Hypothyroidism is a common disorder, potentially severe, often clinically ignored, easily diagnosed by laboratory tests, and highly treatable. It may cause chronic illnesses if left untreated. Saudi Society of Endocrinology and Metabolism (SSEM) assembled a panel of twelve endocrinologists with experience in thyroid diseases in adults and children and made up a task force. An initial concept proposal that included types of hypothyroidism, population, scope, and prevalence in Saudi Arabia was obtained. The proposal was divided into several topics discussed in February 2022. The panel approved that the consensus will include all types of hypothyroidism in Saudi Arabia, screening, diagnosis, management, and special population. A literature review was carried out. Most of the latest international guidelines were screened in Europe and USA. The literature search was completed in March 2022. They drafted a report that was distributed to the entire panel. Approval of the recommendations required consensus, defined as a majority approval. The recommendations were revised to accommodate any differences of opinion until a consensus was reached. Recommendations were finally formulated on April 2022. Subsequently, the panel reviewed and discussed the supporting rationale of the revised recommendations. This article presents these practical recommendations.
The American Thyroid Association (2019) Clinical Thyroidology ® for the Public. A Publication of the American Thyroid Association, 12, 1-20. https://www.thyroid.org/wp-content/uploads/publications/ctfp/ct_public_v123.pdf
Aljabri, K.S.J., Alnasser, I.M., Facharatz, Bokhari, S.A., Alshareef, M.A., et al. (2019) The Frequency of Hypothyroidism in Saudi Community-Based Hospital a Retrospective Single Centre Study. Trends in Diabetes and Metabolism, 2, 1-2. https://doi.org/10.15761/TDM.1000107
Alqahtiani, N.M., Alramadhan, Z.T., Obaid, M.R.B., Kurdi, A.N., et al. (2020) Hypothyroidism in Saudi Arabia; Prevalence, Risk Factors, and Its Relation with Diabetes Mellitus. Archives of Pharmacy Practice, 11, 56-62.
Shaikh, A.A., Alsofyani, A., Shirah, B., Noaim, K.A., Ahmed, M.E., Babiker, A. and Alwan, I.A. (2021) Congenital Hypothyroidism in Saudi Population in Two Major Cities: A Retrospective Study on Prevalence and Therapeutic Outcomes. International Journal of Health Sciences, 15, 17-21.
Rugge, J.B., Bougatsos, C. and Chou, R. (2015) Screening and Treatment of Thyroid Dysfunction: An Evidence Review for the U.S. Preventive Services Task Force. Annals of Internal Medicine, 162, 35-45. https://doi.org/10.7326/M14-1456
Garber, J.R., Cobin, R.H., Gharib, H., Hennessey, J.V., Klein, I., Mechanick, J.I., et al. (2012) American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid, 22, 1200-1235. https://doi.org/10.1089/thy.2012.0205
Ford, G. and LaFranchi, S.H. (2014) Screening for Congenital Hypothyroidism: A Worldwide View of Strategies. Best Practice & Research. Clinical Endocrinology & Metabolism, 28, 175-187. https://doi.org/10.1016/j.beem.2013.05.008
Grosse, S.D. and Van Vliet, G. (2011) Prevention of Intellectual Disability through Screening for Congenital Hypothyroidism: How Much and at What Level? Archives of Disease in Childhood, 96, 374-379. https://doi.org/10.1136/adc.2010.190280
Kaplowitz, P., Bloch, C., The Section on Endocrinology, Sills, I.N., et al. (2016) Evaluation and Referral of Children with Signs of Early Puberty. Pediatrics, 137, e20153732. https://doi.org/10.1542/peds.2015-3732
Sisley, S., Trujillo, M.V., Khoury, J. and Backeljauw, P. (2013) Low Incidence of Pathology Detection and High Cost of Screening in the Evaluation of Asymptomatic Short Children. Journal of Pediatrics, 163, 1045-1051. https://doi.org/10.1016/j.jpeds.2013.04.002
Munns, C.F., Shaw, N., Kiely, M., Specker, B.L., Thacher, T.D., et al. (2016) Global Consensus Recommendation on Prevention and Management of Nutritional Rickets. The Journal of Clinical Endocrinology & Metabolism, 101, 394-415. https://doi.org/10.1210/jc.2015-2175
Gertig, A.M., Niechcial, A. and Skowronska, B. (2012) Thyroid Axis Alterations in Childhood Obesity. Pediatric Endocrinology, Diabetes and Metabolism, 18, 116-119.
Vaidya, B., Anthony, S., Bilous, M., Shields, B., Drury, J., Hutchison, S. and Bilous, R. (2007) Detection of Thyroid Dysfunction in Early Pregnancy: Universal Screening or Targeted High-Risk Case Finding? The Journal of Clinical Endocrinology and Metabolism, 92, 203-207. https://doi.org/10.1210/jc.2006-1748
Horacek, J., Spitalnikova, S., Dlabalova, B., Malirova, E., Vizda, J., Svilias, I., Cepkova, J., Mc Grath, C. and Maly, J. (2010) Universal Screening Detects Two-Times More Thyroid Disorders in Early Pregnancy than Targeted High-Risk Case Finding. European Journal of Endocrinology, 163, 645-650. https://doi.org/10.1530/EJE-10-0516
Brent, G.A. (2007) Diagnosing Thyroid Dysfunction in Pregnant Women: Is Case Finding Enough? The Journal of Clinical Endocrinology and Metabolism, 92, 39-41. https://doi.org/10.1210/jc.2006-2461
Ladenson, P.W., Singer, P.A., Ain, K.B., et al. (2000) American Thyroid Association Guidelines for Detection of Thyroid Dysfunction. Archives of Internal Medicine, 160, 1573-1575. https://doi.org/10.1001/archinte.160.11.1573
Baskin, H.J., Cobin, R.H., Duick, D.S., et al. (2002) American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Hyperthyroidism and Hypothyroidism. Endocrine Practice, 8, 457-469. https://doi.org/10.4158/1934-2403-8.6.457
American Academy of Family Physicians (2002) Introduction to AAFP Summary of Policy Recommendations for Periodic Health Examinations. American Family Physician, 65, Article 1467.
