Thyroid hormone replacement therapy

被引:86
作者
Wiersinga, WM [1 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Endocrinol & Metab, NL-1105 AZ Amsterdam, Netherlands
关键词
hypothyroidism; replacement therapy; thyrotropin; thyroxine; triiodothyronine; euthyroidism;
D O I
10.1159/000048140
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thyroid hormone replacement has been used for more than 100 years in the treatment of hypothyroidism, and there is no doubt about its overall efficacy. Desiccated thyroid contains both thyroxine (T-4) and triiodothyronine (T-3); serum T-3 frequently rises to supranormal values in the absorption phase, associated with palpitations. Liothyronine (T-3) has the same drawback and requires twice-daily administration in view of its short half-life. Synthetic levothyroxine (L-T-4) has many advantages: in view of its long half-life, once-daily administration suffices, the occasional missing of a tablet causes no harm, and the extrathyroidal conversion of T-4 into T-3 (normally providing 80% of the daily T-3 production rate) remains fully operative, which may have some protective value during illness. Consequently, L-T-4 is nowadays preferred, and its long-term use is not associated with excess mortality. The mean T-4 dose required to normalize serum thyroid stimulating hormone (TSH) is 1.6 mug/kg per day, giving rise to serum free T-4 (fT(4)) concentrations that are slightly elevated or in the upper half of the normal reference range. The higher fT(4) values are probably due to the need to generate from T-4 the 20% of the daily T-3 production rate that otherwise is derived from the thyroid gland itself. The daily maintenance dose of T-4 varies widely between 75 and 250 mug. Assessment of the appropriate T-4 dose is by assay of TSH and fT(4), preferably in a blood sample taken before ingestion of the subsequent T-4 tablet. Dose adjustments can be necessary in pregnancy and when medications are used that are known to interfere with the absorption or metabolism of T-4. A new equilibrium is reached after approximately 6 weeks, implying that laboratory tests should not be done earlier. With a stable maintenance dose, an annual check-up usually suffices. Accumulated experience with L-T-4 replacement has identified some areas of concern. First, the bioequivalence sometimes differs among generics and brand names. Second, many patients on T-4 replacement have a subnormal TSH. TSH values of less than or equal to0.1 mU/I carry a risk of development of atrial fibrillation and are associated with bone loss although not with a higher fracture rate. It is thus advisable not to allow TSH to fall below - arbitrarily - 0.2 mU/I. Third, recent animal experiments indicate that only the combination of T-4 and T-3 replacement, and not T-4 alone, ensures euthyroidism in all tissues of thyroidectomized rats. It is indeed the experience of many physicians that there exists a small subset of hypothyroid patients who, despite biochemical euthyroidism, continue to complain of tiredness, lack of energy, discrete cognitive disorders and mood disturbances. As organs vary in the extent to which their T-3 content is derived from serum T-3 or locally produced T-3 from T-4, these complaints may have a biologic substrate; for example, brain T-3 content is largely determined by local deiodinase type II activity. Against this background it is of interest that a number of psychometric scores improved significantly in hypothyroid patients upon substitution of 50 mug of their T-4 replacement dose by 12.5 mug T-3. Confirmatory studies on this issue are urgently awaited. It could well be that a slow-release preparation containing both T-4 and T-3 might improve the quality of life, compared with T-4 replacement alone, in some hypothyroid patients. Copyright (C) 2001 S. Karger AG, Basel.
引用
收藏
页码:74 / 81
页数:8
相关论文
共 41 条
  • [1] THYROID-HORMONE LEVELS AFFECTED BY TIME OF BLOOD-SAMPLING IN THYROXINE-TREATED PATIENTS
    AIN, KB
    PUCINO, F
    SHIVER, TM
    BANKS, SM
    [J]. THYROID, 1993, 3 (02) : 81 - 85
  • [2] Increased need for thyroxine in women with hypothyroidism during estrogen therapy
    Arafah, BM
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (23) : 1743 - 1749
  • [3] CARDIAC EFFECTS OF LONG-TERM THYROTROPIN-SUPPRESSIVE THERAPY WITH LEVOTHYROXINE
    BIONDI, B
    FAZIO, S
    CARELLA, C
    AMATO, G
    CITTADINI, A
    LUPOLI, G
    SACCA, L
    BELLASTELLA, A
    LOMBARDI, G
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1993, 77 (02) : 334 - 338
  • [4] Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients
    Biondi, B
    Palmieri, EA
    Fazio, S
    Cosco, C
    Nocera, M
    Saccà, L
    Filetti, S
    Lombardi, G
    Perticone, F
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (12) : 4701 - 4705
  • [5] Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism
    Bunevicius, R
    Kazanavicius, G
    Zalinkevicius, R
    Prange, AJ
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (06) : 424 - 429
  • [6] LEAN BODY-MASS IS A PREDICTOR OF THE DAILY REQUIREMENT FOR THYROID-HORMONE IN OLDER MEN AND WOMEN
    CUNNINGHAM, JJ
    BARZEL, US
    [J]. JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 1984, 32 (03) : 204 - 207
  • [7] Bioequivalence of generic and brand-name levothyroxine products in the treatment of hypothyroidism
    Dong, BJ
    Hauck, WW
    Gambertoglio, JG
    Gee, L
    White, JR
    Bubp, JL
    Greenspan, FS
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1997, 277 (15): : 1205 - 1213
  • [8] Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat
    EscobarMorreale, HF
    delRey, FE
    Obregon, MJ
    deEscobar, GM
    [J]. ENDOCRINOLOGY, 1996, 137 (06) : 2490 - 2502
  • [9] Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats
    EscobarMorreale, HF
    Obregon, MJ
    delRey, FE
    deEscobar, GM
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (06) : 2828 - 2838
  • [10] Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism
    Ferretti, E
    Persani, L
    Jaffrain-Rea, ML
    Giambona, S
    Tamburrano, G
    Beck-Peccoz, P
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1999, 84 (03) : 924 - 929