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Russian national consensus. Diagnostics and treatment of hypopituitarism in children and adolescences

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Abstract


The materials of the National Consensus reflect the modern domestic and international experience on this issue.

Before conducting a specialized endocrinological examination of a short child, all other causes of short stature should be excluded: severe somatic diseases in a state of decompensation that can affect growth velocity, congenital systemic skeletal diseases, syndromic short stature (all girls with growth retardation require a mandatory study of karyotype, depending on the presence or absence of phenotypic signs of Turner syndrome), endocrine diseases in decompensation.

A specialized examination of the state of GH-IGF-I axis is carried out when the proportionally folded child has pronounced short stature: if the child’s height is < –2.0 SDS, if the difference between the child’s height SDS and child’s midparental height SDS exceeds 1.5 SDS and/or a low growth velocity.

The consensus reflects clear criteria for the diagnosis of GH-deficiency, central hypothyroidism, central hypocorticosolism, central hypogonadism, diabetes insipidus, hypoprolactinemia, and also the criteria for their compensation.

The dose of somatropin with GH-deficiency in children and adolescents is 0.025–0.033 mg/kg/day. With total somatotropic insufficiency, especially in young children, it is advisable to start therapy with somatropin from lower doses: 25–50% of the substitution, gradually increasing it within 3–6 months to optimal. In children with a growth deficit when entering puberty, the dose may be increased to 0.045–0.05 mg/kg/day.

With the development of side effects, the dose of somatropin can be reduced (by 30–50%), or temporarily canceled (depending on the severity of the clinical picture) until the complete disappearance of undesirable symptoms. With swelling of the optic nerve, treatment is temporarily stopped until the picture of the fundus of the eye fully normalizes. If therapy has been temporarily discontinued, treatment is resumed in smaller doses (50% of the initial) with a gradual (within 1–3 months) return to the optimum.

GH treatment at pediatric doses not continue beyond attainment of a growth velocity below 2–2.5 cm/year, closure of the epiphyseal growth zones, or earlier, when: the achievement of genetically predicted height, but not more than 170 cm in girls, 180 cm in boys, the patient’s desire and his parents / legal representatives satisfied with the achieved result of the final height.

Re-evaluation of the somatotropic axis is carried out after reaching the adult height, after 1–3 months GH therapy will be discontinued. Patients with isolated GH-deficiency or patients with 1 (besides GH) pituitary hormone deficiencies in the presence of a normal IGF-1 level (against the background of somatropin withdrawal) and not having molecular genetic confirmation of the diagnosis need re- evaluation. Patients with two or more (besides GH) pituitary hormone deficiencies, acquired hypothalamic-pituitary lesions due to operations on the pituitary and irradiation of the hypothalamic-pituitary area (if the IGF-1 level is low against somatropin withdrawal), specific pituitary/ hypothalamic structural defect on MRI, gene defects of the GH-IGF-I system do not need re- evaluation.

If GH deficiency is confirmed, treatment with somatropin is resumed at metabolic doses of 0.01—0.003 mg/kg/day under the control of the IGF-I level in the blood (measurement 1 time in 6 months), the indicator should not exceed the upper limit of the reference value for the corresponding age and floor.


Elena V. Nagaeva

Endocrinology Research Centre

Author for correspondence.
Email: nagaeva_ev@mail.ru
ORCID iD: 0000-0001-6429-7198
SPIN-code: 4878-7810

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

MD, PhD

Tatiana Y. Shiryaeva

Endocrinology Research Centre

Email: tasha-home@list.ru
ORCID iD: 0000-0002-2604-1703
SPIN-code: 1322-0042

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

MD, PhD

Valentina A. Peterkova

Endocrinology Research Centre

Email: peterkovava@hotmail.com
ORCID iD: 0000-0002-5507-4627
SPIN-code: 4009-2463

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

MD, PhD, Professor

Olga B. Bezlepkina

Endocrinology Research Centre

Email: Olgabezlepkina@mail.ru
ORCID iD: 0000-0001-9621-5732
SPIN-code: 3884-0945

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

MD, PhD, Professor

Anatoly N. Tiulpakov

Endocrinology Research Centre

Email: anatolytiulpakov@gmail.com
ORCID iD: 0000-0001-8500-4841
SPIN-code: 8396-1798

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

MD, PhD

N. A. Strebkova

Endocrinology Research Centre

Email: lepet_morozko@mail.ru

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

Alexey V. Kiiaev

Urals State Medical University

Email: thyroend@mail.ru
ORCID iD: 0000-0002-5578-5242
SPIN-code: 7092-7894

Russian Federation, 3, Repina street, Ekaterinburg, 620028

MD, PhD

Elena E. Petryaykina

RUDN University Medical Institute

Email: lepet_morozko@mail.ru
ORCID iD: 0000-0002-8520-2378
SPIN-code: 5997-7464

Russian Federation, 6, Miklukho-Maklaya street, Moscow, 117198

MD, PhD, Professor

Elena B. Bashnina

North-Western State Medical University named after I.I Mechnikov

Email: bashnina@mail.ru
ORCID iD: 0000-0002-7063-1161
SPIN-code: 5568-0690

Russian Federation, 41, Kirochnaya street, Saint-Petersburg, 191015

MD, PhD, Professor

Oleg A. Мalievsky

Bashkortostan State Medical University

Email: malievsky@list.ru
ORCID iD: 0000-0003-2599-0867
SPIN-code: 6813-5061

Russian Federation, 450008, Ufa, Lenin street, 3

MD, PhD, Professor

Тatyana Е. Тaranushenko

Krasnoyarsk State Medical University

Email: tetar@rambler.ru
ORCID iD: 0000-0003-2500-8001
SPIN-code: 4777-0283

Russian Federation, 1, P. Zeleznyaka street, Krasnoyarsk, 660022

MD, PhD, Professor

Irina B. Коstrova

Children Republic Ckinical Hospital named after N.M. Kuraev

Email: ira-kostrova@mail.ru
ORCID iD: 0000-0003-0112-3785
SPIN-code: 9224-7047

Russian Federation, Makhachkala

Lyubov A. Shapkina

Pacific State Medical University

Email: shapkinala@mail.ru
ORCID iD: 0000-0001-7333-9089

Russian Federation, 2, Ostryakova Prospekt, Vladivostok, 690002

MD, PhD, Professor

Ivan I. Dedov

Endocrinology Research Centre; I.M.Sechenov First Moscow State Medical University (Sechenov University)

Email: dedov@endocrincentr.ru

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036; 8-2, Trubetskaya street, Moscow, 119992

MD, PhD, Professor

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Copyright (c) 2019 Nagaeva E.V., Shiryaeva T.Y., Peterkova V.A., Bezlepkina O.B., Tiulpakov A.N., Strebkova N.A., Kiiaev A.V., Petryaykina E.E., Bashnina E.B., Мalievsky O.A., Тaranushenko Т.Е., Коstrova I.B., Shapkina L.A., Dedov I.I.

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