Treatment of Zollinger-Ellison syndrome

In this article, we have reviewed the main therapeutic measures for the treatment of Zollinger-Ellison syndrome (ZES). Review of the literature was based on computer searches (Pub-Med, Index Medicus) and personal experiences. We have evaluated all the measures now available for treating patients with sporadic gastrinomas or gastrinomas associated with Multiple Endocrine Neoplasia Type 1, (MEN 1) including medical therapy such as antisecretory drugs and somatostatin analogs (SST), chemotherapy and chemoembolization, and surgical procedures. In ZES patients, the best therapeutic procedure is surgery which, if radical, can be curative. Medical treatment can be the best palliative therapy and should be used, when possible, in association with surgery, in a multimodal therapeutic approach.     

Very low or undetectable intact parathyroid hormone levels in patients with surgically verified parathyroid adenomas

Objectives To report and explore potential reasons for undetectable or low‐normal serum intact PTH levels in patients with surgically verified primary hyperparathyroidism with parathyroid adenomas, review the relevant literature, and offer suggestions for management of such patients occasionally encountered in clinical practice. For future research, to help understand mechanisms underlying ‘undetectable’ or inappropriately low serum intact PTH levels. Methods Serum intact PTH levels were measured pre‐ and postoperatively by immunochemiluminescent assay (ICMA) and the results were confirmed by at least two repeated measurements on different occasions in each patient. Patients We encountered two unusual patients with primary hyperparathyroidism who had suggestive biochemical and/or clinical features of primary hyperparathyroidism. However, serum intact PTH levels were either very low or undetectable in the context of hypercalcaemia, with no other obvious cause. A ^99mTc sestamibi scan showed increased uptake in one of the parathyroid glands, suggesting a single adenoma in each case that was confirmed at surgery. Results In the first patient, from India, mean ± SD serum calcium was 2·6 ± 0·32 mmol/l (reference range 2·12–2·74 mmol/l) with intact PTH of 0·11 pmol/l (reference range 1·1–7·59 pmol/l). In the second patient, from the USA, mean ± SD serum calcium and intact PTH were 2·9 ± 0·07 mmol/l (reference range 2·17–2·51 mmol/l) and 1·35 pmol/l (reference range 1·1–7·59 pmol/l), respectively. Following curative parathyroidectomy, serum calcium levels normalized in both patients. By contrast, serum intact PTH levels, which were either suppressed or very low before surgery, rose into the low‐normal reference range in all patients. Conclusions When the clinical suspicion is high, the diagnosis of primary hyperparathyroidism should be pursued despite suppressed or low‐normal serum intact PTH levels after carefully excluding other causes of hypercalcaemia. Further research on various intact PTH molecular species secreted by parathyroid adenomas or post‐translational changes in the intact PTH molecule that might interfere with in vitro measurements should be undertaken to understand the precise reason(s) for such anomalous findings.     

Peroperative echography in 14 cases of pancreatic insulinoma and gastrinoma

Fourteen cases of endocrine tumors (10 insulinomas and 4 gastrinomas) were to studied by intraoperative ultrasonography (IOU). Localization was established by preoperative ultrasonography in 1/14, by CT scan in 1/11, by arteriography in 6/12 and by pancreatic venous sampling in 7/8. Tumor size ranged from 0.5 cm to 2.5 cm. Manual palpation was positive in 10/14. The tumor was accurately and completely localized by IOU in 9/10 insulinomas: the one false negative was probably due to micro-adenoma. The intrapancreatic tumor was localized only in 1/14 gastrinomas. Intraoperative sonography localized lymph nodes in all cases. One distal pancreatectomy was improperly performed because of an accessory spleen. After reviewing 59 other cases in the literature, we propose: a) to abandon venous sampling in insulinomas because of adequate performance of IOU; b) to use IOU as a complementary investigative method along with other preoperative methods of localization in gastrinoma.     

