Patient medical records from the Chinese People’s Liberation Army General Hospital for the period 2013–2018 were reviewed, and the following discharge diagnoses were identified: “adrenal tumor,” “adrenal adenoma,” “adrenal lesion,” “adrenal hyperplasia,” “pheochromocytoma,” “primary aldosteronism,” “aldosterone-producing adenoma (APA),” “idiopathic hyperaldosteronism (IHA),” “Cushing’s Syndrome (CS),” “primary bilateral macronodular adrenocortical hyperplasia (PBMAH),” “primary pigmented nodular adrenocortical disease (PPNAD),” “Cushing’s disease,” “ectopic adrenocorticotropic hormone (ACTH) syndrome,” “ tuberculosis,” “adrenocortical adenoma,” “adrenocortical carcinoma(ACC),” “ adrenal lymphoma,” and “congenital adrenal hyperplasia (CAH).” A total of 4,156 patients hospitalized in hematology, endocrinology, and other departments were screened for adrenal abnormalities using adrenal CT or magnetic resonance imaging (MRI), based on the above search results.
The inclusion criteria entailed radiological examinations of patients with the following conditions: 1) bilateral adrenal diffuse hyperplasia, 2) unilateral adrenal diffuse hyperplasia combined with contralateral adrenal nodular hyperplasia or adenomas, and 3) bilateral adrenal nodular hyperplasia or adenomas. All included patients underwent hormonal evaluation. The exclusion criteria were as follows: 1) radiological examinations of patients with unilateral adrenal diffuse or nodular hyperplasia or adenomas or atrophy and a contralateral, normal-looking adrenal gland; 2) bilateral adrenal atrophy; and 3) patients without hormonal evaluation or radiological examinations.
Finally, 777 patients hospitalized with bilateral adrenal lesions were included in the study. The baseline demographic and imaging characteristics of patients were extracted at initially radio-graphical diagnosis of bilateral adrenal lesions. This retrospective study was approved by the relevant Institutional Review Board (No. 2019 − 229), and informed consent was obtained from all participants. The information retrieved from the records at the onset of bilateral adrenal lesions included demographic data, clinical features, hormonal evaluation, imaging details of adrenals, and histopathological findings.
2.2 Endocrine investigation
Basic biochemical evaluations included plasma glucose, serum cortisol, plasma ACTH, 24-h urinary free cortisol (UFC), plasma free metanephrine (PFMN) normetanephrine (PFNMN), plasma active renin concentration, plasma aldosterone, and serum 17-hydroxyprogesterone (17-OHP) levels.
1) Subclinical Cushing’s syndrome (SCS) was defined as a cortisol concentration ≥ 1.8 ug/dL after the dexamethasone suppression test (DST) in combination with at least one other abnormal test of the hypothalamic-pituitary-adrenal axis, not associated with typical signs and symptoms of hypercortisolism. 2) Cushing’s syndrome was defined as at least two first-line biochemical tests (DST, UFC, and midnight serum cortisol) returning clearly abnormal results, included typical Cushing’s syndrome and SCS .
3) A screening test for pheochromocytoma was considered positive if PFMN was ≥ 0.50 nmol/L and/or PFNMN ≥ 0.21 nmol/L, and a 131I-metaiodobenzylguanidine (MIBG) scan was performed to confirm the diagnosis of pheochromocytoma . 4) A screening test for primary aldosteronism (PA) was considered positive if plasma ARR was > 20 (plasma aldosterone concentration expressed in pg/mL and plasma active renin concentration in ng/mL/h), and saline infusion and/or captopril challenge testing were performed to confirm PA. The diagnoses of APA and IHA have been described in the literature . 5) The subtypes of Cushing’s syndrome with bilateral adrenal lesions, included Cushing's disease (CD), Ectopic ACTH dependent CS, PBMAH, PPNAD, bilateral adrenocortical carcinoma (ACC), and bilateral adrenocortical adenoma (BAA) secreting cortisol on both sides, Which is a rare cause of ACTH independent CS, were diagnosed according to the International Society of Endocrinology guidelines [5, 8]. 6) CAH was confirmed using clinical history, current clinical signs, hormonal levels (predominantly 17-OHP, ACTH, cortisol, plasma active renin concentration, plasma aldosterone, and androgens), and/or CYP21A2 gene mutational analysis . 7) After excluding the above status, a diagnosis of nonfunctional adrenal lesions was established.
2.3 Histologically or image evaluation
Adrenal lymphoma was defined as a histologically proven lymphomatous lesion , and adrenal metastases were confirmed by biopsy or positron emissiontomography/ computed tomography (PET/CT). ACC was determined by histopathology according to the scoring system of Lin-Weiss-Bisceglia . Adrenal tuberculosis was defined histologically or by imaging . Benign, non-functional adrenal lesions were defined as characteristic images of masses with a baseline HU ≤ 10 , homogeneous internal texture, and benign washout patterns (for instance, absolute washout > 60% and relative washout > 40%) on CT scans [14, 15],signal dropout on opposed-phased imaging for chemical shift MRI , or benign-proven histopathology, which were non-functional diagnosed by endocrine examination. Dignosis of bilateral adrenal thickening was defined as radiologically diffuse thickening of bilateral adrenal glands. Size of adrenal tumors refered to the diameter of the largest adrenal tumor.
2.4 Statistical analysis
Normally distributed continuous variables are presented as means and standard deviations, and non-normally distributed variables are presented as medians and ranges. Categorical variables are expressed as frequencies and percentages. Continuous data were compared using a one-way analysis of variance. Categorical data were analyzed using the chi-squared test or Fisher’s exact probability test. Statistical significance was set at P < 0.05. All data analyses were performed using SPSS (version 26.0; IBM, Armonk, NY, USA).