Hypertrophic cardiomyopathy in the context of primary hyperaldosteronism, Sjögren’s syndrome, and obstructive uropathy: A case report

Abstract

BACKGROUND

A considerable proportion of patients diagnosed with hypertrophic cardiomyopathy (HCM) or HCM-like phenotypes lack an identifiable genetic mutation and are classified as non-familial cases. This observation suggests that hormonal, autoimmune, and structural mechanisms may contribute to myocardial hypertrophy in selected patients.

CASE SUMMARY

A 45-year-old woman with a history of hypertension and hypothyroidism was evaluated and found to have hypokalemia, metabolic alkalosis, and asymmetric left ventricular hypertrophy. Transthoracic echocardiography revealed dynamic left ventricular outflow tract obstruction, while cardiac magnetic resonance imaging demonstrated diffuse asymmetric hypertrophy with mid-wall late gadolinium enhancement consistent with non-ischemic myocardial fibrosis. Hormonal evaluation showed markedly elevated aldosterone levels with suppressed renin activity, confirming primary hyperaldosteronism. Autoimmune testing and minor salivary gland biopsy established Sjögren’s syndrome. Abdominal imaging revealed a right adrenal adenoma and left-sided obstructive uropathy with severe unilateral renal dysfunction.

CONCLUSION

Endocrine and autoimmune disorders should be considered in patients presenting with HCM-like phenotypes.

Key Words: Hypertrophic cardiomyopathy-like phenotype; Primary hyperaldosteronism; Sjögren’s syndrome; Obstructive uropathy; Myocardial fibrosis; Case report

Core Tip: Hypertrophic cardiomyopathy-like phenotypes without identifiable genetic mutations may arise from secondary systemic conditions rather than primary sarcomeric disease alone. This case highlights the rare coexistence of primary hyperaldosteronism, Sjögren’s syndrome, and obstructive uropathy contributing synergistically to myocardial hypertrophy and fibrosis. Recognition of endocrine and autoimmune contributors is essential, as targeted treatment may help limit disease progression and improve outcomes.

INTRODUCTION

A substantial proportion of patients presenting with hypertrophic cardiomyopathy (HCM) do not have an identifiable sarcomeric mutation or a family history, suggesting that endocrine, autoimmune, and other systemic mechanisms may contribute to an HCM-like phenotype in selected individuals[1-3]. Chronic hormonal activation and immune-mediated inflammation can promote endothelial dysfunction, microvascular ischemia, and interstitial fibrosis, leading to secondary myocardial hypertrophy and, in some cases, dynamic left ventricular outflow tract (LVOT) obstruction[2,3]. Primary hyperaldosteronism (PHA) is a common and potentially treatable cause of secondary hypertension; its prevalence among hypertensive patients ranges from 4.6% to 13.0%, increasing to approximately 20% in those with resistant hypertension[4,5]. Because excess aldosterone is associated with adverse cardiovascular remodeling and fibrosis, early recognition is critical. Sjögren’s syndrome (SS) is a chronic autoimmune exocrinopathy that may involve multiple organs, and emerging data suggest an increased cardiovascular risk in SS, although overt cardiac involvement remains uncommon[6]. Here, we report a rare and clinically instructive case of an HCM-like phenotype in the setting of concomitant PHA, SS, and obstructive uropathy, emphasizing the need to evaluate secondary and potentially modifiable contributors in patients with unexplained hypertrophic remodeling.

CASE PRESENTATION

Chief complaints

A 45-year-old woman with known hypertension and hypothyroidism underwent routine assessment. The patient was admitted for routine evaluation and was asymptomatic at presentation.

History of present illness

Laboratory testing revealed hypokalemia and metabolic alkalosis, prompting further investigation.

History of past illness

The patient had a history of hypothyroidism treated with levothyroxine sodium. She had previously undergone meningioma surgery and double-J stent placement for hydronephrosis.

Personal and family history

There was no known family history of cardiomyopathy or sudden cardiac death.

