Skip to main content
SpringerLink
Log in

Thyrotropin-secreting pituitary adenomas. Clinical and biological heterogeneity and current treatment

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Thyrotropin (TSH)-secreting pituitary adenomas represent about 1–2% of all pituitary adenomas and cause secondary or central hyperthyroidism. TSH-secreting adenomas are part of the syndrome of ‘inappropriate secretion of TSH’ (SITSH). The hormonal profile is characterized by nonsuppressed TSH in the presence of high levels of free thyroid hormones (FT3 and FT4). Previous reports have described the surgical cure of TSH adenoma to be more difficult than other functional adenomas because of large and invasive features. However, with the current introduction of ultrasensitive immunometric assays, TSH-secreting adenomas are more often recognized. Early diagnosis of TSH-secreting adenomas leads to a high rate of remission of hyperthyroidism after surgery. However, some of those type of adenomas have clinical heterogeneity, and subsequently cannot be cured by surgery alone. We present our experiences and review reported cases of TSH-secreting adenomas to direct current nobreak management.

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. Losa M, Giovanelli M, Persani L, Mortini P, Faglia G, Beck-Peccoz P: Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 81: 3086–3090, 1996

    Google Scholar 

  2. Ambrosi B, Faglia G and the Multicenter Pituitary Tumor Study Group, Lombrardia Region: Epidermiology of pituitary tumors. In: Faglia G, Beck-Peccoz P, Ambrosi B, Travaglini P, Spada (eds) Pituitary Adenomas: New Trends in Basic and Clinical Research. Vol 961 Excerota Medica, International Congress Series, Elsevier Science Publishers, Amsterdam, 1991, pp 158–168

    Google Scholar 

  3. Beck-Peccoz P, Brucker-Davis F, Persani L, Smallridge RC, Weintraub BD: Thyrotropin-secreting pituitary tumors. Endocr Rev 17: 610–638, 1996

    Google Scholar 

  4. Brucker-Davis F, Oldfield EH, Skarulis MC, Doppman JL, Weintraub BD: 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: 476–486, 1999

    Google Scholar 

  5. Gesundheit N, Petrick PA, Nissim M, Dahlberg PA, Doppman JL, Emerson CH, Brawerman LE, Oldfield EH, Weintraub BD: Thyrotropin-secreting pituitary adenomas: clinical and biochemical heterogeneity: case reports and follow-up of nine patients. Ann InternMed 11: 827–35, 1989

    Google Scholar 

  6. Greenman Y, Melmed S: Thyrotropin-secreting pituitary tumors. In: Melmed S (ed) The Pituitary. Blackwell, Boston, 1995, pp 546–558

    Google Scholar 

  7. McCutcheon IE, Weintraub BD, Oldfield EH: Surgical treatment of thyrotropin-secreting pituitary adenomas. J Neurosurg 73: 674–683, 1990

    Google Scholar 

  8. Mindermann T, Wilson CB: Thyrotropin-producing pituitary adenomas. J Neurosurg 79: 521–527, 1993

    Google Scholar 

  9. Hill SA, Falko JM, Wilson CB, Hunt WE: Thyrotropinproducing pituitary adenomas. J Neurosurg 57: 515–519, 1982

    Google Scholar 

  10. Ridgway EC: Glycoprotein hormone production by pituitary tumors. In: Black PM (eds) SecretoryTumors of the Pituitary Gland. Progress in Endocrine Research and Therapy 1. Raven Press, New York, 1984, pp 343–350

    Google Scholar 

  11. Terzolo M, Orlandi F, Bassetti M, Medri G, Paccotti D, Cortelazzi D, Angeli A, Beck-Peccoz P: Hyperthyroidism due to a pituitary adenoma composed of two different cell types, one secreting α-subunit alone and another cosecreting α-subunit and thyrotropin. J Clin Endocrinol Metab 72: 415–421, 1991

    Google Scholar 

  12. Sanno N, Teramoto A, Matsuno A, Inada K, Itoh J, Osamura RY: Clinical and immunohistochemical studies on TSH-secreting pituitary adenoma: its multihormonality and expression of Pit-1. Mod Pathol 7: 893–899, 1994

    Google Scholar 

  13. Sanno N, Teramoto A, Matsuno A, Takekoshi S, Osamura RY: GH and PRL gene expression by nonradioisotopic in situ hybridization in TSH-secreting pituitary adenomas. J Clin Endocrinol Metab 80: 2518–2522, 1995

    Google Scholar 

  14. Bodner M, Castrillo J-L, Theill LE, Deerinck T, Ellisman M, Karin M: The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein. Cell 55: 505–518, 1988

