Skip to main content
SpringerLink
Log in

Association between thyroid function and serum cortisol in cortisol-producing adenoma patients

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Thyroid dysfunction has been reported in hypercortisolism. Previous findings regarding changes in thyroid function due to cortisol-producing adenoma (CPA) have been inconsistent. The study aimed to investigate the association between thyroid function and excessive cortisol secretion in patients with CPA and to explore the changes in pituitary function after adrenalectomy.

Methods

We conducted a retrospective study; thyroid function was evaluated in 94 patients with CPA and 94 healthy controls (HC) matched for age and sex. A total of 94 patients with nonfunctioning adrenal incidentalomas (NFAIs) were recruited as a second control group.

Results

Serum thyroid stimulating hormone (TSH) and free thyroxine (T4) levels were significantly lower in the CPA group than in the HC and NFAIs groups (P < 0.001). The prevalence of central hypothyroidism was 12.8% in the CPA group and increased according to serum cortisol quartiles (P for trend = 0.025). According to the stepwise multiple linear regression analysis, serum cortisol was negatively associated with TSH and free T4 levels in the CPA group after adjustment for body mass index and age. Furthermore, decreased TSH levels were corrected by adrenalectomy [0.75 (0.50, 1.14) vs. 1.91 (1.36, 2.71) µIU/ml, P < 0.001], in parallel with a recovery in free T4 levels [11.20 (10.00, 12.43) vs. 12.04 (11.24, 13.01), P < 0.001]. Postoperative growth hormone and prolactin levels did not change compared with baseline.

Conclusion

Serum TSH and free T4 levels were decreased in patients with CPA, and dysfunction of the hypothalamic–pituitary–thyroid axis might be reversible after surgery.

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

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. A. Lacroix, R.A. Feelders, C.A. Stratakis, L.K. Nieman, Cushing’s syndrome. Lancet 386(9996), 913–927 (2015). https://doi.org/10.1016/S0140-6736(14)61375-1

    Article  CAS  PubMed  Google Scholar 

  2. N. Mathioudakis, S. Thapa, G.S. Wand, R. Salvatori, ACTH-secreting pituitary microadenomas are associated with a higher prevalence of central hypothyroidism compared to other microadenoma types. Clin. Endocrinol. 77(6), 871–876 (2012). https://doi.org/10.1111/j.1365-2265.2012.04442.x

    Article  CAS  Google Scholar 

  3. S.C. Dogansen, G.Y. Yalin, B. Canbaz, S. Tanrikulu, S. Yarman, Dynamic changes of central thyroid functions in the management of Cushing’s syndrome. Arch. Endocrinol. Metab. 62(2), 164–171 (2018). https://doi.org/10.20945/2359-3997000000019

    Article  PubMed  Google Scholar 

  4. J.T. Nicoloff, D.A. Fisher, M.D. Appleman, The role of glucocorticoids in the regulation of thyroid function in man. J. Clin. Investig. 49(10), 1922–1929 (1970). https://doi.org/10.1172/JCI106411

    Article  CAS  PubMed  Google Scholar 

  5. G. Brabant, A. Brabant, U. Ranft, K. Ocran, J. Köhrle, R.D. Hesch, A. von zur Mühlen, Circadian and pulsatile thyrotropin secretion in euthyroid man under the influence of thyroid hormone and glucocorticoid administration. J. Clin. Endocrinol. Metab. 65(1), 83–88 (1987). https://doi.org/10.1210/jcem-65-1-83

    Article  CAS  PubMed  Google Scholar 

  6. A. Brabant, G. Brabant, T. Schuermeyer, U. Ranft, F.W. Schmidt, R.D. Hesch, A. von zur Mühlen, The role of glucocorticoids in the regulation of thyrotropin. Acta Endocrinol. 121(1), 95–100 (1989). https://doi.org/10.1530/acta.0.1210095

    Article  CAS  PubMed  Google Scholar 

  7. F. Roelfsema, A.M. Pereira, N.R. Biermasz, M. Frolich, D.M. Keenan, J.D. Vedhuis, J.A. Romijn, Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing’s syndrome. Eur. J. Endocrinol. 161(5), 695–703 (2009). https://doi.org/10.1530/EJE-09-0580

