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Hypopituitarism

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Pediatric Endocrinology

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

The pituitary gland is formed of anterior (adenohypophysis) and posterior (neurohypophysis) parts, which are embryologically derived from two different sources (1). The primordium of the anterior pituitary, Rathke’s pouch, forms by the upward invagination of the stomodeal ectoderm in the region of contact with the neuroectoderm of the primordium of the ventral hypothalamus (2). Rathke’s pouch can be identified by the third week of pregnancy (3). The posterior pituitary arises from the neural ectoderm of the forebrain.

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References

  1. Asa SI, Kovacs K. Functional morphology of the human fetal pituitary. Pathos Annu 1984. 19: 275–315.

    Google Scholar 

  2. Dutour A. A new step understood in the cascade of tissue-specific regulators orchestrating pituitary lineage determination: the Prophet of Pit-I (Prop-I). Euri Endocrinol 1997; 137 (6): 616–617.

    Article  CAS  Google Scholar 

  3. Rosenfeld RG. Disorders of growth hormone and insulin-like growth factor secretion and action, in Pediatric Endocrinology Sperling MA, ed, 1996. W.B. Saunders, PA. Philadelphia. 117–169.

    Google Scholar 

  4. Reichlin S. Neurocndocrinology, in: Williams Textbook of Endocrinology Wilson JD and Foster DW, eds. 1991, W.B. Saunders: Philadelphia. 1079–1138.

    Google Scholar 

  5. Gorcyzca W, Hardy.1. Arterial supply of human pituitary gland. Neurosurgery 1987: 20: 360.

    Google Scholar 

  6. Blethen SL. Hypopituitarism, in: Pediatric Endocrinology, Lifshitz F, ed. 1996, Marcel Dekker Inc. New York. 19–31.

    Google Scholar 

  7. DeNoto FM. Moore DD. Goodman HM. Human growth hormone DNA sequence and mRNA structure: possible alternative splicing. Nucl Acids Res 1981; 9 (15): 3719. 3730.

    Google Scholar 

  8. Cooke NE, Ray J, Watson MA, et al. Human growth hormone gene and the highly homologous growth hormone variant gene display different splicing patterns. J Clin Invest 1988; 82 (1): 270–275.

    Article  PubMed  CAS  Google Scholar 

  9. Baumann G, Stolar WM, Ambarn K, et al. A specific growth hormone-binding protein in human plasma: initial characterization..1 Clin Endocrinol Metab 1986; 62: 134–141.

    CAS  Google Scholar 

  10. Chen EY, Lino Y-C, Smith DH, et al. The human growth hormone locus: nucleotide sequence, biology, and evolution. Genomics 1989; 4: 479–497.

    Article  PubMed  CAS  Google Scholar 

  11. Misra-Press A, Cooke NE, Liebhaber SA. Complex alternative splicing partially inactivates the human chorionic somatomammotropin-like (hC5-L) gene. J Biol Chern 1994; 269:23, 220–23, 229.

    Google Scholar 

  12. Nielsen PV, Pedersen H. Kampmann EM. Absence of human placental lactogen in an otherwise uneventful pregnancy. Am J Obstetr Gynecol 1979; 135: 322–326.

    CAS  Google Scholar 

  13. Frankenne F. Scippo, ML, van Beeumen J, et al. Identification of placental human growth hormone as the growth hormone-V gene expression product. J Clin Endocrinol Metab 1990; 71: 15 - I8.

    Article  PubMed  CAS  Google Scholar 

  14. de Zegher F, Vanderschueren-Lodeweyckx M, Spitz B, et a]. Perinatal growth hormone (GH) physiology: Effect of GH-releasing factor on maternal and fetal secretion of pituitary and placental GH. J Clin Endocrinol Metab 1990; 71: 520–522.

    Article  PubMed  Google Scholar 

  15. Campbell RM. Scanes CG. Evolution of the growth hormone-releasing factor (GHRF) family of peptides. Growth Reg 1992; 2: 175–191.

    CAS  Google Scholar 

  16. Mayo KE. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol Endocrinol 1992; 6 (10): 1734–1744.

    Article  PubMed  CAS  Google Scholar 

  17. Chen C. Clarke IJ. Modulation ofCa2+ influx in the ovine somatotroph by growth hormone-releasing factor. Am J Physiol, 1995; 268: E204 - E212.

    PubMed  CAS  Google Scholar 

  18. Mayo KE, Godfrey PA, Suhr ST, et al. Growth hormone-releasing hormone: synthesis and signaling. Recent Prog Honn Res 1995; 50: 35–73.

    CAS  Google Scholar 

  19. Barinaga M, Yamonoto, G, Rivier C, et al., Transcriptional regulation of growth hormone gent expression by growth hormone-releasing factor. Nature 1983; 306: 84–85.

    Article  PubMed  CAS  Google Scholar 

  20. Bilezikjian LM. Vale MM. Stimulation of adenosine 3’,5’-monophosphate production by growth hormone-releasing factor and its inhibition by somatostatin in anterior pituitary cells in vitro. Endocrinology 1983; 113: 1726–1731.

    Article  PubMed  CAS  Google Scholar 

  21. Cohen LE, et a]. CREB-independent regulation by CBP is a nove] mechanism of human growth hormone gene expression. J Clin Invest 1999; 104 (1123–1128).

    Google Scholar 

  22. Raynor K, Murphy W. Coy D, et al. Cloned SRIF receptors: identification of subtype selective peptides and demonstration of high affinity binding of linear peptides. Mol Pharmacol 1993; 43: 838–844.

    PubMed  CAS  Google Scholar 

  23. Law S, Manning D, Reisine T. Identification of the subunits of GTP binding proteins couples to SRIF receptors. J Biol Chem 1991; 266:17, 885–17, 897.

    Google Scholar 

  24. Law S, Yasuda, K, Bell GI, et al. Gias and Goa selectively associate with the cloned SRIF receptor subtype STR2. J Biol Chem 1993; 268; 10, 721–10, 727.

    Google Scholar 

  25. Fujii Y, Gonoi T, Yamada Y, et al. Somatostatin receptor subtype SSTR2 mediates the inhibition of high voltage activated calcium channels by somatostatin and its analogue SMS. FEES Letters 1996; 355:117-.120.

    Google Scholar 

  26. Tannenbaum GS, Ling N. Evidence for autoregulation of growth hormone secretion via the central nervous system. Endocrinology 1980; 115: 1952–1957.

    Article  Google Scholar 

  27. Turner P, Tannenbaum GS. In vivo evidence of a positive role for somatostatin to optimize pulsatile growth hormone secretion. Am J Physiol 1995; 269: E683 - E690.

    PubMed  CAS  Google Scholar 

  28. Miller JD, Esparaza, A, Wright NM, et al. Spontaneous growth hormone release in term infants: Changes during the first four days of life. J Clin Endocrinol Metab 1993; 76: 1058–1062.

    Article  PubMed  CAS  Google Scholar 

  29. Costin G, Ratman-Kaufman F, Brasel J. Growth hormone secretory dynamics in subjects with normal stature. J Pediatr 1989; 115: 537–544.

    Article  PubMed  CAS  Google Scholar 

  30. Mauras N, Blizzard RM, Link K, et al. Augmentation of growth hormone secretion during puberty: Evidence for a pulse amplitude-modulated phenomenon. J Clin Endocrinol Metab 1987; 64: 596–601.

    Article  PubMed  CAS  Google Scholar 

  31. Rose SR, Municchi, G, Barnes KM, et al. Spontaneous growth hormone secretion increases during puberty in normal girls and boys. J Clin Endocrinol Metab 1991; 73: 428–435.

    Article  PubMed  CAS  Google Scholar 

  32. Martha PM, Gorman KM, Blizzard RM, et al. Endogenous growth hormone secretion and clearance rates in normal boys as determined by deconvolution analysis: Relationship to age, pubertal status and body mass. J Clin Endocrinol Metab 1992; 74: 336–344.

    Article  PubMed  CAS  Google Scholar 

  33. Dudl RJ, Ensinck JW, Palmer HE, et al. Effect of age on growth hormone secretion in man. J Clin Endocrinol Metab 1973; 37 (1): 11–16.