    Google Scholar 

  15. Ingraham HA, Chen R, Mangalam HJ, et al.: A tissuespecific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell 55: 519–529, 1988

    Google Scholar 

  16. Lloyd RV, Jin L, Chandler WF: Pituitary specific transcription factor messenger ribonucleic expression in adenomatous and nontumorous human pituitary tissues. Lab Invest 69: 570–575, 1993

    Google Scholar 

  17. Sanno N, Teramoto A, Matsuno A, Itoh J, Takekoshi S, Osamura RY: In situ hybridization analysis of Pit-1 mRNA and hormonal production in human pituitary adenomas. Acta Neuropathol 91: 263–268, 1996

    Google Scholar 

  18. Asa SL, Puy LA, Lew AM, Sundmark VB, Elsholtz HP: Cell type-specific expression of the pituitary transcription activator Pit-1 in the human pituitary and pituitary adenoma. J Clin Endocrinol Metab 77: 1275–1280, 1993

    Google Scholar 

  19. Friend KE, Chiour W-K, Laws ER Jr, Lopes MB, Shupnik MA: Pit-1 messenger ribonucleic acid is differentially expressed in human pituitary adenomas. J Clin Endocrinol Metab 77: 1281–1286, 1993.

    Google Scholar 

  20. Mantovani S, Beck-Peccoz P, Saccomanno K, Spada A, Faglia G, Barbetti F: TSH-secreting pituitary adenomas are monoclonal in origin. Proceedings of the 77th Annual Meeting of the Endocrine Society, Washington, DC, 1995, p 412

  21. Landis C, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L: GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumors. Nature 340: 692–696, 1989

    Google Scholar 

  22. Spada A, Vallar L, Faglia G: G protein oncogenes in pituitary tumors. Trends Endocrinol Metab 3: 355–360, 1992

    Google Scholar 

  23. Cai WY, Alexander JM, Hedley-Whyte ET, Scheithauer BW, Jameson JL, Zervas NT, Klibanski A: Ras mutation in human prolactinomas and pituitary carcinomas. J Clin Endocrinol Metab 78: 89–93, 1994

    Google Scholar 

  24. Alvaro V, Levy L, Dubray C, Roche A, Peillon F, Querat B, Joubert D: Invasive human pituitary tumors express a pointmutated a-protein kinase-C. J Clin Endocrinol Metab 77: 1125–1129, 1993

    Google Scholar 

  25. Cryns VL, Alexander JM, Klibanski A, Arnold A: The retinoblastoma gene in human pituitary tumors. J Clin Endocrinol Metab 77: 644–646, 1993

    Google Scholar 

  26. Zhu J, Leon SP, Beggs AH, Busque L, Gilliland DG, Black PM: Human pituitary adenomas show no loss of heterozygosity at the retinoblastoma gene locus. J Clin Endocrinol Metab 78: 922–927, 1994

    Google Scholar 

  27. Herman V, Drazin NZ, Gonsky R, Melmed S: Molecular screening of pituitary adenomas for gene mutations and rearrangements. J Clin Endocrinol Metab 77: 50–55, 1993

    Google Scholar 

  28. Sumi T, Stefaneanu L, Kovacs K, Asa SL, Rindi G: Immunohistochemical study of p53 protein in human and animal pituitary tumors. Endocrinol Pathol 4: 95–99, 1993

    Google Scholar 

  29. Chandrasekharappa SC, Guru SC, Manickam P, Olufemi S-E, Collins FS, Emmert-Buck MR, Debelenko LV, Zhuang Z, Lubensky IA, Liotta L, et al.: Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 276: 404–407, 1997

    Google Scholar 

  30. Agarwal SK, Kester MB, Debelenko LV, Heppner C, Emmert-Buck MR, Skarulis MC, Doppman JL, Kim YS, Lubensky IA, Zhuang Z, Green JS, Guru SC, Manickam P, Olufemi SE, Liotta LA, Chandrasekharappa SC, Collins FS, Spiegel AM, Burns AL, Marx SJ: Germline mutations of the MEN1 gene in familial MEN1 and related states. Hum Mol Genet 6: 1169–1175, 1997

    Google Scholar 

  31. Boggild MD, Jenkinson S, Pistorello M, Boscaro M, Scanarini M, McTernan P, Perrett CW, Thakker RV, Clayton RN: Molecular genetics studies of sporadic pituitary tumors. J Clin Endocrinol Metab 78: 387–392, 1994

    Google Scholar 

  32. Fukino K, Kitamura H, Sanno N, Teramoto A, Emi M: Analysis of the MEN1 gene in sporadic pituitary adenomas from Japanese patients. Cancer lett 144: 85–92, 1999

