The association between treatment and systemic inflammation in acromegaly.

OBJECTIVE: Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function. DESIGN: Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment. RESULTS: Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment. CONCLUSIONS: Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.

EFFECT OF EXPERIMENTAL DYSGLYCEMIA ON UNDER-CARBOXYLATED OSTEOCALCIN PRODUCTION IN HUMAN PRIMARY OSTEOBLAST-LIKE CELL CULTURES.

CONTEXT: The undercarboxylated form of osteocalcin (ucOC) and osteoprotegerin (OPG) are bone-derived molecules involved in the endocrine crosstalk governing the bone, the adipose tissue and the pancreas. In addition, glucocorticoids are major determinants of both insulin resistance and osteoporosis. OBJECTIVE: We aimed to investigate the response of ucOC and OPG to dysglycemia and/or dexamethasone (DXM) in primary human osteoblastic cell (HOC) cultures. DESIGN AND METHODS: Third-passage sub-confluent primary HOC cultures were treated with glucose: 2.8 mmol/L, 5.6 mmol/L, 11.1 mmol/L and 28 mmol/L, respectively. Alternatively, HOC cultures were subjected to DXM 1 µmol/L. In more complex experiments, HOC cultures were pre-treated with glucose (5.6 mmol/L) with/without insulin (1 pmol/L) followed by DXM (1 µmol/L). 24-hours post-treatment, culture medium ucOC and OPG were measured by ELISA. RESULTS: ucOC production differed significantly (p<0.05) between cell groups, decreasing in a dose-dependent manner as glucose concentration in the medium increased. Insulin prevented this effect. OPG levels appeared not to be significantly influenced by the hyperglycemic culture medium and were not related to ucOC concentration (p>0.05). Addition of DXM resulted in significantly lower ucOC concentrations compared to vehicle-treated cells (p<0.05). However, the effect of insulin co-treatment on ucOC was not counteracted by DXM (p<0.05). CONCLUSIONS: An obvious alteration of OC production/metabolism was observed as glucose levels changed in the bone microenvironment, to potentially be involved in diabetes-related osteopenia. DXM suppressed ucOC levels however not in insulin-rich environment.

ASSOCIATION OF COL1A1 SP1 AND FOK-I VDR GENETIC POLYMORPHISMS IN YOUNG MALE IDIOPATHIC OSTEOPOROSIS.

INTRODUCTION: Primary osteoporosis during childhood and adolescence represents an uncommon condition, and secondary forms are more likely to manifest at this age due to chronic disease and adverse effects of medical treatment. CASE REPORT: The authors report the case of a young male patient with a history of multiple idiopathic non-vertebral fragility fractures in addition to a family history of maternal osteoporosis and fracture, in whom osteoporosis was confirmed according to 2013 International Society for Clinical Densitometry (ISCD) criteria. Bone markers indicated low bone formation marker osteocalcin. Genetic testing revealed homozygosity for Sp1 COL1A1 gene polymorphism in combination to Fok-I vitamin D receptor (VDR) heterozygous polymorphism, to contribute to low bone mass and increased fracture risk. Severe premenopausal osteoporosis was present in the patient's mother, who was also tested positive for both gene polymorphisms. CONCLUSION: This case report highlights the association between COL1A1 and VDR candidate gene polymorphisms and fragility fractures in a family. Individual genetic testing might be of clinical value in idiopathic osteoporosis in young patients, identifying subjects at increased fracture risk.

SURGERY OUTCOMES IN PATIENTS WITH SECONDARY HYPERPARATHYROIDISM AND IMPACT OF INTRA-OPERATIVE PTH MEASUREMENT.

CONTEXT: The current therapeutical management of secondary hyperparathyroidism (S-HPTH) is difficult to obtain due to the lack of kidney donors. Surgical intervention on the pathologic parathyroid tissue has been suggested as a method to alleviate symptoms in patients with chronic kidney disease (CKD). OBJECTIVE: The aim of our study was to evaluate the outcomes of parathyroid surgery in patients with S-HPTH and the advantages of intraoperative quick PTH (iqPTH) to improve surgical results. MATERIAL AND METHODS: In a real-life study, we compared one group of S-HPTH with iqPTH performed after removing all suspected glands and before wound suture (Group 1) and one group in that iqPTH was not assessed (Group 2). When iqPTH dropped less than 50%, additional exploration followed. RESULTS: Eight out of the 34 patients from Group 1, who underwent subtotal parathyroidectomy, showed elevated levels of serum PTH and calcium, which remained elevated during follow-up, thus, suggesting disease persistence. From the 21 patients in Group 2, none showed early postoperative disease persistence. Serum calcium, but not PTH was increased in one patient from the iqPTH group but normalized after one month. Overall, iqPTH allowed detection of a supplementary parathyroid gland in one case, thereby increasing early post-surgery remission to 100% in Group 2 compared to 76.47% in Group 1. Late postoperative remission of hyperparathyroidism with no further increase in the rate of hypoparathyroidism was obtained in Group 2. CONCLUSIONS: Assessment of intra-operative PTH levels proved to be a useful tool in augmenting the outcome of S-HPTH surgery. In patients which are eligible for renal transplantation who undergo a subtotal resection, iqPTH can enhance the post-operative quality of life by lowering disease recurrence rates until the kidney transplant procedure.