Effects of Single Vitamin D₃ Injection (200,000 Units) on Serum Fibroblast Growth Factor 23 and Sclerostin Levels in Subjects with Vitamin D Deficiency.
Zhang Dongdong,Seo Da Hea,Choi Han Seok,Park Hye Sun,Chung Yoon Sok,Lim Sung Kil
Endocrinology and metabolism (Seoul, Korea)
BACKGROUND:Vitamin D deficiency remains common in all age groups and affects skeletal and non-skeletal health. Fibroblast growth factor 23 is a bone-derived hormone that regulates phosphate and 1,25-dihydroxyvitamin D homeostasis as a counter regulatory factor. 1,25-Dihydroxyvitamin D stimulates fibroblast growth factor 23 synthesis in bone, while fibroblast growth factor 23 suppresses 1,25-dihydroxyvitamin D production in the kidney. The aim of this study was to evaluate the effects of vitamin D₃ intramuscular injection therapy on serum fibroblast growth factor 23 concentrations, and several other parameters associated with bone metabolism such as sclerostin, dickkopf-1, and parathyroid hormone. METHODS:A total of 34 subjects with vitamin D deficiency (defined by serum 25-hydroxyvitamin D levels below 20 ng/mL) were randomly assigned to either the vitamin D injection group (200,000 units) or placebo treatment group. Serum calcium, phosphate, urine calcium/creatinine, serum 25-hydroxyvitamin D, fibroblast growth factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were serially measured after treatment. RESULTS:Comparing the vitamin D injection group with the placebo group, no significant changes were observed in serum fibroblast growth factor 23, parathyroid hormone, or dickkopf-1 levels. Serum sclerostin concentrations transiently increased at week 4 in the vitamin D group. However, these elevated levels declined later and there were no statistically significant differences as compared with baseline levels. CONCLUSION:Serum fibroblast factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were not affected significantly by single intramuscular injection of vitamin D₃.
10.3803/EnM.2017.32.4.451
Parathyroid function and vitamin D metabolism during human growth hormone replacement.
Gertner J M,Horst R L,Broadus A E,Rasmussen H,Genel M
The Journal of clinical endocrinology and metabolism
Changes in calcium and phosphorus metabolism were studied in nine children with GH deficiency before and during human GH replacement therapy. Parathyroid function and serum concentrations of physiologically important vitamin D metabolites were examined to determine their relationship to changes in mineral metabolism. By comparison with pretreatment values, the GH-treated children showed significant increases in growth rate and renal tubular phosphate reabsorption and a significant decrease in urinary calcium excretion after a standardized oral load. There was no significant change in serum concentrations of parathyroid hormone, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, or 24,25-dihydroxyvitamin D or in nephrogenous cAMP excretion. Although GH has been proposed as a regulator of vitamin D metabolism, the present study demonstrates that the anabolic changes in calcium and phosphorus metabolism accompanying GH therapy are not mediated via changes in parathyroid hormone or vitamin D status.
10.1210/jcem-49-2-185
TRABECULAR BONE SCORE CHANGE DIFFERS WITH REGARD TO 25(OH)D LEVELS IN PATIENTS TREATED FOR ADULT-ONSET GROWTH HORMONE DEFICIENCY.
Kužma Martin,Binkley Neil,Bednárová Adriana,Killinger Zdenko,Vaňuga Peter,Payer Juraj
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
OBJECTIVE:Vitamin D is important in bone health. However, potential relationships of concomitant vitamin D deficiency with growth hormone deficiency (GHD) and the possibility that vitamin D inadequacy may alter the skeletal effects of growth hormone (GH) replacement therapy have not been adequately evaluated. METHODS:A prospective study was conducted in adult-onset GHD patients treated with recombinant human GH (rhGH) for 2 years. Trabecular bone score (TBS), lumbar spine (LS) bone mineral density (BMD), total hip (TH) BMD, and 25-hydroxyvitamin D (25(OH)D) levels were assessed at baseline and 24 months. The study cohort was divided based on 25(OH)D levels into 2 groups with the cutoff defined as the 50(th) percentile at each follow-up time point. RESULTS:Fifty-seven patients (29 males/28 females, mean age 34.4 years) were studied. After 24 months of GH replacement, LS BMD increased by 7.6% and TH BMD increased by 4.5% (both P<.05), with no difference according to 25(OH)D levels. TBS increased (+1.39 ± 3.6%) in those whose 25(OH)D was above the 50(th) percentile but decreased (-1.36 ± 5.6%, P<.05) in the cohort below the 50(th) percentile of 25(OH)D. Positive correlations were observed between baseline levels of IGF-1 and 25(OH)D (R = 0.37, P<.001) and between 24-month 25(OH)D and TBS (R = 0.25, P<.05). CONCLUSION:A differential effect of GH on TBS change was observed; TBS increased only in the cohort with 25(OH)D above the 50(th) percentile. Vitamin D sufficiency may be required to obtain optimal effects of GH treatment on bone quality, as assessed by TBS, in GHD adults. ABBREVIATIONS:AO-GHD = adult-onset GHD BMD = bone mineral density BMI = body mass index Ca = calcium CTx = carboxyterminal collagen crosslinks CV = coefficient of variation DXA = dual energy X-ray absorptiometry ECLIA = enzyme-labeled chemiluminescent immunometric assay GH = growth hormone GHD = growth hormone deficiency IGF-1 = insulin-like growth factor 1 LS BMD = lumbar spine BMD OC = osteocalcin 25(OH)D = 25-hydroxyvitamin D P = phosphorus PTH = parathyroid hormone rhGH = recombinant human GH TBS = trabecular bone score TH BMD = total hip BMD.
10.4158/EP151183.OR
Serum transforming growth factor-beta levels in patients with vitamin D deficiency.
