Onset of pituitary hormone deficiencies in optic nerve hypoplasia: a temporal trend analysis of 32 children at Mayo Clinic

Heather D. Wadams 1 , 2 , Nidhi Guptahttp://orcid.org/https://orcid.org/0000-0001-6485-3318 2 , 3 , Paul Novotny 4  and Peter J. Tebben 2 , 5
  • 1 Division of Pediatric Endocrinology, Department of Pediatrics, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
  • 2 Division of Endocrinology and Metabolism, Department of Pediatric and Adolescent Medicine, Mayo Clinic, MN, Rochester, USA
  • 3 Department of Pediatrics, Vanderbilt University Medical Center, TN, Nashville, USA
  • 4 Department of Health Sciences Research, Mayo Clinic, MN, Rochester, USA
  • 5 Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, MN, Rochester, USA
Heather D. Wadams
  • Division of Pediatric Endocrinology, Department of Pediatrics, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
  • Division of Endocrinology and Metabolism, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
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, Nidhi GuptaORCID iD: https://orcid.org/0000-0001-6485-3318
  • Division of Endocrinology and Metabolism, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
  • Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA
  • orcid.org/0000-0001-6485-3318
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, Paul Novotny and Peter J. Tebben
  • Corresponding author
  • Division of Endocrinology and Metabolism, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
  • Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN, USA
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Abstract

Background

The objective of this study was to evaluate the age at onset and frequency of individual pituitary hormone deficiencies (PHDs) in optic nerve hypoplasia (ONH).

Methods

We performed a retrospective chart review of patients ≤21 years of age evaluated between 1996 and 2014. Patients were included if they had: (1) ONH diagnosed by an ophthalmologist and/or magnetic resonance imaging (MRI), (2) documentation of pituitary hormone function on at least two separate occasions and (3) at least one PHD documented or a midline abnormality of the brain on MRI.

Results

Thirty-two patients (18 females, 14 males) were included (median age, 8 years [range, 1.1–21.0 years]). All patients had ONH (bilateral, n = 31; unilateral, n = 1) and at least one midline abnormality of the brain. At least one PHD was present in 75% of patients (n = 24). The remaining 25% of patients (n = 8) did not develop any PHD at least until the last follow-up (<2–8.6 years of follow-up), despite the presence of ONH and a midline abnormality of the brain. The median age (years) at diagnosis of antidiuretic hormone (ADH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and growth hormone (GH) deficiencies was 0.5, 0.6, 0.7 and 1.6, respectively. Twenty-three percent of all PHDs were identified during the neonatal period, 56% by 12 months and 72% by 36 months of age. The latest age at diagnosis of GH, ACTH and TSH deficiencies was 9.6, 9.9 and 12.6 years, respectively.

Conclusions

The majority of the PHDs in ONH develop within the first 3 years of life. We propose evaluation for endocrinopathies at the time of diagnosis of ONH, with repeat assessment for new deficiencies every 3–4 months until age 3 years and at least semi-annually until growth and puberty are complete.

  • 1.

    Garcia-Filion P, Epport K, Nelson M, Azen C, Geffner ME, et al. Neuroradiographic, endocrinologic, and ophthalmic correlates of adverse developmental outcomes in children with optic nerve hypoplasia: a prospective study. Pediatrics 2008;121:e653–9.

    • Crossref
    • PubMed
    • Export Citation
  • 2.

    Mohney BG, Young RC, Diehl N. Incidence and associated endocrine and neurologic abnormalities of optic nerve hypoplasia. JAMA Ophthalmol 2013;131:898–902.

    • Crossref
    • PubMed
    • Export Citation
  • 3.

    Patel L, McNally RJ, Harrison E, Lloyd IC, Clayton PE. Geographical distribution of optic nerve hypoplasia and septo-optic dysplasia in Northwest England. J Pediatr 2006;148:85–8.

    • Crossref
    • PubMed
    • Export Citation
  • 4.

