Rare coexistence of aldosterone resistance and adrenal insufficiency in asymptomatic infant with persistent hyperkalaemia: A case report

Abstract

BACKGROUND

Hyperkalaemia is a potentially life-threatening electrolyte disturbance, most commonly encountered in neonates and infants with renal or endocrine abnormalities. Persistent hyperkalaemia in an otherwise clinically well child is unusual and warrants careful investigation. This case illustrates a rare coexistence of pseudohypoaldosteronism and adrenal insufficiency in an otherwise well infant, presenting solely with persistent hyperkalaemia.

CASE SUMMARY

We report a 6-month-old male infant who was incidentally found to have persistent hyperkalaemia during hospitalisation for acute bronchiolitis. He remained asymptomatic, with no clinical or electrocardiographic features of hyperkalaemia. Laboratory investigations revealed persistent hyperkalaemia with normal serum sodium and chloride levels, low serum bicarbonate, elevated serum aldosterone, and suppressed plasma renin activity which consistent with features of aldosterone resistance. Further testing demonstrated low basal serum cortisol with inadequate response to synacthen stimulation, while serum 17-hydroxyprogesterone levels were normal, excluding congenital adrenal hyperplasia. The child was managed with hydrocortisone, high-dose fludrocortisone, and potassium-binding resins, with subsequent improvement.

CONCLUSION

This case illustrates a rare coexistence of aldosterone resistance and adrenal insufficiency in an otherwise well infant, presenting solely with persistent hyperkalaemia. It emphasises the importance of considering overlapping endocrine pathologies and highlights the need for early hormonal profiling in infants with unexplained electrolyte disturbances.

Key Words: Hyperkalemia; Aldosterone resistance; Adrenal insufficiency; Electrolyte imbalance; Diagnosis; Case report

Core Tip: A 6-month-old male was incidentally found to have persistent hyperkalaemia despite being asymptomatic with normal electrocardiogram documented during hospitalization for bronchiolitis. Laboratory evaluation showed elevated serum aldosterone, suppressed plasma renin activity, normal serum sodium and chloride with low serum bicarbonate, consistent with aldosterone resistance. Additionally, a short synacthen test confirmed adrenal insufficiency, with normal serum 17-hydroxyprogesterone excluding (congenital adrenal hyperplasia). He required escalating fludrocortisone alongside hydrocortisone and potassium binders, indicating mineralocorticoid resistance. Genetic testing was not performed, but clinical and biochemical findings strongly support coexisting aldosterone resistance and adrenal insufficiency; an exceptionally rare dual endocrinopathy.

INTRODUCTION

Hyperkalaemia is defined as a serum or plasma potassium (K⁺) concentration exceeding 5.5 mmol/L in adults and older children, while in premature infants and neonates, the upper reference limit may extend to 6.5 mmol/L[1,2]. This physiologically higher potassium level in infancy reflects reduced renal potassium excretion due to relative aldosterone insensitivity and a lower glomerular filtration rate[1]. Clinical manifestations of hyperkalaemia are often nonspecific but primarily involve skeletal or cardiac muscle dysfunction. It is a potentially life-threatening electrolyte imbalance that requires prompt recognition and management, particularly in the paediatric patients[3].

In infants and young children, hyperkalaemia most frequently arises from renal impairment, congenital adrenal hyperplasia (CAH), or disorders of aldosterone synthesis and action such as hypoaldosteronism and pseudohypoaldosteronism (PHA)[4]. We describe an unusual case of a clinically well infant with persistent hyperkalaemia who was found to have elevated aldosterone levels with inadequate cortisol response, suggesting a rare coexistence of aldosterone resistance and adrenal insufficiency.

CASE PRESENTATION

Chief complaints

A 6-month-old male infant, previously well with no known medical illness, was incidentally found to have persistent hyperkalaemia during hospitalisation for acute bronchiolitis.

History of present illness

He remained clinically asymptomatic, with no features suggestive of hyperkalaemia such as muscle weakness, nausea, vomiting or electrocardiographic features of hyperkalaemia.

