Personalized approach to growth hormone replacement in adults

Abstract

Growth hormone (GH) deficiency (GHD) in adults is well-characterized and includes abnormal body composition, reduced bone mass, an adverse cardiovascular risk profile, and impaired quality of life. In the early 1990s, it was also shown that patients with hypopituitarism without GH replacement therapy (GHRT) had excess mortality. Today, GHRT has been shown to decrease or reverse the negative effects of GHD. In addition, recent papers have shown that mortality and morbidity are approaching normal in hypopituitary patients with GHD who receive modern endocrine therapy including GHRT. Since the first dose-finding studies, it has been clear that efficacy and side effects differ substantially between patients. Many factors have been suggested as affecting responsiveness, such as sex, age, age at GHD onset, adherence, and GH receptor polymorphisms, with sex and sex steroid replacement having the greatest impact. Therefore, the individual tailoring of GH dose is of great importance to achieve sufficient efficacy without side effects. One group that stands out is women receiving oral estrogen replacement, who needs the highest dose. Serum insulin-like growth factor-1 (IGF-1) is still the most used biochemical biomarker for GH dose titration, although the best serum IGF-1 target is still debated. Patients with GHD due to acromegaly, Cushing's disease, or craniopharyngioma experience similar effects from GHRT as others.

Exogenous insulin-like growth factor 1 accelerates growth and maturation of follicles in human cortical xenografts and increases ovarian output in mice

“…Given the extended period of follicle development that occurs before the gonadotropin-dependent phase, commencing GH treatment in poor responders weeks (or months) in advance of ovarian hyperstimulation may be more effective in amplifying the reservoir of responsive follicles. However, GH is not approved by the US Food and Drug Administration for use in patients with IVF outside of GH deficiency, and longterm use can have unwelcome side effects (51). The present study is limited in that the delivery of IGF1 is sustained for the life of the graft and at levels that are not well defined, but augmented growth evident among early-stage follicles (Fig.…”

Dose–exposure–IGF-I response of once-weekly somapacitan in adults with GH deficiency

“…It is well established that women, and in particular, women on oral oestrogen, respond less to GH treatment than men ( 4 , 25 ), a difference that has largely been attributed to interactions between GH and sex steroids ( 25 , 26 ). Indeed, oral oestrogen was reported to impair GH action and lower IGF-I levels ( 6 , 25 , 26 , 27 ).…”

GH Replacement in the Elderly: Is It Worth It?

“…We can conclude by stating that the main goal of GHrt in the elderly patient is to improve QoL, prolong independence, and avoid frailty ( 69 , 70 ). The age-related decline in GH-IGF-1 levels does not justify GHrt supplementation, but patients with established GHD should be considered for treatment, regardless of age, but rather taking into account general conditions, comorbidities, and life expectancy, analysing each case individually ( 34 , 37 , 38 ). We add that considering the costs of GHrt and the mainly long-term effects, the cost/benefit ratio must always be carefully evaluated ( 38 ), especially in a population with a reduced life expectancy ( 71 ).…”

“…Based on our clinical experience with EGHD, the treatment goal should be to maintain IGF-1 between -1 and +1 SD, in accordance with the findings of a study by Van Bunderen et al., specifically aimed at comparing different target IGF-1 therapeutics ( 36 ). However, clinical practice is not uniform ( 25 , 37 , 38 ) and the therapeutic goal is not univocal: for example, American guidelines suggest a wider range (IGF-1 between -2 and + 2 SD) ( 16 ).…”