Michael S. Freemark, MD



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Professor of Pediatrics
Division Chief, Pediatric Endocrinology
Robert C. Atkins, MD, and Veronica Atkins Professor of Pediatrics
Vice Chair of Pediatric Research
Department / Division:
Pediatrics / Pediatrics-Endocrinology
DUMC 102820
Durham, NC 27710
Appointment Telephone:
Office Telephone:
  • MD, Duke University School of Medicine, 1976
  • Pediatrics, Duke University Medical Center, 1976-1979
  • Pediatric Endocrinology, Duke University Medical Center, 1980-1984
  • Molecular Endocrinology, Lineberger Cancer Center, University of North Carolina, 1990
  • Molecular Endocrinology, Necker Hospital for Sick Children (France), 1993, 2006
Other Training:
  • BA, Brandeis University (Massachusetts), 1972
Clinical Interests:
Pediatric endocrinology; hypothalamic-pituitary dysfunction; disorders of growth, thyroid function, and sexual development; diabetes mellitus; insulin resistance; celiac disease in diabetic children, hyperlipidemia
Representative Publications:
  • Haqq, AM; Muehlbauer, MJ; Newgard, CB; Grambow, S; Freemark, M. The metabolic phenotype of Prader-Willi syndrome (PWS) in childhood: heightened insulin sensitivity relative to body mass index. Journal of Clinical Endocrinology and Metabolism. 2011;96:E225-E232.  Abstract
  • Arumugam, R; Horowitz, E; Noland, RC; Lu, D; Fleenor, D; Freemark, M. Regulation of islet beta-cell pyruvate metabolism: interactions of prolactin, glucose, and dexamethasone. Endocrinology. 2010;151:3074-3083.  Abstract
  • Brown, WV; Wilson, DP; Freemark, M; Kwiterovich, PO. The use of lipid-lowering drugs in children. Journal of Clinical Lipidology. 2010;4:449-461.  Abstract
  • Freemark, M. Placental hormones and the control of fetal growth. Journal of Clinical Endocrinology and Metabolism. 2010;95:2054-2057.  Abstract
  • Artz, E; Warren-Ulanch, J; Becker, D; Greenspan, S; Freemark, M. Seropositivity to celiac antigens in asymptomatic children with type 1 diabetes mellitus: association with weight, height, and bone mineralization. Pediatric Diabetes. 2008;9:277-284.  Abstract
  • Arumugam, R; Horowitz, E; Lu, D; Collier, JJ; Ronnebaum, S; Fleenor, D; Freemark, M. The interplay of prolactin and the glucocorticoids in the regulation of beta-cell gene expression, fatty acid oxidation, and glucose-stimulated insulin secretion: implications for carbohydrate metabolism in pregnancy. Endocrinology. 2008;149:5401-5414.  Abstract
  • August, GP; Caprio, S; Fennoy, I; Freemark, M; Kaufman, FR; Lustig, RH; Silverstein, JH; Speiser, PW; Styne, DM; Montori, VM; Endocrine Society. Prevention and treatment of pediatric obesity: an endocrine society clinical practice guideline based on expert opinion. Journal of Clinical Endocrinology and Metabolism. 2008;93:4576-4599.  Abstract
  • Haqq, AM; Grambow, SC; Muehlbauer, M; Newgard, CB; Svetkey, LP; Carrel, AL; Yanovski, JA; Purnell, JQ; Freemark, M. Ghrelin concentrations in Prader-Willi syndrome (PWS) infants and children: changes during development. Clinical Endocrinology. 2008;69:911-920.  Abstract
  • Higgins, SP; Freemark, M; Prose, NS. Acanthosis nigricans: a practical approach to evaluation and management. Dermatology Online Journal. 2008;14:2.  Abstract
  • Viengchareun, S; Servel, N; Fève, B; Freemark, M; Lombès, M; Binart, N. Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth factor-2. PLoS One. 2008;3:e1535.  Abstract
