Photo of Stephen A. Huang,  MD

Stephen A. Huang, MD

Boston Children's Hospital

Boston Children's Hospital


stephen.huang@childrens.harvard.edu

Stephen A. Huang, MD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Director, Thyroid Program, Medicine, Boston Children's Hospital

Research Abstract

Our group discovered that infantile hemangiomas express high levels of the thyroid hormone-inactivating enzyme type 3 deiodinase and that children with large tumor burden can succumb to severe hypothyroidism from the rapid inactivation of circulating thyroid hormone at rates which exceed the synthetic capacity of the normal thyroid axis. Because 3-4 IQ points are lost for each month of untreated hypothyroidism during infancy, we provided screening guidelines for children with large hemangiomas and treatment recommendations to use supernormal doses of exogenous thyroid hormone in severe cases. This has led to the diagnosis and treatment of hundreds of affected infants, and we named this condition “consumptive hypothyroidism”. My group has recently discovered that this mechanism of pathophysiology extends to adults with gastrointestinal stromal tumors, the most common mesenchymal tumor of the alimentary canal, and that their tumoral deiodinase activity is stimulated by treatment with tyrosine kinase inhibitors.

The goals of my current research are to determine the clinical consequences of D3 expression in hemangiomas and in other tumors, to understand the molecular explanation for its expression in consumptive hypothyroidism, and to determine if there are other conditions in which D3 causes hypothyroxinemia due to the accelerated degradation of thyroid hormones.

In addition to my studies of deiodinase regulation, I am a clinical thyroidologist with a special focus in the care of children with thyroid cancer. In collaboration with clinical researchers from numerous disciplines, including radiology, surgery, pathology, oncology, and genetics, we are performing clinical and translational studies of this rare pediatric cancer population.

 

