The diagnosis of acromegalyAcromegaly is an uncommon but serious disease due to anexcessive production of growth hormone (GH), usually from apituitary tumour. Although it has an insidious onset, onceclinically suspected its diagnosis is not usually difficult. Whileit appears that the condition is being diagnosed earlier and thatfewer patients are presenting with visual field defects, aproportion of patients are still not diagnosed until eitherpermanent visual loss occurs or there are irreversible effects ofGH excess, for example on the joints or the heart. As theduration of disease has an adverse effect upon mortality,vigilance is needed to ensure early diagnosis and to introduceeffective treatment to prevent the morbidity and mortality ofthis condition.EpidemiologyThe annual incidence of acromegaly is 3–4 cases per million,with a prevalence of 50–70 cases per million (Alexander et al.,1980). Males and females are affected equally, with a mean ageat diagnosis of 42 years in men and 44 years in women. Thediagnosis is often delayed as the clinical symptoms and signsevolve slowly: the delay from onset of symptoms to diagnosis isbetween 5 and 15 years with a mean delay of 8·7 years(Molitch, 1992). Younger patients tend to have more aggressivetumours which are larger at presentation and are diagnosedearlier (Melmed, 1990); older patients have a more delayeddiagnosis (Nabarro, 1987; Rajasoorya et al., 1994). In additionto the considerable morbidity associated with acromegaly,mortality is two to four times that of the general population(Wright et al., 1970; Nabarro, 1987; Bengtsson et al., 1988;Molitch, 1992). The major causes of death are cardiovascularand respiratory diseases and malignancy. There has been adebate in the literature as to whether malignancy is a significantcause of increased mortality because not all series have shownthis to be the case (Nabarro, 1987). However, most series doshow an increased mortality and death for colon and breastcancer, in particular, are increased (Ron et al., 1991). Bothmorbidity and mortality outcomes are strongly correlated withpre- and post-treatment levels of GH, as are duration ofsymptoms prior to diagnosis, older age at diagnosis and thepresence of cardiovascular disease and hypertension atdiagnosis (Rajasoorya et al., 1994). Successful treatment, asindicated by the return of GH secretion to a mean level over24h of less than 5mU/l, may be associated with a return tonormal life expectancy (Bates et al., 1993). This importantobservation, based on very small numbers, needs to beconfirmed and amplified. We do not yet know the effect oftreatment induced GH deficiency on outcome or the effect ofother forms of induced hypopituitarism.Normal GH secretory controlGH release from somatotroph cells of the anterior pituitarygland is under hypothalamic control with opposing effectsexerted by GH releasing hormone [GHRH] and somatostatin.GHRH increases transcription of the GH gene, and synthesisand secretion of GH. Somatostatin inhibits the secretion of GH,without affecting transcription or synthesis. There are manyother influences on GH release which include cholinergic andadrenergic pathways, oestrogens, thyrotrophin releasing hor-mone (TRH), insulin-like growth factor 1 (IGF-1), glucocorti-coids and opioids. Their effects are usually exerted at thehypothalamic level (Bertherat et al., 1995).‘Growth hormone’ refers to a heterogeneous family ofproteins. The 22kDa protein appears to be the major secretedform, with remaining GH consisting of a 20kDa form withquestionable biological role (it does not bind to liver GHreceptors), dimers, aggregates, deamidated GH and acylatedGH. A further human growth hormone variant is secreted solelyby the placenta. The ratio between differing forms of GH maybe altered by stimulation of secretion and tumours may producea predominant isoform of GH. Different forms of GH may bedetected with varying degrees of accuracy by various radio-immunoassays (Baumann, 1991). GH is carried by two serumgrowth hormone binding proteins. Two have been identified,one of high affinity and one of low affinity. The 60-kDa highaffinity BP corresponds to the extra cellular domain of thehepatic receptor. GH receptors are found in differing concen-tration in different tissues—with very high expression in liverand adipose tissue (Casaneuva, 1992). The plasma half-life ofGH is about 20min.