Glucose intolerance in acromegaly is driven by low insulin secretion; results from an intravenous glucose tolerance test.

PURPOSE: Insulin sensitivity (Si) and its role in glucose intolerance of acromegaly has been extensively evaluated. However, data on insulin secretion is limited. We aimed to assess stimulated insulin secretion using an intravenous glucose tolerance test (IVGTT) in active acromegaly. METHODS: We performed an IVGTT in 25 patients with active acromegaly (13 normal glucose tolerance [NGT], 6 impaired glucose tolerance [IGT] and 6 diabetes mellitus [DM]) and 23 controls (8 lean NGT, 8 obese NGT and 7 obese IGT). Serum glucose and insulin were measured at 20 time points along the test to calculate Si and acute insulin response (AIRg). Medical treatment for acromegaly or diabetes was not allowed. RESULTS: In acromegaly, patients with NGT had significantly (p for trend < 0.001) higher AIRg (3383 ± 1082 pmol*min/L) than IGT (1215 ± 1069) and DM (506 ± 600). AIRg was higher in NGT (4764 ± 1180 pmol*min/L) and IGT (3183 ± 3261) controls with obesity than NGT (p = 0.01) or IGT (p = 0.17) acromegaly. Si was not significantly lower in IGT (0.68 [0.37, 0.88] 106*L/pmol*min) and DM (0.60 [0.42, 0.84]) than in NGT (0.81 [0.58, 1.55]) patients with acromegaly. NGT (0.33 [0.30, 0.47] 106*L/pmol*min) and IGT (0.37 [0.21, 0.66]) controls with obesity had lower Si than NGT (p = 0.001) and IGT (p = 0.43) acromegaly. CONCLUSION: We demonstrated that low insulin secretion is the main driver behind glucose intolerance in acromegaly. Compared to NGT and IGT controls with obesity, patients with NGT or IGT acromegaly had higher Si. Together, these findings suggest that impaired insulin secretion might be a specific mechanism for glucose intolerance in acromegaly.

Acromegaly versus hypogonadism: Bone fragility and evaluation.

INTRODUCTION: Osteopathy in patients with acromegaly is characterized by increased prevalence of vertebral fragility fractures (VF). However, the diagnostic criteria for osteoporosis are seldomly met in terms of bone mineral density (BMD), as patients with acromegaly frequently present normal BMD for age and gender. METHODOLOGY: We performed a cross-sectional study on 71 patients with acromegaly and 75 patients with hypogonadism. Turnover markers comprised alkaline phosphatase, osteocalcin, the C-terminal telopeptide of type I collagen and total procollagen type-1 amino-terminal propeptide; imaging comprised dual x-ray absorptiometry for BMD, T and Z scores of the lumbar spine, femoral neck and total hip, trabecular bone score (TBS), and x-ray scans of the thoracic and lumbar spine. RESULTS: Vertebral fractures (VF) in subjects with acromegaly were significantly more frequent than in subjects with hypogonadism, with a prevalence of 29.6% compared to 9.3%. Patients with acromegaly had significantly higher BMD at all skeletal sites but lower TBS than hypogonadal subjects. This difference remained statistically significant after grouping patients with acromegaly according to gonadal status and comparing them with patients with hypogonadism. However, presence of hypogonadism in patients with acromegaly did not influence BMD, TBS or VF prevalence. Moreover, patients with active acromegaly did not have significantly different BMD, TBS and VF prevalence compared to patients with controlled disease. Patients with acromegaly with VF had significantly lower BMD at all skeletal sites than those without VF, but no difference in TBS. CONCLUSIONS: Vertebral fractures are frequent in acromegaly, and are associated with lower BMD but not with TBS. Patients with acromegaly, regardless of gonadal status, have significantly higher BMD but lower TBS than hypogonadal patients. Moreover, disease activity and hypogonadism do not influence BMD, TBS or VF in acromegaly.

Vitamin D Status and VDR Polymorphisms as Prognostic Factors in Differentiated Thyroid Carcinoma.

