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. European Journal of Endocrinology 136 277–281

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SUN-LB61 Differential and Opposite Regulation of Acid Labile Subunit (ALS) Versus Insulin-Like Growth Factor I (IGF-I) by Oral Estrogens in Premenopausal Women

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2276 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Katharina Schilbach ◽

Michael Haenelt ◽

Shiva Sophia Nicolay ◽

Laura Schwerdt ◽

Rita Schwaiger ◽

...

Keyword(s):

Postmenopausal Women ◽

Negative Correlation ◽

Premenopausal Women ◽

Oral Contraception ◽

Limit Of Quantification ◽

Igf I ◽

Igf Binding ◽

Post Hoc ◽

The Impact ◽

Igfbp 3

Abstract Background: The impact of estrogens (E2) on the growth hormone (GH)/IGF-I axis is known to depend on route of administration: While oral E2 increases GH and decreases IGF-I, transdermal E2 has only limited or no effect. However, data concerning the impact of E2 on IGF binding protein 3 (IGFBP 3) and ALS are less clear. One study in girls demonstrated higher ALS with oral E2, while the opposite was suggested for postmenopausal women. No data are available for healthy premenopausal women.Methods: We measured IGF-I, IGFBP 3 and ALS in fasted healthy adults (93 males (M), 35 premenopausal women without E2-containing oral contraception (FPRE), 37 premenopausal women with E2-containing oral contraception (FPREOC) and 34 postmenopausal women (FPOST)). IGF-I and IGFBP 3 were measured using the IDS-iSYS chemiluminescence immunoassay, and ALS by an in-house immunofluorometric assay (limit of quantification (LoQ) < 50 mU/ml, range 50 - 4000 mU/mL).Results: Median age (range) was 33 (20 - 76), 28 (20 - 44), 24 (21 - 36) and 56 (49 - 70) years for M, FPRE, FPREOC and FPOST, respectively. As expected, IGF-I was lower in FPREOC compared to FPRE (median IGF-I xULN (IQR) 0.56 (0.45 - 0.73) and 0.72 (0.63 – 0.80), P = 0.0017, Kruskal-Wallis). ALS was significantly higher in FPREOC compared to all other groups (mean ALS in M, FPRE, FPREOC and FPOST: 636, 708, 861 and 648 mU/mL, respectively, ANOVA P < 0.0001, Dunnett’s post-hoc test: M vs FPREOC: P < 0.0001, FPRE vs FPREOC: P = 0.0007, FPOST vs FPREOC: P < 0.0001). IGFBP 3 was not different in females with and without oral E2 (median IGFBP 3 xULN (IQR) FPREOC vs FPRE: 0.62 (0.54 - 0.67) vs 0.60 (0.49 – 0.76), Kruskal-Wallis P = 0.295, Dunn’s post-hoc test: P > 0.9999). This was also true between all other groups (Dunn’s post-hoc test: P ≥ 0.4). In our adult cohort, ALS exhibited negative correlation with age (Pearson r = -0.282, P = 0.0003), similar to IGF-I and IGFBP 3. While IGF-I exhibited a moderate negative correlation to BMI (Pearson r = -0.25, P = 0.0013), IGFBP 3 and ALS were not significantly related to BMI.Conclusion: While IGF-I, IGFBP 3 and ALS all are known to be secreted in response to GH, and IGF-I and ALS are assumed to be produced by the same cells in the liver (hepatocytes), the three GH dependent biomarkers appear to be differently regulated by metabolic factors and oral E2. Only IGF-I has some modest association with BMI. Oral E2 is associated with reduced IGF-I, unchanged IGFBP 3 but increased ALS. While the mechanism behind the differential regulation remains to be uncovered, E2 therapy must be taken into account when interpreting IGF-I and ALS concentrations.

