Acromegaly caused by a somatotroph adenoma in patient with neurofibromatosis type 1

Kaori Hozumi, Hidenori Fukuoka, Yukiko Odake, Takehito Takeuchi, Tomoko Uehara, Takeshi Sato, Naoko Inoshita, Kenichi Yoshida, Ryusaku Matsumoto, Hironori Bando, Yushi Hirota, Genzo Iguchi, Masaaki Taniguchi, Naoki Otsuki, Chikako Nishigori, Kenjiro Kosaki, Tomonobu Hasegawa, Wataru Ogawa, Yutaka Takahashi

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17 Citations (Scopus)


Although acromegaly has been reported in patients with Neurofibromatosis type 1 (NF1), these cases have not been associated with growth hormone (GH)-producing somatotroph adenoma, but with optic pathway glioma. A 68 year-old Japanese woman, who had been clinically diagnosed with NF1, was referred to our hospital due to a thyroid tumor and hypercalcemia. Acromegaly was suspected due to her facial features, and subsequent examinations revealed the presence of GH excess with a pituitary tumor, leading to the diagnosis of acromegaly. Histological and immunohistochemical analysis demonstrated an eosinophilic pituitary adenoma with diffuse positivity for GH, indicating typical somatotroph adenoma. In addition, her thyroid tumor was diagnosed histologically as follicular thyroid carcinoma (FTC) with primary hyperparathyroidism (PHPT). To investigate the pathogenesis of this untypical multiple endocrine tumor case of NF1, genetic analysis was performed using peripheral leukocytes and tissue of resected tumors. A heterozygous novel germline nonsense mutation (p.Arg1534*) in exon 35 of the NF1 gene was detected from peripheral leukocytes, which results in a truncated protein lacking the critical domain for GTPase activity, strongly suggesting its causal role in NF1. The loss of heterozygosity (LOH) in exon 35 of the NF1 gene was not detected in the somatotroph adenoma, parathyroid adenoma, and FTC. Although any mutations of the following genes; MEN1, CDKN1B, and PAX8-PPAR? were not detected, a heterozygous GNAS R201C mutation was detected in the somatotroph adenoma. To our knowledge, this is the first rare MEN1-like case of genetically diagnosed NF1 complicated with acromegaly caused by a somatotroph adenoma.

Original languageEnglish
Pages (from-to)853-857
Number of pages5
JournalEndocrine journal
Issue number10
Publication statusPublished - 2019


  • Acromegaly
  • NF1
  • Primary hyperparathyroidism
  • Somatotroph adenoma
  • Thyroid follicular carcinoma

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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