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.

Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients.

We performed a randomized crossover open comparative study to evaluate the efficacy and safety of voglibose and acarbose in 30 patients with type 2 diabetes who were not well controlled with diet therapy. There was no significant reduction of FBG with either voglibose or acarbose at 4 and 8 weeks after treatment. The 1 h postprandial blood glucose (PPBG) level was significantly decreased from 224.9+/-42.8 to 204.1+/-37.6 (P=0.005) and 206.1+/-38.9 mg/dl (P=0.038) after voglibose therapy at 4 and 8 weeks, respectively. Significant decrease was also obtained after acarbose treatment from 228.3+/-37.4 to 182.7+/-35.5 (P<0.001) and 186.6+/-36.1 mg/dl (P<0.001). The decrease of 1 h PPBG was associated with a significant fall of serum insulin concentration. HbA(1c) levels were also significantly decreased from 7.07+/-1.21 to 6.83+/-1.11 (P=0.017) and 6.79+/-1.33% (P=0.036) after voglibose and 6.98+/-0.98 to 6.70+/-1.04 (P<0.001) and 6.59+/-1.04% (P<0.001) after acarbose at 4 and 8 weeks. In contrast to voglibose, treatment with acarbose significantly decreased the 2 h PPBG at 4 and 8 weeks and the 2 h postprandial serum insulin concentration at 8 weeks. Adverse drug events were more commonly reported in acarbose-treated patients (P<0.05). Increased flatulence was observed in 56.7 and 90% of the patients taking voglibose and acarbose, respectively, while abdominal distention was noted in 10 and 16.7%. Significantly decreased body weights of 0.9 and 0.8 kg were recorded at 8 weeks after voglibose and acarbose therapy, respectively. We conclude that both voglibose (0.2 mg) and acarbose (100 mg) thrice daily significantly decreased HbA(1c), PPBG and postprandial insulin levels. At these dose levels, voglibose was associated with less gastrointestinal side effects and slightly less efficacy for postprandial glucose reduction.

Dose-expanded study in the reinforcement of efficacy of simvastatin.

UNLABELLED: Two hundred and twenty two hyperlipidemic patients were recruited for a 12-week prospective, multicenter, open-label, titrate-to-goal study to evaluate the efficacy and safety of 20 to 40 mg per day of simvastatin in a Thai population. The efficacy on lipid lowering was evaluated at 4 weeks and 8 weeks after medication. Based on NCEP ATP II guideline and ADA position statement, subjects were categorized into three groups according to LDL-C goals; group I: patients without CHD and with < 2 CHD risk factors, group II: patients without CHD and with > or = 2 CHD risk factors and group III: CHD patients or diabetic patients with > or = 1 risk factors. Significant changes of all lipid parameters from baselines were noted at 4 weeks after medication except for HDL-C levels. Reduction of serum LDL-C, TC and TG by 40 per cent, 29 per cent and 16 per cent respectively and increase of serum HDL-C by 5 per cent were observed at 8 weeks of therapy (p<0.05). At 4 weeks after taking simvastatin 20 mg/day, 78.9 per cent of patients in group I, 67.4 per cent in group II and 40.9 per cent in group III achieved LDL-C goals. Seventeen per cent of the patients who were evaluated at 8 weeks increased the simvastatin dosage to 40 mg per day in the second month of treatment. At 8 weeks of therapy with simvastatin 20-40 mg/day, 90.1 per cent of patients in group I, 77.4 per cent in group II and 66.7 per cent in group III achieved LDL-C goals. Adverse symptoms during therapy, mostly mild, developed in 6.3 per cent of the 222 patients. CONCLUSION: Simvastatin 20-40 mg/day was effective and well tolerated in managing lipid parameters in Thai patients similar to other ethnic populations.

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.

Assessment of baseline characteristics, glycemic control and oral antidiabetic treatment in Asian patients with diabetes: The Registry for Assessing OAD Usage in Diabetes Management (REASON) Asia study.

BACKGROUND: To assess baseline characteristics, glycemic control, and treatment with oral antidiabetic drugs (OAD) in type 2 diabetes mellitus (T2DM) patients. METHODS: This multinational, observational study recruited patients ≥ 21 years of age who were newly diagnosed and/or treated with OAD monotherapy for <6 months but were inadequately controlled. In cross-sectional phase, data on demographics, medical history, diabetic complications and comorbidities, OAD treatment, glycosylated hemoglobin (HbA1c), and fasting blood glucose (FBG) were collected. In longitudinal phase evaluating 6-month follow-up of sulfonylurea (SU)-treated patients, additional data on reasons for not achieving HbA1c targets were collected. RESULTS: Of 1487 patients (mean [± SD] age 52.0 ± 11.6 years; 46.7% men; mean BMI 25.8 ± 4.4 kg/m(2) ) recruited, 75.9% were newly diagnosed, 73.3% had central obesity, 43.8% had hypertension, and 60.5% had dyslipidemia. The mean HbA1c was 9.8 ± 2.4%, and the mean FBG was 11.3 ± 4.3 mmol/L. At T0 (baseline) and T6 (month 6 visit), 99.8% (n=1066) and 97.1% (n=830) patients received SU, respectively. There was decrease from T0 to T6 in mean HbA1c (10.2% vs 7.3%, respectively; P<0.0001) and mean FBG (12.0 vs 7.6 mmol/L, respectively; P<0.0001). Number of patients with HbA1c <7% increased from T0 (4.5%) to T6 (46.8%). Reasons for not achieving target HbA1c included poor diabetes education (50.7%), non-compliance to OADs (21.4%), and fear of hypoglycemia (19.7%). CONCLUSION: Marked reductions in HbA1c and FBG are achievable in T2DM patients managed with OADs. However, patient education and compliance are important for achieving and maintaining treatment targets.

