eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Hyposomatotropism: Differential Diagnoses & Workup

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

Differential Diagnoses

Child Abuse & Neglect: Failure to Thrive
Hypothyroidism
Child Abuse & Neglect: Psychosocial Dwarfism
Malnutrition
Constitutional Growth Delay
Rickets
Growth Hormone Deficiency
Skeletal Dysplasia
Hypopituitarism

Other Problems to Be Considered

  • Primary growth disorders
    • Osteochondrodysplasias - Group of disorders characterized by intrinsic abnormalities of cartilage and/or bone
    • Chromosomal abnormalities - Aberrations of autosomes and sex chromosomes
    • Intrauterine growth retardation - Infections, syndromes, placental abnormalities, and maternal disorders
    • Genetic short stature
    • Constitutional delay of growth and maturation
  • Secondary growth disorders
    • Chronic diseases - GI, renal, cardiovascular, and autoimmune
    • Endocrine disorders - Hypothyroidism, Cushing syndrome, pseudohypoparathyroidism, growth hormone (GH) insensitivity, and insulinlike growth factor (IGF) deficiency
    • Rickets

Workup

Laboratory Studies

The diagnosis of growth hormone (GH) deficiency (GHD), or hyposomatotropism, remains controversial. The Growth Hormone Research Society convened an international workshop of acknowledged authorities to address this issue.4 The diagnosis of GHD is a multifaceted process requiring comprehensive clinical and auxologic assessment combined with biochemical testing of the GH-insulinlike growth factor (IGF) axis and radiologic evaluation. Biochemical testing of the GH-IGF axis includes radioimmunoassays (RIAs) of GH, IGF, and insulinlike growth factor binding proteins (IGFBPs).

RIA for GH

Many RIAs are available to measure GH levels, and all offer limited accuracy. Repeated measurements may vary by as much as 3-fold, even when the tests are conducted in laboratories with personnel experienced in the procedures. This variation is observed because several molecular forms of GH are identified in the serum and because polyclonal (instead of monoclonal) antibodies are used. To improve standardization, use of a 22-kDa recombinant human growth hormone (rhGH) GH-reference preparation with an assigned potency of 3 IU/mg has been recommended. When assay data are reported, a clear statement of the method should be included. Today, the optimal assay measures the 22-kDa hGH species by using a monoclonal antibody.

Serum GH concentrations remain constitutively elevated from the newborn period to as late as 6 months of age. Therefore, a serum GH level of less than 20 ng/mL in infants younger than 6 months suggests GHD. However, a random hGH level is not diagnostic in patients older than 6 months because hGH is intermittently secreted in brief nocturnal pulses (of 10-15 minutes during deep sleep) beyond early infancy. GHD cannot be diagnosed on the basis of a single random serum GH concentration at any age.

RIA for IGF

Specific RIAs distinguish IGF-1 and IGF-2. Serum IGF-1 concentrations are depend on GH and vary with the patient's age, nutritional status, and sexual maturation. In children younger than 8 years, serum IGF-1 levels may be indistinguishable from levels measured in children with GHD. Concentrations of serum IGF-2 vary less than IGF-1 levels do at a given age; however, serum IGF-2 is less GH dependent than IGF-1.

Rosenfeld and colleagues evaluated the effectiveness of using IGF-1 and IGF-2 RIAs to identify children with GHD.5 When performed alone, assays for both produced false-positive and false-negative results. However, combined assays helped in correctly identifying 96% of children with GHD. Only 0.5% of healthy children had serum concentrations of both IGF-1 and IGF-2 that were below the reference ranges for their age and sex.

Total serum IGF-1 levels represent the combined quantity of unbound IGF-1 (free IGF-1) plus IGF-1 bound to IGFBP-3. Free IGF-1 is postulated to be the bioactive fraction, but it accounts for only a small fraction of the total amount.

Hasegawa and colleagues developed an immunoradiometric assay for free IGF-1 in plasma and reported the relationship of free IGF-1 to GH-secretory status.6 Low serum levels of free IGF-1 assayed by using this method were highly correlated highly complete GHD but not partial GHD. Despite their reduced diagnostic usefulness in patients with partial GHD, free IGF-1 levels may prove useful for assessing compliance with or the effectiveness of rhGH therapy.

RIA for IGFBPs

To diagnose GHD, assaying the serum IGFBP-3 concentration may be superior to measuring the free IGF-1 concentration for at least 2 reasons. First, IGFBP-3 levels vary less with nutritional status than free IGF-1 values do. Second, serum IGFBP-3 levels, even in young children, are typically more than 500 mg/mL; therefore, the detection of low levels is feasible.

Imaging Studies

Radiography

Radiography to assess skeletal maturation, similar to an examination of growth and development, is a useful diagnostic tool to determine a patient's GH secretory status. Anteroposterior radiographs of the left hand and wrist (knee or ankle in children <1 y) are used to evaluate the progress of epiphyseal ossification by comparing the results to age-matched and sex-matched reference ranges.

Crude estimates of skeletal maturation can also be obtained by assessing dental eruption. Primary teeth begin to erupt at approximately 6 months of age, and exfoliation starts at 6-12 years.