BACKGROUND/AIM: Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms are involved in a variety of biological processes including cell proliferation, apoptosis, and adhesion in malignant tumors. This study investigated whether vitamin D levels and genetic variations of VDR are risk factors for thyroid cancer. PATIENTS AND METHODS: Patients who underwent surgery for differentiated thyroid carcinoma (n=113) and those with benign thyroid pathology (n=150) were genotyped for VDR gene polymorphisms (ApaI, TaqI, FokI, and BsmI) and their 25(OH)D levels were simultaneously measured. Demographic data and histopathologic reports were also acquired for all patients. RESULTS: Vitamin D levels were significantly lower in the thyroid cancer group (p=0.03). FokI and TaqI polymorphisms were more frequent in the thyroid cancer patients (p<0.001). Compared to control, the proportion of the FokI Ff genotype was increased (p<0.0006) and the proportion of the TaqI Tt genotype was also higher among patients with thyroid cancer (p<0.0001). The Ff genotype of FokI was also associated with multifocality, invasive pattern, and risk for local metastasis. CONCLUSION: The VDR gene polymorphism FokI may be associated with the risk of thyroid cancer and its more aggressive forms.

Matrix metalloproteinase-9 (MMP-9) promoter -1562C/T functional polymorphism is associated with an increased risk to develop micropapillary thyroid carcinoma.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an important mediator of tumor initiation and progression. The MMP-9 promoter -1562C/T functional polymorphism increases gene expression and was identified as a susceptibility factor for various cancers. OBJECTIVE: To evaluate the influence of the MMP-9 promoter genotype on the risk of developing papillary thyroid cancer (PTC) and to correlate cancer patient genotype with the clinical and pathological phenotype. METHODS: We evaluated 236 patients with nodular thyroid disease pre-thyroidectomy (119 benign disease, 117 PTC). Genomic DNA was isolated from whole blood and the MMP-9 -1562C/T genotype was evaluated by PCR-RFLP analysis. RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium for all groups. The T allele was significantly more frequent in cancer compared to benign disease (17.5% vs 10.1%), p= 0.019. Patients with the CT or CT+TT genotype had an increased risk of developing PTC, specifically micropapillary thyroid carcinoma (MPTC) (CT genotype: OR = 6.467, p= 0.00006; CT+TT: OR = 6.859, p= 0.00002), but not more advanced stages (CT: p= 0.094; CT+TT: p= 0.157). The -1562C/T genotype did not significantly correlate with tumor histological subtype, invasion or TNM stage. CONCLUSION: The MMP-9 -1562C/T functional polymorphism may indicate susceptibility to develop thyroid cancer, specifically intrathyroidal clinically non-relevant MPTC. This suggests that although this genotype might be a predisposing factor, other genetic/epigenetic events are needed for cancer progression.

Serum soluble urokinase plasminogen activator receptor as a potential biomarker of renal impairment severity in diabetic nephropathy.

AIMS: To investigate serum soluble form of urokinase-type plasminogen activator receptor (suPAR) in patients with diabetic kidney disease (DKD) and biopsy-proven diabetic nephropathy (DN), its correlation with histological parameters and its capacity as a biomarker for renal impairment severity. METHODS: We conducted a cross-sectional study on 75 patients with diabetes mellitus (DM) and DKD, among whom 28 had biopsy-proven DN. RESULTS: Among the 75 patients, 9 (12%) had type 1 and 66 (88%) type 2 DM. The median value of the serum suPAR level was 2857.2 pg/mL (1916.4-3700) in the entire cohort and 2472.1 pg/mL (1782.6-3745.8) in the biopsy-proven DN subgroup, respectively. suPAR was significantly correlated with diabetes duration, diabetic retinopathy, anti-proteinuric treatment, albuminuria, kidney function, DN class, interstitial fibrosis and tubular atrophy (IFTA) score and with interstitial inflammation score. suPAR had a good accuracy for the association with chronic kidney disease (CKD) stages G3b-5, macroalbuminuria, DN class IV, IFTA score 3 and interstitial inflammation score 2. CONCLUSIONS: Serum suPAR was increased in DN patients and was associated with DM duration, diabetic retinopathy, renoprotective treatment, kidney function, proteinuria, DN class, IFTA and interstitial inflammation scores. Also, suPAR had a good capacity as a biomarker for advanced renal impairment and severe histological lesions of DN.

Thresholds of Basal- and Calcium-Stimulated Calcitonin for Diagnosis of Thyroid Malignancy.

