Conversion of CSF monomeric growth hormone to large growth hormone with exposure to serum

We have found a dissociation between CSF and serum growth hormone heterogeneity in a patient with suprasellar extension of a growth hormone-secreting pituitary tumour. When CSF was studied using gel chromatography, virtually all the growth hormone eluted as monomeric growth hormone with only 2.4% eluting before albumin as large growth hormone ('big, big' growth hormone). In contrast, the large component comprised 15.4% of the total immunoreactivity in simultaneously obtained serum. When the CSF specimen was incubated with growth hormone-poor serum, the elution pattern changed remarkably with 16% of the total immunoreactivity eluting as large growth hormone causing it to resemble the serum elution pattern. We also measured growth hormone heterogeneity in the inferior petrosal vein (a site very close to pituitary venous drainage) during inferior petrosal venography in 3 patients. As the growth hormone concentration increased, the percentage eluting as monomeric growth hormone increased, whereas that eluting as large growth hormone decreased. When the growth hormone concentration fell towards baseline, the percentage of growth hormone eluting as monomeric growth hormone fell while that eluting as large growth hormone increased. Thus, our studies suggest that large growth hormone results from binding of monomeric growth hormone to serum proteins or aggregation of monomeric growth hormone in the presence of protein. Our studies also show that when blood is sampled at a site close to the pituitary, the growth hormone is released primarily as monomeric growth hormone.