Anti-Thyroid Stimulating Hormone monoclonal antibody

Objective: We aimed to investigate neutrophil lymphocyte ratio (NLR), leukocyte count (WBC), mean platelet volume (MPV) and C-reactive protein levels (CRP) as inflammatory markers according to thyroid function status in hypo-hyperthyroidism patients. Methods: Data of patients (n=454, age>18) who applied to the Eskisehir Osmangazi University Hospital between March 2018 and December 2018 were evaluated retrospectively. There were 79 patients in hyperthyroidism group (TSH<0.27 mu IU/ml, group I), 297 patients in euthyroid group (TSH=0.27-4.2 mu IU/ml, group II) and 78 patients in hypothyroidism group (TSH>4.2 mu IU/ml, group III). Results: Serum TSH, fT4, fT3, anti-TG and anti-TPO levels were found statistically different between groups (p<0.001) but there were no significant difference in WBC, NLR and MPV between groups. There was a positive correlation between the NLR and CRP (r=0,295, p<0.01). In addition, NLR was positively correlated with WBC (r=0,412, p<0.001). Serum CRP levels were statistically higher in group I (3.5 mg/L [1.50-11]) than group II (2.1 mg/L [0.86-5.42]), (p<0.001). Although CRP levels were higher in group III (2.5 mg/L [1.18-5.73]) than group II, there was no significant difference. CRP showed weak positive correlation with fT4 (r=0,118, p<0.05) and negative correlation with TSH (r=-0,108, p<0.05). Conclusion: High CRP levels may play an important role in the evaluation of hyperthyroidism in terms of thyroid dysfunction observed in the present study.

Background:Isolated central congenital hypothyroidism (ICCH) is a rare form (1:50,000 newborns) of congenital hypothyroidism, which can present with growth and neuropsychological retardation. Unlike the more common primary CH (1:1,500-1:4,000), which presents on newborn screening with elevated serum thyroid-stimulating hormone (TSH) and low thyroxine (T-4) and triiodothyronine (T-3), ICCH presents with low TSH and low thyroid hormone levels. ICCH, therefore, may be missed in most newborn screens that are based only on elevated TSH. Most cases of ICCH have been associated with mutations in theTSH beta gene.Patient:We present a consanguineous Sudanese family where the proband was diagnosed with "atypical" CH (serum TSH was low, not high).Intervention and Outcome:The propositus underwent whole-exome sequencing, and the C47W TSH beta mutation was identified. Sanger sequencing confirmed the proband to be homozygous for C47W, and both parents were heterozygous for the same mutation. The mutation was predicted by several in silico methods to have a deleterious effect (SIFT 0.0, Damaging; Polyphen2_HDIV 0.973, probably damaging; MutationTaster 1, disease causing; and CADD 3.17, 16.62). C47W affects the first cysteine of the cysteine knot of the TSH beta subunit. The cysteine knot region of TSH beta is highly conserved across species and is critical for binding to the TSH receptor. Only two other mutations were previously reported along the cysteine knot and showed consistently low or undetectable serum TSH and low T-4 and T-3 levels. OtherTSH beta gene mutations causing ICCH have been reported in the "seatbelt" region, necessary for TSH beta dimerization with the alpha subunit.Conclusions:Identification of a mutation in theTSH beta gene reinforces the importance of identifying ICCH that can occur in the absence of elevated serum TSH and demonstrates the functional significance of the TSH beta cysteine knot.