Between 2012-2016, twenty-five patients completed full work-up and were diagnosed with PA; 14 with BD and 11 with UD, see Table 1 for baseline characteristics. Seven additional patients, listed in Online Resource 1, were diagnosed during the period and treated as BD, without undergoing AVS. Two of them were unable to discontinue treatment affecting the RAAS because of comorbidities, four had no SIT because of comorbidities (aldosterone/renin ratio, ARR, range 177-318 pmol/mIU) and one rejected AVS. These seven patients all had a long history of HT and hypokalemia and responded well to MRA. They have been excluded from statistical analysis regarding subgroups. One more patient completed work-up and was diagnosed with pheochromocytoma and therefore excluded. See Fig. 1 for overview of patients. Ten out of 11 patients with UD underwent adrenalectomy, all were histopathologically diagnosed with cortical adenoma. One patient emigrated before surgery. One patient with BD (no. 11, Online Resource 2) underwent adrenalectomy as an attempt to lower aldosterone levels since extensive HTM, including MRA, was insufficient and the patient was severely ill. The decision was made after expert consultation from abroad and repeated AVS. Histopathological examination revealed hyperplasia, as expected.
From BG, 12/14 patients initially had morning s-aldosterone levels >430 pmol/l, all had values >430 pmol/l on repetition. In UG, one patient had s-aldosterone <430 pmol/l despite elevated 24 h urinary aldosterone, further addressed in Discussion chapter. Urinary aldosterone was >25 mg/24 h in 5/10 from BG, and 6/8 from UG. See Table 2 for results from case detection. Seven patients highly clinically suspective for PA had DRC >5 mIU/l at case detection (range 5,6-21,0 mIU/l). They all went through full work-up and PA was confirmed, see Online Resource 3. Three of them had DRC ≤5mIU/l later on and all seven had s-aldosterone >190 pmol/l after SIT. For the 10-year period, DRC at 8 am was significantly lower after 10 h bedrest (median 4,25; IQR 3,7) compared with that after 15 min sitting (median 5; IQR 9,4), p=0,03.
Saline infusion test
All twenty-five confirmed PA patients had post-infusion s-aldosterone >190 pmol/l. No statistical difference was seen in post-infusion s-aldosterone for the two subgroups during the 5-year period, see Table 2. One patient rejected further work-up after SIT and six patients were unable to undergo SIT because of comorbidities. These seven patients are listed in Online Resource 1. Five patients underwent more than one SIT; one had subcutaneous saline infusion on the first test, one had borderline results and three needed repetition because of HTM interfering with RAAS and/or excessive liquorice consumption. These test results were excluded and the patient with excessive liquorice consumption was tested again after three months without liquorice consumption.
Following a positive SIT, all patients underwent an adrenal CT scan. Roughly half of the patients with BD had an adrenal nodule on CT, see Table 2. In total, fifteen patients had a unilateral adrenal nodule, 9 of whom had ipsilateral UD confirmed by AVS, positive predictive value of 0,6. Six patients with adrenal nodule had BD.
Adrenal venous sampling and success rate
Thirty AVS were performed on 25 confirmed PA patients during the 5-year period. Four tests were excluded and repeated because of difficulties accessing the right adrenal vein and/or HTM greatly affecting RAAS. One patient from BG underwent a second AVS to plan adrenalectomy. See Online Resource 2 for borderline AVS results and repeated testing. All except one patient from UG had LI>4. Three patients from BG had LI>3; two of them did not have contralateral suppression of aldosterone secretion and one patient’s sibling had previously been diagnosed with unilateral hyperplasia and relapsed a few years later, therefore the presented patient was classified and treated as BD. See Table 2 for LI of subgroups. Success rate for AVS based on selectivity index during the 5-year period was 87% (26/30).
For the 10-year period, median duration of follow-up was 6 years, IQR 4. In the 2007-2016 cohort, patients went from 157/90-95 mmHg under three HTM before specialized treatment, to 143-145/86-89 mmHg under 1,8-2,3 HTM one year after initiation of specialized treatment. Both the UG and BG had a significant improvement in SBP during follow-up (p<0,001 for both groups) and decreased need for HTM (p=0,002 and p=0,04, respectively). See Table 3 for results from follow-up of patients diagnosed with PA during 2007-2016. A decrease in DBP was seen in both groups, significant for the UG (p<0,001). All 31 patients from BG were started on MRA treatment; 19 (61%) on eplerenone and 12 (39%) on spironolactone. The majority of the eplerenone group (14/19) were men. Two out of 27 (7%) from UG and 1/31 (3%) from BG needed potassium supplementation at the end of follow-up, significantly fewer than at case detection when all patients needed potassium supplementation (p<0,001 for both subgroups).
Comparing values from median of follow-up (6 years) to pre-intervention, SBP and DBP decreased significantly in the UG (mean SBP 157 ± 16 to 138 ± 15 and DBP 95 ± 11 to 84 ± 11), p=0,003 and p=0,01, respectively. Same applies to the BG (SBP 158 ± 19 to 137 ± 11 and SBP 90 ± 11 to 84 ± 7), p<0,001 and p<0,05, respectively. From baseline to median of follow-up, number of HTM decreased for both groups (UG 2,8 ± 0,9 to 2,6 ± 1,5 and BG 2,4 ± 1,0 to 2 ± 0,9) although this difference was not statistically significant, p=0,6 and p=0,1, respectively. Based on PASO criteria  at 12 months post-op, 5/26 (19%) from UG had complete clinical success and 21/26 (81%) had partial clinical success.