eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Hyposomatotropism

Author: Robert J Ferry Jr, MD, Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis, and St Jude Children's Research Hospital; Field Surgeon (Medical Corps), 162nd Area Support Medical Company, Army National Guard
Coauthor(s): Sherry Franklin, MD, Consulting Staff, Department of Pediatrics, Division of Endocrinology, Pediatric Endocrinology of San Diego Medical Group
Contributor Information and Disclosures

Updated: Jul 2, 2009

Introduction

Background

Remarkable research over the past 4 decades has advanced our knowledge of the physiology of the growth hormone (GH) axis.

Human pituitary-derived growth hormone

More than 40 years have elapsed since human pituitary-derived growth hormone (pit-hGH) was purified and the first patient, a 17-year-old male adolescent with growth hormone deficiency (GHD), was treated successfully with pit-hGH. For many years, pituitary glands harvested from human cadavers provided the only practical source of GH with which to treat GHD. Worldwide, more than 27,000 children with GHD received pit-hGH from the 1950s to the mid 1980s.

Pit-hGH was a suboptimal therapy for 3 reasons.

  1. The shortage of pit-hGH limited its use and the dosages administered.
  2. The biopotency of preparations varied. Strict diagnostic criteria for GHD were used to address these problems (eg, peak plasma immunoreactive GH levels of more than 3.5-5 ng/mL after provocative stimuli).
  3. Treatment was often interrupted. The mean age for starting treatment with pit-hGH was often 12-13 years (late in childhood), and severe growth failure (height Z score -4 to -6) was required. As a result, pit-hGH therapy was often discontinued when girls attained a height of 60 inches and when boys attained a height of 65 inches.

Nonetheless, pit-hGH had dramatic effects. Among patients with isolated GHD, final height standard deviation scores increased to approximately -2 in boys and -2.5 to -3 in girls. For children with multiple pituitary-hormone deficiencies, height standard deviation scores increased to between -1 and -2.

The number of patients with GHD who were treated with pit-hGH increased from approximately 150 to more than 3000 by 1985. However, in 1985, studies indicated that pit-hGH was the likely source of contaminated material (prions) responsible for Creutzfeldt-Jakob disease (a slowly developing, progressive, fatal neurologic disorder) in 3 young men. As a consequence, production and distribution of pit-hGH for therapy was discontinued.

Recombinant human growth hormone

The commercial introduction of recombinant human growth hormone (rhGH) in 1985 dramatically changed the field of therapy for GH. Since then, rhGH has been administered to more than 50,000 children worldwide, making it one of the most extensively studied therapies in the pediatric pharmacopoeia.

US Food and Drug Administration (FDA)–approved indications for the administration of rhGH in children include treatment of the following conditions:

Achievement of final adult height consistent with a child's genetic potential remains the primary therapeutic endpoint for rhGH therapy in the pediatric population. In addition to its effects on bone mass, GH regulates muscle mass, muscular strength, body composition, lipid and carbohydrate metabolism, and cardiac function. Patients with GHD typically have hyperlipidemia, increased body fat, premature atherosclerotic plaques, delayed bone maturation, and impaired cardiac function.

At present, GHD in adults is recognized as a distinct clinical syndrome that encompasses reduced psychological well-being and specific metabolic abnormalities. Such abnormalities, including hypertension, central obesity, insulin resistance, dyslipidemia, and coagulopathy, closely resemble those of metabolic insulin resistance syndrome. The increased rates of cardiovascular morbidity and mortality reinforce the close association between the syndromes.

Replacement of GH in adults with GHD markedly reduces central obesity and substantially reduced total cholesterol levels but has produced little change in other risk factors, particularly, insulin resistance and dyslipidemia. For these patients, concerns are the persistent insulin resistance and dyslipidemia, together with the elevated plasma insulin and lipoprotein(a) levels observed with GH replacement. Long-term follow-up data are required to assess the effect of GH replacement on cardiovascular morbidity and mortality in adults with GHD.