Isik Serhat,Ozuguz Ufuk,Tutuncu Yasemin Ates,Erden Gonul,Berker Dilek,Acar Kadir,Aydin Yusuf,Akbaba Gulhan,Helvaci Nafiye,Guler Serdar
European journal of internal medicine
BACKGROUND:Transforming growth factor-beta 1 (TGF-β1) contributes to tissue repair by promoting tissue fibrosis, and elevations have been reported in patients with bone marrow fibrosis. The aim of this study was to evaluate the relationship between TGF-β1 levels and vitamin D deficiency. METHODS:All patients presenting to the outpatient Endocrinology and Metabolic Diseases clinic between June and September of 2008 were approached, and consenting patients who were deemed suitable candidates were enrolled. Hematological parameters were measured, along with serum levels of total and ionized calcium, phosphorus, parathyroid hormone, iron, folic acid vitamin B12 levels, 25 OH vitamin D3 (25OHD(3)) and TGF-β1. RESULTS:A total of 132 patients were included in the study. Patients were divided into 4 groups based on levels of 25OHD(3) [group 1 (<5 ng/ml), 20 patients; group 2 (5-15 ng/ml), 38 patients; group 3 (16-30 ng/ml); and group 4 (>30 ng/ml), 28 patients]. TGF-β1 levels were higher in patients in group 1 compared to the other groups. Transforming growth factor-beta levels correlated negatively with vitamin D3 and positively with leukocyte count, platelet count, of MCV and MCH. Multiple regression analyses revealed TGF-β1 levels to be associated with 25OHD(3) as well as with platelet count. CONCLUSIONS:Results of this study are suggestive of the presence of a significant relationship between TGF-β and vitamin D deficiency. Increased TGF-β1 and platelet count may be an early indicator of bone marrow fibrosis in patients with vitamin D deficiency.
10.1016/j.ejim.2011.09.017
Association Between Vitamin D and Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen in Children During Growth Hormone Replacement Therapy.
Witkowska-Sędek Ewelina,Stelmaszczyk-Emmel Anna,Kucharska Anna,Demkow Urszula,Pyrżak Beata
Advances in experimental medicine and biology
Growth hormone and insulin-like growth factor-1 (IGF-1) play a crucial role in the regulation of bone turnover. Adequate vitamin D status supports proper bone remodeling, leading to normal longitudinal bone growth and normal peak bone mass. The aim of this study was to evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] and carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) in children and adolescents with growth hormone deficiency at baseline and during recombinant human growth hormone (rhGH) replacement therapy. The study was prospective and included 30 children and adolescents aged 5 to 17 years. Concentrations of 25(OH)D, ICTP, and IGF-1 were measured at baseline and during the first year of rhGH therapy. Baseline serum 25(OH)D concentration correlated with ICTP concentrations during the first trimester of rhGH therapy (r = 0.38, p < 0.050); the correlation was stronger in the second trimester of therapy (r = 0.6, p = 0.002). We conclude that proper vitamin D status is important in reaching the adequate dynamics of bone remodeling during growth, which is essential to achieve a catch-up growth during rhGH therapy.
10.1007/5584_2017_109
Clinical Implications of Growth Hormone Deficiency for Oral Health in Children: A Systematic Review.
Torlińska-Walkowiak Natalia,Majewska Katarzyna Anna,Kędzia Andrzej,Opydo-Szymaczek Justyna
Journal of clinical medicine
Growth hormone (GH) is involved in the regulation of the postnatal dental and skeletal growth, but its effects on oral health have not been clearly defined. This paper aims to provide a review of current clinical knowledge of dental caries, tooth wear, developmental enamel defects, craniofacial growth and morphology, dental maturation, and tooth eruption in growth hormone deficient (GHD) children. A systematic review was carried out using Scopus, MEDLINE-EbscoHost and Web of Science from 2000 to May 2021. PRISMA guidelines for reporting systematic reviews were followed. All the selected studies involved groups under eighteen years of age, covering a total of 465 GHD patients. The studies that were selected provide reliable evidence for delayed dental maturity and orthodontic disturbances in GHD patients. Data on dental hard tissues pathology are scarce and are limited to occurrences of dental caries. GHD children showed abnormal craniofacial morphology with reduced mandibular dimensions, with a resulting tendency towards Angle's Class II occlusion, which affected up to 31% of patients. Dental age has been shown to be delayed in GHD patients by about 1 to 2 years. Moreover, the risk of dental caries in children with GHD decreases with increasing levels of vitamin D. Hence, further studies would be valuable for evaluating the risk of various oral health problems and to organize targeted dental care for this vulnerable group.
10.3390/jcm10163733
Vitamin D deficiency and fetal growth.
Brunvand L,Quigstad E,Urdal P,Haug E
Early human development
Vitamin D deficiency in pregnancy has been associated with decreased fetal growth, but previous studies have found no direct relation between the weight of the new-born child and the maternal serum level of 25-hydroxyvitamin D3 (calcidiol). The aim of this study was to evaluate the relation between maternal serum calcium and parathyroid hormone with reduced fetal growth in vitamin D deficient pregnant women. Thirty Pakistani women were included in the study at delivery. Only mothers without known chronic diseases who delivered vaginally after an uncomplicated pregnancy were included. Anthropometric data were recorded, and blood samples were drawn from the mothers 1-4 h after delivery. Nearly all (29/30) the Pakistani women had low (< 30 nmol/l) serum levels of 25-hydroxyvitamin D3. Thirteen of the mothers had high serum parathyroid hormone (PTH) levels (> 5.5 pmol/l). The median (range) level of ionised calcium in serum was 1.23 (1.15-1.28) nmol/l. A positive correlation was found between the level of ionised calcium in maternal serum and the crown-heel length of the infant (Spearman's rho = 0.65, P = 0.002, n = 20). The maternal serum PTH was related inversely to the crown-heel length (Spearman's rho = -0.47, P = 0.01, n = 30). No confounding effect of gestational age, sex of the infant, maternal height and body mass index (BMI) was found. The study indicates that vitamin D deficiency affects fetal growth through an effect on maternal calcium homeostasis.
Incidence rate of vitamin D deficiency and FGF23 levels in 12- to 13-year-old adolescents in Japan.