Helfand, M. and Redfern, C.C. (1998) Screening for Thyroid Disease: An Update. Annals of Internal Medicine, 129, 144-158. https://doi.org/10.7326/0003-4819-129-2-199807150-00020
Mariotti, S., Caturegli, P., Piccolo, P., Barbesino, G. and Pinchera, A. (1990) Antithyroid Peroxidase Autoantibodies in Thyroid Diseases. The Journal of Clinical Endocrinology & Metabolism, 71, 661-669. https://doi.org/10.1210/jcem-71-3-661
Rugge, B., Balshem, H., Sehgal, R., Relevo, R., Gorman, P. and Helfand, M. (2011) Screening and Treatment of Subclinical Hypothyroidism or Hyperthyroidism. Comparative Effectiveness Review No. 24. Agency for Healthcare Research and Quality, Rockville, MD.
Boucai, L., Hollowell, J.G. and Surks, M.I. (2011) An Approach for Development of Age-, Gender-, and Ethnicity-Specific Thyrotropin Reference Limits. Thyroid, 21, 5-11. https://doi.org/10.1089/thy.2010.0092
Surks, M.I., Ortiz, E., Daniels, G.H., Sawin, C.T., Col, N.F., Cobin, R.H., et al. (2004) Subclinical Thyroid Disease: Scientific Review and Guidelines for Diagnosis and Management. JAMA, 291, 228-238. https://doi.org/10.1001/jama.291.2.228
Canaris, G.J., Steiner, J.F. and Ridgway, E.C. (1997) Do Traditional Symptoms of Hypothyroidism Correlate with Biochemical Disease? Journal of General Internal Medicine, 12, 544-550. https://doi.org/10.1046/j.1525-1497.1997.07109.x
Utiger, R.D. (1965) Radioimmunoassay of Human Plasma Thyrotropin. The Journal of Clinical Investigation, 44, 1277-1286. https://doi.org/10.1172/JCI105234
Beck-Peccoz, P., Amr, S., Menezes-Ferreira, M.M., Faglia, G. and Weintraub, B.D. (1985) Decreased Receptor Binding of Biologically Inactive Thyrotropin in Central Hypothyroidism. Effect of Treatment with Thyrotropin-Releasing Hormone. The New England Journal of Medicine, 312, 1085-1090. https://doi.org/10.1056/NEJM198504253121703
Cappola, A.R. (2019) The Thyrotropin Reference Range Should Be Changed in Older Patients. JAMA, 322, 1961-1962. https://doi.org/10.1001/jama.2019.14728
Baloch, Z., Carayon, P., Conte-Devolx, B., Demers, L.M., Feldt-Rasmussen, U., Henry, J.F., et al. (2003) National Academy of Clinical Biochemistry. Laboratory Medicine Practice Guidelines. Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease. Thyroid, 13, 3-126.
Surks, M.I. and Hollowell, J.G. (2007) Age-Specific Distribution of Serum Thyrotropin and Antithyroid Antibodies in the US Population: Implications for the Prevalence of Subclinical Hypothyroidism. The Journal of Clinical Endocrinology & Metabolism, 92, 4575-4582. https://doi.org/10.1210/jc.2007-1499
Hollowell, J.G., Staehling, N.W., Flanders, W.D., et al. (2022) Serum TSH, T4, and Thyroid Antibodies in the United States Population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III).The Journal of Clinical Endocrinology & Metabolism, 87, 489-499. https://doi.org/10.1210/jcem.87.2.8182
Vanderpump, M.P.J., Tunbridge, W.M.G., French, J.M., et al. (1995) The Incidence of Thyroid Disorders in the Community: A Twenty-Year Follow-Up of the Whickham Survey. Clinical Endocrinology, 43, 55-68. https://doi.org/10.1111/j.1365-2265.1995.tb01894.x
Huber, G., Staub, J.-J., Meier, C., et al. (2002) Prospective Study of the Spontaneous Course of Subclinical Hypothyroidism: Prognostic Value of Thyrotropin, Thyroid Reserve, and Thyroid Antibodies. The Journal of Clinical Endocrinology & Metabolism, 87, 3221-3226. https://doi.org/10.1210/jcem.87.7.8678
Garber, J.R., Hennessey, J.V., Liebermann, J.A., Morris C.M. and Talbert, R.L. (2006) Managing the Challenges of Hypothyroidism. Journal of Family Practice, 55, S1-S8.