Since medullary thyroid carcinoma is an aggressive cancer, it is important to have an early detection based on stimulated calcitonin (CT), especially when basal-CT is slightly elevated. The objective of this work was to set specific thresholds for basal-CT- and calcium-stimulated calcitonin for prediction of thyroid malignancy in female population. The study included 2 groups: group A-women with elevated basal-CT (>9.82 pg/ml) and group B-women with normal basal-CT (control group). After calcium stimulation test precise protocol, histopathological reports of those that required surgery were correlated with both basal and stimulated calcitonin. The best basal and stimulated calcitonin cut-offs for distinguishing female patients with medullary thyroid carcinoma or C-Cell-hyperplasia from other pathologies or normal cases were: 12.9 pg/ml, respectively 285.25 pg/ml. For basal-CT above 30 pg/ml, malignancy was diagnosed in 9/9 patients (100%): 9 MTC. For stimulated calcitonin above 300 pg/ml, malignancy was diagnosed in 17/21 patients (80.95%): 12 MTC and 5 papillary thyroid carcinomas. The smallest nodule that proved to be medullary thyroid carcinoma had only 0.56/0.34/0.44 cm on ultrasound, with no other sonographic suspicious criteria. In conclusion, we have identified in Romanian female population basal and stimulated calcitonin thresholds to discriminate medullary thyroid carcinoma or C-Cell-hyperplasia from other cases. We recommend thyroid surgery in all women with stimulated calcitonin above 285 pg/ml. Further studies on larger groups are necessary to establish and confirm male and female cut-offs for early diagnosis of medullary thyroid carcinoma, and interestingly, maybe for macro-papillary thyroid carcinomas alike. The calcium administration has minimum side-effects, but continuous cardiac monitoring is required.

Trabecular bone score and bone mineral density in acromegalic osteopathy assessment: a cross-sectional study.

PURPOSE: The evaluation of acromegalic osteopathy is a subject of current interest as there is a lack of evidence concerning proper evaluation techniques and clear diagnostic criteria. The aim of this study was to evaluate lumbar spine trabecular bone score (TBS) and bone mineral density (BMD) in acromegaly patients compared to healthy controls. METHODS: We conducted a cross-sectional study on 43 acromegaly patients recruited between 2018 and 2020 and a healthy control group matched 1:1 for age, gender, and body mass index (BMI). All subjects underwent DXA, lumbar spine TBS, and bone turnover markers measurement. RESULTS: Acromegaly patients showed significantly decreased lumbar spine TBS (1.244 ± 0.117 vs. 1.343 ± 0.124, p < 0.001) and no difference regarding BMD compared to control patients. In the subgroup analysis, TBS was significantly lower in both males and females (1.282 ± 0.075 vs. 1.366 ± 0.113, p = 0.01 and 1.222 ± 0.132 vs. 1.329 ± 0.130, p = 0.005) and, also, in hypogonadal and eugonadal acromegaly subjects compared to their healthy controls (1.231 ± 0.130 vs. 1.306 ± 0.125, p = 0.04 and 1.280 ± 0.065 vs. 1.381 ± 0.113, p = 0.008). Femoral neck BMD was higher in acromegalic hypogonadal patients [1.027 (IQR: 0.939-1.135) vs. 0.876 (IQR: 0.737-1.014), p = 0.004]. CONCLUSION: Our study indicates that TBS, but not BMD, is significantly decreased in acromegaly patients, regardless of gender and gonadal status. This data suggests that TBS could be a valuable tool in the assessment of acromegalic osteopathy.

The Relationship between Advanced Oxidation Protein Products, Vascular Calcifications and Arterial Stiffness in Predialysis Chronic Kidney Disease Patients.

Background and Objectives: Cardiovascular morbidity and mortality are increased in patients with chronic kidney disease (CKD). It is likely that the accumulation of uremic toxins resulting in increased oxidative stress (OS) is a major contributing factor, but no clear link has been identified. The purpose of this research is to establish if advanced oxidation protein product (AOPP) levels in the serum of predialysis patients are a contributing factor to vascular calcification and increased arterial stiffness. Materials and Methods: After obtaining the informed consent, 46 predialysis patients (CKD stages G3-G5) were included in the study. In order to identify vascular calcifications, hand and pelvic radiographs were performed. Valvular calcifications were identified using cardiac ultrasound. AOPP were measured using a commercially available ELISA kit. The relationships between serum AOPP values and biochemical parameters relevant in the evaluation of CKD patients were analyzed. In addition to identifying the differences in AOPP levels between patients with/without vascular or valvular calcifications, the research focused on describing the relationship between OS and arterial stiffness assessed by oscillometric pulse-wave velocity (PWV) measurement. Results: No significant relationship between serum AOPP and vascular or valvular calcifications was highlighted, but significant correlations of AOPP with C-reactive protein (p = 0.025), HDL-cholesterol levels (p = 0.04), HbA1c (p = 0.05) and PWV values (p = 0.02) were identified. Conclusions: The usefulness of (OS) measurement in clinical practice remains debatable; however, the relationship between AOPP and arterial stiffness could be valuable in improving cardiovascular risk assessment of patients with CKD.

