Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency

Charles F. Verge, Daniel Konrad, Michal Cohen, Caterina Di Cosmo, Alexandra M. Dumitrescu, Teresa Marcinkowski, Shihab Hameed, Jill Hamilton, Roy E Weiss, Samuel Refetoff

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Context: Monocarboxylate transporter 8 (MCT8) is a thyroid hormone-specific cell membrane transporter. MCT8 deficiency causes severe psychomotor retardation and abnormal thyroid tests. The great majority of affected children cannot walk or talk, and all have elevated serum T3 levels, causing peripheral tissue hypermetabolism and inability to maintain weight. Treatment with thyroid hormone is ineffective. In Mct8-deficient mice, the thyroid hormone analog, diiodothyropropionic acid (DITPA), does not require MCT8 to enter tissues and could be an effective alternative to thyroid hormone treatment in humans. Objective: The objective of the study was to evaluate the effect and efficacy of DITPA in children with MCT8 deficiency. Methods: This was a multicenter report of four affected children given DITPA on compassionate grounds for 26-40 months. Treatment was initiated at ages 8.5-25 months, beginning with a small dose of 1.8 mg, increasing to a maximal 30 mg/d (2.1-2.4 mg/kg·d), given in three divided doses. Results: DITPA normalized the elevated serum T3 and TSH when the dose reached 1 mg/kg·d and T4and rT3 increased to the lower normal range. The following significant changes were also observed: decline in SHBG (in all subjects), heart rate (in three of four), and ferritin (in one of four). Cholesterol increased in two subjects. There was no weight loss and weight gain occurred in two. None of the treated children required a gastric feeding tube or developed seizures. No adverse effects were observed. Conclusion: DITPA (1-2 mg/kg·d) almost completely normalizes thyroid tests and reduces the hypermetabolism and the tendency for weight loss. The effects of earlier commencement and long-term therapy remain to be determined.

Original languageEnglish (US)
Pages (from-to)4515-4523
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number12
DOIs
StatePublished - Dec 2012
Externally publishedYes

Fingerprint

Thyroid Hormones
Acids
Weight Loss
Thyroid Gland
Tissue
Therapeutics
Membrane Transport Proteins
Enteral Nutrition
Cell membranes
Ferritins
Serum
Weight Gain
Reference Values
Seizures
Heart Rate
Cholesterol
Cell Membrane
Allan-Herndon-Dudley syndrome
Weights and Measures

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Verge, C. F., Konrad, D., Cohen, M., Di Cosmo, C., Dumitrescu, A. M., Marcinkowski, T., ... Refetoff, S. (2012). Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency. Journal of Clinical Endocrinology and Metabolism, 97(12), 4515-4523. https://doi.org/10.1210/jc.2012-2556

Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency. / Verge, Charles F.; Konrad, Daniel; Cohen, Michal; Di Cosmo, Caterina; Dumitrescu, Alexandra M.; Marcinkowski, Teresa; Hameed, Shihab; Hamilton, Jill; Weiss, Roy E; Refetoff, Samuel.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 12, 12.2012, p. 4515-4523.

Research output: Contribution to journalArticle

Verge, CF, Konrad, D, Cohen, M, Di Cosmo, C, Dumitrescu, AM, Marcinkowski, T, Hameed, S, Hamilton, J, Weiss, RE & Refetoff, S 2012, 'Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency', Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 12, pp. 4515-4523. https://doi.org/10.1210/jc.2012-2556
Verge CF, Konrad D, Cohen M, Di Cosmo C, Dumitrescu AM, Marcinkowski T et al. Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency. Journal of Clinical Endocrinology and Metabolism. 2012 Dec;97(12):4515-4523. https://doi.org/10.1210/jc.2012-2556
Verge, Charles F. ; Konrad, Daniel ; Cohen, Michal ; Di Cosmo, Caterina ; Dumitrescu, Alexandra M. ; Marcinkowski, Teresa ; Hameed, Shihab ; Hamilton, Jill ; Weiss, Roy E ; Refetoff, Samuel. / Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 12. pp. 4515-4523.
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