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Unilateral agenesis of internal carotid artery associated with congenital combined pituitary hormone deficiency and pituitary stalk interruption without HESX1, LHX4 or OTX2 mutation: a case report

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Abstract

Agenesis of internal carotid artery (ICA) is an unusual finding in subjects with congenital Combined Pituitary hormone deficiency (CPHD) with only nine cases being reported to date but to our best knowledge none of them was genetically investigated. A 10-years old girl presented with severe growth failure (height 103 cm) with substantial bone age delay (3 years). She had no history of perinatal insults or familial CPHD. There was no evidence of mental retardation or craniofacial dysmorphism or ophtalmological abnormalities. She was first diagnosed with GH and TSH deficiency. Cerebral magnetic resonance imaging (MRI) showed hypoplastic anterior pituitary, flat sella turcica, absent pituitary stalk with ectopic posterior pituitary as well as agenesis of the left ICA and the left carotid canal. Genomic analysis of pituitary transcription factor HESX1, LHX4 and OTX2 showed no mutations. Treatment with GH and thyroxine was started. The patient remained free of neurovascular symptoms for 5 years but she presented at the age of 15 years with delayed puberty related to an evolving gonadotropin deficiency. ICA agenesis associated with CPHD is unusual and is often asymptomatic in children. Since the CPHD with pituitary stalk interruption cannot be due to HESX1, LHX4 or OTX2 mutation in our case, other pathogenetic mechanisms may be responsible for CPHD associated with unilateral ICA agenesis.

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References

  1. Reynaud R, Gueydan M, Saveanu A, Vallette-Kasic S, Enjalbert A, Brue T, Barlier A (2006) Genetic screening of combined pituitary hormone deficiency: experience in 195 patients. J Clin Endocrinol Metab 91:3329–3336

    Article  PubMed  CAS  Google Scholar 

  2. Kleinberg D, Melmed S (2008) Pituitary failure. In: Kroenenberg (ed) Williams textbook of endocrinology, 10th edn. Elsevier, Philadelphia, pp 235–263

    Google Scholar 

  3. Mehta A, Hindmarsh PC, Mehta H, Turton JPG, Russel-Eggitt I, Taylor D, Chong WK, Dattani MT (2009) Congenital hypopituitarism: clinical, molecular and neuroradiological correlates. Clin Endocrinol (Oxf) 71:376–382

    Article  Google Scholar 

  4. Triulzi F, Scotti G, Di Natale B, Pellini C, Lukezic M, Scognamiglio M, Chiumello G (1994) Evidence of a congenital midline brain anomaly in pituitary dwarfs: a magnetic resonance imaging study in 101 patients. Pediatrics 93:409–416

    PubMed  CAS  Google Scholar 

  5. Shulman DI, Martinez CR (1996) Association of ectopic posterior pituitary and anterior pituitary hypoplasia with absence of the left internal carotid. J Pediatr Endocrinol Metab 9:539–542

    Article  PubMed  CAS  Google Scholar 

  6. Tanaka R, Tokuda M, Shinakawa S, Okasora K, Suzuki S (1996) A multiple pituitary hormone deficiency patient with anomaly of internal carotid artery. Program of the 21st international symposium on growth hormone and growth factors in endocrinology and metabolism

  7. Blustajn J, Netchine I, Frédy D, Bakouche P, Piekarski JD, Meder JF (1999) Dysgenesis of the internal carotid artery associated with transsphenoidal encephalocele: a neural crest syndrome? AJNR Am J Neuroradiol 20:1154–1157

    PubMed  CAS  Google Scholar 

  8. Mellado JM, Merino X, Ramos A, Salvadό E, Saurί A (2001) Agenesis of the internal carotid artery with a trans-sellar anastomosis: CT and MRI findings in late-onset congenital hypopituitarism. Neuroradiology 43:237–241

    Article  PubMed  CAS  Google Scholar 

  9. Moon WJ, Porto L, Lanfermann H, Weis R, Zanella FE (2002) Agenesis of internal carotid artery associated with congenital anterior hypopituitarism. Neuroradiology 44:138–142

    Article  PubMed  CAS  Google Scholar 

  10. Inamo Y, Harada K (2003) Agenesis of the internal carotid artery and congenital pituitary hypoplasia: proposal of a cause of congenital hypopituitarism. Eur J Pediatr 162:610–612

    Article  PubMed  Google Scholar 

  11. Kjellin IB, Kaiserman KB, Curran JG, Geffner ME (1999) Aplasia of right internal carotid artery and hypopituitarism. Pediatr Radiol 29:586–588

    Article  PubMed  CAS  Google Scholar 

  12. Dattani MT, Martinez-Barbera JP, Thomas PQ, Brickman JM, Gupta R, Mårtensson IL, Toresson H, Fox M, Wales JK, Hindmarsh PC, Krauss S, Beddington RS, Robinson IC (1998) Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat Genet 19:125–133