Combined Effects of Vitamin D Status, Renal Function and Age on Serum Parathyroid Hormone Levels.

Background: Vitamin D status and renal function are well-known independent predictors of serum parathyroid hormone (PTH) levels. We aimed to describe the combined effects of 25-hydroxy vitamin D (25(OH)D), glomerular filtration rate (GFR) and age on serum PTH levels across the whole clinical spectrum. Methods: We retrieved from our endocrinology center database all PTH measurement between 2012 and 2020 for which a simultaneous measurement of serum 25(OH)D, calcium and creatinine was available. Age, sex and diagnosis were available for all subjects. Intact PTH was measured using the same electrochemiluminescence assay. Results: There were 6,444 adults and 701 children without a diagnosis of hyper- or hypoparathyroidism or abnormal serum calcium levels. In adults with 25(OH)D≥12 ng/mL multiple regression models showed that serum PTH was negatively correlated with both 25(OH)D and GFR. Regression (-0.68 and -1.59 vs. -0.45 and -0.22 respectively), partial correlation (-0.16 and -0.35 vs. -0.12 and -0.10 respectively) and determination coefficients (0.14 vs. 0.031) were higher in CKD than in normal renal function. In subjects with 25(OH)D<12 ng/mL, GFR was the only significant predictor in those with CKD (ß-coefficient=-2.5, r=-0.55) and 25(OH)D was the only significant predictor in those with normal renal function (ß-coefficient=-2.05, r=-0.11). Increasing age was associated with higher PTH levels only in those with normal renal function and 25(OH)D≥12 ng/mL. Conclusions: We showed that declining vitamin D and renal function have additive effects on serum PTH in subjects without vitamin D deficiency. In vitamin D deficient subjects this dependency is stronger but is not additive anymore.

Thyroglobulin in lymph node fine-needle aspiration biopsy washout fluid. A tertiary center experience.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Most PTC secretes thyroglobulin, a useful marker in monitoring preoperative staging and postoperative progression; in addition to serum thyroglobulin, fine needle aspiration washout thyroglobulin (FNA-Tg) is also used. Our aim was to determine the cut-off value for FNA-Tg in our center and to describe major discrepancies between FNA-Tg, cytology and pathology results of the lymph nodes. METHODS: We retrospectively retrieved from the electronic database of our endocrinology center all the FNA-Tg measurements between December 10, 2019 and September 2021. For each measurement we also retrieved the corresponding sex, FNAB results and the pathology reports. FNA-Tg was measured by ECLIA immunoelectro-chemiluminescent method. RESULTS: There were 58 FNAB and FNA-Tg of suspect cervical lymph nodes in 40 patients. There were 17 cytologically benign lymph nodes of which 13 had low and 4 had high FNA-Tg; 3 non-diagnostic cytology results of which one had high FNA-Tg; 38 PTC metastases of which 6 had low and 32 had high FNA-Tg titers. The cut-off value of FNA-Tg in our center is 10 ng/ml, with a sensitivity of 86.6% (in those with pathology reports available after surgery). CONCLUSIONS: Washout TG is useful in suspicious lymph nodes and has added value to cytology in selected cases. The cut-off value of FNA-Tg in our center is 10 ng/ml, with a sensitivity of 86.6%. However, we must consider the possible false negative results that may occur in some histological types of PTC.

