar]
  • 45.Monticone S, Burrello J, Tizzani D, et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol 69: 1811-1820, 2017. [DOI] [PubMed] [Google Scholar]
  • 46.Umakoshi H, Sakamoto R, Matsuda Y, et al. Role of aldosterone and potassium levels in sparing confirmatory tests in primary aldosteronism. J Clin Endocrinol Metab 105: dgz148, 2020. [DOI] [PubMed] [Google Scholar]
  • 47.Lenzini L, Rossitto G, Maiolino G, Letizia C, Funder JW, Rossi GP. A meta-analysis of somatic KCNJ5 K+ channel mutations in 1636 patients with an aldosterone-producing adenoma. J Clin Endocrinol Metab 100: E1089-E1095, 2015. [DOI] [PubMed] [Google Scholar]
  • 48.Monticone S, Hattangady NG, Nishimoto K, et al. Effect of KCNJ5 mutations on gene expression in aldosterone-producing adenomas and adrenocortical cells. J Clin Endocrinol Metab 97: E1567-E1572, 2012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Okamura T, Nakajima Y, Katano-Toki A, et al. Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations. Endocr J 64: 39-47, 2017. [DOI] [PubMed] [Google Scholar]
  • 50.Knochel JP. Mechanisms of rhabdomyolysis. Curr Opin Rheumatol 5: 725-731, 1993. [DOI] [PubMed] [Google Scholar]
  • 51.Allison RC, Bedsole DL. The other medical causes of rhabdomyolysis. Am J Med Sci 326: 79-88, 2003. [DOI] [PubMed] [Google Scholar]
  • 52.Weiner ID. Endocrine and hypertensive disorders of potassium regulation: primary aldosteronism. Semin Nephrol 33: 265-276, 2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Al-Ismaili Z, Piccioni M, Zappitelli M. Rhabdomyolysis: pathogenesis of renal injury and management. Pediatr Nephrol 26: 1781-1788, 2011. [DOI] [PubMed] [Google Scholar]
  • 54.Khan FY. Rhabdomyolysis: a review of the literature. Neth J Med 67: 272-283, 2009. [PubMed] [Google Scholar]

Associated Data

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Supplementary Materials

Supplementary Table 1. Results of adrenal vein sampling.

The selective index, calculated by dividing the cortisol concentration in the adrenal vein by that in the inferior vena cava, after administration of tetracosactide (0.25 mg) in the elbow vein was 18.0 for the right side and 22.0 for the left side. The lateralization index for the left side, calculated by dividing the aldosterone-to-cortisol concentration ratio (ACR) in the left adrenal vein by that in the right adrenal vein, before and after administration of tetracosactide in the elbow vein was 7.9 and 28.5, respectively. The contralateral ratio, calculated by dividing the ACR in the right adrenal vein by that in the inferior vena cava, before and after administration of tetracosactide was 0.36 and 0.12, respectively.

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