Skip to main content
SpringerLink
Log in

The relationship between hyperthyrotropinemia and metabolic and cardiovascular risk factors in a large group of overweight and obese children and adolescents

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

Mild TSH elevations are frequently observed in obese patients, in the absence of any detectable thyroid disease. Our objective is to evaluate the relationship between the raised TSH levels and the biochemical and clinical consequences of obesity.

Methods

This is a retrospective cross-sectional study of a large population of obese children and adolescents. We evaluated 833 subjects (340 m, 493 f), aged 14.4 ± 2.5 (range 5.2–18.5) years, height SDS 0.27 ± 1.04 (−3.49–4.35), and BMI SDS 2.94 ± 0.59 (1.60–4.68). Body composition, free T4, TSH, anti-TPO antibodies, anti-TG antibodies, inflammation markers (total WBC and the subtypes, ultrasensitive C-reactive protein), and metabolic parameters [AST, ALT, γGT, ALP, glycaemia, insulin, total cholesterol (TC), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C), triglycerides (TG)] were measured, and oral disposition index (ODI) and cardiovascular risk factors (TC/HDL-C and TG/HDL-C) were calculated. After exclusion of the subjects showing anti-thyroid antibodies, the remaining 779 (325 m, 454 f) were then subdivided into two subgroups according to a TSH value below (group A) or above (group B) 4.5 mU/L.

Results

Clinical characteristics and hematological markers of patients with and without positive anti-thyroid antibodies were similar, with the exception of higher TSH levels in the latter group. Using analysis of covariance, the subjects of group B had significantly higher values of TC (170.3 ± 28.7 vs 163.3 ± 32.9 mg/dL; p < 0.05), systolic (125.8 ± 13.5 vs 124.5 ± 13.1 mm/Hg), and diastolic blood pressure (79.2 ± 8.0 vs 77.9 ± 8.2 mm/Hg) than subjects of group A. No difference was observed in body composition, ODI, and the cardiovascular risk factors between these two groups.

Conclusion

TSH elevation in overweight and obese children and adolescents, being associated with a higher TC and blood pressure, might negatively influence the cardiac status. Longitudinal studies are requested, however, to confirm this hypothesis and, therefore, to conclude whether a substitutive treatment with l-thyroxine is really needed in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Reinehr T, de Sousa G, Andler W (2006) Hyperthyrotropinemia in obese children is reversible after weight loss and is not related to lipids. J Clin Endocrinol Metab 91:3088–3091

    Article  CAS  PubMed  Google Scholar 

  2. Reinehr T, Andler W (2002) Thyroid hormones before and after weight loss in obesity. Arch Dis Child 87:320–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sari R, Balci MK, Altunbas H, Karayalcin U (2003) The effect of body weight and weight loss on thyroid volume and function in obese women. Clin Endocrinol (Oxf) 59:258–262

    Article  Google Scholar 

  4. Buscemi S, Verga S, Maneri R, Blunda G, Galluzzo A (1997) Influences of obesity and weight loss on thyroid hormones. A 3–3.5-year follow-up study on obese subjects with surgical bilio-pancreatic by-pass. J Endocrinol Invest 20:276–281

    Article  CAS  PubMed  Google Scholar 

  5. Kiortsis DN, Durack I, Turpin G (1999) Effects of a low-calorie diet on resting metabolic rate and serum tri-iodothyronine levels in obese children. Eur J Pediatr 158:446–450

    Article  CAS  PubMed  Google Scholar 

  6. Hill JO, Sparling PB, Shields TW, Heller PA (1987) Effects of exercise and food restriction on body composition and metabolic rate in obese women. Am J Clin Nutr 46:622–630

    CAS  PubMed  Google Scholar 

  7. Tagliaferri MA, Berselli ME, Calo G, Minocci A, Savia G, Petroni ML, Viberti GC, Liuzzi A (2001) Subclinical hypothyroidism in obese patients: relation to resting energy expenditure, serum leptin, body composition, and lipid profile. Obes Res 9:196–201

