scholarly journals Growth Failure in Children with Systemic Juvenile Idiopathic Arthritis and Prolonged Inflammation despite Treatment with Biologicals: Late Normalization of Height by Combined Hormonal Therapies

2018 ◽  
Vol 90 (5) ◽  
pp. 337-343 ◽  
Author(s):  
Francis de Zegher ◽  
Nele Reynaert ◽  
Lien De Somer ◽  
Carine Wouters ◽  
Mathieu Roelants
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Pubertal Development ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Growth Failure ◽  
High Dose ◽  
Combination Strategy ◽  
Glucocorticoid Treatment ◽  
Height Gain ◽  
Adult Stature

Background: Biologicals targeting the interleukin (IL)-1β or IL-6 pathway are becoming prime choices for the treatment of children with systemic juvenile idiopathic arthritis (sJIA). Up to 1 in 3 sJIA children receiving such treatment continues to have inflammatory activity and to require supra-physiological glucocorticoid doses which may reduce growth velocity for years and may lead to an extremely short stature for age, if not for life. Currently, there is no long-term proposal to normalize the adult height of these children with sJIA. Methods and Results: We present long-term (up to 10 years), proof-of-concept evidence that the adult stature and adipose body composition of short sJIA children can be normalized with a hormonal combination strategy: (i) pubertal onset is postponed with a gonadotropin-releasing hormone analog (triptorelin) until a minimum height is reached, or until prepubertal growth is exhausted, and (ii) height gain is promoted with growth hormone (≈50 μg/kg/day), once inflammation is under control and high glucocorticoid doses are no longer needed. The latter treatment takes advantage of the window of relative glucocorticoid deficiency, which is known to open after prolonged glucocorticoid administration, and to be uniquely favorable to height gain. Conclusion: A long-term combination of biological and hormonal treatments for short sJIA children can be guided by a simple concept that involves (i) postponement of pubertal development and (ii) growth-promoting therapy after the episodes of major inflammation and high-dose glucocorticoid treatment. Limited long-term experience in short sJIA children suggests that this strategy leads consistently – albeit late – to a normal adult stature.

[18F]Fluoride PET Indicates Reduced Bone Formation in Severe Glucocorticoid-induced Osteoporosis

1998 ◽  
Vol 37 (02) ◽  
pp. 76-79 ◽  
Author(s):  
T. D. Kirchhoff ◽  
W. Burchert ◽  
J. v. d. Hoff ◽  
H. Zeidler ◽  
H. Hundeshagen ◽  
...  
Keyword(s):  
Bone Formation ◽  
Multiple Organ ◽  
High Dose ◽  
Multiple Fractures ◽  
Glucocorticoid Treatment ◽  
Organ Manifestations ◽  
Diagnostic Benefit ◽  
Sharp Syndrome ◽  
18F Fluoride

SummaryA 61-year-old female patient presenting with mixed connective tissue disease (Sharp syndrome), underwent a long-term high dose glucocorticoid treatment because of multiple organ manifestations. Under steroid therapy she developed severe osteoporosis resulting in multiple fractures. A dynamic [18F]fluoride PET study in this patient revealed reduced fluoride influx in non-fractured vertebrae. This finding corresponds to pathogenetic concepts which propose an inhibition of bone formation as major cause of glucocorticoid-induced osteoporosis. In the light of the presented case it seems to be promising to evaluate the diagnostic benefit of [18F]fluoride PET in osteoporosis.

Reverse circadian glucocorticoid treatment in prepubertal children with congenital adrenal hyperplasia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ilja Dubinski ◽  
Susanne Bechtold Dalla-Pozza ◽  
Martin Bidlingmaier ◽  
Nicole Reisch ◽  
Heinrich Schmidt
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Pubertal Development ◽  
Adrenal Crisis ◽  
Adrenal Hyperplasia ◽  
Glucocorticoid Treatment ◽  
Steroid Synthesis ◽  
Prepubertal Children ◽  
Salt Wasting ◽  
17 Hydroxyprogesterone

