Horm Metab Res 2004; 36(7): 480-484
DOI: 10.1055/s-2004-825731
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Adrenomedullin Immunoreactivity Tissue Distribution in Parathyroids of the Patients with Primary Hyperparathyroidism

C.  Letizia 1 , F.  Ricci 2 , G.  De Toma 3 , R.  Cianci 1 , P.  Alo 1 , M.  Celi 1 , G.  Panzironi 3 , P.  L.  Mingazzini 2 , E.  D’Erasmo 1 , G.  F.  Mazzuoli 1
  • 1Department of Clinical Science, La Sapienza University, Rome, Italy
  • 2Department of Experimental Medicine and Pathology, La Sapienza University, Rome, Italy
  • 3Department of Surgery, La Sapienza University, Rome, Italy
Further Information

Publication History

Received 8 July 2003

Acceped after second Revision 27 January 2004

Publication Date:
11 August 2004 (online)

Abstract

Adrenomedullin (ADM) is a new potent vasorelaxant peptide identified originally in extracts of pheochromocytoma, and is widely distributed within the tissue. Although histopathological studies have demonstrated the presence of ADM-immunoreactivity (ir-ADM) in some human neuroendocrine tumors (such as insulinoma, pituitary adenoma, and gastrointestinal neuroendocrine tumors), data on the presence of ADM in normal and pathological parathyroid gland are not available. Plasma AM concentrations were recently reported to be elevated in patients with PHP (primary hyperparathyroidism). The aim of our study was to determine tissue distribution of ir-AM in 34 patients with PHP (27 female and 7 male, mean age 50 ± 6 years) undergoing surgery. Six normal parathyroid samples incidentally found during thyroidectomy for neoplastic diseases and ten sections of human rectus abdominis muscle tissue were used as controls (C). Adenomatous parathyroids were found in 22 PHP and hyperplastic parathyroids in twelve PHP patients. Four hyperplastic parathyroids were found in three PHP patients and three parathyroids in 10 PHP patients. Eight parathyroids revealed a prevalent diffuse growth pattern and four showed a prevalent nodular growth pattern. Immunohistochemical ADM expression was seen in seven of twelve (58.3 %) hyperplastic parathyroids and in fourteen of twenty-two (66.6 %) adenomatous glands. Parathyroid chief cells showed strong cytoplasmatic staining, whereas oncocytic cells showed a faintly aspecific cytoplasmatic staining. Normal parathyroids were negative for ir-ADM. In conclusion, we found the presence of ADM in parathyroid chief cells of PHP patients using immunohistochemistry in our study.