The large commercial supply of rhGH fuels research and debate over the proper indications for this potent and expensive therapy. Few disagree that many patients with childhood-onset GHD require continuous GH replacement therapy into adulthood. However, the diagnostic criteria for GHD in patients of any age remain controversial. This ambiguity stems from the wide variability in current tools used to diagnose GHD, as discussed below (see Workup).

Clinicians and researchers alike will continue to grapple with these dilemmas in the foreseeable future. However, commercial interests and patient advocates continue to pressure the medical community to expand the accepted indications for rhGH. Therefore, the clinician and the clinical researcher must examine published data critically and must educate individual patients and their families about the risk-benefit ratio of rhGH therapy for them.

Pathophysiology

Anatomy

Most of the pituitary gland is dedicated to synthesizing and secreting GH from somatotrophs of the adenohypophysis (anterior pituitary).

T1-weighted sagittal MRI through the pituitary fo...

T1-weighted sagittal MRI through the pituitary fossa shows a normal pituitary gland.

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T1-weighted sagittal MRI through the pituitary fo...

T1-weighted sagittal MRI through the pituitary fossa shows a normal pituitary gland.


The adenohypophysis derives from the Rathke pouch, a diverticulum of the primitive oral cavity. The adenohypophysis consists of 3 lobes, namely, the pars distalis, the pars intermedia (which is vestigial in humans), and the pars tuberalis. The pars distalis is the largest lobe and contains most of the somatotrophs. The pituitary gland lies within the sella turcica, covered superiorly by the diaphragma sellae and the optic chiasm.

Growth hormone

The hypothalamus communicates with the anterior pituitary gland by releasing of hypothalamic peptides, which are subsequently transported in the hypophyseal portal circulation (ie, the blood supply and communication between the hypothalamus and the adenohypophysis). GH is secreted in a pulsatile pattern as a single-chain, 191-amino acid, 22-kDa protein.

Two specific hypothalamic peptides play major regulatory roles in GH secretion: growth hormone-releasing hormone (GHRH) and somatotropin-releasing factor. Amplitudes and frequencies for release of GHRH and somatotropin-releasing factor, as well as GH, differ between boys and girls and may partially account for differences in the phenotypes between the sexes.

Several neurotransmitters and neuropeptides also control GH secretion by directly acting on somatotrophs or by indirectly acting by means of hypothalamic pathways. These neurotransmitters include pituitary adenylate cyclase activating polypeptide (PACAP), galanin, pituitary-specific transcription factor-1 (Pit-1), prophet of Pit-1 (PROP1), HESX1, serotonin, histamine, norepinephrine, dopamine, acetylcholine, gamma-aminobutyric acid, thyrotropin-releasing hormone, vasoactive intestinal peptide, gastrin, neurotensin, substance P, calcitonin, neuropeptide Y, vasopressin, and corticotropin-releasing hormone.

Insulinlike growth factors

Insulinlike growth factors (IGFs) are a family of peptides that partially depend on GH and that mediate many of its anabolic and mitogenic actions.

Two theories have been proposed regarding the relationship between GH and IGFs: the somatomedin hypothesis and the dual-effector hypothesis. According to the somatomedin hypothesis, IGF mediates all of the anabolic actions of GH. Although this theory is partially correct, GH also has various other independent metabolic actions, such as enhancement of lipolysis, stimulation of amino acid transport in the diaphragm and the heart, and enhancement of hepatic protein synthesis. The attempt to resolve this discrepancy lies in the dual-effector model. According to this theory, GH stimulates precursor cells to differentiate and secrete IGF, which, in turn, exerts mitogenic and stimulatory effects.

Insulinlike growth factor binding proteins

Six high-affinity insulinlike growth factor binding proteins (IGFBPs) bind IGFs in the circulation and tissues, regulating IGF bioavailability to the IGF receptors. Under most conditions, IGFBPs appear to inhibit the action of IGFs by competing with IGF receptors for IGF peptides. However, under specific conditions, several IGFBPs can enhance IGF actions or exert IGF-independent actions.

