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Frontiers in Endocrinology 2024We present the evolution of GHD in adolescent males with persistent growth failure, in whom the diagnosis was established after a second GH stimulation test (GST).
INTRODUCTION
We present the evolution of GHD in adolescent males with persistent growth failure, in whom the diagnosis was established after a second GH stimulation test (GST).
METHODS
We performed a retrospective chart review of children who presented for short stature (height less < 2SD for mean/mid-parental height) and/or growth failure (sustained growth velocity < 0 SD) to pediatric endocrinology at Mount Sinai Kravis Children's Hospital, New York and who had 2 GSTs. Data collected from electronic medical records were analyzed using SPSS v28.0.
RESULTS
Of 53 patients included, 42 were males. Average GH peak on initial GST was 15.48 ± 4.92 ng/ml, at 10.07 ± 2.65 years, mean height -1.68 ± 0.56SD(28% had <2SD), IGF-1 -1.00 ± 0.88SD. After 2.23 ± 1.22 years, at 12.04 ± 2.41years, height SDs decreased to -1.82 ± 0.63SD and IGF-1 was -1.08 ± 0.84SD. At repeat GST, average GH peak was 7.59 ± 2.12 ng/dL, with 36% ≤7 ng/dl and 32% in puberty. 12 males reached adult height of 0.08 ± 0.69 SD with a mean height gain of 1.83 ± 0.56SD(p<0.005), IGF-1 of -1.15 ± 0.81SD after 4.64 ± 1.4 years of GH.
CONCLUSION
We offer evidence for Evolving Growth Hormone Deficiency (EGHD) through repeat GST in children with persistent growth slowdown, even with pubertal progression; emphasizing the need for careful longitudinal follow-up to make accurate diagnosis.
Topics: Humans; Male; Human Growth Hormone; Adolescent; Retrospective Studies; Child; Growth Disorders; Female; Body Height; Insulin-Like Growth Factor I; Proof of Concept Study; Dwarfism, Pituitary
PubMed: 38752175
DOI: 10.3389/fendo.2024.1398171 -
Endocrine Jun 2024The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to...
PURPOSE
The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort.
METHODS
Twenty-six IGHD individuals and 26 controls matched by age, sex, ethnicity, and occupation were submitted to a biochemical, dermatological and a functional skin assessment by the Multi Probe Adapter Cutometer® MPA 580.
RESULTS
There was no difference in the number of skin cancers and in the degrees of photodamage between the groups. The melanin content in the forearm was similar between the groups but was lower in the buttocks (p = 0.005), as well as skin resistance (p < 0.0001) and elasticity (p = 0.003), lower in the IGHD. There was no difference in hydration and sebum content between the two groups.
CONCLUSION
IGHD is apparently associated with a neutral profile in terms of skin cancer and photodamage, with similar melanin on the forearm and lower buttocks, lower skin resistance and elasticity, with hydration and sebum similar to controls.
Topics: Humans; Male; Female; Adult; Skin; Human Growth Hormone; Middle Aged; Skin Neoplasms; Skin Aging; Young Adult; Skin Physiological Phenomena; Dwarfism, Pituitary; Adolescent
PubMed: 38703329
DOI: 10.1007/s12020-024-03840-1 -
Frontiers in Endocrinology 2024Serum levels of growth hormone (GH) and insulin-like growth factor (IGF)-I are crucial in the diagnosis and management of GH-related diseases. However, these levels are...
