Octreotide-related exocrine pancreatic insufficiency (EPI) in congenital hyperinsulinism

Purificación Ros-Pérez 1 , 2 , Luz Golmayo 1 , María L. Cilleruelo 1 , 2 , Carolina Gutiérrez 1 , 2 , Patricia Celaya 1 , Nerea Lacámara 1 , Itziar Martínez-Badás 1 , María Güemes 3 , 4 ,  and Jesús Argente 2 , 3 , 4 , 5 , 6
  • 1 Department of Pediatrics, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
  • 2 Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain
  • 3 Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
  • 4 Centro de Investigación Biomédica en Red de obesidad y nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
  • 5 Instituto de Investigación la Princesa, Madrid, Spain
  • 6 IMDEA Food Institute, Campus of International Excellence (CEI) UAM + CSIC, Madrid, Spain
Purificación Ros-Pérez
  • Corresponding author
  • Department of Pediatrics, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
  • Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain
  • Email
  • Search for other articles:
  • degruyter.comGoogle Scholar
, Luz Golmayo
  • Department of Pediatrics, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
  • Search for other articles:
  • degruyter.comGoogle Scholar
, María L. Cilleruelo
  • Department of Pediatrics, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
  • Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain
  • Search for other articles:
  • degruyter.comGoogle Scholar
, Carolina Gutiérrez
  • Department of Pediatrics, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
  • Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain
  • Search for other articles:
  • degruyter.comGoogle Scholar
, Patricia Celaya
  • Department of Pediatrics, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
  • Search for other articles:
  • degruyter.comGoogle Scholar
, Nerea Lacámara
  • Department of Pediatrics, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
  • Search for other articles:
  • degruyter.comGoogle Scholar
, Itziar Martínez-Badás
  • Department of Pediatrics, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
  • Search for other articles:
  • degruyter.comGoogle Scholar
, María Güemes
  • Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
  • Centro de Investigación Biomédica en Red de obesidad y nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
  • Search for other articles:
  • degruyter.comGoogle Scholar
and Jesús Argente
  • Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain
  • Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
  • Centro de Investigación Biomédica en Red de obesidad y nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
  • Instituto de Investigación la Princesa, Madrid, Spain
  • IMDEA Food Institute, Campus of International Excellence (CEI) UAM + CSIC, Madrid, Spain
  • Search for other articles:
  • degruyter.comGoogle Scholar

Abstract

Background

Congenital hyperinsulinism (CH) is the most frequent cause of persistent hypoglycemia in the newborn. Octreotide, a long-acting somatostatin receptor analog (SSRA), is a second line treatment for diazoxide unresponsive CH patients. Although it has been found to be a safe and effective treatment, long-term benefits and side effects, have not been thoroughly evaluated.

Case presentation

Some authors have indicated that exocrine pancreatic insufficiency (EPI) is a common but under-recognized adverse reaction in adults treated with octreotide. However, no pediatric patient with SSRA-induced EPI has been reported to date. Here we report a case of an infant with diazoxide unresponsive, diffuse CH, caused by a heterozygous pathogenic paternally inherited mutation in the ABCC8 gene (NM_000352.4:c.357del), that developed exocrine pancreatic insufficiency and secondary vitamin K deficiency associated to chronic octreotide therapy.

Conclusions

We point out the atypical clinical onset with a cutaneous hemorrhagic syndrome, emphasizing the clinical relevance of this potential side effect.

  • 1.

    Kostopoulou, E, Shah, P. Hyperinsulinaemic hypoglycaemia-an overview of a complex clinical condition. Eur J Pediatr 2019;178:1151–60. https://doi.org/10.1007/s00431-019-03414-8.

    • Crossref
    • PubMed
    • Export Citation
  • 2.

    Galcheva, S, Demirbilek, H, Al-Khawaga, S, Hussain, K. The genetic and molecular mechanisms of congenital hyperinsulinism. Front Endocrinol 2019;10:111. https://doi.org/10.3389/fendo.2019.00111.

    • Crossref
    • Export Citation
  • 3.

    Rosenfeld, E, Ganguly, A, De Leon, DD. Congenital hyperinsulinism disorders: genetic and clinical characteristics. Am J Med Genet Part C 2019;181C:682–92. https://doi.org/10.1002/ajmg.c.31737.

  • 4.

    Banerjee, I, Salomon-Estebanez, M, Shah, P, Nicholson, J, Cosgrove, KE, Dunne, MJ. Therapies and outcomes of congenital hyperinsulinism-induced hypoglycaemia. Diabet Med 2019;36:9–21. https://doi.org/10.1111/dme.13823.

    • Crossref
    • PubMed
    • Export Citation
  • 5.

    Hosokawa, Y, Kawakita, R, Yokoya, S, Ogata, T, Ozono, K, Arisaka, O, et al. Efficacy and safety of octreotide for the treatment of congenital hyperinsulinism: a prospective, open-label clinical trial and an observational study in Japan using a nationwide registry. Endocr J 2017;64:867–80. https://doi.org/10.1507/endocrj.EJ17-0024.

    • Crossref
    • Export Citation
  • 6.

    McMahon, AW, Wharton, GT, Thornton, P, De Leon, DD. Octreotide use and safety in infants with hyperinsulinism. Pharmacoepidemiol Drug Saf 2017;26:26–31. https://doi.org/10.1002/pds.4144.

    • Crossref
    • PubMed
    • Export Citation
  • 7.

    Saif, MW, Larson, H, Kaley, K, Shaib, W. Chronic octreotide therapy can induce pancreatic insufficiency: a common but under recognized adverse effect. Expert Opin Drug Saf 2010;9:867–73. https://doi.org/10.1517/14740338.2010.510130.

    • Crossref
    • PubMed
    • Export Citation
  • 8.

    Lamarca, A, McCallum, L, Nuttall, C, Barriuso, J, Backen, A, Frizziero, M, et al. Somatostatin analogue-induced pancreatic exocrine insufficiency in patients with neuroendocrine tumors: results of a prospective observational study. Expert Rev Gastroenterol Hepatol 2018;12:723–31. https://doi.org/10.1080/17474124.2018.1489232.

    • Crossref
    • PubMed
    • Export Citation
  • 9.

    Saint-Martin, C, Zhou, Q, Martin, GM, Vaury, C, Leroy, G, Arnoux, JB, et al. Monoallelic ABCC8 mutations are a common cause of diazoxide-unresponsive diffuse form of congenital hyperinsulinism Clin Genet 2015;87:448–54. https://doi.org/10.1111/cge.12428.

    • Crossref
    • PubMed
    • Export Citation
  • 10.

    Szabo, CE, Man, OI, Şerban, RS, Kiss, E, Lazăr, CF. Bruising as the first sign of exocrine pancreatic insufficiency in infancy. Med Pharm Rep 2019;92:200–4. https://doi.org/10.15386/mpr-1231.

    • PubMed
    • Export Citation
Purchase article
Get instant unlimited access to the article.
$42.00
Log in
Already have access? Please log in.


or
Log in with your institution

Journal + Issues

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.

Search