#1
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Ïðîñòåíüêèé âîïðîñ
Âñå òóò â îäèí ãîëîñ óòâåðæäàþò, ÷òî äîçà òèðîêñèíà 25 ìêã ñëèøêîì ìàëà, ÷òîáû èìåòü õîòü êàêîé-òî áèîëîãè÷åñêèé ýôôåêò.
Íî â òî æå âðåìÿ, íè÷òîæå ñóìíÿøåñÿ, ìû âñå äîáàâëÿåì òå æå 25 ìêã, è äàæå 12.5 ìêã ê ðåæèìó , åñëè çàìåñòèòåëüíàÿ äîçà â, - ñêàæåì,- 125 ìêã íå íîðìàëèçóåò ÒÒÃ, íî äîâîäèò åãî îò, îïÿòü æå ñêàæåì, 25 äî 6-7. È ýòî ðàáîòàåò. Tàê åñòü áèîëîãè÷åñêè çíà÷èìûé ýôôåêò òèðîêñèíà 25 ìêã èëè íåò?
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Dr.B |
#2
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Äîáðîå óòðî!
Ìíå äóìàåòñÿ, èñõîäÿ èç ôàðìàêîäèíàìèêè ïðåïàðàòà òàêàÿ îñîáåííîñòü. Ïîòîìó ïðè òèðåîòîêñèêîçå ïåðèîä ïîëóâûâåäåíèÿ óêîðà÷èâàåòñÿ äî 3-4 äíåé, à ïðè ãèïîòèðåîçå óäëèíÿåòñÿ äî 9-10 äíåé. |
#3
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îòâåòîì íà âîïðîñ ìîæåò áûòü, êàêèå öåëè íàçíà÷åíèÿ ýòèõ 25 ìêã - åñëè ëå÷åíèå ãèïîòèðîçà, òî 25 ìêã â äåíü çà ìåñÿö íå äàñò îæèäàåìîãî ðåçóëüòàòà, åñëè òàì äåéñòâèòåëüíî ãèïî- ñ ÒÒà 50-60:
full starting levothyroxine dose of 1.6 μg/kg with a low starting dose of 25 μg (increased every 4 weeks) in patients with newly diagnosed cardiac asymptomatic hypothyroidism... the severity of hypothyroidism and age were comparable in the full-dose (n = 25) vs the low-dose group (n = 25): thyrotropin, 61 vs 48 mIU/L; free thyroxine, 0.56 vs 0.64 ng/dL (7.2 vs 8.2 pmol/L); and age, 47 vs 47 years. No cardiac complaints or events were documented during treatment or at bicycle ergometry at baseline, 12 weeks, or 24 weeks. Euthyroidism was reached in the full-dose vs the low-dose group in 13 vs 1 (4 weeks)//Roos A, et al. The starting dose of levothyroxine in primary hypothyroidism treatment. Arch Intern Med. August 8/22 2005;165:1714-20 åñëè æå ðå÷ü î òîì, ÷òî äà¸ò äîïîëíèòåëüíûå 25 ìêã ê òîìó, ÷òî èìååòñÿ, òî è îæèäàåìûé ýôôåêò äðóãîé, äàæå 12.5 ìêã (ê 60 ìêã èëè +20%, ÷òî ñîïîñòàâèìî ñ 25 ìêã ê 120 ìêã èëè òå æå ~1.6 ìêã/êã ïðè âåñå 70-75 êã), ñíèæàþò ÒÒà â 5 ðàç Their daily dose of levothyroxine ranged from 25 to 100 mcg (average 59 mcg)... after increasing LT4 dose by an additional 12.5 µg/d, and finally 3 months after returning to the baseline Serum thyroid-stimulating hormone (TSH) concentrations decreased at the higher LT4 dose (1.95 ± 2.16 vs 0.47 ± 1.09 mIU/L, P < .001) and recovered after returning to the baseline dose. effect of increased levothyroxine dose on depressive mood in older adults undergoing thyroid hormone replacement therapy. Clin Endocrinol. 2020 Apr 13. PMID: 3228295
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Èñêðåííå, Âàäèì Âàëåðüåâè÷. |
#4
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Âñå ïðàâèëüíî, íî åùå íå ñòîèò çàáûâàòü, ÷òî ÒÒà è Ò4 ñâÿçàíû íå ëèíåéíî à ëîãàðèôìè÷åñêîé çàâèñèìîñòüþ è ðàçíèöà ìåæäó 100 è 112,5 ìêã áóäåò âëèÿòü ñèëüíåå, ÷åì ìåæäó 0 è 25 ìêã.