  • Arumugam, R; Fleenor, D; Freemark, M. Effects of lactogen resistance and GH deficiency on mouse metabolism: pancreatic hormones, adipocytokines, and expression of adiponectin and insulin receptors. Endocrine. 2007;32:182-191.  Abstract
  • Arumugam, R; Fleenor, D; Freemark, M. Lactogenic and somatogenic hormones regulate the expression of neuropeptide Y and cocaine- and amphetamine-regulated transcript in rat insulinoma (INS-1) cells: interactions with glucose and glucocorticoids. Endocrinology. 2007;148:258-267.  Abstract
  • Freemark, M. Liver dysfunction in paediatric obesity: a randomized, controlled trial of metformin. Acta Paediatrica: promoting child health. 2007;96:1326-1332.  Abstract
  • Freemark, M. Pharmacotherapy of childhood obesity: an evidence-based, conceptual approach. Diabetes Care. 2007;30:395-402.  Abstract
  • Haqq, AM; Muehlbauer, M; Svetkey, LP; Newgard, CB; Purnell, JQ; Grambow, SC; Freemark, MS. Altered distribution of adiponectin isoforms in children with Prader-Willi syndrome (PWS): association with insulin sensitivity and circulating satiety peptide hormones. Clinical Endocrinology. 2007;67:944-951.  Abstract
  • Fleenor, D; Arumugam, R; Freemark, M. Growth hormone and prolactin receptors in adipogenesis: STAT-5 activation, suppressors of cytokine signaling, and regulation of insulin-like growth factor I. Hormone Research in Paediatrics: from developmental endocrinology to clinical research. 2006;66:101-110.  Abstract
  • Freemark, M. Regulation of maternal metabolism by pituitary and placental hormones: roles in fetal development and metabolic programming. Hormone Research in Paediatrics: from developmental endocrinology to clinical research. 2006;65 Suppl 3:41-49.  Abstract
  • Artz, E; Haqq, A; Freemark, M. Hormonal and metabolic consequences of childhood obesity. Endocrinology and Metabolism Clinics of North America. 2005;34:643-ix.  Abstract
  • Fleenor, D; Oden, J; Kelly, PA; Mohan, S; Alliouachene, S; Pende, M; Wentz, S; Kerr, J; Freemark, M. Roles of the lactogens and somatogens in perinatal and postnatal metabolism and growth: studies of a novel mouse model combining lactogen resistance and growth hormone deficiency. Endocrinology. 2005;146:103-112.  Abstract
  • Speiser, PW; Rudolf, MC; Anhalt, H; Camacho-Hubner, C; Chiarelli, F; Eliakim, A; Freemark, M; Gruters, A; Hershkovitz, E; Iughetti, L; Krude, H; Latzer, Y; Lustig, RH; Pescovitz, OH; Pinhas-Hamiel, O; Rogol, AD; Shalitin, S; Sultan, C; Stein, D; Vardi, P; Werther, GA; Zadik, Z; Zuckerman-Levin, N; Hochberg, Z; Obesity Consensus Working Group. Childhood obesity. Journal of Clinical Endocrinology and Metabolism. 2005;90:1871-1887.  Abstract
  • Artz, E; Freemark, M. The pathogenesis of insulin resistance in children: metabolic complications and the roles of diet, exercise and pharmacotherapy in the prevention of type 2 diabetes. Pediatric Endocrinology Reviews. 2004;1:296-309.  Abstract
  • Freemark, M. Editorial: Growth hormone treatment of "idiopathic short stature": not so fast. Journal of Clinical Endocrinology and Metabolism. 2004;89:3138-3139.  Abstract
  • Freemark, M; Kiess, W. Anti-obesity medication use in adolescents: risks and benefits. Pediatric Endocrinology Reviews. 2004;2 Suppl 1:168-170.  Abstract
  • Freemark, M. Pharmacologic approaches to the prevention of type 2 diabetes in high risk pediatric patients. Journal of Clinical Endocrinology and Metabolism. 2003;88:3-13.  Abstract
