Clinical, genetic, and radionuclide characteristics of the focal form of congenital hyperinsulinism

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  • Authors: Gubaeva D.N.1, Melikyan M.A.1, Ryzhkova D.V.2, Poyda M.D.2, Bairov V.G.2, Sukhotskaya A.A.2, Sokolov Y.Y.3, Efremenkov A.M.3, Mitrofanova L.B.2, Christesen H.4, Nikitina I.L.2
  • Affiliations:
    1. Endocrinology Research Certre
    2. Almazov National Medical Research Center
    3. Russian Medical Academy of Postgraduate Education
    4. Odense University Hospital
  • Issue: Vol 65, No 5 (2019)
  • Pages: 319-329
  • Section: Clinical endocrinology
  • URL: https://probl-endojournals.ru/probl/article/view/10317
  • DOI: https://doi.org/10.14341/probl10317
  • Cite item
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Abstract


BACKGROUND: Congenital hyperinsulinism (CHI) is a severe disease with a high risk of complications including neurological deficit. Persistent hypoglycemia in patients with focal form of CHI can not be managed with medical treatment in 96.4% of cases, what subsequently leads to surgical treatment. Currently, there is a lack of information regarding patients with focal form of CHI. This study is aimed at finding better approaches for diagnosis and treatment of patients with focal form of CHI.

AIMS: To study clinical, genetic and PET/CT findings of the focal form of CHI in Russian group of patients.

MATERIALS AND METHODS: The observational research included all patients with a histologically confirmed focal form of CHI, who were admitted to Endocrinology Research Centre during the period from January 2008 to January 2019. A statistical analysis of clinical data, genotype, and positron emission tomography (PET) with 18F-dihydroxyphenylalanine (18F-DOPA) was performed. The median follow-up was 18 months.

RESULTS: The study included 31 patients with focal CHI (14 boys, 45.2%). All patients had a neonatal presentation of the disease and demanded high levels of continuous glucose infusion to maintain euglycemia. The difference between the age of hypoglycemia presentation and the age of diagnosis ranged from 1 day to 3.9 months. In all cases, diazoxide was found to be ineffective. However, in 9 patients, it was possible to withdraw continuous glucose infusion and maintain euglycemia using octreotide in the preoperative period. A molecular genetic study allowed us to detect diverse pathogenic variants in ABCC8 and KCNJ11 genes in 30 patients. According to PET data with 18F-DOPA, the pancreatic index (PI) varied widely from 1.16 to 3.59. After partial resection of the pancreatic region with insulin hypersecretion, all patients showed complete recovery.

CONCLUSIONS: The focal form of CHI is a severe condition with high prevalence of neurological complications. For preoperative diagnosis of the morphological form of the disease, it is necessary to conduct genetic analysis and radionuclide studies. Solely evaluation of mathematical parameters in 18F-DOPA PET without taking into account the visual data and the results of genetic analysis does not allow establishing the robust diagnosis. Timely diagnosis, identification of risk factors, and prevention of complications of persistent hypoglycemia are important tasks for clinicians.


Diliara N. Gubaeva

Endocrinology Research Certre

Author for correspondence.
Email: gubaevadn@gmail.com
ORCID iD: 0000-0003-3922-2869
SPIN-code: 3431-3323

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD

Maria A. Melikyan

Endocrinology Research Certre

Email: melikian.maria@gmail.com
ORCID iD: 0000-0002-1491-2460
SPIN-code: 4184-4383

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD, leading research associate

Daria V. Ryzhkova

Almazov National Medical Research Center

Email: d_ryjkova@mail.ru
ORCID iD: 0000-0002-7086-9153
SPIN-code: 7567-6920

Russian Federation, 2, Akkuratova str., Saint- Petersburg, 197341

MD, PhD, Professor

Mikhail D. Poyda

Almazov National Medical Research Center

Email: mikhailpoyda@gmail.com
ORCID iD: 0000-0002-0351-9874

Russian Federation, 2, Akkuratova str., Saint- Petersburg, 197341

PhD-student

Vladimir G. Bairov

Almazov National Medical Research Center

Email: vbairov@gmail.com
ORCID iD: 0000-0002-8734-2227
SPIN-code: 6025-8991
2, Akkuratova str., Saint- Petersburg, 197341

PhD, Professor

Anna A. Sukhotskaya

Almazov National Medical Research Center

Email: anna.a.sukhotskaya@gmail.com
ORCID iD: 0000-0002-8446-830X
SPIN-code: 6863-7436

Russian Federation, 2, Akkuratova str., Saint- Petersburg, 197341

PhD

Yurij Yu. Sokolov

Russian Medical Academy of Postgraduate Education

Email: sokolov-surg@yandex.ru
ORCID iD: 0000-0003-3831-768X
SPIN-code: 9674-1049

Russian Federation, 125993, 2/1 Barrikadnaya, build. 1, Moscow

PhD, Professor

Artem M. Efremenkov

Russian Medical Academy of Postgraduate Education

Email: efremart@yandex.ru
ORCID iD: 0000-0002-5394-0165
SPIN-code: 6873-6732

Russian Federation, 125993, 2/1 Barrikadnaya, build. 1, Moscow

PhD

Lubov B. Mitrofanova

Almazov National Medical Research Center

Email: lubamitr@yandex.ru
ORCID iD: 0000-0003-0735-7822
SPIN-code: 9552-8248

Russian Federation, 2, Akkuratova str., Saint- Petersburg, 197341

MD, PhD

Henrik Christesen

Odense University Hospital

Email: Henrik.christesen@rsyd.dk
ORCID iD: 0000-0001-5330-6853

Denmark, J. B. Winsløws Vej 4, 5000 Odense

PhD, Professor

Irina L. Nikitina

Almazov National Medical Research Center

Email: nikitina0901@gmail.com
ORCID iD: 0000-0003-4013-0785
SPIN-code: 7707-4939

Russian Federation, 2, Akkuratova str., Saint- Petersburg, 197341

MD, PhD

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Supplementary files

Supplementary Files Action
1. Fig. 1. Schematic location of focal points in patients with focal form of IGI (n = 24). View (25KB) Indexing metadata
2. Fig. 2. Schematic representation of the genetic mechanisms that generate the focus of hyperinsulinism. View (41KB) Indexing metadata
3. Fig. 3. PET/CT results with 18F-ДОФА in patients with different morphological forms of IGI. (a) View (72KB) Indexing metadata
4. Fig. 3. PET/CT results with 18F-ДОФА in patients with different morphological forms of IGI. (b) View (107KB) Indexing metadata
5. Fig. 3. PET/CT results with 18F-ДОФА in patients with different morphological forms of IGI. (c) View (127KB) Indexing metadata
6. Fig. 4. Histological examination of pancreatic tissue in a patient with a focal form of BGI. (a) View (456KB) Indexing metadata
7. Fig. 4. Histological examination of pancreatic tissue in a patient with a focal form of BGI. (b) View (502KB) Indexing metadata
8. Fig. 4. Histological examination of pancreatic tissue in a patient with a focal form of BGI. (c) View (384KB) Indexing metadata
9. Fig. 4. Histological examination of pancreatic tissue in a patient with a focal form of BGI. (d) View (301KB) Indexing metadata

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Copyright (c) 2020 Gubaeva D.N., Melikyan M.A., Ryzhkova D.V., Poyda M.D., Bairov V.G., Sukhotskaya A.A., Sokolov Y.Y., Efremenkov A.M., Mitrofanova L.B., Christesen H., Nikitina I.L.

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