Horm Metab Res 2002; 34(3): 137-143
DOI: 10.1055/s-2002-23197
Original Clinical

© Georg Thieme Verlag Stuttgart · New York

A Retrospective Hormonal and Immunohistochemical Evaluation of 47 Acromegalic Patients: Prognostic Value of Preoperative Plasma Prolactin

L.  De Marinis 1 , P.  Zuppi 2 , D.  Valle 3 , A.  Mancini 1 , A.  Bianchi 1 , L.  Lauriola 4 , P.  Pasquini 4 , C.  Anile 5 , G.  Maira 5 , A.  Giustina 6
  • 1Institute of Endocrinology, Catholic University School of Medicine, Rome, Italy
  • 2Azienda ospedaliera San Camillo - Forlanini, Rome, Italy
  • 3Eli-Lilly, Florence, Italy
  • 4Institute of Pathology, Catholic University School of Medicine, Rome, Italy
  • 5Institute of Neurosurgery, Catholic University School of Medicine, Rome, Italy
  • 6Endocrine Section, Department of Internal Medicine, University of Brescia, Italy
Further Information

Publication History

15 February 2001

12 October 2001

Publication Date:
26 March 2002 (online)

Abstract

This study was performed to investigate the correlations between preoperative prolactin (PRL) plasma values, immunohistochemical picture and the clinical course in growth hormone (GH) secreting pituitary adenomas. In 47 patients (19 males and 28 females; mean age 40 years; range 13 - 70 years), we measured GH, IGF-1 and prolactin plasma values both before and after transsphenoidal surgery, and basal IGF-1 and GH after an oral glucose tolerance test (OGTT) during four years of follow-up. We considered those patients as “controlled” who presented an undetectable growth hormone after OGTT (GH < 1 µg/l), IGF-I plasma values in the normal range, matched for age and sex, and no clinical activity or neuroradiological recurrence after a four-year follow-up. We considered patients as “poorly controlled” who still showed elevated GH and IGF-I plasma levels, uninhibited GH after OGTT (GH > 1 µg/l), presence of clinical activity and/or radiological signs of adenoma recurrence, even if a reduction of tumor size had been demonstrated. Results: Controlled patients (n = 22) exhibited mean preoperative PRL levels (± SEM) lower than the group of poorly controlled (n = 25) ones (21.40 ± 5.51 vs. 38.44 ± 5.16 µg/l; p < 0.03). From 3 to 12 months after surgery, postoperative PRL levels were also lower in the controlled patients compared to the poorly controlled ones (8.31 ± 1.20 vs. 25.32 ± 3.20 µg/l; p < 0.0001). Eighty percent (20/25) of poorly controlled patients showed both PRL and GH positivity after immunostaining. Only 3/22 (13.6 %) of controlled patients showed the same double positivity. In conclusion, preoperative hyperprolactinemia identifies a group of acromegalic patients at elevated risk of disease persistence after surgery. We hypothesize that most of these high-risk patients may have more aggressive mixed GH-PRL secreting adenomas.

