Guest Editor: Raffaella Origa THYROID DISORDERS IN HOMOZYGOUS β-THALASSEMIA: CURRENT KNOWLEDGE, EMERGING ISSUES AND OPEN PROBLEMS

Main Article Content

Vincenzo De Sanctis *
(*) Corresponding Author:
Vincenzo De Sanctis | vdesanctis@libero.it

Abstract

Abstract. Changes in thyroid function and thyroid function tests occur in patients with β-thalassemia major (TM). The frequency of hypothyroidism in TM patients ranges from 4% to 29 % in different reports. The wide variation has been attributed to several factors such as patients' genotype, age, ethnic variations, treatment protocols of transfusions and chelation, and varying compliance to treatment. Hypothyroidism is the result of primary gland failure or insufficient thy­roid gland stimulation by the hypothalamus or pituitary gland. The main laboratory parameters of thyroid function are the assessments of serum thyroid-stimulating hor­mone (TSH) and serum free thyroxine (FT4). It is of primary importance to interpret these measure­ments within the context of the laboratory-specific normative range for each test. An ele­vated serum TSH level with a normal range of serum FT4 level is consistent with subclinical hypothyroidism. A low serum FT4 level with a low, or inappropriately normal, serum TSH level is consistent with secondary hypothyroidism. Doctors caring for TM patients most commonly encounter subjects with subclinical primary hypothy­roidism in the second decade of life. Several aspects remain to be elucidated as the frequency of thyroid cancer and the possible existence of a relationship between thyroid dysfunction on one hand, cardiovascular diseases, components of metabolic syndrome (insulin resistance) and hypercoagulable state on the other hand. Further studies are needed to explain these emerging issues. Following a brief description of thyroid hormone regulation, production and actions, this article is conceptually divided into two parts; the first reports the spectrum of thyroid disease occurring in patients with TM, and the second part focuses on the emerging issues and the open problems in TM patients with thyroid disorders.


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References

1. Fibach E, Rachmilewitz EA. Pathophysiology and treatment of patients with beta-thalassemia - an update. F1000Res. 2017 Dec 20;6:2156. doi: 10.12688/f1000research.12688.1. eCollection 2017.
2.Cappellini MD, Motta I. New therapeutic targets in transfusion-dependent and -independent thalassemia. Hematology Am Soc Hematol Educ Program. 2017;2017:278-283.
3. Baldini M, Marcon A, Cassin R, Ulivieri FM, Spinelli D, Cappellini MD, Graziadei G. Beta-thalassaemia intermedia: evaluation of endocrine and bone complications. Biomed Res Int. 2014;2014:174581. doi: 10.1155/2014/174581.
4. De Sanctis V, Elsedfy H, Soliman AT, Elhakim IZ, Soliman NA, Elalaily R, C Kattamis. Endocrine profile of β-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center. Indian J Endocr Metab. 2016;20:451-459.
5. Jackson IMD. Thyrotropin-releasing hormone. N Engl J Med. 1982:306: 145–155.
6. Yamada M, Mori M. Mechanisms related to the pathophysiology and management of central hypothyroidism. Nat Clin Pract Endocrinol Metab. 2008; 4:683–694.
7. Lania A, Persani L, Beck-Peccoz P. Central hypothyroidism. Pituitary. 2008;11:181–186.
8. Rose SR. Cranial irradiation and central hypothyroidism.Trends Endocrinol Metab. 2001: 12:97–104.
9. Gary KA, Winokur A, Douglas SD, Kapoor S, Zaugg L, Dinges DF. Total sleep deprivation and the thyroid axis: effects of sleep and waking activity. Aviat Space Environ Med. 1996;67: 513–519.
10. Gómez JM.Serum leptin, insulin-like growth factor-I components and sex-hormone binding globulin. Relationship with sex, age and body composition in healthy population. Protein Pept Lett. 2007;14:708-811.
11. Zhang Z, Boelen A, Kalsbeek A, Fliers E. TRH Neurons and Thyroid Hormone Coordinate the Hypothalamic Response to Cold. Eur Thyroid J. 2018;7:279-288.
12. Ortiga-Carvalho TM, Chiamolera MI, Pazos-Moura CC, Wondisford FE. Hypothalamus-Pituitary-Thyroid Axis. Compr Physiol. 2016;6:1387-1428.
13. Mebis L, van den Berghe G. The hypothalamus-pituitary-thyroid axis in critical illness. Neth J Med. 2009;67:332-340.
14. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001; 344:501–509.