    Article  PubMed  CAS  Google Scholar 

  34. Rudman D, Kutner MH, Rogers CM, et al. Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest 1981; 67 (5): 1361–1369.

    Article  PubMed  CAS  Google Scholar 

  35. Smith RG, Van der Ploeg LHT, Cheng K, et al. Peptidomimetic regulation of growth hormone (OH) Secretion. Endo Rev 1997; 18: 621–645.

    Article  CAS  Google Scholar 

  36. Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996: 273: 972–977.

    Article  Google Scholar 

  37. Kojima M, Hosoda, H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1 999; 402 (1999): 656–660.

    Article  CAS  Google Scholar 

  38. Nakazato M, Murakanti M, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 200; 1409: 194–198.

    Google Scholar 

  39. Bazan]F. Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci USA, 1990; 87: 6934–6938.

    Article  Google Scholar 

  40. Godowski PJ, Leung DW, Meacham I.R, et al. Characterization of the human growth hormone receptor gene with demonstration of a partial gene deletion in two patients with Laron-type dwarfism. Proc Natl Acad Sci USA 1989; 86: 8083–8087.

    Article  PubMed  CAS  Google Scholar 

  41. Campbell GS, Christian LJ, Carter-Su C. Evidence for involvement of the growth hormone receptor-associated tyrosine kinase in actions of growth hormone. J Biol Chem 1993; 268: 7427–7434.

    PubMed  CAS  Google Scholar 

  42. Argetsinger LS, Cambell GS, Yang X. et al. Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. Cell 1993; 74: 237–244.

    Article  PubMed  CAS  Google Scholar 

  43. Finbloom DS, Petricoin EF, Hackett RH, et al. Growth hormone and erythropoietin differentially activate DNA-binding proteins by tyrosine phosphorylation. Mol Cell Biol 1994; 14: 2113–2118.

    PubMed  CAS  Google Scholar 

  44. Silva CM, Weber MJ, Timmer MO. Stimulation of tyrosine phosphorylation in human cells by activation of the human growth hormone receptor. Endocrinology 1995; 132: 101–108.

    Article  Google Scholar 

  45. Silva CM, Lu H, Day RN. Characterization and cloning of STAT5 from IM-9 cells and its activation by growth hormone. Mol Endocrinol 1996; 10: 508–518.

    Article  PubMed  CAS  Google Scholar 

  46. Smit LS, Meyer DJ, Billestrup N, et al. The role of the growth hormone receptor and Jakl and Jak2 kinases in the activation of STATs 1, 3, and 5 by growth hormone. Mol Endocri nol. 1996; 10: 519–533.

    Google Scholar 

  47. Salmon WDJ, Daughaday WH. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vivo.] Lab Clin Med 1957; 49: 825.

    Google Scholar 

  48. Rinderknecht E, Humhel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem 1978; 253 (8): 2769–2776.

    PubMed  CAS  Google Scholar 

  49. Daughaday WH, Rotwein, IP. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endo Rev 1989; 10 (1): 68–91.

    CAS  Google Scholar 

  50. Gluckman PD, Barrett-Johnson JJ, Butler JH, et al. Studies of insulin-like growth factor 1 and II by specific radioligand assays in umbilical cord blood. Clin Endocrinol 1983; 19: 405.

    Article  CAS  Google Scholar 

  51. Bennet A, Wilson DM, Wibbelsman CJ, et al. Levels of insulin-like growth factor-1 and -II in human cord blood. J Clin Endocrinol Metab 1983; 57: 609.

    Article  Google Scholar 

  52. Luna AM, Wilson DM, Wibbelsman CJ, et al. Somatomedins in adolescence: A cross sectional study of the effect of puberty on plasma insulin-like growth factor i and II levels. J Clin Endocrinol Metab 1983; 57: 258.

    Article  Google Scholar 

  53. Cara FJ, Rosenfield RL, Furlanetto RW, A longitudinal study of the relationship of plasma somatomedin-C concentrations to the pubertal growth spurt. Am J Dis Child 1987; 141: 562.

    PubMed  CAS  Google Scholar 

  54. Johanson AJ. Blizzard RM. Low somatomediti-C levels in older men rise in response to growth hormone administration. John Hopkins Med J 1981; 149: 115.

    CAS  Google Scholar 

  55. Rudman D, Feller AG, Nagraj HS, et al. Effects of human gorwth hormone in men over 60 years old. N Engl J Med 1990; 312: 1.

    Article  Google Scholar 

  56. Ohlsson C, Bengtsson, B-A, Isaksson OGP, et al. Growth hormone and bone. Endocr Rev 1998; 19 (1); 55–79.

    Article  PubMed  CAS  Google Scholar 

  57. Isaksson O, Jansson G, Gause IA. Growth hormone stimulates longitudinal hone growth directly. Science, 1982; 216 (4551): 1237–1239.

    Article  PubMed  CAS  Google Scholar 

  58. Maor G, Hochberg Z, Silbermann M. Growth hormone stimulates the growth of mouse neonatal condylar cartilage in vitro. Acta Endocrinol 1989; 120 (4): 526–532.

    PubMed  CAS  Google Scholar 

  59. Maor G, Hochberg Z, von der Mark K, et al. Human growth hormone enhances chondrogenesis and osteogenesis in a tissue culture system of chondroprogenitor cells. Endocrinology 1989; 125 (3): 1239–1245.

    Article  PubMed  CAS  Google Scholar 

  60. lsgaard J, Moller COG, Nilsson A, et al. Regulation of insulin-like growth factor messenger ribonucleic acid in rat growth plate by growth hormone. Endocrinology 1988; 122 (4): 1515–1520.

    Article  Google Scholar 

  61. Zamboni G, Antoniazzi F, Radetti G, et al. Effects of two different regimens of recombinant human growth hormone therapy on the bone mineral density of patients with growth hormone deficiency. J Pediatr 1991; 119: 483–485.

    Article  PubMed  CAS  Google Scholar 

  62. Elgin RG, Busby WHJ, Clemmons DR. An insulin-like growth factor(IGF) binding protein enhances the biologic response to 10F-I. Proc Nail Acad Sci USA 1987; 84 (10): 3254–3258.

    Article  CAS  Google Scholar 

  63. Ritvos O, Rama T. Jalkanen J, et al. Insulin-like growth factor (10F) binding protein from human decidua inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells. Endocrinology 1.988; 122 (5):2150–2157.

    Google Scholar 

  64. Lamson G, Giudice LD, Rosenfeld RG. Insulin-like growth factor binding proteins (IGFBPs): Structural and molecular relationships. Growth Factors 1991; 5: 19–28.

    Article  PubMed  CAS  Google Scholar 

  65. Kelley KM, Oh Y,Gargosky SE, et al. Insulin-like growth factor binding proteins (IGFBPs) and their regulatory dynamics. Intl J Biochcm Cell Biol 1996; 28: 619–637.

    Article  CAS  Google Scholar 

  66. Chernausek S, Jacobs S, van Wyk, JJ. Structural similarities between receptors for somatomedin C and insulin: analysis by affinity labeling. Biochem 1981; 20: 7345.

    Article  CAS  Google Scholar 

  67. Massague J, Czech MP. The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor. J Biol Chem 1982; 257: 5038.

    PubMed  CAS  Google Scholar 

  68. Muller HL, Neely EK, et al. New concepts in insulin-like growth factor receptor physiology. Growth Reg 1993; 3: 113.

    Google Scholar 

  69. Rona RJ, Tanner JM. Aetiology of idiopathic growth hormone deficiency in England and Wales. Arch Dis Child 1977; 52: 197–208.

    Article  PubMed  CAS  Google Scholar 

  70. Vimpani GV, Vampani AF, Lidgard GP, et al. Prevalence of severe growth hormone deficiency. Br Med J 1977; 2: 427–430.

    Article  PubMed  CAS  Google Scholar 

  71. Shulman DI. Growth hormone therapy: An update. Contemporary Pediatrics, 1998; 15 (8): 95–100.

    Google Scholar 

  72. Gluckman PD, Gunn AJ, Wray A, et al. Congenital idiopathic growth hormone deficiency associated with prenatal and early postnatal growth failure. J Pediatr 1992; 121: 920–923.

