Quo vadis, hypophysis? Some news and prospects

Česká verzia

Authors: J. Marek
Authors place of work: III. interní klinika 1. lékařské fakulty UK a VFN Praha, přednosta prof. MUDr. Štěpán Svačina, DrSc., MBA
Published in the journal: Vnitř Lék 2007; 53(7-8): 789-794
Category:

Summary

Knowledge of hypophysis could hardly stagnate in a context of general progress in medical science as such. New knowledge in physiology, pathology and treatment of hypophysis diseases is vast and only some of it could be included in the article. New regulators of hypophysial secretion have been discovered. Among them are hypothalamic chemokines and the KISS-1 gene product – kisspeptin. Impulses coming to the hypophysis from the brain centres and the periphery need to be integrated. This is provided by a system of folliculo- stellate cells, paracrine mechanisms and hypophysial microcirculation. Are there stem cells in the hypophysis, too? It seems there are. It could be the above mentioned folliculo-stellate system cells, or the recently discovered SP (side population) cells. Massive injuries such as multiple traumas, severe burns and shock states provoke a double-phase response of the hypophysis. The acute phase is characterised by hypersecretion of most of hypophysial hormones and peripheral resistance to their actuation. In the subsequent chronic phase, however, the secretion of all hypophysial hormones is reduced, except for ACTH. Clinically relevant hypophysial adenomas affect approximately 1‰ of population. Two thirds of the above number are prolactinomas. Most prolactinomas can be cured without major difficulty, only those resistant to pharmacological treatment can become a problem. In such cases, Leksell gamma knife can play an important role. The treatment of acromegaly is far more difficult, though. We have developed our own acromegaly treatment method. We treat adenomas surgically, expose possible residua to Leksell gamma knife irradiation and apply pharmacological therapy until the effect of irradiation has been achieved. The therapeutic options are ordered in a cost sequence: cabergolin, somatostatin analogues, pegvisomant. Similar approach is applied to patients with central etiology Cushing's syndrome, the only difference being the fact that the pharmacological therapy preceding the effect of the gamma knife treatment uses ketoconazol and metyrapone. Like in the case of acromegaly, also in that of Cushing's disease, new drugs are developed which promise greater therapeutic advantages.

Key words:
hypophysis – chemokins – kisspeptin – stem cells of the hypophysis – emergency states of the human organism – hypophysial adenomas – prolactinomas – acromegalia – Cushing’s disease

Zdroje

1. Callewaere C, Banisadr G, Rostène W et al. Chemokines and chemokine receptors in the brain: implication in neuroendocrine regulation. J Mol Endocrinol 2007; 38: 355-363.

2. Murphy KG. Kisspeptins Regulators of metastasis and the hypothalamic-pituitary-gonadal axis). J Neuroendocrinol 2005; 17: 519-525.

3. Gottsch ML, Clifton DK, Steiner RA Kisspeptin-GPR54 signaling in the neuroendocrine reproductiev axis. Mol Cell Endocrinol 2006; 254-255: 91-96.

4. Shirasawa N, Mabuchi Y, Sakuma E et al. Intercellular communication within the rat anterior pituitary gland: Immunohistochemistry of S-100 amd connexin 43 of folliculo-stellate cells in the rat anterior pituitary gland. Anat Rec Part A 2004; 278A: 462-473.

5. Horvath E, Kovacs K. Folliculo-stellate cells of the human pituitary: a type of adult stem cell? Ultrastruct Pathol 2002; 26: 219-228.

6. Inoue K, Mogi C, Ogawa S et al. Are folliculo-stellate cells in the anterior pituitary gland supportive cells or organ-specific stem cells? Arch Physiol Biochem 2002; 110: 50-53.

7. Chen J, Hersmus N, Van Duppen V et al. The adult pituitary contains a cell population displaying stem/progenitor cell and erealy embryonic characteristics. Endocrinology 2005; 146: 3985-3998.

8. van den Berghe G. Dynamic neuroendocrine response to critical illness. Frontiers Neuroendocrinol 2002; 23: 370-391.

9. Gauna C, van den Berghe GH, van der Lely AJ. Pituitary function during severe and life-threatening illnesses. Pituitary 2005; 8: 213-217.

10. Fomicheva EE, Nemirovich-Danchenko EA, Korneva EA. Immunoprotective eddects of prolactin during stress-induced immune dysfunction. Bull Exp Biol Med 2004; 137: 544-547.

11. Molitch ME, Russel EJ The pituitary „incidentaloma“. Ann Intern Med 1990; 112: 925-931.

12. Hall WA, Luciano MG, Doppman JL et al. Pituitary magnetic resonance imaging in normal human volunteers: ocult adenomas in the general population. Ann Intern Med 1994; 120: 817-820.