Usefulness of selective arterial calcium injection test and secretin test in patients with insulinoma

Preoperatively, it is sometimes very difficult to localize pancreatic endocrine tumors by conventional imaging techniques. Insulinoma is often solitary and benign, but 10% of insulinomas are multiple and malignant. To perform a curative resection of insulinomas, it is important not to leave any tumor postoperatively. In patients with gastrinomas, the selective arterial secretin injection test has been demonstrated to be useful for the curative resection of gastrinomas, since this test tells us whether there is a gastrinoma in the area of interest. The principle of this test is based on the observation that gastrinomas promptly release gastrin when stimulated by secretin. Following a principle analogous to that underlying the secretin test, we have used calcium solution as a stimulant for insulinoma. This selective arterial calcium injection (SACI) test has been used in Kyoto and in National Institute in Health, Bethesda, USA, NIH since 1990. In three patients with insulinoma, curative resection was performed successfully, based on localization by the SACI test. For the differential diagnosis of insulinoma and B cell hyperplasia, we used the intravenous secretin test in 14 patients who had had episodes of hypoglycemia; the test was useful, showing 75% sensitivity and 100% specificity.     

Immunocytochemical staining for islet amyloid polypeptide in pancreatic endocrine tumors

Aims/hypothesis: Islet amyloid polypeptide is originally identified as the chief constituent of amyloid in insulinomas and type 2 diabetic islets. This study aimed to identify islet amyloid polypeptide by immunocytochemical staining in pancreatic endocrine tumors including 30 cases of insulinomas and non-β-cell pancreatic endocrine tumors.

Results: In normal islets, 62% of islet cells and 52% of insulin cells were granularly positive for insulin and IAPP, respectively, with more insulin positive cells than IAPP positive cells and some densely positive staining for insulin and IAPP in irregularly shaped a nuclear, degenerating islet β-cells. In pancreatic endocrine tumors, all 10 insulinomas were positive for islet amyloid polypeptide but 2 glucogonomas, 1 somatostatinoma, 6 of 7 pancreatic polypeptidomas, all 7 gastrinomas and all 3 non-functioning pancreatic endocrine tumors were negative for islet amyloid polypeptide whereas one pancreatic polypeptidoma was positive for islet amyloid polypeptide.

Methods: Using commercially available rabbit anti-islet amyloid polypeptide antibody, immunocytochemical staining was performed on 30 cases of pancreatic endocrine tumors, consisting of 10 insulinomas, 2 glucagonomas, 1 somatostatinoma, 7 pancreatic polypeptidomas, 7 gastrinomas and 3 non-functioning pancreatic endocrine tumors. Pancreatic tissues containing pancreatic endocrine tumors were systematically immunostained for insulin, glucagon, somatostatin, pancreatic polypeptide, gastrin and chromogranin A, in addition to islet amyloid polypeptide. When normal pancreatic tissues adjacent to pancreatic endocrine tumors were present, insulin, glucagon, somatostatin and islet amyloid polypeptide positive cells were counted for a total of 20 islets, which were divided into large islets and medium islets for each case.

Conclusions/Interpretations: All 10 insulinomas and 1 pancreatic polypeptidoma were granularly positive for islet amyloid polypeptide, suggesting all 10 insulinomas contained enough insulin granules for IAPP whereas only one non-β-cell pancreatic endocrine tumor was co-localized with islet amyloid polypeptide in their secretary granules.     

Immunocytochemical staining for islet amyloid polypeptide in pancreatic endocrine tumors