Height predictions rely on the observation that the greater the delay in bone age relative to chronologic age, the longer the time before epiphyseal fusion occurs and, thus, final height is achieved. The method of height prediction is based on formulas Bayley and Pinneau developed using information from Greulich and Pyle's classic radiographic atlas.7 Tanner and colleagues and Roche and colleagues subsequently refined these predictions by linking skeletal maturation to a rating of sexual maturity.8,9

Each system is useful for estimating the range of a patient's likely adult height to within 2 inches above or below the predicted value. A major limitation of current methods for predicting height is that the standards Greulich and Pyle established are based on calculations from a few Caucasian children who lived in 2 affluent suburbs in the United States during the 1940s. Normal skeletal maturation varies with ethnicity and is likely to vary with socioeconomic status. Moreover, most industrialized countries are home to a heterogeneous population. A modern reappraisal of these radiographic standards is overdue.

MRI

A lateral skull image may provide evidence of enlargement or distortion of the sella turcica, as well as suprasellar calcification, which indicates a craniopharyngioma. As a result of the high false-negative rate of skull findings with plain radiography, MRI is the procedure of choice to exclude intracranial masses or developmental abnormalities arising from pituitary anlagen. Before rhGH therapy is started, patients with GHD should undergo MRI of the brain to exclude the possibility of an organic lesion.

Contemporary MRI techniques can be overly sensitive, with MRIs depicting clinically insignificant signal intensity in the hypothalamus or pituitary gland. Most of these lesions require only clinical evaluation (eg, ophthalmologic examination, growth surveillance). A thickened pituitary stalk or asymmetric elevation of the pituitary contour warrants further evaluation.

Other Tests

Regarding clinical and auxologic assessment, history taking and physical examination are the most useful diagnostic tools because the diagnosis of GHD rests on clinical judgment. The foundation for the diagnosis of GHD is careful, serial documentation of the patient's height and a determination of height velocity.

In the absence of other evidence of pit-hGH secretory dysfunction, testing for GH secretion is typically unnecessary.

Procedures

Diagnostic Criteria for Hyposomatotropism and Provocative Testing

Random testing of serum GH concentrations is of no use in establishing the diagnosis of GHD. Provocative GH testing is not the current criteria standard. Current diagnostic criteria include the following:

  • Growth-velocity Z score below -2, evidence of certain genetic mutations (eg, GH1 deletion; IGF1 deletion; mutations involving SHOX, PIT1, PROP1, Turner syndrome, and Prader-Willi syndrome)
  • Predicted adult height (Bayley-Pinneau value more than 1.5 standard deviations below the calculated midparental target height)
  • Serum-free or total IGF-1 Z score below -2 (ie, more than 2 standard deviations below the mean for the patient's age, sex, and Tanner stage)

Provocative GH testing is criticized for several reasons, including the following:

  • None of the tests reproduces the physiologic secretory pattern of GH because they involve the use of pharmacologic stimuli to indirectly assess physiologic GH production.
  • Individual clinicians assign what are essentially arbitrary definitions for subnormal responses (ie, cutoffs for peak serum GH values) to provocation.
  • The reproducibility of provocative tests and GH RIAs is limited. Many pediatric endocrinologists apply other clinical criteria (eg, growth velocity Z score below -2) and do not perform provocative GH tests to diagnose GHD.

Despite limitations, provocative GH tests remain helpful ways to measure GH reserve. Pediatric endocrinologists use physiologic stimuli (eg, strenuous exercise, fasting, deep sleep) and pharmacologic stimuli (eg, clonidine, levodopa-propranolol, glucagon, arginine, insulin) to provoke GH secretion. In euthyroid children, all of the tests must be performed after overnight fasting.

To improve diagnostic sensitivity and specificity, at least 2 provocative tests are performed. Immediately before and during the earliest phases of puberty, GH production is often indistinguishable in unaffected children and in children with GHD. Serum GH concentrations typically rise during puberty. Many investigators suggest that children approaching puberty should be given gonadal steroids to prime the growth hormone-releasing hormone (GHRH)-GH axis before testing.

Specific provocative tests are described below.

Insulin tolerance test

Insulin-induced hypoglycemia is the most potent stimulus for GH secretion and the most dangerous tool for provocative GH testing in patients who may have GH deficiency. Insulin tolerance testing makes advantage of the hormonal counterregulatory response to hypoglycemia. In patients without GHD, plasma concentrations of glucagon, epinephrine, norepinephrine, cortisol, corticotropin, and GH are elevated in response to acute hypoglycemia.

To perform the test, patients fast for 8 hours. Then, lispro insulin 0.1 U/kg of body weight is administered rapidly as an intravenous bolus. Serial blood samples are subsequently obtained to measure GH, cortisol, and glucose concentrations at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 75 minutes, 90 minutes, and 120 minutes. With each sample, the blood glucose level is simultaneously determined by using a bedside glucometer to document an appropriate reduction and to ensure safety. Performance of the test is considered adequate when the blood glucose level decreases below 50% of its baseline value.

Adverse effects expected during the procedure include symptoms secondary to hypoglycemia, such as lethargy, shaking, confusion, headache, abdominal pain, nausea, vomiting, syncope, and seizure activity. The test must be performed under the watchful eye of the physician who can begin prompt resuscitation with glucose and/or glucagon as soon as the diagnostic samples have been obtained. To date, the insulin tolerance test is the only provocative test associated with fatalities; therefore, personnel must be trained and conduct the test judiciously.

Clonidine stimulation test

Clonidine acts centrally to stimulate alpha-adrenergic receptors, which are involved in regulating GH release. Serum GH levels are obtained at baseline and at 60 minutes and 90 minutes after the oral administration of clonidine 0.1 mg/kg. Clonidine may induce hypotension during the test. Therefore, warn parents that they may experience lethargy and/or depression for 24 hours after clonidine is administered.

