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A Case of pituitary somatotroph adenoma with concomitant secretion of growth hormone, prolactin, and adrenocorticotropic hormone — an adenoma derived from primordial stem cell, studied by immunohistochemistry, in situ hybridization, and cell culture

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Summary

Somatotroph adenomas often secrete prolactin (PRL) besides growth hormone (GH) and are sometimes immunostained for other anterior pituitary hormones or their subunits, such as thyroid-stimulating hormone (TSH) β-subunit and glycoprotein hormone α-subunit (αSU). However, Somatotroph adenomas showing hypersecretion of adrenocorticotropic hormone (ACTH) are extremely rare. There have been, to our knowledge, only five published reports on Somatotroph adenomas accompanied by excessive ACTH secretion. Here we report a case of intracavernously invading Somatotroph macro-adenoma with high serum GH, PRL, and ACTH levels. We examined the case using immunohistochemistry (IHC), in situ hybridization (ISH), and cell culture, and confirmed GH, PRL, and ACTH, as well as αSU, production, and the expression of Pit-1 protein by the adenoma, which is known as a transcriptional factor for GH, PRL, and TSH, not for ACTH. Therefore, the presence of unknown transcriptional factor other than Pit-1, common to GH, PRL, and ACTH, may be speculated to be expressed in this adenoma. In our previous study, we had found plurihormonal mRNA expression, especially for ACTH, the β-subunit of follicle-stimulating hormone and luteinizing hormone in some Somatotroph adenomas, using non-radio-isotopic ISH, and suggested that these adenomas might be derived from plurihormonal primordial stem cells. Our present case is significant from the viewpoint of histogenesis of pituitary adenomas, because it further supports the cell origin of Somatotroph adenomas from plurihormonal primordial stem cells, and moreover it suggests the presence of unknown transcriptional factor other than Pit-1, common to GH, PRL, and ACTH.

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References

  1. Alexander JM, Biller BMK, Bikkal H, Zervas NT, Arnold A, Klibanski A (1990) Clinically nonfunctioning pituitary tumors are monoclonal in origin. J Clin Invest 86: 336–340

    PubMed  Google Scholar 

  2. Arita K, Uozumi T, Kuwabara S, Mukada K, Kawamoto K, Takechi A, Onda J, Hara H, Egusa G (1991) A case of pituitary adenoma producing both growth hormone (GH) and adrenocorticotropic hormone (ACTH). Endocrinol Jpn 38: 271–278

    PubMed  Google Scholar 

  3. Asa SL, Kovacs K, Horvath E, Singer W, Smyth HS (1992) Hormone secretion in vitro by plurihormonal pituitary adenomas of the acidophil cell line. J Clin Endocrinol Metab 75: 68–75

    PubMed  Google Scholar 

  4. Biller BMK, Alexander JM, Zervas NT, Hedley-Whyte ET, Arnold A, Klibanski A (1992) Clonal origins of adrenocorticotropin-secreting pituitary tissue in Cushing's disease. J Clin Endocrinol Metab 75: 1303–1309

    PubMed  Google Scholar 

  5. Bugalho MJGM, Nunes JFM, Sobrinho LG, Medina E, Campos JAM, da Silva CG, Clode AL (1993) Multihormonal response to CRH in a patient with Cushing's syndrome and a pituitary adenoma producing ACTH and GH. Acta Endocrinol 128: 289–292

    PubMed  Google Scholar 

  6. Chatelain A, Dupouy JP, Dubois MP (1979) Ontogenesis of cells producing polypeptide hormones (ACTH, MSH, LPH, GH, prolactin) in the fetal hypophysis of the rat: influence of the hypothalamus. Cell Tissue Res 196: 409–427

    PubMed  Google Scholar 

  7. Clore JN, Sharpe AR, Sahni KS, Kovacs K, Blackard WG (1988) Thyrotropin-induced hyperthyroidism: evidence for a common progenitor stem cell. Am J Med Sci 295: 3–5

    PubMed  Google Scholar 

  8. Fukamachi Y, Yokoyama Y, Miyasato H, Matsusaki I, Kanzaki K, Tanaka H, Nawada S, Ibayashi H (1988) A case of Cushing's disease presenting with hypersecretion of GH and PRL five years after adrenalectomy. Clin Endocr (Tokyo) [Suppl 9] 35: 2123 (Jpn)

    Google Scholar 

  9. Gicquel C, Bouc YL, Luton JP, Girard F, Bertagna X (1992) Monoclonality of corticotroph macroadenomas in Cushing's disease. J Clin Endocrinol Metab 75: 472–475

    PubMed  Google Scholar 

  10. Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S (1990) Clonal origin of pituitary adenomas. J Clin Endocrinol Metab 71: 1427–1433

    PubMed  Google Scholar 

  11. Jacoby LB, Hedley-Whyte ET, Pulaski K, Seizinger BR, Martuza RL (1990) Clonal origin of pituitary adenomas. J Neurosurg 73: 731–735

    PubMed  Google Scholar 

  12. Kovacs K, Horvath E (1986) Tumors of the pituitary gland. In: Hartmann WH (eds) Atlas of tumor pathology. Second series, Fascicle 21. Armed Forces Institute of Pathology, Washington, pp 70–93

