Dose Titration and Monitoring GH Treatment in the Adult

Author(s):  
S J Howell ◽  
A Rahim ◽  
S M Shalet
Keyword(s):  
2007 ◽  
Vol 92 (7) ◽  
pp. 2480-2486 ◽  
Author(s):  
Pinchas Cohen ◽  
Alan D. Rogol ◽  
Campbell P. Howard ◽  
George M. Bright ◽  
Anne-Marie Kappelgaard ◽  
...  

Abstract Context: Weight-based dosing of GH is the standard of care for short children, although IGF-I is thought to be the main mediator of GH actions on growth. Objective: The objective of the study was to test whether IGF-I levels achieved during GH therapy are determinants of the growth responses to GH treatment. Design: This was a 2-yr, open-label, randomized, IGF-I concentration-controlled trial. Prepubertal short children [n = 172, mean age 7.53 yr, mean height sd score (HT-SDS) −2.64] with low IGF-I levels (mean IGF-I SDS −3.56) were randomized to receive one of two GH dose-titration arms in which GH dosage was titrated to achieve an IGF-I SDS at the mean [IGF(low) group, n = 70] or the upper limit of the normal range [+2 SDS, IGF(high) group, n = 68] or to a comparison group of conventional GH dose of 40 μg/kg/d (n = 34). Setting: The study was conducted in a multicenter, outpatient setting. Primary Outcome Measure: Change in HT-SDS over 2 yr was measured. Results: One hundred forty-seven patients completed the trial. Target IGF-I levels were achieved in the dose-titration arms within 6–9 months. The changes in HT-SDS were +1.0, +1.1, and +1.6 for conventional, IGF(low), and IGF(high), respectively, with IGF(high) showing significantly greater linear growth response (P < 0.001, compared with the other two groups). The IGF(high) arm required higher doses (>2.5 times) than the IGF(low) arm, and these GH doses were highly variable (20–346 μg/kg/d). Multivariate analyses suggested that the rise in the IGF-I SDS significantly impacted height outcome along with the GH dose and the pretreatment peak-stimulated GH level. Conclusion: IGF-I-based GH dosing is clinically feasible and allows maintaining serum IGF-I concentrations within the desired target range. Titrating the GH dose to achieve higher IGF-I targets results in improved growth responses, although at higher average GH doses.


2020 ◽  
Vol 105 (8) ◽  
pp. 2566-2574
Author(s):  
Amanda Cleemann Wang ◽  
Casper P Hagen ◽  
Leila Nedaeifard ◽  
Anders Juul ◽  
Rikke Beck Jensen

Abstract Context Girls with Turner syndrome (TS) suffer linear growth failure, and TS is a registered indication for growth hormone (GH) treatment. GH is classically dosed according to body weight, and serum insulin-like growth factor-1 (IGF-1) concentrations are recommended to be kept within references according to international guidelines. Objective To assess the effect of long-term GH treatment in girls with TS following GH dosing by IGF-1 titration. Design and setting A retrospective, real-world evidence, observational study consisting of data collected in a single tertiary center from 1991 to 2018. Patients A cohort of 63 girls with TS treated with GH by IGF-1 titration with a median duration of 6.7 years (interquartile range [IQR]: 3.4-9.7 years). Main outcome measures Longitudinal measurements of height, IGF-1, and adult height (AH) following GH treatment were evaluated and compared between the different karyotypes (45,X, 45,X/46,XX, or miscellaneous). Results Using GH dose titration according to IGF-1, only 6% of girls with TS had supranormal IGF-1 levels. Median dose was 33 µg/kg/day (IQR: 28-39 µg/kg/day) with no difference between the karyotype groups. AH was reached for 73% who attained a median AH of 1.25 standard deviation score (SDS) for age specific TS references (IQR: 0.64-1.50 SDS), and a median gain in height (ΔHSDS: AH SDS minus baseline height SDS of TS references) of 0.50 SDS, equal to 3.2 cm (SD 7.68) for all karyotypes. Conclusion Our real-world evidence study suggested that titration of GH dose to keep IGF-1 levels within the normal range resulted in a lower AH gain than in studies where a fixed dose was used.


2011 ◽  
Vol 8 (2) ◽  
pp. 11-17
Author(s):  
Vladimir Vladimirovich Vaks ◽  
Olga Aleksandrovna Gerasimenko ◽  
Larisa Konstantinovna Dzeranova

Adult-onset growth hormone deficiency (GHD) remains one of the issues in clinical endocrinology. In this article, which is addressed to practitioners, physiology of growth hormone in adults is reviewed along with etiology and diagnostic criteria of this medical condition. In general, a stimulation test is required to recognize GHD. Insulin tolerance test (ITT) has been considered the gold standard by the most important scientific societies, although alternative tests, in particular GHRH plus arginine have been proposed as valuable alternative to ITT. The results of different clinical studies regarding the impact of adult-onset GH-deficiency on metabolism and quality of life are summarized and beneficial effects of growth hormone replacement therapy on many of the manifestations of GHD reviewed. The management of GHD in adults is discussed including initiation of GH treatment, dose titration and assessment of response during trail period.


