Somatostatin receptor scintigraphy in localization of pancreatic neuroendocrine tumors: A preliminary study.

Objective: To study the ability of somatostatin receptor scintigraphy using Tc-99m-hydrazinonicotinyl-Tyr3-octreotide (Tc-99m-HYNIC-TOC) for localization of pancreatic neuroendocrine tumors. Methods: Five patients (3 female, 2 male; age range: 53 to 80 years; mean age: 65 years) with either histologically proven or clinically suspected insulinoma were studied. Ten mCi of Tc-99m-HYNIC-TOC were intravenously injected. Whole body scans were obtained 2 and 4 hours after injection. SPECT/CT studies of areas of interest were performed after the 4-hour whole body image. Scintigraphic findings were correlated not only with the results of conventional imaging methods, including computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound but also through 1-year clinical follow-up. Results: The Tc-99m-HYNIC-TOC study showed true-negatives in two patients suspected of insulinoma proven by intraoperative ultrasound in one case and 1-year clinical follow-up with no evidence of hypoglycemia in the other patient. Abnormal Tc-99m-HYNIC-TOC accumulation was demonstrated in three patients with pancreatic tumors. Additional metastatic lesions to lung and bone were detected in one patient formerly diagnosed of malignant insulinoma with multiple liver metastases. Conclusion: Tc-99m-HYNIC-TOC SPECT/CT imaging may provide more accurate staging of pancreatic neuroendocrine tumors than conventional imaging. It is an optional technique to recruit patients for somatostatin analogs therapy.

Hypercalcemia of malignancy: a study of clinical features and relationships among circulating levels of calcium, parathyroid hormone and parathyroid hormone-related peptide.

OBJECTIVE: Examine the clinical and biochemical features including serum intact PTH (iPTH) and plasma PTH-related peptide (PTHrP) levels in patients with malignancy-associated hypercalcemia (MAHC). MATERIAL AND METHOD: Forty-eight patients with histopathological or cytological proven malignancies and MAHC who were admitted to Siriraj Hospital were studied. RESULTS: The malignancies that caused MAHC were squamous cell carcinoma (45.8%), non-squamous cell solid tumors (31.3 %), and hematological malignancies (22.9%). Most patients (93.8%) had advanced stage malignancies. Corrected serum total calcium (cTCa) levels were 10.8-19.1 mg/dL (13.6 +/- 2.4) and severe hypercalcemia was observed in 17 cases (40.5%). Serum iPTH levels were 0.95-17.1 pg/mL (3.9 +/- 3.6). Most patients had suppressed serum iPTH levels of < 10 pg/mL. Plasma PTHrP levels were 0.2-44.0 pmol/L (3.8 +/- 6.8). There were 27 cases (56.3%) that had humoral hypercalcemia of malignancy (HHM) with plasma PTHrP levels of > 1.5 pmol/L, and 22 cases had squamous cell carcinoma. There was no difference in serum cTCa, phosphorus, alkaline phosphatase, and iPTH levels between patients with HHM and non-HHM. In 48 MAHC patients, serum cTCa correlated to plasma PTHrP (r = 0.35, p = 0.029) and to serum iPTH (r = 0.49, p = 0.003). In 25 patients with HHM, a stronger correlation between serum cTCa and serum iPTH (r = 0.55, p = 0.005) but not between serum cTCa and plasma PTHrP levels (r = 0.41, p = 0.05) was observed. Stepwise multiple regression analyses showed that serum iPTH but not plasma PTHrP levels independently correlated to serum cTCa levels (r = 0.39, p = 0.04). CONCLUSION: The clinical manifestations of MAHC observed in the present study were similar to those previously reported. Serum calcium correlated to serum iPTH more strongly than to plasma PTHrP levels. The low but detectable serum iPTH level might play a role in the development of severe MAHC particularly in HHM.

Craniopharyngioma : A review of 14 cases at Siriraj Hospital.

