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Journal of Endocrinological... Dec 2023The aim of this study was to produce evidence on quality of life (QoL) among Italian growth hormone deficiency (GHD) children and adolescents treated with growth hormone...
PURPOSE
The aim of this study was to produce evidence on quality of life (QoL) among Italian growth hormone deficiency (GHD) children and adolescents treated with growth hormone (GH) and their parents.
METHODS
A survey was conducted among Italian children and adolescents aged 4-18 with a confirmed diagnosis of GHD and treated with GH therapy and their parents. The European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) and the Quality of Life in Short Stature Youth (QoLISSY) questionnaires were administered between May and October 2021 through the Computer-Assisted Personal Interview (CAPI) method. Results were compared with national and international reference values.
RESULTS
The survey included 142 GHD children/adolescents and their parents. The mean EQ-5D-3L score was 0.95 [standard deviation (SD) 0.09], while the mean visual analogue scale (VAS) score was 86.2 (SD 14.2); the scores are similar to those of a reference Italian population aged 18-24 of healthy subjects. As for the QoLISSY child-version, compared to the international reference values for GHD/ idiopathic short stature (ISS) patients, we found a significantly higher score for the physical domain, and lower scores for coping and treatment; compared to the specific reference values for GHD patients, our mean scores were significantly lower for all domains except the physical one. As for the parents, we found a significantly higher score for the physical domain, and a lower score for treatment; compared to reference values GHD-specific, we found lower score in the social, emotional, treatment, parental effects, and total score domains.
CONCLUSIONS
Our results suggest that the generic health-related quality of life (HRQoL) in treated GHD patients is high, comparable to that of healthy people. The QoL elicited by a disease specific questionnaire is also good, and comparable with that of international reference values of GHD/ISS patients.
Topics: Humans; Adolescent; Quality of Life; Caregivers; Dwarfism, Pituitary; Italy; Human Growth Hormone; Growth Hormone; Surveys and Questionnaires
PubMed: 37209402
DOI: 10.1007/s40618-023-02106-3 -
Indian Journal of Dermatology,... 2013
Topics: Child; Dwarfism; Humans; Hypogonadism; Intellectual Disability; Male; Xeroderma Pigmentosum
PubMed: 24177634
DOI: 10.4103/0378-6323.120760 -
Nefrologia : Publicacion Oficial de La... 2015Pediatric chronic kidney disease (CKD) has peculiar features. In particular, growth impairment is a major clinical manifestation of CKD that debuts in pediatric age... (Comparative Study)
Comparative Study Review
Pediatric chronic kidney disease (CKD) has peculiar features. In particular, growth impairment is a major clinical manifestation of CKD that debuts in pediatric age because it presents in a large proportion of infants and children with CKD and has a profound impact on the self-esteem and social integration of the stunted patients. Several factors associated with CKD may lead to growth retardation by interfering with the normal physiology of growth plate, the organ where longitudinal growth rate takes place. The study of growth plate is hardly possible in humans and justifies the use of animal models. Young rats made uremic by 5/6 nephrectomy have been widely used as a model to investigate growth retardation in CKD. This article examines the characteristics of this model and analyzes the utilization of CKD induced by high adenine diet as an alternative research protocol.
Topics: Adenine; Administration, Oral; Adolescent; Animals; Chemokines; Child; Child, Preschool; Disease Models, Animal; Dwarfism; Female; Growth Plate; Humans; Infant; Infant, Newborn; Male; Mesothelin; Nephrectomy; Postoperative Complications; Rats; Renal Insufficiency, Chronic; Young Adult
PubMed: 26522663
DOI: 10.1016/j.nefro.2015.08.004 -
Journal of Korean Medical Science Mar 2022The study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic,... (Comparative Study)
Comparative Study
Growth Responses During 3 Years of Growth Hormone Treatment in Children and Adolescents With Growth Hormone Deficiency: Comparison Between Idiopathic, Organic and Isolated Growth Hormone Deficiency, and Multiple Pituitary Hormone Deficiency.