13. Daly AF, Rixhon M, Adam C et al. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 2006; 91: 4769-4775.

14. Faglia G, Spada A Genesis of pituitary adenomas: state of the art. J Neuro-Oncol 2001; 54: 95-110.

15. Lania A, Mantovani G, Spada A. Genetics of pituitary tumors: Focus on G-protein mutations. Exp Biol Med 2003; 228: 1004-1017.

16. Spada A, Mantovani G, Lania A. Pathogenesis of prolactinomas. Pituitary 2005; 8: 7-15.

17. Gillam MP, Molitch ME, Lombardi G et al. Advances in treatment of prolactinomas. Endocr Rev 2006; 27: 485-534.

18. Crosignani PG Current treatment issues in female hyperprolactinaemia. Europ J Obstetr Gynecol Reprod Biol 2006; 125: 152-164.

19. Colao A, di Sarno A, Pivonello R et al. Dopamine receptor agonists for treating prolactinomas. Expert Opin Investig Drugs 2002; 11: 787-800.

20. Casanueva FF, Molitch ME, Schlecht JA et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol 2006; 65: 265-273.

21. Doporučení hypofyzární společnosti pro diagnostiku a léčbu prolaktinomů. Diabetol Metabol Endokrinol Výživa 2006; 9: 149-155.

22. Gillam GP, Middler S, Freed DJ et al. The novel use of very high doses of cabergoline and combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma. J Clin Endocrinol Metab 2002; 87: 4447-4451.

23. Schade R, Andersohn F, Suissa S et al. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med 2007; 356: 29-38.

24. Zanettini R, Antonini A, Gatto G et al. Valvular heart disease and the use of dopamine agonists for Parkinson´s disease. N Engl J Med 2007; 356: 39-46.

25. Melmed S Acromegaly. N Engl J Med 2006; 355: 2558-2573.

26. Melmed S, Casanueva F, Cavagnini F et al. Consensus statement: medical management of acromegaly. Eur J Endocrinol 2005; 153: 737-740.

27. Ježková J, Marek J, Hána V et al. Gamma knife radiosurgery for acromegaly - long-term experience. Clin Endocrinol 2006; 64: 588-595.

28. Abs R, Verhelst J, Maiter D et al. Cabergoline in the treatment of acromegaly: a study in 64 patients. J Clin Endocrinol Metab 2003; 88: 3105-3112.

29. Cook DM, Cook MB. Managing acromegaly with somatostatin analogs. Endocrinologist 2006; 16: 100-108.

30. Colao A, Pivonelo R, Auriemma RS et al. Efficacy of 12 month treatment with growth hormone antagonist pegvisomant in patients resistant to long-term, high dose somatostatin analog treatment: effect on IGF I levels, tumour mass, hypertension and glucose tolerance. Eur J Endocrinol 2006; 154: 467-477.

31. Jorgensen JO, Feldt-Rasmussen U, Frystyk J et al. Cotreatment of acromegaly with somatostatin analogs and growth hormone receptor antagonistst. J Clin Endocrinol Metab 2005; 90: 5627-5631.

32. Čáp J. Medikamntózní léčba akromegalie. Diabetol Metab Endokrinol Výživa 2004; 7 (Suppl 2): 19-23.

33. Fedele M, De Martino I, Pivonello R et al. SOM230, a new somatostatin analogue, is highly effective in the therapy of growth hormone/prolactin-secreting pituitary adenomas. Clin Cancer Res 2007; 13: 2738-2744.

34. Jaquet P, Gunz G, Savenau A et al. BIM-23A760, a chimeric molecule directed towards somatostatin and dopamine receptors, vs universal somatostatin receptors ligands in GH-secreting pituitary adenomas partial responders to octreotide. J Endocrinol Invest 2005; 28 (Suppl 11): 21-27.

35. Liščák R, Vladyka V, Marek J. Pituitary radiosurgery. Techniques Neurosurg. 2003; 9: 143-151.

36. Hána V, Dokoupilová M, Marek J et al. Recurrent ACTH-independent Cushing’s syndrome in multiple pregnancies and its treatment with metyrapone. Clin Endocrinol 2001; 54: 277-281.

37. Berwaerts JJ, Verhelst JA, Verhaegen AA et al. Corticotropin-dependent Cushing’s syndrome in older people: presentation of five cases and therapeutical use of ketokonazole. J Am Geriatr Soc 1998; 46: 880-884.

38. Sonino N, Boscaro M, Fallo F. Pharmacologic management of Cushing syndrome: new targets for therapy. Treat Endocrinol 2005; 4: 87-94.

39. Arnaldi G, Polenta B, Cardinaletti M et al. Potential indications for somatostatin analogs in Cushing´s syndrome. J Endocrinol Invest 2005; 28 (Suppl 11): 106-110.

40. van der Hoek J, Lamberts SWJ, Hofland LJ The role of somatostatin analogs in Cushing’s disease. Pituitary 2004; 7: 257-264.

41. Buijsman RC, Hermkens PH, van Rijn RD et al. Non-steroidal steroid receptor modulators. Curr Med Chem 2005; 12: 1017-1075.