, Volume 22, Issue 1, pp 79–88 | Cite as

Thyrotropin-secreting pituitary adenomas: a systematic review and meta-analysis of postoperative outcomes and management

  • Giulia CossuEmail author
  • Roy Thomas Daniel
  • Katarzyna Pierzchala
  • Moncef Berhouma
  • Nelly Pitteloud
  • Faiza Lamine
  • Annamaria Colao
  • Mahmoud Messerer



TSH-secreting pituitary adenomas are rare pituitary tumors. An efficient treatment is essential to limit the mortality and morbidity in untreated patients. The aim of this study is to summarize the evidence about the postoperative outcomes and management of this rare pathology.


A systematic search and meta-analysis of surgical series was performed.


Our analysis included 23 articles (536 patients). No sex difference was observed and mean age at diagnosis was 45 years. Hyperthyroidism was reportedly clinical in 67% and biochemical in 90% of patients. Co-secretion of other pituitary hormones was present in 42% of cases. Macroadenomas were found in 79% of patients, showing in 44% and 30% of cases respectively extrasellar extension and cavernous sinus invasion. The pooled rate of postoperative biochemical remission was 69.7% and a gross total resection (GTR) was observed in 54% of patients. The extent of resection was significantly increased in microadenomas (p < 0.001) and cavernous sinus invasion was predictive of lower GTR rate (p < 0.001). A biochemical remission was achieved in 66% of patients after adjuvant radiation therapy and in 76% after adjuvant medical treatment. The combination of both allowed remission in 67% of cases. At final follow-up the overall biochemical remission rate was significantly improved (85.8%) when compared to the postoperative biochemical remission (p < 0.001).


When compared to the early postoperative period, at last follow-up biochemical remission was significantly greater (p < 0.001). GTR was achieved in half of patients; the size of tumor and cavernous sinus invasion determined the extent of resection.


Endoscopy Pituitary adenoma SITSH Thyrotropin secreting adenoma Transsphenoidal TSH-secreting adenoma 


Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.