Aims/hypothesis: Islet amyloid polypeptide is originally identified as the chief constituent of amyloid in insulinomas and type 2 diabetic islets. This study aimed to identify islet amyloid polypeptide by immunocytochemical staining in pancreatic endocrine tumors including 30 cases of insulinomas and non-β-cell pancreatic endocrine tumors. Results: In normal islets, 62% of islet cells and 52% of insulin cells were granularly positive for insulin and IAPP, respectively, with more insulin positive cells than IAPP positive cells and some densely positive staining for insulin and IAPP in irregularly shaped a nuclear, degenerating islet β-cells. In pancreatic endocrine tumors, all 10 insulinomas were positive for islet amyloid polypeptide but 2 glucogonomas, 1 somatostatinoma, 6 of 7 pancreatic polypeptidomas, all 7 gastrinomas and all 3 non-functioning pancreatic endocrine tumors were negative for islet amyloid polypeptide whereas one pancreatic polypeptidoma was positive for islet amyloid polypeptide. Methods: Using commercially available rabbit anti-islet amyloid polypeptide antibody, immunocytochemical staining was performed on 30 cases of pancreatic endocrine tumors, consisting of 10 insulinomas, 2 glucagonomas, 1 somatostatinoma, 7 pancreatic polypeptidomas, 7 gastrinomas and 3 non-functioning pancreatic endocrine tumors. Pancreatic tissues containing pancreatic endocrine tumors were systematically immunostained for insulin, glucagon, somatostatin, pancreatic polypeptide, gastrin and chromogranin A, in addition to islet amyloid polypeptide. When normal pancreatic tissues adjacent to pancreatic endocrine tumors were present, insulin, glucagon, somatostatin and islet amyloid polypeptide positive cells were counted for a total of 20 islets, which were divided into large islets and medium islets for each case. Conclusions/Interpretations: All 10 insulinomas and 1 pancreatic polypeptidoma were granularly positive for islet amyloid polypeptide, suggesting all 10 insulinomas contained enough insulin granules for IAPP whereas only one non-β-cell pancreatic endocrine tumor was co-localized with islet amyloid polypeptide in their secretary granules.     

Value of endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localization of insulinomas and gastrinomas. Experience of 54 cases

AIM: The classic morphological techniques for the localization of insulinomas and gastrinomas are of limited value. Endoscopic ultrasonography and somatostatin receptor scintigraphy have shown high sensitivity for the detection of gastroenteropancreatic endocrine tumors. The aim of the study was to evaluate the sensitivity of endoscopic ultrasonography and that of somatostatin receptor scintigraphy in the localization of insulinomas and gastrinomas.PATIENTS AND METHODS: This retrospective study concerned 54 patients with insulinoma (n=29) or gastrinoma (n=26) operated on between March 1991 and March 2000 and who had at least one among the two tested examinations. Forty-two patients had scintigraphy (17 with insulinoma, 25 with gastrinoma), 47 had endoscopic ultrasonography (28 with insulinoma, 17 with gastrinoma). One of the ten patients with MEN 1 had both tumors. All diagnosis were confirmed by histologic examination.RESULTS: The sensitivity of scintigraphy for the localization of insulinomas was 47%. There was one false positive. Sensitivity of endoscopic ultrasonography for insulinomas was 85%. The sensitivity of scintigraphy in the detection of gastrinomas was 65% for the tumors in the duodenopancreatic area, 20% for the tumors in the pancreatic tail and 71% for metastasis. The sensitivity of endoscopic ultrasonography was 46% for duodenal tumors, 75% for pancreatic tumors and 57% for lymph node metastasis. The combination of both localization studies increased sensitivity to 94%.CONCLUSION: Endoscopic ultrasonography and somatostatin receptor scintigraphy are the gold standard for localization of gastrinomas. Association of both examinations increases the sensitivity. Scintigraphy for the detection of insulinomas should be performed when endoscopic ultrasonography is negative.     

Immunocytochemical localization of prohormone convertase 1/3 and 2 in pancreatic islet cells and islet cell tumors

Peptide hormones are synthesized as bigger prohormones, which are processed posttranslationally into smaller active hormones. Proinsulin and proglucagon are processed into insulin and glucagon by prohormone convertase (PC) 1/3 and 2. The current study was performed to test a hypothesis that there may be some difference in immunoreactive PC levels between normal islet cells and islet cell tumors, as the latter contain more prohormones than the former. All islet cell tumors, including insulinomas, gastrinomas, glucagonomas, pancreatic polypeptide-omas (PP-omas), and nonfunctioning islet cell tumors, contain fewer PCs than normal islet cells. The smaller PC levels in islet cell tumors may be responsible for the higher levels of prohormones in islet cell tumors, and the smaller levels of PCs in islet cell tumors may be another distinguishing characteristic of islet cell tumors.     

