Should Aldosterone Suppression Tests Be Conducted During a Particular Phase of the Menstrual Cycle, and, If So, Which Phase?

Results of a Preliminary Study

Ashraf H. Ahmed; Richard D. Gordon; Gregory Ward; Martin Wolley; Cynthia Kogovsek; Michael Stowasser

Disclosures

Clin Endocrinol. 2015;83(3):303-307. 

In This Article

Materials and Methods

Setting

This study was completed between July 2012 and May 2014 in the Endocrine Hypertension Research Centre (EHRC), Greenslopes and Princess Alexandra Hospitals, Brisbane. The diagnosis of PA and its subtype was based on the Centre's strict protocol.[17] The institutional ethics committee approved the study.

Confirmation of the Diagnosis of PA

All hypertensive patients with a plasma ARR greater than 70 (plasma aldosterone expressed in pmol/l, plasma active renin concentration in mU/l) on at least 2 occasions were offered FST to definitively confirm or exclude PA. After hypokalaemia had been corrected with potassium supplements and while encouraged to maintain a liberal dietary salt intake, patients undergoing FST were admitted to hospital to ensure adherence to the dietary and posture requirements of the test protocol and to facilitate monitoring of plasma potassium levels and other parameters. Blood was collected at 0700 h after overnight recumbency and at 1000 h after at least 2 h of upright posture, for measurement of ARR. Prior to testing, diuretics (including spironolactone and amiloride) were always ceased for at least 4 weeks, and, wherever possible, beta-blockers, dihydropyridine-type calcium channel antagonists, angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists were ceased for at least 2 weeks and withheld throughout the subsequent diagnostic steps. Control of hypertension was maintained where necessary during the period of diagnostic workup by replacing these agents with prazosin and verapamil slow-release, with or without hydralazine.

The diagnosis of PA was confirmed when, after 4 days administration of a high sodium diet and slow-release sodium chloride (Slow Na, 30 mmol three times daily with meals) and of fludrocortisone acetate (0·1 mg every 6 h), plasma aldosterone concentration, measured at 1000 h in seated patients after at least 2 h upright (sitting, standing or walking), failed to suppress to less than 165 pmol/l, provided that on day 4: (i) upright plasma DRC was suppressed to less than 8·4 mU/l; (ii) plasma potassium was within the normal range, thereby avoiding the possibility of a missed diagnosis due to hypokalaemia-induced suppression of aldosterone release, or conversely a false-positive FST due to stimulation of aldosterone by hyperkalaemia from over-replacement; and (iii) plasma cortisol concentration was lower at 1000 h (seated or standing) than at 0700 h (recumbent overnight), excluding an acute increase in corticotropin, which could prevent suppression of aldosterone. Thus, if plasma DRC was unsuppressed, cortisol rose or plasma potassium was raised on day 4, or alternatively if plasma potassium was subnormal on day 4, an otherwise positive or negative result, respectively, would be labelled 'inconclusive'.

Reporting the Menstrual History During FST

For premenopausal women who completed the FST between July 2012 and May 2014, the menstrual history was recorded as follows: date of the last menstrual period (LMP) before FST, date of the last day of FST, date of the next period after FST, regularity of the cycle and duration. Based on the premise that duration of the luteal phase is 14 days regardless of the duration of the cycle, the above information was used to calculate the ovulation date (regarded as 14 days before the date of the next period after FST) and the phase of the cycle during the last day of FST. Aldosterone levels in both luteal and follicular groups were compared with those in 10 age-matched hypertensive male patients who were also undergoing FST as part of their diagnostic workup for suspected PA.

Analytic Methods

Plasma DRC was determined by direct renin assay which uses chemiluminescent immunoassay technology (DiaSorin, Liaison, Italy). DRC levels that were below the lower limit of quantification were rounded up to 2 mU/l. The interassay coefficient of variation was 7·4% at 26 mU/l and 6·0% at 106 mU/l. The intra-assay coefficients of variation at 15, 33, 82 and 258 mU/l were 3·7%, 2·8%, 2·0% and 1·2%, respectively. The assay working range was up to 500 mU/l. PRA was assayed by GammaCoat radioimmunoassay (DiaSorin). The interassay coefficients of variation were 5·6%, 7·6% and 6·8% at 1·6, 10·7 and 15·2 ng/ml/h, respectively. The intra-assay coefficient of variation was 10·0% at 1·6 ng/ml/h, 4·6% at 6·2 ng/ml/h and 9·4% at 17·9 ng/ml/h. LH, FSH, oestradiol and progesterone were measured by immunoassay (Abbott Diagnostics-Abbott Architect, Sydney, NSW, Australia). Cortisol was measured by immunoassay (Beckman Coulter Australia). Plasma aldosterone was measured by HPLC-MS/MS, using a method recently validated in our laboratory.[16] The interassay coefficient of variation for aldosterone was 9·3% at 242 pmol/l and 6·0% at 1321 pmol/l. The intra-assay coefficient of variation for aldosterone was 7·3% at 238 pmol/l and 4·3% at 1344 pmol/l.

Statistical Analysis

SPSS 18 for Windows (SPSS, Chicago, IL, USA) was used to analyse the data. Data are presented as median (range in parenthesis) unless otherwise stated. Nonparametric testing (Mann–Whitney test) was used for comparisons between the three groups. A 'P' value of less than 0·05 was considered statistically significant.

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