Koyama Satomi,Kubota Takuo,Naganuma Junko,Arisaka Osamu,Ozono Keiichi,Yoshihara Shigemi
Journal of bone and mineral metabolism
INTRODUCTION:The incidence rate of vitamin D deficiency is increasing throughout the world. We measured the incidence rate of vitamin D deficiency and fibroblast growth factor 23 (FGF23) levels in 12- to 13-year-old adolescents in Japan. MATERIALS AND METHODS:A total of 492 adolescents (247 boys and 245 girls) from Japanese community enrolled in this study. 25 hydroxyvitamin D (25(OH)D) was measured with radioimmunoassay. In the subjects with low 25(OH)D levels (≦ 20 ng/ml), intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), albumin (Alb), alkaline phosphatase (ALP) and FGF23 were measured. RESULTS:25(OH)D levels were significantly lower in girls (20.9 ± 3.1 ng/ml) than in boys (22.2 ± 3.3 ng/ml) (p < 0.0001). Fifty-five boys (22.3%) and 83 (33.9%) girls showed vitamin D deficiency (< 20 ng/ml). One-hundred eighty-six (75.3%) boys and 162 (66.1%) girls showed vitamin D insufficiency (≧ 20 ng/ml, < 30 ng/ml). In the subjects whose 25(OH)D levels were ≦ 20 ng/ml, the levels of iPTH, Ca, P, Alb, ALP and FGF23 were 22.3 ± 9.0 pg/ml, 9.5 ± 0.4 mg/dl, 4.7 ± 0.6 mg/dl, 4.6 ± 0.3 g/dl, 920.8 ± 339.3 U/l and 42.6 ± 26.0 pg/ml, respectively. There was a significant negative association between serum 25(OH)D levels and iPTH [r = - 0.290 (p < 0.0001)]. There was no significant association between serum 25(OH)D levels and FGF23. CONCLUSION:We show that 28% of Japanese 12- to 13-year-old early adolescents suffer from vitamin D deficiency. Findings from this study indicate that vitamin D deficiency requires close oversight in public health during adolescence to ensure proper bone health.
10.1007/s00774-020-01173-3
The relationship between alkaline phosphatase and bone alkaline phosphatase activity and the growth hormone/insulin-like growth factor-1 axis and vitamin D status in children with growth hormone deficiency.
Witkowska-Sędek Ewelina,Stelmaszczyk-Emmel Anna,Majcher Anna,Demkow Urszula,Pyrżak Beata
Acta biochimica Polonica
The relationships between bone turnover, the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and vitamin D are complex, but still not fully explained. The GH/IGF-1 axis and vitamin D can mutually modulate each other's metabolism and influence the activation of cell proliferation, maturation, and mineralization as well as bone resorption. The aim of this study was to evaluate the reciprocal associations between bone formation markers [alkaline phosphatase (ALP), bone alkaline phosphatase (BALP)], the GH/IGF-1 axis and 25-hydroxyvitamin D [25(OH)D] in children with growth hormone deficiency at baseline and during recombinant human growth hormone (rhGH) therapy. ALP, BALP, 25(OH)D and IGF-1 levels were evaluated in 53 patients included in this prospective three-year study. ALP, BALP and IGF-1 increased during rhGH therapy. Baseline ALP activity correlated positively with baseline height velocity (HV). ALP and BALP activity at 12 months correlated positively with HV in the first year of therapy. We found positive correlations between ALP and IGF-1 at baseline and during the first year of therapy, between BALP activity at 12 months and rhGH dose in the first year of therapy, and between doses of cholecalciferol in the first year of rhGH therapy and early changes in BALP activity during rhGH therapy. Our results indicate that vitamin D supplementation enhances the effect of rhGH on bone formation process, which could improve the effects of rhGH therapy. ALP and BALP activity are useful in the early prediction of the effects of rhGH therapy, but their utility as long-term predictors seemed insufficient.
10.18388/abp.2017_2541
Relationship Between 25(OH)D and IGF-I in Children and Adolescents with Growth Hormone Deficiency.
Witkowska-Sędek E,Kucharska A,Rumińska M,Pyrżak B
Advances in experimental medicine and biology
Recent studies have shown that vitamin D has an impact on the production and secretion of IGF-I in the liver. The aim of our study was to investigate the relationship between the concentrations of 25-hydroxy vitamin D [25(OH)D] and insulin-like growth factor I (IGF-I) in growth hormone deficient children and adolescents before recombinant human growth hormone (rhGH) treatment. The study was retrospective and included 84 children and adolescents aged 4-17. Prior to initiating rhGH therapy, concentrations of 25(OH)D and IGF-I were measured in all patients. IGF-I concentrations were normalized for bone age. The studied group was divided into two subgroups according to serum 25(OH)D levels. Significant positive correlations between 25(OH)D concentration and IGF-I SDS-normalized for bone age were observed in both studied subgroups. The results of our study suggest that vitamin D deficiency could influence IGF-I concentrations in children and adolescents with growth hormone deficiency, and vitamin D deficiency should be normalized before the measurement of IGF-I concentrations to obtain the reliable and unbiased IGF-I values.
10.1007/5584_2016_212
The role of parathyroid hormone during pregnancy on the relationship between maternal vitamin D deficiency and fetal growth restriction: a prospective birth cohort study.
Meng Deng-Hong,Zhang Ying,Ma Shuang-Shuang,Hu Hong-Lin,Li Jing-Jing,Yin Wan-Jun,Tao Rui-Xue,Zhu Peng
The British journal of nutrition
Previous studies have shown conflicting findings regarding the relationship between maternal vitamin D deficiency (VDD) and fetal growth restriction (FGR). We hypothesised that parathyroid hormone (PTH) may be an underlying factor relevant to this potential association. In a prospective birth cohort study, descriptive statistics were evaluated for the demographic characteristics of 3407 pregnancies in the second trimester from three antenatal clinics in Hefei, China. The association of the combined status of vitamin D and PTH with birth weight and the risk of small for gestational age (SGA) was assessed by a multivariate linear and binary logistic regression. We found that declined status of 25-hydroxyvitamin D is associated with lower birth weight (for moderate VDD: adjusted β = -49·4 g, 95 % CI -91·1, -7·8, P < 0·05; for severe VDD: adjusted β = -79·8 g, 95 % CI -127·2, -32·5, P < 0·01), as well as ascended levels of PTH (for elevated PTH: adjusted β = -44·5 g, 95 % CI -82·6, -6·4, P < 0·05). Compared with the non-VDD group with non-elevated PTH, pregnancies with severe VDD and elevated PTH had the lowest neonatal birth weight (adjusted β = -124·7 g, 95 % CI -194·6, -54·8, P < 0·001) and the highest risk of SGA (adjusted risk ratio (RR) = 3·36, 95 % CI 1·41, 8·03, P < 0·01). Notably, the highest risk of less Ca supplementation was founded in severe VDD group with elevated PTH (adjusted RR = 4·67, 95 % CI 2·78, 7·85, P < 0·001). In conclusion, elevated PTH induced by less Ca supplementation would further aggravate the risk of FGR in pregnancies with severe VDD through impaired maternal Ca metabolism homoeostasis.