Levodopa-propranolol HCl test

Levodopa is a dopamine receptor agonist. Dopamine is involved in the stimulation of GH secretion. In the converse, beta-adrenergic control negatively regulates GH release.

Propranolol is a beta-blocker used to hinder inhibitory input affecting GH release while levodopa simultaneously stimulates GH release by means of the dopaminergic pathway. Propranolol 0.75-1 mg/kg is orally administered before levodopa. The dosage of levodopa for levodopa-propranolol HCl testing varies with weight so that children weighing less than 15 kg receive 125 mg, children weighing 10-30 kg receive 250 mg, and children weighing less than 30 kg receive 500 mg.

Blood samples for GH testing are drawn at 0 minutes, 60 minutes, and 90 minutes after the administration of levodopa. Adverse effects include nausea and, in rare cases, emesis. In addition, the patient's heart rate may decrease because of the use of propranolol. Closely monitor his or her vital signs, and ensure that appropriate resuscitative measures are available.

Arginine HCl test

Arginine appears to exert a direct depolarizing action on somatropic neurons, increasing GH secretion. After an overnight fast, patients are given 10% arginine HCl in 0.9% NaCl 0.5 g/kg (not to exceed 30 g) as a constant intravenous infusion over 30 minutes. Blood samples for GH testing are obtained at 0 minutes, 15 minutes, 30 minutes, 45 minutes, and 60 minutes after the infusion of arginine is begun. Arginine has historically been used as a primer before insulin is administered during insulin tolerance testing.

Glucagon test

Glucagon increases peripheral glucose concentrations by means of glycogenolysis and gluconeogenesis. Because glucagon is rapidly metabolized, an abrupt reduction in serum glucose concentration ensues and triggers the release of counterregulatory hormones.

After fasting overnight, patients receive an intramuscular injection of glucagon 0.03 mg/kg (not to exceed 1 mg). Some clinicians advocate the concomitant use of propranolol to inhibit the catecholaminergic response to hypoglycemia. Serum GH concentrations are determined at 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, and 180 minutes after glucagon administration. Nausea and, occasionally, emesis may occur.

Expected Results

Most clinicians use a peak serum GH concentration of more than 10 ng/mL (30 IU) to exclude GHD in children.

New Models for Diagnosis

Basal, oscillating, and pulsatile GH inputs and the wide range of intrasubject and intersubject variance in GH pharmacokinetics negate the assumption of a uniform relationship between GH secretion and serum GH concentration. Because of this, peak GH concentration is an oversimplified outcome of GH testing. Bright and colleagues postulated that serum GH concentrations reflect multiple components of GH input and that a composite pharmacokinetic model that accounts for pulsatile (infused), basal, and oscillatory components is required to accurately estimate each individual's pharmacokinetic parameters.10 Ongoing research may aid in applying these complex mathematic models to daily practice.

More on Hyposomatotropism

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

  1. [Best Evidence] Marconi AM, Ronzoni S, Bozzetti P, Vailati S, Morabito A, Battaglia FC. Comparison of fetal and neonatal growth curves in detecting growth restriction. Obstet Gynecol. Dec 2008;112(6):1227-34. [Medline].

  2. Tatsumi K, Miyai K, Notomi T, Kaibe K, Amino N, Mizuno Y. Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene. Nat Genet. Apr 1992;1(1):56-8. [Medline].

  3. Dattani MT, Martinez-Barbera JP, Thomas PQ, Brickman JM, Gupta R, Martensson IL. Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat Genet. Jun 1998;19(2):125-33. [Medline].

  4. [Guideline] Clayton PE, Cohen P, Tanaka T, Hintz RL, Laron Z, Sizonenko PC. Diagnosis of growth hormone deficiency in childhood. On behalf of the Growth Hormone Research Society. Horm Res. 2000;53 Suppl 3:30. [Medline].

  5. Rosenfeld RG, Wilson DM, Lee PD, Hintz RL. Insulin-like growth factors I and II in evaluation of growth retardation. J Pediatr. Sep 1986;109(3):428-33. [Medline].

  6. Hasegawa Y, Hasegawa T, Takada M, Tsuchiya Y. Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents. Eur J Endocrinol. Feb 1996;134(2):184-9. [Medline].

  7. Bayley N, Pinneau SR. Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards. J Pediatr. Apr 1952;40(4):423-41. [Medline].

  8. Tanner JM, Whitehouse RH, Marshall WA, Carter BS. Prediction of adult height from height, bone age, and occurrence of menarche, at ages 4 to 16 with allowance for midparent height. Arch Dis Child. Jan 1975;50(1):14-26. [Medline].

  9. Roche AF, Davila GH, Eyman SL. A comparison between Greulich-Pyle and Tanner-Whitehouse assessments of skeletal maturity. Radiology. Feb 1971;98(2):273-80. [Medline].

  10. Bright GM, Veldhuis JD, Iranmanesh A, Baumann G, Maheshwari H, Lima J. Appraisal of growth hormone (GH) secretion: evaluation of a composite pharmacokinetic model that discriminates multiple components of GH input. J Clin Endocrinol Metab. Sep 1999;84(9):3301-8. [Medline].

  11. Jeschke MG, Barrow RE, Herndon DN. Recombinant human growth hormone treatment in pediatric burn patients and its role during the hepatic acute phase response. Crit Care Med. May 2000;28(5):1578-84. [Medline].