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.

Dose-expanded study in the reinforcement of efficacy of simvastatin.

Two hundred and twenty two hyperlipidemic patients were recruited for a 12-week prospective, multicenter, open-label, titrate-to-goal study to evaluate the efficacy and safety of 20 to 40 mg per day of simvastatin in a Thai population. The efficacy on lipid lowering was evaluated at 4 weeks and 8 weeks after medication. Based on NCEP ATP II guideline and ADA position statement, subjects were categorized into three groups according to LDL-C goals; group I: patients without CHD and with < 2 CHD risk factors, group II: patients without CHD and with > or = 2 CHD risk factors and group III: CHD patients or diabetic patients with > or = 1 risk factors. Significant changes of all lipid parameters from baselines were noted at 4 weeks after medication except for HDL-C levels. Reduction of serum LDL-C, TC and TG by 40 per cent, 29 per cent and 16 per cent respectively and increase of serum HDL-C by 5 per cent were observed at 8 weeks of therapy (p<0.05). At 4 weeks after taking simvastatin 20 mg/day, 78.9 per cent of patients in group I, 67.4 per cent in group II and 40.9 per cent in group III achieved LDL-C goals. Seventeen per cent of the patients who were evaluated at 8 weeks increased the simvastatin dosage to 40 mg per day in the second month of treatment. At 8 weeks of therapy with simvastatin 20-40 mg/day, 90.1 per cent of patients in group I, 77.4 per cent in group II and 66.7 per cent in group III achieved LDL-C goals. Adverse symptoms during therapy, mostly mild, developed in 6.3 per cent of the 222 patients. Conclusion: Simvastatin 20-40 mg/day was effective and well tolerated in managing lipid parameters in Thai patients similar to other ethnic populations.

The effect of combined oral contraceptives on thyrotoxicosis.

The influence of combined oral contraceptives, namely, ethinyl estradiol (30 µg) and levonorgestrel (150 µg) was studied in nine cases of thyrotoxicosis divided into two groups: one group of htyrotoxic woman treated with propyl thiouracil (PTU) and another untreated group. The latter group of patients were than maintained on both PTU and the combined oral contraceptive pills; some cases were studied for 16-33 months. Before, during and after treatment, all patients were tested and confirmed by clinical examinations and thyroid function tests which were divided into two group: in vivo (24h 131/I uptake and T3-suppression test) and in vivo (total serum thyroxine (TT4), total T3 (TT3), T3 uptake (T3U), free thyroxine index (FTI) and thyrotropin (TSH). The results revealed that the values of TT4, TT3 and FTI were markedly high in the untreated group but these values decreased significantly (P<0.001) and remained within normal ranges after treatment with PTU and the contraceptive pills was initiated. Improved clinical symptoms and sings were also observed. However, the levels of TT4, TT3 and T3 uptake were elevated in the long-term treatments of both groups, but the FTI and TSH values were within normal limits, indicating that the values of FTI as well as TSH gave effective measurements of thyroid activity in evaluating the patients whose total thyroid hormones were abnormal because of altered TBG concentration and binding capacity. Therefore, our finding suggested that the prolonged use of combined oral contraceptive pills dose not interfere with medical treatment of thyrotoxic patients.

Prothrombin fragment 1+2 and fibrinogen in Thai type 2 diabetic patients.

Since the evidence for the hypercoagulable state in terms of prothrombin fragment 1+2 (F1+2) in Thai diabetic patients has never been reported, we studied plasma F1+2 levels in 68 type 2 diabetic patients and in 20 normal age-matched volunteers. Fibrinogen, D- dimer, glucose, HbA1C, cholesteroi, triglyceride, HDL-cholesterol and creatinine were also determined. It was found that the levels of F1+2 and fibrinogen in the diabetic patients were significantly higher than in the controls (p<0.001 and p<0.01 respectively), while D-dimer was detected positively in 17 out of 64 patients whereas none could be detected in the 20 healthy volunteers. A total of 23 out of 68 patients had higher levels of F1+2 than the normal range. When we compared the clinical characteristics, blood chemistry analysis and hypercoagulable markers of the diabetic patients between the groups of high F1+2 and normal F1+2, there were significantly higher numbers of positive D-dimer cases in the high F1+2 group compared with the normal F1+2 group (p=1.01). The correlation between F1+2 vs diabetic duration was 0.29 with p value less than 0.05. This study suggests that there are hypercogulable states in Thai diabetic patients.

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.