Serum Matrix metalloproteinase-9 (MMP-9) can help identify patients with papillary thyroid cancer at high risk of persistent disease: Value and limitations of a potential marker of neoplasia.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an important mediator of invasion and metastasis in neoplasia. In thyroid cancer expression levels correlate with aggressiveness but data on peripheral MMP-9 levels are less definitive. OBJECTIVE: Prospective study evaluating serum MMP-9 in the diagnosis and prognosis of papillary thyroid cancer. METHODS: Serum samples of MMP-9 were drawn before surgery in 185 consecutively enrolled patients with nodular thyroid disease, stratified on pathology as benign disease (N= 88) and papillary thyroid cancer (N= 97). Serum MMP-9 was measured by an immunometric assay. RESULTS: MMP-9 levels were not different between benign vs malignant pathology (p= 0.3). In papillary thyroid cancer there was no significant difference in MMP-9 levels between histologies, TNM stage and invasive/non-invasive cancers. High-risk patients with multiple features of aggressiveness had significantly higher MMP-9 levels compared to low-intermediate risk patients (767.5 ± 269.2 ng/ml vs 563.7 ± 228.4 ng/ml, p= 0.019). A cut-off of 806 ng/ml distinguished high from low-intermediate risk patients with a sensitivity of 60% and a specificity of 87.36%, p= 0.018. In patients with available follow-up data (N= 78), MMP-9 was higher in patients who required ⩾ 2 doses of 131I therapy (p= 0.009) and in those with biochemical evidence of persistent disease/who required additional therapy to achieve disease-free status (p= 0.017). CONCLUSION: Serum MMP-9 is not useful in the diagnosis of PTC, but preliminary data shows that high pre-surgical serum MMP-9 levels may identify patients at higher risk of persistent disease who require intensive treatment. Large volume prospective studies are required to confirm this observation.

Seasonal periodicity of serum parathyroid hormone and its relation with vitamin D in Romania.

We measured serum parathyroid hormone in 8409 Romanian subjects and found a mild seasonal variation with highest levels in March and lowest levels in September. PTH was dependent on serum vitamin D, particularly below 12.82 ng/mL. Together, these suggest that vitamin D supplementation is warranted only in at-risk groups. PURPOSE: Seasonal variation of parathyroid hormone (PTH) and its dependency on serum 25-hydroxy vitamin D (25(OH)D) levels are well-described. However, there are few studies from Europe, and genetic, nutritional, and cultural differences are important. We describe the seasonal variation of serum PTH and its relation with serum 25(OH)D levels in Romania. METHODS: We retrieved from our endocrinology center database all PTH measurements between 2011 and 2019 together with age, sex, diagnosis, and date of blood sampling. Simultaneous serum 25(OH)D levels were partially available. Intact PTH was measured using the same electrochemiluminescence assay. RESULTS: There were 8409 subjects (median age 49 (36, 60) years; 20.5% men) without a diagnosis of hyperparathyroidism (primary or secondary to chronic kidney disease), hypoparathyroidism, or low bone mass. Serum PTH showed a mild seasonal variation with highest levels at the end of March (47.61 pg/mL) and lowest levels at the end of September (43.15 pg/mL). All sex and age subgroups showed highest levels in the spring and lowest levels in the fall. Males had significantly lower PTH levels than females irrespective of season. PTH correlated inversely with serum 25(OH)D with a breakpoint of 12.82 ng/mL in 2800 subjects who had a simultaneous measurement of 25(OH)D. Increasing age was associated with increasing PTH levels independently of serum 25(OH)D. CONCLUSIONS: We showed a mild seasonal variation of serum PTH in Romania, at an inverse sinusoidal pattern than serum 25(OH)D. The breakpoint on the PTH-25(OH)D correlation suggests that vitamin D supplementation is warranted only in at-risk groups.

Improvement of acromegaly control with multimodal therapy in Romania.

INTRODUCTION: In Romania, there is no acromegaly national register and there are no nationwide data available. However, some studies have reported the control rates in the country's main referral centres. Our aim was to assess the overall control rate in our tertiary referral centre. Also, we assessed the control rate in the last three years, and we compared the results with our previous reports. MATERIAL AND METHODS: We reviewed the charts of 186 patients with acromegaly assessed in our department between January 1st, 2012 and May 31st, 2019. We also compared the control rates for patients treated between April 1st, 2016 and May 31st, 2019 with historical controls (assessed between January 1st, 2012 and March 31st, 2016). RESULTS: Primary analysis: There were 19 untreated and 167 treated patients, mean age 52.46 years, surgery being the most commonly used treatment. The surgical cure rate was 14.8%, and disease control with medical treatment was 35.3%. Secondary analysis: In the first group there were 45 patients, surgery also being the most commonly used treatment. The surgical cure rate was 26.9%, and disease control was 30.4%. In the second group (historical controls) there were 42 patients, surgery being the most commonly used treatment. The surgical cure rate was 9.7%, and disease control with medical treatment was 15.4%. Random GH and IGF-1 after surgery were lower in the first group (p < 0.05) CONCLUSIONS: Changes in the Romanian protocol and highly specialised pituitary centres has improved the cure rate and disease control in patients with acromegaly.

Bone turnover correlates with bone quantity but not bone microarchitecture in chronic hemodialysis.