    Article  PubMed  CAS  Google Scholar 

  73. Wabitsch M, Heinze E. Body fat in GH deficient children and the effect of treatment. Horm Res 1993; 5: 43–52.

    Google Scholar 

  74. Barreca T, Perrie C. Sannia A, et al. Evaluation of anterior pituitary function in patients with post-traumatic diabetes insipidus. J Clin Endocrinol Metab 1980; 51: 1279–1282.

    Article  PubMed  CAS  Google Scholar 

  75. Yamanaka C, Momoi T, Fuisawa I, et al. Acquired growth hormone deficiency due to pituitary stalk transection after head trauma in childhood. Eur J Pediatr 1993; 152 (2): 99–101.

    Article  PubMed  CAS  Google Scholar 

  76. Craft WH, Underwood JJ, van Wyk LE. High incidence of perinatal insult in children with idiopathic hypopituitarism. J Pediatr 1980; 96: 397–402.

    Article  PubMed  CAS  Google Scholar 

  77. C’ruikshank DP. Breech presentation. Clin Obstet Gynecol 1986; 29:255–263

    Google Scholar 

  78. Dunger DB, Broadbent V, Yocman E. The frequency and natural history of diabetes insipidus in children with Langerhans-cell histiocytosis. N Engl J Med 1989; 321: 1157–1162.

    Article  PubMed  CAS  Google Scholar 

  79. lien RD, Newton TH, McDermott MW, et al. Thickened pituitary stalk on MR images in patients with diabetes insipidus and Langerhans-cell histiocytosis. Am J Neuro Radiol 1990; 11: 703–708.

    Google Scholar 

  80. O’Sullivan RM, Sheehan M, Poskitt KJ, et al. Langerhans cell histiocytosis of hypothalamus and optic chiasm: CT and MR studies. J Comput Assist Tomogr 1991; 15: 52–55.

    Article  PubMed  Google Scholar 

  81. Freda PU, Silverberg SJ, Kalmon KD, et al. Hypothalamic-pituitary sarcoidosis. Trends Endo-crinol Metab 1992; 2: 321–325.

    Article  Google Scholar 

  82. Bevan JS, Othman S, Lazarus JH, et al. Reversible adrenocorticotropin deficiency due to probably autoimmune hypophysitis in a woman with postpartum thyroiditis. J Clin Endocrinol Metab 1992; 74: 548–552.

    Article  PubMed  CAS  Google Scholar 

  83. Duranteau L, Chanson P. Bumbcrg-Tick J. et al. Non-responsiveness of serum gonadotropins and testosterone to pulsatile GnRH in hemochromatosis suggesting a pituitary defect. Acta Endocrinol 1993; 128 (4): 351–354.

    PubMed  CAS  Google Scholar 

  84. Oerter KE, Kamp GA, Munson PJ, et al. Multiple hormone deficiencies in children with hemochromatosis. J Clin Endocrinol Metab 1993; 76: 357–361.

    Article  PubMed  CAS  Google Scholar 

  85. Pollack IF. Brain tumors in children. New Engl J Med 1994; 331 (22): 1500 1507.

    Google Scholar 

  86. Rappaport R, Brauner R. Growth and endocrine disorders secondary to cranial irradiation. Pediatr Res 1989; 25: 561–567.

    Article  PubMed  CAS  Google Scholar 

  87. Clayton PE, Shalet, SM. Dose dependency of time on onset of radiation-induced growth hormone deficiency. J Pediatr 1991; 118:226–228

    Google Scholar 

  88. Shalet SM. Growth and endocrine sequelae following the treatment of childhood cancer, in Clinical Paediatric Endocrinology, B. C.G.D., ed. 1995; Blackwell Science Ltd.: Oxford. 383–396.

    Google Scholar 

  89. Shalet SM, Gibson B, Swindell R, et al. Effect of spinal irradiation on growth. Arch Dis Child 1987; 62: 461–464.

    Article  PubMed  CAS  Google Scholar 

  90. Godfrey P, Rabat JO, Beanter WG, et al. GHRH receptor of little mice contains a missense mutation in the extraceilular domain that disrupts receptor function. Nat Genet 1993; 4 (3):227–232.

    Google Scholar 

  91. Lin SC, Lin CR, Gukovsky I, et al. Molecular basis of the little mouse phenotype and implications for cell type-specific growth (see comments). Nature 1993; 364 (6434): 208–213.

    Article  PubMed  CAS  Google Scholar 

  92. Wajnrajch MP. Gertner JM, Harbison MD, et al. Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse. Nat Genet 1996; 12: 88–90.

    Article  PubMed  CAS  Google Scholar 

  93. Maheshwari HG, Silverman BL, Dupuis J, et al. Phenotype and genetic analysis of a syndrome caused by an inactivating mutation in the growth hormone-releasing hormone receptor: Dwarfism of Sindh. J Clin Endocrinol Metab 1998; 83 (11): 4065–4074.

    Article  PubMed  CAS  Google Scholar 

  94. Dattani M, Martinez-Barbera J-P, Thomas PQ, et al. Mutations in the homeobox gene HESX 1 /Hesx 1 associated with septo-optic dysplasia in human and mouse. Nat Genet 1998; 19: 125–133.

    Article  PubMed  CAS  Google Scholar 

  95. Hermesz E,Mackern S. Mahon, Rpx: a novel anterior-restricted homeobox gene progressively activated in the prechordal plate, anterior neural plate and Rathke’s pouch of the mouse embryo. Development 1996; 122 (1):41–52.

    Google Scholar 

  96. Tremblay JJ, C. Lanctot, Drouin J. The pan-pituitary activator of transcription. Ptx i (pituitary homeobox I). acts in synergy with SF-1 and Pit and is an upstream regulator of the Limhomeodomain gene Lim3ILhx3. Mol Endocrinol 1998. 12 (3): 428–441.

    Article  PubMed  CAS  Google Scholar 

  97. Thomas PQ, Dattani MT, Brickman JM, et al. Heterozygous HESX l mutations associated wtih isolated congenital pituitary hypoplasia and septo-optic dysplasia, Hum Mol Genet 2001; 10 (1): 39–45.

    Article  PubMed  CAS  Google Scholar 

  98. Lamonerie T, Tremblay ii. Lanctot C, et al. Ptx 1, a bicoid-related homeo box transcription factor involved in transcription of the pro-opiomelanocortin gene. Genes Dev 1996; 10 (10):1284–1295.

    Google Scholar 

  99. Drouin J, Lamolet B, Lamonerie T, et al. The PTX family of homeodomain transcription factors during pituitary development. Mol and Cell Endocrinol 1998; 140: 31–36.

    Article  CAS  Google Scholar 

  100. Gage PJ, Camper SA. Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation. Hum Mol Genet 1997; 6 (3):457–464.

    Google Scholar 

  101. Semina EV, Reiter R, Leysens NJ, et al. Cloning and characterization of a novel hicoid-related homeobox transcription factor gene, MEG, involved in Rieger Syndrome. Nat Genet 1996; 14 (4): 392–399.

    Article  PubMed  CAS  Google Scholar 

  102. IO2. Amend(BA, Sutherland LB, Semina EV, et al. The molecular basis of Rieger syndrome. J Biol Chem 1998; 273 (32):20, 066–20, 072.

    Google Scholar 

  103. Zhadanov AB, Bertuzzi S, Taira M, et al. Expression pattern of the mucine LIM class homeobox gene Lhx3 in subsets of neural and neurocndocrinc tissues. Dev Dyn 1995; 202 (4):354–364.

    Google Scholar 

  104. Mbikay M, Tadros H, Seidah NG, et al. Linkage mapping of the gene for the LIM-homeoprotein LIM3 (locus Lhx3) to mouse chromosome 2. Mamm Genorne 1995; 6 (11):818–819.