15. Crunkhorn S, Patti ME. Links between thyroid hormone action, oxidative metabolism, and diabetes risk? Thyroid. 2008;18: 227–237.
16. De Sanctis V, Eleftheriou A, Malaventura C, Thalassaemia International Federation Study Group on Growth and Endocrine Complications in Thalassaemia.Prevalence of endocrine complications and short stature in patients with thalassaemia major: a multicenter study by the Thalassaemia International Federation (TIF). Pediatr Endocrinol Rev. 2004;2 (Suppl 2):249-255
17. De Sanctis V, Soliman A, Campisi S,M Yassin. Thyroid disorders in thalassaemia: An update. Curr Trends Endocrinol. 2012;6:17–27.
18. Grundy RG, Woods KA, Savage MO, Evans JP. Relationship of endocrinopathy to iron chelation status in young patients with thalassaemia major.Arch Dis Child.1994;71:128–132.
19. Zervas A, Katopodi A, Protonotariou A, Livadas S, Karagiorga M, Politis C, Tolis G. Assessment of thyroid function in two hundred patients with beta-thalassemia major.Thyroid.2002;12:151-154.
20. Skordis N, Michaelidou M, Savva SC, Ioannou Y, Rousounides A, Kleanthous M, Skordos G, Christou S.The impact of genotype on endocrine complications in thalassaemia major. Eur J Haematol.2006;77:150–156.
21.Gamberini MR, De SanctisV, Gilli G. Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre. Pediatr Endocrinol Rev.2008;6 (Suppl 1):158–169.
22. Eshragi P, Tamaddoni A, Zarifi K, Mohammadhasani A, Aminzadeh M. Thyroid function in major thalassemia patients: Is it related to height and chelation therapy? Caspian J Intern Med.2011;2:189-193.
23. Kurtoglu AU, Kurtoglu E, Temizkan AK. Effect of iron overload on endocrinopathies in patients with beta-thalassaemia major and intermedia. Endokrynol Pol. 2012;63:260-263.
24. Salih KM, Al-Mosawy WF. Evaluation some consequences of thalassemia major in splenectomized and non-splenectomized Iraqi patients. Int J Pharm Pharm Sci.2013; 5(Suppl 4):385-358.
25. Belhoul KM, Bakir ML, Saned MS, Kadhim AM, Musallam KM, Taher AT. Serum ferritin levels and endocrinopathy in medically treated patients with β thalassemia major.Ann Hematol. 2012;91:1107-114.
26. Tavazzi D, Duca L, Graziadei G, Comino A, Fiorelli G, Cappellini MD. Membrane-bound iron contributes to oxidative damage of beta-thalassaemia intermedia erythrocytes. Br J Haematol. 2001;112:48-50.
27. Malik SA, Syed S, Ahmed N. Frequency of hypothyroidism in patients of beta-thalassaemia. J Pak Med Assoc.2010; 60:17-20.
28. Rindang CK, Batubara JRL, Amalia P, Satari H. Some aspects of thyroid dysfunction in thalassemia major patients with severe iron overload. Paediatr Indones. 2011;51:66–72.
29. Pirinççioğlu AG, Deniz T, Gökalp D, Beyazit N, Haspolat K, Söker M. Assessment of thyroid function in children aged 1-13 years with Beta-thalassemia major. Iran J Pediatr.2011;21:77-82.
30.Saleem M, Ghafoor MB, Anwar J, Saleem MM. Hypothyroidism in beta thalassemia major patients at Rahim Yar Khan. JSZMC.2016;7:1016-1019.
31. Upadya SH, Rukmini MS, Sundararajan S, Baliga BS, Kamath N. Thyroid Function in Chronically Transfused Children with Beta Thalassemia Major: A Cross-Sectional Hospital Based Study. Int J Pediatr. 2018 Sep 16;2018:9071213. doi: 10.1155/2018/9071213.
32. Landau H, Matoth I, Landau-Cordova Z, Goldfarb A, Rachmilewitz EA, Glaser B. Cross-sectional and longitudinal study of the pituitary thyroid axis in patients with thalassaemia major. Clin Endocrinol (Oxf).1993;38:55-61.
33. Tatò L, Lahlou N, Zamboni G, De Sanctis V, De Luca F, Arrigo T, Antoniazzi F, Roger M. Impaired response of free alpha-subunits after luteinizing hormone-releasing hormone and thyrotropin-releasing hormone stimulations in beta-thalassemia major.Horm Res. 1993;39:213-217.
