Efekti rane supstitucije supkliničkog hipotiroidizma na kvalitet života, biohumoralne parametre, srčanu i vaskularnu funkciju

Abstract

Efekti rane supstitucije supkliničkog hipotiroidizma na kvalitet života, biohumoralne parametre, srčanu i vaskularnu funkciju Uvod/Cilj. Supklinička hipotireoza (SCH) definiše se kao povišen TSH uz normalne vrednosti tiroksina. Podaci o efektima rane supstitucije na psihofizički status individua sa SCH nisu dovoljno konzistentni da bi podržali njeno uvodjenje. Cilj ove studije je ispitati efekat tromesečne supstitucije LT4-om na na kvalitet života, biohumoralne parametre, srčanu i vaskularnu funkciju u simptomatskoj SCH sa TSH < 10 mIU/L.Metode. Antropometrijski i klinički parametri (bolest-specifičan upitnik), kvalitet života, (Short Form-36 upitnik), biohemijski, elektro i ehokardiogtrafski parametri evaluirani su u 35 pacijenata sa perzistentnom simptomatskom SCH pre intervencije (TSH 7.0±2.1 mIU/L) i 3 meseca nakon postizanja zadovoljavajućeg kvaliteta supstitucije. Rezultati. Zabeležena je značajna redukcija telesne mase (p=0,030), sistolnog i dijastolnog krvnog pritiska (p=0,024,p=0,019), homocisteina (p<0,001), leukocita i neutrofila u krvi (p=0,011, p=0,001), INR-a (p=0,049), nivoa K (p=0,040, p=0,013), HbA1c (p=0,001), insulinemije bazno (p<0,001) i insulinske rezistencije merene HOMA indeksom (p<0,001), lipidnih parametara (ukupnog holesterola (p<0,001), LDL-holesterola (p<0,001), triglicerida (p=0,007), apoB (p=0,022), Lp(a) (p<0,001), LDL/HDL (p=0,008), LAP (p=0,04) i apoB/apoA1 (p<0.023)), TSH (p<0,001) i tAbs (p<0.001). Učestalost masne jetre (sa 20% na 2,9%, p=0,016), hiperlipidemije (sa 85% na 65,7%, p=0,001) i metaboličkog sindroma (sa 34,3% na 2,9%, p=0,070) značajno je snižena. Statistički značajna pozitivna povezanost nadjena je izmedju prosečne doze levotiroksina i promena u fizičkom funkcionisanju (r=0,391, p=0,020), vitalnosti (r=0,393, p=0,020), mentalnom zdravlju (r=0,374, p=0,027) i ukupnoj dimenziji mentalnog zdravlja (r=0,376, p=0,026). Sa porastom doze levotiroksina, prethodno navedeni skorovi SF 36 su rasli (r=0,296, p=0,084). Medijana Zulewski indeksa je značajno snižena nakon lečenja LT4-om: 5.0 (4.0-7.0) vs 3.0 (2.0-5.0) (p <0.001), ilustrujući smanjenje tegoba. Najučestalija tegoba pre tretmana je bila suva koža (71.4%), promuklost (65.7%) i gruba i perutava koža (54.3 %). Nakon lečenja, zabeležen je značajan pad u učestalosti opstipacije (p=0.004), suve kože (p=0.022), promuklosti (p=0.002), smanjenog znojenja (p=0.006), i produženog Ahilovog refleksa (p=0.002). Kvalitet života nije značajno promenjen ovim tretmanom. Zabeležene su značajne redukcije PR (pre: 0.16 ± 0.02, posle: 0.15 ± 0.02; p<0.001), QT (pre: 389.58 ± 10.12, posle: 383.54 ± 8.62; p<0.001) korigovanog QT (pre: 428.77 ± 20.11, posle: 411.77 ± 14.73; p<0.001) intervala kao i porast u srčanoj frekvenci (p=0.001) u grupi na supstituciji levotiroksinom. Sledeći parametri leve i desne komore su bili značajno sniženi u grupi lečenih: indeks mase leve komore (pre: 76.81 ± 13.52, posle : 70.62 ± 16.45; p<0.001), ESV (pre: 38.86 ± 9.6, posle: 36.95 ± 9.25; p<0.001), EDV (pre: 114.83 ± 20.6, posle : 108.43 ± 18; p<0.001), MAPSE 2D (pre: 1.67 (1.55-1.89), posle: 1.53 (1.34-1.65); p<0.001), sistolni i dijastolni intervali: IVCT (pre: 53.23 ± 11.07, posle: 46.54 ± 11.13; p<0.001), IVRT (pre: 78.71 ± 11.35, posle: 72.69 ± 10.1; p<0.001), IVCT/ET (pre: 0.18 ±0.04, posle: 0.16 ±0.04; p<0.001).Skok je zabeležen u vrednosti frakcionog skraćenja (pre: 39.40 (35.40-46.80), posle: 42.40 (38.80-47.20), p<0.001) i pritiska punjenja u ranoj sistoli (dP/dt: pre: 2163.29 ± 454.48, posle: 2385.17 ± 542.83; p<0.001), dijametrima desne pretkomore i debljini zida: DP duga osa (pre: 4.59 (4.18-5.11), posle: 4.81 (4.31-5.70); p<0.001) i kratka osa (pre: 3.67 (3.16-3.87), posle: 3.88 (3.38-4.14); p<0.001)), debljna zida (pre: 0.43 (0.40-0.46), posle: 0.44 (0.40-0.48); p<0.001). Posle lečenja levotiroksinom, zabeležen je statistički značajno smanjenje ESV i EDV (p<0.001, p<0.001 respektivno). LT4 terapija je značajano povećala vrednost EF (p<0.001) kao i globalnog longitudinalnog, circumferentnog i radijalnog strejna (p<0.001, p<0.001, p<0.001 respektivno). Registrovana je pozitivna korelacija izmedju promene u titru anti TPO antitela i promena u vrednostima globalnog longitudinalnog strejna nakon terapije (p = 0.027)...

