Adult growth hormone deficiency (GHD) is a syndrome characterized by adverse phenotypic, metabolic, and quality-of-life features. Over the past 2 decades, there is accumulating evidence demonstrating improvement of most of these parameters when GH is optimally replaced. Appropriate selection of patients at risk of GHD is crucial when considering and performing testing to establish the diagnosis. While generally safe, GH replacement requires careful dose initiation and monitoring to assure effectiveness and tolerance in treated patients. Several consensus clinical practice guidelines recommend evaluation of adults presenting with hypothalamic-pituitary disorders for GHD. However, the clinical practice of managing such patients varies among countries largely due to lack of recognition of the condition, lack of GH availability, and lack of reimbursement of the drug, as demonstrated from a large online survey prepared by the European Society of Endocrinology involving 2148 patients from Europe and Australia. These data reinforce the notion of the large variability of disease recognition, clinical practice and education of adult GHD amongst healthcare professionals, and the lack of availability and reimbursement of the drug contributing to the under-utilization of GH replacement therapy in several countries. This commentary article highlights the fact that despite the publication of several guideline recommendations and positive long-term safety and efficacy data of GH replacement, there is still a need for increased education to enhance the awareness in the general population and improve the knowledge of healthcare professionals and administrators of adult GHD as a disease state to allow for early identification and treatment optimization.
Kevin C J Yuen, Maria Koltowska-Häggström, David M Cook, Janet L Fox, Peter J Jönsson, Mitchell E Geffner, and Roger Abs
Adults with childhood-onset (CO) craniopharyngioma (COCP) have poor quality of life (QoL) and clinical outcomes, but few studies have compared these patients with adults with other causes of CO hypothalamic–pituitary dysfunction. In this study, we compared baseline clinical characteristics and patient-reported outcomes before starting GH replacement therapy in adults with GH deficiency (GHD) due to COCP with those of adults either with CO idiopathic/congenital hypopituitarism (COH) or with CO extrasellar (COE) tumours, and evaluated the 1- and 5-year effects of GH replacement therapy.
Subjects and methods
Retrospective analysis of the data recorded in KIMS (Pfizer International Metabolic Database) was carried out. Patients with COCP, COH and COE tumours were evaluated at baseline, and after 1 and 5 years of therapy.
Compared with COH and COE patients, more COCP patients underwent surgery, had greater abnormalities of body composition and higher prevalence of pituitary hormone deficits (all P<0.001), but comparable fasting glucose, HbA1c, total cholesterol and LDL-cholesterol levels, marital status, parenthood, living arrangements, education, employment and annual sick-leave days. After 1 and 5 years of GH replacement therapy, similar changes were evident with regard to body composition, fasting glucose and HbA1c levels, QoL, and the level of and satisfaction with physical activity across the three groups.
Adults with untreated COCP with GHD at baseline demonstrated more co-morbidities including greater abnormalities of body composition, pituitary hormone deficits and visual field defects. Overall, adults with COCP, COH and COE tumours responded comparably to short- and long-term GH replacement therapy, suggesting that patients with GHD due to COCP benefited from GH replacement therapy to a similar degree as those with other causes of CO hypothalamic–pituitary dysfunction did.
Jens Sandahl Christiansen, Philippe F Backeljauw, Martin Bidlingmaier, Beverly M K Biller, Margaret C S Boguszewski, Felipe F Casanueva, Philippe Chanson, Pierre Chatelain, Catherine S Choong, David R Clemmons, Laurie E Cohen, Pinchas Cohen, Jan Frystyk, Adda Grimberg, Yukihiro Hasegawa, Morey W Haymond, Ken Ho, Andrew R Hoffman, Jeff M P Holly, Reiko Horikawa, Charlotte Höybye, Jens Otto L Jorgensen, Gudmundur Johannsson, Anders Juul, Laurence Katznelson, John J Kopchick, K O Lee, Kuk-Wha Lee, Xiaoping Luo, Shlomo Melmed, Bradley S Miller, Madhusmita Misra, Vera Popovic, Ron G Rosenfeld, Judith Ross, Richard J Ross, Paul Saenger, Christian J Strasburger, Michael O Thorner, Haim Werner, and Kevin Yuen
The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH).
A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry.
Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues.
Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors.
LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.