Objective: 1) To characterize clinical presentations of craniophryngioma in the hypothalamic- pituitary region. 2) To examine both pre-treatment and post-treatment endocrine dysfunction of patients with craniopharyngioma. Methods: Medical records of patients with craniopharyngiomas from the Endocrine Division, Department of Medicine from 1997 to 2005 (9 years) were retrospectively reviewed. Data were expressed as mean+ SD (range) or percent as appropriate. Results: There were 14 cases (7 males and 7 females) with histological-proven diagnosis of craniopharyngioma. Their mean age was 32.3 + 13.0 years (15-56). The major distinguishing feature leading to diagnosis was visual field defects (85.7%), and a quarter of them were blind. Other distinguishing symptoms were headaches (78.6%), and menstrual disorders (28.6%). Pre-operative evaluations of their pituitary function revealed hypogonadotropic hypogonadism (55.6%), diabetes insipidus (DI) (42.9%), secondary adrenal insufficiency (18%) and elevated prolactin levels (36.4%) with a mean level of 36.1+39.2 ng/ml (12-138). All tumors were confirmed by pituitary CT or MRI. Mean tumor size was 3.83+1.3 cm. (2-6), and hydrocephalus was found in 54.5% of all patients. Craniotomy was performed in 13 cases with one transphenoidal surgery. Post-operative endocrine evaluations revealed more frequent hypogonadotropic hypogonadism (90%), both secondary adrenal insufficiency and diabetes insipidus (85.7%). 50% of DI cases were permanent DI. Secondary hypothyroidism was found post-operatively (78%). All cases of elevated serum prolactin levels became normal post-operatively and 44% of all patients had visual field improvement within a follow up period of 2.1+2.3 years (0-7). Conclusion: Craniopharyngioma is associated with high morbidity pre and post-operation. Visual field tests should be carefully evaluated in all patients with headaches to make early diagnosis in order to improve the treatment outcome.

Hyperthyroidism induces glucose intolerance by lowering both insulin secretion and peripheral insulin sensitivity.

OBJECTIVE: The objectives of this study were to examine the effects of hyperthyroidism on glucose tolerance, insulin secretion, and insulin sensitivity. MATERIAL AND METHOD: Thirty-eight patients with hyperthyroidism and twenty-six healthy volunteers with matching age and body mass index were included. Patients with conditions known to affect glucose metabolism were excluded. An oral glucose tolerance test was performed after the diagnosis of hyperthyroidism and again when they achieved euthyroid state. Areas under the glucose and insulin curves were used to assess plasma glucose and insulin responses, respectively. Beta-cell function was determined by the corrected insulin response (CIR) and homostatic model assessment model 2 (HOMA2-%B). Peripheral insulin sensitivity was determined by the insulin activity (IA) and HOMA2-%S. RESULT: The prevalence of glucose intolerance in hyperthyroid state was 39.4% [impaired glucose tolerance (IGT) 31.5% and diabetes mellitus (DM) 7.9%]. This was significantly higher than that of 30.7% [IGT 19.2% and DM 11.5%] in healthy volunteers (p < 0.05). Glucose intolerance was associated with higher systolic blood pressure, higher mean arterial pressure, lower CIR, and higher T4 levels but not with the levels of T3. IA and HOMA2-%S significantly improved when achieving a euthyroid state despite the increase in body mass index. CONCLUSION: In conclusion, glucose intolerance is common in hyperthyroidism. Both impaired insulin secretion and decreased peripheral insulin sensitivity are the factors contributing to the development of abnormal glucose tolerance in the hyperthyroid state.

Postprandial leptin response to Thai meals with different macronutrient mixtures.

The objective of this study was to investigate the postprandial response of leptin, an appetite-regulating hormone, to different macronutrient mixtures in Thai meals. A within-subject repeat measurement was performed. Two groups of healthy Thais (10 men and 10 women in each group) received a single meal of equal calories composed either a high carbohydrate, low fat, low protein diet (HC-LFLP, carbohydrate:fat:protein = 70%:15%:15%) or a low carbohydrate, high fat, high protein diet (LC-HFHP, carbohydrate:fat:protein = 20%:50%:30%). Fasting and 30-minute interval postprandial blood levels of leptin, insulin and glucose were measured for a 2-hour period. In comparison to the LC-HFHP meal, the HC-LFLP meal produced a greater increase in glucose and insulin levels, but halted leptin from decreasing. Postprandial leptin levels were suppressed by a LC-HFHP meal but not by a HC-LFLP meal. The reduced leptin in conjunction with lower glucose and insulin levels may encourage overeating in habitual LC-HFHP diet consumers.

