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Objective:To investigate the changes of thyroid hormone level in children with type 1 diabetic mellitus (T1DM) complicated with ketoacidosis.Methods:Sixty-seven children with acute T1DM and ketoacidosis admitted in Department of Endocrinology, Shanxi Children′s Hospital from December 2017 to December 2020 were enrolled as acidosis group; and 44 T1DM children without ketoacidosis at admission served as control group. According to blood gas analysis, in acidosis patients there were 22 cases in mild group (pH<7.3), 16 cases in moderate group (pH<7.2) and 29 cases in severe group (pH<7.1). Serum levels of triiodothyronine (T 3), thyroxine (T 4), free T 3(FT 3), free T 4(FT 4), thyroid stimulating hormone (TSH) were measured in all patients at admission and recovery, retrospectively. Patients in the acidosis group at acute stage were treated with balanced fluid infusion, insulin infusion and eritone. Results:The serum levels of T 3 [0.48(0.19, 0.67)nmol/L vs. 0.97(0.74, 1.18)nmol/L, Z=-5.97, P<0.001], T 4 [(49.99±26.06) nmol/L vs. (73.48±23.32)nmol/L, t=4.68, P<0.001], FT 3 [1.80(1.24, 2.51) pmol/L vs. 3.31(2.56, 3.98) pmol/L, Z=-6.15, P<0.001], FT 4 [9.74 (7.21, 12.85)pmol/L vs. 14.54 (11.29, 16.75)pmol/L, Z=-5.23, P<0.001] and TSH [0.86(0.31, 1.81) mIU/L vs. 1.92(1.01, 3.56)mIU/L, Z=-4.19, P<0.001] in acidosis group at acute stage were significantly lower than those in the control group. In acidosis group at recovery stage serum levels of T 3 [1.58 (1.25, 1.86)nmol/L], T 4 [(92.52±27.03) nmol/L], FT 3 [5.03(4.15, 5.78) pmol/L], FT 4 [15.94 (14.40, 18.38)pmol/L], and TSH [2.21(1.58, 3.16)mIU/L] were significantly higher than those at acute stage ( Z=-6.96, t=-11.34, Z=-7.00, Z=-6.39, Z=-5.28,all P<0.001). There was an decreasing trend of T 3 and FT 3 levels from mild group [0.60 (0.47, 0.78)nmol/L, 2.20(1.47, 2.89) pmol/L], moderate group [0.36(0.18, 0.64)nmol/L, 1.90(1.11, 2.31)pmol/L] to severe acidosis group [0.35(0.16, 0.54) nmol/L, 1.48(1.08, 1.89)pmol/L](T 3: Z=-3.44, P=0.001; Z=-3.97, P<0.001; Z=-5.63, P<0.001;FT 3: Z=-3.44, P=0.001; Z=-4.13, P<0.001; Z=-5.86, P<0.001). Compared to control group serum T 4 and FT 4 levels in moderate group [(47.34±29.89)nmol/L and 9.75(5.74,12.29)pmol/L] and severe group [(44.08±22.27)nmol/L and 8.82 (6.40, 9.89)pmol/L] were significantly decreased (T 4: t=3.66, t=5.01,all P<0.001; FT 4: Z=-3.40, P=0.001; Z=-5.73, P<0.001). The TSH level in severe acidosis group [0.63 (0.27, 1.33)mIU/L] was lower than that in the control group ( Z=-4.23, P<0.001). At the recovery stage the serum levels of T 3 [1.69 (1.22, 1.87)nmol/L,1.68 (1.24, 1.84)nmol/L,1.55(1.25, 1.86) nmol/L], FT 3 [5.27 (4.37, 5.76)pmol/L,4.32(4.17, 5.73)pmol/L,5.04(3.81, 5.79)pmol/L], T 4 [(87.41±18.40)nmol/L,(90.02±30.41)nmol/L,(97.34±30.10)nmol/L] and FT 4 [16.05(14.23, 17.71) pmol/L,15.26(14.40, 16.11)pmol/L,16.88(13.98, 18.89) pmol/L] in the mild, moderate and severe acidosis groups were higher than those in the control group (T 3: Z=-4.55, Z=-3.87, Z=-4.93,all P<0.001;FT 3: Z=-4.72, Z=-3.72, Z=-4.52,all P<0.001;T 4: t=-2.01, P=0.047; t=-2.15, P=0.034; t=-3.88, P<0.001;FT 4: Z=-2.21, P=0.027; Z=-0.84, P=0.399; Z=-2.67, P=0.008); while there was no significant difference in TSH levels [2.28(1.88, 3.16)mIU/L, 2.19(1.26, 3.57) mIU/L, 2.18(1.36, 3.09) mIU/L] between mild, moderate, severe acidosis groups and the control group (all P>0.05). Conclusions:Thyroid function in T1DM children complicated with ketoacidosis is decreased significantly with the aggravation of acidosis. After correction of ketoacidosis, the level of thyroid function can basically return to normal.
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Objective To analyze the correlation of clinical phenotype and genotype and gene mutation frequency characteristics of 21-hydroxylase deficiency,and to provide the basis for clinical diagnosis and methods for early intervention.Methods The clinical phenotypic signs and examination results of 14 cases with 21-hydroxylase deficiency were collected from September 2008 to December 2016 in Children's Hospital of Shanxi Province.Point mutations,deletions and conversion mutations for gene CYP21A2 coding 21-hydroxylase were detected through using next generation sequencing(NGS) and multiplex ligation-dependent probe amplification (MLPA).The captured mutations were further confirmed with Sanger sequencing.Furthermore,the family members underwent the co-segregation validation through the Sanger sequencing or MLPA in those captured mutated sites.Results Among the total 14 cases,9 cases were identified as the salt wasting,5 cases the simple virilizing;10 cases of compound heterozygous mutations,and 4 cases of homozygous mutations.Analysis of the 14 patients revealed 8 different kinds of mutations in CYP21A2 gene.The most frequent mutations of CYP21A2 gene were I2G [50％ (14/28)] and I173N [21.4％ (6/28)],followed by Arg357Trp[10.7％ (3/28)].Del[10.7％ (3/28)] mutations including E247fs,Gly1 1 1fs and R484fs.Q319X [3.6％ (1/28)] and Arg355His[3.6％ (1/28)] were rarely found.Missense mutation was found in 10 cases,splicing mutation in 14 cases,frameshifi mutations in 3 cases,nonsense mutations in 1 case.All of the mutations were inherited from their parents,and no new mutation was found.The most common mutations for salt wasting and simple virilizing were respectively I2G[50％ (9/18)] and I173N [50％ (5/10)].Collectively,genotypes and phenotypes were matched with each other.Conclusions The combination of clinical phenotypes with laboratory examination by gene sequencing and comprehensive analysis,is helpful to early diagnosis,differential diagnosis and optimized treatment,which will improve prognosis and provide guidance for genetic consultancy.