Novel AIP mutation in exon 6 causing acromegaly in a German family

J Endocrinol Invest. 2023 Aug;46(8):1705-1709. doi: 10.1007/s40618-023-02031-5. Epub 2023 Feb 9.


The most frequent genetic alteration of familial isolated growth hormone producing pituitary neuroendocrine tumors is a germline mutation of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Various AIP mutations are already known; however, an AIP mutation in exon 6 (c.811_812del; p.Arg271Glyfs*16) has not been reported yet. Here, we report a German family with two identical twins who were both affected by acromegaly and carried the above-mentioned novel AIP mutation. The father was found to be an unaffected carrier, while the paternal aunt most likely suffered from acromegaly as well and died from metastatic colorectal cancer. Apart from reporting a novel AIP mutation, this study does not only highlight the different clinical and histological features of the AIP mutated growth hormone producing pituitary neuroendocrine tumors but also confirms the poor responsiveness of dopamine agonists in AIP mutated acromegaly. Furthermore, it highlights the increased mortality risk of comorbidities typically associated with acromegaly.

Keywords: AIP; Acromegaly; Colorectal cancer; Familial; GH; Gene; Growth hormone; Mutation; Pituitary adenoma; Twins.

Publication types

  • Case Reports

MeSH terms

  • Acromegaly* / genetics
  • Acromegaly* / pathology
  • Adenoma* / pathology
  • Exons / genetics
  • Growth Hormone
  • Growth Hormone-Secreting Pituitary Adenoma* / genetics
  • Growth Hormone-Secreting Pituitary Adenoma* / pathology
  • Humans
  • Mutation
  • Neuroendocrine Tumors* / genetics
  • Pituitary Neoplasms* / pathology


  • aryl hydrocarbon receptor-interacting protein
  • Growth Hormone