Relative concentrations of the IGFBPs vary among biologic fluids. IGFBP-3 is the most abundant IGFBP species in human serum and circulates as part of a ternary complex consisting of IGFBP-3, an IGF molecule, and a glycoprotein called the acid-labile subunit. IGFBP-3 is the only IGFBP that clearly demonstrates GH dependence. Therefore, IGFBP-3 is a clinically useful tool for the diagnosis of GHD and the follow-up care of patients.

Sex steroids

Androgens and estrogens substantially contribute to growth during the adolescent growth spurt. Children with GHD lack the normal growth spurt despite adequate amounts of exogenous or endogenous gonadal steroids. The relationship among the sex steroids, GH, and skeletal maturation is not clearly understood. However, GH secretion is lower in frequency and higher in amplitude among males than in among females.

Androgen and estrogen receptors have been identified in the hypothalamus and are suspected to play an important regulatory role in the release of somatostatin, the hypothalamic hormone that inhibits GH secretion. Somatostatin regulation is believed to direct the frequency and amplitude of GH secretion. Therefore, it may be one of the sources of the differences between male and female individuals.

Thyroid hormone

Thyroid hormone is essential for postnatal growth. Growth failure, which may be profound, is the most common and prominent manifestation of hypothyroidism. The interrelationships between the thyroid and the pituitary-GH-IGF axis are complex and not yet fully defined. Hypotheses include a direct effect of thyroid hormone on the growth of epiphyseal cartilage and a permissive effect on GH secretion. Proof of the permissive effect on GH secretion derives from studies revealing that spontaneous GH secretion is decreased and that the response to provocative GH testing is blunted in patients with hypothyroidism (see Workup).

In addition, growth velocity is markedly decreased among rhGH-treated patients with GHD and hypothyroidism until thyroid hormone replacement is begun. Downregulation of GH receptors and decreased production of IGF-1 and IGFBP-3 have been reported in the hypothyroid state. An unexplained relationship exists between the treatment of patients with GHD by using rhGH and the development and unmasking of hypothyroidism.

Frequency

United States

The prevalence is 1 case per 3480 children or adolescents aged 4-15 years.

International

No strong data about the international prevalence of hyposomatotropism are available.

Mortality/Morbidity

Morbidity

Sequelae of hyposomatotropism include the following:

  • Behavioral and educational difficulties
  • Peripheral vascular disease and reduced myocardial function
  • Lean body mass, reduced muscular strength, and reduced exercise capacity
  • Reduced thermoregulation
  • Abnormal metabolism of thyroid hormone
  • Impaired psychosocial well-being
  • Decreased bone mineral content

Mortality

The overall crude mortality rate for patients with tumor-related, trauma-related, or iatrogenic GHD is 2.7%.

Clinicians must be cognizant of the increased incidence of mortality among patients with multiple pituitary hormone insufficiency secondary to adrenal crisis.

Race

A racial ascertainment bias may be noted. Demographic and diagnostic features of GHD in children in the United States reveal that black children with idiopathic GHD are shorter than white children are at the time of diagnosis. The low overall representation of black children in the population with GHD (6%) compared with their representation in the at-risk population (12.9%) also suggests an ascertainment bias between the races.

Sex

A male ascertainment bias may be observed. The predominance of GHD diagnosed in boys in the United States and the observation that girls with idiopathic GHD are comparatively shorter than boys at the time of diagnosis suggest a sex-based ascertainment bias.

Age

The age of patients with GHD is depends on the etiology of the disease (see Causes).

