Endocrine Pathology

, Volume 10, Issue 1, pp 55–64 | Cite as

Pars intermedia of the human pituitary revisited: Morphologic aspects and frequency of hyperplasia of POMC-peptide immunoreactive cells

  • Eva Horvath
  • Kalman Kovacs
  • Ricardo V. Lloyd
Clinical Research


The human pituitary has no distinct pars intermedia (PI). Instead, the proopiomelanocortin (POMC) producing, adrenocorticotropin (ACTH)- and β-endorphin-immunoreactive PI cells are incorporated within the pars anterior, thereby participating in the formation of the pars distalis. Two hundred fifty autopsy pituitaries (156 males, 94 females) have been studied by histology and immunohistochemistry to determine the frequency of clinically non-functioning ACTH- and β-endorphin immunoreactive (POMC) cell hyperplasia/adenoma probably attributable to PI-derived cells. Such hyperplasia occurred in 29% of men and 14% of women; 80% of the male and 77% of the female subjects were over 50 yr of age. In two of the women, POMC cell adenoma was present as well. Except for hypothyroidism, none of the cases with POMC cell hyperplasia had endocrine disorder. No obvious correlation was evident between POMC cell hyperplasia/adenoma and clinical presentation. Hyperplasia of PI-derived POMC cells may be suspected by virtue of differential intraglandular localization of these cells. Except for cases of glucocorticoid treatment, leading to Crooke’s hyalinization of ACTH cells, but not affecting PI cells, no conclusive separation of various POMC-producing subsets is possible at present. The PI-derived cells probably give rise to silent “corticotroph” adenoma subtype 1 and subtype 2.