10.1017/S0007114520001105
Does Vitamin D Status Correlate with Cardiometabolic Risk Factors in Adults with Growth Hormone Deficiency?
Uzunova Ivayla,Kirilov Georgi,Zacharieva Sabina,Zlatareva Naydenka,Kalinov Krasimir
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
Apart from being individually associated with cardiometabolic health, 25(OH)D and IGF-1 interplay with a positive correlation between them, which raises questions about the role of vitamin D for the adverse cardiovascular (CV) risk profile in hyposomatotropism. Thus, we aimed to investigate vitamin D status in GH deficiency (GHD) and the association between 25(OH)D and metabolic syndrome (MetS), its components, and other surrogate markers of CV risk. A total of 129 GHD adults (childhood-onset GHD, 41.9%) underwent blood testing (glucose, insulin, lipid profile, uric acid); blood pressure, anthropometric and bioelectrical-impedance measurements. Other CV risk markers were examined in a subsample of the initial population - hsCRP, adiponectin, and asymmetric dimethylarginine (n=88); carotid intima-media thickness (n=44). Total serum 25(OH)D, measured by electro-chemiluminescence binding assay, was used for vitamin D status assessment (adequate,≥30 ng/ml; insufficient, 20-29.9 ng/ml; deficient,<20 ng/ml). Data demonstrated high prevalence of hypovitaminosis D in GHD (deficiency 79.1%; insufficiency 14.7%), with lower 25(OH)D among adult-onset GHD subjects (14.0±7.2 vs. 16.8±8.0 ng/ml, p=0.039) and patients with MetS (11.8±4.5 vs. 16.3±8.1 ng/ml, p<0.0001). 25(OH)D correlated negatively and weakly with BMI, waist circumference, percent body fat, visceral fat area, and systolic BP. Regardless of whether vitamin D is a cause or a consequence of these metabolic abnormalities, 25(OH)D testing in hyposomatotropism is advisable. Normalization of vitamin D status is not proven to improve CV outcomes in general population, but it might have favorable effects in GHD, as its benefits might be restricted to patients with both low 25(OH)D and certain risk factors.
10.1055/s-0043-100114
Dental caries and vitamin D3 in children with growth hormone deficiency: A STROBE compliant study.
Wójcik Dorota,Krzewska Aleksandra,Szalewski Leszek,Pietryka-Michałowska Elżbieta,Szalewska Magdalena,Krzewski Szymon,Pels Elżbieta,Beń-Skowronek Iwona
Medicine
Vitamin D may prevent dental caries. To date, no attempts have been made to examine the correlation between the incidence of caries and the concentrations of vitamin D in children with pituitary growth hormone deficiency.The study observed patients of the Department of Endocrinology and Diabetology of the University Paediatric Hospital of the Medical University of Lublin treated with human recombinant growth hormone for pituitary growth hormone deficiency (GHD). The study was conducted between October 2014 and June 2015. The study group consisted of 121 children and adolescents (6-17 years old), including 56 children from rural areas and 65 children from urban areas. The study group was stratified by area of residence.In our study, the increase in vitamin D3 [25(OH)D] levels reduced the D component by 0.66 per each 10 ng/mL of vitamin D3 concentration. The percentage of children with active caries in rural areas is 91.07% (n = 51), which is significantly higher than the percentage of children with active caries in urban areas (81.54%, n = 53).To date, information regarding the potential possibility of reducing the incidence of dental caries by means of increasing the levels of vitamin D was sidelined by paediatricians and dentists alike. Therefore, this aspect of caries prevention should be highlighted.
10.1097/MD.0000000000009811
Effects of early vitamin D deficiency rickets on bone and dental health, growth and immunity.
Zerofsky Melissa,Ryder Mark,Bhatia Suruchi,Stephensen Charles B,King Janet,Fung Ellen B
Maternal & child nutrition
Vitamin D deficiency is associated with adverse health outcomes, including impaired bone growth, gingival inflammation and increased risk for autoimmune disease, but the relationship between vitamin D deficiency rickets in childhood and long-term health has not been studied. In this study, we assessed the effect of early vitamin D deficiency on growth, bone density, dental health and immune function in later childhood to determine if children previously diagnosed with rickets were at greater risk of adverse health outcomes compared with healthy children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone, bone mineral density, anthropometric measures, dietary habits, dental health, general health history, and markers of inflammation in 14 previously diagnosed rickets case children at Children's Hospital Oakland Research Center. We compared the findings in the rickets cases with 11 healthy children selected from the population of CHO staff families. Fourteen mothers of the rickets cases, five siblings of the rickets cases, and seven mothers of healthy children also participated. Children diagnosed with vitamin D deficiency rickets had a greater risk of fracture, greater prevalence of asthma, and more dental enamel defects compared with healthy children. Given the widespread actions of vitamin D, it is likely that early-life vitamin D deficiency may increase the risk of disease later in childhood. Further assessment of the long-term health effects of early deficiency is necessary to make appropriate dietary recommendations for infants at risk of deficiency.
10.1111/mcn.12187
Vitamin D status in prepubertal children with isolated idiopathic growth hormone deficiency: effect of growth hormone therapy.
Hamza Rasha Tarif,Hamed Amira I,Sallam Mahmoud T
Journal of investigative medicine : the official publication of the American Federation for Clinical Research
Few studies, and with controversial results, analyzed vitamin D status in children before and after growth hormone (GH) treatment. Thus, we aimed to assess vitamin D status in prepubertal children with idiopathic growth hormone deficiency (GHD), and to evaluate the effect of GHD and GH treatment on vitamin D levels. Fifty prepubertal children with isolated GHD were compared with 50 controls. All were subjected to history, anthropometric assessment and measurement of 25 hydroxyvitamin D (25(OH)D), serum calcium, phosphorous, alkaline phosphatase and parathyroid hormone (PTH) at diagnosis and 1 year after GH therapy. Serum 25(OH)D levels <30 ng/mL and 20 ng/mL were defined as vitamin D insufficiency and deficiency, respectively. 25(OH)D was lower in cases than controls. Forty per cent of children with GHD were 25(OH)D insufficient and 44% deficient, while 16% were sufficient at baseline. There was a positive correlation between 25(OH)D and peak GH levels. Peak GH was a significant predictor of 25(OH)D levels. After 1 year of GH therapy, 25(OH)D increased (18.42±5.41 vs 34.5±10.1 ng/mL; P<0.001). Overall, 22% of cases remained insufficient and 24% deficient, with an increase in prevalence of children with normal levels (54%; P<0.001). 25(OH) correlated negatively with PTH (r=-0.71, P=0.01). In conclusion, hypovitaminosis D is prevalent in children with GHD and significantly improved 1 year after GH therapy. 25(OH)D should be assessed in children with GHD at diagnosis and during follow-up.
