Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, typically diagnosed in childhood. However, atypical or mild phenotypes may delay diagnosis until adulthood. Electrolyte disturbances are uncommon initial manifestations, particularly in adults.1–3 We report a rare case of adult-diagnosed CF presenting solely with recurrent summer-associated hypokalemia and metabolic alkalosis.

A 28-year-old Turkish male presented in July 2024 with generalized weakness and excessive sweating during the summer months. Physical examination, chest X-ray, and electrocardiography were unremarkable, and blood pressure was 118/74mmHg. Laboratory tests revealed moderate hypokalemia (2.9mEq/L) with metabolic alkalosis; other parameters were normal. Intravenous potassium replacement (60mmol KCl in 1L saline) normalized potassium levels, which remained stable during follow-up in November 2024, January 2025, and April 2025 (Table 1).

In June 2025, he was re-admitted with recurrent weakness. Serum potassium was 2.6mEq/L and increased to 3.4mEq/L after intravenous replacement. Additional tests revealed sodium 137mEq/L, magnesium 1.1mEq/L, bicarbonate 34mmol/L, urinary potassium 50.8mmol/L, and elevated renin and aldosterone levels. Vomiting, diarrhea, and diuretic use were excluded.

His medical history included idiopathic pancreatitis in 2017. He denied smoking or alcohol use, and his BMI was 24kg/m2. The coexistence of summer-associated hypokalemia, normotension, prior pancreatitis, and excessive sweating prompted evaluation for CF. Sweat chloride was 76.3mmol/L (normal <60mmol/L). Genetic analysis of the CFTR gene revealed two heterozygous variants: c.2843C>T (p.Ser945Leu) and c.922T>C (p.Ser308Pro). The patient was informed about the diagnosis and expressed relief at having a clear explanation for his recurrent symptoms. Written informed consent was obtained for publication.

CF is a multisystem disease caused by CFTR mutations leading to defective or absent CFTR protein, clinically characterized by recurrent respiratory infections, pancreatic insufficiency, and malabsorption-related complications, and other systemic manifestations.1 In the present case, the diagnosis was delayed due to several atypical features: the occurrence of hypokalemia only during the summer months, adult age at diagnosis, absence of a history of recurrent pulmonary infections, and lack of other organ involvement apart from an episode of pancreatitis.

In CFTR mutation carriers, excessive sweat sodium and chloride loss during hot months can cause extracellular fluid (ECF) depletion and secondary hyperaldosteronism.4 ECF volume contraction, activation of the renin–angiotensin–aldosterone system, hypokalemia, and the development and maintenance of metabolic alkalosis have all been proposed as interconnected mechanisms in this context.5 Consistent with this pathophysiological framework, both renin and aldosterone levels were found to be elevated above the reference range in our patient.

Hypokalemia with sodium and chloride loss can worsen metabolic alkalosis, as chloride depletion alone may sustain alkalosis regardless of volume or potassium status.6 In the setting of CF, luminal chloride deficiency leads to impaired bicarbonate excretion by the renal collecting ducts despite increased pendrin activity during chloride-depletion alkalosis.7 This failure to eliminate bicarbonate contributes to the persistence of systemic metabolic alkalosis.

Hyperaldosteronism can promote potassium loss both through sweat and urine, thereby contributing to hypokalemia.8 Urinary potassium excretion was disproportionately high for the degree of hypokalemia, indicating renal potassium wasting. Excessive sweat loss during hot months likely worsened total potassium depletion. Chronic salt loss and secondary hyperaldosteronism in CF can enhance renal potassium and magnesium loss, while intestinal malabsorption further reduces magnesium absorption. Resulting hypomagnesemia aggravates potassium wasting by impairing Na+/K+-ATPase activity, making hypokalemia more resistant to correction.3,5 The mild hypomagnesemia detected in our patient likely contributed to the persistence of both hypokalemia and metabolic alkalosis through a synergistic effect with hyperaldosteronism and salt loss. However, the persistence of hypokalemia despite magnesium replacement rules out the possibility of hypokalemia secondary to hypomagnesemia alone in this patient. In fact, under high sweat flow rates, sweat potassium concentrations in individuals with CF can reach up to 17.8mEq/L, compared to 8.4mEq/L in healthy controls.9 This difference may be further accentuated during hot summer months, exacerbating potassium depletion in CF patients. A similar summer-related CF case was previously reported in an African American patient.3

The c.2843C>T (p.Ser945Leu) variant is classified as pathogenic in several databases and has been associated with classical CF phenotypes.10 The c.922T>C (p.Ser308Pro) is considered a variant of uncertain significance, but its presence in trans with a pathogenic variant supports the diagnosis in the appropriate clinical context.

Awareness and adult diagnosis of CF are increasing. We report a rare adult case presenting solely with hypokalemia and metabolic alkalosis, emphasizing the need for clinical suspicion even when typical features are absent. CF should be considered in unexplained summer hypokalemia. The detection of the c.922T>C (p.Ser308Pro) variant highlights the importance of early genetic evaluation.