Optimizing growth hormone replacement therapy

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J Clin Endocrinol Metab. 1998 Nov;83(11):3913-9.
Optimizing growth hormone replacement therapy by dose titration in hypopituitary adults.
Drake WM, Coyte D, Camacho-Hübner C, Jivanji NM, Kaltsas G, Wood DF, Trainer PJ, Grossman AB, Besser GM, Monson JP.
Source

Department of Endocrinology, St Bartholomew's and The Royal London School of Medicine and Dentistry, St Bartholomew's Hospital, United Kingdom.
Abstract

Although growth hormone (GH) replacement therapy is increasingly utilized in the management of adult hypopituitary patients, optimum dosing schedules are poorly defined. The use of weight-based or surface area-based dosing may result in overtreatment, and individual variation in susceptibility on the basis of gender and other factors is now being recognized. To optimize GH replacement and to explore further gender differences in susceptibility, we used a dose titration regimen, starting at the initiation of GH replacement therapy, in 50 consecutive adult-onset hypopituitary patients, and compared the results with those in 21 patients previously treated using a weight-based regimen. Titrated patients commenced GH 0.8 IU/day subcutaneously (0.4 IU/day if hypertensive or glucose tolerance impaired). Serum insulin-like growth factor I (IGF-I) was measured at 0, 2, 4, 6, 8, 10, and 12 weeks in all patients. Serum IGF binding protein 3 and acid labile subunit were measured at the same time points in 17 patients (8 male, 9 female). Patients were reviewed every 4 weeks and the dose of GH increased, if necessary, to achieve a serum IGF-I level between the median and the upper end of the age-related reference range. There was no significant difference between mean serum IGF-I at 2 and 4 weeks, or between 6 and 8 weeks, indicating that the full effects of a change in dose are evident within 2 weeks of that change. Maintenance doses were significantly higher in females than males [1.2 (0.8-2.0) vs. 0.8 (0.4-1.6) IU/day; median (range); P < 0.0001], and the median time to achieve maintenance dose was significantly shorter in males [4 (2-12) vs. 9 (2-26) weeks; P < 0.0001]. Median maintenance dose was lower overall than in a group of 21 patients initially commenced on GH using a weight-based dosing schedule, with subsequent adjustment of dose during clinical follow-up [1.5 (0.4-3.2) IU/day; P = 0.02]. Reduction in waist measurement and waist to hip ratio at 6 and 12 months was similar in females (P < 0.001) and males (P < 0.01). Well-being improved significantly after 3 months of GH therapy (14.2 +/- 5.9 vs. 7.4 +/- 4.5 SD; P < 0.0001), and there were no gender differences. Adult Growth Hormone Deficiency Assessment (AGHDA) scores at 6 months were similar to maintenance scores in patients commenced on weight-based regimens. Measurements of ALS and IGFBP-3 added no useful extra information to IGF-I in managing the dose titration. The practical scheme outlined for dose titration of GH replacement resulted in rapid achievement of lower maintenance doses than those achieved using conventional weight-based regimens without loss of efficacy. It was particularly important in female patients who demonstrated decreased overall sensitivity to GH and required higher doses to achieve the same effects as males. This constitutes the first report of a uniform titration regimen based on a defined target range of serum IGF-I in a large patient cohort.

PMID:
9814468
[PubMed - indexed for MEDLINE]

[Glycomann]

Eur J Endocrinol. 2003 Apr;148 Suppl 2:S9-14.
Long-term experience with GH replacement therapy: efficacy and safety.
Monson JP.
Source

Department of Endocrinology, Division of General and Developmental Medicine, St Bartholomew's Hospital, West Smithfield, London ECIA 7BE, UK. J.P.Monson@qmul.ac.uk
Abstract

Demonstration of the long-term efficacy of GH replacement in GH-deficient adults has depended on a combination of single-centre studies and data from large multinational databases, which, by virtue of their size, are likely to detect rare adverse events and also permit analysis of mortality rates. The Pharmacia International Metabolic Surveillance (KIMS) study (a pharmacoepidemiological survey of the safety and efficacy of GH replacement in adults, sponsored by Pharmacia) is currently the largest database, with information on over 8000 patients from a total of 27 countries. Abundant epidemiological evidence confirms that hypopituitarism is associated with premature mortality, with an increase in cardiovascular and cerebrovascular disease as a primary underlying cause. Central adiposity, hyperlipidaemia, insulin resistance, and diabetes mellitus are common in adults with hypopituitarism. GH replacement is associated with improvements in central fat mass and mean reductions in serum total and low-density lipoprotein cholesterol which may be additive to those achieved with hydroxymethylglutaryl-coenzyme A reductase inhibitors. These beneficial effects are maintained for at least 2 Years after initiation of therapy, as are reductions in central adiposity, with similar benefits seen in men and women when the GH dose is titrated to achieve a serum IGF-I between the median and the upper end of the age-related reference range. Fasting plasma glucose and glycated haemoglobin increase, usually within the reference range, during prolonged GH replacement, but do not tend to rise further above baseline in subjects with pre-existing impaired glucose tolerance. Bone remodelling increases during GH replacement therapy, but indices tend to return to baseline within 5 Years of commencing treatment. Bone mineral density increases in men whereas, in women, improvement is limited to stabilisation of bone density. Data from the KIMS study demonstrate that prolonged GH replacement is associated with a reduction in the number of patients requiring assistance with daily living and a significant reduction in sick leave and hospital admissions. GH replacement therapy improves psychological well-being, particularly in those patients with the greatest deficit prior to treatment, with improvement maintained beyond 6 Months of therapy and sustained during long-term follow-up. Data from the KIMS population show that there is no increase in the overall occurrence of de novo neoplasia or the rate of regrowth of primary pituitary tumours. There is an apparent increase in intracranial neoplasia, which may be an artefact of comparing a surveillance population with general population data. Unlike mortality in untreated hypopituitary GH-deficient patients, mortality in the KIMS study is currently similar to that predicted for the normal population.

PMID:
12670295
[PubMed - indexed for MEDLINE]

[willi]

This is a great post!