Aspects of diagnosis and treatment of hypopituitarism in adult life

Sammanfattning: Management of adult patients with hypopituitarism can improve with better char¬ac¬terisation of idiopathic pituitary insufficiency (IPI) and clearer diagnosis of central hy¬pothy¬roidism (CH). Moreover, optimised treatment strategies for glucocorticoid (GC) re¬placement therapy and of long-term growth hormone (GH) in GH deficiency (GHD) are needed. This thesis contains four studies addressing these issues. By evaluating patients with IPI, mutations generating hypopituitarism were identified in an unselected adult IPI population. A new allel constellation in a compound PROP1 mutation was re¬vealed in two siblings, with a phenotype of very late onset ACTH-insufficiency. Those cases were only detected in patients with documented childhood onset disease. A pilot study investigated the response of the thyroid gland after stimulation with 0.9 mg re¬combinant human thyreotropin (rhTSH) in patients with newly diagnosed CH and healthy controls. The untreated CH patients had lower free thyroxine response than controls. A database study containing 2424 hypopituitary patients, di¬vided into ACTH-insufficient and ACTH-sufficient (AS) patients, demonstrated a clear GC dose-re¬sponse relation with metabolic outcome. Patients with hydrocortisone equivalent doses of<20 mg/day had a similar metabolic profile as AS patients. In a large study on GHD patients on long-term GH treatment quality of life (QoL), body composition, and metabolic outcome were evaluated during 4-month-GH-dis¬continuation in a dou¬ble blind, placebo controlled design. QoL deteriorated, body com¬position moved towards a GHD state and metabolic parameters were impaired during placebo treatment. These studies infer that genetic hypopituitarism should be searched for in IPI cases, especially in childhood onset disease and where there is a family history. The diag¬nosis of CH can be improved by an rhTSH test. In many cases, doses of GC can be reduced in ACTH-insufficient patients in order to improve their metabolic outcome and continuous long-term GH replacement is needed to maintain beneficial effects on QoL, body composition, and metabolism.