Neurofibromatosis Type 1 with Concurrent Multiple Endocrine Disorders: Adenomatous Goiter, Primary Hyperparathyroidism, and Acromegaly

Abstract

We encountered a 70-year-old Japanese woman with neurofibromatosis type 1 (NF1) who had a history of pheochromocytoma and concurrently developed adenomatous goiter, primary hyperparathyroidism, and acromegaly. The patient had a somatotroph adenoma of the adenohypophysis that predisposed her to multinodular goiter. Three parathyroid tumors were detected by cervical ultrasonography and cervicothoracic computed tomography. Genetic analyses did not reveal genetic alterations (e.g. loss-of-function mutation) in the causative genes of endocrine tumors, including MEN1, RET, VHL, CDKN1B, and CDKN2C. The NF1 gene could not be analyzed genetically due to the patient's refusal. The pathophysiologic mechanisms of endocrinopathy concurrence in NF1 remain to be elucidated.

Keywords: acromegaly; adenomatous goiter; neurofibromatosis type 1; primary hyperparathyroidism.

Figure 1.

Skin lesions and facial features characteristic of neurofibromatosis type 1 and acromegaly. (a) Innumerable, tender neurofibromas of about 1 cm in diameter in the abdomen, with a surgical scar resulting from adrenalectomy. (b) Café-au-lait spots on the dorsal aspect of the right forearm. (c) Characteristics of neurofibromatosis (freckles around the eyelids and lips) as well as the characteristics of acromegaly (protruding mandibles and eyebrows, and a swollen nose and lips).

Figure 2.

Cervical ultrasonography. (a) A cyst 2 cm in diameter in the right thyroid lobe (arrow). (b) A solid nodule 9 mm in diameter in the right thyroid lobe (arrow). (c) A solid nodule 7 mm in diameter in the left thyroid lobe (arrow). (d) A solid nodule 15 mm in diameter in the lower pole of the left lobe of the thyroid glands (arrow).

Figure 3.

Cervical computed tomography. (a) Axial tomography image showing a tumor 15 mm in diameter on the dorsal aspect of the lower pole of the left thyroid gland (arrow). (b and c) Axial and coronal images showing a tumor 10 mm in diameter on the left side of the upper mediastinum (arrows). (d) Coronal tomography image showing a tumor 12 mm in diameter at the upper border of the aortic arch (arrow).

Figure 4.

T1-weighted magnetic resonance imaging of the pituitary gland in the intermediate phase of gadolinium enhancement. A coronal magnetic resonance image showing a tumor 10.9×6.7 mm in size at the adenohypophysis adjacent to the right internal carotid artery (arrow).

Figure 5.

¹²³I-metaiodobenzylguanidine scintigraphy. Scintigrams of the whole body showing no abnormal accumulation of the radioisotope in the cervix or abdomen, indicating the development of neither recurrent pheochromocytoma nor paraganglioma.

Figure 6.

Histological and immunohistochemical staining of a somatotroph adenoma of the adenohypophysis. (a) Hematoxylin and Eosin staining showing an eosinophilic adenoma. (b) Immunoreactive growth hormone is diffusely stained in the cell body. (c) CAM5.2 staining showing that perinuclear patterns are more predominant than intracytoplasmic dot patterns. (d) Ki-67-positive cells are scarce, with an MIB-1 index of 0.2%.