Stephen Huang

Stephen Huang, MD

Director, Thyroid Program

Associate Professor of Pediatrics, Harvard Medical School

  • Contact: Endocrine: 617-355-7476

  • Fax: 617-730-0194

Medical Services

Specialties

  • Hyperthyroidism
  • Hypothyroidism
  • Thyroid Cancer
  • Thyroid Nodules
  • Thyroid Disease

Departments

  • Endocrinology
  • Medicine

Programs

  • Thyroid Program
  • Endocrinology Program
  • Vascular Anomalies Center
  • Center for Pediatric Polyposis
  • Pediatric Cancer Risk Program
To schedule an appointment: Call Endocrine: 617-355-7476 or Request an Appointment

Experience and Education

Education

Medical School

University of Pennsylvania, 1995

Philadelphia, PA

Pediatric Endocrinology Fellowship

Boston Children's Hospital, 2001

Boston, MA

Thyroidology Fellowship

Brigham and Women's Hospital, 2002

Boston, MA

Pediatric Internship

Boston Children's Hospital, 1996

Boston, MA

Pediatric Residency

Boston Children's Hospital, 1998

Boston, MA

Certifications

  • Pediatric Endocrinology

Research

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

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  1. Yi T, Arthanari H, Akabayov B, Song H, Papadopoulos E, Qi HH, Jedrychowski M, Güttler T, Guo C, Luna RE, Gygi SP, Huang SA, Wagner G. eIF1A augments Ago2-mediated Dicer-independent miRNA biogenesis and RNA interference. Nat Commun. 2015; 6:7194.
  2. 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 Oct; 155(10):4069-80.
  3. 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 Oct; 155(10):4061-8.
  4. Maynard MA, Huang SA. Thyroid hormone inactivation in gastrointestinal stromal tumors. N Engl J Med. 2014 Jul 3; 371(1):86-7.
  5. Huang SA. Commentary. Clin Chem. 2014 Jun; 60(6):821.
  6. 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 Apr 3; 370(14):1327-34.
  7. 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 Mar; 164(3):658-60.
  8. 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 Aug; 98(8):3238-45.
  9. 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 Jun; 22(6):595-603.
  10. 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 Mar; 46(3):437-42.
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  12. 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 Jan; 96(1):34-7.
  13. 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 Dec; 151(12):5952-60.
  14. Simmen FA, Mercado CP, Zavacki AM, Huang SA, Greenway AD, Kang P, Bowman MT, Prior RL. Soy protein diet alters expression of hepatic genes regulating fatty acid and thyroid hormone metabolism in the male rat. J Nutr Biochem. 2010 Nov; 21(11):1106-13.
  15. 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 Nov; 150(11):5171-80.
  16. Huang, SA, Neves L. Thyroid Hormone Metabolism (Chapter, commissioned, in press). Thyroid Function Tests, Brent G editor. 2009.
  17. Huang SA. Deiodination and cellular proliferation: parallels between development, differentiation, tumorigenesis, and now regeneration. Endocrinology. 2009 Jan; 150(1):3-4.
  18. Huang, SA. The Thyroid Gland and its Disorders (Chapter, commissioned, in press). Principles and Practice of Pediatric Endocrinology, Kappy MS, Allen DB, and Geffner ME editors. 2009.
  19. Huang SA. Can hyperthyroidism relapse after antithyroid drug treatment be predicted in children with Graves disease? Nat Clin Pract Endocrinol Metab. 2009 Feb; 5(2):74-5.
  20. LaFranchi S Huang SA. Newborn Thyroid Disorders and Screening (Chapter, commissioned, in press). Manual of Endocrinology and Metabolism, Lavin N editor. 2008.
  21. 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 Apr; 150(4):1976-83.
  22. 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 Dec; 29(7):898-938.
  23. 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 Nov; 43(5):921-30.
  24. Kellogg MD, Law TC, Huang S, Rifai N. A girl with goiter and inappropriate thyroid-stimulating hormone secretion. Clin Chem. 2008 Jul; 54(7):1241-4.
  25. 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 Jun; 22(6):1382-93.
  26. 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 Mar; 118(3):975-83.
  27. Huang SA, Bianco AC. Reawakened interest in type III iodothyronine deiodinase in critical illness and injury. Nat Clin Pract Endocrinol Metab. 2008 Mar; 4(3):148-55.
  28. Huang SA. Hypothyroidism (Chapter). Pediatric Endocrinology, Lifshitz F editor. 2007.
  29. Huang SA. Thyromegaly (Chapter). Pediatric Endocrinology, Lifshitz F editor. 2007.
  30. Huang SA. Thyroid Disease in Adolescents (Chapter). Neinstein’s Adolescent Healthcare: A Practical Guide, Neinstein LS, Mellet KC, Gordon C editors. 2007.