    Google Scholar 

  105. Bach 1, Rhodes Si, Pearse RV, et al. P-Lim, a LIM homeodomain factor, is expressed during pituitary organ and cell commitment and synergizes with Pit-1. Proc Nad Acad Sci USA, 1995; 92 (7): 2720–2724.

    Google Scholar 

  106. Sheng HZ, Zhadanov AB, Mosinger B. Jr., et al.. Specification of pituitary cell lineages by the LIM homeobox gene Lhx3. Science 1996; 272 (5264): 1004–1007.

    Article  PubMed  CAS  Google Scholar 

  107. Nctchine I, Sobrier M-L, Krude H, et al. Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency. Nat Genet 2000; 25: 182–186.

    Article  CAS  Google Scholar 

  108. Sloop KW, Parker GE, Hanna KR, et al. LHX3 transcription factormutations associated with combined pituitary hormone deficiency impair the activation of pituitary target genes. Gene 2001; 265: 61–69.

    Article  PubMed  CAS  Google Scholar 

  109. Flock C, Deladoey J, Rutishauser K, et al. Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP gene mutation resulting in the substitution of Arg Cys at codon 120 (R120C). J Clin Endocrinol Metab 1998; 83 (10): 3727–3734.

    Article  Google Scholar 

  110. Wu W. Cogan JD. Pfaffle RW, et al. Mutations in PROP! cause familial combined pituitary hormone deficiency. Nat Genet 1998; 18 (2): 147–149.

    Article  PubMed  CAS  Google Scholar 

  111. Fofanova OV, Takamura N, Kinoshita F-J, set al. A mutational hot spot in the Prop-1 gene in Russian children with combined pituitary hormone deficiency. Pituitary 1998; 45–49.

    Google Scholar 

  112. Fofanova O, Takntura N, Kinoshita E, et al. Compound heterozygous deletion of the Prop-I gene in children with combined pituitary hormone deficiency. J Clin Endocrinol Metab 1998; 83 (7): 2601–2604.

    Article  Google Scholar 

  113. Cogan JD, Wu W, Phillips 111 JA, et al. The PROP] 2-hase pair deletion is a common cause of combined pituitary hormone deficiency. J Clin Endocrinol Metab 1998; 83 (9): 3346–3349.

    Article  PubMed  CAS  Google Scholar 

  114. Pernasetti F, Toledo SPA, Vasilyev VV, et al. Impaired adrenocorticotropin-adrenal axis in combined pitiutary hormone deficiency caused by a two-base pair deletion (301–302delAG) in the Prophet of Pit-1 Gene. J Clin Endocrinol Metab 2000; 85: 390–397.

    Article  PubMed  CAS  Google Scholar 

  115. Agarwal G, Bhatia V, Cook S, et al. Adrenocorticotropin deficiency in combined pituitary hormone deficiency patients homozygous for a novel PROP! mutation. J Clin Endocrinol Metab., 2000; 85 (12): 4556–4561.

    Article  PubMed  CAS  Google Scholar 

  116. Osorio MOP, Kopp P, Mami S, et al. Combined pituitary hormone deficiency caused by a novel mutation of a highly conserved residue (F88S) in the homeodomain of PROP-1. J Clin Endocrinol Metab 2000; 85 (8):2779–2785.

    Google Scholar 

  117. Duquesnoy P, Roy A, Dastot F, et al. Human Prop- I: cloning, mapping. gnomic structure. Mutations in familial combined pituitary hormone deficiency. FEES Letters, 1998; 437 (3): 216–220.

    Google Scholar 

  118. Bodner M, Castrillo JL, Theill LE, et al. The pituitary-specific transcription factor GHF- I is a homeohox-containing protein. Cell 1988; 55 (3): 505–518.

    Article  PubMed  CAS  Google Scholar 

  119. Simmons DM, Voss JW, Ingraham HA, et al. Pituitary cell phenotypes involve cell-specific Pit-1 mRNA translation and synergistic interactions with other classes of transcription factors. Genes Dev 1990; 4 (5): 695–711.

    Article  PubMed  CAS  Google Scholar 

  120. Radovick S, Nations M, Du Y, et al. A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency. Science I992; 257 (5073):1115–1118.

    Google Scholar 

  121. Cohen LE, Wondisford FE, Salvatoni A, et al. A “hot spot” in the Pit-gene responsible for combined pituitary hormone deficiency: clinical and molecular correlates. J Gin Endocrinol Metab I995; 80 (2):679–684.

    Google Scholar 

  122. Ohta K, Nobukuni Y, Mitsubuchi H, et al. Mutations in the Pit-I gene in children with combined pituitary hormone deficiency. Biochem Biophys Res Commun 1992; 189 (2): 851–855.

    Article  PubMed  CAS  Google Scholar 

  123. Okamoto N, Wada Y, Ida S, et al. Monoallelic expression of normal mRNA in the PITT mutation heterozygotes with normal phenotype and hiallelic expression in the abnormal phenotype. Human Mol Genet 1994; 3: 1565–1568.

    Article  CAS  Google Scholar 

  124. de Zegher F. Pernasetti F, Vanhole C, et al. The prenatal role of thyroid hormone evidenced by fetomaternal Pit-1 deficiency. J Clin Endocrinol Metab 1995; 80 (11): 3127–3130.

    Article  PubMed  Google Scholar 

  125. Holl RW, Pfaffle R, Kim C, et ai. Combined pituitary deficiencies of growth hormone, thyroid stimulating hormone and prolactin due to Pit-1 gene mutation: a case report. Eur J Pediatr 1997; 156 (11)1835–837.

    Google Scholar 

  126. Aarskog D, Eiken HG, Bjerknes R, et al. Pituitary dwarfism in the R27 W Pit-I gene mutation. Eur J Pediatr 1997; 156 (11): 829–34.

    Article  PubMed  CAS  Google Scholar 

  127. Arnhold IJ, Nery M, Brown, MR, et al. Clinical and molecular characterization of a Brazilian patient with Pit-f deficiency.1 Ped Endocrinol Metab 1998; 11 (5): 623–630.

    CAS  Google Scholar 

  128. Ward L, Chavez M, Huot C, et al. Severe congenital hypopituitarism with low prolactin levels and age-dependent anterior pituitary hypoplasia: A clue to a PIT-1 mutation. J Pediatr 1998; 132: 1036–1038.

    Article  PubMed  CAS  Google Scholar 

  129. Jacobson EM, Li P, Leon-del-Rio A. et al. Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev 1997; 11 (2): 198–212.

    Article  PubMed  CAS  Google Scholar 

  130. Cohen LE, Zanger K, Brue T, et al. Defective retinoic acid regulation of the pit-1 gene enhancer: A novel mechanism of combined pituitary hormone deficiency. Mol Endocrinol 1999; 13: 476–484.

    Article  PubMed  CAS  Google Scholar 

  131. Pellegrini-Bouiller I, Belicar P, Barlier A, et al. A new mutation of the gene encoding the transcription factor Pit-I is responsible for combined pituitary hormone deficiency. J Clin Endocrinol Metab 1996; 81 (8):2790–2796.

    Google Scholar 

  132. Pfaffle RW, DiMattia GE, Parks JS, et al. Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia. Science 1992; 257 (5073):1 l 18–1121.

    Google Scholar 

  133. Brown MR, Parks JS, Adess ME, et al. Central hypothyroidism reveals compound heterozygous mutations in the Pit-1 gene. Horne Res 1998; 49 (2): 98–102.

    Article  CAS  Google Scholar 

  134. Tatsumi K, Miyai K, Notomi T, et al. Cretinism with combined hormone deficiency caused by a mutation in the PITI gene. Nat Genet 1992; 1 (1): 56–58.

    Article  PubMed  CAS  Google Scholar 

  135. Frisch H, Kim, C, Hausler G, et al. Combined pituitary hormone deficiency and pituitary hypoplasia due to a mutation of the Pit-1 gene. Clin Endocrinol 2000; 52 (5): 661–665.

    Article  CAS  Google Scholar 

  136. Inc Y. Tatsumi K, Ogawa M, et al. A novel E250X mutation of the PIT1 gene in a patient with combined pituitary hormone deficiency. F.ndocrJ 1995; 42 (3): 351–354.

