Biochemical assessment of adequate levothyroxine replacement in primary hypothyroidism differs with different TSH assays: potential clinical implications.

AIM: Thyroid stimulating hormone (TSH) assays provided by Abbott Laboratories and Roche Diagnostics are used by approximately 75% of laboratories in the UK. We assessed the potential impact of Abbott and Roche TSH assay differences on the biochemical assessment of levothyroxine replacement in primary hypothyroidism. METHOD: Samples from 100 consecutive primary care patients (83 women, median age 64 years, IQR 51-73 years) with primary hypothyroidism on adequate levothyroxine based on an Abbott Architect TSH in the reference range were analysed for TSH on Roche cobas within 24 hours. The Abbott and Roche TSH results were compared. Over 1 year, TSH results from patients in primary care from the laboratories with Abbott and Roche methods were compared. RESULTS: The median (IQR) Roche TSH (2.5 (1.3-3.6) mIU/L) was 30%±10% higher (p<0.001) than Abbott TSH (1.9 (1.1-2.6) mIU/L). Although all Abbott TSH results were in the Abbott specific reference range, 14 patients (14%) had Roche TSH results above the Roche specific reference range. In the 1 year gather, Roche TSH (1.9 (1.3-2.9) mIU/L, n=103 932) results were higher (p<0.001) than Abbott TSH (1.5 (1.0-2.2) mIU/L, n=1 10 544) results. The TSH results were above their assay-specific upper reference limit in 10.7% of Roche results and 4.2% of Abbott results. CONCLUSION: Biochemical assessment of levothyroxine replacement may be dependent on the type of TSH assay. Laboratorians and clinicians should be aware that the lack of harmonisation between TSH methods and their assay-specific reference ranges may potentially lead to different patient management decisions. We suggest lot verification in laboratories should include processes to identify cumulative drift in assay performance.

The Relationship Between Intact Parathyroid Hormone and 25-Hydroxyvitamin D in United Kingdom Resident South Asians and Whites: A Comparative, Cross-Sectional Observational Study.

Ethnic differences in intact parathyroid hormone (iPTH) at similar total 25 hydroxyvitamin D [25(OH)D] concentrations have been reported between US resident Whites, Blacks, and Hispanics, but this has not been studied between South Asians and Whites. We, therefore, compared the iPTH relationship to 25(OH)D in UK resident South Asians and Whites. A comparative, cross-sectional observational study in which demographic and laboratory data on South Asian and White residents of Wolverhampton, UK were analyzed. Log-log models measured the association between 25(OH)D and the interaction term of ethnicity and iPTH. Seven hundred and seventy-two patients consisting of 315 white subjects (208 women) and 457 South Asian subjects (331 women) were studied. Compared to South Asians, White subjects were older, had higher serum concentrations of 25(OH)D, creatinine (lower eGFR), adjusted calcium and magnesium, but similar concentrations of iPTH and phosphate. In an adjusted model, variables significantly associated with 25(OH)D included age, creatinine, adjusted calcium and ethnicity; but not iPTH and the interaction term of ethnicity and iPTH (beta coefficient -0.071, 95% CI -0.209, 0.067, p=0.32). In our study cohort, iPTH was not, per se, influenced by 25 (OH)D. We found no ethnic differences in the association between iPTH and 25(OH)D between South Asians and White UK residents.

The diagnosis and management of subclinical hypothyroidism is assay-dependent- Implications for clinical practice.

OBJECTIVE: We assessed the commutativity of Roche and Abbott thyroid assays in the diagnosis and management of subclinical hypothyroidism (SCH). The Roche and Abbott thyroid assays are used by approximately 75% of clinical laboratories in the UK. METHOD: Consecutive samples received from primary care on patients with SCH who had a raised thyroid-stimulating hormone (TSH) <10 mIU/L and a normal free thyroxine (fT4) from two laboratories using either Roche or Abbott thyroid assays were identified over 10 working days. Following identification, samples were analysed at the other site within 24 hours. Diagnostic and management discordance were studied using the relevant manufacturer-provided reference ranges. RESULTS: We identified 93 patients with SCH (53 using the Roche assay). Roche TSH and fT4 results were respectively 40% ± 15% and 16% ± 7% higher (P < .001) compared to Abbott results. Of the 93 patients, 41 (44%) were concordant for SCH on both methods. Of the 53 patients with SCH on the Roche assays, 40 (75.5%) had normal thyroid function and 13 (24.5%) had SCH when analysed using the Abbott assays. Of the 40 patients with SCH on the Abbott assays, 28 (70%) had SCH and 12 (30%) had results indicative for levothyroxine replacement when analysed on the Roche assays. Of these 12 patients, four had TSH > 10 mIU/L, five had low fT4 and three had both. CONCLUSION: The diagnosis and management of SCH is strikingly different when using TSH and fT4 assays provided by Abbott Laboratories and Roche Diagnostics. Clinicians and laboratorians should be aware that between-assay differences and variations in reference ranges will directly impact the diagnosis and management of subclinical hypothyroidism.