BACKGROUND
The study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic, organic, isolated (IGHD), and multiple pituitary hormone deficiency (MPHD).
METHODS
Total 163 patients aged 2-18 years (100 males and 63 females; 131 idiopathic and 32 organic GHD; 129 IGHD and 34 MPHD) were included from data obtained from the LG Growth Study. Parameters of growth responses and biochemical results were compared during the 3-year GH treatment.
RESULTS
The baseline age, bone age (BA), height (Ht) standard deviation score (SDS), weight SDS, mid-parental Ht SDS, predicted adult Ht (PAH) SDS, and insulin like growth factor-1 (IGF-1) SDS were significantly higher in the organic GHD patients than in the idiopathic GHD patients, but peak GH on the GH-stimulation test, baseline GH dose, and mean 3-year-GH dosage were higher in the idiopathic GHD patients than in the organic GHD patients. The prevalence of MPHD was higher in the organic GHD patients than in the idiopathic GHD patients. Idiopathic MPHD subgroup showed the largest increase for the ΔHt SDS and ΔPAH SDS during GH treatment, and organic MPHD subgroup had the smallest mean increase after GH treatment, depending on ΔIGF-1 SDS and ΔIGF binding protein-3 (IGFBP-3) SDS. The growth velocity and the parental-adjusted Ht gain were greater in the idiopathic GHD patients than the organic GHD patients during the 3-year GH treatment, which may have been related to the different GH dose, ΔIGF-1 SDS, and ΔIGFBP-3 SDS between two groups. Multiple linear regression analysis revealed that baseline IGF-1 SDS, BA, and MPH SDS in idiopathic group and baseline HT SDS in organic group are the most predictable parameters for favorable 3-year-GH treatment.
CONCLUSION
The 3-year-GH treatment was effective in both idiopathic and organic GHD patients regardless of the presence of MPHD or underlying causes, but their growth outcomes were not constant with each other. Close monitoring along with appropriate dosage of GH and annual growth responses, not specific at baseline, are more important in children and adolescents with GHD for long-term treatment.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01604395.
Topics: Adolescent; Body Height; Child; Child, Preschool; Congenital Hypothyroidism; Dwarfism, Pituitary; Female; Human Growth Hormone; Humans; Male
PubMed: 35315601
DOI: 10.3346/jkms.2022.37.e90 -
Hormone Research in Paediatrics 2021The current differential diagnosis for a short child with low insulin-like growth factor I (IGF-I) and a normal growth hormone (GH) peak in a GH stimulation test (GHST),... (Review)
Review
The current differential diagnosis for a short child with low insulin-like growth factor I (IGF-I) and a normal growth hormone (GH) peak in a GH stimulation test (GHST), after exclusion of acquired causes, includes the following disorders: (1) a decreased spontaneous GH secretion in contrast to a normal stimulated GH peak ("GH neurosecretory dysfunction," GHND) and (2) genetic conditions with a normal GH sensitivity (e.g., pathogenic variants of GH1 or GHSR) and (3) GH insensitivity (GHI). We present a critical appraisal of the concept of GHND and the role of 12- or 24-h GH profiles in the selection of children for GH treatment. The mean 24-h GH concentration in healthy children overlaps with that in those with GH deficiency, indicating that the previously proposed cutoff limit (3.0-3.2 μg/L) is too high. The main advantage of performing a GH profile is that it prevents about 20% of false-positive test results of the GHST, while it also detects a low spontaneous GH secretion in children who would be considered GH sufficient based on a stimulation test. However, due to a considerable burden for patients and the health budget, GH profiles are only used in few centres. Regarding genetic causes, there is good evidence of the existence of Kowarski syndrome (due to GH1 variants) but less on the role of GHSR variants. Several genetic causes of (partial) GHI are known (GHR, STAT5B, STAT3, IGF1, IGFALS defects, and Noonan and 3M syndromes), some responding positively to GH therapy. In the final section, we speculate on hypothetical causes.