    Google Scholar 

  137. Li S, Crenshaw ER, Rawson EJ, et al. Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-l. Nature 1990; 347 (6293): 528–533.

    Article  PubMed  CAS  Google Scholar 

  138. Pernasetti F, Milner RUG, Al Ashwal AAZ, et al. Pro239Ser: A novel recessive mutation of the Pitt gene in seven Middle Eastern children with growth hormone, prolactin, and thyrotropin deficiency. J Clin Endocrinol Metab 1998; 83: 2079–2083.

    Article  PubMed  CAS  Google Scholar 

  139. Illig R, Prader A, Ferrandez A, et al. Hereditary prenatal growth hormone deficiency with increased tendency to growth hormone antibody formation (A-type) of isolated growth hormone deficiency. Acta Paed Scand 1971; 60: 607.

    Google Scholar 

  140. Phillips JA, Hjelle BL, Seeburg PH, et al. Molecular basis of familial isolated growth hormone deficiency. Proc Natl Acad Sci USA, 1981; 78: 6372–6375.

    Article  PubMed  CAS  Google Scholar 

  141. Braga S, Phillips JA, Joss E, et al. Familial growth hormone deficiency resulting from a 7.6 kb deletion within the growth hormone gene cluster. Am J Med Genet 1986; 25: 443–452.

    Article  PubMed  CAS  Google Scholar 

  142. Perez Jurado LA, Argente J. Molecular basis of familial growth hormone deficiency. Horm Res 1994; 42 (4–5): 189–197.

    Article  PubMed  CAS  Google Scholar 

  143. Vnencak-Jones CL, Phillips JA. Hot spots for growth hormone gene deletions in homologous regions outside of Alu repeats. Science 1990; 250: 1745–1748.

    Article  PubMed  CAS  Google Scholar 

  144. Prader A, Zachmann M, Poley JR, et al. Long-term treatment with human growth hormone (Raben) in small doses: evaluation of 18 hypopituitary patients. Helv Paediatr Acta 1967; 22: 423–440.

    PubMed  CAS  Google Scholar 

  145. Phillips JA. Inherited defects in growth hormone synthesis and action, in Metabolic Basis of Inherited Disease CR, Scriver, et al., eds. 1995, McGraw Hill: St. Louis, MO. p. 3023–3044.

    Google Scholar 

  146. Phillips JA, Cogan JD. Molecular basis of familial human growth hormone deficiency. J Clin Endocrinol Metab 1994; 78: 11–16.

    Article  PubMed  CAS  Google Scholar 

  147. Binder G, Ranke MB. Screening for growth hormone (GH) gene splice-site mutaitons in sporadic cases with severe isolated GH deficiency using ectopic transcript analysis. J Clin Endocrinol Metab 1995; 80: 1247–1252.

    Article  PubMed  CAS  Google Scholar 

  148. Cogan JD, Phillips, JA, Schenkman SS, et al. Familial growth hormone deficiency: A model of dominant and recessive mutations affecting a monomeric protein. J Clin Endocrinol Metab 1994; 79: 1261–1265.

    Article  PubMed  CAS  Google Scholar 

  149. Igarashi Y, Kamijo T, Ogawa M, et al. A new type of inherited growth hormone deficiency: A compound heterozygote of a 6.7 kb deletion, including the GH-1 gene, and two base deletion deletion in the third exon of the GH-1 gene. Pediatr Res 1993; 33: S35.

    Article  Google Scholar 

  150. Duquesnoy P, Amselem S, Gourmelen M, et al. A frameshift mutaiton causing isolated growth hormone deficiency type IA. Am J Hum Genet 1990; 47: A110.

    Google Scholar 

  151. Cogan JD, Phillips JA, Sakati N, et al. Heterogeneous growth hormone (GH) gene mutations in familial GH deficiency. J Clin Endocrinol Metab 1993; 76: 1224–1228.

    Article  PubMed  CAS  Google Scholar 

  152. Cogan, JD, Ramel B, Lehto M, et al. A recurring dominant negative mutation causes autosomal dominant growth hormone gene deficiency–A clinical research center study. J Clin Endocrinol Metab 1995; 80: 3591–3595.

    Article  PubMed  CAS  Google Scholar 

  153. Kamijo T, Kinoshita E, Yoshimoto M, et al. An identical mutation in GH 1 gene associated with IGHD in two sporadic Japanese patients. Horm Res 1997; 48 (suppl 2): 92.

    Google Scholar 

  154. Saitoh H, Fukushima T, Kamoda T, et al. A Japanese family with autosomal dominant growth hormone deficiency. Eur J Pediatr 1999; 158: 624–627.

    Article  PubMed  CAS  Google Scholar 

  155. Fleisher TA, White RM, Broder S, et al. X-linked hypogammaglobulinemia and isolated growth hormone deficiency. N Engl J Med 1980; 302: 1429–1434.

    Article  PubMed  CAS  Google Scholar 

  156. Conley ME, Burk W, Herrod HG, et al. Molecular analysis of X-linked agammaglobulinemia with growth hormone deficiency. J Pediatr 1991; 119: 392–397.

    Article  PubMed  CAS  Google Scholar 

  157. Goossens M, Brauner R, Czernichow P, et al. Isolatd growth hormone (GH) deficiency type Ia associated with a double deletion in the human GH gene cluster. J Clin Endocrinol Metab 1986; 62: 712–716.

    Article  PubMed  CAS  Google Scholar 

  158. Akinci A, Kanaka C, Eble A, et al. Isolated growth hormone (GH) deficiency type IA associated with a 45-kilobase gene deletion within the human GH gene cluster. J Clin Endocrinol Metab 1992; 75: 437–441.

    Article  PubMed  CAS  Google Scholar 

  159. Takahashi Y, Kaji, H, Okimura Y, et al. Brief report: Short stature caused by a mutant growth hormone. N Engl J Med 1996; 334: 432–436.

    Article  PubMed  CAS  Google Scholar 

  160. Takahashi Y, Shirono H, Arisaka O, et al. Biologically inactive growth hormone caused by an amino acid substitution. J Clin Invest 1997; 100: 1159–1165.

    Article  PubMed  CAS  Google Scholar 

  161. Laron A, Pertzelan A, Mannheimer S. Genetic pituitary dwarfism with high serum concentration of growth hormone. A new inborn error of metabolism ? Israel J Med Science 1966; 2: 152–155.

    CAS  Google Scholar 

  162. Amselem S, Duquesnoy P, Attree O, et al. Laron dwarfism and mutations of the growth hormone-receptor gene. N Engl J Med 1989; 321: 989–995.

    Article  PubMed  CAS  Google Scholar 

  163. Amselem S, Sobrier ML, Duquesnoy P, et al. Recurrent nonsense mutations in the growth hormone receptor from patients with Laron dwarfism. J Clin Invest 1991; 87: 1098–1102.

    Article  PubMed  CAS  Google Scholar 

  164. Berg MA, Guevara-Agurre J, Rosenbloom AL, et al. Mutation creating a new splice site in the growth hormone receptor genes of 37 Ecuadorean patients with Laron syndrome. Human Mutation 1992; 1: 24–34.

    Article  PubMed  CAS  Google Scholar 

  165. Berg MA, Argente J, Chernausek S, et al. Diverse growth hormone receptor gene mutations in Laron Syndrome. Am J Hum Genet 1993; 52: 998–1005.

    PubMed  CAS  Google Scholar 

  166. Goddard AD, Covello R, Luoh SM, et al. Mutations of the growth hormone receptor in children with idiopathic short stature. N Engl J Med 1995; 333: 1094–1098.

    Article  Google Scholar 

  167. Woods KA, Fraser NC, Postel-Vinay MC, et al. A homozygous splice site mutation affecting the intracellular domain of the growth hormone (OH) receptor resulting in Lawn syndrome with elevated GH-binding protein. J Clin Endocrinol Metab 1996; 81: 1686–1690.

    Article  PubMed  CAS  Google Scholar 

  168. Ayling RM, Ross R, Towner P, et al. A dominant-negative mutation of the growth hormone receptor causes familial short stature. Nat Genet 1997; 16: 13–14.