The effect of early substitution of subclinical hypothyroidism on quality of life, biochemical blood parameters, and cardiovascular function Background / Aim. Subclinical hypothyroidism (SCH) is defined as high TSH and normal thyroxine. Data on the effects of early substitution by levothyroxine on psychophysical health in SCH are still not consistent enough to support its introduction. The aim of this study was to examine the effect a 3-month LT4 treatment on clinical presentation, quality of life, biochemical parameters and cardiovascular function in symptomatic SCH with TSH < 10 mIU/L. Methods. Anthropometric and clinical parameters (disease-specific score), quality of life (Short Form 36 questionnaire), biochemical data, electro and echocardiographic indices were measured in 35 patients with persistent symptomatic SCH before the intervention (TSH 7.0±2.1 mIU/L), and 3 months after the euthyroid state had been achieved. Results. Significant reduction in body weight (p=0.030), systolic and diastolic blood pressure (p=0.024, p=0.019), homocysteine (p<0.001), leukocytes and neutrophils (p=0.011, p=0.001), INR (p=0.049), K levels (p=0.040, p=0.013), HbA1c (p=0.001), fasting insulin (p<0.001) and insulin resistance measured by HOMA index (p<0.001), lipid parameters (total cholesterol (p<0.001), LDL-cholesterol (p<0.001), triglycerides (p=0.007), apoB (p=0.022), Lp(a) (p<0.001), LDL/HDL (p=0.008), LAP (p=0.04) and apoB/apoA1 ratios (p<0.023)), TSH (p<0.001) and tAbs (p<0.001) was recorded. Frequency of fatty liver (20% to 2.9%, p=0.016), hyperlipidemia (85% to 65.7%, p=0.001) and metabolic syndrome (34.3% to 2.9%, p=0.070) significantly decreased. A statistically significant positive association was found between the average dose of levothyroxine and changes in physical functioning (r=0.391, p=0.020), vitality (r=0.393, p=0.020), mental health (r=0.374, p=0.027) and overall dimensions of mental health (r=0.376, p=0.026). With increasing doses of levothyroxine, the previously listed scores of SF36 grew (r=0.296, p=0.084). The median of Zulewski index significantly decreased after the treatment with LT4: 5.0 (4.0-7.0) vs 3.0 (2.0-5.0) (p <0.001) representing a reduction of symptoms. The most common ailments before treatment were dry skin (71.4%), hoarseness (65.7%) and rough skin (54.3 %). After the treatment, there was a significant reduction in the frequency of constipation (p=0.004), dry skin (p=0.022), hoarseness (p=0.002), decreased sweating (p=0.006), and delayed Achilles reflex (p=0.002). Significant reduction in PR (before: 0.16 ± 0.02, after: 0.15 ± 0.02; p<0.001), QT (before: 389.58 ± 10.12, after: 383.54 ± 8.62; p<0.001) and QT corrected (before: 428.77 ± 20.11, after: 411.77 ± 14.73; p<0.001) intervals as well as increase in heart rate (p=0.001) were recorded in the group on levothyroxine therapy. The following parameters of the left and right ventricle were significantly decreased in the treatment group: left ventricular mass index (before: 76.81 ± 13.52, after: 70.62 ± 16.45; p<0.001 respectively), ESV (before: 38.86 ± 9.6, after: 36.95 ± 9.25; p<0.001), EDV (before: 114.83 ± 20.6, after: 108.43 ± 18; p<0.001), MAPSE 2D (before: 1.67 (1.55-1.89), after: 1.53 (1.34-1.65); p<0.001). systolic and diastolic time intervals: IVCT (before: 53.23 ± 11.07, after: 46.54 ± 11.13; p<0.001), IVRT (before: 78.71 ± 11.35, after: 72.69 ± 10.1; p<0.001), IVCT/ET (before: 0.18 ±0.04, after: 0.16 ±0.04; p<0.001). The increase was recorded as fractional shortening (before: 39.40 (35.40-46.80), after: 42.40 (38.80-47.20), p<0.001) and pressure rise in early systole (dP/dt: before: 2163.29 ± 454.48, after: 2385.17 ± 542.83; p<0.001), right atrial wall thickness and diameters (RA long axis (before: 4.59 (4.18-5.11), after: 4.81 (4.31-5.70); p<0.001) and short axis (before: 3.67 (3.16-3.87), after: 3.88 (3.38-4.14); p<0.001)), wall thickness (before: 0.43 (0.40-0.46), after: 0.44 (0.40-0.48); p<0.001). After the levothyroxine therapy, there was a statistically significant decrease in ESV and EDV (p<0.001, p<0.001 respectively). LT4 therapy significantly increased values of EF (p<0.001) as well as global longitudinal circumferential and radial strains (p<0.001, p<0.001, p<0.001 respectively). There is a moderate, positive, statistically significant correlation between the change in the titre of anti TPO antibodies and the change in global longitudinal strain values after the therapy (p = 0.027)...