INTRODUCTION: In chronic hemodialysis, high-turnover bone disease was associated with decreased bone mineral density (BMD), poor bone quality (chemical and structural), and increased fracture risk. Our aim was to correlate bone turnover markers (BTMs) with bone microarchitecture measured by trabecular bone score (TBS) before and after correction for BMD. MATERIALS AND METHODS: We measured lumbar spine (LS), femoral neck, and 1/3 radius BMD and LS TBS by dual X-ray absorptiometry in 81 patients on permanent hemodialysis. Bone turnover was assessed using serum parathyroid hormone, osteocalcin, C-terminal crosslaps of type 1 collagen, procollagen 1 N-terminal propeptide (P1NP), and alkaline phosphatase (ALP). No patient had any partial or total parathyroidectomy and no previous or current treatment with anti-osteoporotic drugs. RESULTS: All BTMs correlated significantly with each other. Univariate regressions showed significant negative correlations between BTMs and BMD (best r = - 0.53, between P1NP and 1/3 radius Z-score) or BTMs and TBS (best r = - 0.27, p < 0.05 between ALP and TBS T-score). TBS correlated significantly with BMD at all three sites (best r = 0.5, between LS BMD and TBS T-score). Multivariate regression showed that TBS, crude or adjusted, correlated with LS BMD. No model retained any of the BTMs as independent variables due to the better prediction of BMD and multicollinearity. CONCLUSION: We showed a progressively impaired bone microarchitecture with increasing bone turnover in chronic hemodialysis. However, this correlation is no longer present when controlling for bone mass. This suggests that impaired bone microarchitecture and increased fracture risk are dependent upon factors other than high bone turnover.

Disposition Index in Active Acromegaly.

Background: The relative contribution of reduced insulin sensitivity (Si) or insulin secretion to impaired fasting glucose (IFG) or diabetes mellitus (DM) has not been clarified in active acromegaly. An intravenous glucose tolerance test (IVGTT) was never used for the calculation of Si, acute insulin response (AIRg), and disposition index (DI) in this population. Our aim was to assess Si, AIRg and DI using an IVGTT in acromegaly with normal (NGT) and abnormal glucose tolerance. Methods: We performed an IVGTT in 13 patients (8 NGT, 2 IFG, and 3 DM; 5 males, age 47.9 ± 11 years, body mass index 29.7 ± 4.1 kg/m2) with active acromegaly (insulin-like growth factor-1 4.1 ± 1.3 × upper limit of normal, basal GH 29.1 ± 25 ng/mL) and 3 healthy controls (2 males, age 39 ± 3 years, body mass index 23 ± 5 kg/m2). No patient had any growth hormone- or glucose-lowering medication. Results: NGT patients had significantly lower Si than healthy controls but higher AIRg. Hyperglycemic and normoglycemic patients had similar Si. DM patients had severely diminished AIRg (5-260 pmol × min/L) while IFG patients maintained their insulin secretion (3,862 and 912 pmol × min/L). Patients with abnormal glucose tolerance (IFG + DM) had a significantly lower DI (353 ± 350) than both NGT patients (3,685 ± 2,544) and healthy controls (5,837 ± 1,894; p < 0.01 for ANOVA). Conclusions: Disposition index suggests that although reduced insulin sensitivity is characteristic of active acromegaly it is the impaired insulin secretion that mainly drives glucose intolerance. The clinical utility of DI in predicting DM in acromegaly must be further investigated.

Metabolic and bone profile in postmenopausal women with and without type 2 diabetes: a cross-sectional study.

INTRODUCTION: Current studies support the implication of metabolic changes associated with type 2 diabetes in altering bone metabolism, structure and resistance. OBJECTIVE: We conducted a cross-sectional study on postmenopausal women aimed to analyze the differences in metabolic and bone profile in patients with and without type 2 diabetes Methods. We analyzed the metabolic and bone profile in postmenopausal women with and without type 2 diabetes (T2DM). Clinical, metabolic, hormonal parameters, along with lumbar, hip and femoral bone mineral density (BMD) and trabecular bone score (TBS) were evaluated. RESULTS: 56 women with T2DM(63.57±8.97 years) and 83 non-T2DM (60.21±8.77 years) were included. T2DM patients presented a higher value of body mass index (BMI) and BMD vs. control group (p = 0.001; p = 0.03-lumbar level, p = 0.07-femoral neck and p = 0.001-total hip). Also, BMI correlated positively with lumbar-BMD and glycated hemoglobin (HbA1c) (r = 0.348, p = 0.01; r = 0.269, p = 0.04), correlation maintained even after age and estimated glomerular filtration rate (eGFR) adjustment (r = 0.383, p = 0.005; r = 0.237, p = 0.08). Diabetic patients recorded lower levels of 25(OH)D(p = 0.05), bone markers (p ≤ 0.05) and TBS(p = 0.07). For the entire patient group we found a negative correlation between HbA1c level and bone markers: r = -0.358, p = 0.0005-osteocalcin, r = -0.40, p = 0.0005-P1NP, r = -0.258, p = 0.005-crosslaps. CONCLUSIONS: Our results indicate the presence of altered bone microarchitecture in T2DZ patients according to the TBS score, combined with lower levels of bone markers, with a statistically significant negative correlation between HbA1c level and bone markers.