Clinical

History

  • Congenital hyposomatotropism
    • Infants with congenital growth hormone (GH) deficiency (GHD) are typically born with a length and weight between the 5th and 10th percentiles for their gestational age. A family history of short stature or parental consanguinity may suggest a genetic etiology.
    • A recent study compared fetal an neonatal growth curves in detecting growth restriction.1
    • Newborns with congenital hypopituitarism (defined as deficiencies of all anterior pituitary hormones) often present with midline craniofacial abnormalities (eg, single central maxillary incisor, cleft lip or palate, optic hypoplasia), hypoglycemia, blindness, micropenis, and hyperbilirubinemia.
    • Hypoglycemia can be profound and clinically resembles congenital hyperinsulinism in patients with GHD or, especially, hypopituitarism. Hypoglycemia results from the lack of counterregulatory hormones important for glucose homeostasis; these include GH, corticotropin, and thyroid-stimulating hormone. Although not usually considered a source for hypoglycemia, thyroid hormone may stimulate gluconeogenesis and increase insulin clearance. This mechanism could account for the hyperinsulinemic hypoglycemia observed in a small number of patients with congenital hypothyroidism.
    • The combination of microcephalus, cryptorchidism, and hypoplasia of the scrotum can occur with coexistent GHD and gonadotropin deficiencies. Testosterone bioactivity plays an essential role in the differentiation and development of the male genitalia. During the first trimester, GH modulates fetal testosterone production, perhaps by regulating placental chorionic gonadotropins. During the second and third trimesters, testosterone production appears to be independent of GH and relies on fetal pituitary gonadotropins.
    • Liver disease has been associated with neonatal hypopituitarism. Hypothyroidism is a well-recognized cause of neonatal jaundice, typically an indirect hyperbilirubinemia. The current theory regarding conjugated hyperbilirubinemia is based on the relationship of GH to bile acid synthesis. GH stimulates the synthesis of bile acids, which are major determinants for the induction of canalicular bile secretion. Cholestasis associated with congenital hypopituitarism resolves with hormonal replacement.
    • Neonatal hypoglycemia, persistent cholestatic jaundice, or hypogonadism in a male patient should immediately suggest the possibility of GHD. Neonatal hypopituitarism is potentially fatal if untreated.
  • Acquired hyposomatotropism
    • Acquired GHD can have multiple sources (see Causes).
    • By the age of 6-12 months, infants with GHD clearly demonstrate an abnormally low growth velocity. Skeletal proportions remain normal, but skeletal age is delayed, often to less than 60% of the infant's chronologic age. Delay in dental eruption may precede this finding. Characteristic facies in patients with GHD result from retarded growth of the facial bones. Closure of the fontanelles is often delayed and results in frontal bossing and hydrocephalus. The nasal bridge may be markedly underdeveloped, and the orbits may be shallow; these alterations result in disproportionate cephalofacial relationships.
    • The weight-to-height ratio tends to be increased, just as the ratio of fat to lean muscle is elevated the absence of the effect of GH on the peripheral tissues. Decreased development of lean muscle results in poor muscular tone during infancy and early childhood; this sometimes leads to gross motor delays. Hair growth is sparse, and nails are thin and grow slowly. Laryngeal hypoplasia results in continuation of the prepubescent voice in boys with GHD.
    • Puberty may be delayed by 3-7 years despite normal gonadotropin release. This is likely related to the delay in skeletal age. For reasons that remain incompletely understood, skeletal development must be of a certain age (at least 9 y for girls and 10 y for boys) for puberty to ensue. Despite this delay, sexual function and fertility are normal in people with GHD. Although micropenis may occur during infancy in the congenital form of GHD, the penis is normal for the person's body size during adulthood.

Physical

Findings in patients with congenital or acquired hyposomatotropism are summarized below.

  • Congenital hyposomatotropism
    • Normal length at birth
    • Midline defects
    • Cleft lip
    • Cleft palate
    • Blindness
    • Single central maxillary incisor
    • Hypogonadotropic hypogonadism
    • Jaundice
    • Icterus
    • Hepatosplenomegaly
    • Hypoglycemia
    • Shaking
    • Irritability
    • Lethargy
    • Hypotonia
    • Diaphoresis
    • Tachycardia
    • Pallor
    • Seizures
  • Acquired hyposomatotropism
    • Short stature
    • Characteristic facies
      • Frontal bossing
      • Flattened nasal bridge
      • Forehead prominence
  • Other findings
    • Delayed dental eruption and exfoliation
    • Delayed bone age
    • Increased weight-to-height ratio
    • Poor muscle tone (motor delay may result)
    • Laryngeal hypoplasia
    • Poor hair and nail growth
    • Delayed puberty
    • Normal genitalia
    • Normal skeletal proportions