10.1136/jim-2017-000618
Vitamin D status and response to growth hormone treatment in prepubertal children with growth hormone deficiency.
Durá-Travé T,Gallinas-Victoriano F,Moreno-González P,Urretavizcaya-Martinez M,Berrade-Zubiri S,Chueca-Guindulain M J
Journal of endocrinological investigation
PURPOSE:To analyze whether vitamin D deficiency could condition the growth response to GH therapy, as well as to analyze if GH treatment modifies both seasonal variations and vitamin D levels in these patients. METHODS:Retrospective study in 98 prepubertal children with GH deficiency (GHD), aged 4.1-8.9 years treated with GH. Growth rate and blood testing (calcium, phosphorus, IGF-I, 25(0H)D and PTH) were monitored at diagnostic and every six months until 24 months of treatment. A control group was recruited (247 healthy children, aged 3.8-9.7 years). The criteria of the US Endocrine Society were used for the definition of hypovitaminosis D. RESULTS:There were no significant differences in vitamin D deficiency among control (12.5%) and GHD groups (15.3%) before starting treatment. Growth rate and IGF-1 and PTH increased (p < 0.05) during GH treatment, but there were no significant differences in calcium, phosphorus and 25(OH)D. There were no significant differences in growth rate and IGF-1, calcium and phosphorus levels in relation to the seasons along GH treatment. There was no correlation between 25(OH)D and IGF-1 during GH therapy. In every programmed control, patients with vitamin D deficiency showed lower growth rate (p < 0.05) compared to patients with vitamin D insufficiency or sufficiency. CONCLUSION:GH treatment, at least during the first two years, does not modify the vitamin D levels. Vitamin D deficiency could condition the response to GH therapy so vitamin D monitoring should be considered as part of the routine evaluation of children with GH treatment.
10.1007/s40618-020-01227-3
Functions of vitamin D in bone.
Goltzman D
Histochemistry and cell biology
Vitamin D, synthesized in the skin or absorbed from the diet, undergoes multi-step enzymatic conversion to its active form, 1,25-dihydroxy vitamin D [1,25(OH)D], followed by interaction with the vitamin D receptor (VDR), to modulate target gene expression. Loss-of function mutations in the genes encoding the enzymes regulating these processes, or in the VDR, result in human diseases, which have demonstrated the paramount role of 1,25(OH)D in mineral and skeletal homeostasis. Mouse genetics has been used to create disease phenocopies which have produced considerable insight into the mechanisms of 1,25(OH)D regulation of mineral and skeletal metabolism. Hypophosphatemia resulting from 1,25(OH)D deficiency or resistance can inhibit apoptosis in hypertrophic chondrocytes leading to abnormal development of the cartilaginous growth plate in rickets. Decreased 1,25(OH)D may also cause decreased vascular invasion associated with reduced chondroclast and osteoclast activity and thereby contribute to growth plate abnormalities. Reduced 1,25(OH)D-mediated intestinal and renal calcium transport can reduce calcium availability, increase parathyroid hormone secretion and phosphaturia, and impair mineral availability for normal matrix mineralization, resulting in reduced growth plate mineralization and osteomalacia. 1,25(OH)D may exert an anabolic effect in bone, apparently via the VDR in mature osteoblasts, by increasing osteoblast activity and reducing osteoclast activity. High ambient levels of exogenous 1,25(OH)D, or of elevated endogenous 1,25(OH)D in the presence of reduced calcium balance, can enhance bone resorption, and apparently prevent mineral deposition in bone. These actions demonstrate the critical role of vitamin D in regulating skeletal homeostasis both indirectly and directly via the 1,25(OH)D/VDR system.
10.1007/s00418-018-1648-y
ANALYSIS OF THE VITAMIN D RECEPTOR BSMI GENE POLYMORPHISM IN CHILDREN WITH GROWTH HORMONE DEFICIENCY.
Bolshova Elena V,Ryznychuk Mariana A,Kvacheniuk Dmitry A
Wiadomosci lekarskie (Warsaw, Poland : 1960)
OBJECTIVE:The aim: The objective of the study was to investigate the polymorphism of the vitamin D receptor (VDR) BsmI gene in children with growth hormone deficiency and the level of their vitamin D supply. PATIENTS AND METHODS:Materials and methods: Sixteen children diagnosed with of growth hormone deficiency who were treated at the State Institution «V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine» were examined. The patient's gender and age, the anthropometric data, the vitamin D level in the blood, the bone age, the GH level, the IGF-1 levels, the level of calcium in the blood and VDR gene polymorphism were taken into account. RESULTS:Results: It was shown that in the presence of the G/A genotype, the risk of growth hormone deficiency development was increased OR = 1,096 (95% CI 0.39-3.02; p = 0.86). For BsmI, mean values of height, body mass, height SDS, serum 25(OH)D, in the studied population (16 children) were 123.49 ± 19.62 cm, 26.96 ± 11.11 kg, -2.25 ± 0.85, 48.86 ± 16.71 nmol/l, respectively; total calcium level consisted of 2.40 ± 0.12 mmol/l, serum phosphorus - 1.43 ± 0.11 mmol/l. CONCLUSION:Conclusions: The allele frequency of the VDR BsmI polymorphism was 62.5% for the G allele (n = 20) and 37.5% for the allele A (n = 12). The G allele carrier of the polymorphic locus BsmI rs1544410 of the VDR gene (rs11568820) is associated with an increased risk of growth hormone deficiency development OR = 1.31 (95% CI 0.62-2.75; p = 0.47).
Vitamin D in children with growth hormone deficiency due to pituitary stalk interruption syndrome.