34. De Sanctis V, Soliman A, Candini G, Campisi S, Anastasi S, Yassin M. High prevalence of central hypothyroidism in adult patients with β-thalassemia major. Georgian Med News. 2013;(222):88-94.
35.Delaporta P, Maria Karantza M, Sorina Boiu S, Stokidis K, Petropoulou T, Papasotiriou I, Kattamis C, Kattamis A. Thyroid function in Greek patients with thalassemia major. Blood 2012;120: Abs. 5176. DOI:http//dx.doi.org.
36. Soliman AT, Al Yafei F, Al-Naimi L, Almarri N, Sabt A, Yassin M, De Sanctis V. Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years. Indian J Endocrinol Metab. 2013;17:1090-1095.
37. Persani L. Clinical review: Central hypothyroidism: pathogenic, diagnostic, and therapeutic challenges. J Clin Endocrinol Metab. 2012;97:3068-3078.
38. Alexopoulou O, Beguin C, De Nayer P, Maiter D.Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients. Eur J Endocrinol.2004;150:1–8
39. Andersen S, Pedersen KM, Bruun NH, Laurberg P. Narrow individual variations in serum T4 and T3 in normal subjects: a clue to understanding of subclinical thyroid disease. J Clin Endocrinol Metab. 2002; 87:1068–1072.
40. Christoforidis A, Haritandi A, Tsitouridis I, Tsatra I, Tsantali H, Karyda S, Dimitriadis AS, Athanassiou-Metaxa M. Correlative study of iron accumulation in liver, myocardium, and pituitary assessed with MRI in young thalassemic patients. J Pediatr Hematol Oncol. 2006;28:311–315.
41. Hekmatnia A, Radmard AR, Rahmani AA, Adibi A, Khademi H. Magnetic resonance imaging signal reduction may precede volume loss in the pituitary gland of transfusion-dependent beta-thalassemic patients. Acta Radiol. 2010;5171-5177.
42. Noetzli LJ, Panigrahy A, Hyderi A, Dongelyan A, Coates TD, Wood JC. Pituitary iron and volume imaging in healthy controls. AJNR Am J Neuroradiol. 2012;33:259-265.
43. De Sanctis V, Govoni MR, Sprocati M, Marsella M, Conti E. Cardiomyopathy and pericardial effusion in a 7 year-old boy with beta-thalassaemia major, severe primary hypothyroidism and hypoparathyroidism due to iron overload. Pediatr Endocrinol Rev.2008;6 (Suppl 1):181-184.
44. De Sanctis V, De Sanctis E, Ricchieri P, Gubellini E, Gilli G, Gamberini MR. Mild subclinical hypothyroidism in thalassaemia major: prevalence, multigated radionuclide test, clinical and laboratory long-term follow-up study.Pediatr Endocrinol Rev.2008;6 (Suppl 1):174-180.
45. Mariotti S, Pigliaru F, Cocco MC, Spiga A, Vaquer S, Lai ME. β-thalassemia and thyroid failure: is there a role for thyroid autoimmunity? Pediatr Endocrinol Rev.2011;8 (Suppl 2):307-309.
46. Pes GM, Tolu F, Dore MP. Anti-Thyroid Peroxidase Antibodies and Male Gender Are Associated with Diabetes Occurrence in Patients with Beta-Thalassemia Major. J Diabetes Res. 2016;2016:1401829. doi: 10.1155/2016/1401829.
47. Pitrolo L, Malizia G, Lo Pinto C, Malizia V, Capra M. Ultrasound thyroid evaluation in thalassemic patients: correlation between the aspects of thyroidal stroma and function. Pediatr Endocrinol Rev. 2004;2 (Suppl 2):313-315.
48. Filosa A, Di Maio S, Aloj G, Acampora C. Longitudinal study on thyroid function in patients with thalassemia major. J Pediatr Endocrinol Metab. 2006;19:1397-1404.
49. Sostre S, Reyes MM. Sonographic diagnosis and grading of Hashimoto's thyroiditis. J Endocrinol Invest.1991;14:115-121.
50. Krittayaphong R, Viprakasit V, Saiviroonporn P, Wangworatrakul W, Wood JC. Serum ferritin in the diagnosis of cardiac and liver iron overload in thalassaemia patients’ real-world practice: a multicentre study.Br J Haematol. 2018;182:301-305.