Analysis of the reg1alpha and reg1beta gene transcripts in patients with fibrocalculous pancreatopathy.

Fibrocalculous pancreatopathy is a form of diabetes, associated with tropical chronic calcific pancreatitis, in which islet beta-cell loss and pancreatic stone formation are found. It is likely to be a multifactorial disease with both genetic and environmental components. Regenerating (reg) gene encodes protein that has been involved in pancreatic lithogenesis and the regeneration of islet cells and therefore the abnormality of reg genes could be associated with fibrocalculous pancreatopathy. In this study, regla and reg1beta mRNAs were isolated from peripheral blood lymphocytes obtained from 16 patients with fibrocalculous pancreatopathy, 42 patients with type 1 diabetes, 37 patients with type 2 diabetes, and 22 normal controls. mRNAs were amplified by reverse-transcription polymerase chain reaction (RT-PCR) and analysed by a single strand conformation polymorphism (SSCP) technique. The reg1alpha and reg1beta mRNAs were isolated, indicating the ectopic expression of these genes in peripheral blood lymphocytes; however, variation among mobility patterns was not observed in the SSCP analysis of the RT-PCR products. The results indicated that there was no abnormality of the regla and reg1beta mRNAs obtained from the study groups.

Association between estrogen receptor concentration in breast cancer tissue and bone mineral density.

Both bone and the breast are major target tissues of estrogen actions. The biological actions of estrogen depend on the interaction between estrogen and estrogen receptors (ER) in the target tissues. Therefore, ER concentration in tissues such as breast cancer might be associated with the amount of bone mass. The present study was aimed to examine whether there is a relationship between ER concentration in breast cancer tissue (ER-BCA) and bone mineral density (BMD). Forty-seven pre-menopausal and 34 post-menopausal women with newly diagnosed breast cancer were studied. The ER-BCA ranged from 0 to 339 fmol/mg cytosol protein (mean +/- SD = 68.6 +/- 97.0). Pearson's correlation analyses showed that ER-BCA negatively correlated to BMD of the spine (r = -0.251, p = 0.024), forearm (r = -0.341, p = 0.002), hip (r = -0.373, p = 0.001) and total body (r = -0.317, p = 0.004) in all 81 women. In 47 pre-menopausal women, the ER-BCA negatively correlated to the hip (r = -0.455, p = 0.001) and total body (r = -0.395, p = 0.006) but not to the spine and forearm BMD. Whereas, in 34 post-menopausal women, the ER-BCA negatively correlated to forearm BMD (r = -0.399, p = 0.019). Stepwise multiple regression analyses showed that the ER-BCA independently correlated to hip BMD in all 81 women (r = -0.373, p < 0.01) and in pre-menopausal women (r = -0.486, p < 0.001) and independently correlated to forearm BMD in post-menopausal women (r = -0.399, p < 0.05). The results of this study suggest that the presence of high estrogen receptor concentration in breast cancer tissue might induce a deleterious effect on bone mass particularly in pre-menopausal women.

Primary hyperparathyroidism due to parathyriod carcinoma: Report of a case and review of literature.

A 21-year-old male with a history of bone pain for four months is described. He lost 2 cm of his height and also had polyuria and weight loss. Physical examination revealed a cachectic and mildly pale man with a firm mass of 0.8 cm in diameter on the fight side of his neck, generalized muscle wasting and proximal muscle weakness. kyphoscliosis and deformed thoracic cage. Skeletal X-ray showed finding compatible with the changes found in primary hyperparathyroidism. Biochemical parameters revealed a serum corrected total calcium of 15 mg/dl (8.5-10.5 mg/dl), inorganic phosphate of 3.7 mg/dl (305-5.0 mg/dl) and alkaline phosphatase of 1,008 U/l (39-117 U/l). Primary hyperparathyroidism was confirmed by a serum parathyroid hormone level of 1,733 pmol/l (0.100 pmol/l), Ultrasonography and computerized tomography of the neck showed a right neck mass with a diameter of 2 x 2.2 x 3 cm cm which was visualized by 99mTc-sestamibi scan. The patient underwent an uneventful surgical exploration of the neck. Histopathological study of the excised neck mass showed findings consistent with parathyroid carcinoma.