Delecroix Cécile,Brauner Raja,Souberbielle Jean-Claude
BMC pediatrics
BACKGROUND:Recent studies have shown a relationship between vitamin D status and growth hormone (GH) and insulin-like growth factor 1 (IGF1). The objective of this study was to assess vitamin D status in children with GH deficiency due to pituitary stalk interruption syndrome (PSIS) and to investigate the relationship between 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25 (OH) D) serum levels and patient characteristics. METHODS:A retrospective single-center study of 25OHD and 1,25(OH)D serum concentrations in 50 children with PSIS at the initial evaluation before treatment. RESULTS:Mean concentrations of 33.2 ± 18.0 ng/mL for 25OHD and 74.5 ± 40.7 ng/L for 1,25(OH)D were measured. Additionally, 25OHD concentrations were significantly higher in boys than in girls (p = 0.04) and lower in the cold season than in the sunny season (p = 0.03). Significant positive correlations were observed between the GH peak and serum 1,25 (OH) D concentrations (Rho = 0.35; p = 0.015) and the 1,25(OH)D/25OHD ratio (Rho = 0.29; p < 0.05). No correlation was found for other characteristics, including IGF1. CONCLUSIONS:Vitamin D status in children with hypothalamic-pituitary deficiency due to PSIS was similar to that reported in national and European studies in healthy children. The positive significant correlations between the GH peak and the 1,25 (OH)D concentration as well as with the 1,25 (OH)D/25OHD ratio suggest that even in these patients who had severely impaired GH secretion and low IGF1 levels, an interplay between the GH/IGF1 axis and the vitamin D system still exists.
10.1186/s12887-018-0992-3
Vitamin D and Dental Caries in Children with Growth Hormone Deficiency.
Wójcik Dorota,Szalewski Leszek,Pietryka-Michałowska Elżbieta,Borowicz Janusz,Pels Elżbieta,Beń-Skowronek Iwona
International journal of endocrinology
Vitamin D deficiency is a common risk factor for multifactorial diseases, and it seems to be associated with growth hormone deficiency (GHD). Vitamin D could prevent dental caries. The goal of this study was to identify whether there is an association between hormonal therapy with growth hormone (GH), vitamin D supplementation, vitamin D levels, and the occurrence of caries among children affected by GHD. The study group consisted of patients from the Department of Endocrinology and Diabetology of the University Paediatric Hospital at the Medical University of Lublin treated with recombinant human GH for pituitary GHD. It was conducted between October 2014 and June 2015. The study group included 121 children and adolescents aged 6 to 18 years, with 56 children from rural areas and 65 from urban areas. The study group was stratified by the area of residence. We found the statistically significant impact of vitamin D concentration on the average value of the DMFT (decayed, missed, and filled teeth) index and its component-DT (decayed teeth), which was noted in subjects from rural areas. Among patients from urban areas, we found a statistically significant correlation between duration of therapy and the DMFT index. An increase in duration of GH therapy by 10 months leads to a mean increase in DMFT index by 0.70. Based on multiple regression analysis, we developed the following model: value of DT = 3.10 - 0.73category of vitamin D concentration - 0.07duration of supplementation (in months). In this model, variables with a significant impact on the value of DT in the group of patients from rural areas include time of vitamin D supplementation and category of vitamin D concentration. Greater emphasis should be placed on promoting vitamin D as a potentially effective agent reducing the number of dental caries, especially among patients with GHD.
10.1155/2019/2172137
Effect of Vitamin D Combined with Recombinant Human Growth Hormone in Children with Growth Hormone Deficiency.
Disease markers
Objective:Growth hormone deficiency (GHD) refers to the complete or partial lack of pituitary growth hormone synthesis and secretion. This study is aimed at investigating the efficacy of vitamin D and recombinant human growth hormone (rhGH) in children with GHD. Methods:A total of 100 children with GHD at our hospital were included between 1 January 2018 and 31 October 2020. The patients were divided into a study group ( = 70, received vitamin D combined with rhGH) and a control group ( = 30, received rhGH). The growth and development (bone age, growth rate, and height), bone metabolism (bone alkaline phosphatase (BAP), -collagen degradation product (-CTX), osteocalcin (OC), and amino-terminal propeptide type I procollagen (PINP)), insulin-like growth factor 1 (IGF-1), ghrelin, and adverse reactions in the two groups were measured before and 12 months after treatment. Results:There were no significant differences in the bone age, growth rate, and height between the two groups before treatment. After 12 months of treatment, the bone age, growth rate, and height of the study group were significantly higher than those of the control group. After 12 months of treatment, the levels of serum BAP, PINP, and OC in the study group were significantly higher than those in the control group, while the levels of -CTX in the study group were significantly lower than those in the control group. The serum IGF-1 level in the study group was significantly higher than that in the control group, while the ghrelin level in the study group was lower. There was no significant difference in the incidence of adverse reactions between the two groups. Conclusion:Combined rhGH and vitamin D treatment can promote growth and development, improve bone metabolism, and regulate IGF-1 and ghrelin levels.
10.1155/2022/7461958
Vitamin D and growth hormone in children: a review of the current scientific knowledge.
Esposito Susanna,Leonardi Alberto,Lanciotti Lucia,Cofini Marta,Muzi Giulia,Penta Laura
Journal of translational medicine
BACKGROUND:Human growth is a complex mechanism that depends on genetic, environmental, nutritional and hormonal factors. The main hormone involved in growth at each stage of development is growth hormone (GH) and its mediator, insulin-like growth factor 1 (IGF-1). In contrast, vitamin D is involved in the processes of bone growth and mineralization through the regulation of calcium and phosphorus metabolism. Nevertheless, no scientific study has yet elucidated how they interact with one another, especially as a dysfunction in which one influences the other, even if numerous biochemical and clinical studies confirm the presence of a close relationship. MAIN BODY:We reviewed and analyzed the clinical studies that have considered the relationship between vitamin D and the GH/IGF-1 axis in pediatric populations. We found two main areas of interest: the vitamin D deficiency status in patients affected by GH deficit (GHD) and the relationship between serum vitamin D metabolites and IGF-1. Although limited by some bias, from the analysis of the studies presented in the scientific literature, it is possible to hypothesize a greater frequency of hypovitaminosis D in the subjects affected by GHD, a reduced possibility of its correction with only substitution treatment with recombinant growth hormone (rGH) and an improvement of IGF-1 levels after supplementation treatment with vitamin D. CONCLUSIONS:These results could be followed by preventive interventions aimed at reducing the vitamin D deficit in pediatric age. In addition, further research is needed to fully understand how vitamin D and growth are intertwined.
