Gebelik ve Hipotiroidi
Özet
Gebelikte maternal tiroid bezi fizyolojisinde, fetüsün normal beyin ve beden gelişimi için kritik olan yeterli tiroid hormonunu sağlamak amacıyla önemli değişiklikler meydana gelir. Maternal tiroid hormon eksikliği; aşikar hipotiroidizm, subklinik hipotiroidizm ve izole hipotiroksinemi olarak sınıflandırılmaktadır. Dünya genelinde en yaygın neden iyot eksikliyken, iyot yeterli bölgelerde otoimmün tiroidit (Hashimoto) öne çıkar. Gebelikte östrojen artışına bağlı olarak tiroksin bağlayıcı globulin (TBG) konsantrasyonu iki ila üç kat yükselir; bu durum toplam T4 ve T3 seviyelerini artırırken, renal klirensin artması iyot ihtiyacını doğurur. İlk trimesterde hCG hormonunun tirotropik aktivitesi nedeniyle TSH seviyelerinde geçici düşüşler görülebilir. Aşikar hipotiroidizm; preeklampsi, plasenta dekolmanı, düşük doğum ağırlığı ve fetal ölüm gibi ciddi obstetrik risklerin yanı sıra çocukta nörogelişimsel bozukluklara yol açabilir. Tanıda trimestere özgü TSH referans aralıklarının kullanılması önerilir. Tedavide altın standart levotiroksin (LT4) monoterapisidir; gebelik doğrulanır doğrulanmaz LT4 dozu %30-50 oranında artırılmalı ve tiroid fonksiyon testleri 4 haftada bir yakından izlenmelidir. Subklinik vakaların yönetimi tartışmalı olsa da risk faktörleri ve antikor durumuna göre tedavi planlanır.
During pregnancy, maternal thyroid physiology undergoes substantial adaptations to maintain adequate hormone levels crucial for normal fetal brain development, as the fetal thyroid gland is not mature until 18-20 weeks. Thyroid deficiency is categorized into overt hypothyroidism, subclinical hypothyroidism, and isolated hypothyroxinemia. Worldwide, iodine deficiency is the primary cause, whereas autoimmune thyroiditis dominates in iodine-sufficient areas. Elevated estrogen increases thyroxine-binding globulin (TBG) two- to three-fold, raising total T4 and T3 levels, while increased glomerular filtration enhances renal iodine clearance. Concurrently, high hCG levels in early pregnancy exert thyrotropic activity, transiently suppressing TSH. Overt maternal hypothyroidism significantly correlates with adverse outcomes, including gestational hypertension, preeclampsia, placental abruption, low birth weight, and impaired neurointellectual development. Diagnosis relies ideally on trimester-specific TSH reference ranges. Levothyroxine (LT4) monotherapy is recommended for overt cases; pre-existing LT4 doses should be increased by 30-50% immediately upon pregnancy confirmation, followed by monitoring every 4 weeks. Management of subclinical hypothyroidism remains controversial, yet treatment is tailored according to specific maternal risk factors and thyroid peroxidase (TPO) antibody status.
Referanslar
Brenta G, Vaisman M, Sgarbi JA, et al. Clinical practice guidelines for the management of hypothyroidism. Arquivos brasileiros de endocrinologia e metabologia. 2013;57(4):265-291. doi:10.1590/s0004-27302013000400003
Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid : official journal of the American Thyroid Association. 2011;21(10):1081-1125. doi:10.1089/thy.2011.0087
López-Muñoz E, Mateos-Sánchez L, Mejía-Terrazas GE, et al. Hypothyroidism and isolated hypothyroxinemia in pregnancy, from physiology to the clinic. Taiwanese journal of obstetrics & gynecology. 2019;58(6):757-763. doi:10.1016/j.tjog.2019.09.005
Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid : official journal of the American Thyroid Association. 2017;27(3):315-389. doi:10.1089/thy.2016.0457
Teng W, Shan Z, Patil-Sisodia K, et al. Hypothyroidism in pregnancy. The lancet. Diabetes & endocrinology . 2013;1(3):228-237. doi:10.1016/S2213-8587(13)70109-8
Negro R, Mestman JH. Thyroid disease in pregnancy. Best practice & research. Clinical endocrinology & metabolism. 2011;25(6):927-943. doi:10.1016/j.beem.2011.07.010
TEMD Tiroid Hastalıkları Tanı ve Tedavi Kılavuzu 2020 [Online] https://temd.org.tr/yayinlar/kilavuzlar [Accessed: 16th June 2022]
Fantz CR, Dagogo-Jack S, Ladenson JH, et al. Thyroid function during pregnancy. Clinical Chemistry, 1999, 45.12: 2250-2258.
