Serum IGF-I levels in the diagnosis and monitoring of acromegaly

Abstract

Insulin-Like Growth Factor-I (IGF-I) is a reliable marker of disease activity and growth hormone (GH) status in acromegaly, but its clinical utility has been hampered over the years by various issues including a lack of robust reference range data and variability in assay sensitivity and specificity. In acromegaly IGF-I correlates well with GH activity and nadir GH on oral glucose tolerance test (OGTT) and is the most sensitive and specific test in diagnosis, where serum IGF-I is persistently seen to be elevated to a range that is distinct from that in healthy individuals. However it should not be relied on exclusively for diagnosis or used as the sole indication of disease severity and GH burden. Successful medical or surgical treatment of acromegaly is usually associated with normalisation of serum IGF-I but there is discordance between GH and IGF-I in some patients. Patients with a normal IGF-I but an abnormal GH suppression to OGTT are at risk of relapse and therefore it should not be used alone to establish disease remission. In contrast to the diagnosis of acromegaly, there is also considerable overlap in serum IGF-I with normality after primary treatment of disease, even in the presence of persisting GH excess. Gender, age and prior radiotherapy alters the relationship between GH and IGF-I and reliance on one marker of disease activity such as IGF-I is particularly precarious in certain disease states. However an elevated serum IGF-I has been shown to be associated with excess mortality and normalising IGF-I normalises mortality making it a useful marker. The tightening up of the assays means that establishing absolute concentrations as well as standard deviation scores are essential to allow cross-study comparisons. This becomes especially important in the use of Pegvisomant, where IGF-I becomes the sole biochemical marker of disease activity.

Fractionated stereotactic radiotherapy in patients with acromegaly: an interim single-centre audit

“…Discordance between normalisation of the biochemical acromegaly status in regard to IGF1 and GH/nadir GH can be useful in the treatment and followup strategies, since elevated IGF1 alone seems to have a different prognosis compared with elevated GH/nadir GH alone (22,23). Patients with elevated IGF1 and normal GH/nadir GH are at risk of having persisting clinical manifestations of acromegaly and can therefore indeed benefit from the treatment with a GH receptor antagonist (24,25), while patients with elevated GH/nadir GH and normal IGF1 are at a risk of relapse of the tumour (22,23).…”

“…Patients with elevated IGF1 and normal GH/nadir GH are at risk of having persisting clinical manifestations of acromegaly and can therefore indeed benefit from the treatment with a GH receptor antagonist (24,25), while patients with elevated GH/nadir GH and normal IGF1 are at a risk of relapse of the tumour (22,23). The origin of discordance is likely to be that IGF1 and GH/nadir GH seem to represent two different aspects of acromegaly (26), and RT in general reduces rather than cures the hypersecretion of GH (3,24).…”

“…The origin of discordance is likely to be that IGF1 and GH/nadir GH seem to represent two different aspects of acromegaly (26), and RT in general reduces rather than cures the hypersecretion of GH (3,24). Discordance is seen in up to 27% of acromegalic patients (22). This makes the discussion about criteria for cure relevant, and probably also substantiates a need for age-related limits in regard to GH/nadir GH and consensus regarding methods of analysis (27)(28)(29).…”

Composite MET-PET Fusion 3.0 Tesla MRI is a New Sensitive Method for the Detection of GH Secreting Adenomas with Abnormal GH Secretary Dynamics

“…Freda [24] concluded that a cutoff value of 1 µg/l fails to identify 50% of patients with active disease. Moreover, we must consider the influence of GH and IGF-1 levels in other conditions, such as diabetes mellitus, hepatic J Metabolic Synd ISSN: 2167-0943 JMS, an open access journal Pathophysiology and Treatment of Acromegaly or renal failure, hypothyroidism, pregnancy, adolescence, and anorexia nervosa, and that they are influenced by oral estrogen, age and sex [3,8,21,[23][24][25]. About 50% of patients with acromegaly experience a rapid increase in plasma GH concentrations after stimulation of the TRH secretion and/or gonadotropin-releasing hormone (GnRH) secretion.…”

“…Acromegaly is associated with a 2-3-fold higher mortality rate and a reduction of life expectancy by 10-15 years compared with the general population. These outcomes are mainly attributed to the presence of other severe diseases, such as diabetes mellitus, hypertension, hyperlipidemia, cardiovascular and respiratory disease, and neoplasms [1,3,5,[7][8][9][10][11][12][13]. The duration of the disease is a prognostic factor.…”