Changes of hormones and lipoprotein parameters in infants with hypothyroidism; influence of the disease and replacement therapy

Abstract

Clinical signs of thyroid gland hormones deficiency appear at different ages in infants with different concentrations of hormones. They depend on causes which had caused the hypothyroid degree of subsequents. Concentrations of hormones parameters: tT3, tT4, TSH, fT3, fT4, TBG and Tg (fluoroimmunoassay, DELFIA) and lipid parameters: total cholesterol (Chol), triglycerides (TRG), high density lipoprotein, (HDL-chol) and density lipoprotein, (LDLchol) were determined in order to establish changes that appear under the influence of the disease and replacement therapy in infants with hypothyroidism. In order to establish the influence of infant’s age on a determined parameter, all parameters where determined in the sample of healthy infants. A group of healthy infants (N=100) aged one mounth to 18 years, was devided in 5 age subgroups. The group of patients was devided into the same age groups as healthy group of the moment of diagnosis (N=56). Metabolic condition of an infant was established according to found by ANOVA test according to Tudey Snedecor method for the following parameters; T3 (d=0.35 p lt 0.001), fT3 (d=1.63 p lt 0.001) fT4 (d=2.59 p lt 0.001), TSH (d=2.27 p lt 0.001), TBG (d=90.82 p lt 0.001), Tg (d=4.59 p lt 0.02), Cho. (d=0.48 p lt 0.001) and LDL-chol. (d=0.51 p lt 0.001). These findings must be taken into account when the influence of replacement therapy on the observed parameters concentration changes is interpreted. The average concentration values were compared by Student’s t-test in infant before replacement therapy with that of the control subgroup of infants of the same age in order to evaluate the influence on values of the examined parameters. The average concentration values in infants after the replecement therapy were compared that before the replacement therapy as well as the control group, findings in order to the influence on the examined parameters. We observed significant changes hormone parameters in all agesubgroups under hypothyroid condition and return to control levels, except for T4 where the values were significantly higher in all age groups (p lt 0.05) in comparison to the control group. As for lipids, we found significantly higher values in all age subgroups for chol (p lt 0.01) and LDL-chol (p lt 0.001); they did not differ from that in control group after the replacement therapy. Patients were classified at the moment of clinical examination into the following categories: normometabolic (NM) and hypometabolic (HM). They were compared by Student’s T-test of different pairs with the condition before the replacement therapy. The percentage share in the change of TRG concentrations (p lt 0.02), LDL-chol (p lt 0.025) and T3 (p lt 0.001) was significantly different between NM and HM, and the long-lasting replacement therapy caused significant individual differences in Chol concentrations (NM ’ 37.90% p lt 0.001, HM ’ 15.14% p lt 0.001), HDL-chol (NM ’ 7.81% p lt 0.001, HM ’ 12.05% p lt 0.001), LDL-chol (NM ’ 50.15% P lt 0.001 HM 20.03 p lt 0.01) and T3 (NM ’ 105.04% p lt 0.001, HM 32.18% p>0.005). We conclude that hypothyroidism caused significant hormonal and metabolic changes in infants; however there is no clinical and laboratory index regarding the results of replacement therapy; this is the reason why the patient’s condition must be evaluated individually.

Zavisno od uzroka koji su doveli do hipotiroidnog stanja kod deteta (dishormonogeneza, hipoplazija, ektopija, atireoza), a time i težine poremećaja, klinički znaci deficita hormona štitne žlezde ispoljavaju se u različitom uzrastu deteta, s različitim koncentracijama ispitivanih hormona. U cilju utvrđivanja promena nastalih pod uticajem bolesti i supstitucione terapije kod dece s hipotiroidizmom određene su koncentracije hormonskih parametara: tT3, tT4, TSH, fT3, fT4, TBG i Tg (fluoroimunotest DELFIA), kao i lipidnih: ukupni holesterol, trigliceridi, HDL-holesterol i LDL-holesterol. Za utvrđivanje uticaja starosti deteta na ispitivani parametar isti su obrađeni u uzorku zdrave dece. Grupa zdrave dece N=100 uzrasta od 1 meseca do 18 godina podeljena je u 5 starosnih podgrupa. Posebnu grupu sačinjava uzorak uzet iz pupčane vrpce, zdravo rođene dece. Grupa obolele dece je podeljena po istim starosnim grupama kao i zdrava grupa i to: u momentu otkrivanja bolesti (N=58) i u momentu kasnijeg pregleda, posle dugovremene supstitucione terapije sa L-T4 (N=56). Metaboličko stanje deteta utvrđeno je po kriterijumu specifičnih klinički znakova i simptoma. ANOVA testom po metodi Tudey Snedecor-a utvrđena je statistički značajna razlika između starosnih podgrupa za sledeće parametre: T3 (d=0,35 p lt 0,001), fT3 (d=1,63 p lt 0,001) fT4 (d=2,59 p lt 0,001), TSH (d=2,27 p lt 0,001), TBG (d=90,82 p lt 0,001), Tg (d=4,59 p lt 0,02), holesterola (d=0,48 p lt 0,001) i LDL-holesterola (d=0,51 p lt 0,001), što se mora uzeti u obzir kod tumačenja uticaja supstitucione terapije na izmenu koncentracija posmatranih parametara. Koncentracije svih hormonskih parametara u uzorku pupčane vrpce se razlikuje od koncentracija u ostalim starosnim grupama dece, osim za T4. Da bi se procenio uticaj bolesti na vrednosti ispitivanih parametara, upoređene su vrednosti srednjih koncentracija Studentovim T-testom podgrupa dece pre supstitucije sa kontrolnim grupama dece iste starosne dobi. Za procenu uticaja supstitucije na ispitivane parametre upoređene su srednje koncentracije ispitivanih parametara, grupe dece posle supstitucije sa grupom dece pre supstitucije kao i sa kontrolnom grupom. Za posmatrane hormonske parametre imamo značajne izmene u svim starosnim podgrupama, sa nastankom hipotiroidnog stanja i vraćanje na nivo vrednosti kontrolne grupe sem za T4 kada su vrednosti značajno više u svim starosnim grupama (p lt 0,05) u odnosu na kontrolu. Kod lipida značajno veće vrednosti nađene su u svim starosnim podgrupama za holesterol (p lt 0,01) i LDL-holesterol (p lt 0,001) koje se ne razlikuju od kontrolne grupe posle supstitucione terapije. Pacijente su u momentu kliničkog pregleda razvrstali u kategorije normometabolični (NM) i hipometabolični (HM) i upoređeni Studentovim T-testom razlike parova sa sopstvenim stanjem pre supstitucione terapije. Procentualni udeo u izmeni koncentracija triglicerida (p lt 0,02) LDL-holesterola (p lt 0,025) i T3 (p lt 0,001) je značajno različit između NM I HM, a dugogodišnja supstituciona terapija dovodi do značajnih interindividualnih razlika u koncentracijama holesterola (NM ’ 37,90% p lt 0.001, HM - 15,14% p lt 0,001) HDL-holesterola (NM - 7,81% p lt 0.001, HM - 12,0,05% p lt 0.001), LDL-holesterola (NM - 50,15% P lt 0,001 HM 20,03 p lt 0,01) i T3 (NM 105,04% p lt 0,001, HM - 32,18% p>0,005). Zaključujemo da hipotiroidizam dovodi do značajnih hormonskih i metaboličkih promena kod obolele dece, ali ne postoji generalni klinički i laboratorijski indeks postignutog rezultata supstitucione terapije, te zbog toga se individualno procenjuje stanje bolesnika.