Bhandare, N., Kennedy, L., Malyapa, R.S., Morris, C.G. and Mendenhall, W.M. (2007) Primary and Central Hypothyroidism after Radiotherapy for Head-and-Neck Tumors. International Journal of Radiation Oncology, Biology, Physics, 68, 1131-1139. https://doi.org/10.1016/j.ijrobp.2007.01.029
Alexopoulou, O., Beguin, C., De Nayer, P. and Maiter, D. (2004) Clinical and Hormonal Characteristics of Central Hypothyroidism at Diagnosis and during Follow-Up in Adult Patients. European Journal of Endocrinology, 150, 1-8. https://doi.org/10.1530/eje.0.1500001
Yamada, M. and Mori, M. (2008) Mechanisms Related to the Pathophysiology and Management of Central Hypothyroidism. Nature Clinical Practice Endocrinology & Metabolism, 4, 683-694. https://doi.org/10.1038/ncpendmet0995
Kondo, Y., Ozawa, A., Kohno, D., Saito, K., Buyandalai, B., Yamada, S., et al. (2002) The Hypothalamic Paraventricular Nucleus Is the Center of the Hypothalamic-Pi-tuitary-Thyroid Axis for Regulating Thyroid Hormone Levels. Thyroid: Official Journal of the American Thyroid Association, 32, 105-114.
Persani, L., Ferretti, E., Borgato, S., et al. (2000) Circulating Thyrotropin Bioactivity in Sporadic Central Hypothyroidism. The Journal of Clinical Endocrinology & Metabolism, 85, Article 3631. https://doi.org/10.1210/jc.85.10.3631
Persani, L., Brabant, G., Dattani, M., Bonomi, M., Feldt-Rasmussen, U., Fliers, E., Gruters, A., Maiter, D., Schoenmakers, N. and Van Trotsenburg, A.S.P. (2018) 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism. European Thyroid Journal, 7, 225-237. https://doi.org/10.1159/000491388
Goldsmith, R.E., Sturgis, S.H., Lerman, J. and Stanbury, J.B. (1952) The Menstrual Pattern in Thyroid Disease. The Journal of Clinical Endocrinology and Metabolism, 12, 846-855. https://doi.org/10.1210/jcem-12-7-846
Abalovich, M., Gutierrez, S., Alcaraz, G., Maccallini, G., Garcia, A. and Levalle, O. (2002) Overt and Subclinical Hypothyroidism Complicating Pregnancy. Thyroid: Official Journal of the American Thyroid Association, 12, 63-68. https://doi.org/10.1089/105072502753451986
Krassas, G.E., Pontikides, N., Kaltsas, T., Papadopoulou, P., Paunkovic, J., Paunkovic, N. and Duntas, L.H. (1999) Disturbances of Menstruation in Hypothyroidism. Clinical Endocrinology, 50, 655-659. https://doi.org/10.1046/j.1365-2265.1999.00719.x
Hallengren, B., Lantz, M., Andreasson, B., and Grennert, L. (2009) Pregnant Women on Thyroxine Substitution Are Often Dysregulated in Early Pregnancy. Thyroid: Official Journal of the American Thyroid Association, 19, 391-394. https://doi.org/10.1089/thy.2008.0206
Stagnaro-Green, A., Abalovich, M., Alexander, E., Azizi, F., Mestman, J., Negro, R., et al. (2011) American Thyroid Association Taskforce on Thyroid Disease during Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum. Thyroid, 21, 1081-1125. https://doi.org/10.1089/thy.2011.0087
De Groot, L., Abalovich, M., Alexander, E.K., Amino, N., Barbour, L., Cobin, R.H., et al. (2012) Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, 97, 2543-2565. https://doi.org/10.1210/jc.2011-2803
Haddow, J.E., Palomaki, G.E. and McClain, M.R. (2006) Thyroid-Stimulating Hormone in singleton and Twin Pregnancy: Importance of Gestational Age-Specific Reference Ranges. Obstetrical & Gynecological, 107, 205-206. https://doi.org/10.1097/01.AOG.0000195268.33533.8a
Soldin, O.P., Soldin, D. and Sastoque, M. (2007) Gestation Specific Thyroxine and Thyroid Stimulating Hormone Levels in the United States and Worldwide. Therapeutic Drug Monitoring, 29, 553-559. https://doi.org/10.1097/FTD.0b013e31815709ac
Haddow, J.E., McClain, M.R., Lambert-Messerlian, G., Palomaki, G.E., Canick, J.A., Cleary-Goldman, J., et al. (2008) First and Second Trimester Evaluation of Risk for Fetal Aneuploidy Research Consortium: Variability in Thyroid-Stimulating Hormone Suppression by Human Chorionic Gonadotropin during Early Pregnancy. The Journal of Clinical Endocrinology & Metabolism, 93, 3341-3347. https://doi.org/10.1210/jc.2008-0568
Zhang, D., Cai. K., Wang, G., Xu, S., Mao, X., Zheng, A., Liu, C. and Fan, K. (2019) Trimester-Specific Reference Ranges for Thyroid Hormones in Pregnant Women. Medicine, 98, e14245. https://doi.org/10.1097/MD.0000000000014245
Pop, V.J., Kuijpens, J.L., Van Baar, A.L., Verkerk, G., Van Son, M.M., de Vijlder, J.J., et al. (1999) Low Maternal Free Thyroxine Concentrations during Early Pregnancy are Associated with Impaired Psychomotor Development in Infancy. Clinical Endocrinology, 50, 149-155. https://doi.org/10.1046/j.1365-2265.1999.00639.x
