Abstract Disclosure: U.D. Gupta: None. M. Al-Ghuraibawi: None. R. Abdulhussein: None. K. Panigrahi: None. Z. Deribe: None. Distinguishing between the various subtypes of primary hyperaldosteronism (PHA) poses a clinical challenge. Nevertheless, it is notable that primary hyperaldosteronism is a prominent contributor to secondary hypertension, accounting for less than 1% of cases. The triad of hypertension, hypokalemia, and metabolic alkalosis demands screening for PHA. While bilateral adrenal hyperplasia and aldosterone-producing adenomas (APA) are common, rarer forms like unilateral adrenal hyperplasia and glucocorticoid-responsive aldosteronism can also occur. In our case, a 61-year-old patient has been diagnosed and treated for primary hyperaldosteronism for last 10-years. Presently, the patient is undergoing management for blood pressure with a medication regimen comprising Amiloride, Nifedipine, Minoxidil, Atenolol, and Eplerenone over the past decade. No abnormal findings were observed in the computed tomography or magnetic resonance imaging of the adrenal gland, and adrenal venous sampling test results were non-conclusive. The patient has exhibited favorable outcomes with medications, also subsequent imaging has not revealed the presence of an adrenal mass. This case is presented as unique due to its atypical presentation, characterized by the absence of anatomical lesions in the adrenal gland and non-conclusive sampling test results. Nevertheless, the patient responded positively to treatment, supported by the diagnostic significance of preliminary lab tests for primary hyperaldosteronism (aldosterone level: 20.5; plasma renin activity: 0.19, initially aldosterone levels were 17 and 7 before and after saline infusion). Notably, literature acknowledges that the aldosterone-producing adenomas (APAs) can be very small, sometimes <3 mm in diameter, and lesions <1 cm may be overlooked on CT scans. The limitation of adrenal venous sampling (AVS) is the challenge in obtaining good sample due to technical difficulties and variations in local expertise, success rates in AVS may vary. This case exemplifies the diagnostic complexities encountered in primary hyperaldosteronism cases, where imaging and adrenal venous sampling, though frequently recommended, may pose challenges. In conclusion, we share insights from this case and its treatment outcome. Clinically, a thorough assessment of symptoms, along with laboratory results, is crucial for diagnosis and treatment and further categorization may be challenging without imaging and adrenal venous sampling. Presentation: 6/3/2024