References

  • 1 Ikeda K, Weir E C, Sakaguchi K, Burtis W J, Zimering M, Mangin M, Dreyer B E, Brandi M L, Aurbach G D, Broadus A E. Clonal rat parathyroid cell line expresses a parathyroid hormone-related peptide but not parathyroid hormone itself.  Biochem Biophys Res Commun. 1989;  162 108-115
  • 2 Zajac J D, Callaghan J, Eldridge C, Diefenbach-Jagger H, Suva L J, Hudson P, Moseley J M, Michelangeli V P, Pasquini G. Production of parathyroid hormone-related protein by a rat parathyroid cell line.  Mol Cell Endocrinol. 1989;  67 107-112
  • 3 Fujii Y, Moreira J E, Orlando C, Maggi M, Aurbach G D, Brandi M L, Sakaguchi K. Endothelin as an autocrine factor in the regulation of parathyroid cells.  Proc Natl Acad Sci USA. 1991;  88 4235-4239
  • 4 Nickols G A, Nana A D, Nickols M A, DiPette D J, Asimakis G K. Hypotension and cardiac stimulation due to the parathyroid hormone-related protein, humoral hypercalcemia of malignancy factor.  Endocrinology. 1989;  125 834-841
  • 5 Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells.  Nature. 1988;  332 411-415
  • 6 Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, Eto T. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma.  Biochem Biophys Res Commun. 1993;  192 553-560
  • 7 Ishiyama Y, Kitamura K, Ichiki Y, Nakamura S, Kida O, Kangawa K, Eto T. Hemodynamic effects of a novel hypotensive peptide, human adrenomedullin, in rats.  Eur J Pharmacol. 1993;  241 271-273
  • 8 Kato J, Kitamura K, Kangawa K, Eto T. Receptors for adrenomedullin in human vascular endothelial cells.  Eur J Pharmacol. 1995;  289 383-385
  • 9 Eguchi S, Hirata Y, Kano H, Sato K, Watanabe Y, Watanabe T X, Nakajima K, Sakakibara S, Marumo F. Specific receptors for adrenomedullin in cultured rat vascular smooth muscle cells.  FEBS Lett. 1994;  340 226-230
  • 10 Washimine H, Asada Y, Kitamura K, Ichiki Y, Hara S, Yamamoto Y, Kangawa K, Sumiyoshi A, Eto T. Immunohistochemical identification of adrenomedullin in human, rat, and porcine tissue.  Histochem Cell Biol. 1995;  103 251-254
  • 11 Marinoni E, di Iorio R, Letizia C, Villaccio B, Scucchi L, Cosmi E V. Immunoreactive adrenomedullin in human fetoplacental tissues.  Am J Obstet Gynecol. 1998;  179 784-787
  • 12 Ichiki Y, Kitamura K, Kangawa K, Kawamoto M, Matsuo H, Eto T. Distribution and characterization of immunoreactive adrenomedullin in human tissue and plasma.  FEBS Lett. 1994;  338 6-10
  • 13 Letizia C, Tamburrano G, Alò P, Paoloni A, Caliumi C, Marinoni E, di Iorio R, D'Erasmo E. Adrenomedullin, a new peptide, in patients with insulinoma.  Eur J Endocrinol. 2001;  144 517-520
  • 14 Murakami O, Takahashi K, Satoh F, Totsune K, Sone M, Arihara Z, Andoh N, Mouri T. Expression of adrenomedullin and adrenomedullin mRNA in ectopic ACTH-secreting tumors.  Eur J Endocrinol. 1998;  138 436-439
  • 15 Letizia C, Di Iorio R, De Toma G, Marinoni E, Cerci S, Celi M, Subioli S, D'Erasmo E. Circulating adrenomedullin is increased in patients with corticotropin-dependent Cushing's syndrome due to pituitary adenoma.  Metabolism. 2000;  49 760-763
  • 16 Letizia C, De Toma G, Caliumi C, Cerci S, Massa R, Di Iorio R, Alo P, Marinoni E M, Diacinti D, D'Erasmo E. Plasma adrenomedullin concentrations in patients with adrenal pheochromocytoma.  Horm Metab Res. 2001;  33 290-294
  • 17 Ehlenz K, Koch B, Preuss P, Simon B, Koop I, Lang R E. High levels of circulating adrenomedullin in severe illness: correlation with C-reactive protein and evidence against the adrenal medulla as site of origin.  Exp Clin Endocrinol Diabetes. 1997;  105 156-162
  • 18 Di Iorio R, Marinoni E, Scavo D, Letizia C, Cosmi E V. Adrenomedullin in pregnancy.  Lancet. 1997;  349 (letter) 328
  • 19 Letizia C, Caliumi C, Delfini E, Celi M, Subioli S, Diacinti D, Minisola S, D'Erasmo E, Mazzuoli G F. Adrenomedullin concentrations are elevated in plasma of patients with primary hyperparathyroidism.  Metabolism.. 2003;  52 159-162
  • 20 Kitamura K, Ichiki Y, Tanaka M, Kawamoto M, Emura J, Sakakibara S, Kangawa K, Matsuo H, Eto T. Immunoreactive adrenomedullin in human plasma.  FEBS Lett. 1994;  341 288-290
  • 21 Sato K, Hirata Y, Imai T, Iwashina M, Marumo F. Characterization of immunoreactive adrenomedullin in human plasma and urine.  Life Sci. 1995;  57 189-194
  • 22 Meeran K, O'Shea D, Upton P D, Small C J, Ghatei M A, Byfield P H, Bloom S R. Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study.  J Clin Endocrinol Metab. 1997;  82 95-100
  • 23 Massart P E, Hodeige D, Donckier J. Adrenomedullin: view on a novel vasodilatory peptide with natriuretic properties.  Acta Cardiol. 1996;  51 259-269
  • 24 Kano H, Kohno M, Yasunari K, Yokokawa K, Horio T, Ikeda M, Minami M, Hanehira T, Takeda T, Yoshikawa J. Adrenomedullin as a novel antiproliferative factor of vascular smooth muscle cells.  J Hypertens. 1996;  14 209-213
  • 25 Horio T, Kohno M, Kano H, Ikeda M, Yasunari K, Yokokawa K, Minami M, Takeda T. Adrenomedullin as a novel antimigration factor of vascular smooth muscle cells .  Circ Res. 1995;  77 660-664
  • 26 Miller M J, Martinez A, Unsworth E J, Thiele C J, Moody T W, Elsasser T, Cuttitta F. Adrenomedullin expression in human tumor cell lines. Its potential role as an autocrine growth factor.  J Biol Chem. 1996;  271 23 345-23 351
  • 27 Satoh F, Takahashi K, Murakami O, Totsune K, Sone M, Ohneda M, Abe K, Miura Y, Hayashi Y, Sasano H. et al . Adrenomedullin in human brain, adrenal glands and tumor tissues of pheochromocytoma, ganglioneuroblastoma and neuroblastoma.  J Clin Endocrinol Metab. 1995;  80 1750-1752
  • 28 Letizia C, Delfini E, De Toma G, Subioli S, Minisola S, Caliumi C, Diacinti D, D'Erasmo E, Mazzuoli G F. Renin-angiotensin-aldosterone and endothelin-1 systems in primary hyperparathyroidism associated with arterial hypertension.  Ital J Electrol Metab. 2001;  15 21-26
  • 29 Takahashi K, Yoshinoya A, Murakami O, Totsune K, Shibahara S. Production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1, by cultured human adrenocortical carcinoma cells.  Peptides. 2000;  21 251-256

Prof. C. Letizia, M. D.

Department of Clinical Science

Policlinico Umberto I · 00156 Rome · Italy ·

Phone: 39/6/4997-0944 (650)

Fax: 39/6/4997-0524

Email: claudio.letizia@uniroma1.it