Journal of Endocrinological Investigation

, Volume 41, Issue 4, pp 447–454 | Cite as

Diagnosis and treatment of TSH-secreting adenomas: review of a longtime experience in a reference center

  • D. M. Nazato
  • J. Abucham
Original Article



TSH-secreting pituitary adenomas are among the less prevalent pituitary tumors, corresponding to 0.9–1.5% of all pituitary adenomas in surgical series.


A series of 11 patients with TSH-secreting and cosecreting adenomas diagnosed and treated in the last 25 years in a single center is described.


The mean age at diagnosis was 37 years (range 18–80 years; median 23 years); the ratio of male-to-female patients was similar (6M:5F). Only three patients was the correct diagnosis established shortly after the initial medical evaluation. Other four patients were initially diagnosed with other pituitary adenomas (prolactinoma, acromegaly, and non-secreting pituitary tumor) and another four diagnosed with primary hyperthyroidism. There was a mean diagnostic delay of 6.0 years (range 0.5–25 years; median 2 years). Nine patients had macroadenomas and two patients had microadenomas. Seven patients underwent pituitary surgery which controlled the disease in only two (one micro- and one noninvasive macroadenoma). The other treatments were directed to the thyroid gland (surgery or 131I radiotherapy), pituitary radiotherapy, and somatostatin analog.


In spite of its relatively straightforward diagnosis, which includes clinical/subclinical hyperthyroidism with or without goiter, increased free thyroxine and nonsuppressed TSH levels, and pituitary mass, the diagnosis of TSH-secreting and cosecreting adenomas was frequently unrecognized and thus much delayed. Serum alpha-subunit levels were high in nearly all patients with TSH-secreting adenomas and useful in excluding other conditions in the differential diagnosis. Proper indication and interpretation of simple laboratory tests should be emphasized in medical education to improve diagnostic accuracy.


TSH-secreting pituitary adenoma Thyrotropinoma Pituitary tumors Hyperthyroidism Central hyperthyroidism 



The authors express their appreciation to Drs. Jose Gilberto Vieira and Maria Izabel Chiamolera for their technical support in TSH chromatography and THRB gene sequencing, respectively.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

With the approval of our ethical institution, a formal consent was not required for this retrospective study.