Topics: Child; Child, Preschool; Diagnosis, Differential; Dwarfism; Dwarfism, Pituitary; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Muscle Hypotonia; Noonan Syndrome; Spine
PubMed: 34091447
DOI: 10.1159/000516407 -
Physiology (Bethesda, Md.) Mar 2020Pedomorphy, maintenance of juvenile traits throughout life, is most pronounced in extraordinarily long-lived naked mole-rats. Many of these traits (e.g., slow growth... (Review)
Review
Pedomorphy, maintenance of juvenile traits throughout life, is most pronounced in extraordinarily long-lived naked mole-rats. Many of these traits (e.g., slow growth rates, low hormone levels, and delayed sexual maturity) are shared with spontaneously mutated, long-lived dwarf mice. Although some youthful traits likely evolved as adaptations to subterranean habitats (e.g., thermolability), the nature of these intrinsic pedomorphic features may also contribute to their prolonged youthfulness, longevity, and healthspan.
Topics: Adaptation, Physiological; Aging; Animals; Dwarfism; Humans; Longevity; Mice; Mole Rats; Oxidative Stress; Species Specificity
PubMed: 32024425
DOI: 10.1152/physiol.00032.2019 -
Frontiers in Endocrinology 2022The growth hormone deficiency (GHD) diagnosis is controversial especially due to low specificity of growth hormone (GH) stimulation tests. It is therefore believed that...
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 ( and ). Interestingly, in 10 (67%) children we discovered a primary growth plate disorder (, , , , , , , , [2x]), in one (7%) a genetic variant impairing IGF-1 action () and in two (12%) a variant in miscellaneous genes (, ).
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.
Topics: Adolescent; Child; Female; Humans; Male; Dwarfism, Pituitary; Human Growth Hormone; Insulin-Like Growth Factor I; Reproducibility of Results
PubMed: 36714562
DOI: 10.3389/fendo.2022.1102968 -
Genes Dec 2022Disproportionate dwarfism phenotypes represent a heterogeneous subset of skeletal dysplasias and have been described in many species including humans and dogs. In this...
Disproportionate dwarfism phenotypes represent a heterogeneous subset of skeletal dysplasias and have been described in many species including humans and dogs. In this study, we investigated Vizsla dogs that were affected by disproportionate dwarfism that we propose to designate as skeletal dysplasia 3 (SD3). The most striking skeletal changes comprised a marked shortening and deformation of the humerus and femur. An extended pedigree with six affected dogs suggested autosomal recessive inheritance. Combined linkage and homozygosity mapping localized a potential genetic defect to a ~4 Mb interval on chromosome 33. We sequenced the genome of an affected dog, and comparison with 926 control genomes revealed a single, private protein-changing variant in the critical interval, :XM_038583131.1:c.673T>C, predicted to cause an exchange of a highly conserved amino acid, XP_038439059.1:p.(Y225H). We observed perfect co-segregation of the genotypes with the phenotype in the studied family. When genotyping additional Vizslas, we encountered a single dog with disproportionate dwarfism that did not carry the mutant allele, which we hypothesize was due to heterogeneity. In the remaining 130 dogs, we observed perfect genotype-phenotype association, and none of the unaffected dogs were homozygous for the mutant allele. loss-of-function variants cause spondylometaphyseal dysplasia with cone-rod dystrophy (SMD-CRD) in humans. The skeletal changes in Vizslas were comparable to human patients. So far, no ocular phenotype has been recognized in dwarf Vizslas. We propose the missense variant as a candidate causative variant for SD3. Our data facilitate genetic testing of Vizslas to prevent the unintentional breeding of further affected puppies.
Topics: Animals; Dogs; Choline-Phosphate Cytidylyltransferase; Dwarfism; Genome; Genotype; Homozygote; Mutation, Missense
PubMed: 36553621
DOI: 10.3390/genes13122354 -
Journal of Veterinary Internal Medicine Sep 2022Primary congenital hypothyroidism (CH) is a rare endocrine disorder in cats with a largely unknown genetic cause.
