Evaluation of the ADVIA (R) Centaur (TM) TSH-3 assay

An analytical evaluation of the thyroid stimulating hormone (TSH-3) assay on the Sayer ADVIA(R) Centaur(TM) immunoassay system was performed. General analytical requirements (linearity, resistance to typical interferences, absence of a carry-over effect) were fulfilled and reproducibility was satisfactory. Inter-assay coefficient of variation (CV) of a human serum pool with a concentration of 0.014 mU/l was 22.3%; at concentrations between 0.26 and 83 mU/l CV was below 6%. Method comparison study demonstrated close agreement of TSH results compared to those obtained with the Roche Elecsys(R) 2010 TSH assay (ADVIA Centaur = 1.08 x Elecsys - 0.18 mU/l; r = 0.987; n = 324). Handling and practicability of the ADVIA Centaur system proved to be convenient with a very high sample throughput. We conclude that the ADVIA Centaur TSH-3 assay meets requirements for clinical use

A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma

BACKGROUND: Fractionated plasma metanephrine measurements are commonly used in biochemical testing in search of pheochromocytoma. METHODS: We aimed to critically appraise the diagnostic efficacy of fractionated plasma free metanephrine measurements in detecting pheochromocytoma. Nine electronic databases, meeting abstracts, and the Science Citation Index were searched and supplemented with previously unpublished data. Methodologic and reporting quality was independently assessed by two endocrinologists using a checklist developed by the Standards for Reporting of Diagnostic Studies Accuracy Group and data were independently abstracted. RESULTS: Limitations in methodologic quality were noted in all studies. In all subjects (including those with genetic predisposition): the sensitivities for detection of pheochromocytoma were 96%–100% (95% CI ranged from 82% to 100%), whereas the specificities were 85%–100% (95% CI ranged from 78% to 100%). Statistical heterogeneity was noted upon pooling positive likelihood ratios when those with predisposition to disease were included (p < 0.001). However, upon pooling the positive or negative likelihood ratios for patients with sporadic pheochromocytoma (n = 191) or those at risk for sporadic pheochromocytoma (n = 718), no statistical heterogeneity was noted (p = 0.4). For sporadic subjects, the pooled positive likelihood ratio was 5.77 (95% CI = 4.90, 6.81) and the pooled negative likelihood ratio was 0.02 (95% CI = 0.01, 0.07). CONCLUSION: Negative plasma fractionated free metanephrine measurements are effective in ruling out pheochromocytoma. However, a positive test result only moderately increases suspicion of disease, particularly when screening for sporadic pheochromocytoma

Beneficial effects of propylthiouracil plus L-thyroxine treatment in a patient with a mutation in MCT8

Context: Mutations of the monocarboxylate transporter 8 (MCT8) gene determine a distinct X-linked phenotype of severe psychomotor retardation and consistently elevated T-3 levels. Lack of MCT8 transport of T-3 in neurons could explain the neurological phenotype. Objective: Our objective was to determine whether the high T-3 levels could also contribute to some critical features observed in these patients. Results: A 16-yr-old boy with severe psychomotor retardation and hypotonia was hospitalized for malnutrition (body weight = 25 kg) and delayed puberty. He had tachycardia (104 beats/min), high SHBG level (261 nmol/liter), and elevated serum free T-3 (FT3) level (11.3 pmol/liter), without FT4 and TSH abnormalities. A missense mutation of the MCT8 gene was present. Oral overfeeding was unsuccessful. The therapeutic effect of propylthiouracil (PTU) and then PTU plus levothyroxine (LT4) was tested. After PTU(200 mg/d), serum FT4 was undetectable, FT3 was reduced (3.1 pmol/liter) with high TSH levels (50.1 mU/liter). Serum SHBG levels were reduced (72 nmol/liter). While PTU prescription was continued, high LT4 doses (100 mu g/d) were needed to normalize serum TSH levels (3.18 mU/liter). At that time, serum FT4 was normal (16.4 pmol/liter), and FT3 was slightly high (6.6 pmol/liter). Tachycardia was abated (84 beats/min), weight gain was 3 kg in 1 yr, and SHBG was 102 nmol/liter. Conclusions: 1) When thyroid hormone production was reduced by PTU, high doses of LT4 (3.7 mu g/kg.d) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone. 2) High T-3 levels might exhibit some deleterious effects on adipose, hepatic, and cardiac levels. 3) PTU plus LT4 could be an effective therapy to reduce general adverse features, unfortunately without benefit on the psychomotor retardation

Beneficial effects of propylthiouracil plus L-thyroxine treatment in a patient with a mutation in MCT8

Context: Mutations of the monocarboxylate transporter 8 (MCT8) gene determine a distinct X-linked phenotype of severe psychomotor retardation and consistently elevated T3levels. Lack of MCT8 transport of T3in neurons could explain the neurological phenotype. Objective: Our objective was to determine whether the high T3levels could also contribute to some critical features observed in these patients. Results: A 16-yr-old boy with severe psychomotor retardation and hypotonia was hospitalized for malnutrition (body weight = 25 kg) and delayed puberty. He had tachycardia (104 beats/min), high SHBG level (261 nmol/liter), and elevated serum free T3(FT3) level (11.3 pmol/liter), without FT4and TSH abnormalities. A missense mutation of the MCT8 gene was present. Oral overfeeding was unsuccessful. The therapeutic effect of propylthiouracil (PTU) and then PTU plus levothyroxine (LT4) wastested. After PTU (200 mg/d), serum FT4was undetectable, FT3was reduced (3.1 pmol/liter) with high TSH levels (50.1 mU/liter). Serum SHBG levels were reduced (72 nmol/liter). While PTU prescription was continued, high LT4doses (100 μg/d) were needed to normalize serum TSH levels (3.18 mU/liter). At that time, serum FT4was normal (16.4 pmol/liter), and FT3was slightly high (6.6 pmol/liter). Tachycardia was abated (84 beats/min), weight gain was 3 kg in 1 yr, and SHBG was 102 nmol/liter. Conclusions: 1) When thyroid hormone production was reduced by PTU, high doses of LT4(3.7 μg/kg·d) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone. 2) High T3levels might exhibit some deleterious effects on adipose, hepatic, and cardiac levels. 3) PTU plus LT4could be an effective therapy to reduce general adverse features, unfortunately without benefit on the psychomotor retardation. Copyrigh