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.

Thailand diabetes registry project: prevalence and risk factors of stroke in thai diabetic patients.

OBJECTIVE: To determine the prevalence of stroke and its risk factors in Thai diabetic patients who attended the diabetes clinics of university and tertiary-care hospitals. MATERIAL AND METHOD: A cross-sectional, multi-center hospital-based diabetes registry was carried out at diabetes clinics of 11 university and tertiary-care hospitals. Demographic data, clinical characteristics, common drugs used and laboratory parameters were analyzed for prevalence and risk factors associated with stroke. RESULTS: The prevalence of stroke in the patients studied was 3.5%. Most of the patients were type 2 diabetes and had ischemic stroke. One of the risk factors associated with stroke was age greater than 60 years, and the risk appeared to be highest if the patients' age was greater than 70 years (adjust OR = 3.29, p = 0.012). Other risk factors included male sex, systolic blood pressure of > or =140 mmHg, use of oral hypoglycemic agents, lipid lowering agents and aspirin. There was no association between stroke and duration of diabetes, occupation, educational level, BMI, smoking, alcohol drinking, diastolic blood pressure, use of antihypertensive drugs or insulin, glycemic control, lipid profiles and kidney function. CONCLUSION: Ischemic stroke was common among Thai patients with diabetes especially in the elderly. The present result emphasizes the relationship between level of systolic blood pressure and the occurrence of stroke. Optimal blood pressure control should be underscored in caring for diabetic patients.

Randomized controlled trial of Tinospora crispa for additional therapy in patients with type 2 diabetes mellitus.

A randomized double blind placebo controlled trial was conducted to determine the efficacy of Tinospora crispa as additional treatment in patients with type 2 diabetes mellitus who did not respond to oral hypoglycemic drugs and refused insulin injection. Twenty patients were allocated to receive Tinospora crispa powder in capsule form at a dosage of 1 gram thrice daily for 6 months. Twenty patients received a placebo. The main outcomes were changes in fasting plasma glucose, glycosylated hemoglobin and insulin levels. The baseline characteristics of the patients in both groups were not significantly different. There were no significant changes in fasting plasma glucose, glycosylated hemoglobin and insulin levels among the patients within the group and between groups. Two patients who received Tinospora crispa showed marked elevation of liver enzymes that returned to normal after discontinuing Tinospora crispa. Moreover, patients in the Tinospora crispa group had significant weight reduction and cholesterol elevation while taking Tinospora crispa. It is concluded that there is no evidence to support the use of Tinospora crispa 3 grams a day for additional therapy in patients with type 2 diabetes mellitus who did not respond to oral hypoglycemic drugs. The patients receiving Tinospora crispa may have an increased risk of hepatic dysfunction.

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.

Flow cytometry for the analysis of T cells expressing CD69 after stimulation with glutamic acid decarboxylase.

Type 1 diabetes mellitus is a T-cell mediated autoimmune disease in which the insulin-producing pancreatic beta cells are selectively destroyed. We recently found that the detection of cell-mediated immune response to glutamic acid decarboxylase (GAD) was more useful than the detection of specific autoantibodies for the diagnosis of type 1 diabetes mellitus. In this study, we established a flow cytometric analysis for the detection of activated T cells in whole venous blood, obtained from diabetic patients and normal controls after stimulation by GAD. Two millitiers of peripheral venous blood and 6 hours incubation time were used for performing the test. It was found that 33% (3/9) type 1 diabetic patients, 7.7% (1/13) type 2 diabetic patients and neither patients with fibrocalculous pancreatopathy nor normal controls had > or = 20% CD8+ T cells expressing CD69. The results suggest that flow cytometry may be a useful tool for the detection of surrogate markers of type 1 diabetes mellitus.

Management pattern and hospital charge of repairing cleft palate at Siriraj Hospital.

Management pattern and hospital charge for repairing cleft palate at Siriraj Hospital during 1996-1999 were studied retrospectively. From the examination of 100 patient records, four cases were excluded since no surgical correction was performed during hospitalization. Fifty-nine percent were female and the average age was 5.54 years old. Fever and otitis media were associated with two and three cases respectively. Other underlying diseases included hypothyroidism, patent ductus arteriosus and ventricular septal defect were found one in each case. The cleft palate was successfully repaired in all cases. Surgical correction was done in 84 percent of cases within the first five days of hospitalization. The average length of stay was 5.89 + 2.85 days and ranged from 2-20 days. The hospital charge for cleft palate repair was 7,031.22 + 1,365.33 Baht per case. This study illustrate that a small variation is practiced in the management of a reasonably straight forward condition and better preparation of the patients before hospitalization could reduce the hospital stay or avoid unnecessary hospitalization.

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.

Fatal nosocomial infection in medical wards of a University Hospital.

Nosocomial infection is one of the most common morbidity among hospitalized patients. While study dealing with epidemiologic pattern of those in living patients are numerous, studies focusing on patients who died of them are few. In this prevalence study, we found that patients having fatal nosocomial infections presented some distinguishable features. From May 1982 to December 1983, 109 out of 300 cases had fatal nosocomial infections (36.3%). There was a total of 168 episodes of infection in these patients (1.5 episodes per patient). The ages ranged from 13-91 years and both sexes were equally affected. Septicemia was the most common infection related directly to death (a causal relationship). Pneumonia was commonly contributing to death while urinary tract infection was the most common infection not related to death. Most patients had either rapidly fatal or ultimately fatal underlying diseases. The infections disease episodes in both types of underlying diseases were not significantly different. There was a bimodal age group distribution of those who died of infections (30 and 60 years). The peak survival was rather short (mode of 20.0 days) and the fatal infection occurred early in the hospitalized course (mode of 5.0 days). These data suggested that the prevalence of fatal nosocomial infection was high severe infection occurred early and types of infection may be a predictor of fatal outcome,. Any intervention focusing on prevention of severe infection, such as septicemia and pneumonia, should be encouraging.