Pop, V.J., Brouwers, E.P., Vader, H.L., Vulsma, T., Van Baar, A.L. and De Vijlder, J.J. (2003) Maternal Hypothyroxinaemia during Early Pregnancy and Subsequent Child Development: A 3-Year Follow-Up Study. Clinical Endocrinology, 59, 282-288. https://doi.org/10.1046/j.1365-2265.2003.01822.x
Henrichs, J., Bongers-Schokking, J.J., Schenk, J.J., Ghassabian, A., Schmidt, H.G., Visser, T.J., et al. (2010) Maternal Thyroid Function during Early Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study. The Journal of Clinical Endocrinology & Metabolism, 95, 4227-4234. https://doi.org/10.1210/jc.2010-0415
Finken, M.J., Van Eijsden, M., Loomans, E.M., Vrijkotte, T.G. and Rotteveel, J. (2013) Maternal Hypothyroxinemia in Early Pregnancy Predicts Reduced Performance in Reaction Time Tests in 5-to 6-Year-Old Offspring. The Journal of Clinical Endocrinology & Metabolism, 98, 1417-1426. https://doi.org/10.1210/jc.2012-3389
Henrichs, J., Ghassabian, A., Peeters, R.P. and Tiemeier, H. (2013) Maternal Hypothyroxinemia and Effects on Cognitive Functioning in Childhood: How and Why? Clinical Endocrinology, 79, 152-162. https://doi.org/10.1111/cen.12227
Pramanik, S., Mukhopadhyay, P. and Ghosh, S. (2020) Total T4 Rise in Pregnancy: A Relook? Thyroid Research, 13, Article No. 14. https://doi.org/10.1186/s13044-020-00088-5
Van Trotsenburg, P., Stoupa, A., Léger, J., et al. (2021) Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid, 31, 387-419. https://doi.org/10.1089/thy.2020.0333
American Academy of Pediatrics, Rose S.R., Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown, S., et al. (2006) Update of Newborn Screening and Therapy for Congenital Hypothyroidism. Pediatrics, 117, 2290-2303. https://doi.org/10.1542/peds.2006-0915
Rastogi, M.V. and LaFranchi, S.H. (2010) Congenital Hypothyroidism. Orphanet Journal of Rare Diseases, 5, Article No. 17. https://doi.org/10.1186/1750-1172-5-17
Jonklaas, J., Bianco, A.C., Bauer, A.J., Burman, K.D., Cappola, A.R., Celi, F.S., et al. (2014) American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid, 24, 1670-1751. https://doi.org/10.1089/thy.2014.0028
Yen, P.M. (2001) Physiological and Molecular Basis of Thyroid Hormone Action. Physiological Reviews, 81, 1097-1142. https://doi.org/10.1152/physrev.2001.81.3.1097
Brent, G.A. (2012) Mechanisms of Thyroid Hormone Action. Journal of Clinical Investigation, 122, 3035-3043. https://doi.org/10.1172/JCI60047
Braverman, L.E., Ingbar, S.H. and Sterling, K. (1970) Conversion of Thyroxine (T4) to Triiodothyronine (T3) in Athyreotic Human Subjects. Journal of Clinical Investigation, 49, 855-864. https://doi.org/10.1172/JCI106304
Yue, C.S., Scarsi, C. and Ducharme, M.P. (2012) Pharmacokinetics and Potential Advantages of a New Oral Solution of Levothyroxine vs. Other Available Dosage Forms. Arzneimittelforschung, 62, 631-636. https://doi.org/10.1055/s-0032-1329951
Oppenheimer, J.H., Braverman, L.E., Toft, A., Jackson, I.M. and Ladenson, P.W. (1995) A Therapeutic Controversy. Thyroid Hormone Treatment: When and What? The Journal of Clinical Endocrinology & Metabolism, 80, 2873-2883. https://doi.org/10.1210/jcem.80.10.7559868
Dong, B.J., Hauck, W.W., Gambertoglio, J.G., et al. (1997) Bioequivalence of Generic and Brand-Name Levothyroxine Products in the Treatment of Hypothyroidism. JAMA, 277, 1205-1213. https://doi.org/10.1001/jama.1997.03540390035032
Blakesley, V., Awni, W., Locke, C., Ludden, T., Granneman, G.R. and Braverman, L.E. (2004) Are Bioequivalence Studies of Levothyroxine Sodium Formulations in Euthyroid Volunteers Reliable? Thyroid, 14, 191-200. https://doi.org/10.1089/105072504773297867
U.S. Food and Drug Administration. FDA Acts to Ensure Thyroid Drugs Don’t Lose Potency before Expiration Date. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-acts-ensure-thyroid-drugs-dont-lose-potency-expiration-date
Kabadi, U.M. and Kabadi, M.M. (2001) Serum Thyrotropin in Primary Hypothyroidism: A Reliable and Accurate Predictor of Optimal Daily Levothyroxine Dose. Endocrine Practice, 7, 16-18. https://doi.org/10.4158/EP.7.1.16
Papoian, V., Ylli, D., Felger, E.A., Wartofsky, L. and Rosen, J.E. (2019) Evaluation of Thyroid Hormone Replacement Dosing in Overweight and Obese Patients after a Thyroidectomy. Thyroid, 29, 1558-1562. https://doi.org/10.1089/thy.2019.0251
Pang, X., Pu, T., Xu, L. and Sun, R. (2020) Effect of L-Thyroxine Administration before Breakfast vs at Bedtime on Hypothyroidism: A Meta-Analysis. Clinical Endocrinology, 92, 475-481. https://doi.org/10.1111/cen.14172