Causes

  • Hypothalamic regulatory peptides: Decreased or abnormal production of any of the regulatory peptides discussed above, or their respective receptors, may result in GHD.
  • Genetic abnormalities of GH production
    • A great deal has been learned about the genetic causes of hypopituitarism. By 1979, many families with isolated GHD or diminished production of GH and one or more additional pituitary hormones had been described. The development of a complementary DNA probe for the pit-hGH gene permitted scientists to recognize GH gene deletions in 1981 and placental GH and chorionic somatotropin gene deletions in 1982. The power of polymerase chain reaction (PCR) amplification and DNA sequencing subsequently revealed mutations and small deletions affecting GH in other families with isolated GHD.
    • The path to understanding the mechanisms that underlie multiple pituitary hormone deficiency was less straightforward than that regarding single genetic defects. Solutions emerged with the discovery of transcriptional activation factors that direct embryonic development of the anterior pituitary. This story began with the discovery in 1988 of a homeobox protein, called Pit-1, that binds to sequences in the promoter for the GH gene. The story continued with the recognition of many other pituitary and hypothalamic factors that orchestrated pituitary development; 3 main transcriptional factors have been implicated as causes of multiple pituitary hormone deficiency in humans. In chronologic order of their association with human disease, they are Pit-1, PROP1, and HESX1.
    • The PIT1 gene, located on chromosome 3, is a member of a large family of transcription factor genes responsible for the development and function of somatotrophs and of other neuroendocrine cells of the adenohypophysis. At least 7 point mutations of the PIT1 gene have been associated with hypopituitarism in Dutch, American, Japanese, and Tunisian families.
    • In 1992, Tatsumi et al described the first human example of pituitary hormone deficiency due to a PIT1 mutation.2 Two sisters born to parents who were second cousins had profound neonatal hypothyroidism without elevated levels of thyroid-stimulating hormone. One died from aspiration pneumonia at the age of 2 months. The surviving sister also had deficiencies of GH and prolactin. Multiple recessive and dominant types of PIT1 mutations have been recognized over the years. Sporadic cases have also been reported.
    • The first examples of PROP1 mutations in humans with pituitary hormone deficiencies were reported in early 1998. In humans, the hormonal phenotype involves deficiencies of luteinizing hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone, and GH. Mutations recognized to date involve the paired-like DNA-binding domain encoded by exons 2 and 3 and demonstrate autosomal recessive inheritance.
    • The HESX1 gene plays an important role in the development of the optic nerves and the anterior pituitary gland. The human gene is located on chromosome 3p21.2. Dattani et al identified the first human patients with a mutation in HESX1 after 135 patients with pituitary disorders were screened.3
  • Developmental malformations: Developmental malformations commonly associated with GHD include anencephaly, holoprosencephaly, and septooptic dysplasia (de Morsier syndrome). Septooptic dysplasia, in its complete form, combines hypothalamic insufficiency with hypoplasia (or absence) of the optic chiasm, optic nerves, septum pellucidum, and corpus callosum. Consider this diagnosis in any child with growth failure and impaired vision, especially in one with accompanying nystagmus. HESX1 mutations have been associated with septooptic dysplasia.
  • Trauma, infections, tumors, and cranial irradiation
    • Trauma, infections, sarcoidosis, tumors, and cranial irradiation of the hypothalamus, pituitary stalk, or anterior pituitary may also result in isolated GHD or anterior hypopituitarism.
    • GHD is most commonly associated with breech delivery, prolonged labor, placental abruption, and other complicated deliveries.
    • Hypothalamic tumors or pituitary tumors (eg, craniopharyngioma, glioma) are major causes of hypothalamic-pituitary insufficiency.
    • In rare cases, metastasis from extracranial carcinomas (eg, histiocytosis, germ cell tumor) lead to hypopituitarism.
    • Craniopharyngiomas and histiocytosis X are major etiologies of pituitary insufficiency. Craniopharyngiomas arise from remnants of the Rathke pouch, which is a diverticulum arising from the roof of the embryologic oral cavity and which gives rise to the anterior pituitary.
    • Most patients present in mid childhood with symptoms of increased intracranial pressure, such as headaches, vomiting, visual field deficits, and oculomotor abnormalities. Short stature often coexists, but this is usually not the first complaint. Most children with craniopharyngiomas have growth failure at the time of presentation. Because of this association, any child in whom GHD is diagnosed should undergo MRI to exclude a brain tumor before the start of GH therapy.
    • Irradiation-induced hypothalamic-pituitary dysfunction is dose related. Low-dose irradiation usually results in isolated GHD, whereas high doses most often result in multiple hormonal deficiencies. One study group reported that 2-5 years after irradiation, 100% of children receiving doses of at least 3000 cGy to the hypothalamic-pituitary axis over 3 weeks had subnormal GH responses to provocative testing. Hypothalamic irradiation also damages the growth plate cartilage and is associated with an increased incidence of precocious puberty (advanced bone age and premature epiphyseal fusion); both of these processes compound the effect on linear growth.
  • Developmental abnormalities of the pituitary: Congenital absence or hypoplasia of the pituitary has also been identified. Common findings on MRI include an ectopic neurohypophysis, an absent infundibulum, a small adenohypophysis, and absence of the usual high signal intensity (bright spot) in the posterior pituitary as seen on T1-weighted MRIs.

