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Vitamin D and insulin-like growth factor-1 (IGF-1) are involved in a complex interplay that may have implications for growth hormone dosing, researchers found.

In a review of the literature, patients with growth hormone deficiency who had higher vitamin D levels were more likely to achieve serum IGF-1 levels closer to the normal range, according to , of the University of Genova in Italy, and colleagues.

These patients were also more likely to be treated with lower doses of growth hormone, they reported online in .

"Vitamin D status may have an impact on the titration of [growth hormone] according to IGF-1 concentrations in patients with growth hormone deficiency," they wrote.

Since both IGF-1 and vitamin D are expressed throughout the body and have a broad spectrum of effects, the interplay between the two hormones is complex.

A positive correlation between serum concentrations of IGF-1, 25(OH)D and 1,25(OH)₂D has been "repeatedly demonstrated" in healthy patients, the researchers wrote, adding that evidence indicates the association is at least in part causal.

Specifically, vitamin D has been shown to increase circulating IGF-1 and IGF binding proteins (IGFBP-3), while administration of growth hormone and IGF-1 has been shown to increase vitamin D levels in several studies, they reported.

There's no conclusive information on mechanisms, Ferone and colleagues wrote, but it is well established that IGF-1 stimulates the synthesis of 1,25(OH)₂D in the kidney, and it is possible that vitamin D promotes production of IGF-1 and IGFBP-3 in the liver by "directly inducing the transcription of the relevant genes and/or by enhancing growth hormone stimulation," they wrote.

They also reported that IGF-1 induces the synthesis and activity of renal 1-alpha-hydroxylase, which ultimately can help increase calcium and phosphate availability while suppressing parathyroid hormone.

This may account for improvements in bone metabolism associated with growth hormone treatment in deficient patients, the researchers wrote.

Data on paracrine and autocrine interactions between vitamin D and IGF systems on other tissues and cells are insufficient to be pooled together in a comprehensive way, so it's not possible to draw a comprehensive picture of the physiological or pathological interrelations between vitamin D, IGF-1, and IGFBP, Ferone and colleagues noted.

However, in breast cancer, the interactions can be "rather comprehensively summarized," as it is known that IGF is central to development of hyperplasia, precancerous lesions, and tumors of the mammary gland. Some of the binding proteins may oppose the hormone's tumorigenic action by binding it and preventing it from interacting with its receptor.

At the same time, vitamin D has been shown to decrease proliferation and stimulate apoptosis of non-neoplastic mammary epithelia cells and breast cancer cells.

The researchers cautioned, however, that this interaction "may not be relevant in the clinical setting" and "may characterize only one or some breast cancer subtypes."

In terms of the clinical relevance of their findings, Ferone and colleagues said vitamin D may play an important role in dosing for growth hormone deficiency, as higher levels of the vitamin have been associated with better improvements in IGF-1 levels with growth hormone administration.

Looking retrospectively at a series of adult patients with growth hormone deficiency on replacement therapy, they found that cases with higher concentrations of 25(OH)D were more likely to have serum IGF-1 levels at least equal to sex-age-specific median in the normal population.

These patients were also more likely to be treated with lower amounts of growth hormone, they reported.

"Therefore, assessment of vitamin D status might be indicated to better determine the dose of growth hormone for treatment of adult patients with growth hormone deficiency," they wrote.

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