Acromesomelic Dysplasia, Type Maroteaux: Impact of Long-Term (8 Years) High-Dose Growth Hormone Treatment on Growth Velocity and Final Height in 2 Siblings

2020 ◽  
Vol 93 (5) ◽  
pp. 335-342
Author(s):  
Ved Bhushan Arya ◽  
Meena Raj ◽  
Maha Younes ◽  
Simon Chapman ◽  
Melita Irving ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Serum Insulin ◽  
Final Height ◽  
Hormone Treatment ◽  
High Dose ◽  
Childhood And Adolescence ◽  
Loss Of Function ◽  
Gh Treatment ◽  
Height Gain

<b><i>Introduction:</i></b> Acromesomelic dysplasia, type Maroteaux (AMDM) is a rare autosomal recessive skeletal dysplasia, characterized by severe dwarfism and disproportionate limb shortening. It results from loss-of-function <i>NPR2</i> mutations affecting the C-type natriuretic peptide receptor. Resistance to growth hormone (GH) action has previously been suggested. We describe outcomes of 2 siblings with AMDM after prolonged high-dose GH treatment. <b><i>Patients/Methods:</i></b> Two siblings (Pt-A and Pt-B; consanguineous parents) presented in early childhood with severe disproportionate short stature and radiological features of AMDM. Subsequent genetic testing identified a novel homozygous <i>NPR2</i> mutation. GH provocation testing showed relatively high GH levels. Serum insulin-like growth factor 1 (IGF-1) was ∼2 SD below age/sex-specific mean. High-dose GH (0.075 mg/kg/day) was started. Pre-GH height velocities were 3.7 (Pt-A) and 4.5 (Pt-B) cm/year. GH dose was adjusted to sustain serum IGF-1 towards +3 SDS for age/sex. Annualized height velocities for first 3 years on GH were 7.0, 5.4, and 4.7 cm/year for patient A and 9.4, 8.0, and 5.9 cm/year for patient B. Height gain during puberty was 10.6 (Pt-A) and 5.9 (Pt-B) cm. Final heights after 8.5 years of GH treatment were 130.5 cm (−6.57 SDS, Pt-A) and 134 cm (−4.58 SDS, Pt-B). <b><i>Conclusions:</i></b> To the best of our knowledge, this is the first report of final height in patients with AMDM after long-term GH treatment. Our results confirm the finding of relative GH resistance in AMDM, which when overcome with high-dose GH treatment resulted in improved height SDS during childhood and adolescence and associated quality of life. The final height of our patients was significantly higher than average reported final height (120 cm) of AMDM patients.

Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children

2017 ◽  
Vol 30 (2) ◽  
Author(s):  
Lucia Schena ◽  
Cristina Meazza ◽  
Sara Pagani ◽  
Valeria Paganelli ◽  
Elena Bozzola ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Final Height ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Gh Treatment ◽  
Short Children ◽  
Igf I ◽  
Height Gain ◽  
The Cost

AbstractBackground:In recent years, several studies have been published showing different responses to growth hormone (GH) treatment in idiopathic short stature children. The aim of the present study was to investigate whether non-growth-hormone-deficient (non-GHD) short children could benefit from long-term GH treatment as GHD patients.Methods:We enrolled 22 prepubertal children and 22 age- and sex-matched GHD patients, with comparable height, body mass index (BMI), bone age, and insulin-like growth factor 1 (IGF-I) circulating levels. The patients were treated with recombinant human GH (rhGH) and followed until they reach adult height.Results:During GH treatment, the two groups grew in parallel, reaching the same final height-standard deviation score (SDS) and the same height gain. On the contrary, we found significantly lower IGF-I serum concentrations in non-GHD patients than in GHD ones, at the end of therapy (p=0.0055).Conclusions:In our study, the response to GH treatment in short non-GHD patients proved to be similar to that in GHD ones. However, a careful selection of short non-GHD children to be treated with GH would better justify the cost of long-term GH therapy.

