Concordance between thyroglobulin antibody assays.

BACKGROUND: Antithyroglobulin antibodies are a prevalent cause of interference in serum thyroglobulin immunoassays. Current guidelines recommend that antithyroglobulin antibodies should be measured concurrently with thyroglobulin when monitoring thyroid cancer patients post-thyroidectomy. However, the concordance between different antithyroglobulin assays has been questioned despite the availability of an international thyroglobulin antibody Reference Preparation. METHODS: Four antithyroglobulin assays currently in use in UK laboratories (Siemens Immulite(®), Brahms GmbH, PerkinElmer AutoDELFIA and Siemens ADVIA Centaur(®)) were compared in a cohort of 145 thyroid cancer patients. RESULTS: Using reference data provided by the kit manufacturer, concordance between the assays was 74%. Adjusting the cut-offs to maximize agreement increased concordance to 90%. Recovery of exogenous thyroglobulin using the Brahms Tg-plus immunoradiometric assay was neither a specific nor a sensitive test for the presence of a positive antibody result by any assay. CONCLUSIONS: Despite the availability of an international reference preparation, current antithyroglobulin assays show unacceptable variance.

Primary hyperaldosteronism due to adrenal microadenoma: a curable cause of refractory hypertension.

UNLABELLED: The diagnosis of primary hyperaldosteronism due to microadenoma or unilateral adrenal hyperplasia can be challenging, since hypokalaemic alkalosis, high plasma aldosterone and a definite adenoma on imaging may all be absent. METHOD AND RESULT: We describe three cases of resistant hypertension (on > or = 5 antihypertensives) where hyperaldosteronism was suspected because of a suppressed plasma renin level despite treatment with multiple drugs which normally elevate renin. Renin mass was measured by a double-site chemi-immunoluminometric assay. All patients had normal plasma aldosterone levels. Hypokalaemia was present in the first two cases but computed tomography did not show clear cut adenomas. Adrenal vein sampling (AVS) revealed lateralisation (> 4 times higher aldosterone to cortisol ratio (ACR) on the affected than contra-lateral side). The third patient was normokalaemic and AVS showed only minimal lateralisation (ACR 1.3:1). The severe hypertension in all cases was reversed by adrenalectomy, with blood pressure falling to target despite withdrawal of all but one to two drugs. CONCLUSIONS: The robotic assay of renin mass permits rapid detection of patients in whom plasma renin is suppressed below the normal range. A suppressed plasma renin indicates abnormal Na+-retention, and--when not overcome by drugs such as angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers--may be the only clue to a curable adrenal adenoma. AVS is required to demonstrate lateralisation of aldosterone secretion, justifying adrenalectomy.

The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio.

BACKGROUND: There is continuing variation in diagnosis and estimated prevalence of primary hyperaldosteronism. The higher estimates encourage search for adrenal adenomas in patients with elevated ratios of plasma aldosterone to renin. However, it is more likely that patients with normal plasma K+ and aldosterone belong to the polygenic spectrum of low-renin hypertension rather than have the same monogenic syndrome as classic Conn's. Our primary hypothesis was that in low-renin patients with normal plasma K+ and aldosterone, a thiazide diuretic, bendroflumethiazide, would be as effective as spironolactone in overcoming the Na+ retention and lowering blood pressure. Secondary objectives were to compare the dose response for each diuretic and to evaluate amiloride as an alternative to spironolactone. METHODS AND RESULTS: Fifty-seven patients entered and 51 patients completed a placebo-controlled, double-blind, randomized crossover trial. Entry criteria included low plasma renin, normal K+, elevated aldosterone-renin ratio, and a previous systolic blood pressure response to spironolactone of > or = 20 mm Hg. Two doses each of spironolactone and bendroflumethiazide were compared. The crossover also included amiloride and losartan. Outcome measures were blood pressure, plasma renin, and other biochemical markers of diuretic action. Spironolactone 100 mg and bendroflumethiazide 5 mg caused similar falls in systolic blood pressure, whereas bendroflumethiazide 2.5 mg was 5/2 mm Hg less effective in reducing blood pressure than either bendroflumethiazide 5 mg or spironolactone 50 mg (P<0.005). Amiloride 40 mg was as effective as the other diuretics. Biochemical indices of natriuresis showed bendroflumethiazide to be less effective than either spironolactone or amiloride; plasma renin rose 4-fold on spironolactone but only 2-fold on bendroflumethiazide (P=0.003). CONCLUSIONS: In hypertensive patients with a low plasma renin but normal K+, bendroflumethiazide 5 mg was as effective as spironolactone 100 mg in lowering blood pressure, despite patients being selected for a previous large fall in blood pressure on spironolactone. Because this result differs from that expected in primary hyperaldosteronism, our finding argues against low-renin hypertension including a large, undiagnosed pool of primary hyperaldosteronism. However, spironolactone was the more effective natriuretic agent, suggesting that inappropriate aldosterone release or response may still contribute to the Na+ retention of low-renin hypertension.

The effect of potassium EDTA on the stability of parathyroid hormone in whole blood.

BACKGROUND: The stability of parathyroid hormone (PTH) in whole blood has not been well characterized. Previous studies show EDTA plasma samples to be more stable than serum samples. METHODS: Blood from 17 haemodialysis patients and five healthy volunteers was collected into serum separator tubes (SSTs) and potassium EDTA tubes (EDTA-Ts) and incubated at room temperature before separation and storage for PTH analysis using the Bayer Advia Centaur. RESULTS: Initial PTH concentrations were 7% higher (95% confidence interval [CI] 2-16%, P=0.016) in EDTA-Ts compared to the SSTs in the renal cohort. PTH concentrations in SSTs were significantly lower after 8 (10%, 95% CI 3-17%) and 20 h (22%, 95% CI 11-31%) but did not change significantly in EDTA-Ts (P=0.1543). PTH concentration in EDTA-Ts from healthy volunteers was also independent of incubation time (P=0.1165). CONCLUSION: The greater stability of PTH in whole blood anticoagulated with potassium EDTA allows PTH analysis to be offered to sites such as satellite clinics and primary care sites which do not have centrifugation and refrigeration facilities.