Vitamin D across growth hormone (GH) disorders: From GH deficiency to GH excess

Abstract

The interplay between vitamin D and the growth hormone (GH)/insulin-like growth factor (IGF)-I system is very complex and to date it is not fully understood. GH directly regulates renal 1 alpha-hydroxylase activity, although the action of GH in modulating vitamin D metabolism may also be IGF-I mediated. On the other hand, vitamin D increases circulating IGF-I and the vitamin D deficiency should be normalized before measurement of IGF-I concentrations to obtain reliable and unbiased IGF-I values. Indeed, linear growth after treatment of nutritional vitamin D deficiency seems to be mediated through activation of the GH/IGF-I axis and it suggests an important role of vitamin D as a link between the proliferating cartilage cells of the growth plate and GH/IGF-I secretion. Vitamin D levels are commonly lower in patients with GH deficiency (GHD) than in controls, with a variable prevalence of insufficiency or deficiency, and this condition may worsen the already known cardiovascular and metabolic risk of GHD, although this finding is not common to all studies. In addition, data on the impact of GH treatment on vitamin D levels in GHD patients are quite conflicting. Conversely, in active acromegaly, a condition characterized by a chronic GH excess, both increased and decreased vitamin D levels have been highlighted, and the interplay between vitamin D and the GH/IGF-I axis becomes even more complicated when we consider the acromegaly treatment, both medical and surgical. The current review summarizes the available data on vitamin D in the main disorders of the GH/IGF-I axis, providing an overview of the current state of the art.

The relationships of alkaline phosphatase and bone alkaline phosphatase to the growth hormone/insulin-like growth factor-1 axis and vitamin D status in children with growth hormone deficiency

“…In children with growth hormone deficiency (GHD), ALP and BALP levels are decreased and rise significantly after the initiation of recombinant human growth hormone (rhGH) treatment (Juul et al, 1994;Ono et al, 1996;Tobiume et al, 1997;Eapen et al, 2008;Korpal-Szczyrska et al, 2008;Witkowska-Sędek et al, 2014). Vitamin D, which is necessary for normal calcium-phosphorus homeostasis and skeleton mineralization, also influences bone turnover during growth, but its role has not been fully explained (Barnes et al, 2006;Paradowska et al, 2007;Anderson et al, 2013;Koszowska et al, 2014;Thiering et al, 2015;Larijani et al, 2016;Ciresi et al, 2017;Schwetz et al, 2017). The effects of the GH/IGF-1 axis on bone turnover can be evaluated using the measurement of bone turnover markers (BTMs), including ALP and BALP (Ono et al, 1996;Locatelli et al, 2014;Devesa et al, 2016).…”

“…The effects of the GH/IGF-1 axis on bone turnover can be evaluated using the measurement of bone turnover markers (BTMs), including ALP and BALP (Ono et al, 1996;Locatelli et al, 2014;Devesa et al, 2016). The GH/IGF-1 axis can modulate vitamin D metabolism and, conversely, vitamin D can influence IGF-1 concentrations (Soliman et al, 2008;Bogazzi et al, 2011;Ameri et al, 2013;Ciresi et al, 2014;Witkowska-Sędek et al, 2016;Ciresi et al, 2017;Schwetz et al, 2017). Activation of vitamin D receptor (VDR) localised in osteoblasts, osteocytes, chondrocytes, and osteoclasts regulates cell proliferation, maturation, and mineralization as well as bone resorption.…”

“…Activation of vitamin D receptor (VDR) localised in osteoblasts, osteocytes, chondrocytes, and osteoclasts regulates cell proliferation, maturation, and mineralization as well as bone resorption. The effects of vitamin D on bone turnover are complex, but the results of studies evaluating associations between vitamin D and BTMs are divergent (Barnes et al, 2006;Anderson et al, 2013;Thiering et al, 2015;Larijani et al, 2016;Ciresi et al, 2017;Schwetz et al, 2017).…”

Evaluation of Calcium Regulating Hormones and Some Biochemical Parameters in Growth Hormone Deficient Patients

“…In children and adults, it has been reported that GH had no effect on vitamin D levels, while other studies confirmed a stimulatory effect [39].This may be due to the fact that vitamin D forms about 80-90% of the metabolites and can be obtained externally from exposure to sunlight, diet, or dietary supplements [40]. Also, the mutual interplay between vitamin D with the GH and IGF-I system is very complex.…”

“…Also, the mutual interplay between vitamin D with the GH and IGF-I system is very complex. Physiologically,GH regulates renal 1 alpha-hydroxylase activity and plasma concentrations of vitamin D. Also,vitamin D affects and increases circulating IGF-1 because they are produced by the liver [39].…”