scholarly journals Long-Term Effectiveness and Safety of Childhood Growth Hormone Treatment in Noonan Syndrome

2020 ◽  
Vol 93 (6) ◽  
pp. 380-395
Author(s):  
Tilman R. Rohrer ◽  
Jennifer Abuzzahab ◽  
Philippe Backeljauw ◽  
Anna Camilla Birkegård ◽  
Joanne Blair ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Adverse Events ◽  
Noonan Syndrome ◽  
Standard Deviation Score ◽  
Hormone Treatment ◽  
Gh Treatment ◽  
Serious Adverse Events ◽  
Height Gain ◽  
The Mean

<b><i>Introduction:</i></b> Few data exist on long-term growth hormone (GH) treatment in patients with Noonan syndrome (NS). <b><i>Objective:</i></b> To evaluate the effectiveness and safety of GH treatment in NS in clinical practice. <b><i>Methods:</i></b> Height gain, near-adult height (NAH), and safety were assessed in 2 complementary non-interventional studies: NordiNet® IOS and ANSWER. The safety analysis included 412 patients, and the effectiveness analysis included 84 GH-treated patients (male, <i>n</i> = 67) with ≥4 years’ height standard deviation score (HSDS) data. HSDS was determined using national reference (NR) and NS-specific (NSS) data. <b><i>Results:</i></b> The mean (SD) baseline age was 8.38 (3.57) years; HSDS, −2.76 (1.03); GH dose, 41.6 (11.1) µg/kg/day. The mean (SD) HSDS increase from baseline (ΔHSDS) was 0.49 (0.37) (first year), 0.79 (0.58) (second year), and 1.01 (0.60) (third year) (NR). The mean (SD) HSDS at year 3 was −1.66 (1.00) (NR; 1.06 [1.12] [NSS]). Twenty-four patients achieved NAH. The mean (SD) NAH SDS (NR) was −1.51 (0.60) (154.90 [3.21] cm) in females and −1.79 (1.09) (165.61 [7.19] cm) in males; 70.8% (17/24) had NAH SDS ≥ −2. Adverse drug reactions and GH-unrelated serious adverse events (<i>n</i> = 34) were reported in 22/412 (5.3%) patients. Four neoplasms and 3 cases of scoliosis were reported; no cardiovascular adverse events occurred. <b><i>Conclusions:</i></b> GH-treated children with NS achieved substantial height gain during the first 3 years of follow-up. Overall, 24 patients achieved NAH, with 70.8% having NAH SDS ≥ –2. There was no evidence to support a higher prevalence of neoplasm, or cardiac or other comorbidities.

scholarly journals Is a Two-Year Growth Response to Growth Hormone Treatment a Better Predictor of Poor Adult Height Outcome Than a First-Year Growth Response in Prepubertal Children With Growth Hormone Deficiency?

2021 ◽  
Vol 12 ◽  
Author(s):  
Saartje Straetemans ◽  
Raoul Rooman ◽  
Jean De Schepper
Keyword(s):  
Growth Hormone ◽  
Growth Response ◽  
Adult Height ◽  
Poor Response ◽  
Hormone Treatment ◽  
Hormone Deficiency ◽  
First Year ◽  
Gh Treatment ◽  
Height Gain ◽  
Design And Methods