Abstract Objectives Children with salt-wasting congenital adrenal hyperplasia (CAH) have an impaired function of steroid synthesis pathways. They require therapy with glucocorticoid (GC) and mineralocorticoid hormones to avoid salt-wasting crisis and other complications. Most commonly, children receive hydrocortisone thrice daily with the highest dose in the morning, mimicking the regular physiology. However, reverse circadian treatment (RCT) had been suggested previously. In this study, we aimed to determine the efficacy of RCT in prepubertal children with CAH by comparing the salivary 17-hydroxyprogesterone (s17-OHP) levels individually. Methods In this retrospective study, we analyzed the records of children with classical CAH and RCT who were monitored by s17-OHP levels. The study included 23 patients. We identified nine prepubertal children with RCT schemes (three boys and six girls) and compared the s17-OHP levels in the morning, afternoon, and evening. The objective of this study was to demonstrate the non-effectiveness of RCT in terms of lowering the morning s17-OHP concentration. In addition, we compared s17-OHP day profiles in six patients on RCT and non-RCT therapy (intraindividually). Results Eight of nine children with RCT showed higher s17-OHP levels in the morning compared to the evening. In addition, none of the children showed a significant deviation of development. Three children were overweight. No adrenal crisis or pubertal development occurred. Comparison of RCT and non-RCT regimens showed no difference in 17-OHP profiles. Conclusions Our data do not support the use of RCT schemes for GC replacement in children with CAH due to lack of benefits and unknown long-term risks.

Fludarabine and Mitoxantrone Followed by Yttrium-90 Ibritumumab Tiuxetan in Untreated Patients with Follicular Lymphoma. Long Term Efficacy and Toxicity Results of the FLUMIZ Trial.

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1604-1604
Author(s):  
Pier Luigi Zinzani ◽  
Enrico Derenzini ◽  
Cinzia Pellegrini ◽  
Luigi Rigacci ◽  
Alberto Fabbri ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Disease Progression ◽  
Conflicts Of Interest ◽  
High Dose ◽  
Treatment Schedule ◽  
Combination Strategy ◽  
Term Efficacy ◽  
Yttrium 90

Abstract Abstract 1604 We previously reported the results of a multicenter non-randomized phase II trial of fludarabine and mitoxantrone plus radioimmunotherapy (RIT) [FLUMIZ (Fludarabine, Mitoxantrone, Zevalin) trial], demonstrating that this combination was safe and very effective in untreated patients with follicular non-Hodgkin lymphoma. We are now providing long term efficacy and toxicity results of this combination strategy. Sixty-one patients with stage III and IV untreated follicular lymphoma were enrolled between June 2004 and April 2006, at 13 Italian institutions. Briefly, treatment schedule was the following: oral fludarabine 40 mg/m2 on days 1–3, intravenous mitoxantrone 10 mg/m2 on day 1 every 28 days for six cycles, followed by one course of yttrium-90 (90Y)-labelled ibritumumab tiuxetan (Zevalin), which consisted in two weekly infusions of Rituximab 250 mg/m2 followed by a weight based dose of 90Y-ibritumumab tiuxetan. Primary endpoints at the time of the first analysis were complete response and hematological toxic effects, secondary endpoints were overall survival (OS) and progression free survival (PFS). Fifty-seven patients were treated with RIT after the completion of six courses of fludarabine and mitoxantrone (FN) regimen. Four patients were excluded because of disease progression (n=1) and bone marrow infiltration > 25% (n=3) at the end of the FN regimen. Median follow up at the time of the last analysis was 52 months (range 24–75). Five-year PFS was estimated to be 68%, 5-year OS was estimated to be 93.0%. Noteworthy, late hematological side effects such as myelodisplastic syndromes or acute myeloid leukemias have not been observed so far. All patients had a complete hematological recovery after the completion of the sequential treatment. 16 patients relapsed during the follow-up period and 4 patients died due to disease progression. 22 patients (38%) are in first complete remission after more than 4 years of follow-up. All relapsed patients underwent second line chemotherapy and high dose chemotherapy with stem cell rescue was performed in 4 patients. These results confirm the long term efficacy and safety of 6 cycles of fludarabine and mitoxantrone followed by consolidation with 90Y-ibritumumab tiuxetan: the 5-year PFS and OS compare favourably with the results of chemoimmunotherapy alone in untreated follicular lymphoma, with no increased incidence of secondary hematologic malignancie Disclosures: No relevant conflicts of interest to declare.

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.

Long-Term Safety and Efficacy of Rilonacept in Patients With Systemic Juvenile Idiopathic Arthritis

2013 ◽  
Vol 65 (9) ◽  
pp. 2486-2496 ◽  
Author(s):  
Daniel J. Lovell ◽  
Edward H. Giannini ◽  
Andreas O. Reiff ◽  
Yukiko Kimura ◽  
Suzanne Li ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Safety And Efficacy
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