Normal parathyroid hormone levels in a diabetic patient with parathyroid adenoma

Objective The incidence of diabetes mellitus in patients with primary hyperparathyroidism and, conversely, primary hyperparathyroidism in diabetic patients are approximately threefold higher than the respective expected prevalence in the general populace. The diagnosis is straightforward when the patient presents hypercalcemia and inappropriately elevated serum parathyroid hormone (PTH) levels. We report a case of parathyroid adenoma in a diabetic patient with persistent hypercalcemia and normal PTH levels. Patient A 50-year-old female patient who was referred to our outpatient clinic presented with persistent hypercalcemia (serum Ca levels between 10.5 and 11 mg/dl) with a normal serum intact PTH level of 46.1 pg/ml. Her blood pressure was 120/80 mmHg, and she was being treated with antihypertensive therapy. Her HbA1c was 7.2%, and her triglycerides were in the normal range. A bone densitometry exam revealed osteopenia of radius −1.39, femoral neck −1.39, and the total hip −1.04. A neck ultrasound revealed a mass of 13 mm next to the inferior and posterior of the right thyroid lobe. A dual phase Tc-99m-sestamibi scan revealed an area of increased uptake in the same region, which is indicative of a parathyroid adenoma. The parathyroid adenoma was removed, which resulted in the achievement of normocalcemia. Conclusion Diabetic patients should be evaluated for hyperparathyroidism as associated hypertension can complicate the course of the disease. These patients should be evaluated for primary hyperparathyroidism when they exhibit persistent hypercalcemia and when clinical suspicion is aroused even if the serum PTH levels are within the normal range.     

Endocrine tumors of the pancreas (EPTs) in multiple endocrine neoplasia (MEN1): up-date on prognostic factors, diagnostic procedures and treatment

Endocrine pancreatic tumors (EPTs) are uncommon tumors, representing 1-2% of all pancreatic neoplasms. They are categorized on the basis of their clinical features into functioning and non-functioning tumors. EPTs may be part of the multiple endocrine neoplasia type 1 (MEN 1), an autosomal dominant syndrome due to inactivating germline mutation of the menin gene. Somatic mutations of menin are present in about 20% of sporadic neoplasms, particularly gastrinomas and insulinomas. 30-75% of patients with MEN1 have EPTs. The most prevalent are the gastrinomas (20-60%), then the insulinomas (5-10%), the glucagonamas and VIPomas (6-10%), whereas the nonfunctioning EPTs are present in 20-40% of patients. The most important biochemical screening marker for EPTs is chromogranin A, as it increases in 50-80% of patients. The most important negative prognostic factors are the presence of metastases, the gross invasion of adjacent organs, the angioinvasion, the perineural invasion and an immunopositivity for Ki-67 > 2%. Among the different imaging techniques, echoendoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) are indicated for the detection of the primary tumor, but (III)In-octreotide scintigraphy has the highest sensitivity for detecting metastases. The choice of treatment is still debated and is different when the tumor occurs as a part of the MEN syndrome. The surgical treatment is the first choice for insulinomas and is more controversial for gastrinomas. The medical treatment includes somatostatin analogues (SA), chemotherapy and interferon-alpha (IFN-alpha). SA seem to improve the symptoms and have an antiproliferative effect, the most striking effect being seen in patients with VIPomas. Chemotherapy, which is generally proposed as a combination of streptozotocin (STZ) and 5-fluorouracil (5-FU) or doxorubicin, is indicated when the tumors tend to grow. Interferon-alpha (IFN-alpha) stimulates the immune system, blocks the tumor cells in the G1/S-phase of the cell cycle, inhibits protein and hormone synthesis and inhibits angionenesis. Treatment with IFN has been shown to produce symptomatic response in 40-60% of patients, a biochemical response in 30-60% and tumor shrinkage in 10-15%.     

