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.
- MeSH
- 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.
- MeSH
- 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
OBJECTIVE: To describe real-life dosing patterns in children with growth hormone deficiency (GHD), born small for gestational age (SGA) or with Turner syndrome (TS) receiving growth hormone (GH) and enrolled in the NordiNet International Outcome Study (IOS; Nbib960128) between 2006 and 2016. DESIGN: This non-interventional, multicentre study included paediatric patients diagnosed with GHD (isolated (IGHD) or multiple pituitary hormone deficiency (MPHD)), born SGA or with TS and treated according to everyday clinical practice from the Czech Republic (IGHD/MPHD/SGA/TS: n = 425/61/316/119), France (n = 1404/188/970/206), Germany (n = 2603/351/1387/411) and the UK (n = 259/60/87/35). METHODS: GH dosing was compared descriptively across countries and indications. Proportions of patients by GH dose group (low/medium/high) or GH dose change (decrease/increase/no change) during years 1 and 2 were also evaluated across countries and indications. RESULTS: In the Czech Republic, GH dosing was generally within recommended levels. In France, average GH doses were higher for patients with IGHD, MPHD and SGA than in other countries. GH doses in TS tended to be at the lower end of the recommended label range, especially in Germany and the UK; the majority of patients were in the low-dose group. A significant inverse association between baseline height standard deviation score and GH dose was shown (P < 0.05); shorter patients received higher doses. Changes in GH dose, particularly increases, were more common in the second (40%) than in the first year (25%). CONCLUSIONS: GH dosing varies considerably across countries and indications. In particular, almost half of girls with TS received GH doses below practice guidelines and label recommendations.
- MeSH
- dítě MeSH
- hypofyzární nanismus diagnóza farmakoterapie epidemiologie MeSH
- hypotrofický novorozenec * MeSH
- internacionalita * MeSH
- lidé MeSH
- lidský růstový hormon aplikace a dávkování MeSH
- mladiství MeSH
- následné studie MeSH
- poruchy růstu diagnóza farmakoterapie epidemiologie MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- průřezové studie MeSH
- Turnerův syndrom diagnóza farmakoterapie epidemiologie MeSH
- výsledek terapie MeSH
- výzkumná zpráva * MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Francie epidemiologie MeSH
- Německo epidemiologie MeSH
- Spojené království epidemiologie MeSH
- MeSH
- dospělí MeSH
- hypofyzární nanismus diagnóza patologie terapie MeSH
- krční mandle patologie MeSH
- lidé MeSH
- lymfatické nemoci diagnóza patologie terapie MeSH
- obstrukční spánková apnoe etiologie patologie terapie MeSH
- poruchy dýchání diagnóza patologie terapie MeSH
- trvalý přetlak v dýchacích cestách MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- akromegalie diagnóza etiologie terapie MeSH
- hypofyzární nanismus diagnóza etiologie terapie MeSH
- insulinu podobný růstový faktor I fyziologie MeSH
- kosterní svaly metabolismus růst a vývoj MeSH
- kosti a kostní tkáň metabolismus MeSH
- lidé MeSH
- revmatické nemoci etiologie metabolismus MeSH
- růstový hormon fyziologie terapeutické užití MeSH
- vývoj kostí MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- diagnostické techniky a postupy MeSH
- diagnóza MeSH
- dítě MeSH
- hypofyzární nanismus diagnóza terapie MeSH
- kojenec MeSH
- komplikace porodu MeSH
- lidé MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- růstový hormon nedostatek MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