  12. Watanabe S, Mizuno S, Oshima LH, Tsunematsu Y, Fujimoto J, Komiyama A. Leukemia and other malignancies among GH users. J Pediatr Endocrinol. Jan-Mar 1993;6(1):99-108. [Medline].

  13. Abrahams JJ, Trefelner E, Boulware SD. Idiopathic growth hormone deficiency: MR findings in 35 patients. AJNR Am J Neuroradiol. Jan-Feb 1991;12(1):155-60. [Medline].

  14. Albertsson-Wikland K, Lannering B, Marky I, Mellander L, Wannholt U. A longitudinal study on growth and spontaneous growth hormone (GH) secretion in children with irradiated brain tumors. Acta Paediatr Scand. Nov 1987;76(6):966-73. [Medline].

  15. Amit T, Hertz P, Ish-Shalom S, Lotan R, Luboshitzki R, Youdim MB. Effects of hypo or hyper-thyroidism on growth hormone-binding protein. Clin Endocrinol (Oxf). Aug 1991;35(2):159-62. [Medline].

  16. Asa SL, Kovacs K. Functional morphology of the human fetal pituitary. Pathol Annu. 1984;19 Pt 1:275-315. [Medline].

  17. August GP, Lippe BM, Blethen SL, Rosenfeld RG, Seelig SA, Johanson AJ. Growth hormone treatment in the United States: demographic and diagnostic features of 2331 children. J Pediatr. Jun 1990;116(6):899-903. [Medline].

  18. Barinaga M, Yamonoto G, Rivier C, Vale W, Evans R, Rosenfeld MG. Transcriptional regulation of growth hormone gene expression by growth hormone-releasing factor. Nature. Nov 3-9 1983;306(5938):84-5. [Medline].

  19. Bartsocas CS, Pantelakis SN. Human growth hormone therapy in hypopituitarism due to tuberculous meningitis. Acta Paediatr Scand. May 1973;62(3):304-6. [Medline].

  20. Baxter RC. Characterization of the acid-labile subunit of the growth hormone-dependent insulin-like growth factor binding protein complex. J Clin Endocrinol Metab. Aug 1988;67(2):265-72. [Medline].

  21. Baxter RC, Martin JL. Radioimmunoassay of growth hormone-dependent insulinlike growth factor binding protein in human plasma. J Clin Invest. Dec 1986;78(6):1504-12. [Medline].

  22. Beher WT, Beher ME, Semenuk G. The effect of pituitary and thyroid hormones on bile acid metabolism in the rat. Metabolism. Feb 1966;15(2):181-8. [Medline].

  23. Blethen SL. Complications of growth hormone therapy in children. Curr Opin Pediatr. Aug 1995;7(4):466-71. [Medline].

  24. Blum WF, Ranke MB, Kietzmann K, Gauggel E, Zeisel HJ, Bierich JR. A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency. J Clin Endocrinol Metab. May 1990;70(5):1292-8. [Medline].

  25. Brauner R, Rappaport R, Prevot C, Czernichow P, Zucker JM, Bataini P. A prospective study of the development of growth hormone deficiency in children given cranial irradiation, and its relation to statural growth. J Clin Endocrinol Metab. Feb 1989;68(2):346-51. [Medline].

  26. Braunstein GD, Kohler PO. Pituitary function in Hand-Schüller-Christian disease. Evidence for deficient growth-hormone release in patients with short stature. N Engl J Med. Jun 8 1972;286(23):1225-9. [Medline].

  27. Buckler JM. Plasma growth hormone response to exercise as diagnostic aid. Arch Dis Child. Jul 1973;48(7):565-7. [Medline].

  28. Burman P, Johansson AG, Siegbahn A, Vessby B, Karlsson FA. Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J Clin Endocrinol Metab. Feb 1997;82(2):550-5. [Medline].

  29. Clark PA, Rogol AD. Growth hormones and sex steroid interactions at puberty. Endocrinol Metab Clin North Am. Sep 1996;25(3):665-81. [Medline].

  30. Cogan JD, Phillips JA 3rd, Sakati N, Frisch H, Schober E, Milner RD. Heterogeneous growth hormone (GH) gene mutations in familial GH deficiency. J Clin Endocrinol Metab. May 1993;76(5):1224-8. [Medline].

  31. Cohen P, Franklin SL, Rogol AD. What is the optimal dose of growth hormone?. Highlights. 2000;8:4-5.

  32. Collu R, Leboeuf G, Letarte J, Ducharme JR. Stimulation of growth hormone secretion by levodopa-propranolol in children and adolescents. Pediatrics. Aug 1975;56(2):262-6. [Medline].

  33. Copeland KC, Franks RC, Ramamurthy R. Neonatal hyperbilirubinemia and hypoglycemia in congenital hypopituitarism. Clin Pediatr (Phila). Aug 1981;20(8):523-6. [Medline].

  34. Costin G. Endocrine disorders associated with tumors of the pituitary and hypothalamus. Pediatr Clin North Am. Feb 1979;26(1):15-31. [Medline].

  35. Craft WH, Underwoood LE, Van Wyk JJ. High incidence of perinatal insult in children with idiopathic hypopituitarism. J Pediatr. Mar 1980;96(3 Pt 1):397-402. [Medline].

  36. Cutfield WS, Wilton P, Bennmarker H, Albertsson-Wikland K, Chatelain P, Ranke MB. Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment. Lancet. Feb 19 2000;355(9204):610-3. [Medline].