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Evaluation of the risk factors of asymptomatic vertebral fractures in postmenopausal women with osteopenia at the femoral neck

Maturitas ◽

10.1016/j.maturitas.2016.02.014 ◽

2016 ◽

Vol 87 ◽

pp. 95-101 ◽

Cited By ~ 1

Author(s):

A. Cano ◽

F. Baró ◽

C. Fernández ◽

V. Inaraja ◽

C.A. García-Domínguez

Keyword(s):

Risk Factors ◽

Femoral Neck ◽

Postmenopausal Women ◽

Vertebral Fractures

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POS0841 RISK FACTORS OF LOW BONE MINERAL DENSITY IN WOMEN WITH SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1339 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 674.2-675

Author(s):

A. Efremova ◽

N. Toroptsova ◽

N. Demin ◽

O. Dobrovolskaya ◽

O. Nikitinskaya

Keyword(s):

Risk Factors ◽

Bone Mineral Density ◽

Systemic Sclerosis ◽

Postmenopausal Women ◽

Bone Mineral ◽

Cumulative Dose ◽

Premenopausal Women ◽

C Reactive Protein ◽

Mineral Density ◽

Reactive Protein

Background:Chronic inflammatory rheumatic diseases are risk factors of bone loss and fractures. Systemic sclerosis (SSc) has been recognized to be another potential inflammatory joint disease that may affect bone tissue.Objectives:to evaluate bone mineral density (BMD) and risk factors of low BMD in women with SSc.Methods:173 women, among them 110 postmenopausal (median age 60[55,63] years) and 63 premenopausal (median age 35[31,44] years). BMD was measured at lumbar spine (LS), femoral neck (FN) and total hip (TH) by dual energy X-ray absorptiometry (DXA, Hologic 4500A). Low BMD was diagnosed if the T-score was < -1.0 standard deviation (SD) in postmenopausal women and if the Z-score was < -2.0 SD in premenopausal women. The relationship between BMD and SSc patients’ characteristics was evaluated using univariate linear regression analysis.Results:Low BMD was found in 66% patients: 79% - in postmenopausal and 18% - in premenopausal women. Among postmenopausal persons osteoporosis was discovered in 47% and osteopenia – in 32% cases. In postmenopausal woman BMD of LS, FN and TH were associated with body mass index (BMI) (β=0.27, p=0.010; β=0.47, p<0,001 and β=0.45, p<0,001, respectively), duration of glucocorticoids (GCs) using (β=-0.31, p=0.008; β=-0.34, p=0.003 and β=-0.27, p=0.022, respectively); BMD of FN and TH with C-reactive protein (β= -0.32, p=0.016 and β= -0.29, p=0.029, respectively) and LS BMD with current and cumulative GCs dose (β= -0.24, p=0.039 and β= -0.29, p=0.014, respectively). In premenopausal women BMD of LS, FN and TH were associated with BMI (β=0.51, p<0,001; β=0.45, p=0.003 and β=0.47, p=0.002, respectively), duration of GCs using (β= -0.45, p=0.004; β= -0.47, p=0.003 and β= -0.48, p=0.002, respectively) and GCs cumulative dose (β= -0.48, p=0.002; β= -0.51, p=0.001 and β= -0.46, p=0.004, respectively); BMD of FN and TH with 25(ОН)D level (β=0.52, p=0.008 and β=0.54, p=0.005, respectively), and LS BMD with SSc duration (β= -0.44, p=0.004).Conclusion:Low BMD was diagnosed in 66% of women with SSc. Low BMI, GCs cumulative dose and duration of GCs using were independent risk factors for low BMD in both premenopausal and postmenopausal persons. Additional factors as SSc duration and low vitamin D level were found out for premenopausal and current GCs dose and C-reactive protein level for postmenopausal women.Disclosure of Interests:None declared

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Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer

Acta Endocrinologica ◽

10.1530/eje-06-0611 ◽

2007 ◽

Vol 156 (2) ◽

pp. 187-194 ◽

Cited By ~ 12

Author(s):

Kalliopi Pazaitou-Panayiotou ◽

Theodore Kelesidis ◽

Iosif Kelesidis ◽

Athina Kaprara ◽

Jennifer Blakeman ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Breast Cancer Risk ◽