Physical examination

Blood pressure was 169/97 mmHg, and heart rate was 60 beats per minute. No signs of heart failure were observed on physical examination.

Laboratory examinations

Laboratory evaluation demonstrated hypokalemia (3.0 mEq/L), metabolic alkalosis (pH 7.49; bicarbonate 32.9 mmol/L), suppressed renin levels, and markedly elevated aldosterone concentrations with an increased aldosterone-to-renin ratio. Autoimmune serology was positive for antinuclear antibodies, anti-SS-A, anti-SS-B, and anti-Ro-52 antibodies. Given spontaneous hypokalemia, markedly elevated aldosterone levels, and suppressed renin activity, the biochemical findings were considered diagnostic of PHA; therefore, confirmatory suppression testing was not performed in accordance with current guideline recommendations.

Imaging examinations

Electrocardiography demonstrated left ventricular hypertrophy with prominent U waves. Transthoracic echocardiography revealed asymmetric septal hypertrophy and dynamic LVOT obstruction, with a resting peak gradient of 90 mmHg, increasing to 130 mmHg during the Valsalva maneuver (Figure 1). Left ventricular systolic function was preserved. Cardiac magnetic resonance imaging confirmed diffuse asymmetric left ventricular hypertrophy, with a maximal septal thickness of 26 mm (Figure 2). Left ventricular systolic function was preserved, with an ejection fraction of 72%. The left ventricular end-diastolic volume was 128 mL, end-systolic volume was 35 mL, and stroke volume was 92 mL. Mild narrowing of the LVOT was observed, accompanied by turbulent flow at this level. Mid-wall late gadolinium enhancement was present in the hypertrophied septal segments, consistent with non-ischemic myocardial fibrosis. Late gadolinium enhancement was qualitatively assessed and predominantly involved the mid-wall septal regions without precise quantitative percentage measurement. Abdominal imaging revealed a right adrenal adenoma and left-sided obstructive uropathy with markedly reduced renal function.

Figure 1 Transthoracic echocardiography showing asymmetric septal hypertrophy and dynamic left ventricular outflow tract obstruction with a resting gradient of 90 mmHg and 130 mmHg on Valsalva maneuver.

Figure 2 Cardiac magnetic resonance demonstrating diffuse asymmetric left ventricular hypertrophy with mid-wall late gadolinium enhancement consistent with non-ischemic fibrosis.

FINAL DIAGNOSIS

HCM-like phenotype associated with PHA, SS, and obstructive uropathy.

TREATMENT

The patient was started on spironolactone for the management of PHA. Hydroxychloroquine therapy was initiated following the diagnosis of SS. Cardiac management followed guideline-directed therapy for obstructive HCM.

OUTCOME AND FOLLOW-UP

The patient was followed for 9 months under multidisciplinary care involving cardiology, endocrinology, nephrology, and rheumatology services (Table 1). Blood pressure and serum potassium levels improved following mineralocorticoid receptor antagonist therapy, and the patient remained clinically stable without heart failure symptoms. However, repeat imaging has not yet demonstrated significant regression of septal hypertrophy.

Table 1 Clinical timeline of diagnostic and therapeutic milestones.

Time point	Clinical event
Initial evaluation	Routine assessment revealed hypokalemia and metabolic alkalosis
Week 1	Hormonal evaluation demonstrated markedly elevated aldosterone levels with suppressed renin activity, confirming primary hyperaldosteronism
Week 2	Transthoracic echocardiography revealed asymmetric septal hypertrophy and dynamic LVOT obstruction (resting gradient 90 mmHg; 130 mmHg with Valsalva)
Week 3	Cardiac magnetic resonance imaging confirmed septal thickness of 26 mm, preserved ejection fraction (72%), and mid-wall late gadolinium enhancement
Week 4	Autoimmune serology and minor salivary gland biopsy established Sjögren’s syndrome
Week 5	Abdominal imaging identified right adrenal adenoma and left-sided obstructive uropathy
Week 6	Spironolactone therapy was initiated; hydroxychloroquine treatment was started
Month 3	Blood pressure and serum potassium levels improved under therapy
Month 9	Clinical stability was maintained; repeat imaging showed no significant regression of septal hypertrophy

LVOT: Left ventricular outflow tract.

