Optimizing GH Therapy in Adults and Children

Abstract

Until the advent of modern neuroradiological imaging techniques in 1989, a diagnosis of GH deficiency in adults carried little significance other than as a marker of hypothalamo-pituitary disease. The relatively recent recognition of a characteristic clinical syndrome associated with failure of spontaneous GH secretion and the potential reversal of many of its features with recombinant human GH has prompted a closer examination of the physiological role of GH after linear growth is complete. The safe clinical practice of GH replacement demands a method of judging overall GH status, but there is no biological marker in adults that is the equivalent of linear growth in a child by which to judge the efficacy of GH replacement. Assessment of optimal GH replacement is made difficult by the apparent diverse actions of GH in health, concern about the avoidance of iatrogenic acromegaly, and the growing realization that an individual's risk of developing certain cancers may, at least in part, be influenced by cumulative exposure to the chief mediator of GH action, IGF-I. As in all areas of clinical practice, strategies and protocols vary between centers, but most physicians experienced in the management of pituitary disease agree that GH is most appropriately begun at low doses, building up slowly to the final maintenance dose. This, in turn, is best determined by a combination of clinical response and measurement of serum IGF-I, avoiding supraphysiological levels of this GH-dependent peptide. Numerous studies have helped define the optimum management of GH replacement during childhood. The recent requirement to measure and monitor GH status in adult life has called into question the appropriateness of simplistic weight- and surface area-based dosing regimens for the management of GH deficiency in childhood, with reliance on linear growth as the sole marker of GH action. It is clear that the monitoring of parameters other than linear growth to help refine GH therapy should now be incorporated into childhood GH treatment protocols. Further research will be required to define the optimal management of the transition from pediatric to adult GH replacement; this transition will only be possible once the benefits of GH in mature adults are defined and accepted by pediatric and adult endocrinologists alike.

Isolated Growth Hormone Deficiency due to <i>GH1</i> Gene Deletion: Central Nervous System Hypertension during Growth Hormone Treatment

“…Main clinical signs are headaches, nausea, vomiting and visual changes. The prevalence of BIH in GHD patients on rhGH treatment is low (approximately 1.6 per 1,000 patients) [2,3,4,5]. Ocular examination of this patient revealed no abnormalities.…”

THERAPY OF ENDOCRINE DISEASE: GH therapy in adult GH deficiency: A review of treatment schedules and the evidence for low starting doses

“…Research Society (GRS) (6) Recommended that the starting dose in young men and women be 0.2 and 0.3 mg/day respectively, and in older individuals, 0.1 mg/day. Dose determination based on body weight is not recommended due to large inter-individual variation in absorption and in sensitivity to GH, and the lack of evidence that a larger replacement dose is required for heavier individuals in adults Dose escalation should be gradual, individualised, and guided by clinical and biochemical response In elderly patients with GHD, treatment can be achieved with lower doses, concordant with the observed physiological decrease in GH secretion.…”

“…Treatment goals for adults with GHD are to correct the clinical alterations described above, using insulinlike growth factor 1 (IGF1) levels as a marker of treatment, in order to achieve or maintain IGF1 levels in the middle of the normal range appropriate for age and sex, with an optimal level of physical and psychosocial function (5,6,7). GH dosing in adult GHD (AGHD) was initially adopted from paediatric practice and was subsequently found to cause supraphysiological levels of IGF1 and to cause increased levels of common side effects such as arthralgia and peripheral oedema (8).…”

Defining Growth Hormone Status in Adults with Hypopituitarism

“…Consensus guidelines from the GH Research Society (GRS) state that although traditionally a peak GH level on provocative testing of <10 µg/l supports a diagnosis of GHD in a poorly growing child, this value needs to be revised when using newer assays [8]. A GH peak of between 7 and 10 µg/l is usually taken as the cut-off [9]. As in adults, the cut-off value is arbitrarily defined, since in reality GH secretion is a continuum between normality and abnormality.…”