    Article  CAS  PubMed  Google Scholar 

  8. Chomard P, Vernhes G, Autissier N, Debry G (1985) Serum concentrations of total T4, T3, reverse T3 and free T4, T3 in moderately obese patients. Hum Nutr Clin Nutr 39:371–378

    CAS  PubMed  Google Scholar 

  9. Matzen LE, Kvetny J, Pedersen KK (1989) TSH, thyroid hormones and nuclear-binding of T3 in mononuclear blood cells from obese and non-obese women. Scand J Clin Lab Invest 49:249–253

    Article  CAS  PubMed  Google Scholar 

  10. Duntas L, Hauner H, Rosenthal J, Pfeiffer EF (1991) Thyrotropin releasing hormone (TRH) immunoreactivity and thyroid function in obesity. Int J Obes 15:83–87

    CAS  PubMed  Google Scholar 

  11. Naslund E, Andersson I, Degerblad M, Kogner P, Kral JG, Rossner S, Hellstrom PM (2000) Associations of leptin, insulin resistance and thyroid function with long-term weight loss in dieting obese men. J Intern Med 248:299–308

    Article  CAS  PubMed  Google Scholar 

  12. Iacobellis G, Ribaudo MC, Zappaterreno A, Iannucci CV, Leonetti F (2005) Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women. Clin Endocrinol (Oxf) 62:487–491

    Article  CAS  Google Scholar 

  13. Stichel H, l’Allemand D, Gruters A (2000) Thyroid function and obesity in children and adolescents. Horm Res 54:14–19

    Article  CAS  PubMed  Google Scholar 

  14. Radetti G, Kleon W, Buzi F, Crivellaro C, Pappalardo L, di Iorgi N, Maghnie M (2008) Thyroid function and structure are affected in childhood obesity. J Clin Endocrinol Metab 93:4749–4754

    Article  CAS  PubMed  Google Scholar 

  15. Radetti G, Longhi S, Baiocchi M, Cassar W, Buzi F (2012) Changes in lifestyle improve body composition, thyroid function, and structure in obese children. J Endocrinol Invest 35:281–285

    CAS  PubMed  Google Scholar 

  16. Legradi G, Emerson CH, Ahima RS, Flier JS, Lechan RM (1997) Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. Endocrinology 138:2569–2576

    Article  CAS  PubMed  Google Scholar 

  17. Nillni EA, Vaslet C, Harris M, Hollenberg A, Bjorbak C, Flier JS (2000) Leptin regulates prothyrotropin-releasing hormone biosynthesis. Evidence for direct and indirect pathways. J Biol Chem 275:36124–36133

    Article  CAS  PubMed  Google Scholar 

  18. Harris M, Aschkenasi C, Elias CF, Chandrankunnel A, Nillni EA, Bjoorbaek C, Elmquist JK, Flier JS, Hollenberg AN (2001) Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling. J Clin Invest 107:111–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Burman KD, Latham KR, Djuh YY, Smallridge RC, Tseng YC, Lukes YG, Maunder R, Wartofsky L (1980) Solubilized nuclear thyroid hormone receptors in circulating human mononuclear cells. J Clin Endocrinol Metab 51:106–116

    Article  CAS  PubMed  Google Scholar 

  20. Fontenelle LC, Feitosa MM, Severo JS, Freitas TEC, Morais JBS, Torres-Leal FL, Henriques GS, Nascimento Marreiro D (2016) Thyroid function in human obesity: underlying mechanisms. Horm Metab Res 48:787–794

    Article  CAS  PubMed  Google Scholar 

  21. Di Bonito P, Pacifico L, Chiesa C, Valerio G, Miraglia Del Giudice E, Maffeis C, Morandi A, Invitti C, Licenziati MR, Loche S, Tornese G, Franco F, Manco M, Baroni MG, CARdiometabolic risk factors in overweight and obese children in ITALY” (CARITALY) Study Group (2017) Impaired fasting glucose and impaired glucose tolerance in children and adolescents with overweight/obesity. J Endocrinol Invest 40:409–416

