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.

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.

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.

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.

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.