  1. 1.
    Beck-Peccoz P, Brucker-Davis F, Persani L, Smallridge RC, Weintraub BD (1996) Thyrotropin-secreting pituitary tumors. Endocr Rev 17:610–638Google Scholar
  2. 2.
    Onnestam L, Berinder K, Burman P, Dahlqvist P, Engstrom BE et al (2013) National incidence and prevalence of TSH-secreting pituitary adenomas in Sweden. J Clin Endocrinol Metab 98:626–635CrossRefGoogle Scholar
  3. 3.
    Tjornstrand A, Gunnarsson K, Evert M, Holmberg E, Ragnarsson O et al (2014) The incidence rate of pituitary adenomas in western Sweden for the period 2001–2011. Eur J Endocrinol 171:519–526CrossRefGoogle Scholar
  4. 4.
    Dong Q, Brucker-Davis F, Weintraub BD, Smallridge RC, Carr FE et al (1996) Screening of candidate oncogenes in human thyrotroph tumors: absence of activating mutations of the G alpha q, G alpha 11, G alpha s, or thyrotropin-releasing hormone receptor genes. J Clin Endocrinol Metab 81:1134–1140Google Scholar
  5. 5.
    Herman V, Drazin NZ, Gonsky R, Melmed S (1993) Molecular screening of pituitary adenomas for gene mutations and rearrangements. J Clin Endocrinol Metab 77:50–55Google Scholar
  6. 6.
    Minematsu T, Miyai S, Kajiya H, Suzuki M, Sanno N et al (2005) Recent progress in studies of pituitary tumor pathogenesis. Endocrine 28:37–41CrossRefGoogle Scholar
  7. 7.
    Tagami T, Usui T, Shimatsu A, Beniko M, Yamamoto H et al (2011) Aberrant expression of thyroid hormone receptor beta isoform may cause inappropriate secretion of TSH in a TSH-secreting pituitary adenoma. J Clin Endocrinol Metab 96:E948–E952CrossRefGoogle Scholar
  8. 8.
    Ando S, Sarlis NJ, Oldfield EH, Yen PM (2001) Somatic mutation of TRbeta can cause a defect in negative regulation of TSH in a TSH-secreting pituitary tumor. J Clin Endocrinol Metab 86:5572–5576Google Scholar
  9. 9.
    Gittoes NJ, McCabe CJ, Verhaeg J, Sheppard MC, Franklyn JA (1998) An abnormality of thyroid hormone receptor expression may explain abnormal thyrotropin production in thyrotropin-secreting pituitary tumors. Thyroid 8:9–14CrossRefGoogle Scholar
  10. 10.
    Klein I, Ojamaa K (2001) Thyroid hormone and the cardiovascular system. N Engl J Med 344:501–509CrossRefGoogle Scholar
  11. 11.
    Malchiodi E, Profka E, Ferrante E, Sala E, Verrua E et al (2014) Thyrotropin-secreting pituitary adenomas: outcome of pituitary surgery and irradiation. J Clin Endocrinol Metab 99:2069–2076CrossRefGoogle Scholar
  12. 12.
    Yamada S, Fukuhara N, Horiguchi K, Yamaguchi-Okada M, Nishioka H et al (2014) Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: a single-center study of 90 cases. J Neurosurg 121:1462–1473CrossRefGoogle Scholar
  13. 13.
    Azzalin A, Appin CL, Schniederjan MJ, Constantin T, Ritchie JC et al (2016) Comprehensive evaluation of thyrotropinomas: single-center 20-year experience. Pituitary 19:183–193CrossRefGoogle Scholar
  14. 14.
    Marucci G, Faustini-Fustini M, Righi A, Pasquini E, Frank G et al (2009) Thyrotropin-secreting pituitary tumours: significance of “atypical adenomas” in a series of 10 patients and association with Hashimoto thyroiditis as a cause of delay in diagnosis. J Clin Pathol 62:455–459CrossRefGoogle Scholar
  15. 15.
    van Varsseveld NC, Bisschop PH, Biermasz NR, Pereira AM, Fliers E et al (2014) A long-term follow-up study of eighteen patients with thyrotrophin-secreting pituitary adenomas. Clin Endocrinol 80:395–402CrossRefGoogle Scholar
  16. 16.
    Socin HV, Chanson P, Delemer B, Tabarin A, Rohmer V et al (2003) The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients. Eur J Endocrinol 148:433–442CrossRefGoogle Scholar
  17. 17.
    Brucker-Davis F, Oldfield EH, Skarulis MC, Doppman JL, Weintraub BD (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 84:476–486CrossRefGoogle Scholar
  18. 18.
    Losa M, Giovanelli M, Persani L, Mortini P, Faglia G et al (1996) Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 81:3084–3090Google Scholar
  19. 19.
    Elston MS, Conaglen JV (2010) Clinical and biochemical characteristics of patients with thyroid-stimulating hormone-secreting pituitary adenomas from one New Zealand centre. Intern Med J 40:214–219CrossRefGoogle Scholar
  20. 20.
    Rotermund R, Riedel N, Burkhardt T, Matschke J, Schmidt NO et al (2017) Surgical treatment and outcome of TSH-producing pituitary adenomas. Acta Neurochir 159:1219–1226CrossRefGoogle Scholar
