Osjetljivost osi hipofiza-hormoni štitnjače u hipotireoidnih i atireoidnih bolesnika [Pituitary-thyroid feedback control in hypothyroid and athyreotic patients]

Solter, Darko (2014) Osjetljivost osi hipofiza-hormoni štitnjače u hipotireoidnih i atireoidnih bolesnika [Pituitary-thyroid feedback control in hypothyroid and athyreotic patients]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

The overall efficiency of standard levothyroxine replacement therapy for hypothyroidism was observed in 2488 patients. The treatment outcome was acceptable in 90% of patients with spontaneous hypothyroidism and in 82% of patients with induced hypothyroidism following either surgery or I131 treatment. The pituitary-thyroid feedback control was investigated in properly treated randomly selected 250 hypothyroid and 110 athyreotic patients and was compared with 210 healthy subjects. Unlike normal TSH distribution in controls, most hypothyroid patients displayed high normal, and the majority of athyreotic patients, low normal TSH values. In hypothyroid patients the TSH median was significantly higher than in controls, with a significantly higher T4 level, suggesting a decreased ability of T4 to suppress TSH, which was also supported by a lower T4/TSH ratio (TSH Suppressibility Index). Impaired TSH suppressibility in athyreotic patients could be overcome by administering a significantly higher levothyroxine dose (by 50%) than in hypothyroid patients. This treatment resulted in a significantly higher T4 and a significantly lower TSH than in hypothyroid patients and controls. These results, together with an excessively high T4/TSH ratio, raise doubts about athyreotic patients being overtreated. A positive correlation of the T4 vs T4/TSH ratio and a negative correlation of the TSH vs T4/TSH ratio were found in all groups but in different T4 and TSH concentration levels: lower for controls and higher for hypothyroid/athyreotic patients. For the same T4/TSH ratio (TSH Suppressibility Index) a lower serum T4, together with a lower TSH was found in euthyroid subjects than in hypothyroid and athyreotic patients. The difference in TSH suppressibility suggested an impaired pituitary-thyroid feedback control in hypothyroidism and athyreosis. Serum T3 levels for both groups of hypothyroid patients were significantly lower in comparison to healthy subjects, in spite of simultaneously observed higher T4 concentrations. An increased T4/T3 ratio indicated a decreased peripheral T4 to T3 conversion. A decreased serum T3 emerged as a major cause of a diminished T4 ability to adequately suppress (normalize) TSH. The beneficient role of LT3 in combined replacement therapy for hypothyroidism was observed in a defined group of athyreotic patients who failed to suppress (normalize) TSH even with a very high levothyroxine dose and supranormal T4 values. A combined therapy with liotriiodothyronine significantly decreased the need for levothyroxine and normalized both serum TSH and T4.

Abstract in Croatian

Ukupna učinkovitost standardnog nadomjesnog liječenja hipotireoze/atireoze promatrana je u 2488 bolesnika. Liječenje je bilo prihvatljivo u 90% bolesnika sa spontanom hipotireozom i 82% bolesnika s hipotireozom nakon operacije ili primjene J-131, ali nije bilo uspješno u svih. Osjetljivost pituitarno-tireoidne osi ispitana je u propisno liječenih 250 hipotireoidnih i 110 atireoidnih bolesnika (uredan nalaz TSH) u usporedbi s 210 zdravih osoba. Nasuprot normalnoj distribuciji TSH u kontrolnoj skupini, najveći broj hipotireoidnih bolesnika imao je visoko normalni, a najveći broj atireoidnih bolesnika nisko normalni TSH. U hipotireoidnih bolesnika medijan TSH značajno je viši nego u zdravih osoba, uz istodobno značajno veću razinu T4, ukazujući na smanjenu sposobnost supresije TSH, što potvrđuje i niži omjer T4/TSH (Indeks supresibilnosti TSH). U atireoidnih bolesnika nedostatna supresibilnost TSH mogla se prevladati značajno većom dozom levotiroksina (za 50%) u odnosu na hipotireoidne bolesnike. Postignuti serumski T4 značajno je viši, a TSH niži u odnosu na hipotireoidne bolesnike i zdrave osobe. Ti rezultati kao i ekscesivno povišen omjer T4/TSH bude sumnju u prekomjerno liječenje atireoidnih bolesnika. U sve tri grupe ispitanika utvrđena je značajna pozitivna korelacija između koncentracije serumskog T4 i omjera T4/TSH te značajna negativna korelacija između TSH i omjera T4/TSH, no u nižem koncentracijskom području za kontrolnu skupinu, a u višem za hipotireoidne i atireoidne bolesnike. Za isti omjer T4/TSH (Indeks supresibilnosti TSH) u eutireozi je potrebna niža koncentracija T4 uz niži TSH u odnosu na hipotireoidne i atireoidne bolesnike, što sugerira različitost u supresibilnosti TSH i smanjenu ekonomičnost funkcije pituitarno-tireoidne osi. Razina serumskog T3 značajno je niža u obje skupine bolesnika u odnosu na zdrave osobe, usprkos značajno višem T4 u hipotireoidnih, a posebice u atireoidnih osoba. Značajno povišen omjer T4/T3 označava smanjenu perifernu pretvorbu T4 u T3 te sugerira sniženu razinu T3 kao uzrok smanjene sposobnosti T4 u supresiji TSH u hipotireozi. Novo razmatranje uspješnosti dodatka liotrijodtironina u nadomjesnom liječenju potvrđeno je u definiranoj skupini atireoidnih bolesnika koji uz standardnu primjenu levotiroksina nisu uspjeli normalizirati serumski TSH niti uz povišene vrijednosti T4. Dodatkom liotrijodtironina znatno je smanjena potreba za levotiroksinom te je TSH potpuno normaliziran i uz nižu, normalnu razinu serumskog T4.

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