51. Wood JC. Estimating tissue iron burden: current status and future prospects.Br J Haematol. 2015;170:15-28.
52. Soliman AT, De Sanctis V, Yassin M, Wagdy M, Soliman N. Chronic anemia and thyroid function. Acta Biomed. 2017;88:119-127.
53. Shupnik MA, Weck J, Hinkle PM.Thyrotropin (TSH)-releasing hormone stimulates TSH beta promoter activity by two distinct mechanisms involving calcium influx through L type Ca2+ channels and protein kinase C. Mol Endocrinol. 1996;10:90–99.
54. Alcantara O, Obeid L, Hannun Y, Ponka P, Boldt DH. Regulation of protein kinase C (PKC) expression by iron: Effect of different iron compounds on PKC-beta and PKC-alpha gene expression and role of the 5’- flanking region of the PKC-beta gene in the response to ferric transferrin. Blood. 1994;84:3510–3517.
55. Abe H, Murao K, Imachi H, Cao WM, Yu X, Yoshida K, Wong NC, Shupnik MA, Haefliger JA, Waeber G, Ishida T. Thyrotropin-releasing hormone-stimulated thyrotropin expression involves islet-brain-1/c-Jun N-terminal kinase interacting protein-1. Endocrinology. 2004;145:5623–5628.
56. Blackard JT, Kong L, Huber AK, Tomer Y. Hepatitis C virus infection of a thyroid cell line: Implications for pathogenesis of hepatitis C virus and thyroiditis. Thyroid 2013;23:863‑70.
57. Vezali E, Elefsiniotis I, Mihas C, Konstantinou E, Saroglou G. Thyroid dysfunction in patients with chronic hepatitis C: Virus‑ or therapy‑related? J Gastroenterol Hepatol 2009;24:1024‑9.
58. Al-Khabori M, Daar S, Al-Busafi SA, Al-Dhuhli H, Alumairi AA, Hassan M, Al-Rahbi S, Al-Ajmi U. Noninvasive assessment and risk factors of liver fibrosis in patients with thalassemia major using shear wave elastography. Hematology. 2019;24:183-188.
59. De Sanctis V, Tanas R, Gamberini MR, Sprocati M, Govoni MR, Marsella M. Exaggerated TSH response to TRH ("sub-biochemical" hypothyroidism) in prepubertal and adolescent thalassaemic patients with iron overload: prevalence and 20-year natural history. Pediatr Endocrinol Rev. 2008;6 (Suppl 1):170-173.
60. Hashemi A, Ordooei M, Golestan M, Akhavan Ghalibaf M, Mahmoudabadi F. Hypothyroidism and serum ferritin level in patientswith major ß thalassemia. Iran J Pediatr Hematol Oncol. 2012;2:12-15.
61. Musallam KM, CappelliniMD, Wood JC, Motta I, Graziadei G, Tamim H, Taher AT. Elevated liver iron concentration is a marker of increased morbidity in patients with β thalassemia intermedia. Haematologica. 2011; 96:1605–1612.
62. Farhan H, Albulushi A, Taqi A, Al-Hashim A, Al-Saidi K, Al-Rasadi K, Al-Mazroui A, Al-Zakwani I. Incidence and pattern of thyroid dysfunction in patients on chronic amiodarone therapy: experience at a tertiary care centre in Oman. Open Cardiovasc Med J. 2013;7:122–126.
63. Martino E, Safran M, Aghini-Lombardi F, Rajatanavin R, Lenziardi M, Fay M, Pacchiarotti A, Aronin N, Macchia E, Haffajee C. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann Intern Med. 1984;101:28–34.
64. Martino E, Bartalena L, Bogazzi F, Braverman LE. The effects of amiodarone on the thyroid. Endocr Rev. 2001;22:240-254.
65. Eskes SA, Wiersinga WM. Amiodarone and thyroid. Best Pract Res Clin Endocrinol Metab.2009; 23:735-751.
66. Cohen-Lehman J, Dahl P, Danzi S, Klein I. Effects of amiodarone therapy on thyroid function. Nat Rev Endocrinol. 2010;6:34-641.
67. Kotwal A, Clark J, Lyden M, McKenzie T, Thompson G, Stan MN. Thyroidectomy for amiodarone-induced thyrotoxicosis: Mayo Clinic Experience. J Endocr Soc. 2018;2:1226-1235.
68. Alexandrides T, Georgopoulos N, Yarmenitis S, Vagenakis AG. Increased sensitivity to the inhibitory effect of excess iodide on thyroid function in patients with beta-thalassemia major and iron overload and the subsequent development of hypothyroidism. Eur J Endocrinol.2000;143:319-325.
