PDF herunterladen
Horm Metab Res 2019; 51(05): 302-308
DOI: 10.1055/a-0859-4285
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Relationships Between Thyroid Hormones, Insulin-Like Growth Factor-1 and Antioxidant Levels in Hypothalamic Amenorrhea and Impact on Bone Metabolism

Antonio Mancini
1   UOC Endocrinologia e Diabetologia, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
2   Istituto di Patologia Speciale Medica e Semeiotica Medica, Università Cattolica del Sacro Cuore, Rome, Italy
,
Edoardo Vergani
1   UOC Endocrinologia e Diabetologia, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
2   Istituto di Patologia Speciale Medica e Semeiotica Medica, Università Cattolica del Sacro Cuore, Rome, Italy
,
Carmine Bruno
1   UOC Endocrinologia e Diabetologia, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
2   Istituto di Patologia Speciale Medica e Semeiotica Medica, Università Cattolica del Sacro Cuore, Rome, Italy
,
Angelina Barini
3   Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
4   Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy
,
Andrea Silvestrini
3   Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
4   Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy
,
Elisabetta Meucci
3   Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
4   Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy
,
Calogero Messana
5   UOC Ostetricia e Patologia Ostetrica, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
6   Istituto di Clinica Ostetrico e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy
,
Daniela Romualdi
5   UOC Ostetricia e Patologia Ostetrica, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
6   Istituto di Clinica Ostetrico e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy
,
Rosanna Apa
5   UOC Ostetricia e Patologia Ostetrica, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
6   Istituto di Clinica Ostetrico e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy
,
Antonio Lanzone
5   UOC Ostetricia e Patologia Ostetrica, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
6   Istituto di Clinica Ostetrico e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 15. November 2018

accepted 11. Februar 2019

Publikationsdatum:
07. März 2019 (online)

Auch verfügbar auf
   Lizenzen und Reprints

Abstract

Reduced bone mineral density (BMD) in Functional Hypothalamic Amenorrhea (FHA) is mainly related to hypoestrogenism, but other hormonal derangement (reduced conversion of T4–T3 and GH resistance) can play a role. These hormones are involved in antioxidant systems regulation. We evaluated the impact of hormonal alterations, with special focus on low T3 and IGF-1 levels, on antioxidant systems as a link with osteoporosis in FHA. Forty-three FHA patients, 15–34 years, with BMI range 17.3–23.4 kg/m2, were divided in 2 groups according to fT3 levels; group A (n=22), low fT3 (<2.4 pg/ml) and group B (n=21), normal fT3 (≥ 2.4 pg/ml). We evaluated hormonal parameters (fT3, fT4, TSH, IGF-1, FSH, LH, estradiol, DHEAS, testosterone, cortisol), bone metabolism (calcium, phosphorus, 25-OH Vitamin D, PTH, β-crosslaps, bone alkaline phosphatase) and total antioxidant capacity (TAC), expressed as LAG (latency time in radical species appearance using spectrophotometric method). BMD was assessed by DEXA. Group A patients exhibited significantly lower levels of IGF-1 (159.76±14.79 vs. 220.05±15.25 ng/ml) and osteocalcin (17.51±1.14 vs. 21.49±1.56 ng/ml); LAG values were significantly higher in A (66.33±1.74 s) vs. B (54.62±1.74 s). A significant direct correlation was found between both IGF-1 and fT3 with osteocalcin (r²=0.22, p=0.0049 and r²=0.34, p=0.0001, respectively). No difference in LAG between groups according to IGF-1 were found. These data show a correlation between altered bone turnover and low fT3, which is highly prevalent in FHA. Low fT3 levels may contribute to reduced BMD. Oxidative stress could be the link underlying different bone turnover pattern and endocrine dysfunction in FHA.

Key words

amenorrhea - osteoporosis - non-thyroidal illness - osteocalcin - antioxidants

Supplementary Material

    Supplementary Material for this article is available online at http://www.thieme-connect.de/products
  • Supplementary Material
 