Bach-Huynh, T.G., Nayak, B., Loh, J., Soldin, S. and Jonklaas, J. (2009) Timing of Levothyroxine Administration Affects Serum Thyrotropin Concentration. The Journal of Clinical Endocrinology & Metabolism, 94, 3905-3912. https://doi.org/10.1210/jc.2009-0860
Perez, C.L., Araki, F.S., Graf, H. and De Carvalho, G.A. (2013) Serum Thyrotropin Levels Following Levothyroxine Administration at Breakfast. Thyroid, 23, 779-784. https://doi.org/10.1089/thy.2012.0435
Hegedüs, L., Hansen, J.M., Feldt-Rasmussen, U., Hansen, B.M. and Høier-Madsen, M. (1991) Influence of Thyroxine Treatment on Thyroid Size and Anti-Thyroid Peroxidase Antibodies in Hashimoto’s Thyroiditis. Clinical Endocrinology, 35, 235-238. https://doi.org/10.1111/j.1365-2265.1991.tb03528.x
Hayashi, Y., Tamai, H., Fukata, S., Hirota, Y., Katayama, S., Kuma, K., Kumagai, L.F. and Nagataki, S. (1985) A Long Term Clinical, Immunological, and Histological Follow-Up Study of Patients with Goitrous Chronic Lymphocytic Thyroiditis. The Journal of Clinical Endocrinology & Metabolism, 61, 1172-1178. https://doi.org/10.1210/jcem-61-6-1172
Waise, A. and Price, H.C. (2009) The Upper Limit of the Reference Range for Thyroid-Stimulating Hormone Should Not Be Confused with a Cut-Off to Define Subclinical Hypothyroidism. Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 46, 93-98. https://doi.org/10.1258/acb.2008.008113
(2019) Thyroid Disease: Assessment and Management. NICE Guideline, No. 145. National Institute for Health and Care Excellence (NICE), London. https://www.ncbi.nlm.nih.gov/books/NBK550859/
Gadiraju, S., Lee, C.J. and Cooper, D.S. (2016) Levothyroxine Dosing Following Bariatric Surgery. Obesity Surgery, 26, 2538-2542. https://doi.org/10.1007/s11695-016-2314-x
Azizi, F., Belur, R. and Albano, J. (1979) Malabsorption of Thyroid Hormones after Jejunoileal Bypass for Obesity. Annals of Internal Medicine, 90, 941-942. https://doi.org/10.7326/0003-4819-90-6-941
Curran, P.G. and DeGroot, L.J. (1991) The Effect of Hepatic Enzyme-Inducing Drugs on Thyroid Hormones and the Thyroid Gland. Endocrine Reviews, 12, 135-150. https://doi.org/10.1210/edrv-12-2-135
Kim, H.I., Kim, T.H., Kim, H., et al. (2017) Effect of Rifampin on Thyroid Function Test in Patients on Levothyroxine Medication. PLOS ONE, 12, e0169775. https://doi.org/10.1371/journal.pone.0169775
Goldberg, A.S., Tirona, R.G., Asher, L.J., Kim, R.B. and Van Uum, S.H.M. (2013) Ciprofloxacin and Rifampin Have Opposite Effects on Levothyroxine Absorption. Thyroid, 23, 1374-1378. https://doi.org/10.1089/thy.2013.0014
Bugdaci, M.S., Zuhur, S.S., Sokmen, M., Toksoy, B., Bayraktar, B. and Altuntas, Y. (2011) The Role of Helicobacter Pylori in Patients with Hypothyroidism in Whom Could Not Be Achieved Normal Thyrotropin Levels despite Treatment with High Doses of Thyroxine. Helicobacter, 16, 124-130. https://doi.org/10.1111/j.1523-5378.2011.00830.x
Checchi, S., Montanaro, A., Pasqui, L., Ciuoli, C., De Palo, V., Chiappetta, M.C. and Pacini, F. (2008) L-Thyroxine Requirement in Patients with Autoimmune Hypo-thyroidism and Parietal Cell Antibodies. The Journal of Clinical Endocrinology & Metabolism, 93, 465-469. https://doi.org/10.1210/jc.2007-1544
Virili, C., Bassotti, G., Santaguida, M.G., Iuorio, R., Del Duca, S.C., Mercuri, V., Picarelli, A., Gargiulo, P., Gargano, L. and Centanni, M. (2012) Atypical Celiac Disease as Cause of Increased Need for Thyroxine: A Systematic Study. The Journal of Clinical Endocrinology & Metabolism, 97, E419-E422. https://doi.org/10.1210/jc.2011-1851
Collins, D., Wilcox, R., Nathan, M. and Zubarik, R. (2012) Celiac Disease and Hypothyroidism. The American Journal of Medicine, 125, 278-282. https://doi.org/10.1016/j.amjmed.2011.09.003
Morris, J.C. (2009) How Do you Approach the Problem of TSH Elevation in a Patient on High-Dose Thyroid Hormone Replacement? Clinical Endocrinology, 70, 671-673. https://doi.org/10.1111/j.1365-2265.2009.03536.x
Ramadhan, A. and Tamilia, M. (2012) Treatment-Refractory Hypothyroidism. CMAJ, 184, 205-209. https://doi.org/10.1503/cmaj.110994
Benvenga, S. (2014) Solution of a Diagnostic Problem upon Visiting the Patient at Home and Reading Their Medication Leaflet. Endocrine Practice, 20, 517. https://doi.org/10.4158/endp.20.5.028633k1031088p1
Escobar-Morreale, H.F., Botella-Carretero, J.I., del Rey, F.E. and de Escobar, G.M. (2005) Treatment of Hypothyroidism with Combinations of Levothyroxine plus Liothyronine. The Journal of Clinical Endocrinology and Metabolism, 90, 4946-4954. https://doi.org/10.1210/jc.2005-0184