BACKGROUND
Primary congenital hypothyroidism (CH) is a rare endocrine disorder in cats with a largely unknown genetic cause.
OBJECTIVES
Describe the clinical presentation of CH in 11 affected cats and identify the causal genetic variant.
ANIMALS
Eleven CH-cats from 10 unrelated families, 11 CH-free family members, 21 unrelated CH-free cats, and 155 unrelated nondiagnosed cats from different breeds.
METHODS
Case control study of CH-cats and their siblings (2019-2021). Diagnosis was based on low to low-normal serum thyroxine (T4) concentrations, high thyroid-stimulating hormone (TSH) concentrations and clinical signs compatible with CH. We identified the causal variant using Sanger sequencing, genotyping via PCR-RFLP and variant interpretation using ACMG/AMP guidelines.
RESULTS
All CH-cats (5 weeks-8 years) had disproportionate dwarfism. A goiter was not palpable in all. Thyroid scintigraphy with radiopertechnetate showed abnormally high uptake by thyroid glands, whereas scintigraphy with radioiodine showed abnormally low uptake, compatible with a defect in iodine organification by thyroid peroxidase (TPO). All cases were homozygous for TPO variant XM_006930524.4:c.430G>A(p.(Gly144Arg)), while none of the CH-free cats were. All sampled parents were heterozygous for this recessive variant. This variant was found in 15 cat breeds with an estimated allele frequency of 9%.
CONCLUSIONS AND CLINICAL IMPORTANCE
Disproportionate dwarfism, abnormally high TSH and abnormally low to low-normal T4 concentrations are diagnostic for CH in cats. All cases had dyshormonogenesis demonstrated by thyroid scintigraphy. This novel TPO missense variant (not described in humans) causes CH in cats and awareness of it can assist in diagnosis and breeding.
Topics: Animals; Cats; Case-Control Studies; Cat Diseases; Congenital Hypothyroidism; Iodide Peroxidase; Iodine Radioisotopes; Thyrotropin; Thyroxine
PubMed: 36054182
DOI: 10.1111/jvim.16524 -
Tidsskrift For Den Norske Laegeforening... Nov 2005Molecular diagnostic techniques provide an unsurpassed opportunity to understand the pathophysiological basis of endocrine disorders. Diseases have been associated with... (Review)
Review
Molecular diagnostic techniques provide an unsurpassed opportunity to understand the pathophysiological basis of endocrine disorders. Diseases have been associated with mutations in almost every gene known to have a role in either the production or secretion of a hormone or the mediators of hormone signalling. Even though most of these mutations are rare and account for only a small fraction of endocrine diseases, molecular diagnostics offers a valuable tool for the clinician in these cases. The most common endocrine disorders such as autoimmune thyroiditis, type 2 diabetes mellitus, osteoporosis, growth disorders, and obesity have all major genetic components, but these are mostly unknown. In this review the clinical implications of molecular diagnostics are illustrated for some endocrine diseases: congenital adrenal hyperplasia, congenital hypothyroidism, thyroid hormone resistance, familial hypocalciuric hypercalcaemia, growth hormone deficiency and resistance, and monogenic obesity. Improved diagnostic specificity has direct implications for treatment and follow up in these syndromes. Molecular diagnostics in endocrine tumours and diabetes are presented in two other articles in this series.
Topics: Adrenogenital Syndrome; Congenital Hypothyroidism; Diabetes Insipidus; Diagnosis, Differential; Diagnostic Techniques, Endocrine; Dwarfism; Endocrine System Diseases; Female; Genetic Predisposition to Disease; Humans; Male; Molecular Diagnostic Techniques; Mutation; Obesity; Receptors, Calcium-Sensing; Virilism
PubMed: 16276381
DOI: No ID Found