Is there a genetic component to varying IGF-1 levels with AGHD?

Adults who become growth hormone deficient (AGHD)are typically undiagnosed for a long time. Generally, pituitary tumors or other medical issues lead the diagnostician to question GH levels in an adult. IGF-I, even if measured, often is normal with AGHD. Due to cardiovascular and other risks which cause increased mortality and decreased quality of life, understanding AGHD is of utmost importance.

In The use of a GH receptor antagonist (GHRA) to explore the relationship between GH and IGF-I in adults with severe growth hormone deficiency (GHD), the authors research the question of why some folks with deficient GH still have "normal" IGF-I levels but others with deficient GH have low IGF-I levels.

[A]pproximately 50% of middle-aged patients diagnosed with severe GHD, defined by peak stimulated GH levels of <3>Using Pegvisonmant, a highly selective GH receptor antagonist used to treat acromegaly by blocking GH action, they determined those who had low IGF-I levels with AGHD could not increase secretion of GH but "[i]n those with a normal IGF-I, baseline and stimulated GH secretion can be increased by reducing IGF-I." This suggested to them that patients with low IGF-I levels were that way because they weren't regulated by GH (GH independent) but that patients with normal IGF-I levels were GH-dependent.

Does this mean there is a difference in severity in the two types of patients? According to the authors it does:

These data show that in these patients, who meet the consensus criteria for severe adult GHD, the hypothalamic-pituitary axis is capable of increasing GH secretion in response to a fall in IGF-I thereby implying that the previously unexplained paradox of patients with severe adult GHD having normal IGF-I levels can be accounted for by subtle differences in on-going physiological GH secretion not discernable by the ‘crude’ stimulation tests used to diagnose adult GHD. Hence, this study shows that patients with normal and low IGF-I differ in the severity of GHD.

They do admit the need for further study, indicating a possible "genetic contribution to the difference in IGF-I levels between [AGHD] patients with low and normal IGF-I."

CA Berg, A Pokrajac, M Bidlingmaier, CJ Strasburger, SM Shalet, PJ Trainer (2008). The use of a GH receptor antagonist (GHRA) to explore the relationship between GH and IGF-I in adults with severe growth hormone deficiency (GHD) Clinical Endocrinology DOI: 10.1111/j.1365-2265.2008.03481.x