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Ñ óâàæåíèåì, Àíäðåé Âëàäèìèðîâè÷ Ïîëÿêîâ âðà÷-ÓÇÄ |
#5
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íàñêîëüêî ïîíèìàþ, íå äîçà òèðîêñèíà ñâÿçàíà ñ ÒÒÃ, à ñâîáîäíûé Ò4, èç ïðèìåðà âûøå - èçìåíåíèå Ò4 íà 10% äà¸ò ïîâûøåíèå ÒÒà â 5 ðàç, ïðèåì â ñðåäíåì íà 20% òèðîêñèíà áîëüøå ñîïðîâîæäàëñÿ èçìåíåíèåì â 4 ðàçà, òî åñòü ïîâûøåíèå äîçû íà 20% ïîâûøàëî ñâ. Ò4 íà ìåíåå 10% â êðîâè
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Èñêðåííå, Âàäèì Âàëåðüåâè÷. |
#6
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åùå êàê ïðèìåð ðàñ÷åòà äîçû òèðîêñèíà, èñõîäÿ èç ÒÒÃ:
[Ññûëêè äîñòóïíû òîëüêî çàðåãèñòðèðîâàííûì ïîëüçîâàòåëÿì ] è òàì íèæå åùå êàðòèíêè ÷òî äåëàòü ñ äîçîé íà ïðèìåðå òèïè÷íûõ êëèíè÷åñêèõ ñëó÷àåâ
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Èñêðåííå, Âàäèì Âàëåðüåâè÷. |
#7
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Öèòàòà:
Âñå òàêèì îáðàçîì çàâèñèò îò èíäèâèäóàëüíî “ íîðìàëüíîãî” óðîâíÿ òèðîêñèíà. Íîðìàòèâíûé èíòåðâàë ñâ.Ò4 0.8-1.8 íã/äë. ×òî çíà÷èò åñëè ó áîëüíîãî À. åãî íîðìàëüíûé ñâò4 Î.9 óïàë äî 0.7, à ó áîëüíîãî Á. ñ åãî íîðìàëüíîãî 1.7 äî òîãî æå 0.7, òî äîïîëíèòü ÑâÒ4 äî èõ èíäèâèäóàëüíûõ “ íîðì”ó À. ìîæíî 25 ìêã, a ó Á. òîëüêî 150.
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Dr.B |
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#8
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Êàê ðàç ñåãîäíÿ íà ïðè¸ìå ðàññìàòðèâàåìûé ñëó÷àé:
Æ, 42, ñ æàëîáàìè íà çàäåðæêó. Ñ êîíöà âåñíû îáñëåäîâàíà, âûÿâëåí ñóáêëèíè÷åñêèé àóòîèìóíûé ãèïîòèðîç: áûë ÒÒà îêîëî 8 (!). ÀÒ ê ÒÏÎ ïðèìåðíî 200 ñ êîï, Ò3 è Ò4 òî÷íî íå ïîìíþ. Æàëîáû â íà÷àëå çàáîëåâàíèÿ êëàññè÷åñêèå. ÍÀÇÍÀ×ÅÍÎ 50 ìêã òèðîêñèíà. Êîíòðîëü ÷åðåç 3 ìåñ ïðè¸ìà ïîêàçàë ÿâëåíèÿ òèðåîòîêñèêîçà ÒÒà óïàë äî 0,15, Ò4 ÷òî-òî îêëîë 18-20 íà âñêèäêó. Ÿ ýíäîêðèíîëîã èñïóãàëàñü /ìîëîäàÿ äåâî÷êà/ è îòìåíèëà ñîâñåì. Ïàöèåíòêà òîæå èñïóãàëàñü è ðàíüøå âðåìåíè ïîáåæàëà íà ÒÒà - èòîã åãî 74! Âðà÷ ñíîâà íàçíà÷àåò ë-òèðîêñèí. 25 (!) à ýòî êàê èçâåñòíî ïëàöåáî. Ñîîòâåòñòâåííî, ñèìïòîìàòèêà âåðíóëàñü äà åù¸ ñåðäå÷íûå ïðîáëåìû äîáàâèëèñü. Îíà ñîâñåì áðîñèëà ïèòü ïðåïàðàò. Ïðèøëà â æê òåïåðü ñ æàëîáàìè íà íàø ïðîôèëü. Ìû íå ïîëíîìî÷íû êàê ãèíåêîëîãè. Ïîñîâåòîâàëà ïåðåéòè íà 37,5. Ñìåíèòü âðà÷à. Âîïðîñ: êàê áûòü? Äîáàâëåíèå 12,5 äîçó ïëàöåáî äåëàþò ëå÷åáíîé? |
#9
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Âñå: ïðèñëóøèâàÿñü ê ìíîãîîïûòíîìó ÷åëîâåêó ñðàçó âûïüþ 5 ñòàêàíîâ âèñêè , à øåñòîé ãîðäî îòâåãíó è ïîéäó ìàøèíó âåñòè.
