INTRODUCTION: The growth hormone deficiency (GHD) diagnosis is controversial especially due to low specificity of growth hormone (GH) stimulation tests. It is therefore believed that children diagnosed with GHD form a heterogeneous group with growth disorder frequently independent on GH function. No study evaluating the complex etiology of growth failure in children with diagnosed GHD has been performed thus far. AIMS: To discover genetic etiology of short stature in children with diagnosed GHD from families with short stature. METHODS: Fifty-two children diagnosed with primary GHD and vertically transmitted short stature (height SDS in the child and his/her shorter parent <-2 SD) were included to our study. The GHD diagnosis was based on growth data suggestive of GHD, absence of substantial disproportionality (sitting height to total height ratio <-2 SD or >+2 SD), IGF-1 levels <0 for age and sex specific SD and peak GH concentration <10 ug/L in two stimulation tests. All children were examined using next-generation sequencing methods, and the genetic variants were subsequently evaluated by American College of Medical Genetics standards and guidelines. RESULTS: The age of children at enrollment into the study was 11 years (median, IQR 9-14 years), their height prior to GH treatment was -3.0 SD (-3.6 to -2.8 SD), IGF-1 concentration -1.4 SD (-2.0 to -1.1 SD), and maximal stimulated GH 6.3 ug/L (4.8-7.6 ug/L). No child had multiple pituitary hormone deficiency or a midbrain region pathology. Causative variant in a gene that affects growth was discovered in 15/52 (29%) children. Of them, only 2 (13%) had a genetic variant affecting GH secretion or function (GHSR and OTX2). Interestingly, in 10 (67%) children we discovered a primary growth plate disorder (ACAN, COL1A2, COL11A1, COL2A1, EXT2, FGFR3, NF1, NPR2, PTPN11 [2x]), in one (7%) a genetic variant impairing IGF-1 action (IGFALS) and in two (12%) a variant in miscellaneous genes (SALL4, MBTPS2). CONCLUSIONS: In children with vertically transmitted short stature, genetic results frequently did not correspond with the clinical diagnosis of GH deficiency. These results underline the doubtful reliability of methods standardly used to diagnose GH deficiency.
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- dítě MeSH
- hypofyzární nanismus * diagnóza genetika farmakoterapie MeSH
- insulinu podobný růstový faktor I genetika MeSH
- lidé MeSH
- lidský růstový hormon * MeSH
- mladiství MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: Adult growth hormone deficiency (AGHD) is a rare disease characterised by abnormal body composition, reduced strength and exercise capacity and impaired psychological wellbeing. An advisory board of leading Central and Eastern European (CEE) endocrinologists was assembled to gain insights into the status of AGHD care in the CEE region. Topics of discussion included the position of adult hypopituitarism/AGHD in health system priorities, availability and affordability of treatments, awareness of AGHD, practice guidelines used in CEE countries and provisions for long-term care of patients. DESIGN: Prior to the meeting, the advisors were asked to summarise, using an itemised survey questionnaire, the usual standards of care for patients with AGHD in their country. At the meeting, the panel of experts discussed the findings and thereby elucidated similarities and differences among CEE countries; these were compared with international guideline-recommended practices for AGHD. RESULTS: All CEE countries involved reported having some type of infrastructure in place for care of patients with GHD transitioning from adolescence to adulthood. Most countries reported having at least one specialist centre for patients with AGHD. The main variations across the region included initial entry into healthcare systems, tests required to confirm AGHD diagnosis and medication reimbursement by health authorities. Most CEE countries relied on international society-led guidelines, while some countries have developed national guidelines. CONCLUSION: The CEE Adult Endocrinology Advisory Board meeting recognised considerable diversity in the care and patient pathways for AGHD across CEE countries. Additional work is needed to optimise care of patients with AGHD in the CEE region.
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- dospělí MeSH
- hypofyzární nanismus diagnóza genetika terapie MeSH
- hypopituitarismus diagnóza genetika terapie MeSH
- kritické cesty * MeSH
- lidé MeSH
- lidský růstový hormon nedostatek MeSH
- směrnice pro lékařskou praxi jako téma normy MeSH
- standardní péče * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
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- dítě MeSH
- fenotyp MeSH
- homeodoménové proteiny genetika MeSH
- hypofýza růst a vývoj metabolismus MeSH
- hypofyzární nanismus genetika metabolismus patofyziologie MeSH
- jaderné proteiny genetika MeSH
- lidé MeSH
- lidský růstový hormon genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace * MeSH
- mutační analýza DNA MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- protein Gli2 s motivem zinkových prstů genetika MeSH
- proteiny s homeodoménou LIM genetika MeSH
- receptory hormonů regulujících hypofyzární hormony MeSH
- receptory neuropeptidů MeSH
- transkripční faktor Pit-1 genetika MeSH
- transkripční faktory SOXB1 genetika MeSH
- transkripční faktory genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
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- dítě MeSH
- hypofyzární hormony nedostatek MeSH
- hypofyzární nanismus farmakoterapie genetika MeSH
- lidé MeSH
- poruchy růstu farmakoterapie genetika MeSH
- růstový hormon nedostatek MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
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- adrenogenitální syndrom diagnóza genetika MeSH
- barva očí MeSH
- barva vlasů MeSH
- dermatoglyfika MeSH
- hypofyzární nanismus diagnóza genetika MeSH
- Klinefelterův syndrom diagnóza genetika MeSH
- lidé MeSH
- poruchy chuti diagnóza MeSH
- poruchy pohlavního vývoje spojené s poruchami pohlavních chromozomů * diagnóza genetika MeSH
- Turnerův syndrom diagnóza genetika MeSH
- Check Tag
- lidé MeSH
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- antropometrie metody MeSH
- dermatoglyfika MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- dospělí MeSH
- genetický výzkum * MeSH
- hypofyzární nanismus * epidemiologie genetika MeSH
- kraniofaryngeom epidemiologie genetika MeSH
- lékařská genetika MeSH
- lidé MeSH
- mladiství MeSH
- poruchy růstu * epidemiologie etiologie genetika MeSH
- prenatální poškození genetika MeSH
- růstový hormon MeSH
- statistika jako téma MeSH
- studie případů a kontrol MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
