Primary hyperaldosteronism, or Conn’s syndrome, is a condition characterized by non-suppressible hypersecretion of aldosterone, which most frequently results in hypertension and hypokalemia. Previously, it was estimated that approximately 1% of hypertensive patients were affected by primary hyperaldosteronism, but recent developments in screening methods, like the more extensive application of plasma aldosterone to renin ratio, have highlighted the actual prevalence to be up to 12% [10]. A low serum potassium concentration can lead to a variety of symptoms, including electrocardiogram abnormalities, fatigue, and muscle weakness, manifesting as constipation, exercise intolerance, and dyspnea. Additionally, acute respiratory failure is a rare but treatable presentation of this disorder [7]. Hypokalemia causing respiratory failure in primary aldosteronism is extremely rare. Herein, we present a 27-year-old woman with high blood pressure and severe hypokalemia, which caused respiratory failure. She finally underwent laparoscopic surgery after being diagnosed with adrenal adenoma as the cause of hypertension, and the patient recovered.

It is of great importance that primary hyperaldosteronism is considered a leading cause of secondary hypertension, with a prevalence of 10% among the general hypertensive population and 20% in patients with resistant hypertension [11]. Therefore, hypokalemia in hypertensive patients, especially young ones, should be assessed for secondary hypertension due to hyperaldosteronism. It is worth mentioning that only 9–37% of patients with primary aldosteronism have hypokalemia [6]. Thus, the recommendation for case detection has been determined beyond only hypokalemia. In a study by Ruhle et al. [12], only 2.7% of patients among 37,000 with hypertension and hypokalemia were screened for primary aldosteronism. This shows how much this condition may be underdiagnosed even in tertiary centers. Therefore, an optimal screening strategy is needed in this regard.

Severe hypokalemia in our patient led to respiratory failure, extremity weakness, and rhabdomyolysis. These presentations, especially respiratory arrest, as a consequence of hypokalemia are extremely rare in primary aldosteronism. There are, however, a few reports in the literature regarding hypokalemic-induced respiratory failure in other conditions, including renal tubular acidosis [13, 14]. Low potassium levels can interfere with the transmission of signals between nerves and muscles, hindering muscle contractions. In severe cases of hypokalemia, this can result in paralysis, especially when potassium levels are extremely low. This paralysis can impact the muscles involved in breathing, potentially causing respiratory failure [15]. Additionally, severe hypokalemia may cause rhabdomyolysis, leading to kidney injury, similar to our patient [15]. Hypokalemic-induced rhabdomyolysis is also rare, but has been previously reported in a few case reports of primary aldosteronism [16,17,18]. Although we expected ileus and constipation due to severe hypokalemia in our patient, she had diarrhea. We assume that her diarrhea was not related to her electrolyte imbalance and was associated with other causes leading to her gastrointestinal problems. However, it is worth mentioning that, on the other hand, diarrhea may have worsened the hypokalemia in our case.

Considering the severe signs and symptoms of our patient, including respiratory failure and extremity weakness, one would expect very high serum aldosterone values (at least more than 20 or 30 ng/dL). The lower-than-expected value of serum aldosterone in our case might be due to severe hypokalemia (serum potassium: 2.1 mEq/L) at the time of aldosterone and renin estimation.

The first step to identifying the subtype and ruling out adrenal carcinoma is an adrenal CT scan [6]. Although a CT scan is very useful for diagnosis and treatment decisions, it has some limitations. In a study by Young et al. [19], 21.7% of patients would have been wrongly excluded from being considered for adrenalectomy, and 24.7% of patients might have undergone unnecessary or inappropriate adrenalectomy. In a systematic review by Kempers et al. [20], CT/MRI misdiagnosed the cause of primary aldosteronism in 37.8% of patients compared to adrenal venous sampling as the standard test. Therefore, adrenal venous sampling has been suggested as an essential diagnostic tool for patients with a potential surgical therapeutic plan [6]. Notably, based on Dekkers et al. [21], there is no significant difference between the therapeutic outcomes of CT-based and adrenal venous sampling-based diagnoses. Still, this subject is controversial and needs further assessment. On the other hand, magnetic resonance imaging (MRI) has no advantage over CT in subtype evaluation [6]. Moreover, MRI is more expensive and has less spatial resolution than a CT scan [6]. Unfortunately, we did not have the resources to perform adrenal venous sampling in our patient, which was a limitation of our report.