    Article  PubMed  Google Scholar 

  22. Zhang J, Jiang R, Li L, Li P, Li X, Wang Z, Li L, Teng W (2014) Serum thyrotropin is positively correlated with the metabolic syndrome components of obesity and dyslipidemia in chinese adolescents. Int J Endocrinol 2014:289503

    PubMed  PubMed Central  Google Scholar 

  23. Witte T, Ittermann T, Thamm M, Riblet NB, Völzke H (2015) Association between serum thyroid stimulating hormone levels and serum lipids in children and adolescents: a population-based study of german youth. Clin Endocrinol Metab 100:2090–2097

    Article  CAS  Google Scholar 

  24. Kommareddy S, Lee SY, Braverman LE, Pearce EN (2015) Thyroid function and metabolic syndrome: a cross-sectional study in obese and overweight patients. Endocr Pract 21:1204–1210

    Article  PubMed  Google Scholar 

  25. Özer S, Bütün I, Sönmezgöz E, Yılmaz R, Demir O (2015) Relationships among thyroid hormones and obesity severity, metabolic syndrome and its components in Turkish children with obesity. Nutr Hosp 32:645–651

    PubMed  Google Scholar 

  26. Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, Cerutti F, Gargantini L, Greggio N, Tonini G, Cicognani A (2006) Italian cross-sectional growth charts for height, weight and BMI (2–20 years). J Endocrinol Invest 29:581–593

    Article  CAS  PubMed  Google Scholar 

  27. Maffeis C, Banzato C, Talamini G (2008) Waist-to-height ratio, a useful index to identify high metabolic risk in overweight children. J Pediatr 152:207–213

    Article  PubMed  Google Scholar 

  28. Tanner JM, Whitehouse RH (1976) Clinical longitudinal standards from birth to maturity for height, weight, velocity and stages of puberty. Arch Dis Child 51:170–179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yoshimura A, Ohnishi S, Orito C, Kawahara Y, Takasaki H, Takeda H, Sakamoto N, Hashino S (2015) Association of peripheral total and differential leukocyte counts with obesity-related complications in young adults. Obes Facts 8:1–16

    Article  PubMed  Google Scholar 

  30. Imtiaz F, Shafique K, Mirza SS, Ayoob Z, Vart P, Rao S (2012) Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med 5:2

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bhat T, Teli S, Rijal J, Bhat H, Raza M, Khoueiry G, Meghani M, Akhtar M, Costantino T (2013) Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther 11:55–59

    Article  CAS  PubMed  Google Scholar 

  32. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ (2012) The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 55:2005–2023

    Article  PubMed  Google Scholar 

  33. Castelli WP (1996) Lipid, risk factors and ischemic heart disease. Atherosclerosis 124:S1–S9

    Article  CAS  PubMed  Google Scholar 

  34. Urbina EM, Khoury PR, McCoy CE, Dolan LM, Daniels SR, Kimball TR (2013) Triglyceride to HDL-C ratio and increased arterial stiffness in children, adolescents, and young adults. Pediatrics 131:e1082–e1090

    Article  PubMed  PubMed Central  Google Scholar 

  35. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  CAS  PubMed  Google Scholar 

  36. Seltzer HS, Allen EW, Herron AL, Brennan MT (1967) Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest 46:323–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sjaarda LG, Bacha F, Lee S, Tfayli H, Andreatta E, Arslanian S (2012) Oral disposition index in obese youth from normal to prediabetes to diabetes: relationship to clamp disposition index. J Pediatr 161:51–57

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lazzer S, Bedogni G, Agosti F, De Col A, Mornati D, Sartorio A (2008) Comparison of dual-energy X-ray absorptiometry, air displacement plethysmography and bioelectrical impedance analysis for the assessment of body composition in severely obese Caucasian children and adolescents. Br J Nutr 100:918–924