Salivary cortisol and cortisone responses to tetracosactrin (synacthen).

BACKGROUND: To establish cutoff values for salivary liquid chromatography tandem mass spectroscopy cortisol and cortisone in defining adequate adrenocortical function during a standard synacthen test. METHODS: We compared salivary liquid chromatography tandem mass spectroscopy cortisol and cortisone responses to those of serum cortisol measured on the Roche E170 immunoassay analyser and the Abbott Architect i2000 before and 30 min and 60 min following 0.25 mg of intravenous synacthen. RESULTS: Correlations of salivary cortisol and cortisone were bimodal and linear, respectively. Based on these correlations, adequate salivary cortisol and cortisone responses to synacthen were extrapolated from a serum cortisol (Roche) cut-off of 550 nmol/L and defined as 15 nmol/L and 45 nmol/L, respectively. The Abbott method correlated well with the Roche but gave results that were about 20% lower than the Roche method. CONCLUSIONS: Measurement of salivary cortisol and cortisone responses offers an alternative to those of serum cortisol during a synacthen test in the investigation of adrenal hypofunction.

Vitamin D: a negative acute phase reactant.

OBJECTIVE: We evaluated the effect of the systemic inflammatory response (SIR), as provoked by elective orthopaedic surgery, on serum vitamin D [25-(OH)D]. METHODS: Serum 25-(OH)D, serum vitamin D binding protein (VDBP) and urinary VDBP were measured in 30 patients before and 48-hours after knee or hip arthroplasty. C-reactive protein (CRP) was measured to assess the SIR. RESULTS: The mean (SD) CRP increased following surgery [5.0 (5.5) vs 116.0 (81.2) mg/L; P<0.0001] as did urine VDBP/Creatinine ratio [8 (9) vs 20 (25) pg/mmol; p=0.0004]. Serum 25-(OH)D [56.2 (30.3) vs 46.0 (27.6) nmol/L; p = 0.0006] and serum VDBP [334 (43) vs 298 (37) mg/L]; P<0.0001] decreased. CONCLUSIONS: Serum 25-(OH)D is a negative acute phase reactant, which has implications for acute and chronic inflammatory diseases. Serum 25-(OH)D is an unreliable biomarker of vitamin D status after acute inflammatory insult. Hypovitaminosis D may be the consequence rather than cause of chronic inflammatory diseases.

The effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on serum uric acid in patients without gout: a prospective study.

OBJECTIVE: Acute gout is associated with a decrease in serum uric acid (SUA) that is considered to be in response to acute inflammation but it may be a feature of gout itself. We, therefore, aimed to investigate the effect of the acute systemic inflammatory response (SIR) on SUA concentrations in subjects without gout. METHODS: SUA and urinary excretion of uric acid (UA) (expressed as fractional excretion of UA; FEua%) were measured in 30 patients before and 48 h after elective knee or hip surgery. The SIR was assessed by measuring serum CRP and urine microalbumin excretion [expressed as the albumin-creatinine ratio (ACR)] before and after surgery in the same patients. RESULTS: The mean (s.d.) serum CRP increased following surgery [5.0 (5.5) vs 116.0 (81.2) mg/l; P < 0.0001) as did urine ACR [0.85 (1.03) vs 2.10 (2.60) mg/mmol; P = 0.004]. SUA decreased following surgery [312 (64) vs 282 (82) µmol/l; P = 0.0033] but FEua% was unchanged [6.4 (2.3) vs 7.3 (3.3)%; P = 0.1726]. CONCLUSION: The SIR is associated with a decrease in SUA concentrations in normouricaemic patients without gout. The decrease in SUA concentrations is not due to increased urinary excretion of UA. This study supports the notion that the decrease in SUA during acute gout is due to the associated SIR rather than gout per se.

Hypergonadotrophic hypogonadism due to testicular adrenal rest tumours presenting with hypogonadotrophic hypergonadism.

Primary testicular failure is characterized by low serum testosterone with appropriately high serum gonadotrophins, that is hypergonadotrophic hypogonadism. We report on a 27-year-old man with congenital adrenal hyperplasia (CAH) and infertility due to testicular adrenal rest rumours (TART) resulting in primary testicular failure but presenting with azoospermia, elevated serum testosterone and very low serum gonadotrophins. Hypergonadotrophic hypogonadism was unmasked by increasing glucocorticoid dosage. It is important to recognise the limitations of follicle-stimulating hormone, luteinising hormone and testosterone in assessing testicular function in men with CAH. Abnormal semen analysis may be the best indicator of testicular dysfunction in men with CAH.