History of past illness

He was born full term via spontaneous vaginal delivery, with unremarkable antenatal, perinatal, and postnatal histories. He was exclusively breastfed and had recently commenced complementary feeding. Developmental milestones and immunisation status were appropriate for age.

Personal and family history

There was no significant family history, and the parents were non-consanguineous. He was the second of two siblings.

Physical examination

On examination, the infant was active and well. Vital signs included a blood pressure of 90/60 mmHg and pulse rate of 110 bpm. Growth parameters i.e. growth and length were between the 15^th and 25^th percentiles. No dysmorphic features or clinical signs of dehydration such as sunken fontanelle, dry mucous membranes, or reduced skin turgor were observed. Respiratory examination revealed occasional rhonchi, while abdominal and neurological examinations were normal. Genital examination revealed a normal male phenotype without hyperpigmentation of the axillae or areolae. Other systemic examinations were unremarkable. Electrocardiogram (ECG) demonstrated normal sinus rhythm, with no hyperkalaemic changes such as peaked T waves, shortened QT interval, or absent P waves.

Laboratory examinations

Initial laboratory investigations revealed persistent hyperkalaemia, with a peak serum potassium level of 6.9 mmol/L (reference range: 3.5-5.5 mmol/L), in the presence of normal sodium and chloride levels. Venous blood gas analysis showed a normal pH with low bicarbonate of 19 mmol/L (reference range: 22-28 mmol/L) (Table 1). Spot urine electrolytes revealed mildly elevated sodium (30 mmol/L) and inappropriately high potassium (43 mmol/L); however, both fractional excretion of sodium and potassium were within normal ranges. Urine microscopy showed no evidence of urinary tract infection.

Table 1 Serial blood investigations of this patient.

Serum/plasma	Day 1	Day 3		1 month follow-up	3 months follow-up	6 months follow-up	12 months follow-up	Reference range
Sodium (mmol/L)	138	139	Patient on oral hydrocortisone, fludrocortisone and kalimate	133	135	138	136	135-145
Potassium (mmol/L)	6.9	6.5		5.9	4.8	5.1	4.9	3.5-5.5
Urea (mmol/L)	3.3	3.6		5.3	5.0	5.2	4.9	2.7-8.0
Creatinine (µmol/L)	40	28		39	35	37	38	44-80
Chloride (mmol/L)	109	110		110	105	102	101	98-107
Calcium (mmol/L)		2.53		2.29	2.30	2.31	2.30	2.25-2.75
Phosphate (mmol/L)		2.10		1.07	1.17	1.20	1.23	1.15-2.25
Random cortisol (nmol/L)		63.4		221	350	445	515	130-500
Aldosterone (pmol/L)		1825		1050	802	750	735	70-540
Plasma Renin Activity (ng/mL/hour)		< 0.02		< 0.02	< 0.02	< 0.02	< 0.02	0.5-3.3
Venous pH		7.4		7.32	-	-	-	7.35-7.45
HCO3 (mmol/L)		19		23	-	-	-	22-28

Endocrine evaluation demonstrated markedly elevated plasma aldosterone (1825 pmol/L; reference range: 70-540 pmol/L) with suppressed plasma renin activity (< 0.02 ng/mL/hour; reference range: 0.5-3.3 ng/mL/hour). A standard short synacthen test showed low basal serum cortisol with an inadequate cortisol response, consistent with adrenal insufficiency. Basal and stimulated 17-hydroxyprogesterone (17-OHP) levels were within the normal range (Table 2), effectively excluding (CAH). Genetic testing was offered but deferred due to financial constraints.

Table 2 Short synacthen test.

Time (minute)	Cortisol (nmol/L)	17-OHP (nmol/L)
0	17.9	1.57
30	81.1	4.15
60	94.15	6.85

Basal (0 minute) serum cortisol was low for age and gender specific range and shows inadequate response to synacthen test (a normal response shows cortisol rise of more than 374 nmol/L based on assay specific range)[17]. Basal 17-hydroxyprogesterone (17-OHP) and its stimulated level at 60 minutes was normal (normal basal 17-OHP is < 6 nmol/L and a normal stimulated level of 17-OHP is < 30 nmol/L at 60 minutes. 17-OHP: 17-hydroxyprogesterone.