Grozinsky-Glasberg, S., Fraser, A., Nahshoni, E., Weizman, A. and Leibovici L. (2006) Thyroxine-Triiodothyronine Combination Therapy versus Thyroxine Monotherapy for Clinical Hypothyroidism: Meta-Analysis of Randomized Controlled trials. The Journal of Clinical Endocrinology & Metabolism, 91, 2592-2599. https://doi.org/10.1210/jc.2006-0448
Keating F.R., Parkin, T.W., Selby, J.B. and Dickinson, L.S. (1961) Treatment of Heart Disease Associated with Myxedema. Progress in Cardiovascular Diseases, 3, 364-381. https://doi.org/10.1016/S0033-0620(61)90004-4
Catz, B. and Russell, S. (1961) Myxedema, Shock and Coma. Seven Survival Cases. Archives of Internal Medicine, 108, 407-417. https://doi.org/10.1001/archinte.1961.03620090079010
Somwaru, L.L., Arnold, A.M., Joshi, N., Fried, L.P. and Cappola, A.R. (2009) High Frequency of and Factors Associated with Thyroid Hormone Over-Replacement and Under-Replacement in Men and Women Aged 65 and over. The Journal of Clinical Endocrinology & Metabolism, 94, 1342-1345. https://doi.org/10.1210/jc.2008-1696
LaFranchi, S.H. (2011) Approach to the Diagnosis and Treatment of Neonatal Hypothyroidism. The Journal of Clinical Endocrinology and Metabolism, 96, 2959-2967. https://doi.org/10.1210/jc.2011-1175
Selva, K.A., Harper, A., Downs, A., Blasco, P.A. and Lafranchi, S.H. (2005) Neurodevelopmental Outcomes in Congenital Hypothyroidism: Comparison of Initial T4 Dose and Time to Reach Target T4 and TSH. The Journal of Pediatrics, 147, 775-780. https://doi.org/10.1016/j.jpeds.2005.07.024
Selva, K.A., Mandel, S.H., Rien, L., et al. (2002) Initial Treatment Dose of L-Thyroxine in Congenital Hypothyroidism. The Journal of Pediatrics, 141, 786-792. https://doi.org/10.1067/mpd.2002.128887
Heyerdahl, S. and Oerbeck, B. (2003) Congenital Hypothyroidism: Developmental Outcome in Relation to Levothyroxine Treatment Variables. Thyroid, 13, 1029-1038. https://doi.org/10.1089/105072503770867200
Vogiatzi, M.G. and Kirkland, J.L. (1997) Frequency and Necessity of Thyroid Function Tests in Neonates and Infants with Congenital Hypothyroidism. Pediatrics, 100, e6. https://doi.org/10.1542/peds.100.3.e6
Mathai, S., Cutfield, W.S., Gunn, A.J., et al. (2008) A Novel Therapeutic Paradigm to Treat Congenital Hypothyroidism. Clinical Endocrinology, 69, 142-147. https://doi.org/10.1111/j.1365-2265.2008.03172.x
Balhara, B., Misra, M. and Levitsky, L.L. (2011) Clinical Monitoring Guidelines for Congenital Hypothyroidism: Laboratory Outcome Data in the First Year of Life. The Journal of Pediatrics, 158, 532-537. https://doi.org/10.1016/j.jpeds.2010.10.006
LaFranchi, S.H., Haddow, J.E. and Hollowell, J.G. (2005) Is Thyroid Inadequacy during Gestation a Risk Factor for Adverse Pregnancy and Developmental Outcomes? Thyroid: Official Journal of the American Thyroid Association, 15, 60-71. https://doi.org/10.1089/thy.2005.15.60
Leung, A.S., Millar, L.K., Koonings, P.P., Montoro, M. and Mestman, J.H. (1993) Perinatal Outcome in Hypothyroid Pregnancies. Obstetrical & Gynecological Survey, 81, 349-353. https://doi.org/10.1016/0020-7292(93)90343-U
Wasserstrum, N. and Anania, C.A. (1995) Perinatal Consequences of Maternal Hypothyroidism in Early Pregnancy and Inadequate Replacement. Clinical Endocrinology, 42, 353-358. https://doi.org/10.1111/j.1365-2265.1995.tb02642.x
Stagnaro-Green, A., Chen, X., Bogden, J.D., Davies, T.F. and Scholl, T.O. (2005) The Thyroid and Pregnancy: A Novel Risk Factor for Very Preterm Delivery. Thyroid, 15, 351-357. https://doi.org/10.1089/thy.2005.15.351
Männistö, T., Mendola, P., Grewal, J., Xie, Y., Chen, Z. and Laughon, S.K. (2013) Thyroid Diseases and Adverse Pregnancy Outcomes in a Contemporary US Cohort. The Journal of Clinical Endocrinology & Metabolism, 98, 2725-2733. https://doi.org/10.1210/jc.2012-4233
Willoughby, K.A., McAndrews, M.P. and Rovet, J.F. (2014) Effects of Maternal Hypothyroidism on Offspring Hippocampus and Memory. Thyroid, 24, 576-584. https://doi.org/10.1089/thy.2013.0215
Korevaar, T.I.M. (2018) The Upper Limit for TSH during Pregnancy: Why We Should Stop Using Fixed Limits of 2.5 or 3.0 mU/L. Thyroid Research, 11, Article No. 5. https://doi.org/10.1186/s13044-018-0048-7
Medici, M., Korevaar, T.I., Visser, W.E., Visser, T.J. and Peeters, R.P. (2015) Thyroid Function in Pregnancy: What Is Normal? Clinical Chemistry, 61, 704-713. https://doi.org/10.1373/clinchem.2014.236646