  • Freemark, M; Levitsky, LL. Screening for celiac disease in children with type 1 diabetes: two views of the controversy. Diabetes Care. 2003;26:1932-1939.  Abstract
  • Freemark, M; Avril, I; Fleenor, D; Driscoll, P; Petro, A; Opara, E; Kendall, W; Oden, J; Bridges, S; Binart, N; Breant, B; Kelly, PA. Targeted deletion of the PRL receptor: effects on islet development, insulin production, and glucose tolerance. Endocrinology. 2002;143:1378-1385.  Abstract
  • Litton, J; Rice, A; Friedman, N; Oden, J; Lee, MM; Freemark, M. Insulin pump therapy in toddlers and preschool children with type 1 diabetes mellitus. Journal of Pediatrics. 2002;141:490-495.  Abstract
  • Oden, J; Fleenor, D; Driscoll, P; Freemark, M. Leptin in the newborn mouse. Plasma concentrations, characterization of the circulating hormone, and tissue source. Neonatology: foetal and neonatal research. 2002;82:109-116.  Abstract
  • Oden, J; Freemark, M. Thyroxine supplementation in preterm infants: critical analysis. Current Opinion in Pediatrics. 2002;14:447-452.  Abstract
  • Fleenor, DE; Freemark, M. Prolactin induction of insulin gene transcription: roles of glucose and signal transducer and activator of transcription 5. Endocrinology. 2001;142:2805-2810.  Abstract
  • Freemark, M. Ontogenesis of prolactin receptors in the human fetus: roles in fetal development. Biochemical Society Transactions. 2001;29:38-41.  Abstract
  • Freemark, M; Bursey, D. The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. Pediatrics. 2001;107:E55.  Abstract
  • Freemark, M; Fleenor, D; Driscoll, P; Binart, N; Kelly, P. Body weight and fat deposition in prolactin receptor-deficient mice. Endocrinology. 2001;142:532-537.  Abstract
  • Kelly, PA; Binart, N; Freemark, M; Lucas, B; Goffin, V; Bouchard, B. Prolactin receptor signal transduction pathways and actions determined in prolactin receptor knockout mice. Biochemical Society Transactions. 2001;29:48-52.  Abstract
  • Rapaport, R; Rose, SR; Freemark, M. Hypothyroxinemia in the preterm infant: the benefits and risks of thyroxine treatment. Journal of Pediatrics. 2001;139:182-188.  Abstract
  • Fleenor, D; Petryk, A; Driscoll, P; Freemark, M. Constitutive expression of placental lactogen in pancreatic beta cells: effects on cell morphology, growth, and gene expression. Pediatric Research. 2000;47:136-142.  Abstract
  • Handwerger, S; Freemark, M. The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development. Journal of Pediatric Endocrinology and Metabolism. 2000;13:343-356.  Abstract
  • Petryk, A; Fleenor, D; Driscoll, P; Freemark, M. Prolactin induction of insulin gene expression: the roles of glucose and glucose transporter-2. Journal of Endocrinology. 2000;164:277-286.  Abstract
  • Freemark, M. The fetal adrenal and the maturation of the growth hormone and prolactin axes. Endocrinology. 1999;140:1963-1965.  Abstract
  • Rivkees, SA; Sklar, C; Freemark, M. Clinical review 99: The management of Graves' disease in children, with special emphasis on radioiodine treatment. Journal of Clinical Endocrinology and Metabolism. 1998;83:3767-3776.  Abstract
  • Freemark, M; Driscoll, P; Maaskant, R; Petryk, A; Kelly, PA. Ontogenesis of prolactin receptors in the human fetus in early gestation. Implications for tissue differentiation and development. Journal of Clinical Investigation. 1997;99:1107-1117.  Abstract
  • Freemark, M; Driscoll, P; Andrews, J; Kelly, PA; Royster, M. Ontogenesis of prolactin receptor gene expression in the rat olfactory system: potential roles for lactogenic hormones in olfactory development. Endocrinology. 1996;137:934-942.  Abstract