    Article  PubMed  CAS  Google Scholar 

  169. Kaji H, Nose 0, Tajiri H, et al. Novel compound heterozygous mutations of growth hormone (GH) receptor gene in a patient with GH insensitivity syndrome. J Clin Endocrinol Metab 1997; 82: 3705–3709.

    Article  PubMed  CAS  Google Scholar 

  170. Lida K, Takahashi Y, Kaji H, et al. Growth hormone (GH) insensitivity syndrome with high serum GH-binding protein levels caused by a heterozygous splice site mutation of the GH receptor gene producing a lack of intracellular domain. J Clin Endocrinol Metab 1998; 83: 531–537.

    Article  Google Scholar 

  171. Walker JL, Crock PA, Behncken SN, et al. A novel mutation affecting the interdomain link region of the growth hormone receptor in a Vietnamese girl, and response to long-term treatment with recombinant human insulin-like growth factor-I and luteinizing hormone-releasing hormone analogue. J Clin Endocrinol Metab 1998; 83: 2554–2561.

    Article  PubMed  CAS  Google Scholar 

  172. Baumann G, Shaw MA, Winter RI. Absence of the plasma growth hormone binding-protein in Laron-type dwarfism. J Clin Endocrinol Metab 1987; 65: 814–816

    Google Scholar 

  173. Backeljauw PF, Underwood LE, a.t.G.C. Group. Prolonged treatment with recombinant insulin-like growth factor-I in children with growth hormone insensitivity syndrome: A clinical research center study. J Clin Endocrinol Metab 1996; 81: 3312–3317.

    Article  PubMed  CAS  Google Scholar 

  174. Laron Z, Anin S, Klinger B. Long-term IGF- I treatment of children with Laron syndrome. Lessons from Laron syndrome 1966–1992. Pediatr Adolesc Endocrinol 1993; 24: 226–236.

    Google Scholar 

  175. Woods KA, Camacho-Hubner, C, Savage MO, et aI. Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med 1996; 335 (18): 1363–1367.

    Article  PubMed  CAS  Google Scholar 

  176. Bowcock A. Sartorelli V. Polymorphism and mapping of the IGFI gene, and absence of association with stature among African Pygmies. Human Genetics, 1990; 85 (3): 349–354.

    Article  PubMed  CAS  Google Scholar 

  177. Geffner ME. Bailey RC, Bcrsch N, et al. Insulin-like growth factor-I unresponsiveness in an Efe Pygmy. Biochem Biophys Res Commun 1993: 193 (3): 1216–1223.

    Article  PubMed  Google Scholar 

  178. Geffner ME, Bersch N, Bailey RC, et al. Insulin-like growth factor 1 resistance in immortalized Tcell lines from African Efe Pygmies. J Clin Endocrinol Metab 1995; 80 (12): 3732–3738.

    Article  PubMed  CAS  Google Scholar 

  179. Dulloo AG, Shahkhalili Y, Atchou G. et al. Dissociation of systemic GH-IGF-1 axis from a genetic basis for short stature in African Pygmies. Eur J of ClinNutr 1996; 50 (6): 371–380.

    CAS  Google Scholar 

  180. Lanes R. Plotnick LP, Spencer EM, et al. Dwarfism associated with normal serum growth hormone and increased bioassayahle, receptorassayahlc, and immunoassayable somatomedin. J Clin Endocrinol Metab 1980; 50: 85–488.

    Google Scholar 

  181. Bierich Jr, Moeller H. Ranke MB, et al. Pseudopituitary dwarfism due to resistance to somatomedin: A new syndrome. Eur J Pediatr 1984; 142: 186–188.

    Article  PubMed  CAS  Google Scholar 

  182. Heith-Monnig E, Wohltmann Hi, Mills-Dunlap B, et al. Measurement of insulin-like growth factor I (1GF-1) responsiveness of fibroblasts of children with short stature: Identification of a patient with IGF-1 resistance. J Clin Endocrinol Metab 1987; 64: 501–507.

    Article  Google Scholar 

  183. Shales SM, Toogood A, Rahim A, et al. The diagnosis of growth hormone deficiency in children and adults. Endocr Rev 1998; 19 (2): 203–223.

    Article  Google Scholar 

  184. Penny R. Sequential arginine and insulin tolerance test on the same day. J Clin Endocrinol Metab 1969; 29: 1499–1501.

    Article  PubMed  CAS  Google Scholar 

  185. Fass B. Relative usefulness of three growth hormone screening tests. Amer J Dis Child 1974: 133: 931–933.

    Google Scholar 

  186. Gil-Ad I. Oral clonidine as a growth hormone stimulation test. Lancet, 1979; 2: 278–279.

    Article  PubMed  CAS  Google Scholar 

  187. Weldom VV, Gupta SK. Klingensmith G, et al. Evaluation of growth hormone release in children using arginine and L-dopa in combination. J Pediatr 1975:87:540–544.

    Google Scholar 

  188. Gale EA, Bennett T, MacDonald IA, et al. The physiological effects of insulin-induced hypoglycemia in man: responses at different levels of blood glucose. Clin Sci 1983; 65: 263–271.

    PubMed  CAS  Google Scholar 

  189. Merimee TJ. Rabinowitz D, Fineherg SE. Arginine-initiated release of human growth hormone. N Engl J Med 1969; 280:1434–1438.

    Google Scholar 

  190. Mitchell ML, Byrne Mi, Sanchez Y, et al. Detection of growth hormone deficiency: the glucagon stimulation test. N Engl J Med 1979; 282: 539–541.

    Article  Google Scholar 

  191. Chanoine JP, Rebuffat E, Kahn A, et al. Glucose, growth hormone, cortisol, and insulin responses to glucagon injection in normal infants, aged 0.5–12 months. J Clin Endocrinol Metab 1995; 80: 3032–3035.

    Article  PubMed  CAS  Google Scholar 

  192. Gelato MC, Malozowski S, Caruso-Nicoletti M, et al. Growth hormone responses to OH-releasing hormone during pubertal development in normal boys and girls: comparison to idiopathic short stature and GH deficiency. J Clin Endocrinol Metab 1986; 63: 174–179.

    Article  PubMed  CAS  Google Scholar 

  193. Ghigo E, BelloneJ, Aimaretti G, et al. Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. J Clin Endocrinol Metab 1996; 81: 3323–3327.

    Article  PubMed  CAS  Google Scholar 

  194. Ghigo E. Neutransmitter control of growth hormone secretion. Excerpta Medica 1992; 103–106.

    Google Scholar 

  195. Rosenfeld RG. Evaluation of growth and maturation in adolescence. Pediatr Rev 1982; 4: 175.

    Article  Google Scholar 

  196. Deller JJ, Bolulis MW, Harris WE, et al. Growth hormone response patterns to sex hormone administration in growth retardation. Am J Med Sci 1979; 259: 292–296.

    Article  Google Scholar 

  197. Martin LO, Clark JW, Connor TB. Growth hormone secretion enhanced by androgens. J Clin Endocrinol Metab 1968; 28: 425–428.

    Article  PubMed  CAS  Google Scholar 

  198. Marin G, Domene HM, Barnes KM, et al. The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and argininc-insulin in normal girls and boys. J Clin Endocrinol Metab I994; 79 (2):537–54I.

    Google Scholar 

  199. Zadik Z, Chalew SA, Gilula Z, et al. Reproducibility of growth hormone testing procedures: a comparison between 24-hour integrated concentration and pharmacological stimulation. J Clin Endocrinol Metab 1990; 71: 1127–1130.

    Article  PubMed  CAS  Google Scholar 

  200. Caret JC, Tresca JP. Letrait M, et al. Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study. J Clin Endocrinol Mctah 1997; 82 (7):2117–2121.

    Google Scholar 

  201. Greene SA, Torresani T, Prader A. Growth hormone response to a standardized exercise test in relation to puberty and stature. Arch Dis Child 1987; 62: 53–56.

    Article  PubMed  CAS  Google Scholar 

  202. Spiliotis BE, August GP, Hung W, et al. Growth hormone neurnsccretory dysfunction: a treatable cause of short stature. JAMA 1984; 251: 2223–2230.

