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.

• Klíčová slova
• genetics, growth hormone, growth hormone deficiency, next-generation sequencing, short stature,
• 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
• Názvy látek
• insulinu podobný růstový faktor I MeSH
• lidský růstový hormon * 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.

• Klíčová slova
• Adult growth hormone deficiency (AGHD), CEE adult endocrinology advisory board, Central and Eastern Europe (CEE), Growth hormone replacement therapy (GHRT), Practice guidelines, Recombinant human growth hormone (rhGH),
• 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
• Názvy látek
• lidský růstový hormon 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
• Názvy látek
• lidský růstový hormon MeSH

The clonidine stimulation test, using doses of 37.5--75 micrograms clonidine and assessment of growth hormone levels at times 0, 60 minutes, is a suitable, safe and relatively reliable screening test for ambulatory work. As ensues from examinations of 156 children, it is possible to select by this test, as compared with the test of insulin induced hypoglycaemia, more than 70% children with a normal post-stimulation response of growth hormone.

• MeSH
• clonidin * MeSH
• dítě MeSH
• hypofyzární nanismus diagnóza   metabolismus   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• růstový hormon metabolismus   MeSH
• testy funkce hypofýzy * MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• clonidin * MeSH
• růstový hormon MeSH

In order to assess when and on the basis of which developmental parameters it is possible for the community paediatrician to express suspicion of growth hormone deficiency in a child, the authors analyzed anamnestic perinatal and postnatal parameters up to the age of 3 years in 47 children (31 boys, 16 girls), where during subsequent life the classical form of so-called idiopathic growth hormone deficiency (hypothalamo-hypophyseal nanism) was diagnosed. The ratio of breech presentations and other deliveries was 13:18 in the affected boys and 1:15 in the girls. In children delivered by vertex presentation or section we may consider, using the criterion of -2 SD height, a deficit of growth hormone in 67% (boys) and 57% (girls) already at the age of 6 months, and in 88% and 79% resp. at the age of 3 years when the growth retardation is associated only with a minor degree of body weight retardation. In boys delivered by breech presentation growth retardation occurs later. Their development in the first year of life is usually unconspicuous, only at the age of 3 years in 70% growth becomes retarded by more than 2 SD.

• MeSH
• časové faktory MeSH
• hypofyzární nanismus diagnóza   prevence a kontrola   MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• referenční hodnoty MeSH
• růst * MeSH
• růstový hormon nedostatek   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• růstový hormon MeSH

• MeSH
• dermatoglyfika * MeSH
• dítě MeSH
• dospělí MeSH
• hypofyzární nanismus diagnóza   MeSH
• lidé MeSH
• mladiství MeSH
• poruchy růstu diagnóza   MeSH
• předškolní dítě MeSH
• tělesná výška MeSH
• vývojové onemocnění kostí diagnóza   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dítě MeSH
• hypofyzární nanismus diagnóza   metabolismus   MeSH
• lidé MeSH
• poruchy růstu diagnóza   metabolismus   MeSH
• růstový hormon metabolismus   MeSH
• vysoká teplota * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• růstový hormon MeSH

• MeSH
• diencefalon * MeSH
• dítě MeSH
• diuréza MeSH
• dospělí MeSH
• glukokortikoidy MeSH
• hypofyzární nanismus diagnóza   etiologie   MeSH
• hypofyzoadrenální funkční testy MeSH
• hypoglykemie chemicky indukované   MeSH
• inzulin MeSH
• lidé MeSH
• mladiství MeSH
• poruchy růstu diagnóza   MeSH
• voda * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukokortikoidy MeSH
• inzulin MeSH
• voda * MeSH