    Garne E, Rissmann A, Addor MC, Barisic I, Bergman J, et al. Epidemiology of septo-optic dysplasia with focus on prevalence and maternal age—a EUROCAT study. Eur J Med Genet 2018;61:483–8.

    • Crossref
    • PubMed
    • Export Citation
  • 5.

    Birkebaek NH, Patel L, Wright NB, Grigg JR, Sinha S, et al. Optic nerve size evaluated by magnetic resonance imaging in children with optic nerve hypoplasia, multiple pituitary hormone deficiency, isolated growth hormone deficiency, and idiopathic short stature. J Pediatr 2004;145:536–41.

    • Crossref
    • PubMed
    • Export Citation
  • 6.

    Ramakrishnaiah RH, Shelton JB, Glasier CM, Phillips PH. Reliability of magnetic resonance imaging for the detection of hypopituitarism in children with optic nerve hypoplasia. Ophthalmology 2014;121:387–91.

    • Crossref
    • PubMed
    • Export Citation
  • 7.

    Borchert M. Reappraisal of the optic nerve hypoplasia syndrome. J Neuroophthalmol 2012;32:58–67.

    • Crossref
    • PubMed
    • Export Citation
  • 8.

    De Morsier G. [Studies on malformation of cranio-encephalic sutures. III. Agenesis of the septum lucidum with malformation of the optic tract]. Schweiz Arch Neurol Psychiatr 1956;77:267–92.

    • PubMed
    • Export Citation
  • 9.

    St John JR, Reeves DL. Congenital absence of the septum pellucidum: a review of the literature with case report. Am J Surg 1957;94:974–80.

    • Crossref
    • PubMed
    • Export Citation
  • 10.

    Alyahyawi N, Dheensaw K, Islam N, Aroichane M, Amed S. Pituitary dysfunction in pediatric patients with optic nerve hypoplasia: a retrospective cohort study (1975–2014). Horm Res Paediatr 2018;89:22–30.

    • Crossref
    • PubMed
    • Export Citation
  • 11.

    Oatman OJ, McClellan DR, Olson ML, Garcia-Filion P. Endocrine and pubertal disturbances in optic nerve hypoplasia, from infancy to adolescence. Int J Pediatr Endocrinol 2015;2015:8.

    • Crossref
    • PubMed
    • Export Citation
  • 12.

    Garcia-Filion P, Borchert M. Optic nerve hypoplasia syndrome: a review of the epidemiology and clinical associations. Curr Treat Options Neurol 2013;15:78–89.

    • Crossref
    • PubMed
    • Export Citation
  • 13.

    Ahmad T, Garcia-Filion P, Borchert M, Kaufman F, Burkett L, et al. Endocrinological and auxological abnormalities in young children with optic nerve hypoplasia: a prospective study. J Pediatr 2006;148:78–84.

    • Crossref
    • PubMed
    • Export Citation
  • 14.

    Webb EA, Dattani MT. Septo-optic dysplasia. Eur J Hum Genet 2010;18:393–7.

  • 15.

    Polizzi A, Pavone P, Iannetti P, Manfre L, Ruggieri M. Septo-optic dysplasia complex: a heterogeneous malformation syndrome. Pediatr Neurol 2006;34:66–71.

    • Crossref
    • PubMed
    • Export Citation
  • 16.

    Brodsky MC, Glasier CM. Optic nerve hypoplasia. Clinical significance of associated central nervous system abnormalities on magnetic resonance imaging. Arch Ophthalmol 1993;111:66–74.

    • Crossref
    • PubMed
    • Export Citation
  • 17.

    Birkebaek NH, Patel L, Wright NB, Grigg JR, Sinha S, et al. Endocrine status in patients with optic nerve hypoplasia: relationship to midline central nervous system abnormalities and appearance of the hypothalamic-pituitary axis on magnetic resonance imaging. J Clin Endocrinol Metab 2003;88:5281–6.

    • Crossref
    • PubMed
    • Export Citation
  • 18.

    Kelberman D, Dattani MT. Genetics of septo-optic dysplasia. Pituitary 2007;10:393–407.