Key Words

Human pituitary pars intermedia POMC cells hyperplasia adenoma 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hanström B. Gross anatomy of the hypophysis in mammals. In: Harris GW, Donovan BT, eds. The Pituitary Gland, vol. 1, London: Butterworths, 1966: 1–57.Google Scholar
  2. 2.
    Holmes RL, Ball JN. The pituitary gland. A Comparative Account. Cambridge: Cambridge University Press, 1974.Google Scholar
  3. 3.
    Russfield AB. Adenohypophysis. In: Bloodworth JMB Jr, ed. Endocrine Pathology. Baltimore: Williams and Wilkins, 1968; 75–116.Google Scholar
  4. 4.
    Celio MR, Pasi A, Bürgisser E, Buetti G, Höllt V, Gramsch C. “Proopiocortin fragments” in normal human adult pituitary. Distribution and ultrastructural characterization of immunoreactive cells. Acta Endocrinol 95:27–40, 1980.PubMedGoogle Scholar
  5. 5.
    McNicol AM. Patterns of corticotropic cells in the adult human pituitary in Cushing’s disease. Diagn Histopathol 4:335–341, 1981.PubMedGoogle Scholar
  6. 6.
    McNicol AM. A study of intermediate lobe differentiation in the human pituitary gland. J Pathol 150:169–173, 1986.PubMedCrossRefGoogle Scholar
  7. 7.
    McNicol AM, Teasdale GM, Beastall GH. A study of corticotroph adenomas in Cushing’s disease: no evidence of intermediate lobe origin. Clin Endocrinol 24:715–722, 1986.Google Scholar
  8. 8.
    Coates PJ, Doniach I, Hale AC, Rees LH. The distribution of immunoreactive α-melanocyte-stimulating hormone cells in the adult human pituitary gland. J Endocr 111:335–342, 1986.PubMedGoogle Scholar
  9. 9.
    Horvath E, Kovacs K. Fine structural cytology of the adenohypophysis in rat and man. J Electr Micr Techn 8:401–432, 1988.CrossRefGoogle Scholar
  10. 10.
    Horvath E, Kovacs K. The adenohypophysis. In: Kovacs K, Asa SL, eds. Functional Endocrine Pathology, vol. 1, Boston: Blackwell Scientific, 1991: 245–281.Google Scholar
  11. 11.
    Horvath E, Kovacs K. Ultrastructural diagnosis of human pituitary adenomas. Microsc Res Techn 20:107–135, 1992.CrossRefGoogle Scholar
  12. 12.
    Trouillas J, Guigard MP, Fonlupt P, Souchier C, Girod C. Mapping of corticotropic cells in the normal human pituitary. J Histochem Cytochem 44:473–479, 1996.PubMedGoogle Scholar
  13. 13.
    Qian X, Jin L, Grande JP, Lloyd RV. Transforming growth factor-β and p27 expression in pituitary cells. Endocrinology 137:3051–3060, 1996.PubMedCrossRefGoogle Scholar
  14. 14.
    Jin L, Qian X, Kulig E, Sanno N, Scheithauer BW, Kovacs K, et al. Transforming growth factor-β, transforming growth factor-β receptor II, and p27Kipl expression in nontumorous and neoplastic human pituitaries. Am J Pathol 151:509–519, 1997.PubMedGoogle Scholar
  15. 15.
    Rasmussen AT. Origin of the basophilic cells in the posterior lobe of the human hypophysis. Am J Anat 46:461–475, 1930.CrossRefGoogle Scholar
  16. 16.
    Rasmussen AT, Nelson AA: Pars intermedia basophil adenoma of the hypophysis. Am J Pathol 14:297–310, 1938.Google Scholar
  17. 17.
    Halmi NS, Peterson ME, Colurso GJ, Liotta AS, Krieger DT. Pituitary intermediate lobe in dog: two cell types and high bioactive adrenocorticotropin content. Science 211:72–74, 1981.PubMedCrossRefGoogle Scholar
  18. 18.
    Iturriza FC, Gomez Dumm CL. Cytological differences in the localization of glucocorticoid receptor-like immunoreactivity in the normal and transplanted pituitary pars intermedia. J Neur Transpl Plasticity 3:35–38, 1992.CrossRefGoogle Scholar
  19. 19.
    Horvath E, Kovacs K, Killinger DW, Smyth HS, Platts ME, Singer W. Silent corticotropic adenomas of the human pituitary gland: a histologic, immunocytologic and ultrastructural study. Am J Pathol 98:617–638, 1980.PubMedGoogle Scholar
  20. 20.
    Gonzalez de Aguilar JL, Tonon MC, Ruiz-Navarro A, Vaudry H, Gracia-Navarro F. Morphological and functional heterogeneity of frog melanotrope cells. Neuroendocrinology 59:176–182, 1994.PubMedGoogle Scholar
  21. 21.
    Hill JB, Lacy ER, Nagy GM, Gorcs TJ, Frawley LS. Does alpha-melanocyte-stimulating hormone from the pars intermedia regulate suckling-induced prolactin release? Supportive evidence from morphological and functional studies. Endocrinology 133:2991–2997, 1993.PubMedCrossRefGoogle Scholar
  22. 22.
    Landon M, Grossman DA, Ben-Jonathan N. Prolactin-releasing factor: cellular origin in the intermediate lobe of the pituitary. Endocrinology 126:3185–3192, 1990.CrossRefGoogle Scholar
  23. 23.
    Allen AL, Low MJ, Allen RG, Ben-Jonathan N. Identification of two classes of prolactin-releasing factors in intermediate lobe tumors from transgenic mice. Endocrinology 136:3093–3099, 1995.PubMedCrossRefGoogle Scholar
  24. 24.
    Vinson GP, Whitehouse BJ, Dell A, Etienne A, Morris HM. Characterisation of an adrenal zona glomerulosa-stimulating component of posterior pituitary extracts as α-MSH. Nature 284:464–467, 1980.PubMedCrossRefGoogle Scholar
  25. 25.
    Henville KL, Vinson GP. The effect of α-MSH peptides on adrenal steroidogenesis by human adrenal cellsin vitro. J Endocr 111: (Suppl) 91, 1986.Google Scholar
  26. 26.
    Coates PJ, McNicol AM, Doniach I, Rees LH. Increased production of α-melanocyte-stimulating hormone in the pituitary gland of patients with untreated Addison’s disease. Clin Endocrinol 29:421–426, 1988.Google Scholar
  27. 27.
    Nakayama K, Ishida N, Shirane M, Inomata A, Inoue T, Shishido N, et al. Mice lacking p27Kipl display increased body size, multiple organ hyperplasia, retinal displasia, and pituitary tumors. Cell 85:707–720, 1997.CrossRefGoogle Scholar
  28. 28.
    Kiyokowa H, Kineman RD, Manova-Todorova KO, Soares VC, Hoffman ES, Ono M, et al. Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27Kipl. Cell 85:721–732, 1996.CrossRefGoogle Scholar
  29. 29.
    Fero ML, Rivkin M, Tasch M, Porter P, Carow CE, Firpo E, et al. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27Kipl-deficient mice. Cell 85:733–744, 1996.PubMedCrossRefGoogle Scholar
  30. 30.
    Reincke M, Allolio B, Saeger W, Kaulen D, Winkelmann W. A pituitary adenoma secreting high molecular weight adrenocorticotropin without evidence of Cushing’s disease. J Clin Endocrinol Metab 65:1296–1300, 1987.PubMedGoogle Scholar
  31. 31.
    Nagaya T, Seo H, Kuwayama A. Pro-opiomelanocortin gene expression in silent corticotroph-cell adenoma and Cushing’s disease. J Neurosurg 72:262–267, 1990.PubMedCrossRefGoogle Scholar
  32. 32.
    Braithwaite SS, Clasen RA, D’Angelo CM. Silent corticotroph adenoma: case report and literature review. Endocr Prac 3:297–301, 1997.Google Scholar
  33. 33.
    Oka H, Kameya T, Sasano H, Aiba M, Kovacs K, Horvath E, et al. Pituitary choristoma composed of corticotrophs and adrenocortical cells in the sella turcica. Case report. Virchows Arch Pathol Anat 427:613–617, 1996.Google Scholar
  34. 34.
    Coiré CI, Horvath E, Kovacs K, Smyth HS, Sasano H, Iino K, et al. A composite silent “corticotroph” pituitary adenoma with interspersed adrenocortical cells. Neurosurgery 42:650–654, 1998.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 1999

Authors and Affiliations

  • Eva Horvath
    • 1
  • Kalman Kovacs
    • 1
  • Ricardo V. Lloyd
    • 2
  1. 1.Department of Laboratory Medicine, St. Michael’s HospitalUniversity of TorontoTorontoCanada
  2. 2.Department of Laboratory Medicine and PathologyThe Mayo ClinicRochester

Personalised recommendations