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

Research output: Contribution to journalArticle

Abstract

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
Volume66
Issue number10
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Growth Hormone-Secreting Pituitary Adenoma
Neurofibromatosis 1
Acromegaly
Neurofibromatosis 1 Genes
Follicular Adenocarcinoma
Multiple Endocrine Neoplasia Type 1
Pituitary Neoplasms
Growth Hormone
Acidophil Adenoma
Exons
Neoplasms
Thyroid Gland
Leukocytes
Optic Nerve Glioma
Parathyroid Neoplasms
Mutation
Peroxisome Proliferator-Activated Receptors
Primary Hyperparathyroidism
Germ-Line Mutation
Nonsense Codon

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Acromegaly caused by a somatotroph adenoma in patient with neurofibromatosis type 1. / Hozumi, Kaori; Fukuoka, Hidenori; Odake, Yukiko; Takeuchi, Takehito; Uehara, Tomoko; Sato, Takeshi; Inoshita, Naoko; Yoshida, Kenichi; Matsumoto, Ryusaku; Bando, Hironori; Hirota, Yushi; Iguchi, Genzo; Taniguchi, Masaaki; Otsuki, Naoki; Nishigori, Chikako; Kosaki, Kenjiro; Hasegawa, Tomonobu; Ogawa, Wataru; Takahashi, Yutaka.

In: Endocrine journal, Vol. 66, No. 10, 01.01.2019, p. 853-857.

Research output: Contribution to journalArticle

Hozumi, K, Fukuoka, H, Odake, Y, Takeuchi, T, Uehara, T, Sato, T, Inoshita, N, Yoshida, K, Matsumoto, R, Bando, H, Hirota, Y, Iguchi, G, Taniguchi, M, Otsuki, N, Nishigori, C, Kosaki, K, Hasegawa, T, Ogawa, W & Takahashi, Y 2019, 'Acromegaly caused by a somatotroph adenoma in patient with neurofibromatosis type 1', Endocrine journal, vol. 66, no. 10, pp. 853-857. https://doi.org/10.1507/endocrj.EJ19-0035
Hozumi, Kaori ; Fukuoka, Hidenori ; Odake, Yukiko ; Takeuchi, Takehito ; Uehara, Tomoko ; Sato, Takeshi ; Inoshita, Naoko ; Yoshida, Kenichi ; Matsumoto, Ryusaku ; Bando, Hironori ; Hirota, Yushi ; Iguchi, Genzo ; Taniguchi, Masaaki ; Otsuki, Naoki ; Nishigori, Chikako ; Kosaki, Kenjiro ; Hasegawa, Tomonobu ; Ogawa, Wataru ; Takahashi, Yutaka. / Acromegaly caused by a somatotroph adenoma in patient with neurofibromatosis type 1. In: Endocrine journal. 2019 ; Vol. 66, No. 10. pp. 853-857.
@article{e0e62cc597d540a4a8e458494b5dbe99,
title = "Acromegaly caused by a somatotroph adenoma in patient with neurofibromatosis type 1",
abstract = "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.",
keywords = "Acromegaly, NF1, Primary hyperparathyroidism, Somatotroph adenoma, Thyroid follicular carcinoma",
author = "Kaori Hozumi and Hidenori Fukuoka and Yukiko Odake and Takehito Takeuchi and Tomoko Uehara and Takeshi Sato and Naoko Inoshita and Kenichi Yoshida and Ryusaku Matsumoto and Hironori Bando and Yushi Hirota and Genzo Iguchi and Masaaki Taniguchi and Naoki Otsuki and Chikako Nishigori and Kenjiro Kosaki and Tomonobu Hasegawa and Wataru Ogawa and Yutaka Takahashi",
year = "2019",
month = "1",
day = "1",
doi = "10.1507/endocrj.EJ19-0035",
language = "English",
volume = "66",
pages = "853--857",
journal = "Endocrine Journal",
issn = "0918-8959",
publisher = "Japan Endocrine Society",
number = "10",

}

TY - JOUR

T1 - Acromegaly caused by a somatotroph adenoma in patient with neurofibromatosis type 1

AU - Hozumi, Kaori

AU - Fukuoka, Hidenori

AU - Odake, Yukiko

AU - Takeuchi, Takehito

AU - Uehara, Tomoko

AU - Sato, Takeshi

AU - Inoshita, Naoko

AU - Yoshida, Kenichi

AU - Matsumoto, Ryusaku

AU - Bando, Hironori

AU - Hirota, Yushi

AU - Iguchi, Genzo

AU - Taniguchi, Masaaki

AU - Otsuki, Naoki

AU - Nishigori, Chikako

AU - Kosaki, Kenjiro

AU - Hasegawa, Tomonobu

AU - Ogawa, Wataru

AU - Takahashi, Yutaka

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Acromegaly

KW - NF1

KW - Primary hyperparathyroidism

KW - Somatotroph adenoma

KW - Thyroid follicular carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85074184973&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074184973&partnerID=8YFLogxK

U2 - 10.1507/endocrj.EJ19-0035

DO - 10.1507/endocrj.EJ19-0035

M3 - Article

C2 - 31189769

AN - SCOPUS:85074184973

VL - 66

SP - 853

EP - 857

JO - Endocrine Journal

JF - Endocrine Journal

SN - 0918-8959

IS - 10

ER -