    • Crossref
    • PubMed
    • Export Citation
  • 19.

    Morishima A, Aranoff GS. Syndrome of septo-optic-pituitary dysplasia: the clinical spectrum. Brain Dev 1986;8:233–9.

    • Crossref
    • PubMed
    • Export Citation
  • 20.

    Skarf B, Hoyt CS. Optic nerve hypoplasia in children. Association with anomalies of the endocrine and CNS. Arch Ophthalmol 1984;102:62–7.

    • Crossref
    • PubMed
    • Export Citation
  • 21.

    Stanhope R, Preece MA, Brook CG. Hypoplastic optic nerves and pituitary dysfunction. A spectrum of anatomical and endocrine abnormalities. Arch Dis Child 1984;59:111–4.

    • Crossref
    • PubMed
    • Export Citation
  • 22.

    Traggiai C, Stanhope R. Endocrinopathies associated with midline cerebral and cranial malformations. J Pediatr 2002;140:252–5.

    • Crossref
    • PubMed
    • Export Citation
  • 23.

    Cemeroglu AP, Coulas T, Kleis L. Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study. J Pediatr Endocrinol Metab 2015;28:1057–63.

    • PubMed
    • Export Citation
  • 24.

    Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303.

    • Crossref
    • PubMed
    • Export Citation
  • 25.

    Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970;45:13–23.

    • Crossref
    • PubMed
    • Export Citation
  • 26.

    Khaper T, Bunge M, Clark I, Rafay MF, Mhanni A, et al. Increasing incidence of optic nerve hypoplasia/septo-optic dysplasia spectrum: geographic clustering in Northern Canada. Paediatr Child Health 2017;22:445–53.

    • Crossref
    • PubMed
    • Export Citation
  • 27.

    Qian X, Fouzdar Jain S, Morgan LA, Kruse T, Cabrera M, et al. Neuroimaging and endocrine disorders in paediatric optic nerve hypoplasia. Br J Ophthalmol 2018;102:906–10.

    • Crossref
    • PubMed
    • Export Citation
  • 28.

    Haddad NG, Eugster EA. Hypopituitarism and neurodevelopmental abnormalities in relation to central nervous system structural defects in children with optic nerve hypoplasia. J Pediatr Endocrinol Metab 2005;18:853–8.

    • PubMed
    • Export Citation
  • 29.

    Garcia-Filion P, Almarzouki H, Fink C, Geffner M, Nelson M, et al. Brain malformations do not predict hypopituitarism in young children with optic nerve hypoplasia. Horm Res Paediatr 2017;88:251–7.

    • Crossref
    • PubMed
    • Export Citation
  • 30.

    Stewart C, Garcia-Filion P, Fink C, Ryabets-Lienhard A, Geffner ME, et al. Efficacy of growth hormone replacement on anthropometric outcomes, obesity, and lipids in children with optic nerve hypoplasia and growth hormone deficiency. Int J Pediatr Endocrinol 2016;2016:5.

    • Crossref
    • PubMed
    • Export Citation
  • 31.

    Mellado C, Poduri A, Gleason D, Elhosary PC, Barry BJ, et al. Candidate gene sequencing of LHX2, HESX1, and SOX2 in a large schizencephaly cohort. Am J Med Genet A 2010;152A:2736–42.

    • Crossref
    • Export Citation
  • 32.

    Dahl S, Wickstrom R, Ek U, Tear Fahnehjelm K. Children with optic nerve hypoplasia face a high risk of neurodevelopmental disorders. Acta Paediatr 2018;107:484–9.

    • Crossref
    • Export Citation
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The Journal of Pediatric Endocrinology and Metabolism (JPEM) is the only international journal dedicated exclusively to endocrinology in the neonatal, pediatric and adolescent age groups, and publishes the results of clinical investigations in pediatric endocrinology and basic research. JPEM publishes Review Articles, Original Research, Case Reports, Short Communications and Letters to the Editor.

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