Parathyroid Hormone on Osteoprotegerin Levels in Patients with Primary Hyperparathyroidism.

OBJECTIVE: Osteoprotegerin is a glycoprotein that plays a major role in the regulation of bone turnover. The influence of parathyroid hormone, an important regulator of bone remodeling, on osteoprotegerin production is controversial. The purpose of the study was to assess the influence of parathyroid hormone on the circulating level of osteoprotegerin in patients with primary hyperparathyroidism by comparing it with healthy controls. MATERIALS AND METHODS: Forty-four patients with biochemical verification of primary hyperparathyroidism scheduled for the surgical cure and 38 healthy subjects were included. Blood samples of the study group were taken before surgery. Levels of serum parathyroid hormone, osteoprotegerin, calcium, 25-hydroxyvitamin D [25(OH)D], and alkaline phosphatase were analyzed. Bone mineral density at the L1-L4 vertebrae and femoral neck was calculated by dual-energy X-ray absorptiometry. RESULTS: Osteoprotegerin levels and bone mineral density values were significantly lower in patients than in the healthy subjects (P=.002 and P > .0001, respectively). There was no correlation between osteoprotegerin and parathyroid hormone in the groups. Osteoprotegerin was weakly correlated with bone mineral density in patients. No correlation was noted between osteoprotegerin and bone mineral density in the control group. Furthermore, osteoprotegerin levels were not correlated with calcium, 25(OH)D, and alkaline phosphatase levels in each group. CONCLUSION: The production of osteoprotegerin appears to be inhibited by parathyroid hormone in patients with primary hyperparathyroidism. A weak positive correlation found among osteoprotegerin and bone mineral density recommends that osteoprotegerin may be a molecule that impacts bone metabolism and finally bone mineral density.

THE PREVALENCE OF CANCER AND ITS RELATION TO DISEASE ACTIVITY IN PATIENTS WITH ACROMEGALY: TWO CENTERS' EXPERIENCE.

OBJECTIVE: Acromegaly is characterized by increased serum concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Although animal studies have demonstrated a relationship between these hormones and cancer risk, the results of human studies evaluating cancer prevalence in acromegaly are inconsistent. We aimed to investigate the prevalence of malignant neoplasms in patients with acromegaly. METHODS: Cancer risk was evaluated in a cohort of 280 patients (male/female: 120/160; mean age: 50.93 ± 12.07 years) with acromegaly. Patients were categorized into 2 groups according to the presence or absence of cancer. Standard incidence ratios were calculated as compared to the general population. RESULTS: From 280 patients, cancer was diagnosed in 19 (6.8%) patients; 9 (47%) of them had thyroid cancer, which was the most common cancer type. Standard incidence ratios of all cancers were 0.8 (95% CI, 0.5-1.1) and 1.0 (95% CI, 0.8-1.3) in men and women, respectively. Compared to patients without cancer, the current age was higher in patients with cancer (59 [49-65] to 51 [42-59], P = .027). In contrast, the age at diagnosis was similar in both groups. Not only was the time to diagnosis and disease duration similar in both groups but also the basal and current GH and IGF-1 levels. The prevalence of active disease was also similar between the groups (32% to 23%, P = .394). CONCLUSION: Our findings were not consistent with the studies suggesting that patients with acromegaly encounter an increased cancer risk. Furthermore, there were similar basal and current GH and IGF-1 levels in patients with acromegaly, both with and without cancer.

The acromegaly registry of ten different centers in Turkey.

OBJECTIVES: To describe biochemical and clinical features, and therapeutic outcomes of acromegaly patients in Turkey. METHODS: Retrospective multicenter epidemiological study of 547 patients followed in 10 centers of the Turkish Acromegaly registry. RESULTS: A total of 547 acromegaly patients (55% female) with a median age of 41 was included in this study. Majority of patients had a macroadenoma (78%). Transsphenoidal surgery was performed as primary treatment in 92% of the patients (n = 503). Surgical remission rate was 39% (197/503) in all operated patients. Overall disease control was achieved in 70% of patients. Remission group were significantly older than non-remission group (p = .002). Patients with microadenomas had significantly higher remission rates than patients with macroadenomas (p < .001). Patients with microadenomas were significantly older at the time of diagnosis when compared to patients with macroadenomas (p < .001). Preoperative growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were significantly lower in the remission group (p < .001). Initial IGF-1 and GH levels were significantly higher in macroadenomas compared to microadenomas (p < .001). Medical treatment was administered as a second-line treatment (97%) in almost all patients without remission. Radiotherapy was preferred in 21% of the patients mostly as a third line treatment. CONCLUSIONS: This is one of the largest real life studies evaluating the epidemiological characteristics and treatment outcomes of patients with acromegaly who were followed in different centers in Turkey. Transsphenoidal surgery in the treatment of acromegaly still remains the most valid method. Medical treatment options may improve long-term disease outcomes in patients who cannot be controlled with surgical treatment (up to 70%).