  37. Duck SC, Rapaport R. Long-term treatment with GHRH [1-44] amide in prepubertal children with classical growth hormone deficiency. J Pediatr Endocrinol Metab. Jul-Aug 1999;12(4):531-6. [Medline].

  38. Eddy RL, Gilliland PF, Ibarra JD Jr, McMurry JF Jr, Thompson JQ. Human growth hormone release. Comparison of provocative test procedures. Am J Med. Feb 1974;56(2):179-85. [Medline].

  39. Elgin RG, Busby WH Jr, Clemmons DR. An insulin-like growth factor (IGF) binding protein enhances the biologic response to IGF-I. Proc Natl Acad Sci U S A. May 1987;84(10):3254-8. [Medline].

  40. Esch FS, Böhlen P, Ling NC, Brazeau PE, Wehrenberg WB, Guillemin R. Primary structures of three human pancreas peptides with growth hormone-releasing activity. J Biol Chem. Feb 10 1983;258(3):1806-12. [Medline].

  41. Federico G, Street ME, Maghnie M, et al. Assessment of serum IGF-I concentrations in the diagnosis of isolated childhood-onset GH deficiency: a proposal of the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP/ISPED). J Endocrinol Invest. Sep 2006;29(8):732-7. [Medline].

  42. Fish HR, Chernow B, O'Brian JT. Endocrine and neurophysiologic responses of the pituitary to insulin-induced hypoglycemia: a review. Metabolism. Aug 1986;35(8):763-80. [Medline].

  43. Fradkin JE, Schonberger LB, Mills JL, Gunn WJ, Piper JM, Wysowski DK. Creutzfeldt-Jakob disease in pituitary growth hormone recipients in the United States. JAMA. Feb 20 1991;265(7):880-4. [Medline].

  44. Frasier SD. Human pituitary growth hormone (hGH) therapy in growth hormone deficiency. Endocr Rev. 1983;4(2):155-70. [Medline].

  45. Furlanetto RW, Underwood LE, Van Wyk JJ, D'Ercole AJ. Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay. J Clin Invest. Sep 1977;60(3):648-57. [Medline].

  46. Gargosky SE, Pham HM, Wilson KF, Liu F, Giudice LC, Rosenfeld RG. Measurement and characterization of insulin-like growth factor binding protein-3 in human biological fluids: discrepancies between radioimmunoassay and ligand blotting. Endocrinology. Dec 1992;131(6):3051-60. [Medline].

  47. Gerich JE, Lorenzi M, Bier DM, Tsalikian E, Schneider V, Karam JH. Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin. J Clin Invest. Apr 1976;57(4):875-84. [Medline].

  48. Goth MI, Lyons CE, Canny BJ, Thorner MO. Pituitary adenylate cyclase activating polypeptide, growth hormone (GH)-releasing peptide and GH-releasing hormone stimulate GH release through distinct pituitary receptors. Endocrinology. Feb 1992;130(2):939-44. [Medline].

  49. Green H, Morikawa M, Nixon T. A dual effector theory of growth-hormone action. Differentiation. 1985;29(3):195-8. [Medline].

  50. Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist. 2nd ed. Stanford, Calif: Stanford Univ Press; 1959.

  51. Grumbach MM, Bin-Abbas BS, Kaplan SL. The growth hormone cascade: progress and long-term results of growth hormone treatment in growth hormone deficiency. Horm Res. 1998;49 Suppl 2:41-57. [Medline].

  52. Herman SP, Baggenstoss AH, Cloutier MD. Liver dysfunction and histologic abnormalities in neonatal hypopituitarism. J Pediatr. Dec 1975;87(6 Pt 1):892-5. [Medline].

  53. Heuschkel R, Salvestrini C, Beattie RM, Hildebrand H, Walters T, Griffiths A. Guidelines for the management of growth failure in childhood inflammatory bowel disease. Inflamm Bowel Dis. Jun 2008;14(6):839-49. [Medline].

  54. Hintz RL. Eternal vigilance--mortality in children with growth hormone deficiency. J Clin Endocrinol Metab. May 1996;81(5):1691-2. [Medline].

  55. Hjalmarson A, Isaksson O, Ahren K. Effects of growth hormone and insulin on amino acid transport in perfused rat heart. Am J Physiol. Dec 1969;217(6):1795-802. [Medline].

  56. [Guideline] Ho KK. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol. Dec 2007;157(6):695-700. [Medline].

  57. Holl RW, Thorner MO, Leong DA. Intracellular calcium concentration and growth hormone secretion in individual somatotropes: effects of growth hormone-releasing factor and somatostatin. Endocrinology. Jun 1988;122(6):2927-32. [Medline].

  58. Ikeda H, Suzuki J, Sasano N, Niizuma H. The development and morphogenesis of the human pituitary gland. Anat Embryol (Berl). 1988;178(4):327-36. [Medline].

  59. Izenberg N, Rosenblum M, Parks JS. The endocrine spectrum of septo-optic dysplasia. Clin Pediatr (Phila). Nov 1984;23(11):632-6. [Medline].

  60. Jansson C, Boguszewski C, Rosberg S, Carlsson L, Albertsson-Wikland K. Growth hormone (GH) assays: influence of standard preparations, GH isoforms, assay characteristics, and GH-binding protein. Clin Chem. Jun 1997;43(6 Pt 1):950-6. [Medline].

  61. Johannsson G, Bengtsson BA. Growth hormone and the acquisition of bone mass. Horm Res. 1997;48 Suppl 5:72-7. [Medline].