  • References

  • 1 The Practice Committee of the American Society for Reproductive Medicine . Current evaluation of amenorrhea. 2008 Compend Pract Comm Reports 2008; 90: S219-S225
    PubMedGoogle Scholar
  • 2 Gordon CM, Ackerman KE, Berga SL. et al. Functional hypothalamic amenorrhea: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2017; 102: 1413-1439
    CrossrefPubMedGoogle Scholar
  • 3 Berga SL, Mortola JF, Girton L. et al. Neuroendocrine aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 1989; 68: 301-308
    CrossrefPubMedGoogle Scholar
  • 4 Meczekalski B, Podfigurna-Stopa A, Warenik-Szymankiewicz A. et al. Functional hypothalamic amenorrhea: Current view on neuroendocrine aberrations. Gynecol Endocrinol 2008; 24: 4-11
    CrossrefPubMedGoogle Scholar
  • 5 Meczekalski B, Katulski K, Czyzyk A. et al. Functional hypothalamic amenorrhea and its influence on women’s health. J Endocrinol Invest 2014; 37: 1049-1056
    CrossrefPubMedGoogle Scholar
  • 6 Berga SL, Daniels TL, Giles DE. Women with functional hypothalamic amenorrhea but not other forms of anovulation display amplified cortisol concentrations. Fertil Steril 1997; 67: 1024-1030
    CrossrefPubMedGoogle Scholar
  • 7 Laughlin GA, Dominguez CE, Yen SSC. Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 1998; 83: 25-32
    PubMedGoogle Scholar
  • 8 Kavushansky A, Kritman M, Maroun M. et al. β-Endorphin degradation and the individual reactivity to traumatic stress. Eur Neuropsychopharmacol 2013; 23: 1779-1788
    CrossrefPubMedGoogle Scholar
  • 9 Bérubé P, Laforest S, Bhatnagar S. et al. Enkephalin and dynorphin mRNA expression are associated with resilience or vulnerability to chronic social defeat stress. Physiol Behav 2013; 122: 237-245
    CrossrefPubMedGoogle Scholar
  • 10 Kling JM, Clarke BL, Sandhu NP. Osteoporosis prevention, screening, and treatment: A review. J Womens Health (Larchmt) 2014; 23: 563-572
    CrossrefPubMedGoogle Scholar
  • 11 De Souza MJ, Williams NI. Physiological aspects and clinical sequelae of energy deficiency and hypoestrogenism in exercising women. Hum Reprod Update 2004; 10: 433-448
    CrossrefPubMedGoogle Scholar
  • 12 Khosla S. Update on estrogens and the skeleton. J Clin Endocrinol Metab 2010; 95: 3569-3577
    CrossrefPubMedGoogle Scholar
  • 13 Seeman E. Pathogenesis of bone fragility in women and men. Lancet 2002; 359: 1841-1850
    CrossrefPubMedGoogle Scholar
  • 14 Halliwell B, Gutteridge JMC. Free Radicals in Biology and Mededicine. In Halliwell B, Gutteridge JMC. (Eds.). Free radicals in biology and medicine. 3rd Edition Oxford University Press; Oxford: 1999: 1-25
    Google Scholar
  • 15 Manolagas SC. From estrogen-centric to aging and oxidative stress: A revised perspective of the pathogenesis of osteoporosis. Endocr Rev 2010; 31: 266-300
    CrossrefPubMedGoogle Scholar
  • 16 Mancini A, Festa R, Di Donna V. et al. Hormones and antioxidant systems: Role of pituitary and pituitary-dependent axes. J Endocrinol Invest 2010; 33: 422-433
    CrossrefPubMedGoogle Scholar
  • 17 American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders DSM-V. Washington D. C.: 2013
    Google Scholar
  • 18 Rice-Evans C, Miller NJ. Total antioxidant status in plasma and body fluids. Methods Enzymol 1994; 234: 279-293
    PubMedGoogle Scholar
  • 19 Mancini A, Leone E, Festa R. et al. Evaluation of antioxidant systems (coenzyme Q10 and total antioxidant capacity) in morbid obesity before and after biliopancreatic diversion. Metabolism 2008; 57: 1384-1389
    CrossrefPubMedGoogle Scholar
  • 20 Baroncelli GI, Bertelloni S, Sodini F. et al. Osteoporosis in children and adolescents etiology and management. Pediatr Drugs 2005; 7: 295-323
    CrossrefPubMedGoogle Scholar
  • 21 Mancini A, Di Segni C, Raimondo S. et al. Thyroid hormones, oxidative stress, and inflammation. Mediators Inflamm 2016; Article ID 6757154 http://dx.doi.org/10.1155/2016/6757154
    CrossrefPubMedGoogle Scholar
  • 22 Misra M, Klibanski A. Anorexia nervosa and bone. J Endocrinol 2014; 221: R163-R176
    CrossrefPubMedGoogle Scholar
  • 23 Ohlsson C, Mellström D, Carlzon D. et al. Older men with low serum IGF-1 have an increased risk of incident fractures: The MrOS Sweden study. J Bone Miner Res 2011; 26: 865-872
    CrossrefPubMedGoogle Scholar
  • 24 Sugimoto T, Nishiyama K, Kuribayashi F. Serum levels of insulin-like growth factor (IGF) I , osteoporotic patients with and without spinal fractures. J Bone Min Res 1997; 12: 1272-1279
    CrossrefPubMedGoogle Scholar
  • 25 Locatelli V, Bianchi VE. Effect of GH/IGF-1 on bone metabolism and osteoporsosis. Int J Endocrinol 2014; 2014 235060 doi:10.1155/2014/235060
    PubMedGoogle Scholar