More on Hyposomatotropism

Overview: Hyposomatotropism
Differential Diagnoses & Workup: Hyposomatotropism
Treatment & Medication: Hyposomatotropism
Follow-up: Hyposomatotropism
Multimedia: Hyposomatotropism
References
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Further Reading

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Keywords

deficient secretion of pituitary growth hormone, deficient secretion of pituitary somatotropin, growth hormone, GH, human growth hormone, hGH, somatotropin, human pituitary growth hormone, human pituitary-derived growth hormone, pit-hGH, growth hormone deficiency in children, growth hormone deficiency, GHD in children, GHD, GH deficiency in children, GH deficiency, growth hormone inadequacy in children, growth hormone inadequacy

recombinant human growth hormone, rhGH, growth hormone-releasing hormone, GHRH, somatotropin-releasing factor, SRF, somatomedin deficiency , pituitary adenylate cyclase activating polypeptide, PACAP, pituitary-specific transcription factor-1, Pit-1, prophet of Pit-1, PROP1, HESX1, insulinlike growth factor, IGF, insulinlike growth factor-1, IGF-1, IGF deficiency, insulinlike growth factor deficiency, insulinlike growth factor binding protein, IGFBP, thyroid-stimulating hormone, thyroid hormone, sex steroids, treatment, diagnosis

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Contributor Information and Disclosures

Author

Robert J Ferry Jr, MD, Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis, and St Jude Children's Research Hospital; Field Surgeon (Medical Corps), 162nd Area Support Medical Company, Army National Guard
Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society
Disclosure: Nutropin Speakers Bureau Honoraria Speaking and teaching; Genotropin Speakers Bureau Honoraria Speaking and teaching; Eli Lilly & Co. Grant/research funds Independent contractor; MacroGenics, Inc. Grant/research funds Independent contractor; Ipsen, S.A. (formerly Tercica, Inc.) Grant/research funds Independent contractor

Coauthor(s)

Sherry Franklin, MD, Consulting Staff, Department of Pediatrics, Division of Endocrinology, Pediatric Endocrinology of San Diego Medical Group
Sherry Franklin, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, and Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Phyllis W Speiser, MD, Chief of Pediatric Endocrinology, Schneider Children's Hospital; Professor of Pediatrics, New York University School of Medicine
Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London), Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece
George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

 
 
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