Serum levels of growth hormone (GH) and insulin-like growth factor (IGF)-I are crucial in the diagnosis and management of GH-related diseases. However, these levels are affected by nutritional and metabolic status. To elucidate the correlations between GH and IGF-I in various conditions, a retrospective analysis was performed for adult patients in which GH levels were examined by general practitioners during the period from January 2019 to December 2021. Of 642 patients, 33 patients were diagnosed with acromegaly, 21 were diagnosed with GH deficiency (GHD), and 588 were diagnosed with non-GH-related diseases (NGRD). In contrast to the positive correlations found between the levels of GH and IGF-I in patients with acromegaly (=0.50; <0.001) and patients with GHD (=0.39; =0.08), a negative correlation was found in the NGRD group (=-0.23; <0.001). In that group, the results of multivariable analysis showed that GH levels were predominantly influenced by gender and body mass index (BMI), whereas IGF-I levels were modulated by albumin in addition to age and GH. Of note, in the NGRD group, there was an enhanced negative correlation between GH and IGF-I under conditions of BMI < 22 and albumin < 4.0 g/dL (=-0.45; <0.001), and the negative correlation between GH and IGF-I was reinforced by excluding patients with other pituitary diseases and patients taking oral steroids (=-0.51; <0.001 and =-0.59; <0.001, respectively). Collectively, the results indicate that attention should be given to the presence of a negative correlation between serum levels of GH and IGF-I, especially in lean and low-nutritious conditions.
Topics: Adult; Humans; Growth Hormone; Acromegaly; Insulin-Like Peptides; Insulin-Like Growth Factor I; Retrospective Studies; Human Growth Hormone; Dwarfism, Pituitary; General Practice; Albumins
PubMed: 38596224
DOI: 10.3389/fendo.2024.1381083 -
Scientific Reports Apr 2024The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal... (Meta-Analysis)
Meta-Analysis
The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal children with growth hormone deficiency (GHD). We searched the PubMed, Embase, CNKI, and Wanfang databases from inception to July 2023 and identified eleven relevant studies. PEG-LAGH showed better effect on height velocity (mean difference [MD]: - 0.031, 95% credibility interval [CrI]: - 0.278, 0.215) than somatrogon (MD: 0.105, 95% CrI: - 0.419, 0.636), somapacitan (MD: 0.802, 95% CrI: - 0.451, 2.068) and lonapegsomatropin (MD: 1.335, 95% CrI: - 0.3, 2.989) when compared with daily growth hormone (DGH). Furthermore, in terms of height standard deviation score, PEG-LAGH demonstrated better improvement (MD: - 0.15, 95% CrI: - 1.1, 0.66) than somatrogon (MD: - 0.055, 95% CrI: - 1.3, 0.51) and somapacitan (MD: 0.22, 95% CrI: - 0.91, 1.3). PEG-LAGH (risk ratio [RR]: 1.00, 95% CrI: 0.82, 1.2) reduced the risk of adverse events compared with other LAGH (somatrogon, RR: 1.1, 95% CrI: 0.98, 1.2; somapacitan, RR: 1.1, 95% CrI: 0.96, 1.4; lonapegsomatropin, RR, 1.1, 95% CrI: 0.91, 1.3) and was comparable with DGH. This is the first study to indirectly compare the LAGH thorough a network meta-analysis and provide evidence of the optimal efficacy of various LAGH specifically PEG-LAGH and acceptable safety profile in prepubertal children with GHD.
Topics: Child; Humans; Growth Hormone; Network Meta-Analysis; Human Growth Hormone; Dwarfism, Pituitary; Growth Disorders; Hormone Replacement Therapy
PubMed: 38580693
DOI: 10.1038/s41598-024-58616-4 -
Zhongguo Dang Dai Er Ke Za Zhi =... Mar 2024With an increasing understanding of growth hormone deficiency, there has been a growing emphasis on the management of transition growth hormone deficiency (TGHD) in...
With an increasing understanding of growth hormone deficiency, there has been a growing emphasis on the management of transition growth hormone deficiency (TGHD) in clinical practice. The inadequate diagnosis and treatment of TGHD have been a major clinical concern, leading to the development of relevant guidelines and consensus internationally. This article summarizes the evaluation, diagnosis, treatment, and clinical challenges of TGHD based on these guidelines, consensus, and existing clinical studies, aiming to optimize and further improve the clinical diagnosis, treatment, and management of TGHD.
