A 42-year-old man was hospitalized with symptoms of nausea, vomiting and diarrhea for more than one year. The patient, presenting with decreased vision, diminished interest in sex, fatigue, weakness and polyuria, was diagnosed with pituitary adenoma in 1998. His blood prolactin level was high (more than 200 ng/mL, reference range, 2-23 ng/mL). The patient underwent removal of the tumor via the trans-sphenoidal approach in February 1998. Histological examination of the surgical specimen showed a chromophore cell adenoma. The patient’s family history was notable for his brother also having a pituitary adenoma. In 2009, the patient underwent surgical procedures to remove a kidney stone. Recently, the patient had diarrhea, nausea and vomiting lasting for more than one year while gastroscopy and colonoscopy were performed prior to admission. Gastroscopy showed reflux esophagitis, esophageal protrusive lesion, gastric polyp and duodenal ulcer. Colonoscopy was normal. The patient was admitted on March 18, 2012. Physical examination revealed hypopigmentation of skin, sparse hair with normal blood pressure, body temperature, breath sounds and heart rhythms. The abdomen was prominently tender with normal bowel sounds and there was no shifting dullness found on the mass. Rectal examination was normal. Laboratory tests showed the following data: leukocytosis (22.40 × 109), mildly low hemoglobin level (115 g/L), elevated serum calcium (3.05 mmol/L, reference range, 2.1-2.55 mmol/L), low phosphorus level (0.57 μmol/L, reference range, 0.81-1.45 μmol/L), extremely high level of parathyroid hormone (PTH) (627 pg/mL, reference range, 15-65 pg/mL). Serum magnesium, calcitonin, electrolytes, glucose, liver and renal function were normal. Computed tomography (CT) scan of the chest revealed mediastinal emphysema with hypostasis in the inferior lobe of the lung (Figure ). Epigastric CT scan showed accumulation of gas and fluid in the anterior pararenal space just adjacent to the thickened wall of horizontal duodenum as well as accumulation of gas in the right perirenal space, which implied the possibility of duodenal perforation. CT imaging also found renal and hepatic cysts (Figure ). The patient complained of melena two days after admission and the complete blood count showed medium anemia (hemoglobin 86 g/L) and positive stool occult blood (OB). Emergency gastroscopy was performed and revealed chronic superficial gastritis with erosion, reflux esophagitis LA grade C and multiple deep ulcers in the descending part of the duodenum (Figure ). Pathological analysis showed chronic inflammation of duodenal mucosa. CT scan of the small intestine showed bowel wall thickening and strong enhancement of the horizontal part of the duodenum. A nodular mass with rich blood supply in the uncinate process and tail of pancreas led to a diagnosis highly suspicious for Zollinger-Ellison syndrome (ZES), and an adenoma on the left adrenal gland and multiple liver cysts were also found in this CT image (Figure ). Magnetic resonance imaging (MRI) of the pituitary showed no space-occupying lesion in the sellar region (Figure ). PTH was re-examined and the result was 401 pg/mL, which was still significantly higher than the normal value. Laboratory tests also revealed elevated serum gastrin (342.27 pg/mL, reference range, 0-108 pg/mL), elevated prolactin (127.50 ng/mL, reference range, 4.97-23.3 ng/mL) and low testosterone level (0.19 ng/mL, reference range, 2.8-8 ng/mL). Serum progesterone, follicle-stimulating hormone (FSH), luteotropic hormone, estradiol, cortisol, adrenocorticotropic hormone (ACTH), aldosterone and thyroid hormones were normal. CT scan of the thyroid gland showed a mild nodular goiter with nodules posterior and lateral to the thyroid gland, which might originate from an enlargement of the parathyroid glands (Figure ). A radioisotope scan revealed soft tissue masses posterior to the thyroid gland and abnormal uptake of 99mTc-MIBI, considered to be parathyroid adenoma or hyperplasia (Figure ). The patient was diagnosed with MEN1 presenting as hyperparathyroidism, gastrinoma and prolactinoma. He underwent subtotal parathyroidectomy and autotransplantation on April 9, 2012. The pathology of all parathyroid glands was consistent with chief cell hyperplasia with immunohistochemical expression of CK19, CK8, CgA, Syn and NSE and negative expression of TTF-1, TG and Ki67 (Figure ). After operation, the levels of serum calcium and PTH fell to normal. The patient had no evidence of metastatic disease on preoperative studies. With the pancreatic endocrine tumors being well-located in the CT image, pylorus-preserving pancreaticoduodenectomy and pancreatic tail resection were performed on April 24, 2012 for removing gastrinoma and cure of ZES. Pathological analysis showed that tumor cells had an acidophilic cytoplasm and round nucleoli which were uniform in size and shape, arranging in tubular, organoid and gyriform patterns (Figure ). The pathological diagnosis was a well-differentiated neuroendocrine tumor, infiltrating the muscular layer of the duodenal bowel wall, with no blood vessels and nerves involved and a well-differentiated neuroendocrine tumor also formed in the tail of pancreas, with immunohistochemical expression of NSE, Syn, CK8, CgA and α-AT, weakly positive expression of CK, CD56, Vim, CK19 and Ki67, and negative expression of 5-HT, insulin and ACTH. Pathologic examination of three lymph nodes near the duodenum and the head of pancreas showed chronic lymphadenitis. The post-operative level of serum gastrin was 39.34 pg/mL, and was returning to normal. The patient was discharged two weeks after the successful surgical resection of the tumor and is currently doing well but requires careful follow-up.
Figure 1 Computed tomography scan of the case. A: Chest Computed tomography (CT) shows a mediastinal emphysema (arrows); B: Epigastric CT shows accumulation of gas and fluid (arrows) in the anterior pararenal space just adjacent to the thickened wall of the horizontal (more ...)
Gastroscopy reveals reflux esophagitis LA grade C and multiple deep ulcers in the descending part of duodenum, arrows indicate the erosion and ulcer respectively.
Pituitary Magnetic resonance imaging shows no space-occupying lesion in the sellar region (arrow).
Radio-isotope scan reveals soft tissue masses (arrows) posterior to the thyroid gland which displayed abnormal uptake of 99mTc-MIBI.
Figure 5 Histological and Pathological analysis of the case (hematoxylin and eosin staining, × 100). A: Histological analysis shows chief cell hyperplasia of parathyroid gland; B: Pathological analysis shows that tumor cells had acidophilic cytoplasm and (more ...)