Single case report links unilateral adrenalectomy to two-year remission of ACTH-independent hypercortisolism, diabetes and resistant hypertension

A 53-year-old woman with bilateral macronodular adrenocortical disease and ACTH-independent hypercortisolism had persistent cortisol elevation, poorly controlled diabetes and resistant hypertension before undergoing unilateral removal of the larger right adrenal gland. At two-year follow-up, her urinary free cortisol and midnight cortisol remained within reference ranges, and she no longer needed antihypertensive or antidiabetic medication.

The case report described a woman referred to Huzhou Central Hospital in China after her hypertension remained inadequately controlled with amlodipine, irbesartan-hydrochlorothiazide and carvedilol. Her diabetes was treated with twice-daily biphasic insulin aspart 30 and daily linagliptin, but her fasting glucose was 8.0 mmol/L and HbA1c was 8.2%. She also reported polyuria, polydipsia and a 2-kg weight loss over three months. Her blood pressure was 142/96 mmHg and body-mass index was 22.46 kg/m². Examination showed no central obesity, moon facies, purple striae or proximal muscle weakness.

Abdominal ultrasound incidentally identified nodular lesions in both adrenal glands. Hormonal testing showed loss of the normal nocturnal cortisol nadir, with midnight serum cortisol of 27.17 μg/dL, and suppressed ACTH below 5 pg/mL. Her 24-hour urinary free cortisol was 1,656.00 μg/24h compared with a reference range of 75.00–520.00 μg/24h, approximately 3.2 times the upper limit of normal. Cortisol was not suppressed during a low-dose dexamethasone suppression test. Renin, aldosterone, catecholamines, DHEA-S and basal 17α-hydroxyprogesterone were within their respective reference ranges.

Contrast-enhanced CT confirmed multiple nodular lesions in both adrenal glands, with marked asymmetry. The largest right-sided lesion measured 57 × 42 mm, compared with 46 × 35 mm on the left. Suppressed ACTH excluded Cushing disease and ectopic ACTH syndrome, while normal DHEA-S made congenital adrenal hyperplasia unlikely. The investigators established a diagnosis of bilateral macronodular adrenocortical disease, or BMAD, with ACTH-independent hypercortisolism but without classic Cushingoid features. They also reviewed 13 case reports, case series and retrospective cohorts published from 2015 through 2025 to contextualize the case.

After multidisciplinary discussion, the clinicians performed right unilateral adrenalectomy because it was the larger gland. Pathology confirmed macronodular adrenocortical hyperplasia without malignancy. Adrenal venous sampling was not performed; the report notes that its utility in BMAD remains controversial because secretion may arise from multiple nodules in both glands and standardized lateralization criteria are not firmly established. The team considered the marked imaging asymmetry and the limited additional information that sampling might provide.

Clinical and biochemical improvement was reported soon after surgery. One week after adrenalectomy, blood pressure had fallen to 120/82 mmHg and fasting glucose to 5.9 mmol/L. Urinary free cortisol declined to 226.59 μg/24h, while midnight serum cortisol was 1.65 μg/dL. The patient did not require postoperative glucocorticoid replacement, indicating that the remaining adrenal gland maintained adequate function during the reported follow-up.

At two years, midnight serum cortisol was 1.53 μg/dL and 24-hour urinary free cortisol was 185.72 μg/24h, both within the laboratory reference ranges. Fasting glucose was 4.72 mmol/L and HbA1c was 6.0%. The patient remained asymptomatic, had no reported relapse and had discontinued all antihypertensive and antidiabetic medications. These observations document sustained biochemical and metabolic remission in this individual during two years of follow-up; because this was a single case, the findings do not establish the effectiveness of unilateral adrenalectomy for other patients with BMAD.

The literature summarized by the authors provides broader but heterogeneous context. Among patients with overt Cushing syndrome, reported initial remission rates after unilateral adrenalectomy ranged from 70.8% to 100%, while recurrence occurred in 12%–63% of participants, depending on the study. The small number of reported cases involving mild autonomous cortisol secretion was associated with biochemical remission and metabolic improvement, although limited samples and follow-up warrant caution. One cited cohort found that preoperative urinary free cortisol above twice the upper limit of normal predicted persistent hypercortisolism after unilateral adrenalectomy; the present patient’s value was approximately 3.2 times the upper limit, yet she had no recurrence during the two-year observation period.

Important limitations include the single-patient design, the two-year follow-up and the absence of ARMC5 genetic testing. The report states that ARMC5 mutations occur in approximately 20%–25% of BMAD cases and up to 55% of operated patients with severe hypercortisolism. Although this case achieved remission, the authors present adrenal asymmetry and the absence of classic Cushingoid features as possible additional predictors of success, rather than established prognostic factors. The findings support consideration of BMAD in patients with bilateral adrenal nodules, resistant hypertension and poorly controlled diabetes, even in the absence of typical Cushingoid features, while the choice of surgery must be individualized to preserve adrenal function and monitor for persistent or recurrent cortisol excess.

Subject of Research: A single case of bilateral macronodular adrenocortical disease treated with unilateral adrenalectomy

Article Title: Case Report: A case study on bilateral macronodular adrenocortical disease: ACTH-independent hypercortisolism with refractory diabetes and hypertension

Article References: Qiu, Y., Song, P., Yao, J., Wang, L., & Ying, J. (2026). Case Report: A case study on bilateral macronodular adrenocortical disease: ACTH-independent hypercortisolism with refractory diabetes and hypertension. Frontiers in Endocrinology, 17, Article 1917551. https://doi.org/10.3389/fendo.2026.1917551

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1917551

Keywords: bilateral macronodular adrenocortical disease, ACTH-independent hypercortisolism, unilateral adrenalectomy, resistant hypertension, type 2 diabetes, Cushing syndrome, adrenal nodules, cortisol remission, case report, Case, Report, bilateral