LeBeau, S.O. and Mandel, S.J. (2006) Thyroid Disorders during Pregnancy. Endocrinology and Metabolism Clinics of North America, 35, 117-136. https://doi.org/10.1016/j.ecl.2005.09.009
Ashoor, G., Rotas, M., Maiz, N., Kametas, N.A. and Nicolaides, K.H. (2010) Maternal Thyroid Function at 11-13 Weeks of Gestation in Women with Hypothyroidism Treated by Thyroxine. Fetal Diagnosis and Therapy, 28, 22-27. https://doi.org/10.1159/000314906
Taylor, P.N., Minassian, C., Rehman, A., Iqbal, A., Draman, M.S., Hamilton, W., Dunlop, D., Robinson, A., Vaidya, B., Lazarus, J.H., Thomas, S., Dayan, C.M. and Okosieme, O.E. (2014) TSH Levels and Risk of Miscarriage in Women on Long-Term Levothyroxine: A Community-Based Study. The Journal of Clinical Endocrinology & Metabolism, 99, 3895-3902. https://doi.org/10.1210/jc.2014-1954
Kaplan, M.M. (1996) Management of Thyroxine Therapy during Pregnancy. Endocrine Practice, 2, 281-286. https://doi.org/10.4158/EP.2.4.281
Alexander, E.K., Marqusee, E., Lawrence, J., Jarolim, P., Fischer, G.A. and Larsen, P.R. (2004) Timing and Magnitude of Increases in Levothyroxine Requirements during Pregnancy in Women with Hypothyroidism. The New England Journal of Medicine, 351, 241-249. https://doi.org/10.1056/NEJMoa040079
Vadiveloo, T., Mires, G.J., Donnan, P.T. and Leese, G.P. (2013) Thyroid Testing in Pregnant Women with Thyroid Dysfunction in Tayside, Scotland: The Thyroid Epidemiology, Audit and Research Study (TEARS). Clinical Endocrinology, 78, 466-471. https://doi.org/10.1111/j.1365-2265.2012.04426.x
Abalovich, M., Alcaraz, G., Kleiman-Rubinsztein, J., Pavlove, M.M., Cornelio, C., Levalle, O. and Gutierrez, S. (2010) The Relationship of Preconception Thyrotropin Levels to Requirements for Increasing the Levothyroxine Dose during Pregnancy in Women with Primary Hypothyroidism. Thyroid, 20, 1175-1178. https://doi.org/10.1089/thy.2009.0457
Grebe, S.K., Cooke, R.R., Ford, H.C., Fagerström, J.N., Cordwell, D.P., Lever, N.A., Purdie, G.L. and Feek, C.M. (1997) Treatment of Hypothyroidism with Once Weekly Thyroxine. The Journal of Clinical Endocrinology & Metabolism, 82, 870-875. https://doi.org/10.1210/jc.82.3.870
Mohames Shakir, K.M., Turton, D., Aprill, B.S., Drake, A.J. and Eisold, R.J.F. (2000) Anemia: A Cause of Intolerance to Thyroxine Sodium. Mayo Clinic Proceedings Home, 75, 189-192. https://doi.org/10.1016/S0025-6196(11)64193-1
Magner, J., Gerber, P. (1994) Urticaria Due to Blue Dye in Synthroid Tablets. Thyroid, 4, 341. https://doi.org/10.1089/thy.1994.4.341
Choi, Y.H., Choi, W.Y., Kang, H.C., Koh, Y.I., Bae, E.H. and Kim, S.W. (2012) Drug Rash Induced by Levothyroxine Tablets. Thyroid, 22, 1090. https://doi.org/10.1089/thy.2011.0462
Jonklaas, J., Bianco, A.C., Cappola, A.R., Celi, F.S., Fliers, E., Heuer. H., McAninch, E.A., Moeller, L.C., Nygaard, B., Sawka, A.M., Watt, T. and Dayan, C.M. (2021) Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document. Thyroid, 31, 156-182. https://doi.org/10.1089/thy.2020.0720
National Institiute for Health and Care Excellence (NICE) (2019) Thyroid Disease: Assessment and Management. https://www.nice.org.uk/guidance/ng145
Biondi, B., Cappola, A.R. and Cooper, D.S. (2019) Subclinical Hypothyroidism: A Review. JAMA, 322, 153-160. https://doi.org/10.1001/jama.2019.9052
McDermott, M.T. and Ridgway, E.C. (2001) Subclinical Hypothyroidism Is Mild Thyroid Failure and Should Be Treated. The Journal of Clinical Endocrinology & Metabolism, 86, 4585-4590. https://doi.org/10.1210/jcem.86.10.7959
Gharib, H., Tuttle, R.M., Baskin, H.J., Fish, L.H., Singer, P.A. and McDermott, M.T. (2005) Subclinical Thyroid Dysfunction: A Joint Statement on Management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society. The Journal of Clinical Endocrinology & Metabolism, 90, 581-585. https://doi.org/10.1210/jc.2004-1231
Calissendorff, J. and Falhammar, H. (2020) To Treat or Not to Treat Subclinical Hypothyroidism, What Is the Evidence? Medicina, 56, Article 40. https://doi.org/10.3390/medicina56010040
Pearce, S.H., Brabant, G., Duntas, L.H., Monzani, F., Peeters, R.P., Razvi, S. and Wemeau, J.L. (2013) 2013 ETA Guideline: Management of Subclinical Hypothyroidism. European Thyroid Journal, 2, 215-228. https://doi.org/10.1159/000356507
National Guideline Centre (UK) (2019) Management of Subclinical Hypothyroidism: Thyroid Disease: Assessment and Management: Evidence Review G. NICE Guideline, No. 145. National Institute for Health and Care Excellence (NICE), London.
