The biomarker sex hormone-binding globulin – From established applications to emerging trends in clinical medicine

Thaler, Markus; Seifert-Klauss, Vanadin; Luppa, Peter B.

doi:10.1016/j.beem.2015.06.005

Cited by 81 publications

(65 citation statements)

References 91 publications

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“…The model was further validated by known thyrotoxic alterations in biochemical markers, including SHBG, CYTC, and total and LDL-cholesterol [12, 13, 55]. …”

Section: Resultsmentioning

confidence: 99%

“…Additionally, a number of rare severe clinical conditions lead to discordant alterations in serum TSH and FT 4 , including resistance to TH, TSH producing pituitary tumors, or central hypothyroidism [10, 11]. Therefore, peripheral biomarkers such as cholesterol and sex hormone- binding globulin (SHBG) concentrations have been suggested under these conditions as they are strongly correlated with thyroid function [12, 13]. However, because these parameters are also influenced by non-thyroidal disturbances, they were never established in clinical practice and accordingly current guidelines do not recommend their use [14].…”

Section: Introductionmentioning

confidence: 99%

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Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model

Pietzner

Engelmann

Kacprowski

et al. 2017

BMC Med

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BackgroundDeterminations of thyrotropin (TSH) and free thyroxine (FT4) represent the gold standard in evaluation of thyroid function. To screen for novel peripheral biomarkers of thyroid function and to characterize FT4-associated physiological signatures in human plasma we used an untargeted OMICS approach in a thyrotoxicosis model.MethodsA sample of 16 healthy young men were treated with levothyroxine for 8 weeks and plasma was sampled before the intake was started as well as at two points during treatment and after its completion, respectively. Mass spectrometry-derived metabolite and protein levels were related to FT4 serum concentrations using mixed-effect linear regression models in a robust setting. To compile a molecular signature discriminating between thyrotoxicosis and euthyroidism, a random forest was trained and validated in a two-stage cross-validation procedure.ResultsDespite the absence of obvious clinical symptoms, mass spectrometry analyses detected 65 metabolites and 63 proteins exhibiting significant associations with serum FT4. A subset of 15 molecules allowed a robust and good prediction of thyroid hormone function (AUC = 0.86) without prior information on TSH or FT4. Main FT4-associated signatures indicated increased resting energy expenditure, augmented defense against systemic oxidative stress, decreased lipoprotein particle levels, and increased levels of complement system proteins and coagulation factors. Further association findings question the reliability of kidney function assessment under hyperthyroid conditions and suggest a link between hyperthyroidism and cardiovascular diseases via increased dimethylarginine levels.ConclusionOur results emphasize the power of untargeted OMICs approaches to detect novel pathways of thyroid hormone action. Furthermore, beyond TSH and FT4, we demonstrated the potential of such analyses to identify new molecular signatures for diagnosis and treatment of thyroid disorders. This study was registered at the German Clinical Trials Register (DRKS) [DRKS00011275] on the 16th of November 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0770-8) contains supplementary material, which is available to authorized users.

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“…The model was further validated by known thyrotoxic alterations in biochemical markers, including SHBG, CYTC, and total and LDL-cholesterol [12, 13, 55]. …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model

Pietzner

Engelmann

Kacprowski

et al. 2017

BMC Med

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“…SHBG is related to androgen activity because of their ability for binding to TT and therefore regulating the levels of bioavailable free TT. SHBG can be regulated by sex hormones as androgen decreases and estrogen increases SHBG concentration [38, 39]. The positive association of SHBG with DEHP exposure may be due to the anti-androgenic effects of DEHP because testosterone has an inhibitory influence on SHBG [9].…”

Section: Discussionmentioning

confidence: 99%

Phthalate exposure and reproductive hormones and sex-hormone binding globulin before puberty – Phthalate contaminated-foodstuff episode in Taiwan

