Co-existence of Congenital Hypothyroidism (CH) and TBG-Excess in a Boy Causing Simultaneous Elevation in Thyroid Stimulating Hormone (TSH) and Thyroxine (T4) Levels: First Report from India and Review of the Literature

A certain population of patients exhibits discordant thyroid function tests (TFT) consistently along with unclear symptoms may lead to equivocal diagnosis and treatment. Concomitant elevation in TSH and T4 is one of the patterns of discordant TFT which can be associated with different thyroid-related conditions and, hence, warrants differential diagnosis. A case of congenital hypothyroidism was investigated to determine the etiology of the consistent co-elevation in TSH and T4 despite thyroxine supplementation since birth. T4 dose was changed multiple times which caused abrupt fluctuations in TSH and T4 levels in the previous treatment. The index patient, II-1 did not have pituitary or liver abnormality or any transient factors that would elevate thyroid hormone-binding proteins. The results revealed that II-1 had TBG-excess. However, no mutation or copy number variation in the SERPINA7 gene which codes for TBG was detected. Further, II-1 was detected with a homozygous mutation, c.955G > A in the exon 8 of the TPO gene associated with CH. His mother and siblings were heterozygous for the TPO mutation, however, they had normal TBG and TFT. The present study is the first report of the rare combination of endocrine disorders i.e., TBG-excess and CH, and is also the first report of the TPO mutation c.955G > A from Indian ethnic origin. The co-occurrence of two endocrine abnormalities caused TFT discordance and confusion. This study highlights the importance of detailed biochemical and genetic testing for the differential diagnosis of thyroid disorders in patients exhibiting discrepant TFT results which would avoid misdiagnosis and inappropriate treatment.