CFP
HOME HELP CONTACT US FEEDBACK SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES SEARCH
QUICK SEARCH:   [advanced]


     

Can Fam Physician
Vol. 55, No. 8, August 2009, pp.797 - 798
Copyright © 2009 by The College of Family Physicians of Canada
This Article
Right arrow Abstract Freely available
Right arrow Résumé
Right arrow Full Text (PDF)
Right arrow Rapid Responses: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Rapid Responses are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Glatstein, M. M.
Right arrow Articles by Koren, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Glatstein, M. M.
Right arrow Articles by Koren, G.

Motherisk Update

Pharmacologic treatment of hyperthyroidism during lactation

Miguel Marcelo Glatstein, MD, Facundo Garcia-Bournissen, MD, Norberto Giglio, MD, Yaron Finkelstein, MD and Gideon Koren, MD FRCPC FACMT
Methimazole and propylthiouracil are selective inhibitors of thyroid peroxidase–mediated iodination of tyrosine residues in thyroglobulin, which reduce the production of thyroid hormone. They are effective in the treatment of different etiologies of hyperthyroidism.1 Thioamides also inhibit the coupling of these iodotyrosyl residues to form iodothyronines.2 In addition to blocking hormone synthesis, propylthiouracil, unlike methimazole, inhibits the peripheral deiodination of thyroxine (T4) to triiodothyronine.3 These drugs—including carbimazole, a prodrug of methimazole—belong to the thioamide group.4 All drugs in this class have similar efficacy and safety but differ in potency and duration of action. Methimazole has a longer elimination half-life and can be given once daily.5 At low doses, adverse effects are less commonly described with methimazole and carbimazole when compared with propylthiouracil,4 and the infrequent drug-related hepatitis and vasculitis appear to occur relatively more commonly with propylthiouracil.6 Certain β-adrenergic antagonists (not including atenolol or acebutolol), such as propranolol, can be safely used as adjunctive therapy during breastfeeding.7

Absorption of thioamides through the gastrointestinal tract is rapid; these drugs appear in the blood within 30 minutes of administration of oral doses and have a quick onset of action.8 Thioamides are metabolized in the liver to inactive metabolites that are excreted renally. The half-life of propylthiouracil in plasma is about 75 minutes, whereas for methimazole it is 4 to 6 hours.8–10 Mean peak plasma concentration of propylthiouracil after a 200-mg dose is 6.5 µg/mL9,11; a 40-mg oral dose of methimazole produced a peak plasma concentration of 0.54 µg/mL.10

Breastfeeding

For many years breastfeeding was strongly discouraged if treatment with antithyroid drugs was required.12 Both propylthiouracil and methimazole can be detected in milk13–15; however, studies have shown that propylthiouracil crosses into milk only in minute amounts, leading to a milk-plasma ratio of approximately 0.1.15 A woman taking 200 mg/d of propylthiouracil and feeding a baby daily with 150 mL/kg of breast milk would transfer less than 3% of her weight-adjusted dose of propylthiouracil to her infant.16 No adverse effects on neonatal thyroid status in breastfed infants were reported even at high maternal doses of 750 mg/d of propylthiouracil.14

Methimazole, on the other hand, has a milk-plasma ratio close to 115; a woman taking 40 mg/d of methimazole and breastfeeding a volume of 150 mL/kg daily to her baby would transfer a maximum of 12% of her weight-adjusted dose through breast milk. Azizi17 showed in one study of 35 infants of lactating mothers with thyrotoxicosis who were treated with methimazole daily that all babies maintained normal thyroid functions in spite of breastfeeding. In another study,18 no deleterious effects were observed in thyroid function or physical and intellectual development up to 48 to 74 months of age in breastfed infants whose mothers were treated with up to 20-mg/d doses of methimazole. Lamberg et al19 reported outcomes for 11 infants whose mothers were treated with carbimazole (which converts to methimazole in circulation) at dosages ranging from 5 to 15 mg daily during pregnancy and after delivery. All infants in this study had normal serum thyrotropin and T4 levels. Based on these observations, it has been proposed that methimazole (preferably in low dosages) could be used during breastfeeding if the infant’s thyroid status is monitored.20

Conclusion

Thioamides offer substantial therapeutic benefits to women with hyperthyroidism. On the basis of all the current literature, we conclude that either propylthiouracil or methimazole administered to lactating women is likely to be safe for their infants. Careful monitoring of both mother and infant is still advisable, including serum T4 and thyrotropin determinations at least 3 to 4 weeks after initiation of breastfeeding.


MOTHERISK

Motherisk questions are prepared by the Motherisk Team at the Hospital for Sick Children in Toronto, Ont. Dr Giglio is a staff physician at the Hospital de Niños "Ricardo Gutiérrez" in Buenos Aires, Argentina. Drs Glatstein, Garcia-Bournissen, and Finkelstein are members and Dr Koren is Director of the Motherisk Program. Dr Koren is supported by the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation. He holds the Ivey Chair in Molecular Toxicology in the Department of Medicine at the University of Western Ontario in London.

Do you have questions about the effects of drugs, chemicals, radiation, or infections in women who are pregnant or breastfeeding? We invite you to submit them to the Motherisk Program by fax at 416 813–7562; they will be addressed in future Motherisk Updates.