DISCUSSION

HCM represents a heterogeneous clinical spectrum that includes inherited sarcomeric disease as well as non-familial phenotypes driven by systemic conditions. In patients without a clear family history or identifiable genetic variants, endocrine and immune-mediated mechanisms may promote hypertrophic remodeling and myocardial fibrosis, resulting in an “HCM-like phenotype” rather than primary sarcomeric HCM[1-3].

This case is notable for the rare coexistence of PHA, SS, and obstructive uropathy in a patient with asymmetric hypertrophy, dynamic LVOT obstruction, and mid-wall late gadolinium enhancement. While associations between hypertrophic remodeling and PHA or SS have been individually reported, the combined presentation is unusual and clinically instructive because it highlights a diagnostic pathway in which secondary and potentially modifiable contributors should be systematically evaluated before labeling the condition as primary HCM.

Excess aldosterone in PHA contributes not only to sodium retention and hypertension but also to myocardial fibrosis and structural remodeling via mineralocorticoid receptor–mediated pathways[7,8]. Patients with PHA have a higher burden of cardiometabolic events compared with those with essential hypertension, even when blood pressure levels are comparable, supporting a direct pathogenic role of aldosterone in adverse cardiovascular remodeling[7]. Mineralocorticoid receptor antagonists may mitigate remodeling and improve outcomes, reinforcing the importance of timely recognition and targeted therapy[8,9].

SS is primarily an autoimmune exocrinopathy; however, emerging data suggest increased cardiovascular risk, and reported cardiac manifestations include diastolic dysfunction, myocarditis, and arrhythmias[6,10,11]. Chronic systemic inflammation, endothelial dysfunction, and microvascular ischemia may plausibly contribute to hypertrophic remodeling and fibrosis, potentially amplifying the effects of aldosterone excess in susceptible patients.

The patient also had obstructive uropathy with marked unilateral renal dysfunction. Chronic renal impairment can contribute to cardiovascular stress through neurohormonal activation and increased afterload; nevertheless, the relationship between obstructive uropathy and myocardial hypertrophy in this case remains speculative. Therefore, a direct causal link cannot be established.

Alternative explanations must be considered, particularly long-standing hypertension as an independent driver of left ventricular hypertrophy and even dynamic obstruction in some patients. However, the asymmetric pattern of hypertrophy and the presence of non-ischemic fibrosis on cardiac magnetic resonance, together with concomitant endocrine and autoimmune abnormalities, suggest a multifactorial pathophysiology rather than isolated hypertensive heart disease.

Clinically, this case underscores the importance of differentiating true sarcomeric HCM from secondary hypertrophic remodeling with obstruction. In patients with hypertrophic phenotypes accompanied by resistant hypertension, hypokalemia, autoimmune features, or renal pathology, targeted evaluation for secondary causes may alter diagnostic reasoning and management, and may improve outcomes through disease-specific therapy in addition to guideline-directed treatment for obstructive physiology[12].

This report has several limitations. First, genetic testing for sarcomeric mutations was not available; therefore, a genetic etiology cannot be completely excluded. Second, the relationship between obstructive uropathy and myocardial hypertrophy remains speculative, and a direct causal link cannot be definitively established. Finally, as this is a single-patient case report, the findings should be interpreted cautiously and cannot be generalized. Despite these limitations, the case highlights the importance of considering secondary endocrine and autoimmune contributors in patients presenting with hypertrophic cardiomyopathy-like phenotypes.

CONCLUSION

This case underscores the importance of considering endocrine and autoimmune disorders in patients presenting with unexplained left ventricular hypertrophy and obstructive physiology. Early recognition of potentially reversible contributors and a multidisciplinary treatment strategy may help limit disease progression and improve outcomes.