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Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney disease: SSTR5 polymorphism and PKD1 mutation

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Abstract

A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0–5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48–255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Pathologic, cytogenetic, molecular and in silico analysis was undertaken. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.142C>A (p.L48M, rs4988483) in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subjected to extensive morphological, ultrastructural, cytogenetic and molecular studies. The physical proximity of the PKD1 and SSTR5 genes on chromosome 16 suggests a causal relationship between ADPKD and somatotroph adenoma.

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Acknowledgments

Authors are grateful to the Jarislowsky and Lloyd Carr Harris Foundations for their continuous support. RA Toledo is supported by a 2009 FAPESP (Sao Paulo State Research Foundation) post-doctoral fellowship. SAP Toledo is partially supported by a 2010 and 2011 CNPq (National Research Foundation) grants. The ADPKD gene analyses were funded by NIDDK grant DK058816 and the Mayo PKD Translational Center (DK090728). Lastly, the authors thank Mrs. Denise Chase of Mayo Clinic for her excellent secretarial support.

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Authors and Affiliations

  1. Department of Neurosurgery, Hospital Pablo Tobon Uribe and Clinica Medellin, Medellin, Colombia

    Luis V. Syro

  2. Department of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA

    Jamie L. Sundsbak, Christina M. Heyer & Peter C. Harris

  3. Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA

    Bernd W. Scheithauer

  4. Unidade de Endocrinologia Genética, (LIM25), Endocrinology, Hospital das Clínicas, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil

    Rodrigo A. Toledo, Tomoko Sekiya & Sergio P. A. Toledo

  5. Grupo Genetica de Poblaciones, Universidad de Antioquia, Medellin, Colombia

    Mauricio Camargo

  6. Department of Neurosurgery, Clinica SOMA, Medellin, Colombia

    Humberto Uribe

  7. Department of Neurosurgery, Clinica las Americas, Medellin, Colombia

    Jorge I. Escobar

  8. Department of Endocrinology, Hospital Pablo Tobon Uribe, Medellin, Colombia

    Martin Vasquez

  9. Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, ON, Canada

    Fabio Rotondo, Kalman Kovacs & Eva Horvath

  10. Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA

    Dusica Babovic-Vuksanovic

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  1. Luis V. Syro
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Correspondence to Bernd W. Scheithauer.

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Syro, L.V., Sundsbak, J.L., Scheithauer, B.W. et al. Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney disease: SSTR5 polymorphism and PKD1 mutation. Pituitary 15, 342–349 (2012). https://doi.org/10.1007/s11102-011-0325-0

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