Decreased serum IGF-I and dehydroepiandrosterone sulphate may be risk factors for the development of reduced bone mass in postmenopausal women with endogenous subclinical hyperthyroidism

Abstract

Postmenopausal women with endogenous subclinical hyperthyroidism seem to have reduced bone mass, which does not correlate with serum thyroid hormone levels. Relative insufficiencies of IGF-I and dehydroepiandrosterone sulphate (DHEAS) might be additional risk factors for low bone density in these patients. We measured IGF-I, IGF-binding protein-3 (IGFBP-3) and DHEAS levels together with bone mineral density (BMD) of the femoral neck and lumbar spine in women with an autonomously functioning thyroid nodule. Sixty-three women were classified as subclinical hyperthyroid (31 pre- and 32 postmenopausal) and 39 as overt hyperthyroid (16 pre- and 23 postmenopausal) and results were compared with data obtained from 41 age-matched euthyroid healthy women. In premenopausal women BMD was reduced only in the overt hyperthyroid group, and only in the spine, to 92% (P < 0.05). Serum IGF-I as well as IGFBP-3 were increased in the manifest hyperthyroid group, to 157% (P < 0.001) and 129% (P < 0.05) respectively, whereas DHEAS levels did not change in either premenopausal patient group. In postmenopausal women BMD was significantly reduced both in the subclinical hyperthyroid group (spine to 90% and femoral neck to 88%; P < 0.05), as well as in the hyperthyroid group (spine to 78% and femoral neck to 86%; P < 0.01). In contrast to premenopausal women, serum IGF-I and IGFBP-3 did not change in the two groups who were postmenopausal and serum DHEAS levels were reduced to 58% (P < 0.001) in both postmenopausal groups with subclinical as well as overt hyperthyroidism. In the same two groups of patients, serum IGF-I and DHEAS levels correlated with BMD (femoral neck; both r = 0.50, P < 0.05). In conclusion, women with a solitary autonomous thyroid nodule with subclinical hyperthyroidism have reduced BMD only if they are postmenopausal. This is probably due to the effect of subtle increases in thyroid hormone production together with lack of oestrogen protection of the skeleton. But additional risk factors for the development of enhanced bone loss might be a state of relative IGF-I and DHEAS insufficiency in these patients as well as in postmenopausal women with overt hyperthyroidism.

Ovarian Ultrasound and Ovarian and Adrenal Hormones before and after Treatment for Hyperthyroidism

“…Changes in adrenocortical androgens in hyperthyroid patients, including elevated DHEAS levels and a low DHEA/DHEAS ratio, have previously been reported by Földes et al [13]. In contrast to these findings, DHEAS levels were normal in our patients, while the DHEA levels were significantly decreased.…”

Complications of Hyperthyroidism

“…These include a relative deficiency of insulin-like growth factor type I, dehydroepiandrosterone sulfate [287], vitamin D receptor (VDR) polymorphisms [288] and estrogen [289]. The question as to whether prolonged hyperthyroidism due to L-T4 treatment increases the risk of fractures also remains controversial.…”

Advances in Our Understanding of Hyperthyroidism-associated Bone Loss

“…There are fewer data on the effect of sub-clinical hyperthyroidism on BMD in pre-menopausal women, although a few studies have shown no effect. 32,35,38 One study showed a decrease in BMD in femoral neck and phalanges but not lumbar spine. 33 The effect of sub-clinical hyperthyroidism on BMD in men has not been investigated adequately.…”