  31. Dentice M, Luongo C, Huang S, Ambrosio R, Elefante A, Mirebeau-Prunier D, Zavacki AM, Fenzi G, Grachtchouk M, Hutchin M, Dlugosz AA, Bianco AC, Missero C, Larsen PR, Salvatore D. Sonic hedgehog-induced type 3 deiodinase blocks thyroid hormone action enhancing proliferation of normal and malignant keratinocytes. Proc Natl Acad Sci U S A. 2007 Sep 4; 104(36):14466-71.
  32. Olivares EL, Marassi MP, Fortunato RS, da Silva AC, Costa-e-Sousa RH, Araújo IG, Mattos EC, Masuda MO, Mulcahey MA, Huang SA, Bianco AC, Carvalho DP. Thyroid function disturbance and type 3 iodothyronine deiodinase induction after myocardial infarction in rats a time course study. Endocrinology. 2007 Oct; 148(10):4786-92.
  33. da-Silva WS, Harney JW, Kim BW, Li J, Bianco SD, Crescenzi A, Christoffolete MA, Huang SA, Bianco AC. The small polyphenolic molecule kaempferol increases cellular energy expenditure and thyroid hormone activation. Diabetes. 2007 Mar; 56(3):767-76.
  34. Balazs AE, Athanassaki I, Gunn SK, Tatevian N, Huang SA, Haymond MW, Karaviti LP. Rapid resolution of consumptive hypothyroidism in a child with hepatic hemangioendothelioma following liver transplantation. Ann Clin Lab Sci. 2007; 37(3):280-4.
  35. Huang SA. Thyroid (Chapter). Pediatric Nuclear Medicine, Treves ST editor. 2006.
  36. Christoffolete MA, Ribeiro R, Singru P, Fekete C, da Silva WS, Gordon DF, Huang SA, Crescenzi A, Harney JW, Ridgway EC, Larsen PR, Lechan RM, Bianco AC. Atypical expression of type 2 iodothyronine deiodinase in thyrotrophs explains the thyroxine-mediated pituitary thyrotropin feedback mechanism. Endocrinology. 2006 Apr; 147(4):1735-43.
  37. Ruppe MD, Huang SA, Jan de Beur SM. Consumptive hypothyroidism caused by paraneoplastic production of type 3 iodothyronine deiodinase. Thyroid. 2005 Dec; 15(12):1369-72.
  38. Brown RS, Huang SA. The Thyroid and its Disorders (Chapter). Clinical Pediatric Endocrinology, Brook C, Clayton P, and Brown R editors. 2005.
  39. Mackie AS, Booth KL, Newburger JW, Gauvreau K, Huang SA, Laussen PC, DiNardo JA, del Nido PJ, Mayer JE, Jonas RA, McGrath E, Elder J, Roth SJ. A randomized, double-blind, placebo-controlled pilot trial of triiodothyronine in neonatal heart surgery. J Thorac Cardiovasc Surg. 2005 Sep; 130(3):810-6.
  40. 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 Sep; 115(9):2524-33.
  41. Kuijt WJ, Huang SA. Children with differentiated thyroid cancer achieve adequate hyperthyrotropinemia within 14 days of levothyroxine withdrawal. J Clin Endocrinol Metab. 2005 Nov; 90(11):6123-5.
  42. Huang SA. Physiology and pathophysiology of type 3 deiodinase in humans. Thyroid. 2005 Aug; 15(8):875-81.
  43. 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 Dec; 19(12):3126-36.
  44. Brown RS, Huang SA, Fisher DA. The Maturation of Thyroid Function in the Perinatal Period and During Childhood (Chapter). Werner & Ingbar’s the Thyroid: a Fundamental and Clinical Text, Braverman LE and Utiger RD editors. 2005.
  45. Zambrano E, Holm I, Glickman J, Huang S, Perez-Atayde A, Kozakewich HP, Shamberger RC, Nosé V. Abnormal distribution and hyperplasia of thyroid C-cells in PTEN-associated tumor syndromes. Endocr Pathol. 2004; 15(1):55-64.
  46. Huang SA, Gereben B, Callebaut I, Mulcahey MA, Curcio-Morelli C, Mornon J-P, Castro B, Harney JW, Larsen PR, Bianco AC. Identification of conserved amino acids in the iodothyronine deiodinase selenocysteine-containing pocket that are critical for outer but not inner ring deiodination. American Thyroid Association 2003 Meeting. 2003.
  47. Callebaut I, Curcio-Morelli C, Mornon JP, Gereben B, Buettner C, Huang S, Castro B, Fonseca TL, Harney JW, Larsen PR, Bianco AC. The iodothyronine selenodeiodinases are thioredoxin-fold family proteins containing a glycoside hydrolase clan GH-A-like structure. J Biol Chem. 2003 Sep 19; 278(38):36887-96.
  48. 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 Mar; 88(3):1384-8.
  49. Curcio-Morelli C, Gereben B, Zavacki AM, Kim BW, Huang S, Harney JW, Larsen PR, Bianco AC. In vivo dimerization of types 1, 2, and 3 iodothyronine selenodeiodinases. Endocrinology. 2003 Mar; 144(3):937-46.
  50. Huang SA, Larsen PR. Autoimmune Thyroid Disease (Chapter). Pediatric Endocrinology: A Practical Clinical Guide, Radovick S and MacGillivray MH editors. 2003.
  51. 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 Oct; 87(10):4457-61.
  52. 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 Jul 20; 343(3):185-9.
To schedule an appointment: Call Endocrine: 617-355-7476 or Request an Appointment

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