Topics: Humans; Human Growth Hormone; Dwarfism, Pituitary; Body Height; Consensus
PubMed: 38557372
DOI: 10.7499/j.issn.1008-8830.2309173 -
Frontiers in Endocrinology 2024Increased risk of neoplastic events after recombinant human growth hormone (rhGH) treatment in childhood has been an ongoing concern but long-term safety data are...
BACKGROUND
Increased risk of neoplastic events after recombinant human growth hormone (rhGH) treatment in childhood has been an ongoing concern but long-term safety data are limited.
METHODS
A nationwide population-based cohort study in Sweden of patients treated with rhGH during childhood between 1985-2010, due to isolated growth hormone deficiency (GHD), small for gestational age (SGA) and idiopathic short stature (ISS). The comparison group consisted of 15 age-, sex-, and region-matched controls per patient, randomly selected from the general population. Data on neoplastic events and covariates, such as gestational age, birth weight, birth length, socioeconomic status, and height at study start, were collected through linkage with population-based registers. The cohort was followed for neoplastic events until the end of 2020.
RESULTS
53,444 individuals (3,408 patients; 50,036 controls) were followed for up to 35 years, with a median follow-up of 19.8 years and a total of 1,050,977 person-years. Patients showed a moderately increased hazard ratio (HR) for neoplastic events overall compared to controls (HR 1.28, 95% CI: 1.12-1.46), but only significant for males (HR 1.39, 95% CI: 1.17-1.66) and not females (HR 1.15, 95% CI: 0.94-1.41). Longer treatment duration was associated with an increased HR, but no association was found between neoplastic events and mean or cumulative dose. No increased risk of malignant neoplasms was observed for the patients compared to matched controls (HR 0.91 95% CI: 0.66-1.26).
CONCLUSION
No association was found between rhGH treatment during childhood for GHD, SGA, or ISS and malignant neoplastic events in early to mid-adulthood. A moderate increase in overall neoplastic events was observed due to an increased number of events in male patients.
Topics: Humans; Male; Adult; Human Growth Hormone; Growth Hormone; Sweden; Cohort Studies; Birth Weight; Dwarfism, Pituitary; Recombinant Proteins; Neoplasms
PubMed: 38505755
DOI: 10.3389/fendo.2024.1360139 -
Frontiers in Endocrinology 2024It has been proposed that not all children with short stature displaying an inadequate response to tests for growth hormone (GH) secretion truly suffer from GH...
Clinical and laboratory characteristics but not response to treatment can distinguish children with definite growth hormone deficiency from short stature unresponsive to stimulation tests.
INTRODUCTION
It has been proposed that not all children with short stature displaying an inadequate response to tests for growth hormone (GH) secretion truly suffer from GH deficiency (GHD). Only children with a monogenic cause of GHD or an identifiable combined hormonal deficiency or anatomical anomaly in the hypothalamic-pituitary axis should be considered definite GHD (dGHD). The remaining patients can be defined as a separate group of patients, "short stature unresponsive to stimulation tests" (SUS). The aim of this proof-of-concept study, was to assess whether SUS patients treated with rhGH exhibit any differences compared to GHD patients undergoing the same treatment.
METHODS
Retrospective analysis on 153 consecutive patients with short stature and pathological response to two GH stimulation tests. Patients with dGHD were defined as those with a clear genetic or anatomical hypothalamic-pituitary anomaly, as well as those with combined pituitary hormone deficiencies and those with a known insult to the hypothalamic-pituitary axis (i.e. total brain irradiation) (n=38, 25%); those without any of the previous anomalies were defined as SUS (n=115, 75%).