  • Bridges, RS; Freemark, MS. Human placental lactogen infusions into the medial preoptic area stimulate maternal behavior in steroid-primed, nulliparous female rats. Hormones and Behaviour. 1995;29:216-226.  Abstract
  • Freemark, M; Nagano, M; Edery, M; Kelly, PA. Prolactin receptor gene expression in the fetal rat. Journal of Endocrinology. 1995;144:285-292.  Abstract
  • Royster, M; Driscoll, P; Kelly, PA; Freemark, M. The prolactin receptor in the fetal rat: cellular localization of messenger ribonucleic acid, immunoreactive protein, and ligand-binding activity and induction of expression in late gestation. Endocrinology. 1995;136:3892-3900.  Abstract
  • Fowlkes, J; Freemark, M. Placental lactogen-binding sites in isolated fetal fibroblasts: characterization, processing, and regulation. Endocrinology. 1993;132:2477-2483.  Abstract
  • Freemark, M; Kirk, K; Pihoker, C; Robertson, MC; Shiu, RP; Driscoll, P. Pregnancy lactogens in the rat conceptus and fetus: circulating levels, distribution of binding, and expression of receptor messenger ribonucleic acid. Endocrinology. 1993;133:1830-1842.  Abstract
  • Pihoker, C; Robertson, MC; Freemark, M. Rat placental lactogen-I binds to the choroid plexus and hypothalamus of the pregnant rat. Journal of Endocrinology. 1993;139:235-242.  Abstract
  • Fowlkes, J; Freemark, M. Binding of placental lactogen and growth hormone to fetal sheep fibroblasts. Pediatric Research. 1992;32:200-203.  Abstract
  • Fowlkes, J; Freemark, M. Developmental regulation of insulin-like growth factor binding protein production: studies in fetal, postnatal, and pregnant sheep. Journal of Cellular Physiology. 1992;152:19-27.  Abstract
  • Fowlkes, J; Freemark, M. Evidence for a novel insulin-like growth factor (IGF)-dependent protease regulating IGF-binding protein-4 in dermal fibroblasts. Endocrinology. 1992;131:2071-2076.  Abstract
  • Freemark, M; Keen, A; Fowlkes, J; Mularoni, T; Comer, M; Grandis, A; Kodack, L. The placental lactogen receptor in maternal and fetal sheep liver: regulation by glucose and role in the pathogenesis of fasting during pregnancy. Endocrinology. 1992;130:1063-1070.  Abstract
  • Osborn, BH; Fowlkes, J; Han, VK; Freemark, M. Nutritional regulation of insulin-like growth factor-binding protein gene expression in the ovine fetus and pregnant ewe. Endocrinology. 1992;131:1743-1750.  Abstract
  • Freemark, M; Comer, M; Mularoni, T; D'Ercole, AJ; Grandis, A; Kodack, L. Placental lactogen receptors in maternal sheep liver: effects of fasting and refeeding. American Journal of Physiology. 1990;258:E338-E346.  Abstract
  • Freemark, M; Comer, M. Purification of a distinct placental lactogen receptor, a new member of the growth hormone/prolactin receptor family. Journal of Clinical Investigation. 1989;83:883-889.  Abstract
  • Freemark, M; Comer, M; Mularoni, T; D'Ercole, AJ; Grandis, A; Kodack, L. Nutritional regulation of the placental lactogen receptor in fetal liver: implications for fetal metabolism and growth. Endocrinology. 1989;125:1504-1512.  Abstract
  • Freemark, M; Handwerger, S. The role of placental lactogen in the regulation of fetal metabolism and growth. Journal of Pediatric Gastroenterology and Nutrition. 1989;8:281-283.  Abstract
  • Freemark, M; Comer, M; Korner, G. Differential solubilization of placental lactogen (PL)- and growth hormone-binding sites: further evidence for a unique PL receptor in fetal and maternal liver. Endocrinology. 1988;122:2771-2779.  Abstract