Two-site assay of intact parathyroid hormone in the investigation of primary hyperparathyroidism and other disorders of calcium metabolism compared with a midregion assay

We compared the utility of measurements of serum intact human PTH-(1-84) and midregion human PTH-(44-68) in patients with disorders of extracellular calcium metabolism. Serum midregion PTH was determined by RIA, and serum intact PTH was measured by a sensitive and specific immunoradiometric two-site assay. The serum intact PTH concentrations in 70 patients with primary hyperparathyroidism were above the normal range in 69, and thus widely separated from the levels in 40 patients with hypercalcemia of malignancy, in whom serum intact PTH values were usually below normal. In contrast, both groups had overlapping serum midregion PTH values. In patients after renal transplantation and those with chronic renal failure, serum intact PTH levels were in the normal range twice as often as were serum midregion PTH values. The intact PTH assay was also superior in detecting venous gradients of the hormone and changes in PTH secretion caused by altered serum calcium concentrations, and serum intact PTH was remarkably low in hepatic venous effluent. We conclude that this new assay for serum intact PTH is superior to the midregion RIA in investigating parathyroid function in several different clinical conditions.     

Hysteresis in the relationship between serum ionized calcium and intact parathyroid hormone during recovery from induced hyper- and hypocalcemia in normal humans

We have used an immunoradiometric assay for intact PTH in conjunction with calcium and citrate infusions to study whether levels of intact PTH are responsive to reversal of the direction of change in ionized calcium in normal humans. Eleven normal subjects received graded infusions of citrate or calcium on separate days to produce linear rates of decrease or increase in calcium. After discontinuation of the infusions, the return of calcium toward baseline was followed. Six subjects were given an infusion of citrate after the calcium infusion to speed the recovery of calcium toward baseline. Citrate-induced hypocalcemia produced a rise in serum PTH levels from 28.1 +/- 3.6 to 69.4 +/- 4.8 ng/L as calcium fell from 1.26 +/- 0.01 to 1.06 +/- 0.02 mmol/L. As calcium returned toward baseline, PTH levels fell dramatically, reaching levels indistinguishable from baseline despite persistent hypocalcemia. Slopes of regression lines defining the PTH-calcium relationships during decreasing and increasing calcium levels were significantly different. Those subjects receiving a calcium infusion alone showed a prompt suppression of PTH levels. As calcium returned toward baseline after the infusion, a modest decline in calcium produced no significant change in the PTH-calcium relationship. When citrate was used to return calcium to baseline, PTH levels rose from 7.8 +/- 2.0 to 55.0 +/- 6.8 ng/L as calcium fell from 1.42 +/- 0.02 to 1.26 +/- 0.02 mmol/L and defined a regression relationship significantly different from the period of increasing calcium. Thus, a hysteretic relationship between ionized calcium and levels of intact PTH can be induced in normal humans by reversing the direction of change in calcium. Therefore, the role played by calcium concentration per se in controlling PTH secretion may be part of more complex and dynamic regulatory mechanisms.     

Les tumeurs endocrines du pancréas lors de la néoplasie endocrinienne multiple type 1 (NEM1): actualités sur les facteurs pronostiques,l'imagerie et le traitement