Wen

Chen

et al. 2017

PLoS ONE

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BackgroundIn May 2011, a major incident involving phthalates-contaminated foodstuffs occurred in Taiwan. Di-(2-ethylhexyl) phthalate (DEHP) was added to foodstuffs, mainly juice, jelly, tea, sports drink, and dietary supplements. Concerns arose that normal pubertal development, especially reproductive hormone regulation in children, could be disrupted by DEHP exposure.ObjectiveTo investigate the association between phthalate exposure and reproductive hormone levels among children following potential exposure to phthalate-tainted foodstuffs.MethodsA total of 239 children aged <12 years old were recruited from 3 hospitals in north, central, and south Taiwan after the episode. Structured questionnaires were used to collect the frequency and quantity of exposures to 5 categories of phthalate-contaminated foodstuffs to assess phthalate exposure in children. Urine samples were collected for the measurement of phthalate metabolites. The estimated daily intake of DEHP exposure at the time of the contamination incident occurred was calculated using both questionnaire data and urinary DEHP metabolite concentrations. Multiple regression analyses were applied to assess associations between phthalate exposure and reproductive hormone levels in children.ResultsAfter excluding children with missing data regarding exposure levels and hormone concentrations and girls with menstruation, 222 children were included in the statistical analyses. After adjustment for age and birth weight, girls with above median levels of urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and sum of mono-(2-ethylhexyl) phthalate concentrations had higher odds of above median follicle-stimulating hormone concentrations. Girls with above median estimated average daily DEHP exposures following the contamination episode also had higher odds of sex hormone-binding globulin above median levels.ConclusionsPhthalate exposure was associated with alterations of reproductive hormone levels in girls.

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“…With respect to TT, men exhibit higher levels through secretion from the testis whereas in women TT secretion is restricted to small amounts out of the ovaries and adrenal glands causing low circulating levels. Moreover, despite its high binding affinity to steroids serum SHBG is affected by a multitude of circumstances, including liver disorders most likely non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) 18 . In consequence, differing association patterns between men and women in relation to SHBG likely reflect the divergent metabolic state of both within the present cohort, like a higher amount of alcohol consumption and more prevalent severe MetS in men.…”

Section: Discussionmentioning

confidence: 99%

Sex-specific metabolic profiles of androgens and its main binding protein SHBG in a middle aged population without diabetes

Piontek

Wallaschofski

Kastenmüller

et al. 2017

Sci Rep

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The role of androgens in metabolism with respect to sex-specific disease associations is poorly understood. Therefore, we aimed to provide molecular signatures in plasma and urine of androgen action in a sex-specific manner using state-of-the-art metabolomics techniques. Our study population consisted of 430 men and 343 women, aged 20–80 years, who were recruited for the cross-sectional population-based Study of Health in Pomerania (SHIP-TREND), Germany. We used linear regression models to identify associations between testosterone, androstenedione and dehydroepiandrosterone-sulfate (DHEAS) as well as sex hormone-binding globulin and plasma or urine metabolites measured by mass spectrometry. The analyses revealed major sex-specific differences in androgen-associated metabolites, particularly for levels of urate, lipids and metabolic surrogates of lifestyle factors, like cotinine or piperine. In women, in particular in the postmenopausal state, androgens showed a greater impact on the metabolome than in men (especially DHEAS and lipids were highly related in women). We observed a novel association of androstenedione on the metabolism of biogenic amines and only a small sex-overlap of associations within steroid metabolism. The present study yields new insights in the interaction between androgens and metabolism, especially about their implication in female metabolism.

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The biomarker sex hormone-binding globulin – From established applications to emerging trends in clinical medicine

Cited by 81 publications

References 91 publications

Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model

Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model

Phthalate exposure and reproductive hormones and sex-hormone binding globulin before puberty – Phthalate contaminated-foodstuff episode in Taiwan

Sex-specific metabolic profiles of androgens and its main binding protein SHBG in a middle aged population without diabetes

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