Endocrine Test Prince of Wales Hospital Department of Medicine and Therapeutics Division of Endocrinology Document Number: NTEC/PWH/MED-P-RENIN-V3 Prepared by Effective Date: 1 Dec 2014 Approved by Dr. Kitty KT Cheung, Resident Specialist, Department of Medicine & Therapeutics Dr. Jeffrey Kwok, Associate Consultant, Department of Chemical Pathology Dr. CC Chow, Chief of Service, Department of Medicine & Therapeutics Dr. Michael Chan, Consultant, Department of Chemical Pathology Renin-Aldosterone Test (Balance Study) 1. Objectives 1.1 To confirm the diagnosis of primary hyperaldosteronism. 1.2 To differentiate between aldosterone-producing adenoma and bilateral adrenal hyperplasia. 2. Scope 2.1 Patients with suspected primary hyperaldosteronism, including patients with Joint National Commission (JNC) stage 2 (> 160 – 179 / 100 - 109 mmHg), stage 3 (< 180 / 110 mmHg), or drug resistant hypertension; hypertension and spontaneous or diuretic-induced hypokalemia; hypertension with adrenal incidentaloma; or hypertension and a family history of early onset hypertension or cerebrovascular accident at a young age (< 40 years)1. 3. Procedure 3.1 On Day ‘0’ (Friday) to Day ‘5’ (Tuesday), give Na loading: NaCl 1,800 mg TDS orally to patient, this needs to be prescribed in clinic before clinical admission. Advise patient to start taking Na loading 4 days prior to admission and replace K deficit as outpatient by ensuring adequate slow K supplementation. 3.2 On Day ‘5’ (Tuesday), admit patient for investigation in the morning before 9 am. 3.3 Explain the reasons, procedure, and potential complications to the patient. 3.4 Take baseline blood including renal function test (send urgent) to ensure normokalemia (aim K ≥ 4.0 mmol/L). 3.5 Send spot urine for Na and K (send urgent). Page 1 of 4 Endocrine Test Prince of Wales Hospital Department of Medicine and Therapeutics Division of Endocrinology 3.6 If adequately salt loaded, as defined by spot urine Na ≥ 100 mmol/L (assume daily urine output ~ 2 L/day), and plasma K ≥ 4.0 mmol/L, proceed to start 24 Hr urine collection for aldosterone. 3.7 Continue NaCl 1,800 mg TDS orally until after finishing 24 Hr urine aldosterone collection: i. If inadequate spot urine Na, start IV salt loading (if not contraindicated), using IV 0.9% Normal Saline (NS) (=77 mmol Na/500 mL), 500 mL Q4H. ii. Resend urgent spot urine Na at 0 am, if 0 am spot urine Na ≥ 100 mmol/L at 0 am, can stop NS infusion. iii. If 0 am spot urine Na < 100 mmol/L at 0 am, continue NS infusion Q4H, resend urine for urgent spot urine Na at 8 am, proceed with 9 am blood. iv. If 8 am spot urine Na still < 100 mmol/L, discuss with patient to see if he / she would stay one more day for continuation of IV NS infusion (volume to be determined based on urine Na and clinical condition), then proceed to 9 am supine renin / aldosterone and 1 pm erect renin / aldosterone blood tests on the next day (Thursday). Alternatively, patient may choose to wait for the results and then consider readmission for repeating ‘Balance Study’ if the first set of results is inconclusive. v. Ensure spot urine Na adequate before commencement of 24 Hr urine collection for aldosterone. 3.8 Instruct patient to fast and remain recumbent from midnight till after supine renin & aldosterone blood taking. 3.9 Take 6 mL EDTA blood for supine renin & aldosterone and RFT at 9 am Day ‘6’ (Wednesday); send all blood specimens to laboratory immediately. 3.10 Ask patient to ambulate from 9 am to 1 pm (4 Hr). 3.11 Take 6 mL EDTA blood for erect renin & aldosterone at 1 pm Day ‘6’ (Wednesday); send all blood specimens to laboratory immediately. 3.12 Send all specimens to the laboratory according to the ‘NTEC Safe Practice Policy 2009-1: Safe handling of specimen collected by procedure performed at clinical area’. 3.13 Patient to be discharged after completion of 24 Hr urine for aldosterone collection, alternatively, patient can submit the 24 Hr urine specimen as out-patient the day after Page 2 of 4 Endocrine Test Prince of Wales Hospital Department of Medicine and Therapeutics Division of Endocrinology discharge (if necessary, spironolactone / eplerenone should only be started after completion of 24 Hr urine for aldosterone collection). 4. Precautions 4.1 Drugs should be avoided before the test1: i. Stop spironolactone, eplerenone, amiloride, potassium-wasting diuretics, products with liquorice for at least ≥ 4 weeks. ii. Stop -blockers, central α-2 agonists (e.g.: clonidine, α-methyldopa), NSAID, ACEI, ARB, renin inhibitors, and dihydropyridine Ca 2+ channel antagonists for at least ≥ 2 weeks. 4.2 Ensure normal plasma potassium level before proceeding to blood collection for renin and aldosterone at 9 am on Day ‘6’ (Wednesday); replace with syrup KCl for any hypokalemia, and resend renal function test until plasma K documented to be ≥ 4.0 mmol/L. 4.3 If patient cannot tolerate NaCl tablets; consider NS infusion after admission as an alternative mode of salt loading. 4.4 Ensure not to start spironolactone or eplerenone until completion of 24 Hr urine aldosterone collection. 5. Interpretation Reference (by Mass Spectrometry MS) Plasma renin activity 0.08 - 3.84 ng/mL/Hr Plasma aldosterone < 488 pmol/L Page 3 of 4 Endocrine Test Prince of Wales Hospital Department of Medicine and Therapeutics Division of Endocrinology 5.1. Primary hyperaldosteronism is suggested by: i. ii. iii. elevated plasma aldosterone renin suppression may or may not be present increased aldosterone to renin ratio 5.2. Adrenal adenoma (Conn’s syndrome) is suggested by: i. ii. criteria for primary hyperaldosteronism as above paradoxical drop in aldosterone in erect sample 5.3. Bilateral adrenal hyperplasia is suggested by: i. ii. criteria for primary hyperaldosteronism as above elevation in aldosterone in erect sample 6. Reference Document 1. Funder JW, Carey RM, Fardella C, et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 3266 - 81 Page 4 of 4
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