    Google Scholar 

  13. Kovacs K, Lloyd RV, Horvath E, Asa SL, Stefaneanu L, Killinger DW, Smyth HS (1989) Silent somatotroph adenomas of the human pituitary. Am J Pathol 134: 345–353

    PubMed  Google Scholar 

  14. Karin M, Castrillo JL, Theill LE (1990) Growth hormone gene regulation: a paradigm for cell-type-specific gene activation. Trends Genet 6: 92–96

    PubMed  Google Scholar 

  15. Li J, Stefaneanu L, Kovacs K, Horvath E, Smyth HS (1993) Growth hormone (GH) and prolactin (PRL) gene expression and immunoreactivity in GH- and PRL-producing human pituitary adenomas. Virchows Archiv A Pathol Anat 422: 193–201

    Google Scholar 

  16. Lloyd RV, Cano M, Chandler WF, Barkan AL, Horvath E, Kovacs K (1989) Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization. Am J Pathol 134: 605–613

    PubMed  Google Scholar 

  17. Lloyd RV, Jin L, Fields K, Chandler WF, Horvath E, Stefaneanu L, Kovacs K (1991) Analysis of pituitary hormones and chromogranin A mRNAs in null cell adenomas, oncocytomas, and gonadotroph adenomas by in situ hybridization. Am J Pathol 139: 553–564

    PubMed  Google Scholar 

  18. Matsuno A, Teramoto A, Takekoshi S, Sanno N, Osamura RY, Kirino T (1995) Expression of plurihormonal mRNAs in somatotroph adenomas detected using a non-isotopic in situ hybridization method: comparison with lactotroph adenomas. Hum Pathol 26: 272–279

    PubMed  Google Scholar 

  19. Matsuno A, Teramoto A, Takekoshi S, Sanno N, Osamura RY, Kirino T (1995) HGH, PRL and ACTH gene expression in clinically non-functioning adenomas detected with non-isotopic in situ hybridization method. Endocr Pathol 6: 13–20

    PubMed  Google Scholar 

  20. Matsuno A, Teramoto A, Takekoshi S, Utsunomiya H, Ohsugi Y, Kishikawa S, Osamura RY, Kirino T, Lloyd RV (1994) Application of biotinylated oligonucleotide probes to the detection of pituitary hormone mRNA using Northern blot analysis, in situ hybridization at light and electron microscopic levels. Histochem J 26: 771–777

    PubMed  Google Scholar 

  21. Müller OA, Fink R, Werder KV, Scriba PC (1978) Hypersecretion of ACTH, growth hormone and prolactin in a patient with pituitary adenoma. Acta Endocrinol [Suppl 215] 87: 4–5

    Google Scholar 

  22. Sanno N, Inada K, Utsunomiya H, Umemura S, Itoh Y, Matsuno A, Teramoto A, Osamura RY (1994) Expression of Pit-1 product in human pituitaries: histochemical studies using an antibody against synthetic human Pit-1 protein. Med Sci Res 22: 685–687

    Google Scholar 

  23. Sanno N, Teramoto A, Matsuno A, Takekoshi S, Osamura RY (1996) Studies on GH and PRL gene expression by non-radioisotopic in situ hybridization in TSH-secreting adenomas. J Clin Endocrinol Metab 80: 2518–2522

    Google Scholar 

  24. Scanarini M, Mingrino S (1979) Pituitary adenomas secreting more than two hormones. Acta Neuropathol 48: 67–72

    PubMed  Google Scholar 

  25. Schulte HM, Oldfield EH, Allolio B, Katz DA, Berkman RA, Ali IU (1991) Clonal composition of pituitary adenomas in patients with Cushing's disease: determination by X-chromosome inactivation analysis. J Clin Endocrinol Metab 73: 1302–1308

    PubMed  Google Scholar 

  26. Simmoms DM, Voss JM, Ingraham HA, Holloway JM, Broide RS, Rosenfeld MG, Swanson LW (1990) Pituitary cell phenotypes involve cell-specific Pit-1 mRNA transformation and synergistic interactions with other classes of transcription factors. Genes Dev 4: 695–711

    PubMed  Google Scholar 

  27. Song J, Jin L, Lloyd RV (1989) Effects of estradiol on prolactin and growth hormone messenger RNAs in cultured normal and neoplastic (MtT/W15 and GH3) rat pituitary cells. Cancer Res 49: 1247–1253

    PubMed  Google Scholar 

  28. Thaper K, Stefaneanu L, Kovacs K, Horvath E, Asa SL (1993) Plurihormonal pituitary tumors: beyond the one cell-one hormone theory. Endocr Pathol 4: 1–3

    Google Scholar 

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Matsuno, A., Sasaki, T., Mochizuki, T. et al. A Case of pituitary somatotroph adenoma with concomitant secretion of growth hormone, prolactin, and adrenocorticotropic hormone — an adenoma derived from primordial stem cell, studied by immunohistochemistry, in situ hybridization, and cell culture. Acta neurochir 138, 1002–1007 (1996). https://doi.org/10.1007/BF01411291

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