Ain KB, Mori Y, Refetoff S. Reduced clearance rate of thyroxine-binding globulin (TBG) with increased sialylation: a mechanism for estrogen-induced elevation of serum TBG concentration. The Journal of clinical endocrinology and metabolism. 1987;65:686-696.
Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocrine reviews . 1997;18(3):404-433. doi:10.1210/edrv.18.3.0300
Skjöldebrand L, Brundin J, Carlström A, Pettersson T. Thyroid associated components in serum during normal pregnancy. Acta endocrinologica (Copenh). 1982;100(4):504-511. doi:10.1530/acta.0.1000504
Brent GA. Maternal thyroid function: interpretation of thyroid function tests in pregnancy. Clinical obstetrics and gynecology. 1997;40(1):3-15. doi:10.1097/00003081-199703000-00004
Burrow GN, Fisher DA, Larsen PR. Maternal and fetal thyroid function. The New England journal of medicine. 1994;331(16):1072-1078. doi:10.1056/NEJM199410203311608
Fisher DA, Polk DH, Wu SY. Fetal thyroid metabolism: a pluralistic system. Thyroid : official journal of the American Thyroid Association. 1994;4(3):367-371. doi:10.1089/thy.1994.4.367
Yoshimura M, Hershman JM. Thyrotropic action of human chorionic gonadotropin. Thyroid : official journal of the American Thyroid Association. 1995;5(5):425-434. doi:10.1089/thy.1995.5.425
Tomer Y, Huber GK, Davies TF. Human chorionic gonadotropin (hCG) interacts directly with recombinant human TSH receptors. The Journal of clinical endocrinology and metabolism. 1992;74(6):1477-1479. doi:10.1210/jcem.74.6.1317388
Glinoer D, de Nayer P, Bourdoux P, et al. Regulation of maternal thyroid during pregnancy. The Journal of clinical endocrinology and metabolism. 1990;71(2):276-287. doi:10.1210/jcem-71-2-276
Davis LE, Leveno KJ, Cunningham FG. Hypothyroidism complicating pregnancy. Obstetrics and gynecology. 1988;72(1):108-112.
Allan WC, Haddow JE, Palomaki GE, et al. Maternal thyroid deficiency and pregnancy complications: implications for population screening. Journal of medical screening. 2000;7(3):127-130. doi:10.1136/jms.7.3.127
Bernal J, Guadaño-Ferraz A, Morte B. Perspectives in the study of thyroid hormone action on brain development and function. Thyroid : official journal of the American Thyroid Association vol.. 2003;13(11):1005-1012. doi:10.1089/105072503770867174
Moog NK, Entringer S, Heim C, et al. Influence of maternal thyroid hormones during gestation on fetal brain development. Neuroscience. 2017;342:68-100. doi:10.1016/j.neuroscience.2015.09.070
Burrow GN, Fisher DA, Larsen PR. Maternal and fetal thyroid function. The New England journal of medicine. 1994;331(16):1072-1078. doi:10.1056/NEJM199410203311608
Okosieme OE, Lazarus JH. Hypothyroidism in Pregnancy. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; February 11, 2019.
Lee SY, Pearce EN. Testing, Monitoring, and Treatment of Thyroid Dysfunction in Pregnancy. The Journal of clinical endocrinology and metabolism. 2021;106(3):883-892. doi:10.1210/clinem/dgaa945
Shan Z, Teng W. Thyroid hormone therapy of hypothyroidism in pregnancy. Endocrine. 2019;66(1):35-42. doi:10.1007/s12020-019-02044-2
Yassa L, Marqusee E, Fawcett R, et al. Thyroid hormone early adjustment in pregnancy (the THERAPY) trial. The Journal of clinical endocrinology and metabolism. 2010;95(7):3234-3241. doi:10.1210/jc.2010-0013