Hyposomatotropism Clinical Presentation

  • Author: Robert J Ferry Jr, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Mar 27, 2012
 

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.[2]
  • 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.
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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
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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.[3] 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.[4]

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.

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Contributor Information and Disclosures
Author

Robert J Ferry Jr, MD  Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

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, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Eli Lilly & Co Grant/research funds Investigator; MacroGenics, Inc Grant/research funds Investigator; Ipsen, SA (formerly Tercica, Inc) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Grant/research funds Investigator; Bristol-Myers-Squibb Grant/research funds Other; Amylin Other; Pfizer Grant/research funds Other; Takeda Grant/research funds Other

Coauthor(s)

Sherry L Franklin, MD  Medical Director, Pediatric Endocrinology of San Diego Medical Group, Inc; Consulting Physician, Rady Children's Hospital; Assistant Clinical Professor at UCSD

Sherry L Franklin, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Phyllis W Speiser, MD  Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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; UNESCO Chair on Adolescent Health Care, University of Athens, 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, Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

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 for Medical Sciences College of Medicine, 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: Nothing to disclose.

Additional Contributors

The authors thank Gloria Matthews, Nora Eblen, and Debra Tate of the Division of Pediatric Endocrinology, University of Texas Health Science Center at San Antonio, for their administrative assistance. This work was supported in part by National Institutes of Health (NIH) grant K08 DK02876.

References

  1. Rasmussen MH, Juul A, Hilsted J. Effect of weight loss on free insulin-like growth factor-I in obese women with hyposomatotropism. Obesity (Silver Spring). Apr 2007;15(4):879-86. [Medline].

  2. [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].

  3. 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].

  4. 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].

  5. [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].

  6. 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].

  7. 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].

  8. 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].

  9. 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].

  10. 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].

  11. 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].

  12. 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].

  13. 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].

  14. 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].

  15. 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].

  16. 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].

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

  18. 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].

  19. 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].

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

  21. 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].

  22. 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].

  23. 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].

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

  25. 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].

  26. 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].

  27. 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].

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

  29. 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].

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

  31. 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].

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

  33. 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].

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

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

  36. 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].

  37. 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].

  38. 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].

  39. 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].

  40. 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].

  41. 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].

  42. 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].

  43. 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].

  44. 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].

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

  46. 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].

  47. 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].

  48. 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].

  49. 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].

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

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

  52. 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].

  53. 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].

  54. 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].

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

  56. 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].

  57. [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].

  58. 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].

  59. 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].

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

  61. 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].

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

  63. 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].

  64. 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].

  65. 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].

  66. 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].

  67. 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].

  68. 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].

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

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

  71. 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].

  72. 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].

  73. 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].

  74. 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].

  75. 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].

  76. 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].

  77. 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].

  78. 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].

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

  80. 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].

  81. 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].

  82. 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].

  83. 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].

  84. 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].

  85. 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].

  86. 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].

  87. 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].

  88. 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].

  89. 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].

  90. 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].

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

  92. 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].

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

  94. 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].

  95. 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].

  96. 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].

  97. 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].

  98. 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].

  99. 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].

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

  101. 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].

  102. 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].

  103. 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].

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

  105. 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].

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

  107. 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].

  108. 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].

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

  110. 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].

  111. 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].

  112. 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].

  113. 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].

  114. 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].

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

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

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

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

  119. 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].

  120. 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].

  121. 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].

  122. 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].

  123. 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].

  124. 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].

  125. 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].

  126. 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].

  127. 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].

  128. 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].

  129. 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].

  130. 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].

  131. 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].

  132. 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].

  133. 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].

  134. 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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T1-weighted sagittal MRI through the pituitary fossa shows a normal pituitary gland.
Table. Characteristics of the Pubertal Peak of Growth Velocity in Girls and Boys
CharacteristicGirlsBoys
Mean age at peak height velocity, y11.513
Magnitude, cm/y8.59.5
Duration, y56
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