A work-up for multiple endocrine adenomatosis type I was negative with normal serum Ca., PTH, T4 and calcitonin levels. The patient was treated with Cimetidine and Probanthin and was doing relatively well for one year. Two years prior to the current admission, ascites and left pleural effusion developed and he was started on chemotherapy including Streptozocin, Adriamycin and 5FU.
Three months prior to presentation, an epidural injection of steroids was performed because of lumbar radiculopathy.
The familial history revealed that the father and one brother died of prostate carcinoma. The acid phosphatase was 7.8 IU/L (nl 0-5.4 IU/L) and the prostatic fraction 0.7 (0-1.2 IU/L). The alkaline phosphatase was 561 IU/L (nl 21-130 IU/L) and the serum gastrin level greater than 1,000 pg/ml (nl 0-100 pg/ml).
The patient presented with persisting low back pain and irradiation to the left calf.
Bone scintigraphy done to evaluate persisting low back pain showed multiple focal lesions. Lumbar spine X-rays (AP, Lat, and spot view of L5-S1), show sclerosis of the L5 vertebral body corresponding to one of the intense lesions on bone scintigraphy. The iliac lesion seen on the bone scan was biopsied and revealed a histology compatible with the primary pancreatic tumor.
The cardinal features include:
Seventy-five percent of the patients have ulcers localized in the first portion of the duodenum or in the stomach. The ulcer symptoms are fulminant, progressive and persistent and respond poorly to medical and surgical peptic ulcers treatment. Prompt recurrence of ulcer after usual peptic surgery is characteristic of gastrinoma.
The non-beta islet cell tumors are principally localized within the pancreas (90%) and may be single or multiple. Five percent of the gastrinomas are found in the proximal duodenum, and the remainder in hilum of the spleen and in the stomach. Sixty percent of the gastrinomas become malignant and 50-60% have metastases. They are more commonly found in the region lymphnodes and in the liver. Distant metastases are rare but may be found on peritoneal surfaces, in the mediastinum, the skin, the spleen and the bones. Bone metastases are very rare and have only been reported once in the literature (Pederson RT, et al). The radiographic findings were consistent with osteoblastic lesions and were described in the lumbar spine, the iliac bone, the femur and the humerus. A concomitant bone scan revealed multiple areas of increased uptake involving the same regions. The biopsy was also compatible with the primary pancreatic tumor.
Cecchetin and associates (3) found elevated levels of PTH and calcitonin in association to high levels of gastrin. They postulated that increased gastrin stimulates calcitonin secretion, resulting in decreased serum calcium level and calcium, but also in stimulating bone formation. Alkaline phosphatase detected in cytochemical assays increase rapidly, within three minutes, in the bone in vitro after exposure to PTH. Alkaline phosphatase activity in serum is a composite of enzymes from multiple sources. In the adult, most comes from he liver and the bone with lesser contributions from intestine and other tissues. The osteoblast is considered to be a major skeletal source of circulating alkaline phosphatase activity, but this enzyme is also prominent in chondrocytes and matrix vesicles of bone.
Zollinger-Ellison syndrome occurs in approximately 50% of the patients with multiple endocrine adenomatosis (M.E.A.) Type I. This syndrome includes hyperplasia and/or tumors of the parathyroids, pancreatic islets and pituitary. In addition, thyroid nodules, carcinoid tumors and hyperplasia of the adrenal cortex have often been described in family members.
The diagnosis of Zollinger-Ellison syndrome is made on the demonstration of high serum gastrin levels. Fasting gastrin levels in normals and in patients with ordinary duodenal ulcer average approximately 60 pg/ml. Patients with gastrinoma almost always have levels greater than 150 pg/ml and not uncommonly greater than 1,000 pg/ml. The diagnosis is also suspected on the clinical history, marked acid hypersecretion, prominence of mucosal folds in the stomach, duodenum and sometimes jejunum or SR. It may be confirmed by several provocative tests involving measurement of serum gastrin levels in response to calcium infusion, secretin injection or a standard test meal.
The treatment may include total gastrectomy and removal of the tumors where possible, in order to relieve the symptoms due to gastric hypersecretion. H2 receptor antagonist Cimetidin has been widely used and many patients have responded sufficiently well as to not require surgery. The dose is 1.5 to 2 times that used in the treatment of common duodenal ulcer: 200 to 300 mg 4 times daily. Streptozocin is usually restricted to patients who have malignant gastrinomas with proven metastases.
The prognosis is a function of the severity of the ulcer disease. Death is usually not due to the malignant invasion of the tumor, but rather to the excess gastrin, producing marked acid secretion and fulminant ulcer disease.
2) Zollinger RM. Islet cell tumor and the alimentary tract. Am. J. Roentg. 1976; 126(5):933-940.
3) Cecchetin M, Albertini A, et al. Calcitonin, parathyroid hormone and insulin concentrations in sera from patients with gastrinoma. In Gastrointestinal Hormones and Pathology of the Digestive System. Grossman M, Speranza V, et al (editors), New York, Plenum Press, 1978, p. 117.
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