RESULTS
At diagnosis, dGHD and SUS populations did not differ significantly in sex (F 32% vs 28%, p=0.68), age (11.9 vs 12.1, p=0.45), height SDS at diagnosis (-2.2 vs. -2.0, p=0.35) and prevalence of short stature (height <-2 SDS) (56% vs 51%, p=0.45). IGF-1 SDS were significantly lower in dGHD (-2.0 vs -1.3, p<0.01). After 1 year of treatment, the prevalence of short stature was significantly reduced in both groups (31% in dGHD vs. 21% in SUS, p<0.01) without any significant differences between groups (p=0.19), while the increase in IGF-1 SDS for bone age was greater in the dGHD category (+1.9 vs. +1.5, p<0.01), with no further difference in IGF-1 SDS between groups. At the last available follow-up, 59 patients had reached the near adult height (NAH) and underwent retesting for GHD. No differences in NAH were found (-0.3 vs. -0.4 SDS, 0% vs. 4% of short stature). The prevalence of pathological retesting was higher in dGHD (60% vs. 10%, p<0.01) as well as of overweight and obesity (67% vs. 26%).
CONCLUSION
Stimulation tests and the equivalent benefit from rhGH therapy, cannot distinguish between dGHD and SUS populations. In addition, lower IGF-1 concentrations at baseline and their higher increase during treatment in dGHD patients, and the lack of pathological retesting upon reaching NAH in SUS patients, are facts that suggest that deficient GH secretion may not be the cause of short stature in the SUS studied population.
Topics: Child; Adult; Humans; Insulin-Like Growth Factor I; Retrospective Studies; Dwarfism, Pituitary; Human Growth Hormone; Growth Hormone
PubMed: 38495788
DOI: 10.3389/fendo.2024.1288497 -
Clinical Endocrinology May 2024Various biases pertaining to stature account for a male sex predominance in growth hormone deficiency (GHD) cases diagnosed by endocrinology clinics. This manuscript...
OBJECTIVES
Various biases pertaining to stature account for a male sex predominance in growth hormone deficiency (GHD) cases diagnosed by endocrinology clinics. This manuscript will assess the sex distribution when biases are minimised.
METHODS
Retrospective chart review was conducted on patients diagnosed with GHD between 3 and 16 years of age. The sex distribution of cases was ascertained according to: (1) peak GH (pGH) by groups; based on growth hormone provocative testing, (2) pituitary gland imaging results, and (3) isolated GHD (IGHD) versus multiple pituitary hormone deficiencies (MPHD). The relative frequency of each sex was compared according to these subgroups with significance evaluated at α = .05 level.
RESULTS
Of the 5880 clinic referrals for short stature, there were 3709 boys (63%) and 2171 girls (37%). Of these, 20% of boys (n = 745) and 15.3% of girls (n = 332) underwent provocative testing for GHD. Of those tested, 39.2% of boys (n = 292) and 32.2% of girls (n = 107) were diagnosed with GHD, all p < .001. There was a male predominance in GHD cases based on pGH or GHD severity. Though not significant, girls were more likely than boys to have MPHD (p = .056), even across pGH groups (p = .06). Both boys and girls had a similar distribution of imaging abnormalities.
CONCLUSION
Stratifying by sex, we found similar percentages of pituitary imaging abnormalities (including tumours) and the number of pituitary hormone deficiencies in boys and girls as the cause of GHD. For these classifications, we did not find the historically reported male sex predominance.
Topics: Female; Humans; Child; Male; Retrospective Studies; Hypopituitarism; Human Growth Hormone; Dwarfism, Pituitary; Growth Hormone; Sex Distribution
PubMed: 38463009
DOI: 10.1111/cen.15047 -
Journal of Pediatric Endocrinology &... Apr 2024This prospective multicenter study aimed (1) to examine changes in parent-reported health-related quality of life (HRQOL) of children with short stature and the effects...
OBJECTIVES
This prospective multicenter study aimed (1) to examine changes in parent-reported health-related quality of life (HRQOL) of children with short stature and the effects of the children's condition on parents themselves within the first year of human growth hormone (hGH) treatment and (2) to predict based on main and interaction effects of children's HRQOL and increase in height.