    Article  PubMed  CAS  Google Scholar 

  13. Machinis K, Pantel J, Netchine I, Léger J, Camand OJ, Sobrier ML, Dastot-Le Moal F, Duquesnoy P, Abitbol M, Czernichow P, Amselem S (2001) Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4. Am J Hum Genet 69:961–968

    Article  PubMed  CAS  Google Scholar 

  14. Tajima T, Ohtake A, Hoshino M, Amemiya S, Sasaki N, Ishizu K, Fujieda K (2009) OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary. J Clin Endocrinol Metab 94:314–319

    Article  PubMed  CAS  Google Scholar 

  15. Mehta A, Dattani MT (2005) Congenital disorders of the hypothalamic-pituitary axis. In: Brook C, Clayton PE, Brown RS (eds) Clinical pediatric endocrinology. Blackwell, Oxford, pp 67–89

    Chapter  Google Scholar 

  16. Kiritsi O, Noussios G, Tsitas K, Lappas D (2011) Unilateral agenesis of the internal carotid artery presented as transient ischaemic attack: a case report. Surg Radiol Anat 34:475–477

    Google Scholar 

  17. Pilleul F, Guibaus L, Badinand N, Rouviere O, Pracros JP (2001) Bilateral internal carotid agenesis. Value of CT angiography and correlation to embryogenesis. Eur Radiol 11:858–860

    Article  PubMed  CAS  Google Scholar 

  18. Rosenfeld RG, Cohen P (2008) Disorders of growth hormone/insulin-like growth factor secretion and action. In: Fletcher J (ed) Pediatric endocrinology. Saunders, Philadelphia, pp 254–334

    Chapter  Google Scholar 

  19. Kelberman D, Rizzoti K, Lovell-Badge R, Robinson I, Dattani MT (2009) Genetic regulation of pituitary gland development in human and mouse. Endocr Rev 30:790–829

    Article  PubMed  CAS  Google Scholar 

  20. Sobrier ML, Maghnie M, Vié Luton MP, Secco A, Di Lorgi N, Lorini R, Amselem S (2006) Novel HESX1 mutations associated with a life threatening neonatal phenotype, pituitary aplasia, but normally located posterior pituitary and no optic nerve abnormalities. J Clin Endocrinol Metab 91:4528–4536

    Article  PubMed  CAS  Google Scholar 

  21. Bennett CP, Betts DR, Seller MJ (1991) Deletion 14q(q22q23) associated with anophtalmia and pituitary hypoplasia. J Med Genet 28:280–281

    Article  PubMed  CAS  Google Scholar 

  22. Ragge NK, Brown AG, Poloschek CM, Lorenz B, Henderson RA, Clarke MP, Russell-Eggitt I, Fielder A, Gerrelli D, Martinez-Barbera JP, Ruddle P, Hurst J, Collin JR, Salt A, Cooper ST, Thompson PJ, Sisodiya SM, Williamson KA, Fitzpatrick DR, van Heyningen V, Hanson IM (2005) Heterozygous mutations of OTX2 cause severe ocular malformations. Am J Hum Genet 76:1008–1022

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The GENHYPOPIT network for the study of genetic determinants of hypopituitarism, coordinated by Thierry Brue (thierry.brue@mail.ap-hm.fr), was funded by the Groupement d’Intérêt Scientifique Institut des Maladies Rares (GISMR0201) and the Programme Hospitalier de Recherche Clinique (PHRC 25/2003, French Ministry of Health).

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Authors and Affiliations

  1. Department of Endocrinology and Diabetes, Rabta University Hospital, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia

    Faïza Lamine, Faouzi Kanoun, Melika Chihaoui & Hédia Slimane

  2. Department of Molecular Biology, Hôpital de la Conception, 13385, Marseille, France

    Alexandru Saveanu, Anne Barlier & Alain Enjalbert

  3. Department of Radiology, Rabta University Hospital, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia

    Emna Menif

  4. Department of Endocrinology, Centre Hospitalo-Universitaire La Timone, 13385, Marseille, France

    Thierry Brue

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  1. Faïza Lamine
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  2. Faouzi Kanoun
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  3. Melika Chihaoui
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  4. Alexandru Saveanu
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  5. Emna Menif
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  6. Anne Barlier
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  7. Alain Enjalbert
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  8. Thierry Brue
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  9. Hédia Slimane
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Correspondence to Faïza Lamine.

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Lamine, F., Kanoun, F., Chihaoui, M. et al. Unilateral agenesis of internal carotid artery associated with congenital combined pituitary hormone deficiency and pituitary stalk interruption without HESX1, LHX4 or OTX2 mutation: a case report. Pituitary 15 (Suppl 1), 81–86 (2012). https://doi.org/10.1007/s11102-012-0411-y

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  • DOI: https://doi.org/10.1007/s11102-012-0411-y

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