Endocrine pancreatic tumors (EPTs) are uncommon tumors, representing 1–2% of all pancreatic neoplasms. They are categorized on the basis of their clinical features into functioning and non-functioning tumors. EPTs may be part of the multiple endocrine neoplasia type 1 (MEN 1), an autosomal dominant syndrome due to inactivating germline mutation of the menin gene. Somatic mutations of menin are present in about 20% of sporadic neoplasms, particularly gastrinomas and insulinomas. 30–75% of patients with MEN1 have EPTs. The most prevalent are the gastrinomas (20–60%), then the insulinomas (5–10%), the glucagonamas and VIPomas (6–10%), whereas the nonfunctioning EPTs are present in 20–40% of patients. The most important biochemical screening marker for EPTs is chromogranin A, as it increases in 50–80% of patients. The most important negative prognostic factors are the presence of metastases, the gross invasion of adjacent organs, the angioinvasion, the perineural invasion and an immunopositivity for Ki-67 > 2%. Among the different imaging techniques, echoendoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) are indicated for the detection of the primary tumor, but ^IIIIn-octreotide scintigraphy has the highest sensitivity for detecting metastases. The choice of treatment is still debated and is different when the tumor occurs as a part of the MEN syndrome. The surgical treatment is the first choice for insulinomas and is more controversial for gastrinomas. The medical treatment includes somatostatin analogues (SA), chemotherapy and interferon-α (IFN-α). SA seem to improve the symptoms and have an antiproliferative effect, the most striking effect being seen in patients with VIPomas.Chemotherapy, which is generally proposed as a combination of streptozotocin (STZ) and 5-fluorouracil (5-FU) or doxorubicin, is indicated when the tumors tend to grow. Interferon-α (IFN-α) stimulates the immune system, blocks the tumor cells in the G1/S-phase of the cell cycle, inhibits protein and hormone synthesis and inhibits angionenesis. Treatment with IFN has been shown to produce symptomatic response in 40–60% of patients, a biochemical response in 30–60% and tumor shrinkage in 10–15%.     

Pentagastrin stimulation of calcitonin in pheochromocytoma does not always indicate multiple endocrine neoplasia type II

The diagnosis of pheochromocytoma in a 48-year-old man was confirmed by elevated catecholamine secretion and a left adrenal mass on computerized tomography. Because of a plausible family history for Multiple Endocrine Neoplasia Type II, a calcitonin level was determined which was elevated, and pentagastrin stimulation caused a 235% increase. These findings normalized following surgical removal of the single adrenal tumor. It is concluded that pentagastrin stimulation of calcitonin is not necessarily diagnostic of medullary thyroid carcinoma, and such a response in a patient presenting with pheochromocytoma may not indicate underlying Multiple Endocrine Neoplasia Type II.     

Primary hyperparathyroidism in a twin pregnancy and review of fetal/maternal calcium homeostasis

BACKGROUND: Hyperparathyroidism occurs rarely in pregnancy; this is the first reported case in a twin gestation. Management of this unusual case is described and an overview of fetal/maternal calcium homeostasis is discussed. METHODS: The patient presented at 33 weeks' gestation with hypertension and premature labor. Serum calcium and phosphorus were 14.6 and 1.7 mg/dL, respectively. An intact parathyroid hormone (PTH) level was 243 pg/mL (normal, 10-65). RESULTS: The patient was treated with parenteral saline hydration and oral phosphate supplementation that was continued through week 37. Although the calcium remained elevated between 12.6 and 13.3 mg/dL, medical therapy was continued because of the risks of surgery in the third trimester. Alternative medical treatments (bisphosphonates, calcitonin) were considered ill advised in pregnancy. The patient remained asymptomatic without further labor, and at week 37, fraternal twins were delivered by cesarean section. The infants were monitored closely and experienced no hypocalcemic symptoms after delivery. Postpartum, the mother's parathyroid scan and ultrasound were negative. She underwent neck exploration and a single 700-mg adenoma was removed. Transient asymptomatic hypocalcemia (7.5 mg/dL) occurred postoperatively, and she was placed on oral calcium (1500 mg/day) and calcitriol (0.25 mg/day). These were stopped at 8 weeks, when both PTH and parathyroid hormone-related peptide levels were normal. CONCLUSION: Mother and infants continue to do well after 18 months. This case provides an interesting setting to consider the interrelationships between elevated maternal PTH and the fetal/placental factors that regulate calcium metabolism in pregnancy.     