69. Finianos A, Matar CF, Taher A. Hepatocellular Carcinoma in β-Thalassemia Patients: Review of the Literature with Molecular Insight into Liver Carcinogenesis.Int J Mol Sci. 2018 Dec 17;19(12). pii: E4070. doi: 10.3390/ijms19124070.
70. Benetatos L, Alymara V, Vassou A, Bourantas KL. Malignancies in beta-thalassemia patients: a single-center experience and a concise review of the literature. Int J Lab Hematol. 2008;30: 167-172.
71.Karimi M, Giti R, Haghpanah S, Azarkeivan A, Hoofar H, Eslami M. Malignancies in patients with beta-thalassemia major and beta-thalassemia intermedia: a multicenter study in Iran. Pediatr Blood Cancer. 2009;53:1064-1067.
72. Govoni MR, Sprocati M, Fabbri E, Zanforlin N, De Sanctis V. Papillary thyroid cancer in thalassaemia. Pediatr Endocrinol Rev. 2011; 8 (Suppl 2):314-321.
73. Poggi M, Sorrentino F, Pascucci C, Monti S, Lauri C, Bisogni V, Toscano V, Cianciulli P. Malignancies in β-thalassemia patients: first description of two cases of thyroid cancer and review of the literature. Hemoglobin. 2011;35:439-446.
74. De Sanctis V, Campisi S, Fiscina B, Soliman A. Papillary thyroid microcarcinoma in thalassaemia: an emerging concern for physicians? Georgian Med News. 2012; 210:71-76.
75. De Sanctis V, Soliman AT, Duran Canatan D, Tzoulis P , Daar S , Di Maio S , Elsedfy H , Yassin MA , Filosa A, Soliman N , Karimi M , Saki F, Sobti P, Kakkar S, Christou S, Albu A, Christodoulides C, Kilinc Y , Al Jaouni S, Khater D , Alyaarubi SA, Lum SA, Campisi S, Anastasi S, Galati MC, Raiola G, Wali Y, Elhakim IZ, Mariannis D, Ladis V, Kattamis C. An ICET-A survey on occult and emerging endocrine complications in patients with β-thalassemia major: Conclusions and recommendations. Acta Biomed. 2019;89:481-489.
76. Ferri C, La Civita L, Zignego AL, Pasero G. Viruses and cancers: possible role of hepatitis C virus. Eur J Clin Invest.1997; 27:711-718.
77. Russ G, Bonnema SJ, Erdogan MF, Durante C, Ngu R, Leenhardt L. European Thyroid Association Guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: the EU-TIRADS. Eur Thyroid J. 2017;6:225-237.
78. Vargas-Uricoechea H, Sierra-Torres CH. Thyroid hormones and the heart. Horm Mol Biol Clin Investig. 2014;18:15-26.
79. Morselli E, Santos RS, Criollo A, Nelson MD, Palmer BF, Clegg DJ. The effects of oestrogens and their receptors on cardiometabolic health. Nat Rev Endocrinol. 2017;13:352-364.
80. Caicedo D, Díaz O, Devesa P, Devesa J. Growth Hormone (GH) and Cardiovascular System. Int J Mol Sci. 2018 Jan 18;19(1). pii: E290. doi: 10.3390/ijms19010290.
81. Bielecka-Dabrowa A, Godoy B, Suzuki T, Banach M, von Haehling S. Subclinical hypothyroidism and the development of heart failure: an overview of risk and effects on cardiac function. Clin Res Cardiol. 2018 Aug 8. doi: 10.1007/s00392-018-1340-1
82. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344 501–509.
83. Kannan L, Shaw PA, Morley MP, Brandimarto J, Fang JC, Sweitzer NK, Cappola TP, Cappola AR. Thyroid Dysfunction in Heart Failure and Cardiovascular Outcomes. Circ Heart Fail. 2018 Dec;11(12):e005266. doi: 10.1161/CIRCHEARTFAILURE.118.005266.
84. Gamberini MR, Meloni A, Rossi A, Secchi G, D'Ambrosio A, Macchi S, Pulini S, De Franceschi L, Vallone A, Lombardi M, Pepe A. Hypothyroidism and Cardiac Complications In Thalassemia Major Patients. Blood 2013;122: abs.2254.