METHODS
A total of 110 parents of children aged 4-18 years, diagnosed with idiopathic growth hormone deficiency, small for gestational age, or idiopathic short stature, were recruited from 11 participating German pediatric endocrinologists and asked to fill out the short stature-specific Quality of Life in Short Stature Youth (QoLISSY) Questionnaire before hGH treatment was initiated and one year later.
RESULTS
Negative effects of the children's short stature on the parents decrease over time, independent of diagnosis and treatment status. Furthermore, treatment status and height increase moderated the links between children's improved HRQOL as perceived by their parents and decreased caregiving burden.
CONCLUSIONS
Based on the children's improved HRQOL and the parent's decrease in caregiving burden, patient-reported outcomes that consider parental and child's perspectives should be considered when deciding on hGH treatment for children.
Topics: Child; Adolescent; Humans; Quality of Life; Prospective Studies; Body Height; Dwarfism, Pituitary; Surveys and Questionnaires; Parents; Human Growth Hormone
PubMed: 38421314
DOI: 10.1515/jpem-2023-0420 -
Frontiers in Endocrinology 2024Adult growth hormone deficiency (AGHD) is associated with a high prevalence of metabolic syndrome (MS), which contributes to the unfavorable cardiovascular risk profile...
INTRODUCTION
Adult growth hormone deficiency (AGHD) is associated with a high prevalence of metabolic syndrome (MS), which contributes to the unfavorable cardiovascular risk profile in these patients. Insulin like growth factor-1 (IGF-1) is a widely used biomarker, however it does not always reflect the cardiometabolic risk and has a poor relationship with clinical efficacy endpoints. Consequently, there is an unmet need for biomarkers to monitor responses to GH-replacement. Afamin is a hormone-like glycoprotein, expressed in the liver. Higher afamin levels are strongly associated with MS and insulin resistance (IR). Although both MS and IR are very common in AGHD, afamin has not been investigated in these patients.
PURPOSE
To investigate afamin as a potential biomarker in patients with AGHD.
MATERIALS AND METHODS
Participants included 20 AGHD patients (11 GH-substituted and 9 GH-unsubstituted) and 37 healthy controls. Subjects underwent routine laboratory examinations, anthropometric measurements, body composition analysis using multi-frequency bioelectrical impedance analysis (InBody720) and measurement of serum afamin concentrations. In GH-substituted subjects, GH-substitution was withdrawn for 2 months. Measurements were carried out right before GH-withdrawal, at the end of the 2-month withdrawal period, and 1 month after reinstituting GH-replacement therapy (GHRT).
RESULTS
GH-unsubstituted patients demonstrated higher afamin levels compared to controls (p=0.03). Afamin positively correlated with skeletal muscle mass, bone mineral content, total body water, extracellular- and intracellular water content, insulin (all, p<0.01), HOMA-IR (p=0.01) and C-peptide (p=0.03) levels in AGHD but not in healthy controls. In GH-substituted patients 2-month of GH-withdrawal caused significant changes in body composition, including decreased fat-free mass, skeletal muscle mass, total body water, and intracellular water content (all, p<0.01); but these changes almost fully recovered 1 month after reinstituting GHRT. Unexpectedly, afamin levels decreased after GH-withdrawal (p=0.03) and increased with reinstitution (p<0.01). Changes of afamin levels during GH-withdrawal positively correlated with changes of HOMA-IR (r=0.80; p<0.01) and changes of insulin (r=0.71; p=0.02).
CONCLUSION
Higher afamin levels in unsubstituted AGHD patients might indicate severe metabolic dysregulation. Significant changes accompanying GH-withdrawal and reinstitution, along with strong correlations with measures of IR, suggest that afamin could be a promising biomarker to monitor GHRT-associated changes of insulin sensitivity.
Topics: Adult; Humans; Prospective Studies; Human Growth Hormone; Dwarfism, Pituitary; Metabolic Syndrome; Insulin Resistance; Insulin; Biomarkers; Water
PubMed: 38379862
DOI: 10.3389/fendo.2024.1348046