    Article  CAS  PubMed  Google Scholar 

  39. Lukaski HC, Bolonchuk WW, Hall CB, Siders WA (1986) Validation of tetrapolar bioelectrical impedance method to assess human body composition. J Appl Physiol 60:1327–1332

    CAS  PubMed  Google Scholar 

  40. American Diabetes Association (2015) Classification and diagnosis of diabetes. Diabetes Care 38:S8–S16

    Article  Google Scholar 

  41. National, Heart, Lung and Blood Institute (2011) Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 128(suppl 5):S237

    Google Scholar 

  42. Zimmet P, Alberti KG, Kaufmann F, Tajima N, Silink M, Arslanian S, Wong G, Bennett P, Shaw J, Caprio S (2007) IDF consensus group. The metabolic syndrome in children and adolescents—an IDF consensus report. Pediatr Diabetes 8:299–306

    Article  PubMed  Google Scholar 

  43. Brambilla P, Lissau I, Flodmark CE, Moreno LA, Widhalm K, Wabitsch Pietrobelli A (2007) Metabolic risk-factor clustering estimation in children: to draw a line across pediatric metabolic syndrome. Int J Obes (Lond) 31:591–600

    Article  CAS  Google Scholar 

  44. Martino F, Puddu PE, Pannarale G, Colantoni C, Zanoni C, Martino E, Barillà F (2014) Metabolic syndrome among children and adolescents from Southern Italy: contribution from the Calabrian Sierras Community Study (CSCS). Int J Cardiol 177:455–460

    Article  PubMed  Google Scholar 

  45. Marzullo P, Mele C, Mai S, Guzzaloni G, Soranna D, Tagliaferri MA, Berselli ME, Prodam F, Surico D, Aimaretti G, Scacchi M (2016) The impact of the metabolic phenotype on thyroid function in obesity. Diabetol Metab Syndr 8:59

    Article  PubMed  PubMed Central  Google Scholar 

  46. Seppel T, Kosel A, Schlaghecke R (1997) Bioelectrical impedance assessment of body composition in thyroid disease. Eur J Endocrinol 136:493–498

    Article  CAS  PubMed  Google Scholar 

  47. Spadafranca A, Cappelletti C, Leone A, Vignati L, Battezzati A, Bedogni G, Bertoli S (2015) Relationship between thyroid hormones, resting energy expenditure and cardiometabolic risk factors in euthyroid subjects. Clin Nutr 34:674–678

    Article  CAS  PubMed  Google Scholar 

  48. Czarnywojtek A, Owecki M, Zgorzalewicz-Stachowiak M, Wolinnski K, Szczepanek-Parulska E, Budny B, Florek E, Waligorska-Stachura J, Miechowicz I, Baczyk M, Sawicka N, Dhir S, Ruchała M (2014) The role of serum c-reactive protein measured by high-sensitive method in thyroid disease. Arch Immunol Ther Exp 62:501–509

    Article  CAS  Google Scholar 

  49. Ali AT, Ferris WF, Penny CB, Van der Merwe M-T, Jacobson BF, Paiker JE (2013) Lipid accumulation and alkaline phosphatase activity in human preadipocytes isolated from different body fat depots. J Endocrinol Metab Diabetes 18:58–64

    Google Scholar 

  50. Ali AT, Paiker JE, Crowther NJ (2006) The relationship between anthropometry and serum concentrations of alkaline phosphatase isoenzymes, liver enzymes, albumin, and bilirubin. Am J Clin Pathol 126:437–442

    Article  CAS  PubMed  Google Scholar 

  51. Ittermann T, Thamm M, Wallaschofski H, Rettig R, Völzke H (2012) Serum thyroid-stimulating hormone levels are associated with blood pressure in children and adolescents. J Clin Endocrinol Metab 97:828–834

    Article  CAS  PubMed  Google Scholar 

  52. de Giorgis T, Marcovecchio ML, Giannini C, Chiavaroli V, Chiarelli F, Mohn A (2016) Blood pressure from childhood to adolescence in obese youths in relation to insulin resistance and asymmetric dimethylarginine. J Endocrinol Invest 39:169–176

