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58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

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Hereditary infantile gigantism caused by truncated differentiation of pituitary mammosomatotrophs

Erblicher frühkindlicher Riesenwuchs wird durch eine unvollständige Differenzierung der Hypophyse verursacht

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  • corresponding author S. Gläsker - Neurochriurgische Universitätsklinik Freiburg
  • A. O. Vortmeyer - Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, USA
  • A. R. Lafferty - Starship Children’s Hospital, Auckland University, New Zealand
  • J. Li - Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, USA
  • Z. Zhuang - Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, USA
  • E. H. Oldfield - Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, USA

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocDO.06.01

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2007/07dgnc047.shtml

Published: April 11, 2007

© 2007 Gläsker et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Pituitary hyperplasia has exclusively been reported in sporadic cases as a result of excessive secretion of releasing hormones from the hypothalamus or from ectopic sources. We report the first cases of hereditary pituitary hyperplasia. The mother and both of her sons exhibited identical clinical features with the early onset of pituitary gigantism at around two years of age. All three patients began showing abnormally rapid growth at about 1 y/o and had extremely elevated plasma growth hormone (GH, 27-120 ng/ml), prolactin (PRL, 600-6000 ng/ml) and somatomedin (IGF-1) levels. The mother had hypophysectomy for suspected tumor at 2.5 y/o in 1971. Endocrine replacement has permitted her to have 2 children. MRI of both boys revealed a symmetrically enlarged pituitary gland (Fig.1), but no evidence of adenoma. Both boys were operated at 4 y/o and were cured after total removal of the anterior lobe.

Methods: To elucidate the pathogenesis of this novel hereditary disease we investigated the tissue by combining pathologic and molecular approaches.

Results: The pituitary specimens of both boys reveal diffuse mammosomatotroph hyperplasia of the entire pituitary gland without adenoma. Immuno-electron microscopy with double-labeling for GH and PRL revealed that both GH and PRL were expressed by the same cells, even the same secretory granules. No germline mutation was detectable in the receptor for growth hormone releasing hormone (GHRH) and karyotyping revealed no abnormalities. However, we detected abnormal expression of GHRH in clusters of cells throughout the hyperplastic pituitary tissue of both patients detectable by Western blot and immunohistochemistry.

Conclusions: This novel hereditary condition is caused by a germline mutation resulting in truncated differentiation of developing pituicytes and excess secretion of GH and PRL. The results suggest that the expansion and persistence of the embryonic mammosomatotroph pool is an abnormal paracrine and/or autocrine effect of GHRH secretion in the pituitary gland.