    Article  CAS  PubMed  Google Scholar 

  8. B. Xiang, R. Tao, X. Liu, X. Zhu, M. He, Z. Ma, Y. Yang, Z. Zhang, Y. Li, Z. Yao et al. A study of thyroid functions in patients with Cushing’s syndrome: a single-center experience. Endocr. Connect. 8(8), 1176–1185 (2019). https://doi.org/10.1530/EC-19-0309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. L.K. Nieman, B.M. Biller, J.W. Findling, J. Newell-Price, M.O. Savage, P.M. Stewart, V.M. Montori, The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 93(5), 1526–1540 (2008). https://doi.org/10.1210/jc.2008-0125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. M. Fassnacht, W. Arlt, I. Bancos, H. Dralle, J. Newell-Price, A. Sabarin, M. Terzolo, S. Tsagarakis, O.M. Dekkers, Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur. J. Endocrinol. 175(2), G1–G34 (2016). https://doi.org/10.1530/EJE-16-0467

    Article  CAS  PubMed  Google Scholar 

  11. P. Beck-Peccoz, A. Lania, A. Beckers A, K. Chatterjee, J.L. Wemeau, European thyroid association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors. Eur. Thyroid J. 2(2), 76–82 (2013). https://doi.org/10.1159/000351007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. J.G. Hollowell, N.W. Staehling, W.D. Flanders, W.H. Hannon, E.W. Gunter, C.A. Spencer, L.E. Braverman, T.S.H. Serum, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab. 87(2), 489–499 (2002). https://doi.org/10.1210/jcem.87.2.8182

    Article  CAS  PubMed  Google Scholar 

  13. V.M. da Costa, D.G. Moreira, D. Rosenthal, Thyroid function and aging gender-related differences. J. Endocrinol. 171(1), 193–198 (2001). https://doi.org/10.1677/joe.0.1710193

    Article  PubMed  Google Scholar 

  14. G. Benker, M. Raida, T. Olbricht, R. Wagner, W. Reinhardt, D. Reinwein, TSH secretion in Cushing’s syndrome: relation to glucocorticoid excess, diabetes, goitre, and the ‘sick euthyroid syndrome’. Clin. Endocrinol. 33(6), 777–786 (1990). https://doi.org/10.1111/j.1365-2265.1990.tb03915.x

    Article  CAS  Google Scholar 

  15. T.J. Visser, S.W. Lamberts, Regulation of TSH secretion and thyroid function in Cushing’s disease. Acta Endocrinol. 96(4), 480–483 (1981). https://doi.org/10.1530/acta.0.0960480

    Article  CAS  PubMed  Google Scholar 

  16. L. Bartalena, E. Martino, L. Petrini, F. Velluzzi, A. Loviselli, L. Grasso, C. Mammoli, A. Pinchera, The nocturnal serum thyrotropin surge is abolished in patients with adrenocorticotropin (ACTH)-dependent or ACTH independent Cushing’s syndrome. J. Clin. Endocrinol. Metab. 72(6), 1195–1199 (1991). https://doi.org/10.1210/jcem-72-6-1195

    Article  CAS  PubMed  Google Scholar 

  17. D. Tamada, T. Kitamura, T. Onodera, T. Hamasaki, M. Otsuki, I. Shimomura, Clinical significance of fluctuations in thyroid hormones after surgery for Cushing’s syndrome. Endocr. J. 62(9), 805–810 (2015). https://doi.org/10.1507/endocrj.EJ15-0001

    Article  PubMed  Google Scholar 

  18. C.A. Stratakis, G. Mastorakos, M.A. Magiakou, E. Papavasiliou, E.H. Oldfield, G.P. Chrousos, Thyroid function in children with Cushing’s disease before and after transsphenoidal surgery. J. Pediatr. 131(6), 905–909 (1997). https://doi.org/10.1016/S0022-3476(97)70041-6

    Article  CAS  PubMed  Google Scholar 

  19. C. Fekete, R.M. Lechan, Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions. Endocr. Rev. 35(2), 159–194 (2014). https://doi.org/10.1210/er.2013-1087

    Article  CAS  PubMed  Google Scholar 

  20. A. Cintra, K. Fuxe, A.C. Wikström, T. Visser, J.A. Gustafsson, Evidence for thyrotropin-releasing hormone and glucocorticoid receptor immunoreactive neurons in various preoptic and hypothalamic nuclei of the male rat. Brain Res. 506(1), 139–144 (1990). https://doi.org/10.1016/0006-8993(90)91210-8

    Article  CAS  PubMed  Google Scholar 

  21. T. Mitsuma, T. Nogimori, Effects of dexamethasone on the hypothalamic-pituitary-thyroid axis in rats. Acta Endocrinol. 100(1), 51–56 (1982). https://doi.org/10.1530/acta.0.1000051