  21. 21.
    Beck-Peccoz P, Lania A, Beckers A, Chatterjee K, Wemeau JL (2013) 2013 European thyroid association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors. Eur Thyroid J 2:76–82CrossRefGoogle Scholar
  22. 22.
    Kuhn JM, Arlot S, Lefebvre H, Caron P, Cortet-Rudelli C et al (2000) Evaluation of the treatment of thyrotropin-secreting pituitary adenomas with a slow release formulation of the somatostatin analog lanreotide. J Clin Endocrinol Metab 85:1487–1491CrossRefGoogle Scholar
  23. 23.
    Caron P, Arlot S, Bauters C, Chanson P, Kuhn JM et al (2001) Efficacy of the long-acting octreotide formulation (octreotide-LAR) in patients with thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 86:2849–2853CrossRefGoogle Scholar
  24. 24.
    Colao A (2015) Treatment of pituitary tumours in 2014: advances in therapy of adenomas secreting GH, ACTH and TSH. Nat Rev Endocrinol 11:73–74CrossRefGoogle Scholar
  25. 25.
    Colao A, Pivonello R, Di Somma C, Savastano S, Grasso LF et al (2009) Medical therapy of pituitary adenomas: effects on tumor shrinkage. Rev Endocr Metab Disord 10:111–123CrossRefGoogle Scholar
  26. 26.
    Colao A, Filippella M, Pivonello R, Di Somma C, Faggiano A et al (2007) Combined therapy of somatostatin analogues and dopamine agonists in the treatment of pituitary tumours. Eur J Endocrinol 156(Suppl 1):S57–S63CrossRefGoogle Scholar
  27. 27.
    Colao A, Filippella M, Di Somma C, Manzi S, Rota F et al (2003) Somatostatin analogs in treatment of non-growth hormone-secreting pituitary adenomas. Endocrine 20:279–283CrossRefGoogle Scholar
  28. 28.
    Astaf’eva LI, Kadashev BA, Shishkina LV, Kalinin PL, Fomichev DV et al (2016) Clinical and morphological characteristics, diagnostic criteria, and outcomes of surgical treatment of TSH-secreting pituitary adenomas. Zh Vopr Neirokhir Im N N Burdenko 80:24–35CrossRefGoogle Scholar
  29. 29.
    Beckers A, Stevenaert A, Foidart JM, Hennen G, Frankenne F (1990) Placental and pituitary growth hormone secretion during pregnancy in acromegalic women. J Clin Endocrinol Metab 71:725–731CrossRefGoogle Scholar
  30. 30.
    Clarke MJ, Erickson D, Castro MR, Atkinson JL (2008) Thyroid-stimulating hormone pituitary adenomas. J Neurosurg 109:17–22CrossRefGoogle Scholar
  31. 31.
    Gatto F, Grasso LF, Nazzari E, Cuny T, Anania P et al (2015) Clinical outcome and evidence of high rate post-surgical anterior hypopituitarism in a cohort of TSH-secreting adenoma patients: might somatostatin analogs have a role as first-line therapy? Pituitary 18:583–591CrossRefGoogle Scholar
  32. 32.
    Kirkman MA, Jaunmuktane Z, Brandner S, Khan AA, Powell M et al (2014) Active and silent thyroid-stimulating hormone-expressing pituitary adenomas: presenting symptoms, treatment, outcomes, and recurrence. World Neurosurg 82:1224–1231CrossRefGoogle Scholar
  33. 33.
    Losa M, Mortini P, Franzin A, Barzaghi R, Mandelli C et al (1999) Surgical management of thyrotropin-secreting pituitary adenomas. Pituitary 2:127–131CrossRefGoogle Scholar
  34. 34.
    Macchia E, Gasperi M, Lombardi M, Morselli L, Pinchera A et al (2009) Clinical aspects and therapeutic outcome in thyrotropin-secreting pituitary adenomas: a single center experience. J Endocrinol Invest 32:773–779CrossRefGoogle Scholar
  35. 35.
    Mindermann T, Wilson CB (1993) Thyrotropin-producing pituitary adenomas. J Neurosurg 79:521–527CrossRefGoogle Scholar
  36. 36.
    Ness-Abramof R, Ishay A, Harel G, Sylvetzky N, Baron E et al (2007) TSH-secreting pituitary adenomas: follow-up of 11 cases and review of the literature. Pituitary 10:307–310CrossRefGoogle Scholar
  37. 37.
    Sanno N, Teramoto A, Osamura RY (2000) Long-term surgical outcome in 16 patients with thyrotropin pituitary adenoma. J Neurosurg 93:194–200CrossRefGoogle Scholar
  38. 38.
    Wu YY, Chang HY, Lin JD, Chen KW, Huang YY et al (2003) Clinical characteristics of patients with thyrotropin-secreting pituitary adenoma. J Formos Med Assoc 102:164–171Google Scholar
  39. 39.
    Wynne AG, Gharib H, Scheithauer BW, Davis DH, Freeman SL et al (1992) Hyperthyroidism due to inappropriate secretion of thyrotropin in 10 patients. Am J Med 92:15–24CrossRefGoogle Scholar
  40. 40.
