Journal of Endocrinological Investigation

, Volume 29, Issue 3, pp 208–213 | Cite as

Congenital adenohypophysis aplasia: Clinical features and analysis of the transcriptional factors for embryonic pituitary development

  • T. Arrigo
  • M. Wasniewska
  • F. De Luca
  • M. Valenzise
  • F. Lombardo
  • D. Vivenza
  • T. Vaccaro
  • E. Coradi
  • A. Biason-Lauber
Original Articles


Anterior pituitary agenesis (APA) has very rarely been reported. Therefore, its phenotypical and genotypical features are not well known. The aim of this study was to ascertain whether the clinical picture in 4 subjects with APA and multiple pituitary hormone deficiencies (MPHD) was different compared to the one observed in a selected control group consisting of 7 MPHD individuals with hypoplastic (and not aplastic) adenohypophysis and pituitary stalk interruption syndrome. Another goal was to investigate genetic basis of APA by analyzing for the first time in this condition many of the transcriptional factors which are required for both structural development and cellular differentiation of hypophysis. Age at diagnosis was significantly lower in APA children than in controls (1.5±2.3 vs 11.1 ±7.6 yr, p<0.0005). Microphallus and neonatal cholestasis were observed only in APA subjects (chi-squared=4.3, p<0.05) and also neonatal hypoglycemia was more frequent in APA patients than in controls (X2=4.05, p<0.05). Molecular analyses of the genes of the transcriptional factors POU1F1, PROP1, LHX3, LHX4, ISL1 and HESX1 detected no mutations in APA patients. Conclusions: a) if compared with a selected cohort of MPHD patients with both adenohypophysis hypoplasia and pituitary stalk interruption syndrome, the ones with APA show an earlier and more severe picture of hypopituitarism; b) mutations in several transcription factors that are known to be essential for the development of Rathke’s pouch are not necessarily found in humans with APA. (J. Endocrinol. Invest. 29: 208–213, 2006)

Key Words

Multiple pituitary hormone deficiency anterior pituitary agenesis LHX3 LHX4 ISL 1 HESX1 