    Article  PubMed  Google Scholar 

  53. Samuels J, Bell C, Samuel J, Swinford R (2015) Management of hypertension in children and adolescents. Curr Cardiol Rep 17:107

    Article  PubMed  Google Scholar 

  54. Ittermann T, Tiller D, Meisinger C, Agger C, Nauck M, Rettig R, Hofman A, Jørgensen T, Linneberg A, Witteman JC, Franco OH, Greiser KH, Werdan K, Döring A, Kluttig A, Stricker BH, Völzke H (2013) High serum thyrotropin levels are associated with current but not with incident hypertension. Thyroid 23:955–963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. de Souza RJ, Mente A, Maroleanu A, Cozma AI, Ha V, Kishibe T, Uleryk E, Budylowski P, Schünemann H, Beyene J, Anand SS (2015) Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ 351:h3978

    Article  PubMed  PubMed Central  Google Scholar 

  56. Harcombe Z, Baker JS, Cooper SM, Davis B, Sculthorpe N, DiNicolantonio JJ, Grace F (2015) Evidence from randomized controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis. Open Heart 2:e000196

    Article  PubMed  PubMed Central  Google Scholar 

  57. Ramsden CE, Zamora D, Majchrzak-Hong S, Faurot KR, Broste SK, Frantz RP, Davis JM, Ringel A, Suchindran CM, Hibbeln JR (2016) Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968–73). BMJ 353:i1246

    Article  PubMed  PubMed Central  Google Scholar 

  58. Monzani A, Prodam F, Rapa A, Moia S, Agarla V, Bellone S, Bona G (2013) Endocrine disorders in childhood and adolescence. Natural history of subclinical hypothyroidism in children and adolescents and potential effects of replacement therapy: a review. Eur J Endocrinol 168:R1–R11

    Article  CAS  PubMed  Google Scholar 

  59. Iqbal A, Schirmer H, Lunde P, Figenschau Y, Rasmussen K, Jorde R (2007) Thyroid stimulating hormone and left ventricular function. J Clin Endocrinol Metab 92:3504–3510

    Article  CAS  PubMed  Google Scholar 

  60. Villar HCCE, Saconato H, Valente O, Atallah ÁN (2007) Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev 18(3):CD003419

    Google Scholar 

  61. Cerbone M, Capalbo D, Wasniewska M, Alfano S, Mattace Raso G, Oliviero U, Cittadini A, De Luca F, Salerno M (2016) Effects of L-thyroxine treatment on early markers of atherosclerotic disease in children with subclinical hypothyroidism. Eur J Endocrinol 175:11–19

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Marienklinik, via Claudia De Medici 2, 39100, Bolzano, Italy

    G. Radetti

  2. Experimental Laboratory for Auxo-endocrinological Research and Division of Auxology, Istituto Auxologico Italiano, Research Institute, Milan, Verbania, Italy

    G. Grugni, N. Marazzi & A. Sartorio

  3. Department of Pediatrics, Regional Hospital of Bolzano, Bolzano, Italy

    F. Lupi & S. Longhi

  4. Department of Biostatistics, Regional Hospital of Bolzano, Bolzano, Italy

    A. Fanolla

Authors
  1. G. Radetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Grugni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Lupi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Marazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Longhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Fanolla
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Sartorio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Radetti.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the Ethical Committee of the Istituto Auxologico Italiano.

Informed consent

Written informed consent was obtained for all procedures from parents or legal guardians and written assent from children and adolescents were obtained before enrolment.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Radetti, G., Grugni, G., Lupi, F. et al. The relationship between hyperthyrotropinemia and metabolic and cardiovascular risk factors in a large group of overweight and obese children and adolescents. J Endocrinol Invest 40, 1311–1319 (2017). https://doi.org/10.1007/s40618-017-0705-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-017-0705-z

Keywords

Search

Navigation