Genotype-negative multiple endocrine neoplasia type 1 with prolactinoma, hyperparathyroidism, and subclinical Cushing's syndrome accompanied by hyperglycemia: a case report

Abstract

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder, accompanied by multiple endocrine neoplasms of the parathyroid, pancreas, pituitary, and other neoplasms in the adrenal glands. However, in some cases, patients clinically diagnosed with MEN1 may be genotype-negative.

Case presentation: A 56-year-old female was diagnosed with MEN1 based on a macroprolactinoma (19 mm in diameter), primary hyperparathyroidism, and a cortisol-producing adrenal adenoma, without a family history. At first appearance, she had a hemoglobin A1c of 12.0% and a fasting plasma glucose level of 16.3 mmol/L (294 mg/dL). She complained of headaches and had a history of prolactinoma at 28 years of age, with concomitant elevated prolactin 1102.0 μg/L (ng/mL). Insulin therapy was initiated for glucose management following the administration of an oral hypoglycemic agent. Additionally, cabergoline was initiated for due to the prolactinoma, resulting in a normalized prolactin level. Thereafter, medication for diabetes could be withdrawn. Subsequently, surgery was performed for primary hyperparathyroidism and the cortisol-producing adrenal adenoma, which was consistent with the preoperative diagnosis. Additionally, a thyroid tumor resected with primary hyperparathyroidism revealed to be invasive papillary thyroid carcinoma (PTC). Target gene testing revealed a negative genotype for MEN1 gene, with only one common polymorphism that was non-pathogenic.

Conclusions: Genotype-negative MEN1 typically has a favorable clinical course without a third primary MEN1 manifestation. However, the present case had a symptomatic macroprolactinoma with an apparent elevated glucose level and three manifestations of tumors (pituitary, parathyroid, and adrenal) with invasive PTC, and a delayed diagnosis could have caused crucial deterioration. Clinicians should pay attention to the clinical features of MEN1 including glucose intolerance. In such cases, the treatment of endocrine disorders can lead to the normalization of the glucose level.

Keywords: hyperglycemia; multiple endocrine neoplasia type 1; primary hyperparathyroidism; prolactinoma; subclinical Cushing’s syndrome.

Figure 1

Clinical images. (A) A pituitary image on MRI. (B) A thyroid isthmus image on CT. (C) Early- and (D) late-phase of ^99mTc-MIBI. (E) The left adrenal tumor on CT. All tumors are highlighted with a white arrow in each image. MRI, Magnetic Resonance Imaging; CT, computed tomography; MIBI, methoxyisobutylisonitrile.

Figure 2

Clinical time-course. Time course of medication and laboratory data (prolactin, HbA1c, IRI, FPG) are shown. HbA1c, hemoglobin A1c; IRI, immunoreactive insulin; FPG, fasting plasma glucose.

Figure 3

Pathological images. (A) A low-power and (B) high-power field image of parathyroid specimen removed as left lower parathyroid tumor. Histopathologically, dominant chief cells with oxyphil cells with relatively minimal changes of cytoplasmic fat within cells, consistent with parathyroid adenoma or hyperplasia. (C) A macroscopic image of the removed left adrenal gland. The tumor consists of dominant brown area with interspace yellow areas. (D) Histopathological features of the adrenocortical adenoma. Tumor cells harboring eosinophilic cytoplasm with lipofuscin were intermingled with those clear cytoplasm (Hematoxylin and eosin stain). (E) Histopathological features of adenoma: Lipomatous change with intratumoral lymphocytes infiltration was detected in the tumor tissue (Hematoxylin and eosin stain). (F) Immunohistochemistry of c17. Marked immunoreactivity of c17 in tumor cells in the same area as illustrated in (E). (G) Histopathological features of non neoplastic attached adrenal gland. Moderate degree of cortical atrophy of zona fasciculata and reticularis was detected (Hematoxylin and eosin stain). (H) Immunohistochemistry of DHEA-ST in non neoplastic attached adrenal gland in the same area as (G). DHEA-ST immunoreactivity was not detected in the zona reticularis, indicating the long-term suppression of hypothalamus-pituitary axis of the patient prior to surgery. All the specimen were diagnosed and confirmed by the board certificated pathologists.