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  1. 1.
    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: 920–3.PubMedCrossRefGoogle Scholar
  2. 2.
    Fisher DA. Effectiveness of newborn screening programs for congenital hypothyroidism: prevalence of missed cases. Pediatr Clin North Am 1987, 34: 881–90.PubMedGoogle Scholar
  3. 3.
    De Luca F, Bernasconi S, Blandino A, Cavallo L, Cisternino M. Auxological, clinical and neuroradiological findings in infants with early onset growth hormone deficiency. Acta Paediatr 1995, 84: 561–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Herber SM, Milner RDG. Growth hormone deficiency presenting under age 2 years. Arch Dis Child 1984, 59: 557–60.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Wit JM, Van Hunen H. Growth of infants with neonatal growth hormone deficiency. Arch Dis Child 1992, 67: 920–4.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Kosaki K, Matsuo N, Tamai S, Miyama S, Momoshima S. Isolated aplasia of the anterior pituitary as a cause of congenital panhypopituitarism. Horm Res 1991, 35: 226–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Beregszaszi M, Leger J, Garel C, et al. Nasal pyriform aperture stenosis and absence of the anterior pituitary gland: Report of two cases. J Pediatr 1996, 128: 858–61.PubMedCrossRefGoogle Scholar
  8. 8.
    Zucchini S, Mazzanti L, Ambrosetto P, Salardi S, Cacciari E. Unusual magnetic resonance imaging findings in subjects with hypopituitarism: Report of 4 cases. J Pediatr Endocrinol Metab 1998, 11: 35–44.PubMedGoogle Scholar
  9. 9.
    Al-Gazali LI, Sztriha L, Punnose J, Shather W, Nork M. Absent pituitary gland and hypoplasia of the cerebellar vermis associated with partial ophthalmoplegia and postaxial polydactyly: A variant of orofaciodigital syndrome VI or a new syndrome? J Med Genet 1999, 36: 161–6.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Scommegna S, Galeazzi D, Picone S, et al. Neonatal Identification of pituitary aplasia: A life-saving diagnosis. Horm Res 2004, 62: 10–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Takuma N, Sheng HZ, Furuta Y, et al. Formation of Rathke’s pouch requires dual induction from the diencephalons. Development 1998, 125: 4835–40.PubMedGoogle Scholar
  12. 12.
    Parks JS, Brown MR, Hurley DL, Phelps CJ, Wajnrajch MP. Heritable disorders of pituitary development. J Clin Endocrinol Metab 1999, 84: 4362–70.PubMedGoogle Scholar
  13. 13.
    Arrigo T, Crisafulli G, Salamone A, Cucinotta D, De Luca F. Adult height exceeding target height in a patient with congenital panhypopituitarism diagnosed after the age of 25 years. J Pediatr Endocrinol 1994, 7: 269–72.PubMedCrossRefGoogle Scholar
  14. 14.
    Arrigo T, De Luca F, Maghnie M, et al. Relationships between neuroradiological and clinical features in apparently idiopathic hypopituitarism. Eur J Endocrinol 1998, 139: 84–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Argyropoulou M, Perignon F, Brunella F, Brauner R, Rap-paport R. Height of normal pituitary gland as a function of age evaluated by magnetic resonance imaging in children. Pediatr Radiol 1991, 21: 247–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Ohta K, Nobukuni Y, Mitsubuchi H, Fujimoto S, Matsuo N, Inagaki H, Endo F, Matsuda I. Mutations in the Pit-1 gene in children with combined pituitary hormonedeficiency. Biochem Biophys Res Commun 1992, 15: 851–5.CrossRefGoogle Scholar
  17. 17.
    Paracchini R, Giordano M, Corrias A, et al. Two new PROP1 gene mutations responsible for compound pituitari hormone deficiency. Clin Genet 2003, 64: 142–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Schmitt S, Biason-Lauber A, Betts D, Schoenle EJ. Genomic structure, chromosomal localization, and expression pattern of the human LIM-homeobox3 (LHX3) gene. Biochem Biophys Res Commun 2000, 274: 49–56.PubMedCrossRefGoogle Scholar
  19. 19.
    Johnson JD, Albritton WL, Werthemann U, Chistiansen RO. Hypoplasia of the anterior pituitary and neonatal hypoglycaemia. J Pediatr 1973, 82: 634–41.PubMedCrossRefGoogle Scholar
  20. 20.
    Herman SP, Baggenstoss AH, Cloutier MD. Liver disfunction and histologic abnormalities in neonatal hypopituitarism. J Pediatr 1975, 87: 892–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Kauschansky A, Genel M, Smith GJ. Congenital hypopituitarism in female infants. Its association with hypoglycaemia and hypothyroidism. Am J Dis Child 1979, 133: 165–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Heinrichs C, de Zegher F, Vansnick F, Vokaer A, Christophe, Frankenne F. Fetal hypopituitarism: Perinatal endocrine and morphological studies in two cases. Acta Paediatr 1994, 83: 448–51.PubMedCrossRefGoogle Scholar
  23. 23.
    Ellaway CJ, Silink M, Cowell CT, et al. Cholestatic jaundice and congenital hypopituitarism. J Paediatr Child Health 1995, 31: 51–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Choo-Kang Chen-Chih LR, Sun J, Counts DR. Cholestasis and hypoglicemia. Manifestation of congenital anterior hypopituitarism. J Clin Endocrinol Metab 1996, 81: 2786–9.Google Scholar
  25. 25.
    Arrigo T, Wasniewska M, Ghizzoni L, Messina MF, Crisafulli G, De Luca F. Liver disfunction associated with congenital hypopituitarism. J Endocrinol Invest 2000, 23: 215–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Sheehan AG, Martin SR, Stephure D, Scott RB. Neonatal cholestasis, hypoglycaemia, and congenital hypopituitarism. J Pediatr Gastroenterol Nutr 1992, 14: 426–30.PubMedCrossRefGoogle Scholar
  27. 27.
    Pulichino AM, Vallette-Kasic S, Couture C, et al. Human and mouse TPIT gene mutations cause early onset pituitary ACTH deficiency. Genes Dev 2003, 17: 711–6.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Ericson J, Norlin S, Jessell TM, Edlund T. Integrated FGF and BMP signaling controls the progression of progenitor cell differentiation and the emergence of pattern in the embryonic anterior pituitary. Development 1998, 125: 1005–15.PubMedGoogle Scholar
  29. 29.
    Dattani MT, Robinson IC. The molecular basis for developmental disorders of the pituitary gland in man. Clin Genet 2000, 57: 337–46.PubMedCrossRefGoogle Scholar
  30. 30.
    Thomas PQ, Dattani MT, Brickman JM, et al. Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia. Hum Mol Gen 2001, 10: 39–45.PubMedCrossRefGoogle Scholar
  31. 31.
    Dasen JS, Barbera JP, Herman TS, et al Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis. Genes Dev 2001, 15: 3193–207.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Brickman JM, Clements M, Tyrell R, et al. Molecular effects of novel mutations in Hesx1/HEXS1 associated with human pituitary disorders. Development 2001, 128: 5189–99.PubMedGoogle Scholar
  33. 33.
    Sobrier ML, Netchine I, Heinrichs C, et al. Alu-element insertion in the Homeodomain of HESX1 and aplasia of the anterior pituitary. Hum Mutat 2005, 25: 503–11.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2006

Authors and Affiliations

  • T. Arrigo
    • 1
  • M. Wasniewska
    • 1
  • F. De Luca
    • 1
  • M. Valenzise
    • 1
  • F. Lombardo
    • 1
  • D. Vivenza
    • 2
  • T. Vaccaro
    • 3
  • E. Coradi
    • 3
  • A. Biason-Lauber
    • 3
  1. 1.Department of PediatricsUniversity of MessinaMessina
  2. 2.Unit of Pediatrics, Department of Medical SciencesUniversity of Piemonte OrientaleNovaraItaly
  3. 3.Division of Pediatric Endocrinology and DiabetologyUniversity Children HospitalZürichSwitzerland

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