    Zhao W, Ye H, Li Y, Zhou L, Lu B et al (2012) Thyrotropin-secreting pituitary adenomas: diagnosis and management of patients from one Chinese center. Wien Klin Wochenschr 124:678–684CrossRefGoogle Scholar
  41. 41.
    Trouillas J, Roy P, Sturm N, Dantony E, Cortet-Rudelli C et al (2013) A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol 126:123–135CrossRefGoogle Scholar
  42. 42.
    Knosp E, Steiner E, Kitz K, Matula C (1993) Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33:610–617 (discussion 617–618)Google Scholar
  43. 43.
    Beck-Peccoz P, Persani L, Mannavola D, Campi I (2009) Pituitary tumours: TSH-secreting adenomas. Best Pract Res Clin Endocrinol Metab 23:597–606CrossRefGoogle Scholar
  44. 44.
    Osamura RY, Egashira N, Miyai S, Yamazaki M, Takekoshi S et al (2004) Molecular pathology of the pituitary. Development and functional differentiation of pituitary adenomas. Front Horm Res 32:20–33CrossRefGoogle Scholar
  45. 45.
    Kontogeorgos G, Kovacs K, Horvath E, Scheithauer BW (1991) Multiple adenomas of the human pituitary. A retrospective autopsy study with clinical implications. J Neurosurg 74:243–247CrossRefGoogle Scholar
  46. 46.
    Shimono T, Hatabu H, Kasagi K, Miki Y, Nishizawa S et al (1999) Rapid progression of pituitary hyperplasia in humans with primary hypothyroidism: demonstration with MR imaging. Radiology 213:383–388CrossRefGoogle Scholar
  47. 47.
    Vidal S, Horvath E, Kovacs K, Cohen SM, Lloyd RV et al (2000) Transdifferentiation of somatotrophs to thyrotrophs in the pituitary of patients with protracted primary hypothyroidism. Virchows Arch 436:43–51CrossRefGoogle Scholar
  48. 48.
    Nelson DH, Meakin JW, Dealy JB Jr, Matson DD, Emerson K Jr et al (1958) ACTH-producing tumor of the pituitary gland. N Engl J Med 259:161–164CrossRefGoogle Scholar
  49. 49.
    Ahmadi J, North CM, Segall HD, Zee CS, Weiss MH (1986) Cavernous sinus invasion by pituitary adenomas. AJR Am J Roentgenol 146:257–262CrossRefGoogle Scholar
  50. 50.
    Fahlbusch R, Buchfelder M (1988) Transsphenoidal surgery of parasellar pituitary adenomas. Acta Neurochir 92:93–99CrossRefGoogle Scholar
  51. 51.
    Micko AS, Wohrer A, Wolfsberger S, Knosp E (2015) Invasion of the cavernous sinus space in pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification. J Neurosurg 122:803–811CrossRefGoogle Scholar
  52. 52.
    Jho HD (2001) Endoscopic transsphenoidal surgery. J Neurooncol 54:187–195CrossRefGoogle Scholar
  53. 53.
    Jho HD, Carrau RL (1996) Endoscopy assisted transsphenoidal surgery for pituitary adenoma. Acta Neurochir 138:1416–1425CrossRefGoogle Scholar
  54. 54.
    Jho HD, Carrau RL (1997) Endoscopic endonasal transsphenoidal surgery: experience with 50 patients. J Neurosurg 87:44–51CrossRefGoogle Scholar
  55. 55.
    Amlashi FG, Tritos NA (2016) Thyrotropin-secreting pituitary adenomas: epidemiology, diagnosis, and management. Endocrine 52:427–440CrossRefGoogle Scholar
  56. 56.
    Starnoni D, Daniel RT, Marino L, Pitteloud N, Levivier M et al (2016) Surgical treatment of acromegaly according to the 2010 remission criteria: systematic review and meta-analysis. Acta Neurochir 158:2109–2121CrossRefGoogle Scholar
  57. 57.
    Feng M, Liu Z, Liu X, Bao X, Yao Y et al (2018) Diagnosis and outcomes of 341 patients with Cushing’s disease following transsphenoid surgery: a single-center experience. World Neurosurg 109:e75–e80CrossRefGoogle Scholar
  58. 58.
    Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S et al (2010) A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab 95:3141–3148CrossRefGoogle Scholar
  59. 59.
    Nishioka H, Haraoka J (2008) Biochemical cure of acromegaly after transsphenoidal surgery despite residual tumor on magnetic resonance imaging: case report. Neurol Med Chir 48:311–313CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurosurgeryUniversity Hospital of LausanneLausanneSwitzerland
  2. 2.Center for Biomedical ImagingEPFLLausanneSwitzerland
  3. 3.Skull Base Surgery Unit, Department of Neurosurgery B, Pierre Wertheimer Neurological and Neurosurgical HospitalHospices Civils de LyonLyonFrance
  4. 4.Department of EndocrinologyUniversity Hospital of LausanneLausanneSwitzerland
  5. 5.Department of EndocrinologyUniversity Hospital of NaplesNaplesItaly

Personalised recommendations