Endocrine Abstracts

Low-renin hypertension (LRH) with normal or elevated aldosterone levels is considered part of the spectrum of aldosterone-associated hypertension, and can cause poorly-controlled hypertension. We studied patients diagnosed with LRH, comparing their clinical and biochemical characteristics with patients diagnosed with primary hyperaldosteronism (PHA).

Methods

Retrospective. Diagnosis in a general Endocrinology out-patient clinic over 8 years, with strict application of Endocrine-Society Guidelines for PHA screening/diagnosis. Aldosterone/Renin (ARR) screening on medication, except for mineralocorticoid-receptor blockers or amiloride was positive when ≥ 20 (aldosterone and direct renin measured by Radioimmunoassay in pg/ml). Captopril challenge test (CCT) was positive for PHA on doxazosine and/or long-acting verapamil and/or hydralazine if aldosterone level ≥ 130 and/or ARR ≥ 50 2 hours post-25 mg captopril. Patients negative for PHA with normal/high basal CCT aldosterone, together with basal ARR ≥ 50 or low renin throughout CCT, were diagnosed with LRH. Clinical characteristics of both groups were compared. Parametric values expressed as mean (SD); non-parametric values as median [interquartile range]. SPSS 25.

Results

Diagnosis: 46 patients PHA, 80 LRH. Age at diagnosis: PHA: 57.0 (SD:11.2), LRH: 64.7 (SD:12.9), P = 0.001. PHA: 21/46 (46%) women, LRH: 16/80 (20%), P < 0.001.

Moderate hypertension

PHA: 21/46 (45.7%), LRH: 52/80 (65%), P = 0.04. Severe Hypertension: PHA 25/26 (54.3%), LRH: 28/80 (35%), P = 0.04. Resistant hypertension: PHA: 16/46 (34.8%) vs LRH: 5/80 (6.3%), P < 0.0001. All aldosterone and ARR levels were significantly higher in PHA than LRH, with screening and basal CCT values showing overlap. Renin levels were not significantly different at screening, nor throughout CCT. At screening, PHA vs LRH respectively: Aldosterone: 284.3 (SD:202.1) vs 206.11 (SD:99.3), P = 0.023. Renin: 3.8 (SD: 4.9) vs 5.2 (SD:4.6), P = 0.13. ARR: 109.9 (SD:8.5) versus: 52.9 (SD: 33.6), P < 0.0001. Baseline CCT: PHA vs LRHT respectively: Aldosterone 296.2 (SD: 194.5) vs 146.3 (SD:56.7), (P < 0, 001). Renin 3.0 (SD:3.7) vs 3.3 (SD: 2.15), P = 0.54. ARR: 162 (SD: 126.0) vs 57.7 (SD: 38.9). P < 0.001. 2-hour CCT: PHA vs LRH respectively: Aldosterone 221.57 (SD:117.3) vs 80.3 (SD 37.2), P < 0.001. Renin: 2.15 [1.25–4.0] vs 3.2 [2.2–4.8] P = 0.53. ARR: 69.3 [52.1–165.8] vs 22.6 [12.6–37.0], P = 0.001.

Conclusions

LRH can be diagnosed with the CCT when applying Endocrine-Society PHA guidelines. This entity was more frequent in a general Endocrinology out-patient clinic than PHA, and over a third of patients had severe HT. Given LRH’s previously-described favorable response to mineralocorticoid-receptor blockers, we believe that LRH should be diagnosed, and specifically treated as an aldosterone-associated hypertension.