A Neonate with a Diagnosis of Pontocerebellar Hypoplasia Type 6 Treated with Biotin and Developed Biotin Interference with Laboratory Thyroid Function Tests

Abstract

Patient: Male, 2-year-old Final Diagnosis: Pontocerebellar hypoplasia type 6 Symptoms: Feeding problems • lactic acidosis Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Unusual clinical course Background: The interference of biotin administration with thyroid function tests has been reported; however, it remains unclear in clinical practice. In this report, we present the case of a neonate with a diagnosis of pontocerebellar hypoplasia type 6 (PCH6) treated with biotin who developed biotin interference with laboratory thyroid function tests. Case Report: A 1-day-old male infant with hypothermia, tachypnea, and lactic acidosis had a suspected diagnosis of mitochondrial disease. Biotin and several vitamins were administered to improve his condition. On day 14, his laboratory tests revealed a free triiodothyronine level of 4.7 pg/mL, free thyroxine level of 3.7 ng/dL, thyroid-stimulating hormone level of 0.07 μIU/mL, and thyroid-stimulating hormone receptor antibody (TRAb) level of 37.6 IU/L, suggesting Graves’ disease. No goiter or tachycardia developed. The maternal thyroid function was not measured during pregnancy, while the maternal TRAb was negative on the same day. After methimazole administration, the patient’s thyroid function normalized, and methimazole was therefore discontinued. All thyroid function tests were conducted using immunoassay methods with avidin and biotin. Later, reduced oxygen consumption under aerobic conditions in skin fibroblasts and compound heterozygous variants of the mitochondrial arginine tRNA synthetase gene were identified, and the patient was diagnosed with PCH6. Conclusions: In this case, the clinical symptoms and physical findings were incompatible with the thyroid function. These laboratory findings could have mimicked Graves’ disease due to the biotin interference with immunoassays. Therefore, caution is required when evaluating similar cases.

Prevalence of elevated serum concentrations of biotin in patients from South East England, Korea, Singapore and Thailand and risk of immunoassay interference

“…Elevated serum biotin occurs because of high-dose supplementation regimes, which can interfere with the performance of biotin-streptavidin-based immunoassays. Although this source of interference has been recognised by clinical laboratories for many years, ongoing case reports most commonly describing ‘pseudohyperthyroidism’ suggest that some users of laboratory services remain unaware 13 14. Other examples of high-risk analytes where incorrect results may lead to significant patient management error because of biotin interference include hs-troponin, NT-pro-BNP and procalcitonin.…”

Effects of Methimazole vs Propylthiouracil in Newborns: A Comparative Review

“…Thereby, we had a total of 10 case reports which we included in our study [28][29][30][31][32][33][34][35][36][37]. They are listed in Table 1.…”

An Overview on Different L-Thyroxine (l-T4) Formulations and Factors Potentially Influencing the Treatment of Congenital Hypothyroidism During the First 3 Years of Life

“…The correct assessment of thyroid function may be influenced by biotin therapy ( 173 ). High levels of biotin–streptavidin can compete with biotinylated components leading to inaccurate and misleading results characterised by increased FT 3 , FT 4 , levels and a reduction in TSH levels, which may lead to misplaced suspicion of Graves’ disease ( 173 ).…”

“…The correct assessment of thyroid function may be influenced by biotin therapy ( 173 ). High levels of biotin–streptavidin can compete with biotinylated components leading to inaccurate and misleading results characterised by increased FT 3 , FT 4 , levels and a reduction in TSH levels, which may lead to misplaced suspicion of Graves’ disease ( 173 ). This could lead to erroneous therapeutic strategies with serious consequences in the first three years of life given the thyroid dependency of the central nervous system in this period.…”