Growth hormone deficiency in adults: Diagnosis and treatment

Abstract

Growth hormone deficiency (GHD) in adults is a rare clinical syndrome with an incidence of 1.4-4.2 per 100,000 persons per year and a prevalence of 350/million. It is characterized by unfavorable body composition, reduced muscle, and bone mass, lower capacity to endure physical effort, abnormal lipid profile, increased cardiovascular risk and poor quality of life. Despite these clinical manifestations, GHD is often unrecognized, so its diagnosis is often missed or delayed. The reason is the non-specific and subtle clinical characteristics, which require the testing of growth hormone (GH) secretion with stimulation tests. Two tests are in use, the insulin tolerance test and the glucagon test, which require the experience of the team performing them. Recently, an oral secretagogue of growth hormone - macimorelin has been used, which is simple test to perform and is safe for the patient. Insufficient secretion of GH in adults can be manifested as isolated or in combination with deficits of other pituitary hormones. However, GH is the most frequently detected hormonal deficit in adults as part of hypopituitarism. Causes of GHD can be congenital or acquired. Congenital reasons are the result of disorders of the embryogenic development of the pituitary gland and hypothalamus, and acquired are the most common complications of tumors of the sellar region and head trauma. Patients with GHD have an increased mortality rate compared to the general population. The causes of the shortened life span of these patients depend on the etiology of hypopituitarism, the applied therapy of tumors of the hypothalamus/pituitary region (surgery, radiotherapy), and the replacement of other missing pituitary hormones. During the last two decades, growth hormone therapy in adults has entered routine clinical practice. The beneficial effects of this substitution are reflected in the body composition, skeletal system, metabolic status, and improvement of the quality of life. GH replacement in adults returns the mortality rate to that expected for age in the general population. Due to the known proliferative, angiogenic, and anti-apoptotic properties of GH, there is still some caution regarding the recurrence of hypopituitarism-causing tumors or the appearance of new tumors during GH replacement. However, large and long-term follow-up studies of adults on GH therapy have shown a high safety profile of this treatment. Daily injections of GH were until recently the only way of its application, and now longacting weekly forms have been marketed, which will significantly improve adherence to this therapy.