Antacid-induced osteomalacia: a case report with a histomorphometric analysis

The case of a 75-year-old woman with severe osteomalacia secondary to ingestion of large amounts of an aluminum-containing antacid is reported. Biochemical analysis revealed signs of phosphate malabsorption and increased levels of bone markers (S-alkaline phosphatase and U-hydroxyproline). A 99mTc-bone scan revealed multiple areas of increased uptake. The patient was normocalcaemic, with normal serum levels of intact parathyroid hormone and 25-hydroxyvitamin D. Serum 1,25-dihydroxyvitamin D was high normal. A transiliac bone biopsy from the patient showed severe osteomalacia. Symptoms, biochemical parameters, bone scan and bone morphology were all normalized 1 year after stoppage of antacid ingestion and treatment with vitamin D2. calcium phosphate and sodium fluoride because of severe osteopeni. The characteristics of this condition and the role of phosphate depletion and aluminum in the pathogenesis of bone lesions are discussed.     

Coexisting primary hyperparathyroidism and sarcoidosis in a patient with severe hypercalcemia

A 75-year-old woman was admitted to our hospital because of general fatigue. She had suffered from sarcoidosis during her 40s with remission, but subsequently she experienced progression of hypercalcemia and renal dysfunction for 7 years. On admission, she showed marked hypercalcemia (up to 15.5 mg/dl) and renal failure (serum creatinine 2.5 mg/dl). Plasma intact PTH level was elevated (up to 190 pg/ml), and thyroid ultrasonography and (99m) Tc-MIBI scintigraphy detected a parathyroid mass, which was surgically removed and histologically confirmed to be a parathyroid adenoma. However, even after surgery her serum calcium remained elevated, but subsequent administration of glucocorticoid for sarcoidosis completely normalized her hypercalcemia. The simultaneous occurrence of primary hyperparathyroidism and sarcoidosis is rare, and our data suggest that high plasma PTH and 1,25(OH)D exerted an additive effect on the occurrence of severe hypercalcemia.     

Effect of 22-oxacalcitriol on secondary hyperparathyroidism in hemodialysis patients

OBJECTIVE: A synthetic analogue of calcitriol, 22-oxacalcitriol (OCT), strongly suppresses parathyroid hormone (PTH) secretion. This study investigated the influence of OCT on PTH secretion and bone metabolism in 12 hemodialysis patients with secondary hyperparathyroidism. METHODS: OCT was intravenously injected after every hemodialysis session (three times weekly) for 22 weeks. The levels of the following parameters were measured: intact PTH, whole PTH, whole PTH/7-84 PTH ratio, adjusted calcium, phosphorus, alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), intact osteocalcin (OC), type I collagen carboxyterminal propeptide, tartrate-resistant acid phosphatase (TRAP), cross-linked C-terminal telopeptides of type I collagen, and interleukin-6. PATIENTS: The subjects were 12 hemodialysis patients (8 men and 4 women) with an intact PTH level of more than 460 pg/ml, a normal serum calcium level, and a serum phosphorus of less than 7 mg/dl. RESULTS: The levels of intact PTH, whole PTH, whole PTH/7-84 PTH ratio, ALP, BAP, OC, and TRAP were significantly decreased after OCT administration, while adjusted calcium was significantly increased. Serum phosphorus and the other parameters showed no significant changes. CONCLUSION: OCT effectively suppressed the PTH level and bone metabolism parameters in hemodialysis patients with secondary hyperparathyroidism.     

Ectopic growth hormone-releasing hormone secretion by thymic carcinoid tumour

The case of a 33-year-old-woman with Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome and acromegaly due to ectopic growth hormone-releasing hormone (GHRH) secretion by a thymic carcinoid tumour is reported. Immunohistochemistry revealed positive immunoreactivity for GHRH, vasoactive intestinal polypeptide, somatostatin and alpha-subunit in the tumour cells. A previously undescribed new germ line mutation of the MEN1 protein gene was revealed.