10.1186/s12967-019-1840-4
Vitamin D physiology.
Lips P
Progress in biophysics and molecular biology
Vitamin D3 is synthesized in the skin during summer under the influence of ultraviolet light of the sun, or it is obtained from food, especially fatty fish. After hydroxylation in the liver into 25-hydroxyvitamin D (25(OH)D) and kidney into 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite can enter the cell, bind to the vitamin D-receptor and subsequently to a responsive gene such as that of calcium binding protein. After transcription and translation the protein is formed, e.g. osteocalcin or calcium binding protein. The calcium binding protein mediates calcium absorption from the gut. The production of 1,25(OH)2D is stimulated by parathyroid hormone (PTH) and decreased by calcium. Risk factors for vitamin D deficiency are premature birth, skin pigmentation, low sunshine exposure, obesity, malabsorption and advanced age. Risk groups are immigrants and the elderly. Vitamin D status is dependent upon sunshine exposure but within Europe, serum 25(OH)D levels are higher in Northern than in Southern European countries. Severe vitamin D deficiency causes rickets or osteomalacia, where the new bone, the osteoid, is not mineralized. Less severe vitamin D deficiency causes an increase of serum PTH leading to bone resorption, osteoporosis and fractures. A negative relationship exists between serum 25(OH)D and serum PTH. The threshold of serum 25(OH)D, where serum PTH starts to rise is about 75nmol/l according to most surveys. Vitamin D supplementation to vitamin D-deficient elderly suppresses serum PTH, increases bone mineral density and may decrease fracture incidence especially in nursing home residents. The effects of 1,25(OH)2D and the vitamin D receptor have been investigated in patients with genetic defects of vitamin D metabolism and in knock-out mouse models. These experiments have demonstrated that for active calcium absorption, longitudinal bone growth and the activity of osteoblasts and osteoclasts both 1,25(OH)2D and the vitamin D receptor are essential. On the other side, bone mineralization can occur by high ambient calcium concentration, so by high doses of oral calcium or calcium infusion. The active metabolite 1,25(OH)2D has its effects through the vitamin D receptor leading to gene expression, e.g. the calcium binding protein or osteocalcin or through a plasma membrane receptor and second messengers such as cyclic AMP. The latter responses are very rapid and include the effects on the pancreas, vascular smooth muscle and monocytes. Muscle cells contain vitamin D receptor and several studies have demonstrated that serum 25(OH)D is related to physical performance. The active metabolite 1,25(OH)2D has an antiproliferative effect and downregulates inflammatory markers. Extrarenal synthesis of 1,25(OH)2D occurs under the influence of cytokines and is important for the paracrine regulation of cell differentiation and function. This may explain that vitamin D deficiency can play a role in the pathogenesis of auto-immune diseases such as multiple sclerosis and diabetes type 1, and cancer. In conclusion, the active metabolite 1,25(OH)2D has pleiotropic effects through the vitamin D receptor and vitamin D responsive elements of many genes and on the other side rapid non-genomic effects through a membrane receptor and second messengers. Active calcium absorption from the gut depends on adequate formation of 1,25(OH)2D and an intact vitamin D receptor. Bone mineralization mainly depends on ambient calcium concentration. Vitamin D metabolites may play a role in the prevention of auto-immune disease and cancer.
10.1016/j.pbiomolbio.2006.02.016
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF GROWTH HORMONE DEFICIENCY IN ADULTS AND PATIENTS TRANSITIONING FROM PEDIATRIC TO ADULT CARE.
Yuen Kevin C J,Biller Beverly M K,Radovick Sally,Carmichael John D,Jasim Sina,Pantalone Kevin M,Hoffman Andrew R
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPG). Recommendations are based on diligent reviews of clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. The Executive Summary of this 2019 updated guideline contains 58 numbered recommendations: 12 are Grade A (21%), 19 are Grade B (33%), 21 are Grade C (36%), and 6 are Grade D (10%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 357 citations of which 51 (14%) are evidence level (EL) 1 (strong), 168 (47%) are EL 2 (intermediate), 61 (17%) are EL 3 (weak), and 77 (22%) are EL 4 (no clinical evidence). This CPG is a practical tool that practicing endocrinologists and regulatory bodies can refer to regarding the identification, diagnosis, and treatment of adults and patients transitioning from pediatric to adult-care services with growth hormone deficiency (GHD). It provides guidelines on assessment, screening, diagnostic testing, and treatment recommendations for a range of individuals with various causes of adult GHD. The recommendations emphasize the importance of considering testing patients with a reasonable level of clinical suspicion of GHD using appropriate growth hormone (GH) cut-points for various GH-stimulation tests to accurately diagnose adult GHD, and to exercise caution interpreting serum GH and insulin-like growth factor-1 (IGF-1) levels, as various GH and IGF-1 assays are used to support treatment decisions. The intention to treat often requires sound clinical judgment and careful assessment of the benefits and risks specific to each individual patient. Unapproved uses of GH, long-term safety, and the current status of long-acting GH preparations are also discussed in this document. This updated guideline provides evidence-based recommendations regarding the identification, screening, assessment, diagnosis, and treatment for a range of individuals with various causes of adult growth-hormone deficiency (GHD) and patients with childhood-onset GHD transitioning to adult care. The update summarizes the most current knowledge about the accuracy of available GH-stimulation tests, safety of recombinant human GH (rhGH) replacement, unapproved uses of rhGH related to sports and aging, and new developments such as long-acting GH preparations that use a variety of technologies to prolong GH action. Recommendations offer a framework for physicians to manage patients with GHD effectively during transition to adult care and adulthood. Establishing a correct diagnosis is essential before consideration of replacement therapy with rhGH. Since the diagnosis of GHD in adults can be challenging, GH-stimulation tests are recommended based on individual patient circumstances and use of appropriate GH cut-points. Available GH-stimulation tests are discussed regarding variability, accuracy, reproducibility, safety, and contraindications, among other factors. The regimen for starting and maintaining rhGH treatment now uses individualized dose adjustments, which has improved effectiveness and reduced reported side effects, dependent on age, gender, body mass index, and various other individual characteristics. With careful dosing of rhGH replacement, many features of adult GHD are reversible and side effects of therapy can be minimized. Scientific studies have consistently shown rhGH therapy to be beneficial for adults with GHD, including improvements in body composition and quality of life, and have demonstrated the safety of short- and long-term rhGH replacement. = American Association of Clinical Endocrinologists; = American College of Endocrinology; = alpha-2-HS-glycoprotein; = adult-onset growth hormone deficiency; = arginine; = best evidence level; = bone mineral density; = body mass index; = confidence interval; = childhood-onset growth hormone deficiency; = clinical practice guideline; = C-reactive protein; = diabetes mellitus; = dual-energy X-ray absorptiometry; = evidence level; = Food and Drug Administration; = fixed-dose glucagon stimulation test; = Genetics and Neuroendocrinology of Short Stature International Study; = growth hormone; = growth hormone deficiency; = growth hormone-releasing hormone; = glucagon stimulation test; = high-density lipoprotein; = Hypopituitary Control and Complications Study; = insulin-like growth factor-1; = insulin-like growth factor-binding protein; = isolated growth hormone deficiency; = insulin tolerance test; = Kabi International Metabolic Surveillance; = long-acting growth hormone; = low-density lipoprotein; = leukemia inhibitory factor; = multiple pituitary hormone deficiencies; = magnetic resonance imaging; = procollagen type-III amino-terminal pro-peptide; = pituitary hormone deficiencies; = quality of life; = recombinant human growth hormone; = receiver operating characteristic; = relative risk; = subarachnoid hemorrhage; = standard deviation score; = standardized incidence ratio; = secondary neoplasms; = triiodothyronine; = traumatic brain injury; = vitamin D-binding protein; = World Anti-Doping Agency; = weight-based glucagon stimulation test.