Imaging examinations

Imaging examinations were not conducted for this patient.

FINAL DIAGNOSIS

Clinical and biochemical findings support coexisting aldosterone resistance and adrenal insufficiency.

TREATMENT

The patient was commenced on oral hydrocortisone 2 mg three times daily (approximately 15 mg/m²/day), fludrocortisone 400 µg once daily, and sodium polystyrene sulfonate (Kalimate) for the management of persistent hyperkalaemia. Despite initial therapy, serum potassium remained elevated; therefore, the fludrocortisone dose was gradually titrated up to 900 µg/day to optimize mineralocorticoid effect. This adjustment achieved normalization of serum potassium levels, with sustained biochemical stability thereafter. Throughout treatment, the patient remained clinically well, normotensive, and free of electrocardiographic or cardiac manifestations of hyperkalaemia.

The patient continues regular hydrocortisone and fludrocortisone replacement, with periodic monitoring of electrolytes, hormonal profile, and growth parameters. At the time of the latest follow-up (12 months after diagnosis), the patient remains asymptomatic and clinically stable under ongoing therapy. No tapering or discontinuation of corticosteroid or mineralocorticoid therapy has been attempted, as the persistence of aldosterone resistance and adrenal insufficiency warrants continued replacement therapy.

OUTCOME AND FOLLOW-UP

During the follow-up period, patient remain clinically well with growth and developmental milestones appropriate for age.

DISCUSSION

Potassium (K⁺) is the predominant intracellular cation, essential for maintaining membrane potential, propagating nerve impulses, and regulating acid-base balance. Plasma potassium concentration is normally maintained within a narrow range (3.5-5.5 mmol/L) through a combination of internal and external regulatory mechanisms[5]. Internal regulation involves redistribution between the intracellular and extracellular compartments, influenced by insulin (via Na⁺/K⁺-ATPase stimulation), β₂-adrenergic agonists, and acid-base status, with acidosis driving potassium efflux and alkalosis promoting cellular uptake[6]. External regulation occurs primarily through renal handling whereby most filtered potassium is reabsorbed in the proximal tubule and loop of Henle, with fine-tuning in the distal nephron. Principal cells in the collecting duct, under the action of aldosterone, facilitate sodium reabsorption and potassium secretion via the epithelial sodium channel and renal outer medullary potassium channel[6,7].

In infants, pseudohyperkalaemia due to haemolysis is the most common initial consideration, and repeat venous sampling is recommended before treatment[4,8]. True hyperkalaemia most often attributed to impaired renal excretion or disruption of the renin-angiotensin-aldosterone system. Acute or chronic kidney disease reduces glomerular filtration and distal tubular secretion, predisposing to elevated potassium. CAH, particularly 21-hydroxylase deficiency, causes cortisol and aldosterone deficiency, leading to hyponatraemia and hyperkalaemia. Similarly, primary hypoaldosteronism presents in infancy with persistent hyperkalaemia due to impaired aldosterone synthesis (Table 3)[9,10]. In addition, conditions associated with extensive tissue breakdown such as rhabdomyolysis, tumour lysis syndrome, haemolysis, or severe metabolic acidosis can cause hyperkalaemia due to the rapid efflux of intracellular potassium[11]. Persistent hyperkalaemia in paediatrics warrants careful evaluation, as it is most often associated with acute kidney injury, CAH, or hypoaldosteronism (Figure 1)[9].

Figure 1 Diagnostic approach of hyperkalemia in infant. RAAS: Renin-angiotensin-aldosterone system; PAC: Plasma aldosterone concentration; PRA: Plasma renin activity.

Table 3 Causes of persistent hyperkalemia in an infant.