Female Breast Cancer ◽

Cancer Risk Factors ◽

Female Breast ◽

Igf I ◽

Breast Cancer Risk Factors ◽

Igfbp 3

Objective: Several components of the GH and IGF systems have been implicated in the development of malignancies. All components of these hormonal systems have never been jointly evaluated in female breast cancer, and previous studies have not examined the role of IGF-binding proteins (IGFBP-4, IGFBP-6) or GH-binding protein (GHBP). Design: Hospital-based case–control study. Methods: In this sample of primarily postmenopausal women, we obtained serum measures of IGF-I, IGF-II, and binding proteins IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, as well as GHBP, insulin, and leptin from 74 breast cancer cases and 76 control subjects. Results: In crude analyses, we found lower age-standardized mean IGF-I, IGFBP-3, IGFBP-4, IGFBP-6, and higher IGFBP-1 and GHBP in breast cancer cases when compared with controls. Multivariate models mutually adjusted for other GH–IGF system components and classical breast cancer risk factors demonstrated an inverse association between IGFBP-3 and risk of breast cancer (odds ratio (OR) = 0.2, P < 0.01) and a direct association between GHBP and disease risk (OR = 3.3, P < 0.01). No significant associations were detected in multivariate analyses among IGF-I, IGF-II or IGFBP-1, IGFBP-4, IGFBP-6 with risk of breast cancer, indicating that these factors may not have effects independent of and/or comparable with IGFBP-3 and GHBP. Conclusions: These results support a protective role of IGFBP-3 and demonstrate for the first time an increased risk of breast cancer with higher GHBP, after accounting for variation in IGFs, IGFBPs, and classical breast cancer risk factors.

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Longitudinal Changes in IGF-I and IGFBP-3, and Mammographic Density among Postmenopausal Women

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-13-0401 ◽

2013 ◽

Vol 22 (11) ◽

pp. 2116-2120 ◽

Cited By ~ 3

Author(s):

Christy G. Woolcott ◽

Kerry S. Courneya ◽

Norman F. Boyd ◽

Martin J. Yaffe ◽

Anne McTiernan ◽

...

Keyword(s):

Postmenopausal Women ◽

Mammographic Density ◽

Longitudinal Changes ◽

Igf I ◽

Igfbp 3

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Serum concentrations of IGF-I, IGFBP-3 and c-peptide and risk of hyperplasia and cancer of the breast in postmenopausal women

International Journal of Cancer ◽

10.1002/ijc.11624 ◽

2003 ◽

Vol 108 (5) ◽

pp. 773-779 ◽

Cited By ~ 60

Author(s):

Catherine Schairer ◽

Deirdre Hill ◽

Susan R. Sturgeon ◽

Thomas Fears ◽

Michael Pollak ◽

...

Keyword(s):

Postmenopausal Women ◽

Serum Concentrations ◽

C Peptide ◽

Igf I ◽

Igfbp 3

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Premenopausal breast cancer and the association between estrogen receptor status, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and leptin

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.640 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 640-640

Author(s):

J. Eng-Wong ◽

S. Chang ◽

S. Hursting ◽

S. N. Perkins ◽

N. Núñez ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor Status ◽

Premenopausal Women ◽

Normal Weight ◽

Premenopausal Breast Cancer ◽

Receptor Status ◽

Igf I ◽

Er Positive ◽

Er Status ◽

Igfbp 3

640 Background: The IGF pathway and leptin are associated with breast cancer risk in premenopausal women. These proteins are implicated in breast carcinogenesis through their interactions with the estrogen pathway, potentially resulting in specific breast cancer histopathologic subtypes. Methods: Pretreatment serum IGF-I, IGFBP-3 and leptin levels were examined in newly diagnosed premenopausal breast cancer cases to determine whether an association with tumor estrogen receptor status exists. Odds ratios were determined by logistic regression analysis. Likelihood ratio tests for interaction with BMI were conducted. Results: One hundred and eight women were evaluated (mean age 42); 82 were ER positive and 26 were ER negative. 62 were normal weight (BMI<25) and 46 were overweight and obese (BMI≥25). Mean IGF-I, IGFBP-3 and leptin levels did not differ between the ER positive and ER negative tumors. No associations were found between IGF-I, IGFBP-3 or leptin and ER status of tumors overall or by subset analysis in normal weight versus overweight and obese individuals. A suggestion that elevated IGFBP-3 was associated with ER-negative disease did not reach statistical significance. Additionally, normal-weight women with ER-negative disease had higher leptin levels than their normal-weight ER-positive counterparts, although we lacked statistical power to detect an effect of BMI on the association between leptin levels and tumor hormone receptor status. Conclusions: This is the first report examining the IGF pathway and leptin in relation to ER status in premenopausal women with newly diagnosed breast cancer. Our small number of cases suggests a number of intriguing findings that should be evaluated in larger studies. Determining links between ER status and IGFBP-3 and leptin may help better define risk factors and potentially appropriate interventions for ER-negative versus ER-positive breast cancer. No significant financial relationships to disclose.

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