À ñåðüåçíî æå, ÷èòàÿ òóò ðåêîìåíäàöèè , òàê èìåííî êîãäà äîçà, ñêàæåì, ñíèæàåò ÒÒà ñ 50 äî 8, òî äîáàâëÿþòñÿ íè÷òîæíûå 25 ìêã è âñå èäåò õîðîøî.
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Dr.B |
#10
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åùå ñîîáðàæåíèÿ, íî â óçêîì äèàïàçîíå ïðèìåíåíèÿ: êîððåêöèÿ ñóáêëèíè÷åñêîãî ÒÒà áîëåå 4.0 èëè 4.5 ïåðåä áåðåìåííîñòüþ èëè âî âðåìÿ áåðåìåííîñòè - âñå ïóáëèêàöèè, ÷òî ïîïàëèñü, ãîâîðÿò î ìèíèìóìå 50 ìêã, à òî è 75 ìêã
With a dose of 50 mcg/day of thyroxine, 42% of patients reached a TSH level less than 3 μU/mL, and 20.6% had TSH levels higher than 4.5 μU/mL. --- treated based on pre-pregnancy weight and those that were given a fixed dose of 50 mcg/day. The percent of women who reached the target TSH of <2.5 mIU/L within 4-8 weeks 393 women were included: 252 treated using a fixed-dose approach; 141 treated based on pre-pregnancy weight. In the unadjusted analysis, there was no difference between the groups in the percentage of women in the target range within 4-8 weeks (89.6% in the fixed-dose group vs 88.8% in the weight-based group (p = .954) åäèíñòâåííàÿ ñòàòüÿ èç Êèòàÿ ãäå äàâàëè 25 ìêã ïðè ÒÒà áîëåå 4.0, íî òàì íå èçìåðÿëè ÒÒà â äèíàìèêå, à ñìîòðåëè íà êîëè÷åñòâî ïðåðûâàíèé áåðåìåííîñòè, õîòÿ òåîðåòè÷åñêè áåðåìåííûå êèòàéñêèå æåíøèíû ÷óòü ïîëåã÷å åâðîïåéñêèõ è ìåíüøàÿ äîçà íà ñòàðò âûãëÿäèò áîëåå ïðèåìëåìîé; â òàêîé ñèòóàöèè æåíùèíå ìîæíî ñêàçàòü, ÷òî 25 ìêã Âàì íå ïîìîæåò â òå÷åíèå 4-8 íåäåëü äîñòè÷ü æåëàåìûõ ÒÒÃ<2.5 èëè íå îêàæåò æåëàåìûé "áèîëîãè÷åñêèé" ýôôåêò. åùå â ïîäòâåðæäåíèå - áåðåìåííûì ñ ìîìåíòà óñòàíîâëåíèÿ äèàãíîçà ñóáêëèíè÷åñêèé ñ ÒÒà 4.2-10 áûëà íàçíà÷åíà äîçà 1.42 ± 0.31 μg/kg/day è îíè äîñòèãëè åóòèðîçà ÷åðåç ~6 íåäåëü è â 90% îñòàâàëèñü íà ýòîé äîçå äî êîíöà áåðåìåííîñòè, äàæå ñ íèçêèì âåñîì 50-55 êã 75 ìêã òèðîêñèíà âûãëÿäèò áîëåå öåëåâîé, íåæåëè 50 ìêã --- Thyroid. 2013 Nov;23(11):1479-83. Adequate levothyroxine doses for the treatment of hypothyroidism newly discovered during pregnancy òîæå ïðèìåðíî ñðåäè êèòàéñêèõ æåíùèí: group A (n = 29. Baseline TSH between 2.5 and 5.0 mIU/L) received 50 μg/day of LT4; group B (n = 17. Baseline TSH between 5.0 and 8.0 mIU/L) received 75 μg/day of L-T4; group C (n = 10. Baseline TSH >8.0 mIU/L) received 100 μg/day of LT4. All the patients started LT4 therapy around the 8th gestational week. 50, 75, and 100 μg/day can maintain serum TSH level of 79, 82, and 90 % of SCH --- Endocrine. 2013 Dec;44(3):710-5. The pattern of thyroid function of subclinical hypothyroid women with levothyroxine treatment during pregnancy
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Èñêðåííå, Âàäèì Âàëåðüåâè÷. |
#11
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Ñóììèðóÿ: ýêçîãåííûé òèðîêñèí íè â êîåì ñëó÷àå íå ïëàöåáî, îí áèîëîãè÷åñêè àêòèâåí â ËÞÁÛÕ äîçàõ. Ôèøêà æå â òîì, êàêîâ ÄÅÔÈÖÈÒ åãî, è âîò ýòîò äåôèöèò ìû è äîëæíû çàìåùàòü. Ïðîáëåìà â òîì, ÷òî ìû íå çíàåì êàêîâ òîò “íîðìàëüíûé” T4, ê êîòîðîìó ìû äîëæíû èäòè â êàæäîì îòäåëüíîì ñëó÷àå.