Seasonal variation of serum vitamin D levels in Romania.

We measured serum vitamin D in 8024 Romanian subjects and found a marked seasonal variation with highest levels in September and lowest levels in March. The seasonal variation (early autumn vs. early spring) persisted in all age and sex groups. The prevalence of vitamin D deficiency was very high. PURPOSE: Romania is located in Eastern Europe, roughly between 44°N and 48°N latitude. Seasonal variation of serum vitamin D in Romanian subjects is unknown. We assessed the seasonal variation of 25-hydroxy vitamin D [25(OH)D] in Romanian population. METHODS: We retrieved from our endocrinology center database all 25(OH)D measurements between 2012 and 2016. We also evaluated age, sex, diagnosis, and date of blood sampling. The 25(OH)D was measured by two different chemiluminescence or electrochemiluminescence assays. RESULTS: There were 8024 subjects (median age 50 (37, 62); 1429 men (17.8%)) without a diagnosis of low bone mass (osteopenia or osteoporosis). The median serum 25(OH)D was 18.6 (12.7, 25.4) ng/mL. Of the subjects, 0.73, 14.4, 55.6, and 86.1% had a serum 25(OH)D level below 4, 10, 20, and 30 ng/mL, respectively. Serum 25(OH)D showed a marked seasonal variation with highest levels in September (24.1 [18.3, 30.3] ng/mL) and lowest levels in March (13.5 [9.4, 19.6] ng/mL) (p < 0.001). The seasonal variation (early autumn vs. early spring) persisted in all age and sex groups and was maximal for 21-40 years of age (26.5 (20.8, 33.1) vs. 12.9 (9.7, 17.9) ng/mL) and minimal for >65 years of age (18.6 (13.0, 27.2) vs. 12.7 (7.8, 19.7) ng/mL). Men and women showed similar amplitude of serum 25(OH)D variation. CONCLUSION: The prevalence of vitamin D deficiency is high, particularly in the elderly. The data show a strong seasonal variation of serum 25(OH)D in all subgroups of our Romanian population with highest levels in September and lowest levels in March.

Acromegaly treatment in Romania. How close are we to disease control?

INTRODUCTION: In Romania, no nationwide data for acromegaly treatment and control rate are available. Our objective was to assess the acromegaly control rate in a tertiary referral centre, which covers an important part of Romanian territory and population of patients with acromegaly. MATERIALS AND METHODS: We reviewed the records of all 164 patients (49 males and 115 females; median age 55 [47, 63.5] years) with newly or previously diagnosed acromegaly, who have been assessed at least once in our tertiary referral centre between January 1, 2012 and March 31, 2016. This sample represents 13.6% of the total expected 1200 Romanian patients with acromegaly and covers 82.9% of the counties in Romania. Control of acromegaly was defined as a random serum growth hormone (GH) < 1 ng/mL and an age-normalised serum insulin-like growth factor-I (IGF-I) value. The GH and IGF-I values used for calculation of the control rate were those at the last evaluation. The same assays for GH and IGF-I measurement were used in all patients. RESULTS: There were 147 treated and 17 untreated patients. Of the 147 patients assessed after therapy, 137 (93.2%) had pituitary surgery, 116 (78.9%) were on medical treatment at the last evaluation, and 67 (45.5%) had radiotherapy. Seventy-one (48.3%) had a random GH < 1 ng/mL, 54 (36.7%) had a normalised, age-adjusted IGF-I, and 42 (28.6%) had both normal random serum GH and IGF-I. CONCLUSIONS: In Romania, acromegaly benefits from the whole spectrum of therapeutic interventions. However, the control rate remains disappointing.

