Adrenal Androgens Versus Cortisol for Primary Aldosteronism Subtype Determination in Adrenal Venous Sampling

Marianna Viukari; Eeva Kokko; Ilkka Pörsti; Helena Leijon; Tiina Vesterinen; Tero Hinkka; Minna Soinio; Camilla Schalin-Jäntti; Niina Matikainen; Pasi I. Nevalainen

Disclosures

Clin Endocrinol. 2022;97(3):241-249. 

In This Article

Results

Patient Characteristics

Patient characteristics are displayed in Table 1. Most patients presented with normokalaemia, but total of 17 were on MRAs, while 29 were using potassium supplements. According to the AVS results, 29 patients had a unilateral disease and consequently underwent unilateral adrenalectomy. The division to the APA and APN subgroups was based on CYP11B2 staining of the histological samples (Figure S1).

Outcome of the Adrenalectomy and Long-term Cure

Clinical data post-adrenalectomy in the APA and APN subgroups is presented in Table 2. No significant differences in blood pressure, daily defined dose (DDD) of antihypertensive medications, postoperative plasma potassium concentration or aldosterone-to-renin ratio (ARR) were observed between the groups.

In accordance with the PASO criteria,[26] complete or partial biochemical cure 3–6 months after adrenalectomy was achieved in all 29 patients. Postoperative aldosterone and renin analyses were missing from two patients but based on the resolution of their hypokalaemia they were classified as biochemically cured. Complete clinical cure was achieved in 8 (27.6%) patients, partial clinical cure in 19 (65.5%) patients and clinical cure was absent in 2 (6.9%) patients (Table 2).

Patients in the adrenalectomy group were followed up to 7 years (mean 4.3 ± 2 years). The APA subgroup retained normokalaemia without potassium supplements suggesting biochemical remission, while in the APN subgroup three (33.3%) patients lost the postoperative improvement and presented with absent clinical improvement during the long-term follow-up. Two of the patients had low potassium level (<3.3 mmol/l) and one had restarted spironolactone due to hypertension and hypokalaemia. All the remaining patients in the APN subgroup used antihypertensive medication other than MRA at follow-up, but with a lower DDD than before adrenalectomy, and thus they were classified as having reached partial clinical cure. In the APA subgroup, 40% of the patients had no need of antihypertensive medication and presented with complete clinical cure.

Selectivity Index in AVS

Medians for cortisol, androstenedione, DHEA and DHEAS from the left and right AV and IVC, as well as SI values calculated for each hormone are displayed in Table 3. Expectedly, the step-up between DHEAS from each AV compared with IVC was modest but significant (p < .001), resulting in low SI-values when compared with the three other hormones. The right and left SIs for androstenedione and DHEA were significantly higher (p < .001) than for cortisol.

Significant positive correlations (p < .001) were observed between the SI values for cortisol and adrenal androgens, both in the right (r = .639, .689 and .563 for androstenedione, DHEA and DHEAS, respectively) and left (r = .532, .672, and .554 for androstenedione, DHEA and DHEAS, respectively) sides (Figure S2). The concentrations of adrenal androgens and cortisol did not differ in the AVs when the left and right or the dominant and the nondominant sides were compared (Table 3 and Table 4). The same applied for subgroup analysis in the adrenalectomy and the medical therapy groups. In one patient, the right-side SI values for both androstenedione and DHEA were low (2.48 and 3.25, respectively), whereas with cortisol the SI was 20.3.

Lateralisation Index and Contralateral Suppression Index in AVS

The LI values and CSI values are presented in Table 4. There were strong positive correlations between LIs corrected with androstenedione, DHEA and DHEAS in comparison with cortisol-corrected LI (r = .905, .873 and .936, respectively, p < .001 for all, Figure S3). In the adrenalectomy group, no statistically significant differences were detected between LIs corrected with each adrenal androgen when compared with cortisol. However, in the APA subgroup, DHEAS-corrected LI was significantly higher than that with cortisol (p = .035), while in the APN subgroup no such differences were observed.

Similarly, there were strong positive correlations between CSIs with cortisol and adrenal androgens across all patients (r = .907, .963 and .959 for androstenedione, DHEA and DHEAS, respectively, p < .001 for all, data not shown).

We used ROC analysis to estimate the optimal LI cut-off values for the adrenal androgens. These were 4.2, 4.5 and 4.6 for androstenedione, DHEA and DHEAS, respectively (Figure 1). There were no differences between the AUCs of the ROC curves between the adrenal androgens and cortisol.

Figure 1.

ROC curve of lateralisation indexes calculated with cortisol and androstenedione, DHEA and DHEAS. A4, androstenedione; DHEA, dehydroepiandrosterone; DHEAS, DHEA sulphate; ROC, receiver operating characteristics

Analysis of Subjects With Discrepant Results Between Cortisol and Adrenal Androgens

We evaluated whether using the determined LI cut-off values for androstenedione, DHEA and DHEAS would have resulted in a different choice of treatment in any of the patients. Eight cases with cortisol-corrected LI from 2.00 to 5.88 had discrepant LI with adrenal androgens compared to cortisol. Table S1 displays all 13 subjects who fell into this LI range. Single adrenal androgens performed variably when compared with cortisol. In 10 patients with complete analyses available, at least 2 out of the 3 measured adrenal androgen-corrected LIs were concordant with the cortisol-corrected LIs. In the remaining three patients with missing DHEAS analyses, at least one out of two LIs were also concordant with the cortisol-corrected LIs. Similar findings were observed in those patients who underwent adrenalectomy, among whom the long-term cure was retained in four subjects (two with APA and two with APN) and lost in two subjects with APN.

processing....