ObjectiveThe first year response to growth hormone (GH) treatment is related to the total height gain in GH treated children, but an individual poor first year response is a weak predictor of a poor total GH effect in GH deficient (GHD) children. We investigated whether an underwhelming growth response after 2 years might be a better predictor of poor adult height (AH) outcome after GH treatment in GHD children.Design and methodsHeight data of GHD children treated with GH for at least 4 consecutive years of which at least two prepubertal and who attained (near) (n)AH were retrieved from the Belgian Register for GH treated children (n = 110, 63% boys). In ROC analyses, the change in height (ΔHt) SDS after the first and second GH treatment years were tested as predictors of poor AH outcome defined as: (1) nAH SDS &lt;−2.0, or (2) nAH SDS minus mid-parental height SDS &lt;−1.3, or (3) total ΔHt SDS &lt;1.0. The cut-offs for ΔHt SDS and its sensitivity at a 95% specificity level to detect poor AH outcome were determined.ResultsEleven percent of the cohort had a total ΔHt SDS &lt;1.0. ROC curve testing of first and second years ΔHt SDS as a predictor for total ΔHt SDS &lt;1.0 had an AUC &gt;70%. First-year ΔHt SDS &lt;0.41 correctly identified 42% of the patients with poor AH outcome at a 95% specificity level, resulting in respectively 5/12 (4.6%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.0). ΔHt SDS after 2 prepubertal years had a cut-off level of 0.65 and a sensitivity of 50% at a 95% specificity level, resulting in respectively 6/12 (5.5%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.2).ConclusionIn GHD children the growth response after 2 prepubertal years of GH treatment did not meaningfully improve the prediction of poor AH outcome after GH treatment compared to first-year growth response parameters. Therefore, the decision to re-evaluate the diagnosis or adapt the GH dose in case of poor response after 1 year should not be postponed for another year.

Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deficient patients: comparison with intravenous and subcutaneous administration

1996 ◽  
Vol 135 (3) ◽  
pp. 309-315 ◽  
Author(s):  
Torben Laursen ◽  
Birgitte Grandjean ◽  
Jens OL Jørgensen ◽  
Jens S Christiansen
Keyword(s):  
Growth Hormone ◽  
Metabolic Response ◽  
Serum Insulin ◽  
Subcutaneous Administration ◽  
Absolute Bioavailability ◽  
High Dose ◽  
Gh Treatment ◽  
Significant Difference ◽  
Igf I ◽  
Different Doses

Laursen T, Grandjean B, Jørgensen JOL, Christiansen JS. Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deflcient patients: comparison with intravenous and subcutaneous administration. Eur J Endocrinol 1996;135:309–15. ISSN 0804–4643 The current mode of growth hormone (GH) replacement therapy is daily subcutaneous (sc) injections given in the evening. This schedule is unable to mimic the endogenous pulsatile pattern of GH secretion, which might be of importance for the induction of growth and other GH actions. The present study was conducted in order to study the pharmacokinetics of different doses of GH following intranasal (IN) administration and the biological activity of GH after IN administration as compared with sc and intravenous (iv) delivery. Sixteen GH-deficient patients were studied on five different occasions. On three occasions GH was administered intranasally in doses of 0.05, 0.10 and 0.20IU/kg, using didecanoyl-l-α-phosphatidylcholine as an enhancer. On the other two occasions the patients received an sc injection (0.10IU/kg) and an iv injection (0.015IU/kg) of GH, respectively. The nasal doses and the sc injection were given in random order in a crossover design. In a double-blinded manner the subjects received the three nasal doses as one puff in each nostril. The patients received no GH treatment between the five studies or during the last week before the start of each study. Intravenous administration produced a short-lived serum GH peak value of 128.12 ± 6.71 μg/l. Peak levels were 13.98±1.63 μg/l after sc injection and 3.26±0.38. 7.07±0.80 and 8.37± 1.31 μg/l, respectively, after the three nasal doses. The peak values of the 0.05 and the 0.20IU/kg nasal doses were significantly different (p = 0.007). The mean levels obtained by the low nasal dose were significantly lower than those obtained with the medium (p < 0.001) and the high dose (p < 0.001). while there was no significant difference between the medium and the high doses. The absolute bioavailability of GH following sc relative to iv administration was 49.5%. The bioavailabilities of the nasal doses were: 7.8% (0.05 IU), 8.9% (0.10 IU) and 3.8% (0.20 IU). Serum insulin-like growth factor I (IGF-I) levels increased significantly after sc administration only. Mean levels were significantly higher after sc administration as compared with the iv and all three nasal does (p < 0.001). Serum IGF binding protein 3 (IGFBP-3) levels remained unchanged on all five occasions. Mean serum IGFBP-1 levels were significantly lower after sc GH injection than after administration of the iv (p < 0.001) and the three nasal doses (p < 0.005). Subcutaneous GH administration resulted in significantly higher levels of serum insulin and blood glucose (p < 0.001). In conclusion, the bioavailability of nasal GH was low (3.8–8.9%). An iv bolus injection of, on average, 1 IU of GH induced no metabolic response. Only sc GH administration induced increased levels of IGF-I, insulin and glucose. These data reveal that a closer imitation of the physiological GH pulses than achieved by sc GH administration is of limited importance for the induction of a metabolic response to GH. Torben Laursen, Medical Department M (Diabetes & Endocrinology), Aarhus Kommunehospital, DK-8000 Aarhus C. Denmark