  62. Jorgensen JO, Moller N, Lauritzen T, Alberti KG, Orskov H, Christiansen JS. Evening versus morning injections of growth hormone (GH) in GH-deficient patients: effects on 24-hour patterns of circulating hormones and metabolites. J Clin Endocrinol Metab. Jan 1990;70(1):207-14. [Medline].

  63. Juul A. Determination of insulin-like growth factor-I in the monitoring of growth hormone treatment with respect to efficacy of treatment and side effects: should potential risks of cardiovascular disease and cancer be considered?. Horm Res. 1999;51 Suppl 3:141-8. [Medline].

  64. Juul A, Jorgensen JO, Christiansen JS, Muller J, Skakkeboek NE. Metabolic effects of GH: a rationale for continued GH treatment of GH-deficient adults after cessation of linear growth. Horm Res. 1995;44 Suppl 3:64-72. [Medline].

  65. Kaplan SL, Abrams CA, Bell JJ, Conte FA, Grumbach MM. Growth and growth hormone. I. Changes in serum level of growth hormone following hypoglycemia in 134 children with growth retardation. Pediatr Res. Jan 1968;2(1):43-63. [Medline].

  66. Karlberg J, Engström I, Karlberg P, Fryer JG. Analysis of linear growth using a mathematical model. I. From birth to three years. Acta Paediatr Scand. May 1987;76(3):478-88. [Medline].

  67. Kurtoglu S, Tutus A, Aydin K, Genç E, Caksen H. Persistent neonatal hypoglycemia: an unusual finding of congenital hypothyroidism. J Pediatr Endocrinol Metab. Mar-Apr 1998;11(2):277-9. [Medline].

  68. Lanes R, Hurtado E. Oral clonidine-an effective growth hormone-releasing agent in prepubertal subjects. J Pediatr. May 1982;100(5):710-4. [Medline].

  69. Lee MM. Clinical practice. Idiopathic short stature. N Engl J Med. Jun 15 2006;354(24):2576-82. [Medline].

  70. Lemaigre FP, Peers B, Lafontaine DA, Mathy-Hartert M, Rousseau GG, Belayew A. Pituitary-specific factor binding to the human prolactin, growth hormone, and placental lactogen genes. DNA. Apr 1989;8(3):149-59. [Medline].

  71. Lewis UJ, Singh RN, Tutwiler GF, Sigel MB, VanderLaan EF, VanderLaan WP. Human growth hormone: a complex of proteins. Recent Prog Horm Res. 1980;36:477-508. [Medline].

  72. Li S, Crenshaw EB 3rd, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG. Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature. Oct 11 1990;347(6293):528-33. [Medline].

  73. Lindsay R, Feldkamp M, Harris D, Robertson J, Rallison M. Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr. Jul 1994;125(1):29-35. [Medline].

  74. Lombardi G, Colao A, Ferone D, Marzullo P, Orio F, Longobardi S. Effect of growth hormone on cardiac function. Horm Res. 1997;48 Suppl 4:38-42. [Medline].

  75. Lopez-Bermejo A, Buckway CK, Rosenfeld RG. Genetic defects of the growth hormone-insulin-like growth factor axis. Trends Endocrinol Metab. Mar 2000;11(2):39-49. [Medline].

  76. MacGillivray MH, Baptista J, Johanson A. Outcome of a four-year randomized study of daily versus three times weekly somatropin treatment in prepubertal naive growth hormone-deficient children. Genentech Study Group. J Clin Endocrinol Metab. May 1996;81(5):1806-9. [Medline].

  77. Mahan JD, Warady BA. Assessment and treatment of short stature in pediatric patients with chronic kidney disease: a consensus statement. Pediatr Nephrol. Jul 2006;21(7):917-30. [Medline].

  78. Malozowski S, Stadel BV. Prepubertal gynecomastia during growth hormone therapy. J Pediatr. Apr 1995;126(4):659-61. [Medline].

  79. Mangalam HJ, Albert VR, Ingraham HA, Kapiloff M, Wilson L, Nelson C. A pituitary POU domain protein, Pit-1, activates both growth hormone and prolactin promoters transcriptionally. Genes Dev. Jul 1989;3(7):946-58. [Medline].

  80. Martin JL, Baxter RC. Insulin-like growth factor-binding protein from human plasma. Purification and characterization. J Biol Chem. Jul 5 1986;261(19):8754-60. [Medline].

  81. Mauras N, Attie KM, Reiter EO, Saenger P, Baptista J. High dose recombinant human growth hormone (GH) treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial. Genentech, Inc., Cooperative Study Group. J Clin Endocrinol Metab. Oct 2000;85(10):3653-60. [Medline].

  82. Melander T, Hokfelt T, Rokaeus A. Distribution of galaninlike immunoreactivity in the rat central nervous system. J Comp Neurol. Jun 22 1986;248(4):475-517. [Medline].

  83. Mericq MV, Eggers M, Avila A, Cutler GB Jr, Cassorla F. Near final height in pubertal growth hormone (GH)-deficient patients treated with GH alone or in combination with luteinizing hormone-releasing hormone analog: results of a prospective, randomized trial. J Clin Endocrinol Metab. Feb 2000;85(2):569-73. [Medline].

  84. Merimee TJ, Rabinowtitz D, Fineberg SE. Arginine-initiated release of human growth hormone. Factors modifying the response in normal man. N Engl J Med. Jun 26 1969;280(26):1434-8. [Medline].