The new WHO classification supports the terminology of the HISTALDO classification, which employs CYP11B2 immunohistochemistry to pinpoint functional sites of aldosterone production, aiding in predicting the risk of bilateral disease in primary aldosteronism. Aldosterone-producing adrenal cortical carcinoma (APACC) and adenoma (APA) are solitary lesions that are clearly visible with routine H&E and immunohistochemical staining for CYP11B2. Sub-centimeter solitary lesions visible with H&E and immunohistochemical staining are called aldosterone-producing nodules (APNs). Their counterparts, which may be difficult to distinguish with H&E but are always visible with immunohistochemical staining, are known as aldosterone-producing micronodules (APMs). When multifocal, they are termed “multiple APN” (MAPN) and “multiple APM” (MAPM), respectively. Lastly, aldosterone-producing diffuse hyperplasia is characterized by continuous CYP11B2 staining along the zona glomerulosa [22, 23].

A small lesion (< 40 mm) with a regular shape and well-defined margins along with hypodense and homogenous content suggests an adrenal adenoma [24]. The first choice of treatment is surgical resection. Hence, laparoscopic adrenalectomy is a reasonable option for any individual with an aldosterone-producing adenoma, offering fewer complications and similar blood pressure control and hypokalemia correction compared to open adrenalectomy [8, 25]. Laparoscopic surgery with transperitoneal or retroperitoneal approaches can be utilized. A meta-analysis indicated that the body of evidence for the comparison between these two approaches is limited. In this meta-analysis, evidence of very low quality suggests that for relatively small lesions (under 6–7 cm), the retroperitoneal approach might reduce late morbidity. Additionally, some post-operative parameters, such as the time to oral fluid or food intake and the time to ambulation, might favor the laparoscopic retroperitoneal adrenalectomy technique [26]. However, this subject needs further investigation. Furthermore, comparing total and partial adrenalectomy requires future studies to determine whether partial adrenalectomy avoids adrenal insufficiency without increasing the risk of persistent or recurrent aldosteronism [8]. Regarding the clinical outcome, based on a retrospective study of 168 cases diagnosed with primary aldosteronism who underwent adrenalectomy, 77% of patients with a unilateral adenoma had their hypertension resolved or under control [27]. When unilateral disease is clearly confirmed, adrenalectomy corrects hypokalemia, if it was present before surgery, in nearly all patients [8]. Hypertension is cured in approximately 30–60% of cases, and in the remaining patients, a significant improvement in blood pressure is observed [8].

The Primary Aldosteronism Surgery Outcome (PASO) criteria have been introduced to measure the outcome after adrenalectomy for unilateral primary aldosteronism [28]. According to the PASO criteria, our patient achieved complete clinical success as she had normal blood pressure in the last follow-up without any medications. However, we cannot determine the biochemical success due to the lack of an aldosterone-renin ratio after the surgery because the patient was not willing to undergo post-operative hormonal tests. Nevertheless, the serum potassium level was normal in the follow-up. Our follow-up duration was also acceptable as, according to the PASO criteria, the final outcome should be assessed at 6–12 months with annual reassessments.

This report of our patient with primary aldosteronism has limitations. CYP11B2 immunostaining, a useful pathologic tool to diagnose aldosterone overproduction in primary aldosteronism and to determine its subtype, was not utilized in our patient. Additionally, urinary cortisol was requested for the patient instead of dexamethasone-suppressed cortisol, which may be superior for adrenal masses. According to the Endocrine Society guidelines, one or more confirmatory tests are suggested to confirm the diagnosis of primary aldosteronism. The guidelines state that there may be no need for confirmatory tests in the setting of spontaneous hypokalemia, plasma renin below detection levels plus plasma aldosterone concentration > 20 ng/dL [6]. Another limitation of our report is not using confirmatory tests and adrenal venous sampling in our patient. Furthermore, in the follow-up, the patient had normal serum potassium values and controlled blood pressure without any medication, but post-operative aldosterone and renin levels were not measured.