Effects of vitamin D supplementation on insulin resistance and dyslipidemia in overweight and obese premenopausal women.

INTRODUCTION: Vitamin D deficiency is a common problem, and it is related to increased risk of obesity, metabolic syndrome, atherosclerosis, and cardiovascular disease. Vitamin D has a beneficial effect on dyslipidemia and insulin secretion. We aimed to investigate the impact of vitamin D3 supplementation on anthropometric and laboratory parameters in overweight and obese premenopausal women. MATERIAL AND METHODS: Seventy-two overweight and 50 obese vitamin-D-deficient premenopausal women (mean age: 43.1 ±10.4 years) were included in the study. Baseline mean 25-hydroxyvitamin D [25(OH)D] level was 6.1 (min.-max. = 2.9-15.8) ng/ml in overweight and was 5.6 (min.-max. = 3.0-22.0) ng/ml in obese subjects. At baseline and at the sixth month of supplementation, serum 25(OH)D, intact parathormone (iPTH), calcium, phosphorus, homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles were assessed. RESULTS: Following vitamin D3 supplementation in overweight and obese subjects, serum 25(OH)D increased from 6.1 to 34.7 ng/ml and 5.6 to 34.7 ng/ml, respectively (p < 0.001). At the sixth month of supplementation in both overweight and obese subjects, a significant reduction was detected in HOMA-IR (p < 0.001), low-density lipoprotein cholesterol (LDL-C) (p = 0.046, p = 0.044; respectively) and iPTH levels (p ≤ 0.001, p < 0.001; respectively). A negative adjusted correlation was found between changes in 25(OH)D and HOMA-IR (r = -0.581, p < 0.001; r = -0.389, p = 0.005; respectively). A 1 ng/ml increase in serum 25(OH)D level led to a 0.30-fold reduction in HOMA-IR level (p = 0.002). CONCLUSIONS: Our results support the effect of vitamin D3 supplementation in HOMA-IR and LDL-C improvement in both obese and overweight subjects. Further studies focused on low serum 25(OH)D levels with insulin resistance and dyslipidemia are needed.

Matrix metalloproteinase 2 (MMP-2) levels are increased in active acromegaly patients.

PURPOSE: During follow-up of acromegaly patients, there is a discordance rate of 30% between the measurements of growth hormone and insulin-like growth factor-1 levels. Further tests are required to determine disease activity in patients with discordant results. This study was planned to investigate an association of serum levels of matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B with disease activity in acromegaly patients. METHODS: In this study, 64 acromegaly patients followed in our clinic were divided into two groups according to the 2010 consensus criteria for cure of acromegaly as patients with active disease (n = 24) and patients with controlled disease (n = 40). Serum matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B levels were measured by the enzyme-linked immunosorbent assay method. RESULTS: The mean serum matrix metalloproteinase-2 level was significantly higher in the active acromegaly patients than in the controlled acromegaly patients (150.1 ± 54.5 ng/mL vs. 100.2 ± 44.6 ng/mL; p < 0.0001). There was no significant difference between the active and controlled acromegaly patients regarding serum matrix metalloproteinase-9 and cathepsin B levels (p = 0.205 and p = 0.598, respectively). Serum matrix metalloproteinase-2 levels of 118.3 ng/mL and higher had a sensitivity of 75% and a specificity of 77.5% in determining active disease. The risk of active acromegaly was 3.3 fold higher in the patients with a matrix metalloproteinase-2 level of >118.3 ng/mL than in the patients with a matrix metalloproteinase-2 level of <118.3 ng/mL. CONCLUSIONS: In this study, serum matrix metalloproteinase-2 level is increased in the active acromegaly patients and a threshold value in determining active disease was defined for serum matrix metalloproteinase-2 level. This study is the first to compare acromegaly patients having active or controlled disease in terms of matrix metalloproteinase-2 and matrix metalloproteinase-9 levels. The results need to be confirmed by a study that will be conducted in a larger patient group also including a healthy control group to demonstrate the value of this novel marker in disease activity.