    Article  PubMed  CAS  Google Scholar 

  203. Bereu BB, Shulman DJ, Root AW, et al. Growth hormone provocative testing frequently does not reflect endogenous 01–1 secretion. l Clin Endocrinol Metab 1986: 63: 709–716.

    Google Scholar 

  204. Rose SR, Ross IL, Uriarte M. et al. The advantage of measuring stimulated as compared with spontaneous growth hormone levels in the diagnosis of growth hormone deficiency. N Engl J Med 1988; 319: 201–207.

    Article  PubMed  CAS  Google Scholar 

  205. Lanes R. Diagnostic limitations of spontaneous growth hormone measurements in normally growing prepubertal children. Amer J Dis Child 1989, 143: 1284.

    PubMed  CAS  Google Scholar 

  206. Pirazzoli P, Mandini M, Zucchini S. et al. Urinary growth hormone estimation in diagnosing severe growth hormone deficiency. Arch Dis Child 1996; 75: 228–231.

    Article  PubMed  CAS  Google Scholar 

  207. Juul A, Skakkebaek NE. Prediction of the outcome of growth hormone provocative testing in short children by measurement of serum levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3. J Pediatr 1997; 130: 197–204.

    Article  PubMed  CAS  Google Scholar 

  208. Tillman V, BucklerJMH, Kibirige MS, et al. Biochemical test in the diagnosis of childhood growth hormone deficiency..1 Clin Endocrinol Metab 1997; 82: 531–535.

    Article  Google Scholar 

  209. Reiter EO, Lovinger R. The use of commercially available somatomedin-C radioimmunoassay in patients with disorders of growth. J Pediatr 1981; 99: 720–724.

    Google Scholar 

  210. Rosenfeld RG, Wilson DM, Lee PDK, et al. Insulin-like growth factors I and II in the evaluation of growth retardation. J Pediatr 1986; 109 (3): 428–433.

    Article  PubMed  CAS  Google Scholar 

  211. Martin JL, Baxter RC. Insulin-like growth factor-binding protein from human plasma. Purification and characterization. l Biol Chem 1986; 261 (19): 8754–8760.

    CAS  Google Scholar 

  212. Blum WF, Ranke MB, Kietzmann K, et al. A specific radioimmunoassay for the growth hormone-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency. J Clin Endocrinol Metabol 1990; 70: 1292–1298.

    Article  CAS  Google Scholar 

  213. Hasegawa Y, Hasegawa T, Aso T, et al. Usefulness and lirititiation of measurement of insulin-like growth factor binding protein-3 (IGFBP-3) for diagnosis of growth hormone deficiency. Endocrinol Jpn 1992; 1992: 585–591.

    Article  Google Scholar 

  214. Sklar C, Sarafoglou K, Whittam E. Efficacy of insulin-like growth factor-I and IGF-binding protein-3 in predicting the growth hormone response to provocative testing in children treated with cranial irradiation. Acta Endocrinol 1993; 129: 511–515.

    PubMed  CAS  Google Scholar 

  215. Smith WJ, Nam TJ, Underwood LE, et al. Use of insulin-like growth factor binding protein-2 (IGFBP2), IGFBP-3, and IGF-1 for assessing growth hormone status in short children. J Clin Endocrinol Metab 1993; 77: 1294–1299.

    Article  PubMed  CAS  Google Scholar 

  216. Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. Vol. 2. 1959, Stanford, CA: Stanford University Press.

    Google Scholar 

  217. Tanner JM. Assessment of skeletal maturity and prediction of adult height (TW2 method). 1975, New York, Academic Press.

    Google Scholar 

  218. Vogiatzi MG, Copeland, KC. The short child. Pediatr Rev 1998; 19 (3): 92–99.

    Article  PubMed  CAS  Google Scholar 

  219. Bayley N, Penneau SR. Tables for predicting adult height from skeletal age: Revised for use with the Greulich-Pyle hand standards. J Pediatr 1952; 40: 432.

    Google Scholar 

  220. Shulman DI, Beret’, BB. Abstract 1079: Predicted heights in children with growth retardation and bone age delay following 1 to 3 years of growth hormone therapy. in 72nd Annual Meeting of the Endocrine Society. 1990.

    Google Scholar 

  221. Hamilton J, Blaser S, Daneman D. MR imaging in idiopathic growth hormone deficiency. Am J Neuroradiol 1998; 19 (9): 1609–16015.

    Google Scholar 

  222. Fradkin JE. Creutzfcldt-Jakoh disease in pituitary growth hormone recipients. Endocrinologist, 1993; 3: 108.

    Article  Google Scholar 

  223. Stable B, Siegel PT, Clopper RR, et al., Behavior change after growth hormone treatment of children with short stature. J Pediatr 1998; 1998 (3): 366–373.

    Google Scholar 

  224. Attie KM, Hintz RL, Hopwood NJ,et al. Genenthech Collaborative Study Group. Growth hormone treatment of idiopathic short stature and its effect on the onset and tempo of puberty (abstract). Pediatr Res 1992; 31: 72A.

    Google Scholar 

  225. Hopwood NJ, Hintz RI,, Gertner JM, et al. Growth response of children with non-growth hormone deficiency and marked short stature during three year of growth hormone therapy. J Pediatr 1993; 123: 215–227.

    Article  PubMed  CAS  Google Scholar 

  226. Moore WV, Moore KC, Gifford R, et al. Long-term treatment with growth hormone of children with short stature and normal growth hormone secretion. J Pediatr 1992; 120: 702–708.

    Article  PubMed  CAS  Google Scholar 

  227. Kawai M, Momoi T, Yorifuji T, et al. Unfavorable effects of growth hormone therapy on the final height of boys with short stature not caused by growth hormone deficiency. J Pediatr 1997; 130 (2): 205–209.

    Article  PubMed  CAS  Google Scholar 

  228. Hintz RL, Attie KM, Baptista J, et al. Effect of growth hormone treatment on adult height of children with idiopathic short stature. N Engl J Med 1999; 340: 502–507.

    Article  PubMed  CAS  Google Scholar 

  229. Duck SC, Rappaport R. Long-term treatment with GHRH (1–44) amide in prepubertal children with classical growth hormone deficiency. J Pediatr Endocrinol Metab 1999; 12 (4): 531–536.

    Article  PubMed  CAS  Google Scholar 

  230. MacGillivray MH, Blithe SL. Bushels JG, et al. Current dosing of growth hormone in children with growth hormone deficiency: how physiologic? Pediatrics 1998; 102 (2 pt 3):527–530.

    Google Scholar 

  231. Bell JJ. Dana K. Lack of correlation between g’rowth hormone provocative test results and subsequent growth rate during growth hormone therapy. Pediatrics 1998; 102 (2 pt 3): 518–520.

    PubMed  CAS  Google Scholar 

  232. Cutfield W, Lindberg A, Albcrtsson Wikland K, et al. Final height in idiopathic growth hormone deficiency: The KIGS experience. KIGS international board. Acta Paediatrica 1999; 88 (428): 72–75.

    Article  PubMed  CAS  Google Scholar 

  233. August GP, Julius JR, Blethen SL. Adult height in children with growth hormone deficiency who are treated with biosynthetic growth hormone: The National Cooperative Growth Study experience. Pediatrics 2001; 102 (2 pt 3): 512–516.

    Google Scholar 

  234. Saggese G, Federico G, Barsanti S. Management of puberty in growth hormone deficient children. J Pediatr Endocrinol Metab 1999; 12: 329–334.

    PubMed  Google Scholar 

  235. Blethen SL, Alien DB, Graves D, et al. Safety of recombinant deoxyribonucleic acid-derived growth hormone: The National Cooperative Growth Study experience. J Clin Endocrinol Metab 1996; 81 (5): 1704–1710.

    Article  PubMed  CAS  Google Scholar 

  236. Kaufman FR, Sy JP. Regular monitoring of bone age is useful in children treated with growth hormone. Pediatrics 1999: 104 (4 pt 2): 1039–1042.