  85. Miell JP, Taylor AM, Zini M, Maheshwari HG, Ross RJ, Valcavi R. Effects of hypothyroidism and hyperthyroidism on insulin-like growth factors (IGFs) and growth hormone- and IGF-binding proteins. J Clin Endocrinol Metab. Apr 1993;76(4):950-5. [Medline].

  86. Miller WL, Kaplan SL, Grumbach MM. Child abuse as a cause of post-traumatic hypopituitarism. N Engl J Med. Mar 27 1980;302(13):724-8. [Medline].

  87. Milstein SJ, Leipold H, Sarubbi D, Leone-Bay A, Mlynek GM, Robinson JR. Partially unfolded proteins efficiently penetrate cell membranes--implications for oral drug delivery. J Control Release. Apr 30 1998;53(1-3):259-67. [Medline].

  88. Mitchell ML, Byrne MJ, Sanchez Y, Sawin CT. Detecon of growth-hormone deficiency. N Engl J Med. Mar 5 1970;282(10):539-41. [Medline].

  89. Moore DC, Ruvalcaba RH, Smith EK, Kelley VC. Plasma somatomedin-C as a screening test for growth hormone deficiency in children and adolescents. Horm Res. 1982;16(1):49-55. [Medline].

  90. Møller J, Nielsen S, Hansen TK. Growth hormone and fluid retention. Horm Res. 1999;51 Suppl 3:116-20. [Medline].

  91. Nishi Y, Tanaka T, Takano K, Fujieda K, Igarashi Y, Hanew K. Recent status in the occurrence of leukemia in growth hormone-treated patients in Japan. GH Treatment Study Committee of the Foundation for Growth Science, Japan. J Clin Endocrinol Metab. Jun 1999;84(6):1961-5. [Medline].

  92. Parks JS. Molecular pathology of growth hormone deficiency. In: Takker RV, ed. Molecular Genetics of Endocrine Disorders. London, England: Hodder Arnold; 1997:17-38.

  93. Phillips JA 3rd, Hjelle BL, Seeburg PH, Zachmann M. Molecular basis for familial isolated growth hormone deficiency. Proc Natl Acad Sci U S A. Oct 1981;78(10):6372-5. [Medline]. [Full Text].

  94. Portes ES, Oliveira JH, MacCagnan P, Abucham J. Changes in serum thyroid hormones levels and their mechanisms during long-term growth hormone (GH) replacement therapy in GH deficient children. Clin Endocrinol (Oxf). Aug 2000;53(2):183-9. [Medline].

  95. Radovick S, Nations M, Du Y, Berg LA, Weintraub BD, Wondisford FE. A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency. Science. Aug 21 1992;257(5073):1115-8. [Medline].

  96. Raiti S, Davis WT, Blizzard RM. A comparison of the effects of insulin hypoglycaemia and arginine infusion on release of human growth hormone. Lancet. Dec 2 1967;2(7527):1182-3. [Medline].

  97. Ranke MB, Lindberg A, Chatelain P, Wilton P, Cutfield W, Albertsson-Wikland K. Derivation and validation of a mathematical model for predicting the response to exogenous recombinant human growth hormone (GH) in prepubertal children with idiopathic GH deficiency. KIGS International Board. Kabi Pharmacia International Growth Study. J Clin Endocrinol Metab. Apr 1999;84(4):1174-83. [Medline].

  98. Reiter EO, Lovinger RD. The use of a commercially available somatomedin-C radioimmunoassay in patients with disorders of growth. J Pediatr. Nov 1981;99(5):720-4. [Medline].

  99. Reiter EO, Martha PM Jr. Pharmacological testing of growth hormone secretion. Horm Res. 1990;33(2-4):121-6; discussion 126-7. [Medline].

  100. Reiter EO, Morris AH, MacGillivray MH, Weber D. Variable estimates of serum growth hormone concentrations by different radioassay systems. J Clin Endocrinol Metab. Jan 1988;66(1):68-71. [Medline].

  101. Ritvos O, Ranta T, Jalkanen J, Suikkari AM, Voutilainen R, Bohn H. Insulin-like growth factor (IGF) binding protein from human decidua inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells. Endocrinology. May 1988;122(5):2150-7. [Medline].

  102. Rogers AH, Rogers GL, Bremer DL, McGregor ML. Pseudotumor cerebri in children receiving recombinant human growth hormone. Ophthalmology. Jun 1999;106(6):1186-9; discussion 1189-90. [Medline].

  103. Rosenfeld RG. Evaluation of growth and maturation in adolescence. Pediatr Rev. 1982;4:175-8. [Full Text].

  104. Rosenfeld RG, Aggarwal BB, Hintz RL, Dollar LA. Recombinant DNA-derived methionyl human growth hormone is similar in membrane binding properties to human pituitary growth hormone. Biochem Biophys Res Commun. May 14 1982;106(1):202-9. [Medline].

  105. Sacca L, Cittadini A, Fazio S. Growth hormone and the heart. Endocr Rev. Oct 1994;15(5):555-73. [Medline].

  106. Saggese G, Ranke MB, Saenger P, Rosenfeld RG, Tanaka T, Chaussain JL. Diagnosis and treatment of growth hormone deficiency in children and adolescents: towards a consensus. Ten years after the Availability of Recombinant Human Growth Hormone Workshop held in Pisa, Italy, 27-28 March 1998. Horm Res. 1998;50(6):320-40. [Medline].

  107. Salmon WD Jr, Dayghaday WH. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med. Jun 1957;49(6):825-36. [Medline].