85. Waldmeier F, Bruin GJ, Glaenzel U, Hazell K, Sechaud R, Warrington S, Porter JB.Pharmacokinetics, metabolism, and disposition of deferasirox in beta-thalassemic patients with transfusion-dependent iron overload who are at pharmacokinetic steady state. Drug Metab Dispos. 2010;38:808–816.
86. Farmaki K, Tzoumari I, Pappa Ch. Reversal of hypothyroidism in well chelated β-thalassemia major patients. Blood. 2008;112:1323-1324.
87. Farmaki K, Tzoumari I, Pappa C, Chouliaras G, Berdoukas V. Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major. Br J Haematol. 2010;148: 466-475.
88. Farmaki K, Berdoukas V. Reversal of endocrinopathies in transfusional iron overload patients – The next frontier in iron chelation. EJCMO. 2010;2:59-66.
89. Farmaki K, Tzoumari I, Pappa C. Combining oral chelators in transfusion dependents thalassemia major patients, may prevent or reverse iron overload complications. Blood Cell Mol Dis. 2011; 47: 33-40.
90. Casale M, Citarella S, Filosa A, De Michele E, Palmieri F, Ragozzino A, Amendola G, Pugliese U, Tartaglione I, Della Rocca F, Cinque P, Nobili B, Perrotta S. Endocrine function and bone disease during long-term chelation therapy with deferasirox in patients with β-thalassemia major. Am J Hematol. 2014 ;89:1102-1106.
91. Roos A, Linn-Rasker SP, van Domburg RT, Tijssen JP,Berghout A. The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind trial. Arch Intern Med. 2005;165:1714-1720.
92. Reddy PA, Harinarayan CV, Sachan A, Suresh V, Rajagopal G. Bone disease in thyrotoxicosis. Indian J Med Res. 2012;135:277-286.
93. Peeters RP. Thyroid hormones and aging. Hormones. 2008:7:28-35.
94. De Sanctis V, Soliman AT, Elsedfy H, Skordis N, Kattamis C, Angastiniotis M, Karimi M, Yassin MA, El Awwa A, Stoeva I, Raiola G, Galati MC, Bedair EM, Fiscina B, El Kholy M. Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines. Indian J Endocrinol Metab. 2013;17:8-18.
95. De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, Eastman CJ, Lazarus JH, Luton D, Mandel SJ, Mestman J, Rovet J, Sullivan S. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:2543-2565.
96. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, Nixon A, Pearce EN, Soldin OP, Sullivan S, Wiersinga W; American Thyroid Association Task force on Thyroid Disease During Pregnancy and Post partum.Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and post partum.Thyroid. 2011; 21:1081–1125.
97. De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, Eastman CJ, Lazarus JH, Luton D, Mandel SJ, Mestman J, Rovet J, Sullivan S. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:2543–2565.
98. Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, Vaidya B. European Thyroid Association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. 2014;3:76–94.
99. Brabant G, Peeters RP, Chan SY, Bernal J, Bouchard P, Salvatore D, Boelaert K, Laurberg P. Management of subclinical hypothyroidism in pregnancy: are we too simplistic? Eur J Endocrinol. 2015;173:P1–P11.
100. McNeil AR, Stanford PE. Reporting thyroid function tests in pregnancy. Clin Biochem Rev. 2015;36:109–126.
101. Medici M, Korevaar TI, Visser WE, Visser TJ, Peeters RP. Thyroid function in pregnancy: what is normal? Clin Chem. 2015;61:704–713.
102. Grande D, Terlizzese P, Gioia MI, Parisi G, Giagulli VA, Triggiani V, Iacoviello M. New frontiers in the therapeutic approach of patients with cardiovascular and endocrine diseases.Endocr Metab Immune Disord Drug Targets. 2019 Jan 1. doi: 10.2174/1871530319666190101151542.
103. Nakova VV, Krstevska B, Kostovska ES, Vaskova O, Ismail LG. The effect of levothyroxine treatment on left ventricular function in subclinical hypothyroidism.Arch Endocrinol Metab. 2018;62:392-398.
104. Elbers LPB, Squizzato A, Gerdes VEA. Thyroid Disorders and Hemostasis. Semin Thromb Hemost. 2018;44:676-682.
105. US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, Curry SJ, Barry MJ, Davidson KW, Doubeni CA, Epling JW Jr, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Phipps MG, Silverstein M, Simon MA, Siu AL, Tseng CW. Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2017;317:1882-1887.
106. Lin JS, Aiello Bowles EJ, Williams SB, Morrison CC. Screening for thyroid cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2017;317:1888-1903.