10.4158/GL-2019-0405
Vitamin D and Parathyroid Hormone during Growth Hormone Treatment.
Children (Basel, Switzerland)
Background. There is some controversy concerning a potential interaction between vitamin D and PTH and the GH/IGF-1 axis. The goal of this study is to assess vitamin D and PTH status in children with GH deficiency at diagnostic and during treatment with rhGH. Methods. Longitudinal and descriptive study in 110 patients, aged 3.3−9.1 years, with GH deficiency (GHD group) treated with rhGH. At diagnosis and after 12, 24, 36, and 48 months of treatment, a clinical (height, weight, and bone age) and laboratory (phosphorus, calcium, calcidiol, PTH, IGF-1) evaluation was performed. Concurrently, 377 healthy children, aged 3.8−9.7 years, were enrolled and constituted a control group. Vitamin D status was stated in accordance to the U.S. Endocrine Society criteria. Results. No significant differences were found in the prevalence of vitamin D deficiency among control (11.43%) and GHD (13.6%) groups at the moment of diagnosis, remaining without significant changes at 12 (12.9%), 24 (14.6%), 36 (13.1%), and 48 months (13.3%) of treatment. There were not any significant differences in serum levels of calcium, phosphorus, and calcidiol, but a steady increase (p < 0.001) in PTH was detected. Conclusions. Prepubertal patients with GH deficient do not appear to have a higher risk of vitamin D deficiency than healthy subjects, and with treatment with rhGH, no changes in the organic content of vitamin D were observed although a significant increase in PTH levels was detected.
10.3390/children9050725
Vitamin D.
Dusso Adriana S,Brown Alex J,Slatopolsky Eduardo
American journal of physiology. Renal physiology
The vitamin D endocrine system plays an essential role in calcium homeostasis and bone metabolism, but research during the past two decades has revealed a diverse range of biological actions that include induction of cell differentiation, inhibition of cell growth, immunomodulation, and control of other hormonal systems. Vitamin D itself is a prohormone that is metabolically converted to the active metabolite, 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. This vitamin D hormone activates its cellular receptor (vitamin D receptor or VDR), which alters the transcription rates of target genes responsible for the biological responses. This review focuses on several recent developments that extend our understanding of the complexities of vitamin D metabolism and actions: the final step in the activation of vitamin D, conversion of 25-hydroxyvitamin D to 1,25(OH)(2)D in renal proximal tubules, is now known to involve facilitated uptake and intracellular delivery of the precursor to 1alpha-hydroxylase. Emerging evidence using mice lacking the VDR and/or 1alpha-hydroxylase indicates both 1,25(OH)(2)D(3)-dependent and -independent actions of the VDR as well as VDR-dependent and -independent actions of 1,25(OH)(2)D(3). Thus the vitamin D system may involve more than a single receptor and ligand. The presence of 1alpha-hydroxylase in many target cells indicates autocrine/paracrine functions for 1,25(OH)(2)D(3) in the control of cell proliferation and differentiation. This local production of 1,25(OH)(2)D(3) is dependent on circulating precursor levels, providing a potential explanation for the association of vitamin D deficiency with various cancers and autoimmune diseases.
10.1152/ajprenal.00336.2004
Vitamin D across growth hormone (GH) disorders: From GH deficiency to GH excess.
Ciresi A,Giordano C
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society
The interplay between vitamin D and the growth hormone (GH)/insulin-like growth factor (IGF)-I system is very complex and to date it is not fully understood. GH directly regulates renal 1 alpha-hydroxylase activity, although the action of GH in modulating vitamin D metabolism may also be IGF-I mediated. On the other hand, vitamin D increases circulating IGF-I and the vitamin D deficiency should be normalized before measurement of IGF-I concentrations to obtain reliable and unbiased IGF-I values. Indeed, linear growth after treatment of nutritional vitamin D deficiency seems to be mediated through activation of the GH/IGF-I axis and it suggests an important role of vitamin D as a link between the proliferating cartilage cells of the growth plate and GH/IGF-I secretion. Vitamin D levels are commonly lower in patients with GH deficiency (GHD) than in controls, with a variable prevalence of insufficiency or deficiency, and this condition may worsen the already known cardiovascular and metabolic risk of GHD, although this finding is not common to all studies. In addition, data on the impact of GH treatment on vitamin D levels in GHD patients are quite conflicting. Conversely, in active acromegaly, a condition characterized by a chronic GH excess, both increased and decreased vitamin D levels have been highlighted, and the interplay between vitamin D and the GH/IGF-I axis becomes even more complicated when we consider the acromegaly treatment, both medical and surgical. The current review summarizes the available data on vitamin D in the main disorders of the GH/IGF-I axis, providing an overview of the current state of the art.
10.1016/j.ghir.2017.02.002
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