Ïëþñ êî âñåìó, äàæå àáñîëþòíûé äåôèöèò òèðîêñèíà íå äàåò íàì ïîëíîé êàðòèíû: áîëüíûå ñ îäèíàêîâûìè êîíöåíòðàöèÿìè Ò4 òðåáóþò ðàçíûå çàìåñòèòåëüíûå äîçû â çàâèñèìîñòè îò èõ âåñà è îò êîíöåíòðàöèè òèðîêñèí-ñâÿçûâàþùåãî ãëîáóëèíà ( ÒÑÃ), êîòîðàÿ ðåãóëèðóåòñÿ ôàêòîðàìè, íå çàâèñÿùèìè îò ôóíêöèè ùèòîâèäíîé æåëåçû ( âîçðàñò, ýñòðîãåíû ïîâûøàþò, à àíäðîãåíû ñíèæàþò), à òóò åùå ïå÷åíî÷íûå è ïî÷å÷íûå ôóíêöèè è ò.ä.)  îáùåì, ñëîæíî è ïëîõî ïðåäñêàçóåìî. Ìîè ïðåòåíçèè îòíîñÿòñÿ ïðîñòî ê îïðåäåëåíèþ íåâûñîêèõ äîç òèðîêñèíà (25 ìêã) êàê ê “ãîìåîïàòè÷åñêèì”. Ãîìåîïàòèÿ âñåãäà áèîëîãè÷åñêè íåýôôåêòèâíà è ÿâëÿåñÿ èñòèííûì ïëàöåáî. Òèðîêñèí 25 ìêã íè â êîåì ñëó÷àå íå ïëàöåáî, îí ïðîñòî íåäîñòàòî÷åí äëÿ áîëüøèíñòâà áîëüíûõ: ïðàêòè÷åñêè âñåõ ñ âûñîêèì âåñîì, ìóæ÷èí ( ïîíèæåííûé ÒÑÃ), æåíùèí, îñîáåííî áåðåìåííûõ èëè ïðèíèìàþùèõ îðàëüíûå ýñòðîãåíû ( âûñîêèé ÒÑÃ) è ò.ä. Òàê ÷òî íèêàêîé ïðàêòè÷åñêîé ðåâîëþöèè çäåñü íåò è â ïîìèíå: ïðîñòî ïðàâèëüíîå îïðåäåëåíèå ñèòóàöèè. È âîò ýòî-òî è ïîçâîëÿåò íàì ïîäóìàòü â êàæäîì èíäèâèäóàëüíîì ñëó÷àå è íàçíà÷èòü íåáîëüøóþ äîçó òèðîêñèíà ó áîëüíûõ ñ ìàðãèíàëüíî-ïîâûøåííûì ÒÒà áåç îïàñíîñòè ïåðåäîçèðîâêè : êàê íè êðóòè, à òèðîòîêñèêîç ìîæåò áûòü êðàéíå íåæåëàòåëüíûì , èëè äàæå îïàñíûì, îñîáåííî ó ñåðäå÷íèêîâ.  ñëó÷àÿõ ñóáêëèíè÷åñêîãî ãèïîòèðîèäèçìà, âðåìÿ,-êàê ïðàâèëî,- íà íaøåé ñòîðîíå: òîðîïèñü ìåäëåííî.
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Dr.B |