Differential diagnosis	Description	Test findings	Treatment
Congenital adrenal hyperplasia[18]	Inherited autosomal recessive disorder affecting adrenal steroidogenesis, most commonly is 21-hydroxylase deficiency	Raised serum 17-OHP, hypocortisolism, hyperkalaemia, hyponatraemia, Short synacthen test shows adrenal insufficiency, and genetic testing to proved the specific mutated gene involved	Glucocorticoids and mineralocorticoids (to also replace concurrent mineralocorticoid deficiency)
Hypoaldosteronism[19]	Insufficient aldosterone production or action, leading to hyperkalemia and metabolic acidosis. It could coexist with other conditions such as primary adrenal insufficiency or part of RTA type 4	Hyperkalemia and metabolic acidosis. Low urine pH in RTA type 4, hypocorticolism with ACTH stimulation test proved adrenal insufficiency in Addison’s disease	Fludrocortisone, salt supplementation, management of underlying conditions
AKI[20]	KDIGO defined AKI as an increase in serum creatinine (absolute increase of ≥ 0.3 mg/dL within 48 hours or relative increase of ≥ 50% from baseline within 7 days) and reduction in urine output (urine volume less than 0.5 mL/kg/hour for at least 6 hours)	Raised serum creatinine and urea, hyperkalaemia, hyponatraemia, emerging renal biomarker to detect early AKI e.g. neutrophil gelatinase-associated lipocalin	Depending on types (e.g., hydration for pre-renal AKI, renal replacement therapy for severe acute tubular necrosis), correction of electrolyte disturbances

AKI: Acute kidney injury; RTA: Renal tubular acidosis; 17-OHP: 17-hydroxyprogesterone; KDIGO: Kidney disease: Improving global outcomes; ACTH: Adrenocorticotropic hormone.

In this case, the infant’s persistent hyperkalaemia was discovered incidentally during admission for bronchiolitis. The child was clinically well, with no muscular weakness, dehydration, or ECG abnormalities, making the diagnosis less obvious. Biochemical evaluation revealed hyperkalaemia, normonatraemia, slightly low bicarbonate, elevated aldosterone, and suppressed renin activity; a profile consistent with aldosterone resistance, or PHA. The lack of history and clinical finding for urinary tract infection or obstructive uropathy, along with poor response to escalating fludrocortisone doses, supports the diagnosis of aldosterone resistance[12].

The additional finding of low cortisol with inadequate synacthen response confirmed adrenal insufficiency. Normal 17-OHP levels excluded classical CAH, pointing instead to other forms of primary adrenal insufficiency such as CAH or familial glucocorticoid deficiency[13,14]. The coexistence of aldosterone resistance and adrenal insufficiency, particularly in the absence of salt wasting, hypotension, or ambiguous genitalia, is exceptionally rare. To our knowledge, there are no prior reports of such dual endocrine pathology cases.

Management involved fluid and electrolyte monitoring, potassium-binding resins, and hormone replacement. The requirement for higher-than-usual fludrocortisone doses reinforced the presence of mineralocorticoid resistance. In infants, typical fludrocortisone dosing ranges between 0.05-0.2 mg/day[15]. In view of receptor-level aldosterone resistance, high-dose fludrocortisone was initiated, with this infant receiving up to almost 1 mg daily as recommended in the literature[16]. Although genetic confirmation was not obtained, the constellation of biochemical and clinical features strongly suggests a dual endocrinopathy. This case expands the spectrum of presentations for paediatric hyperkalaemia and highlights the importance of thorough hormonal profiling in atypical cases.

CONCLUSION

Hyperkalaemia is a potentially life-threatening electrolyte disturbance that requires urgent recognition and management in the paediatric population. Persistent hyperkalaemia in an otherwise well child without dehydration, hypotension, or systemic illness presents a diagnostic challenge. This case is notable for its rarity; the coexistence of pseudohypoaldosteronism and adrenal insufficiency in an asymptomatic infant. It underscores the critical importance of early and comprehensive endocrine evaluation in unexplained electrolyte disturbances and raises awareness of overlapping endocrine disorders that may present subtly. By reporting this case, we aim to emphasise the need for clinicians to consider dual or atypical endocrine pathologies in persistent paediatric hyperkalaemia, even in the absence of classical clinical features.

ACKNOWLEDGEMENTS

We acknowledge the staff of Chemical Pathology Laboratory for providing the access to laboratory results.