  108. Schuit FC. Factors determining the glucose sensitivity and glucose responsiveness of pancreatic beta cells. Horm Res. 1996;46(3):99-106. [Medline].

  109. Shah A, Stanhope R, Matthew D. Hazards of pharmacological tests of growth hormone secretion in childhood. BMJ. Jan 18 1992;304(6820):173-4. [Medline].

  110. Shim M, Cohen P. IGFs and human cancer: implications regarding the risk of growth hormone therapy. Horm Res. 1999;51 Suppl 3:42-51. [Medline].

  111. Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. Oct 20 1994;331(16):1056-61. [Medline].

  112. Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ, O'Connell SM. Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature. Nov 28 1996;384(6607):327-33. [Medline].

  113. Stabler B, Siegel PT, Clopper RR. Growth hormone deficiency in children has psychological and educational co-morbidity. Clin Pediatr (Phila). Mar 1991;30(3):156-60. [Medline].

  114. Stanfield JP. The blood supply of the human pituitary gland. J Anat. Apr 1960;94:257-73. [Medline].

  115. Stewart PM, Sheppard MC. Mortality and hypopituitarism. Growth Horm IGF Res. Apr 1999;9 Suppl A:15-9. [Medline].

  116. Stuart CA, Neelon FA, Lebovitz HE. Hypothalamic insufficiency: the cause of hypopituitarism in sarcoidosis. Ann Intern Med. May 1978;88(5):589-94. [Medline].

  117. Sönksen P. The Growth Hormone Research Society. Growth Horm IGF Res. Jun 2000;10(3):107-10. [Medline].

  118. Südfeld H, Kiese K, Heinecke A, Brämswig JH. Prediction of growth response in prepubertal children treated with growth hormone for idiopathic growth hormone deficiency. Acta Paediatr. Jan 2000;89(1):34-7. [Medline].

  119. Taback SP, Dean HJ. Mortality in Canadian children with growth hormone (GH) deficiency receiving GH therapy 1967-1992. The Canadian Growth Hormone Advisory Committee. J Clin Endocrinol Metab. May 1996;81(5):1693-6. [Medline].

  120. Thomas PQ, Johnson BV, Rathjen J, Rathjen PD. Sequence, genomic organization, and expression of the novel homeobox gene Hesx1. J Biol Chem. Feb 24 1995;270(8):3869-75. [Medline]. [Full Text].

  121. Thomsett MJ, Conte FA, Kaplan SL, Grumbach MM. Endocrine and neurologic outcome in childhood craniopharyngioma: Review of effect of treatment in 42 patients. J Pediatr. Nov 1980;97(5):728-35. [Medline].

  122. Toublanc JE, Couprie C, Garnier P, Job JC. The effects of treatment combining an agonist of gonadotropin-releasing hormone with growth hormone in pubertal patients with isolated growth hormone deficiency. Acta Endocrinol (Copenh). Jun 1989;120(6):795-9. [Medline].

  123. Underwood LE, Azumi K, Voina SJ, Van Wyk JJ. Growth hormone levels during sleep in normal and growth hormone deficient children. Pediatrics. Dec 1971;48(6):946-54. [Medline].

  124. Underwood LE, D'Ercole AJ, Van Wyk JJ. Somatomedin-C and the assessment of growth. Pediatr Clin North Am. Nov 1980;27(4):771-82. [Medline].

  125. Urzola A, Leger J, Czernichow P. Three cases of congenital growth hormone deficiency with micropenis and hypospadias: what does growth hormone have to do with it?. Horm Res. 1999;51(2):101-4. [Medline].

  126. Veldhuis JD, Roemmich JN, Rogol AD. Gender and sexual maturation-dependent contrasts in the neuroregulation of growth hormone secretion in prepubertal and late adolescent males and females--a general clinical research center-based study. J Clin Endocrinol Metab. Jul 2000;85(7):2385-94. [Medline].

  127. Vosahlo J, Zidek T, Lebl J, Riedl S, Frisch H. Validation of a mathematical model predicting the response to growth hormone treatment in prepubertal children with idiopathic growth hormone deficiency. Horm Res. 2004;61(3):143-7. [Medline].

  128. Wajnrajch MP, Gertner JM, Harbison MD, Chua SC Jr, Leibel RL. Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse. Nat Genet. Jan 1996;12(1):88-90. [Medline].

  129. Wang ED, Drummond DS, Dormans JP, Moshang T, Davidson RS, Gruccio D. Scoliosis in patients treated with growth hormone. J Pediatr Orthop. Nov-Dec 1997;17(6):708-11. [Medline].

  130. Wit JM, Drayer NM, Jansen M, Walenkamp MJ, Hackeng WH, Thijssen JH. Total deficiency of growth hormone and prolactin, and partial deficiency of thyroid stimulating hormone in two Dutch families: a new variant of hereditary pituitary deficiency. Horm Res. 1989;32(5-6):170-7. [Medline].

  131. Wu W, Cogan JD, Pfaffle RW, Dasen JS, Frisch H, O'Connell SM. Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nat Genet. Feb 1998;18(2):147-9. [Medline].

  132. Wurzel JM, Parks JS, Herd JE, Nielsen PV. A gene deletion is responsible for absence of human chorionic somatomammotropin. DNA. 1982;1(3):251-7. [Medline].

  133. Zapf J, Walter H, Froesch ER. Radioimmunological determination of insulinlike growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia. J Clin Invest. Nov 1981;68(5):1321-30. [Medline].

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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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