  • 26 Vandenput L, Boonen S, Van Herck E. et al. Evidence from the aged orchidectomized male rat model that 17β-estradiol is a more effective bone-sparing and anabolic agent than 5α-dihydrotestosterone. J Bone Miner Res 2002; 17: 2080-2086
    CrossrefPubMedGoogle Scholar
  • 27 Fazeli PK, Klibanski A. Anorexia nervosa and bone metabolism. Bone 2014; 66: 39-45
    CrossrefPubMedGoogle Scholar
  • 28 Wang Y, Bikle DD, Chang W. Autocrine and paracrine actions of IGF-I signaling in skeletal development. Bone Res 2013; 1: 249-259
    CrossrefPubMedGoogle Scholar
  • 29 Ghodsi M, larijani B, Keshtkar AA. et al. Mechanisms involved in altered bone metabolism in diabetes: A narrative review. J Diabetes Metab Disord 2016; 15: 52
    CrossrefPubMedGoogle Scholar
  • 30 Tripathi T, Gupta P, Rai P. et al. Osteocalcin and serum insulin-like growth factor-1 as biochemical skeletal maturity indicators. Prog Orthod 2017; 18: 30
    CrossrefPubMedGoogle Scholar
  • 31 Abu EO, Bord S, Horner A. et al. The expression of thyroid hormone receptors in human bone. Bone 1997; 21: 137-142
    CrossrefPubMedGoogle Scholar
  • 32 Kindblom JM, Gevers EF, Skrtic SM. et al. Increased adipogenesis in bone marrow but decreased bone mineral density in mice devoid of thyroid hormone receptors. Bone 2005; 36: 607-616
    CrossrefPubMedGoogle Scholar
  • 33 Williams GR. Thyroid hormone actions in cartilage and bone. Eur Thyroid J 2012; 3-13
    PubMedGoogle Scholar
  • 34 Xing W, Govoni KE, Donahue LR. et al. Genetic evidence that thyroid hormone is indispensable for prepubertal insulin-like growth factor-I expression and bone acquisition in mice. J Bone Miner Res 2012; 27: 1067-1079
    CrossrefPubMedGoogle Scholar
  • 35 Milne M, Quail JM, Rosen CJ. et al. Insulin-like growth factor binding proteins in femoral and vertebral bone marrow stromal cells: expression and regulation by thyroid hormone and dexamethasone. J Cell Biochem 2001; 81: 229-240
    CrossrefPubMedGoogle Scholar
  • 36 Stevens DA, Harvey CB, Scott AJ. et al. Thyroid hormone activates fibroblast growth factor receptor-1 in bone. Mol Endocrinol 2003; 17: 1751-1766
    CrossrefPubMedGoogle Scholar
  • 37 Varga F, Rumpler M, Zoehrer R. et al. T3 affects expression of collagen I and collagen cross-linking in bone cell cultures. Biochem Biophys Res Commun 2010; 402: 180-185
    CrossrefPubMedGoogle Scholar
  • 38 Gouveia CH, Schultz JJ, Bianco AC. et al. Thyroid hormone stimulation of osteocalcin gene expression in ROS 17/2.8 cells is mediated by transcriptional and post-transcriptional mechanisms. J Endocrinol 2001; 170: 667-675
    CrossrefPubMedGoogle Scholar
  • 39 Bassett JHD, Boyde A, Howell PGT. et al. Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts. Proc Natl Acad Sci USA 2010; 107: 7604-7609
    CrossrefPubMedGoogle Scholar
  • 40 Mastorakos G, Pavlatou M. Exercise as a stress model and the interplay between the hypothalamus-pituitary-adrenal and the hypothalamus-pituitary-thyroid axes. Horm Metab Res 2005; 37: 577-584
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 41 Riggs BL. The mechanisms of estrogen regulation of bone resorption. J Clin Invest 2000; 106: 1203-1204
    CrossrefPubMedGoogle Scholar
  • 42 Mircea CN, Lujan ME, Pierson RA. Metabolic fuel and clinical implications for female reproduction. J Obstet Gynaecol Canada 2007; 29: 887-902
    PubMedGoogle Scholar
  • 43 Mödder UIl, Clowes JA, Hoey K. et al. Regulation of circulating sclerostin levels by sex steroids in women and in men. J Bone Miner Res 2011; 26: 27-34
    CrossrefPubMedGoogle Scholar
  • 44 Fazeli PK, Bredella MA, Freedman L. et al. Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa. J Bone Miner Res 2012; 27: 1864-1871
    CrossrefPubMedGoogle Scholar
  • 45 Taes Y, Lapauw B, Vandewalle S. et al. Estrogen-specific action on bone geometry and volumetric bone density: Longitudinal observations in an adult with complete androgen insensitivity. Bone 2009; 45: 392-397
    CrossrefPubMedGoogle Scholar
  • 46 Crandall CJ, Tseng C-H, Karlamangla AS. et al. Serum sex steroid levels and longitudinal changes in bone density in relation to the final menstrual period. J Clin Endocrinol Metab 2013; 98: E654-E663
    CrossrefPubMedGoogle Scholar
  • 47 Mancini A, Di Segni C, Bruno C. et al. Oxidative stress in adult growth hormone deficiency: Different plasma antioxidant patterns in comparison with metabolic syndrome. Endocrine 2018; 59: 130-136
    CrossrefPubMedGoogle Scholar
  • 48 Mancini A, Raimondo S, Di Segni C. et al. Comparison of plasma antioxidant levels in middle-aged and old male with idiopatic osteoporosis: Preliminary data. Eur Rev Med Pharmacol Sci 2014; 18: 2013-2019
    PubMedGoogle Scholar