Primary bilateral macronodular adrenal hyperplasia: clinical and laboratory features

Abstract

BACKGROUND: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is characterized by bilateral benign adrenocortical lesions, which in some cases lead to Cushing syndrome (CS). Due to the low detection, non-specific, erased clinical picture and slow, long-term progression, it is difficult to assess the true prevalence of PBMAH. This also leads to fairly limited literature data. A detailed analysis of biochemical, imaging parameters, the clinical presentations, in particular, an assessment of the course of comorbidities (arterial hypertension (AH), diabetes (DM), osteoporosis), is necessary to develop an algorithm for managing patients with PBMAH.AIM: Analysis of clinical and laboratory characteristics of patients with various forms of PBMAH.MATERIALS AND METHODS: A single-center, retrospective, observational, cross-sectional study was carried out. This study included 110 patients with PBMAH who got referred to the National Research Center for Endocrinology in the period from 2013–2023. We carried out comparative and correlation analysis of hormonal (plasma cortisol concentrations after 1 mg dexamethasone (1-mg DST), urinary free cortisol (СКМ), ACTH), biochemical (glycated hemoglobin), radiological data (nodular tissue volume), course of comorbidities (metabolic syndrome, DM, AH, osteoporosis) in three groups of patients: with overt CS, mild autonomous cortisol excess (MACE) and comorbid diseases, and patients with PBMAH without hormonal activity.RESULTS: Among 110 patients 79.1% were women, median age — 60 [51; 68]. The proportion of hormonally inactive forms of PBMAH was 37.3%, the overt CS and MACE was detected in 25.4 and 37.3% consequently. According to the hormonal ­examination data: the cortisol level during 1-mg DST was 173.8 nmol/l [86.0; 441.0], ACTH — 3.35 pg/ml [1.00; 8.00], СКМ — 445.5 [249.0; 900.0]. Statistically significant positive moderate correlations were found between the volume of nodular tissue and the level of cortisol after PDT1 (r=0.40, p<0.001), СКМ (r=0.29, p<0.004), as well as a negative moderate correlation between the volume and the level of ACTH (r=-0.40, p<0.001). When analyzing the prevalence and clinical severity of comorbid conditions, DM was diagnosed in 22 (53.7%), AH in 36 (87.8%), obesity and osteoporosis — 23 (56%) and 3 (7.3%) patients. There was no statistically significant difference in the prevalence of CS-associated diseases among the above groups (p=0.56).CONCLUSION: PBMAH is a heterogeneous pathology with different clinical, hormonal, and imaging characteristics. A correlation was found between the volume of nodular tissue and the degree of hormonal activity of PBMAH. The obtained results emphasize the difficulty in determining clear indications for surgical treatment in the group of patients with MACE. The radicality of proposed surgical procedure should be weighed against its potential complications.