scholarly journals Final Adult Height after Growth Hormone Treatment in Patients with Turner Syndrome

2019 ◽  
Vol 91 (6) ◽  
pp. 373-379 ◽  
Author(s):  
Jung Min Ahn ◽  
Jung Hwan Suh ◽  
Ah Reum Kwon ◽  
Hyun Wook Chae ◽  
Ho-Seong Kim
Keyword(s):  
Growth Hormone ◽  
Turner Syndrome ◽  
Adult Height ◽  
Final Height ◽  
Early Age ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Height Range ◽  
Final Adult Height ◽  
Height Gain

Aims: This study aimed to evaluate final adult height (AH) after recombinant human growth hormone (GH) treatment of girls with Turner syndrome (TS) and to elucidate the predicting factors for their growth response. Methods: We enrolled 73 patients with TS who underwent GH treatment and reached AH and 14 patients who did not undergo treatment. To assess the effectiveness of GH therapy, we evaluated final AH, height gain over the predicted AH, and height gain over the projected AH. In addition, to analyze the factors affecting final AH, we studied correlations between final AH (or height SDS, height gain) and treatment variables. Results: GH therapy was started at a mean age of 8.87 ± 3.73 years, and the treatment duration was 6.47 ± 3.02 years. The patients in the treated group reached a final AH of 152.03 ± 4.66 cm (final AH SDS for the general population: –1.93 ± 1.03) with a gain over projected AH at the start of treatment of 12.21 ± 4.33 cm. The untreated control subjects had a final AH of 143.57 ± 4.06 cm with a gain over projected AH at the first visit of 3.89 ± 3.80 cm. Final AH and AH SDS were positively correlated to height SDS at the start of treatment. Thirty-five patients out of the 73 GH-treated patients (47.9%) attained to a normal range of height for Korean girls. The patients having attained to a normal height range after GH treatment had shown a higher height SDS at the start of GH treatment, a higher mid-parental height SDS, and a younger age at initiation of estrogen. Conclusions: Our findings demonstrate that GH treatment at an early age is effective in improving the final height SDS and height SDS gain in TS patients. Therefore, GH administration at an early age is important for final height gain.

Improved final height with long-term growth hormone treatment in Noonan syndrome

2007 ◽  
Vol 94 (9) ◽  
pp. 1232-1237 ◽  
Author(s):  
Deborah Osio ◽  
Jovanna Dahlgren ◽  
Kerstin Albertsson Wikland ◽  
Otto Westphal
Keyword(s):  
Growth Hormone ◽  
Noonan Syndrome ◽  
Growth Hormone Treatment ◽  
Final Height ◽  
Hormone Treatment

Final Height after Long-Term Growth Hormone Treatment in Thai Children with Turner Syndrome

1998 ◽  
Vol 49 (Suppl. 1) ◽  
pp. 55-55 ◽  
Author(s):  
Pat Mahachoklertwattana ◽  
Chawalit Preeyasombat ◽  
Lulin Choubtum ◽  
Arporn Sriphrapradang
Keyword(s):  
Growth Hormone ◽  
Turner Syndrome ◽  
Growth Hormone Treatment ◽  
Final Height ◽  
Hormone Treatment
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