    Article  CAS  PubMed  Google Scholar 

  22. M. Szabo, L.A. Frohman, Suppression of cold-stimulated thyrotropin secretion by antiserum to thyrotropin-releasing hormone. Endocrinology 101(4), 1023–1033 (1997). https://doi.org/10.1210/endo-101-4-1023

    Article  Google Scholar 

  23. A. Alkemade, U.A. Unmehopa, W.M. Wiersinga, D.F. Swaab, E. Fliers, Glucocorticoids decrease thyrotropin-releasing hormone messenger ribonucleic acid expression in the paraventricular nucleus of the human hypothalamus. J. Clin. Endocrinol. Metab. 90(1), 323–327 (2005). https://doi.org/10.1210/jc.2004-1430

    Article  CAS  PubMed  Google Scholar 

  24. L.M. Saane, E. Carro, S. Tovar, F.F. Casanueva, C. Dieguez, Regulation of in vivo TSH secretion by leptin. Regul. Pept. 92(1–3), 25–29 (2000). https://doi.org/10.1016/S0167-0115(00)00145-2

    Article  Google Scholar 

  25. B.M. Lewis, C. Dieguez, M.D. Lewis, M.F. Scanlon, Dopamine stimulates release of thyrotropin-releasing hormone from perfused intact rat hypothalamus via hypothalamic D2-receptors. J. Endocrinol. 115(3), 419–424 (1987). https://doi.org/10.1677/joe.0.1150419

    Article  CAS  PubMed  Google Scholar 

  26. A.D. Taylor, J.G. Philip, C.D. John, P.O. Cover, J.F. Morris, R.J. Flower, J.C. Buckingham, Annexin 1 (lipocortin 1) mediates the glucocorticoid inhibition of cyclic adenosine 3’,5’-monophosphate-stimulated prolactin secretion. Endocrinology 141(6), 2209–2219 (2000). https://doi.org/10.1210/endo.141.6.7512

    Article  CAS  PubMed  Google Scholar 

  27. C. Estupina, J. Belmar, L. Tapia-Arancibia, H. Astier, S. Arancibia, Rapid and opposite effects of dexamethasone on in vivo and in vitro hypothalamic somatostatin release. Exp. Brain Res. 113(2), 337–342 (1997). https://doi.org/10.1007/bf02450331

    Article  CAS  PubMed  Google Scholar 

  28. B.R. Haugen, Drugs that suppress TSH or cause central hypothyroidism. Best. Pract. Res Clin. Endocrinol. Metab. 23(6), 793–800 (2009). https://doi.org/10.1016/j.beem.2009.08.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Yu Zhu, MD. Ph.D, Department of Urology; Fukang Sun, MD. Ph.D, Department of Urology; Zhiyuan Wu, MD. Ph.D, Department of Radiology; and Jing Xie, MD, Department of Pathology for their help.

Funding

This work was supported by National Natural Science Foundation of China (Nos. 91857205, 81730023, and 81400779), Shanghai Municipal Commission of Health and Family Planning (201840049 and 201740040), the National Key Research and Development Program of China (2018YFC1311800), National International Science Cooperation Foundation (2015DFA30560), Chinese Society of Endocrinology (13050890474), Shanghai Science and Technology Committee (15411966600), Shanghai Medical and health development foundation (805344), and Shanghai Ruijin Hospital (20193701).

Author information

Author notes

  1. These authors contributed equally: Rongrong Cai, Weiwei Zhou

Authors and Affiliations

  1. Shanghai Key Laboratory for Endocrine Tumors, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, PR China

    Rongrong Cai, Weiwei Zhou, Lei Jiang, Yiran Jiang, Tingwei Su, Cui Zhang, Wenzhong Zhou, Guang Ning & Weiqing Wang

  2. Laboratory for Endocrine & Metabolic Diseases of Institute of Health Science, Shanghai JiaoTong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200025, PR China

    Guang Ning

Authors
  1. Rongrong Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weiwei Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lei Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yiran Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tingwei Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wenzhong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Guang Ning
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Weiqing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Weiqing Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee of the Ruijin Hospital affiliated to Shanghai JiaoTong University School of Medicine.

Informed consent

Written informed consents were obtained from all of the participants.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cai, R., Zhou, W., Jiang, L. et al. Association between thyroid function and serum cortisol in cortisol-producing adenoma patients. Endocrine 69, 196–203 (2020). https://doi.org/10.1007/s12020-020-02278-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-020-02278-5

Keywords

Search

Navigation