    PubMed  CAS  Google Scholar 

  237. Wilson DM. Regular monitoring of bone age is not useful in children treated with growth hormone. Pediatrics 1999: 104 (4 pt 2): 1036–1039.

    PubMed  CAS  Google Scholar 

  238. Cutfield WS, Wilton P, Bennmarker H, et al. Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment. Lancet 2000. 355 (9204): 610–13.

    Article  PubMed  CAS  Google Scholar 

  239. Watanabe S, Yamaguchi N, Tsunematsu Y. et al. Risk factors for leukemia occurring among growth hormone users. Spit J Cancer 1989; 80: 822.

    Article  CAS  Google Scholar 

  240. Nishi Y. Tanaka T, Kakano K. et al. Recent status in the occurrence of leukemia in growth-hormonetreated patients in Japan. GH Treatment Study Committee of the Foundation for Growth Science, Japan. J Clin Endocrinol Metab 1999; 84 (6): 1961–1965.

    Article  PubMed  CAS  Google Scholar 

  241. Fradkin JE, Millis JL, Schonberger LB, et al. Risk of leukemia after treatment with pituitary growth hormone, JAMA 1993; 270 (23): 2829–2832.

    Article  PubMed  CAS  Google Scholar 

  242. Holly JM, Gunnell DJ, Davey Smith G, Growth hormone, IGF-I and cancer. Less intervention to avoid cancer? More intervention to prevent cancer? J Endocrinol 1999; 162 (3): 321–330.

    Article  PubMed  CAS  Google Scholar 

  243. Wilton P. Adverse events during GH treatment: 10 years’ experience in KIGS, a pharmacoepidemiological survey, in Growth Hormone Therapy in KIGS–10 Years’ Experience. Ranke, MB and Wilton P, eds. 1999, Johann Ambrosius Barth Verlag: Heidelberg. p. 349–364

    Google Scholar 

  244. Moshang T, Rundle AC, Graves DA, et al. Brain tumor recurrence in children treated with growth hormone: The National Cooperative Growth Study experience. J Pediatr 1996; 128: S4–7.

    Article  PubMed  Google Scholar 

  245. Packer RJ, Boyctt JM, Janss AJ, et al. Growth hormone replacement therapy (01–1 Rx) for children with 01-I deficiency secondary to treatment for medulloblastoma is not associated with increased likelihood of disease relapse. J Clin Oncol 2001; 18: 480.

    Google Scholar 

  246. Wyatt D. Melanocytic nevi in children treated with growth hormone. Pediatrics 1999; 104 (4 pt 2): 1045–1050.

    PubMed  CAS  Google Scholar 

  247. Crock PA, McKenzie JD, Nicoll AM, et al. Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand. Acta Paediatrica 1998; 87 (4): 381–386.

    Article  PubMed  CAS  Google Scholar 

  248. Blethen SL, Rundle AC, o.b.o.t.G.N.C.G.S. (NCGS), Slipped capital femoral epiphysis in children treated with growth hormone. Horm Res 1996; 46: 113–116.

    Article  PubMed  CAS  Google Scholar 

  249. Cuneo RC, Salomon F, McGauley GA, et al. The growth hormone deficiency syndrome in adults. Clin Endocrinol 1992; 37: 387–397.

    Google Scholar 

  250. de Boer H, Blok GJ, van der Veen EA. Clinical aspects of growth hormone deficiency in adults. Endocr Rev 1995; 16: 63–86.

    Article  PubMed  Google Scholar 

  251. Cowan FJ, Evans WD, Gregory JW. Metabolic effects of discontinuing growth hormone treatment. Arch Dis Child 1999; 80 (6): 517–523.

    Article  PubMed  CAS  Google Scholar 

  252. Ter Maaten JC, de Boer H, Kamp 0, et al. Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency..1 Clin Endocrinol Metab 1999; 84 (7): 2373–2380.

    Article  Google Scholar 

  253. Binnerts A, Swart OR, Wilson JHP. et al. The effect of growth hormone administration in growth hormone deficient adults on hone, protein, carbohydrate and lipid homeostasis, as well as on body composition. Clin Endocrinol 1992; 37: 79–87.

    Article  CAS  Google Scholar 

  254. Jorensen JOL, Thuesen L, Muller J, et al. Three years of growth hormone treatment in growth hormone deficient adults: near normalization of body composition and physical performance. Eur J Endocrinol 1994; 130: 224–228.

    Article  Google Scholar 

  255. Gomez JM, Gomez N, Fiter J, et al. Effects of long-term treatment with OH in the bone mineral density of adults with hypopituitarism and GH deficiency after discontinuation of GH replacement. Horm Metab Res 2000; 32 (2): 66–70.

    Article  PubMed  CAS  Google Scholar 

  256. Amato G, Izzo G, la Montagna G, et al. Low-dose recombinant human growth hormone normalizes hone metabolism and cortical bone density and improves trabecular bone density in growth hormone deficient adults without causing adverse effects. Clin Endocrinol 1996; 45A: 27–32.

    Article  CAS  Google Scholar 

  257. Amato G, Carella C, Fazio S, et aI. Body composition. bone metabolism, and heart structure and function before and after GH replacement therapy at low doses. J Clin Endocrinol Metab 1993 1993: 1671–1676.

    Article  Google Scholar 

  258. Cacciari E, Tassoni P. Cicognani A, et al. Value and limits of pharmacological and physiological tests to diagnose growth hormone (CH) deficiency and predict therapy response: first and second retesting during replacement therapy of patients defined as GH deficient. J Clin Endocrinol Metab 1994; 79: 1663–1669.

    Article  PubMed  CAS  Google Scholar 

  259. Tauber M, Moulin P, Picnkowski C.ct al. Growth hormone (OH) retesting and auxological data in 131 GH-deficient patients after completion of treatment. J Clin Endocrinol Metab 1997; 82: 352–356.

    Article  PubMed  CAS  Google Scholar 

  260. Longobardi S, Merola 13, Pivonello R, et al. Reevaluation of growth hormone (GH) secretion in 69 adults diagnosed as OH-deficient patients during childhood. J Clin Endocrinol Metab 1996; 81: 1244–1247.

    Article  PubMed  CAS  Google Scholar 

  261. Allen DB. Issues in the transition from childhood to adult growth hormone therapy. Pediatrics 1999; 104 (4 pt 2): 1004–1010.

    PubMed  CAS  Google Scholar 

  262. Hoffman DM, O’Sullivan AJ, Baxter RC, et al. Diagnosis of growth hormone deficiency in adults. Lancet 1994; 343: 1064–1068.

    Article  PubMed  CAS  Google Scholar 

  263. Gills MS, Toogood AA. O’ Neill PA, et al. Urinary growth hormone (GH), insulin-like growth factor f (1GF-l), and ‘GE-binding protein-3 measurements in the diagnosis of adult GH deficiency. J Clin Endocrinol Metab 1998; 83 (7):2562–2565.

    Google Scholar 

  264. Hilding A, Hall K, Wivall-Helleryd 1L, et al. Serum levels of insulin-like growth factor I in 152 patients with growth hormone deficiency, aged 19–82 years, in relation to those in healthy subjects. J Clin Endocrinot Metab 1999; 84 (6): 2013–2019.

    Article  CAS  Google Scholar 

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Authors
  1. Diego Botero MD
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  2. Olcay Evliyaoglu MD
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  3. Laurie E. Cohen MD
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Editor information

Editors and Affiliations

  1. Section of Pediatric Endocrinology, University of Chicago Medical Center, Chicago, IL, USA

    Sally Radovick MD

  2. Division of Endocrinology, Children’s Hospital of Buffalo, Buffalo, NY, USA

    Margaret H. MacGillivray MD

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© 2003 Springer Science+Business Media New York

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Botero, D., Evliyaoglu, O., Cohen, L.E. (2003). Hypopituitarism. In: Radovick, S., MacGillivray, M.H. (eds) Pediatric Endocrinology. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-336-1_1

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  • DOI: https://doi.org/10.1007/978-1-59259-336-1_1

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-268-1

  • Online ISBN: 978-1-59259-336-1

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