Pituitary (2006) 9:305–311 DOI 10.1007/s11102-006-0410-y Growth hormone deficiency in the adult M. Doga · S. Bonadonna · M. Gola · G. Mazziotti · A. Giustina Published online: 30 October 2006 C  Springer Science + Business Media, LLC 2006 Abstract Growth hormone deficiency (GHD) in adults may be of either adult or childhood onset and may occur as iso- lated GHD or as multiple hormone deficiencies. Adult-onset GHD (AoGHD) usually results from damage to the pitu- itary gland or hypothalamus. GH is frequently undetectable in normal subjects and thus GHD cannot be distinguished from the normal state using a single random GH measure- ment. In general, a stimulation test is required to recognize GHD. Insulin tolerance test (ITT) has been considered the gold standard by the most important scientific societies, al- though alternative tests, in particular GHRH plus arginine have been proposed as valuable alternative to ITT. The clin- ical syndrome associated with AoGHD is characterized by a wide array of symptoms and important chronic complica- tions, such as cardiovascular complications, which may be responsible for an increased mortality. The rationale for GH replacement in adults GHD patients is justified by the ben- eficial effects on some clinical end-points, such as quality of life (QoL) and cardiovascular risk factors, whereas the effects on mortality risk are still controversial. Over the re- cent years, guidelines on the use of rhGH as a substitution treatment in adult hypopituitarism have been issued by inter- national (Growth hormone research society-GRS, Endocrine Society) and relevant national (National Institute of Clinical Excellence-UK, NICE) institutions. The aim of the paper is to review and discuss these guidelines. Keywords GHD . GH replacement treatment . Guidelines M. Doga · S. Bonadonna · M. Gola · G. Mazziotti · A. Giustina () Endocrine Section, Department of Medical and Surgical Sciences, University of Brescia, Brescia, Italy e-mail: a.giustina@libero.it Demographic and clinical findings Growth hormone deficiency (GHD) in adults may be of either adult or childhood onset and may occur as isolated GHD or as multiple hormone deficiencies. Adult-onset GHD (AoGHD) usually results from damage to the pituitary gland or hy- pothalamus. Such damage may be caused by a tumor in the area or by treatment for a tumor (surgery or radiotherapy) or, according to recent evidence, by traumatic brain injury. AoGHD has been estimated to affect 1 in 10.000 people an- nually, as evidenced by the incidence of pituitary tumors, and its prevalence increases to 3 in 10.000 when adult patients with childhood-onset growth hormone deficiency (CoGHD) are considered [1–3]. The clinical syndrome associated with AoGHD is characterized by a wide array of symptoms and by major complications such as cardiovascular complica- tions, metabolic complications, osteopenia or osteoporosis and reduced quality of life (QoL). Diagnosis GH secretion is pulsatile and has a short half life (19 min), thus serum GH is frequently undetectable in normal subjects [4]. As a consequence, GHD cannot be distinguished from the normal state using a single random GH measurement although a fortuitous sampling during a peak will exclude GHD in normal subjects. In general, a stimulation test is required to recognize GHD [5]. Serum IGF-1 and IGF binding protein-3 are useful in the diagnosis of AoGHD and should be used in concert with provocative testing. However, age and sex–adjusted normative data must be available to use these parameters when we evaluate the patient. Serum IGF-1 concentrations below the normal range are suggestive of GHD, but normal Springer