Published Motherisk Updates are available on the Canadian Family Physician website (www.cfp.ca) and also on the Motherisk website (www.motherisk.org).

 

Acknowledgment

Dr Garcia-Bournissen has received funding from the Clinician Scientist Training Program. This program is funded, fully or in part, by the Ontario Student Opportunity Trust Fund—Hospital for Sick Children Foundation Student Scholarship Program.

Footnotes

Competing interests

None declared

References

  1. Humar M, Dohrmann H, Stein P, Andriopoulos N, Goebel U, Roesslein M, et al. Thionamides inhibit the transcription factor nuclear factor-kappaB by suppression of Rac1 and inhibitor of kappaB kinase alpha. J Pharmacol Exp Ther 2008;324(3):1037–44. Epub 2007 Nov 30.[Abstract/Free Full Text]
  2. Davidson B, Soodak M, Neary JT, Strout HV, Kieffer JD, Mover H, et al. The irreversible inactivation of thyroid peroxidase by methylmercaptoimidazole, thiouracil, and propylthiouracil in vitro and its relationship to in vivo findings. Endocrinology 1978;103(3):871–82.[Abstract/Free Full Text]
  3. Van Doorn J, Roelfsema F, van der Heide D. The effect of propylthiouracil and methimazole on the peripheral conversion of thyroxine to 3,5,3’-triiodothyronine in athyreotic thyroxine-maintained rats. Acta Endocrinol (Copenh) 1983;103(4):509–20.[Abstract/Free Full Text]
  4. Beck-Peccoz P, Persani L, LaFranchi S. Safety of medications and hormones used in the treatment of pediatric thyroid disorders. Pediatr Endocrinol Rev 2004;2(Suppl_1):124–33.[Medline]
  5. Streetman DD, Khanderia U. Diagnosis and treatment of Graves disease. Ann Pharmacother 2003;37(7–8):1100–9.[Abstract/Free Full Text]
  6. Parolin MB, Lopes RW, Telles JE, Ioshii SO, Hajar N. Acute cholestatic hepatitis induced by propylthiouracil. Case report [in Portuguese]. Arq Gastroenterol 2000;37(2):129–32.[Medline]
  7. Gittoes NJ, Franklyn JA. Hyperthyroidism. Current treatment guidelines. Drugs 1998;55(4):543–53.[Medline]
  8. Cooper DS. Antithyroid drugs. N Engl J Med 2005;352(9):905–17.[Free Full Text]
  9. Sitar DS, Abu-Bakare A, Gardiner RJ. Propylthiouracil disposition in pregnant and post-partum women. Pharmacology 1982;25(1):57–60.[Medline]
  10. Hengstmann JH, Hohn H. Pharmacokinetics of methimazole in humans. Klin Wochenschr 1985;63(23):1212–7.[Medline]
  11. Sitar DS, Hunninghake DB. Pharmacokinetics of propylthiouracil in man after a single oral dose. J Clin Endocrinol Metab 1975;40(1):26–9.[Abstract/Free Full Text]
  12. Clementi M, Di Gianantonio E, Pelo E, Mammi I, Basile RT, Tenconi R. Methimazole embryopathy: delineation of the phenotype. Am J Med Genet 1999;83(1):43–6.[Medline]
  13. Momotani N. Current problems in the treatment of Graves’ disease in pregnancy and in lactation [in Japanese]. Nippon Rinsho 2006;64(12):2297–302.[Medline]
  14. Momotani N, Yamashita R, Makino F, Noh JY, Ishikawa N, Ito K. Thyroid function in wholly breast-feeding infants whose mothers take high doses of propylthiouracil. Clin Endocrinol (Oxf) 2000;53(2):177–81.[Medline]
  15. Low LC, Lang J, Alexander WD. Excretion of carbimazole and propylthiouracil in breast milk. Lancet 1979;2(8150):1011.[Medline]
  16. Ito S. Drug therapy for breast-feeding women. N Engl J Med 2000;343(2):118–26. Erratum in: N Engl J Med 2000;343(18):1348.[Free Full Text]
  17. Azizi F. Effect of methimazole treatment of maternal thyrotoxicosis on thyroid function in breast-feeding infants. J Pediatr 1996;128(6):855–8.[Medline]
  18. Azizi F, Bahrainian M, Khamseh ME, Khoshniat M. Intellectual development and thyroid function in children who were breast-fed by thyrotoxic mothers taking methimazole. J Pediatr Endocrinol Metab 2003;16(9):1239–43.[Medline]
  19. Lamberg BA, Ikonen E, Osterlund K, Teramo K, Pekonen F, Peltola J, et al. Antithyroid treatment of maternal hyperthyroidism during lactation. Clin Endocrinol (Oxf) 1984;21(1):81–7.[Medline]
  20. Cooper DS. Antithyroid drugs: to breast-feed or not to breast-feed. Am J Obstet Gynecol 1987;157(2):234–5.[Medline]




This Article
Right arrow Abstract Freely available
Right arrow Résumé
Right arrow Full Text (PDF)
Right arrow Rapid Responses: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Rapid Responses are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Glatstein, M. M.
Right arrow Articles by Koren, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Glatstein, M. M.
Right arrow Articles by Koren, G.

HOME HELP CONTACT US FEEDBACK SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES SEARCH