Vitamin d deficiency in postmenopausal women - biological correlates.

INTRODUCTION: Low vitamin D (VD) is associated with secondary hyperparathyroidism and both contribute to deleterious consequences (reduced bone mineral density (BMD), risk of fractures and falls). OBJECTIVE: To study the VD status and biological correlates in a group of postmenopausal women. MATERIAL AND METHODS: We studied 123 postmenopausal women evaluated in the C.I.Parhon National Institute of Endocrinology, the Pituitary and Neuroendocrine Diseases department. All cases had been reffered for the evaluation of BMD by the general practitioner. The evaluation included serum measurements of total and ionised calcium, phosphorus, alkaline phosphatase (ALP), 25 hydroxi vitaminD (25OHD), parathyroid hormone (PTH), osteocalcin, betacrosslaps. Central DXA osteodensitometry was performed. RESULTS: 91.9% of cases had 25OHD serum levels below 30 ng/ml (74.8% had VD deficiency, 17.1% VD insufficiency). Only 8.1% had sufficient VD levels. A history of fragility fractures was present in 45.83% of the osteoporotic patients, 27.27% of the osteopenic ones and 15.15% of the women with normal BMD. 32 women (26%) were on VD supplementation at the time of evaluation. Among these subjects, the 25OHD level was significantly higher in those with prior fragility fractures (p=0.018) and osteoporosis (p=0.008). 25OHD concentration negatively correlated with PTH, alkaline phosphatase (ALP) and osteocalcin. The bone markers evaluated had a significant inverse correlation with the radius BMD, T and Z scores (p=0.004). 27.17% of the cases with VD deficiency had secondary hyperparathyroidism. The 25OHD concentration was significantly lower in these cases (p=0.000). CONCLUSIONS: VD insufficiency is widely prevalent but still under-recognized and under-treated, possibly leading to secondary hyperparathyroidism. The compliance to VD supplementation is lower in subjects without osteoporosis or fragility fractures. Primary prevention measures should be more actively implemented.

Screening for secondary endocrine hypertension in young patients.

BACKGROUND: Secondary endocrine hypertension accounts for 5-12% of hypertension's causes. In selected patients (type 2 diabetes mellitus, sleep apnea syndrome with resistant hypertension, sudden deterioration in hypertension control), prevalence could be higher. OBJECTIVES: To present etiology of endocrine secondary hypertension in a series of patients younger than 40 years at hypertension's onset. MATERIAL AND METHODS: Medical records of 80 patients (39M/41F), aged 30.1 ± 8.2 years (range: 12-40 years), with maximum systolic blood pressure=190.4 ± 29.2 mm Hg, range: 145-300 mm Hg, maximum diastolic blood pressure=107.7 ± 16.9 mm Hg, range: 80-170 mm Hg) referred by cardiologists for endocrine hypertension screening were retrospectively reviewed. Cardiac and renal causes of secondary hypertension were previously excluded. In all patients, plasma catecholamines were measured by ELISA and plasma cortisol by immunochemiluminescence. Orthostatic aldosterone (ELISA) and direct renin (chemiluminescence) were measured in 48 patients. RESULTS: Secondary endocrine hypertension was confirmed in 16 out of 80 patients (20%). Primary hyperaldosteronism was diagnosed in 7 (4M/3F) out of 48 screened patients (14.6%). i.e. 8.75% from whole group: 5 patients with adrenal tumors (3 left/2 right), 2 patients with bilateral adrenal hyperplasia; all patients were hypokalemic at diagnostic (average nadir K+ levels = 2.5 ± 0.5 mmol/L); four patients were hypokalaemic on diuretic therapy (indapamidum); other 3 patients were hypokalaemic in the absence of diuretic therapy. Cushing's syndrome was diagnosed in 6 patients (7.5%): subclinical Cushing due to 4 cm right adrenal tumour - n = 1, overt ACTH-independent Cushing's syndrome due to: macronodular adrenal hyperplasia associated with primary hyperparathyroidism - n = 1; due to adrenal carcinoma - n = 1; due to adrenal adenomas - n = 2; Cushing's disease - n = 1). Pheochromocytomas were diagnosed in 3 patients (3.75%). CONCLUSION: Primary hyperaldosteronism was the most frequent cause of secondary endocrine hypertension in our series, followed by Cushing's syndrome and pheochromocytomas. Screening of young hypertensive patients for secondary causes, especially primary hyperaldosteronism, is mandatory.