2005 ◽  
Vol 153 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Kazuo Chihara ◽  
Ekaterina Koledova ◽  
Akira Shimatsu ◽  
Yuzuru Kato ◽  
Hitoshi Kohno ◽  
...  

Objectives: To investigate the effects of growth hormone (GH) treatment, using a dose-adjustment regimen based on serum insulin-like growth factor (IGF)-I concentrations, in adult Japanese hypopituitary patients with GH deficiency. Study design: Japanese patients who had initially been administered GH (n = 31) or placebo (n = 28) in a 24-week double-blind study received individualized GH treatment in an open-label study for 48 weeks. Body composition from dual-energy X-ray absorptiometry (DXA) and serum IGF-I, IGF-binding protein 3 (IGFBP-3) and lipid levels were determined centrally. Results: Significant increases in lean body mass (4.5%) and decreases in fat mass (−10.5%) were observed in the group that received individualized GH doses in the present open-label study following placebo in the double-blind study. This was comparable with the changes observed in these parameters (4.7 and −9.2%, respectively) with fixed-dose GH treatment in the double-blind study; this latter group maintained these improvements throughout the open-label study. Individualized dose adjustment allowed for more moderate dose increases than the fixed-dose titration method. Individualized dosing also resulted in a lower mean dose for adult-onset compared with childhood-onset GH-deficient patients (0.032±0.019 versus 0.061±0.023 mg/kg per week for patients treated with GH for 48 weeks in the open-label study following placebo in the double-blind study). Dosing patterns in the two groups were paralleled by the changes in IGF-I and IGFBP-3. The incidence of oedema and cases with high IGF-I level were less frequent under the IGF-I controlled regimen compared with those during the fixed-dose titration method. Conclusion: Individualized GH administration based on IGF-I levels was safe and effective. This regimen demonstrated differences in dose requirements between adult- and childhood-onset patients. An individualized dose regimen is recommended in adult Japanese GH-deficient patients.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kathryn A. Ryan ◽  
Kevin R. Bewley ◽  
Susan A. Fotheringham ◽  
Gillian S. Slack ◽  
Phillip Brown ◽  
...  

AbstractThere is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 106 pfu) and medium (5 × 104 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 102 pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5–15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.


Author(s):  
Mahima Kapoor ◽  
Ryan Keh ◽  
Laura Compton ◽  
Sarah Morrow ◽  
David Gosal ◽  
...  

2021 ◽  
pp. 089719002110273
Author(s):  
Megan M. Pantos ◽  
Daniel R. Kennedy ◽  
Eric C. Nemec

Purpose: The purpose of this drug review was to explore the safety and efficacy of the newly approved benzodiazepine, remimazolam, in order to evaluate its place in therapy. Summary: Remimazolam has a faster onset of action and recovery time than midazolam when given as single IV doses. Additionally, it has no known CYP450 interactions that would contribute to drug-drug interactions. Patients with severe hepatic impairment may require dose titration as well as the elderly who should be closely monitored. Although remimazolam vials should be protected from light and must be reconstituted immediately before use, the reconstituted vial may be stored for later use at room temperature for up to 8 hours. Remimazolam is more expensive than current options used in practice, as such individual institutional formulary and provider preference will require review to see if its advantages are worth the additional cost and to determine its place in therapy. Conclusion: Remimazolam is a novel option when choosing a benzodiazepine for procedural sedation that has pharmacokinetic and pharmacodynamic advantages when compared to other commonly prescribed sedatives. Remimazolam has proved superior to midazolam when analyzing drug-drug interactions, onset, and time to alertness. Remimazolam also has a shorter elimination half-life and decreased volume of distribution when compared to midazolam.


Pituitary ◽  
2021 ◽  
Author(s):  
Jonathan A. Young ◽  
Mat Buchman ◽  
Silvana Duran-Ortiz ◽  
Colin Kruse ◽  
Stephen Bell ◽  
...  

Pituitary ◽  
2021 ◽  
Author(s):  
Margaret C. S. Boguszewski ◽  
Adriane A. Cardoso-Demartini ◽  
Cesar Luiz Boguszewski ◽  
Wassim Chemaitilly ◽  
Claire E. Higham ◽  
...  

AbstractIndividuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.


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