    Google Scholar 

  33. Zhuang Z, Ezzat SZ, Vortmeyer AO, Weil R, Oldfield EH, Park WS, Pack S, Huang S, Agarwal SK, Guru SC, Manickam P, Debelenko LV, Kester MB, Olufemi SE, Heppner C, Crabtree JS, Burns AL, Spiegel AM, Marx SJ, Chandrasekharappa SC, Collins FS, Emmert-Buck MR, Liotta LA, Asa SL, Lubensky IA: Mutations of the MEN1 tumor suppressor gene in pituitary tumors. Mutations of the MEN1 tumor suppressor gene in pituitary tumors. Cancer Res 15: 5446–5451, 1997

    Google Scholar 

  34. Spencer CA, LoPresti JS, Patel A, Guttler RB, Eigen A, Shen D, Gray D, Nicoloff JT: Applications of a new chemiluminometric thyrotropin assay to subnormal measurement. J Clin Endocrinol Metab 70: 453–460, 1990

    Google Scholar 

  35. Kourides IA, Ridgway BC, Weintraub BD, Bigos ST, Gershengorn MC, Maloof F: Thyrotropin-induced hyperthyroidism: use of alpha and beta subunit levels to identify patients with pituitary tumors. J Clin Endocrinol Metab 45: 534–541, 1977

    Google Scholar 

  36. Frank SJ, Gesundheit N, Doppman JL, Miller DL, Merriam GR, Oldfeld EH, Weingraub BD: Preoprative lateralization of pituitary microadenomas by petrosal sinus sampling: utility in two patients with non-ACTH secreting tumors. Am J Med 87: 679–682, 1989

    Google Scholar 

  37. Wood DF, Johnston JM, Johnston DG: Dopamine, the dopamine D2 receptor and pituitary tumors. Clin Endocrinol (Oxf) 35: 455–466, 1991

    Google Scholar 

  38. Bertherat J, Brue T, Enjalbert A, Gunz G, Rasolonjanahary R, Warnet A, Jaquet P, Epelbaum J: Somatostatin receptors on thyrotropin-secreting pituitary adenomas: comparison with the inhibitory effects of octreotide upon in vivo and in vitro hormonal secretions. J Clin Endocrinol Metab 75: 540–546, 1992

    Google Scholar 

  39. Chanson P, Weingraub BD, Harris AG: Octreotide therapy for thyroid-stimulating hormone-secreting pituitary adenomas. A follow-up of 52 patients. Ann Intern Med 119: 236–240, 1993

    Google Scholar 

  40. Comi RJ, Gesundheit N, Murray L, Gorden P, Weintraub BD: Response of thyrotropin-secreting pituitary adenomas to a long-acting somatostatin analogue. N Engl J Med 317: 12–17, 1987

    Google Scholar 

  41. Beckers A, Abs R, Mahler C, Vandalem JL, Pirens G, Hennen G, Stevenaert A: Thyrotropin-secreting pituitary adenomas: report of seven cases. J Clin Endocrinol Metab 72: 477–483, 1991

    Google Scholar 

  42. Frandsen NJ, Transbol I: Coexisting Graves’ disease and TSH-producing pituitary adenoma. Ugeskr Laeger 153: 854–855, 1991

    Google Scholar 

  43. Kamoi K, Mitsuma T, Sato H: Hyperthyroidism caused by a pituitary thyrotropin-secreting tumour with excessive secretion of thyrotropin-releasing hormone and subsequently followed by Graves’ disease in a middle-aged woman. Acta Endocrinol (Copenh) 110: 373–382, 1985

    Google Scholar 

  44. Stevenaert A, Harris AG, Kovacs K: Presurgical octreotide treatment in acromegaly. Metabolism 41: 51–58, 1992

    Google Scholar 

  45. Warnet A, Lajeunie E, Gelbert F: Shrinkage of primary thyrotropin-secreting pituitary adenoma treated with the long-acting somatostatin analogue octreotide (SMS 201-995). Acta Endocrinol 124: 487–491, 1991

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Nippon Medical School, Sendagi Bunkyo-ku, Tokyo, Japan

    Naoko Sanno & Akira Teramoto

  2. Department of Pathology, Tokai University School of Medicine, Boseidai, Isehara, Japan

    R. Yoshiyuki Osamura

Authors
  1. Naoko Sanno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akira Teramoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Yoshiyuki Osamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sanno, N., Teramoto, A. & Osamura, R.Y. Thyrotropin-secreting pituitary adenomas. Clinical and biological heterogeneity and current treatment. J Neurooncol 54, 179–186 (2001). https://doi.org/10.1023/A:1012917701756

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1012917701756

Search

Navigation