  1. 1.
    Onnestam L et al (2013) National incidence and prevalence of TSH-secreting pituitary adenomas in Sweden. J Clin Endocrinol Metab 98(2):626–635CrossRefPubMedGoogle Scholar
  2. 2.
    Melmed S (2011) Thyrotropin-secreting pituitary tumors. In: Melmed S (ed) The pituitary, 3rd edn. Elsevier, Oxford, UKGoogle Scholar
  3. 3.
    van Varsseveld NC et al (2014) A long-term follow-up study of eighteen patients with thyrotrophin-secreting pituitary adenomas. Clin Endocrinol (Oxf) 80(3):395–402CrossRefGoogle Scholar
  4. 4.
    Faglia G et al (1987) Inappropriate secretion of thyrotropin by the pituitary. Horm Res 26(1–4):79–99CrossRefPubMedGoogle Scholar
  5. 5.
    Grisoli F et al (1986) Thyroid-stimulating hormone pituitary adenomas and hyperthyroidism. Surg Neurol 25(4):361–368CrossRefPubMedGoogle Scholar
  6. 6.
    Beck-Peccoz P et al (2009) Pituitary tumours: TSH-secreting adenomas. Best Pract Res Clin Endocrinol Metab 23(5):597–606CrossRefPubMedGoogle Scholar
  7. 7.
    Beck-Peccoz P et al (1996) Thyrotropin-secreting pituitary tumors. Endocr Rev 17(6):610–638PubMedGoogle Scholar
  8. 8.
    Beck-Peccoz P, Persani L (2010) TSH-producing adenomas. In: Jameson LDJL (ed) Endocrinology. WB Saunders, USA, pp 324–332Google Scholar
  9. 9.
    Nakayama Y et al (2012) Thyroid-stimulating hormone (thyrotropin)-secretion pituitary adenoma in an 8-year-old boy: case report. Pituitary 15(1):110–115CrossRefPubMedGoogle Scholar
  10. 10.
    Rabbiosi S et al (2012) Asymptomatic thyrotropin-secreting pituitary macroadenoma in a 13-year-old girl: successful first-line treatment with somatostatin analogs. Thyroid 22(10):1076–1079CrossRefPubMedGoogle Scholar
  11. 11.
    Brucker-Davis F et al (1999) Thyrotropin-secreting pituitary tumors: diagnostic criteria, thyroid hormone sensitivity, and treatment outcome in 25 patients followed at the National Institutes of Health. J Clin Endocrinol Metab 84(2):476–486CrossRefPubMedGoogle Scholar
  12. 12.
    Ness-Abramof R et al (2007) TSH-secreting pituitary adenomas: follow-up of 11 cases and review of the literature. Pituitary 10(3):307–310CrossRefPubMedGoogle Scholar
  13. 13.
    Losa M et al (1996) Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 81(8):3084–3090PubMedGoogle Scholar
  14. 14.
    Macchia E et al (2009) Clinical aspects and therapeutic outcome in thyrotropin-secreting pituitary adenomas: a single center experience. J Endocrinol Invest 32(9):773–779CrossRefPubMedGoogle Scholar
  15. 15.
    Socin HV et al (2003) The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients. Eur J Endocrinol 148(4):433–442CrossRefPubMedGoogle Scholar
  16. 16.
    Maccagnan P et al (1995) Conservative management of pituitary apoplexy: a prospective study. J Clin Endocrinol Metab 80(7):2190–2197PubMedGoogle Scholar
  17. 17.
    Bertholon-Gregoire M et al (1999) Mono- and plurihormonal thyrotropic pituitary adenomas: pathological, hormonal and clinical studies in 12 patients. Eur J Endocrinol 140(6):519–527CrossRefPubMedGoogle Scholar
  18. 18.
    Sanno N, Teramoto A, Osamura RY (2001) Thyrotropin-secreting pituitary adenomas. Clinical and biological heterogeneity and current treatment. J Neurooncol 54(2):179–186CrossRefPubMedGoogle Scholar
  19. 19.
    Refetoff S et al (2014) Classification and proposed nomenclature for inherited defects of thyroid hormone action, cell transport, and metabolism. J Clin Endocrinol Metab 99(3):768–770CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Refetoff S, Weiss RE, Usala SJ (1993) The syndromes of resistance to thyroid hormone. Endocr Rev 14(3):348–399PubMedGoogle Scholar
  21. 21.
    Refetoff S, Dumitrescu AM (2007) Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination. Best Pract Res Clin Endocrinol Metab 21(2):277–305CrossRefPubMedGoogle Scholar
  22. 22.
    Kon YC et al (2001) Thyrotrophin (TSH)-secreting pituitary macroadenoma with cavernous sinus invasion. Singap Med J 42(9):433–437Google Scholar
  23. 23.
    Yamada S et al (2014) Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: a single-center study of 90 cases. J Neurosurg 121(6):1462–1473CrossRefPubMedGoogle Scholar
  24. 24.
    Beck-Peccoz P, Persani L, Faglia G (1992) Glycoprotein hormone alpha-subunit in pituitary adenomas. Trends Endocrinol Metab 3(2):41–45CrossRefPubMedGoogle Scholar
  25. 25.
    Beck-Peccoz P et al (2013) 2013 European thyroid association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors. Eur Thyroid J 2(2):76–82CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Foppiani L et al (2007) TSH-secreting adenomas: rare pituitary tumors with multifaceted clinical and biological features. J Endocrinol Invest 30(7):603–609CrossRefPubMedGoogle Scholar
  27. 27.
    Hall WA et al (1994) Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med 120(10):817–820CrossRefPubMedGoogle Scholar
  28. 28.
    Koulouri O et al (2013) Pitfalls in the measurement and interpretation of thyroid function tests. Best Pract Res Clin Endocrinol Metab 27(6):745–762CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Thompson RJ, Jackson AP, Langlois N (1986) Circulating antibodies to mouse monoclonal immunoglobulins in normal subjects–incidence, species specificity, and effects on a two-site assay for creatine kinase-MB isoenzyme. Clin Chem 32(3):476–481PubMedGoogle Scholar
  30. 30.
    Reinsberg J (1996) Different efficacy of various blocking reagents to eliminate interference by human antimouse antibodies with two-site immunoassay. Clin Biochem 29(2):145–148CrossRefPubMedGoogle Scholar
  31. 31.
    Despres N, Grant AM (1998) Antibody interference in thyroid assays: a potential for clinical misinformation. Clin Chem 44(3):440–454PubMedGoogle Scholar
  32. 32.
    Vieira JG et al (2006) Unexpected high values of TSH: the presence of high molecular weight forms (macro TSH) must be investigated. Arq Bras Endocrinol Metabol 50(3):445–449CrossRefPubMedGoogle Scholar
  33. 33.
    Beck-Peccoz P, Persani L (2002) Medical management of thyrotropin-secreting pituitary adenomas. Pituitary 5(2):83–88CrossRefPubMedGoogle Scholar
  34. 34.
    Gatto F et al (2011) In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma: characterization of somatostatin receptor expression and role of subtype 5. Pituitary 14(2):141–147CrossRefPubMedGoogle Scholar
  35. 35.
    Horiguchi K et al (2007) Somatostatin receptor subtypes mRNA in TSH-secreting pituitary adenomas: a case showing a dramatic reduction in tumor size during short octreotide treatment. Endocr J 54(3):371–378CrossRefPubMedGoogle Scholar
  36. 36.
    Mamanasiri S et al (2006) Mosaicism of a thyroid hormone receptor-beta gene mutation in resistance to thyroid hormone. J Clin Endocrinol Metab 91(9):3471–3477CrossRefPubMedGoogle Scholar
  37. 37.
    Pohlenz J et al (1999) Five new families with resistance to thyroid hormone not caused by mutations in the thyroid hormone receptor beta gene. J Clin Endocrinol Metab 84(11):3919–3928PubMedGoogle Scholar
  38. 38.
    Dumitrescu AM, Refetoff S (2013) The syndromes of reduced sensitivity to thyroid hormone. Biochim Biophys Acta 1830(7):3987–4003CrossRefPubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2017

Authors and Affiliations

  1. 1.Neuroendocrine Unit, Division of Endocrinology and Metabolism, Escola Paulista de MedicinaUniversidade Federal de São PauloVila ClementinoBrazil

Personalised recommendations