Santral Tiroid Hormon Direnci Saptanan Olgularda Tiroid Hormon Reseptör Gen Analizi ve Periferik Direnç Eşliğinin Araştırılması.

Year 2020, Volume: 14 Issue: 1, 72 - 79, 27.01.2020

Rıza Taner Baran , Sema Akçurin Gayaz Akçurin , Esra Manguoğlu Sebahat Özdem

https://doi.org/10.12956/tchd.638141

Abstract

Amaç: Hipofizer tiroid hormon (TH)
direnci düşünülen ve klinik bulguların ayırdettirici olmadığı çocuk olgularda
periferik direnç eşliğinin değerlendirilmesi ve TH β reseptörü (TRβ) mutasyon
sıklığının belirlenmesi amaçlanmıştır.

 Gereç
ve Yöntem: Hipofizer TH direnci tanısı ile izlenen ve yeterli dozda
levotiroksin (L-T4) tedavisi almalarına rağmen izlem süreçlerinde tiroid
stimülan hormon (TSH) düzeyleri baskılanamayan, 20 olgu (13 kız, ort yaş
7.03±2.72 yıl,) çalışmaya alınmıştır. TH periferik etkileri, suprafizyolojik
doz levotriiodotironin (L-T3) uygulaması öncesi ve sonrası serbest T3 (sT3),
serbest T4 (sT4), TSH, seks hormon bağlayıcı globulin (SHBG), total kolesterol,
alkalen fosfataz (ALP), osteokalsin, anjiotensin konverting enzim (ACE)
düzeyleri ve kreatin fosfokinaz (CPK), M-mod ve Doppler ekokardiyografi (EKO)
tetkikleri ile değerlendirilmiş ve TRβ gen analizleri yapılmıştır.

Bulgular: Olguların L-T3 öncesi ve
sonrası biyokimyasal ölçütleri karşılaştırıldığında SHBG, osteokalsin, ACE
düzeylerinde anlamlı artış, total kolesterol ve CPK düzeylerinde ise anlamlı
ölçüde azalma olduğu gözlenmiştir (p<0.001). ALP ve kardiyak parametrelerde
farklılık görülmemiştir.

TRβ gen analizinde, olguların
ikisinde homozigot, dördünde heterozigot rs3752874 ve iki hastada homozigot, 7
hastada heterozigot IVS8 -110 G>A değişimi saptanmıştır.

 Sonuç:
Olgularımızda suprafizyolojik L-T3 konsantrasyonlarına değişik derecelerde
periferik doku yanıtının gözlenmesi, yüksek T3 düzeylerine yanıtın korunduğunun
göstergesidir ve en yüksek yanıtın oluştuğu SHBG ve CPK değişimleri yol
gösterici olabilir. TRβ gen analizinde saptanan iki değişimin direnç
patogenezinde rolü olmadığı düşünülmüştür. Yeterli tedavi kriterleri
taşımalarına rağmen TSH düzeyleri ısrarlı yüksek seyreden doğumsal hipotiroid
olgularda genetik bir anomali eşliğinden çok, hipotalamus-hipofiz-tiroid
ekseninin intrauterin dönem olgunlaşma sürecindeki fonksiyonel bir hatanın
sorumlu olduğu düşünülebilir.

Aim:
This trial was designed to assess the concomitant peripheral resistance in
pediatric cases, who were considered to have pituitary thyroid hormone (TH)
resistance and exhibited indistinguishable clinical results and determine the
incidence of TH β receptor (TRβ) mutation in the “investigational group”.

 Matherials and Methods: 20 patients, monitored
with the diagnosis of pituitary TH resistance, in whom thyroid stimulating
hormone (TSH) level could not be suppressed during monitoring despite an
adequate dose of levothyroxine (L-T4) administered, were included in the trial
(13 girls, mean age: 7.03±2.72 years). TH peripheral effects were assessed
before and after liothyronine (L-T3) administration using free T4 (fT4), TSH,
sex hormone-binding globulin (SHBG), total cholesterol, alkalen fosfatase
(ALP), osteocalcin, anjiotensin coverting enzyme (ACE) levels and creatine
phosphokinase (CPK), M-mod and Doppler ECHO investigations and TRβ gene
analyses were performed.

Results:
The comparison of the pre-L-T3 and post-L-T3 biochemical measurements revealed
a significant increase in SHBG, osteocalcin and ACE levels and a significant
reduction in total cholesterol and CPK levels (p<0.001). No difference was
detected in ALP and cardiac parameters.

TRβ
gene analysis revealed homozygote and heterozygote rs3752874 changes in 2 and 4
patients respectively, and homozygote and heterozygote IVS8 -110 G>A changes
in 2 and 7 patients, respectively.

Conclusion:
Achievement of various degrees of peripheral tissue response to supraphysiological
L-T3 concentrations indicates that the response to high T3 levels is maintained
and the SHBG and CPK changes exhibiting the highest responses may be guiding.
The two changes detected in the TRβ gene analysis were considered not to be involved
in the pathogenesis of resistance. In patients with congenital hypothyroidism,
who sustain high levels of TSH despite meeting adequate therapeutic criteria,
the condition may be attributed to a functional defect in the intrauterine
growth process of the hypothalamic- pituitary-thyroid axis rather than a
concomitant genetic abnormality.

Keywords

Hipotiroidi, tiroid hormon direnci, Hypothyroidism, Thyroid hormone resistance

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