References

  • 1 Adams E F, Buchfelder M, Huttner A, Moreth S, Fahlbusch R. Recent advances in the molecular biology of growth-hormone secreting human pituitary tumors.  Experimental and Clinical Endocrinology. 1993;  101 12-16
  • 2 Zimmerman E A, Defendini R, Frantz A G. Prolactin and growth hormone in patients with pituitary adenomas: a correlative study of hormone in tumor and plasma by immunoperoxidase technique and radioimmunoassay.  Journal of Clinical Endocrinology and Metabolism. 1973;  38 577-584
  • 3 De Marinis L, Mancini A, Zuppi P, Anile C, Maira G. Paradoxical growth hormone response to thyrotropin-releasing hormone in acromegaly. Clinical correlations and prognostic value.  Acta Endocrinologica (Copenh). 1990;  122 433-449
  • 4 Robert F, Pelletier G, Serri O, Hardy J. Mixed growth hormone and prolactin secreting pituitary adenomas: A pathologic, immuno-cytochemical, ultrastructural, and immunoelectron microscopic study.  Human Pathology. 1988;  19 1327-1334
  • 5 Yamada S, Tadashi A, Toshiaki S, Kovacs K, Shishiba Y, Sawano S, Takada K. Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology.  Neurosurgery. 1993;  33 20-27
  • 6 Adams E F, Brockmeier S, Friedmann E, Roth M, Buchfelder M, Fahlbusch R. Clinical and biochemical characteristics of acromegalic patients harbouring gsp-positive and gsp-negative pituitary tumors.  Neurosurgery. 1993;  33 198-203
  • 7 Thapar K, Kovacs K, Muller P J. Clinical-pathological correlations of pituitary tumours.  Baillieres Clin Endocrinol Metab. 1995;  9 (2) 43-70
  • 8 Furuhata S, Kameya T, Otani M, Toya S. Prolactin presents in all pituitary tumors of acromegalic patients.  Human Pathology. 1993;  24 10-15
  • 9 Loyd R V, Gikas P W, Chandler W F. Prolactin and growth hormone-producing pituitary adenomas.  American Journal of Surgical Pathology. 1983;  7 251-260
  • 10 Horvath E, Kovacs K, Scheithauer B W, Randall R V, Laws E R, Thorner M O, Tindall G T, Barrow D L. Pituitary adenomas producing growth hormone, prolactin and one or more glycoprotein hormones: A histologic, immunohistochemical, and ultrastructural study of four surgically removed tumors.  Ultrastructural Pathology. 1983;  5 171-183
  • 11 Kovacs K. Pathology of growth hormone excess.  Pathology, Research and Practice. 1988;  183 565-568
  • 12 Horvath E, Kovacs K, Killinger D W, Smyth H S, Weiss M H, Ezrin C. Mammosomatotroph cell adenomas of the human pituitary.  Virchows Archives [A]. 1983;  398 277-289
  • 13 Nagaya T, Seo H, Kuwayama A, Sakurai T, Tsukamoto N, Sugita K, Matsui N. Prolactin gene expression in human growth hormone secreting pituitary adenomas.  Journal of Neurosurgery. 1990;  72 879-882
  • 14 Robert F, Pelletier G, Serri O, Hardy J. Mixed growth hormone and prolactin-secreting pituitary adenomas: A pathologic, immunocytochemical, ultrastructural, and immunoelectron microscopic study.  Human Pathology. 1988;  19 1327-1334
  • 15 Bassetti M, Spada A, Arosio M, Valler L, Brina M, Giannattasio G. Morphological studies on mixed growth hormone (GH)- and prolactin (PRL)-secreting human pituitary adenomas. Coexistence of GH and PRL in the same secretory granule.  Journal of Clinical Endocrinology. 1986;  62 1093-1100
  • 16 Guyda H, Robert F, Colle E, Hardy J. Hystologic, ultrastructural and hormonal characteristics of a pituitary tumor secreting hGH and prolactin.  Journal of Clinical Endocrinology and Metabolism. 1973;  36 531-538
  • 17 Lloyd R V, Gikas P W, Chandler W F. Prolactin and growth hormone-producing pituitary adenomas. An immunohistochemical and ultrastructural study.  American Journal of Surgical Pathology. 1983;  7 251-260
  • 18 Melmed S, Braunstein G D, Jeffrey R, Becker D P. UCLA conference: Pituitary tumors secreting growth hormone and prolactin.  Annals of Internal Medicine. 1986;  105 238-251
  • 19 Nyquist P, Laws E R, Elliot E. Novel features of tumors that secrete both growth hormone and prolactin acromegaly.  Neurosurgery. 1994;  35 179-183; discussion 183 - 184
  • 20 Hardy J, Vezina J L. Trans-sphenoidal microsurgery of intracranial neoplasm. In: R. A. Thompson, J. R. Green (eds) Advances in neurology. New York; Raven Press 1986 15: 261-264
  • 21 Giustina A, Barkan A, Casanueva F F, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, von Werder K, Melmed S. Criteria for cure of acromegaly: a consensus statement.  Journal of Clinical Endocrinology and Metabolism. 2000;  85 (2) 526-529
  • 22 Daughaday W H, Mariz I K, Blethen S L. Inhibition of access of bound somatomedin to membrane receptor and immunobinding sites: a comparison of radioreceptor and radioimmunoassay of somatomedin in native and acid-ethanol-extracted serum.  Journal of Clinical Endocrinology and Metabolism. 1980;  51 781-788
  • 23 Lamberts S WJ, Liuzzi A, Chiodini P G, Verde S, Klijin J GM. The value of plasma prolactin levels in the prediction of the responsiveness of growth hormone secretion to bromocriptine and TRH in acromegaly.  European Journal of Clinical Investigation. 1982;  12 151-155
  • 24 Melmed S, Braunstein G D, Horvath E, Ezrin C, Kovacs K. Pathophysiology of acromegaly.  Endocrine Reviews. 1983;  4 271-290
  • 25 Loyd R V, Cano M, Chandler W F, Barkan A L, Horvath E, Kovacs K. Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization.  American Journal of Pathology. 1989;  134 605-613
  • 26 Niall H D, Hogan M L, Sauer R. Sequences of pituitary and placental lactogenic and growth hormones: evolution from a primordial peptide by gene reduplication.  Proceedings of the National Academy of Science. 1971;  68 866-870
  • 27 Cooke N E, Coit D, Weiner R I, Baxter J D, Martial J A. Structure of cloned DNA complementary to rat prolactin messenger RNA.  Journal of Biological Chemistry. 1980;  255 6502-6510
  • 28 Cooke N E, Coit D, Shine J, Baxter J D, Martial J A. Human prolactin. cDNA structural analysis and evolutionary comparisons.  Journal of Biological Chemistry. 1981;  256 4007-4016
  • 29 Cooke N E, Baxter J D. Structural analysis of the prolactin gene suggests a separate origin for its 5’ end.  Nature. 1982;  297 603-606
  • 30 Truong A T, Duez C, Belayew A, Renard A, Pictet R, Bell G I, Martial J A. Isolation and characterisation of the human prolactin gene.  EMBO J. 1984;  3 429-437
  • 31 Landis C A, Harsh G, Lyons J, Davis R L, McCormick F, Bourne H R. Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein.  Journal of Clinical Endocrinology and Metabolism. 1990;  71 1416-1420
  • 32 Beckers A, Courtoy R, Stevenaert A. Mammosomatotropes in humans pituitary adenomas as revealed by electron microscopic double gold immunostaining method.  Acta Endocrinologica (Copenh). 1988;  118 503-512

Laura De Marinis, M.D.

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Fax: + 39 (06) 30362322

Email: laurademarinis@yahoo.it

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