Publications

Powered by Harvard Catalyst
  • Guo C, Chen X, Song H, Maynard MA, Zhou Y, Lobanov AV, Gladyshev VN, Ganis JJ, Wiley D, Jugo RH, Lee NY, Castroneves LA, Zon LI, Scanlan TS, Feldman HA, Huang SA. Intrinsic expression of a multiexon type 3 deiodinase gene controls zebrafish embryo size. Endocrinology 2014; 155:4069-80. PubMed
  • Castroneves LA, Jugo RH, Maynard MA, Lee JS, Wassner AJ, Dorfman D, Bronson RT, Ukomadu C, Agoston AT, Ding L, Luongo C, Guo C, Song H, Demchev V, Lee NY, Feldman HA, Vella KR, Peake RW, Hartigan C, Kellogg MD, Desai A, Salvatore D, Dentice M, Huang SA. Mice with hepatocyte-specific deficiency of type 3 deiodinase have intact liver regeneration and accelerated recovery from nonthyroidal illness after toxin-induced hepatonecrosis. Endocrinology 2014; 155:4061-8. PubMed
  • Maynard MA, Huang SA. Thyroid hormone inactivation in gastrointestinal stromal tumors. N Engl J Med 2014; 371:86-7. PubMed
  • Maynard MA, Marino-Enriquez A, Fletcher JA, Dorfman DM, Raut CP, Yassa L, Guo C, Wang Y, Dorfman C, Feldman HA, Frates MC, Song H, Jugo RH, Taguchi T, Hershman JM, Larsen PR, Huang SA. Thyroid hormone inactivation in gastrointestinal stromal tumors. N Engl J Med 2014; 370:1327-34. PubMed
  • Gupta A, Ly S, Castroneves LA, Frates MC, Benson CB, Feldman HA, Wassner AJ, Smith JR, Marqusee E, Alexander EK, Barletta J, Muyide F, Doubilet PM, Peters HE, Webb S, Modi BP, Paltiel HJ, Martins Y, Burmeister K, Kozakewich H, Hollowell M, Cibas ES, Moore FD, Shamberger RC, Larsen PR, Huang SA. How are childhood thyroid nodules discovered: opportunities for improving early detection. J Pediatr 2014; 164:658-60. PubMed
  • Gupta A, Ly S, Castroneves LA, Frates MC, Benson CB, Feldman HA, Wassner AJ, Smith JR, Marqusee E, Alexander EK, Barletta J, Doubilet PM, Peters HE, Webb S, Modi BP, Paltiel HJ, Kozakewich H, Cibas ES, Moore FD, Shamberger RC, Larsen PR, Huang SA. A standardized assessment of thyroid nodules in children confirms higher cancer prevalence than in adults. J Clin Endocrinol Metab 2013; 98:3238-45. PubMed
  • Ben-Shachar R, Eisenberg M, Huang SA, DiStefano JJ. Simulation of post-thyroidectomy treatment alternatives for triiodothyronine or thyroxine replacement in pediatric thyroid cancer patients. Thyroid 2012; 22:595-603. PubMed
  • Scholz S, Smith JR, Chaignaud B, Shamberger RC, Huang SA. Thyroid surgery at Children's Hospital Boston: a 35-year single-institution experience. J Pediatr Surg 2011; 46:437-42. PubMed
  • Smith JR, Marqusee E, Webb S, Nose V, Fishman SJ, Shamberger RC, Frates MC, Huang SA. Thyroid Nodules and Cancer in Children with PTEN Hamartoma Tumor Syndrome. J Clin Endocrinol Metab 2011; 96:34-7. PubMed
  • Marsili A, Ramadan W, Harney JW, Mulcahey M, Castroneves LA, Goemann IM, Wajner SM, Huang SA, Zavacki AM, Maia AL, Dentice M, Salvatore D, Silva JE, Larsen PR. Type 2 iodothyronine deiodinase levels are higher in slow-twitch than fast-twitch mouse skeletal muscle and are increased in hypothyroidism. Endocrinology 2010; 151:5952-60. PubMed
  • Aerts G, Arrojo E Drigo R, Van Herck SL, Sammels E, Mirebeau-Prunier D, Gereben B, Zeöld A, Harney JW, Huang SA, Mulcahey MA, Van der Geyten S, Van den Bergh G, Arckens L, Darras VM, Zavacki AM. Knockdown of the type 3 iodothyronine deiodinase (D3) interacting protein peroxiredoxin 3 decreases D3-mediated deiodination in intact cells. Endocrinology 2009; 150:5171-80. PubMed
  • Grozovsky R, Ribich S, Rosene ML, Mulcahey MA, Huang SA, Patti ME, Bianco AC, Kim BW. Type 2 deiodinase expression is induced by peroxisomal proliferator-activated receptor-gamma agonists in skeletal myocytes. Endocrinology 2009; 150:1976-83. PubMed
  • Huang SA. Deiodination and cellular proliferation: parallels between development, differentiation, tumorigenesis, and now regeneration. Endocrinology 2008; 150:3-4. PubMed
  • Gereben B, Zavacki AM, Ribich S, Kim BW, Huang SA, Simonides WS, Zeöld A, Bianco AC. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr. Rev. 2008; 29:898-938. PubMed
  • Capelo LP, Beber EH, Huang SA, Zorn TM, Bianco AC, Gouveia CH. Deiodinase-mediated thyroid hormone inactivation minimizes thyroid hormone signaling in the early development of fetal skeleton. Bone 2008; 43:921-30. PubMed
  • Sagar GD, Gereben B, Callebaut I, Mornon JP, Zeöld A, Curcio-Morelli C, Harney JW, Luongo C, Mulcahey MA, Larsen PR, Huang SA, Bianco AC. The thyroid hormone-inactivating deiodinase functions as a homodimer. Mol Endocrinol 2008; 22:1382-93. PubMed
  • Simonides WS, Mulcahey MA, Redout EM, Muller A, Zuidwijk MJ, Visser TJ, Wassen FW, Crescenzi A, da-Silva WS, Harney J, Engel FB, Obregon MJ, Larsen PR, Bianco AC, Huang SA. Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats. J Clin Invest 2008; 118:975-83. PubMed
  • Huang SA, Bianco AC. Reawakened interest in type III iodothyronine deiodinase in critical illness and injury. Nat Clin Pract Endocrinol Metab 2008; 4:148-55. PubMed
  • Huang SA, Mulcahey MA, Crescenzi A, Chung M, Kim BW, Barnes C, Kuijt W, Turano H, Harney J, Larsen PR. Transforming growth factor-beta promotes inactivation of extracellular thyroid hormones via transcriptional stimulation of type 3 iodothyronine deiodinase. Mol Endocrinol 2005; 19:3126-36. PubMed
  • Kuijt WJ, Huang SA. Children with differentiated thyroid cancer achieve adequate hyperthyrotropinemia within 14 days of levothyroxine withdrawal. J Clin Endocrinol Metab 2005; 90:6123-5. PubMed
  • Maia AL, Kim BW, Huang SA, Harney JW, Larsen PR. Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. J Clin Invest 2005; 115:2524-33. PubMed
  • Huang SA, Dorfman DM, Genest DR, Salvatore D, Larsen PR. Type 3 iodothyronine deiodinase is highly expressed in the human uteroplacental unit and in fetal epithelium. J Clin Endocrinol Metab 2003; 88:1384-8. PubMed
  • Huang SA, Fish SA, Dorfman DM, Salvatore D, Kozakewich HP, Mandel SJ, Larsen PR. A 21-year-old woman with consumptive hypothyroidism due to a vascular tumor expressing type 3 iodothyronine deiodinase. J Clin Endocrinol Metab 2002; 87:4457-61. PubMed
  • Huang SA, Tu HM, Harney JW, Venihaki M, Butte AJ, Kozakewich HP, Fishman SJ, Larsen PR. Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med 2000; 343:185-9. PubMed
Hide