  • Hill, DJ; Freemark, M; Strain, AJ; Handwerger, S; Milner, RD. Placental lactogen and growth hormone receptors in human fetal tissues: relationship to fetal plasma human placental lactogen concentrations and fetal growth. Journal of Clinical Endocrinology and Metabolism. 1988;66:1283-1290.  Abstract
  • Freemark, M; Comer, M. Epidermal growth factor (EGF)-like transforming growth factor (TGF) activity and EGF receptors in ovine fetal tissues: possible role for TGF in ovine fetal development. Pediatric Research. 1987;22:609-615.  Abstract
  • Freemark, M; Comer, M; Korner, G; Handwerger, S. A unique placental lactogen receptor: implications for fetal growth. Endocrinology. 1987;120:1865-1872.  Abstract
  • Handwerger, S; Freemark, M. Role of placental lactogen and prolactin in human pregnancy. Advances in Experimental Medicine and Biology. 1987;219:399-420.  Abstract
  • Freemark, M. Epidermal growth factor stimulates glycogen synthesis in fetal rat hepatocytes: comparison with the glycogenic effects of insulin-like growth factor I and insulin. Endocrinology. 1986;119:522-526.  Abstract
  • Freemark, M; Comer, M; Handwerger, S. Placental lactogen and GH receptors in sheep liver: striking differences in ontogeny and function. American Journal of Physiology. 1986;251:E328-E333.  Abstract
  • Freemark, M; Handwerger, S. The glycogenic effects of placental lactogen and growth hormone in ovine fetal liver are mediated through binding to specific fetal ovine placental lactogen receptors. Endocrinology. 1986;118:613-618.  Abstract
  • Freemark, M; D'Ercole, AJ; Handwerger, S. Somatomedin-C stimulates glycogen synthesis in fetal rat hepatocytes. Endocrinology. 1985;116:2578-2582.  Abstract
  • Freemark, M; Handwerger, S. Ovine placental lactogen inhibits glucagon-induced glycogenolysis in fetal rat hepatocytes. Endocrinology. 1985;116:1275-1280.  Abstract
  • Freemark, M; Handwerger, S. Glycogenolytic effects of the calcium ionophore A23187, but not of vasopressin or angiotensin, in foetal-rat hepatocytes. Biochemical Journal. 1984;220:441-445.  Abstract
  • Freemark, M; Handwerger, S. Ovine placental lactogen stimulates glycogen synthesis in fetal rat hepatocytes. American Journal of Physiology. 1984;246:E21-E24.  Abstract
  • Freemark, M; Handwerger, S. Synergistic effects of oPL and insulin on glycogen metabolism in fetal rat hepatocytes. American Journal of Physiology. 1984;247:E714-E718.  Abstract
  • Freemark, M; Handwerger, S. Ovine placental lactogen, but not growth hormone, stimulates amino acid transport in fetal rat diaphragm. Endocrinology. 1983;112:402-404.  Abstract
  • Freemark, M; Handwerger, S. Ovine placental lactogen stimulates amino acid transport in rat diaphragm. Endocrinology. 1982;110:2201-2203.  Abstract
  • Dubois, PJ; Freemark, M; Lewis, D; Drayer, BP; Heinz, ER; Osborne, D. Case report. Atypical findings in adrenoleukodystrophy. Journal of Computer Assisted Tomography: a radiological journal dedicated to the basic and clinical aspects of reconstructive tomography. 1981;5:888-891.  Abstract
  • Raffin, BJ; Freemark, M. Streptobacillary rat-bite fever: a pediatric problem. Pediatrics. 1979;64:214-217.  Abstract
  • Freemark, M; Stoff, DM; Moja, EA; Gillin, JC; Wyatt, RJ. Testosterone-attenuated stereotype and hyperactivity induced by beta-phenylethylamine in pargyline-pretreated rats. Biological Psychiatry. 1978;13:455-463.  Abstract