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1. Usefulness of Functional Thyroid-Stimulating and Thyroid-Blocking Immunoglobulin Bioassays in an Atypical Presentation of Graves' Disease.

Author

Sherfan J, Samad N, Hsieh A, Sullivan D, and Fuller PJ

Abstract

Background/objective: Thyroid-stimulating hormone (TSH) receptor antibody (TRAb) is well recognized as the pathogenic antibody that causes the clinical manifestation of Graves' disease (GD). Although the majority of TRAb measured in GD is due to thyroid-stimulating immunoglobulin (TSI), there are other functional classes of TRAb, ie, thyroid-blocking immunoglobulin (TBI) and neutral antibodies, which can alter the clinical course of the disease. We present a case of a patient who demonstrated interesting coexistence of both the forms using Thyretain TSI and TBI Reporter BioAssays., Case Report: A 38-year-old woman presented with thyrotoxicosis (TSH level, 0.01 mIU/L, free thyroxine level, >7.8 ng/mL [>100 pmol/L], and free triiodothyronine level, >32.6 pg/mL [>50 pmol/L]) to her general practitioner. She was treated with 15-mg carbimazole twice daily before the dose was reduced to 10 mg. Four weeks later, she developed severe hypothyroidism, with a TSH level of 57.5 mIU/L, free thyroxine level of 0.5 ng/mL (6.7 pmol/L), and free triiodothyronine level of 2.6 pg/mL (4.0 pmol/L). Carbimazole was ceased; however, she remained severely hypothyroid, with a TRAb level of 35 IU/L. Both TSI (304% signal-to-reference ratio) and TBI (56% inhibition) were present, with predominance of the blocking form of thyroid receptor antibodies (54% inhibition). Thyroxine was commenced, and her thyroid functions remained steady and TSI became undetectable., Discussion: The results of the bioassays confirmed that both TSI and TBI can coexist in a patient and that its action changes within a short period of time., Conclusion: Clinicians and laboratory scientists should be aware of the usefulness of TSI and TBI bioassays in the interpretation of atypical presentations of GD., Competing Interests: The authors have no multiplicity of interest to disclose., (© 2023 AACE. Published by Elsevier Inc.)

Published
2023
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2. Prescribed Water Intake in Autosomal Dominant Polycystic Kidney Disease.

Author

Rangan GK, Wong ATY, Munt A, Zhang JQJ, Saravanabavan S, Louw S, Allman-Farinelli M, Badve SV, Boudville N, Chan J, Coolican H, Coulshed S, Edwards ME, Erickson BJ, Fernando M, Foster S, Gregory AV, Haloob I, Hawley CM, Holt J, Howard K, Howell M, Johnson DW, Kline TL, Kumar K, Lee VW, Lonergan M, Mai J, McCloud P, Pascoe E, Peduto A, Rangan A, Roger SD, Sherfan J, Sud K, Torres VE, Vilayur E, and Harris DCH

Subjects
Humans, Male, Female, Adult, Middle Aged, Kidney pathology, Polycystic Kidney, Autosomal Dominant, Drinking
Abstract

BACKGROUND: Arginine vasopressin promotes kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). Increased water intake reduces arginine vasopressin and urine osmolality and may slow kidney cyst growth. METHODS: In this randomized controlled 3-year clinical trial, we randomly assigned adults with ADPKD who had a height-corrected total kidney volume in Mayo imaging subclass categories 1B to 1E and an estimated glomerular filtration rate of 30 ml/min/1.73 m2 or greater to (1) water intake prescribed to reduce 24-hour urine osmolality to 270 mOsmol/kg or less or (2) ad libitum water intake irrespective of 24-hour urine osmolality. The primary end point was the percentage annualized rate of change in height-corrected total kidney volume. RESULTS: A total of 184 patients participated in either the ad libitum water intake group (n=92) or the prescribed water intake group (n=92). Over 3 years, there was no difference in the annualized rate of change in height-corrected total kidney volume between the ad libitum (7.8% per year; 95% confidence interval [CI], 6.6 to 9.0) and prescribed (6.8% per year; 95% CI, 5.8 to 7.7) water intake groups (mean difference, −0.97% per year; 95% CI, −2.37 to 0.44; P=0.18). The difference in mean 24-hour urine osmolality between the ad libitum and prescribed water intake groups was −91 mOsmol/kg (95% CI, −127 to −54 mOsmol/kg), with 52.3% of patients achieving adherence to the target 24-hour urine osmolality and no reduction in serum copeptin over 3 years. The frequency of adverse events was similar between groups. CONCLUSIONS: For patients with ADPKD, prescribed water intake was not associated with excess adverse events and achieved the target 24-hour urine osmolality for half of the patients but did not reduce copeptin or slow the growth of total kidney volume over 3 years compared with ad libitum water intake. (Funded by the National Health and Medical Research Council of Australia [grant GNT1138533], Danone Research, PKD Australia, the University of Sydney, and the Westmead Medical Research Foundation; Australian New Zealand Clinical Trials Registry number, ACTRN12614001216606).

Published
2022
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