Liu, H., Shan, Z., Li, C., Mao, J., Xie, X., Wang, W., Fan, C., Wang, H., Zhang, H., Han, C., Wang, X., Liu, X., Fan, Y., Bao, S. and Teng, W. (2014) Maternal Subclinical Hypothyroidism, Thyroid Autoimmunity, and the Risk of Miscarriage: A Prospective Cohort Study. Thyroid, 24, 1642-1649. https://doi.org/10.1089/thy.2014.0029
Alexander, E.K., Pearce, E.N., Brent, G.A., Brown, R.S., Chen, H., Dosiou, C., Grobman, W.A., Laurberg, P., Lazarus, J.H., Mandel, S.J., Peeters, R.P. and Sullivan, S. (2017) 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid, 27, 315-389. https://doi.org/10.1089/thy.2016.0457
Negro, R., Formoso, G., Mangieri, T., Pezzarossa, A., Dazzi, D. and Hassan, H. (2006) Levothyroxine Treatment in Euthyroid Pregnant Women with Autoimmune Thyroid Disease: Effects on Obstetrical Complications. The Journal of Clinical Endocrinology & Metabolism, 91, 2587-2591. https://doi.org/10.1210/jc.2005-1603
Lepoutre, T., Debiève, F., Gruson, D. and Daumerie, C. (2012) Reduction of Miscarriages through Universal Screening and Treatment of Thyroid Autoimmune Diseases. Gynecologic and Obstetric Investigation, 74, 265-273. https://doi.org/10.1159/000343759
Nazarpour, S., Ramezani Tehrani, F., Simbar, M., Tohidi, M., Alavi Majd, H. and Azizi, F. (2017) Effects of Levothyroxine Treatment on Pregnancy Outcomes in Pregnant Women with Autoimmune Thyroid Disease. European Journal of Endocrinology, 176, 253-265. https://doi.org/10.1530/EJE-16-0548
Sun, X., Hou, N., Wang, H., Ma, L., Sun, J. and Liu, Y. (2020) A Meta-Analysis of Pregnancy Outcomes with Levothyroxine Treatment in Euthyroid Women with Thyroid Autoimmunity. The Journal of Clinical Endocrinology & Metabolism, 105, 1009-1019. https://doi.org/10.1210/clinem/dgz217
Radetti, G., Maselli, M., Buzi, F., Corrias, A., Mussa, A., Cambiaso, P., Salerno, M., Cappa, M., Baiocchi, M., Gastaldi, R., Minerba, L. and Loche, S. (2012) The Natural History of the Normal/Mild Elevated TSH Serum Levels in Children and Adolescents with Hashimoto’s Thyroiditis and Isolated Hyperthyrotropinaemia: A 3-Year Follow-Up. Clinical Endocrinology, 76, 394-398. https://doi.org/10.1111/j.1365-2265.2011.04251.x
Lazar, L., Frumkin, R.B., Battat, E., Lebenthal, Y., Phillip, M. and Meyerovitch, J. (2009) Natural History of Thyroid Function Tests over 5 Years in a Large Pediatric Cohort. The Journal of Clinical Endocrinology & Metabolism, 94, 1678-1682. https://doi.org/10.1210/jc.2008-2615
Kaplowitz, P.B. (2010) Subclinical Hypothyroidism in Children: Normal Variation or Sign of a Failing Thyroid Gland? International Journal of Pediatrics Endocrinology, Article ID: 281453. https://doi.org/10.1186/1687-9856-2010-281453
Cerbone, M., Bravaccio, C., Capalbo, D., Polizzi, M., Wasniewska, M., Cioffi, D., Improda, N., Valenzise, M., Bruzzese, D., De Luca, F. and Salerno, M. (2011) Linear Growth and Intellectual Outcome in Children with Long-Term Idiopathic Subclinical Hypothyroidism. European Journal of Endocrinology, 164, 591-597. https://doi.org/10.1530/EJE-10-0979
Gottardi, E., Egger, F. and Radetti, G. (2008) TSH and Endothelial Function in Children. European Journal of Pediatrics, 167, 355-356. https://doi.org/10.1007/s00431-007-0476-1
Ittermann, T., Thamm, M., Wallaschofski, H., Rettig, R. and Volzke, H. (2012) Serum Thyroid-Stimulating Hormone Levels Are Associated with Blood Pressure in Children and Adolescents. The Journal of Clinical Endocrinology & Metabolism, 97, 828-834. https://doi.org/10.1210/jc.2011-2768
Zepf, F.D., Vloet, T.D., Polier, G.G., Baurmann, D., Bubenzer, S., Helmbold, K., Gaber, T.J., Schmidt, T., Herpertz-Dahlmann, B. and Wockel, L. (2011) No Association between Affective and Behavioral Dysregulation and Parameters of Thyroid Function in Youths. Journal of Affective Disorders, 134, 478-482. https://doi.org/10.1016/j.jad.2011.05.040
Monzani, A., Prodam, F., Rapa, A., Moia, S., Agarla, V., Bellone, S. and Bona, G. (2013) Endocrine Disorders in Childhood and Adolescence. Natural History of Subclinical Hypothyroidism in Children and Adolescents and Potential Effects of Replacement Therapy: A Review. European Journal of Endocrinology, 168, R1-R11. https://doi.org/10.1530/EJE-12-0656