ACTA ENDOCRINOLOGICA (BUC)

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fragility fractures compared to the general population. The pathogenesis of the elevated fracture risk is multifactorial and still largely elusive. In contrast to primary osteoporosis, in T2DM the bone mineral density (BMD) is increased compared to controls, suggesting that specific alterations in bone quality occur in diabetic patients. Even more, the specific increase in BMD observed in these patients impairs at least in part both the classical diagnosis of osteoporosis by dual-energy X-ray absorptiometry (DXA) and the current fracture risk estimation by FRAX (fracture risk assessment tool). Trabecular bone score (TBS) and TBS-adjusted FRAX could improve fracture risk estimation in patients with T2DM but improved tools are needed in the future as well as specific risk stratification criteria. Decreases in the fracture risk of patients with T2DM can be obtained by optimal diabetes control and standard treatment of osteoporosis (most drugs appear to have similar efficacy in patients with T2DM and primary osteoporosis).

Aggressive pituitary tumors lie between pituitary adenomas and carcinomas, displaying a particular behavior, with invasion, resistance to conventional therapy and early recurrence. The radiological grading, along with prognostic markers such as Ki-67 proliferation index, p53, MGMT and transcription factors are important factors in establishing the benign, aggressive, or malignant nature of pituitary tumors, with a more accurate treatment strategy. In this article, we report the novelties in defining, classifying, and managing aggressive pituitary tumors and their malignant potential, focusing on clinicopathological, histological, molecular and radiological data.

treatment of postmenopausal osteoporosis. It has estrogen agonist effects on bone and on surrogate markers of cardiovascular risk, but estrogen antagonist effects on breast and endometrium. It inhibits bone resorption and decreases bone turnover, increases bone mineral density and reduces the risk of vertebral fractures in postmenopausal women.\r\nObjectives: The main endpoint of our study was to evaluate the effect of raloxifene therapy (60 mg/day) on biochemical markers of bone turnover in romanian osteoporotic postmenopausal women. Secondary endpoints were the effect on bone mineral density (BMD), body mass composition and lipid profile.\r\nMaterials and methods: We performed a longitudinal, prospective, open study, investigating 29 postmenopausal white women with osteoporosis (Group 1) aged 56.9?7.8 years (mean ? SD) and in addition a control group of 29 premenopausal healthy white women (Group 2) with a mean age of 35.10 ? 7.8 years. The diagnosis of osteoporosis was established by dual-energy x-ray absorptiometry. We appreciated in both groups the bone turnover, measuring a marker of bone resorption: serum beta CrossLaps and a marker of bone formation: serum osteocalcin. We determined also the lipid profile: plasma cholesterol (mg/dL), HDL cholesterol (mg/dL), LDL cholesterol (mg/dL) and triglycerides (mg/dL) in all patients. Osteoporotic women received raloxifene 60 mg/day for one year. Biochemical bone markers, lipid profile and body composition have been evaluated at 3, 6 and 12 months of treatment and BMD was performed at 6 and 12 months of therapy.\r\nResults: Postmenopausal osteoporotic women showed an increased bone turnover in comparison with premenopausal women, with statistically significant increased serum values of both resorption and formation biochemical bone markers: respectively 0.48?0.2 vs 0.23?0.1 ng/mL for beta CrossLaps and 27.94?12.1 vs 17.30?8.9 ng/mL for osteocalcin, p<0.001. Raloxifene therapy for three months reduced significantly both bone resorption and formation: 0.36 ? 0.2 vs 0.48 ? 0.2 ng/mL, p< 0.005 for beta CrossLaps and 22.03 ? 10.1 vs 27.94 ?12.1 ng/mL, p< 0.001 for osteocalcin. After 3, 6 and 12 months of therapy with raloxifene the bone markers were statistically significant reduced: -21.2%, -20.4% and respectively -31.6% for osteocalcin and -25%, -39.6% and respectively -50% for beta CrossLaps (p< 0.01). After six months of therapy, serum levels of beta CrossLaps were reduced to premenopausal range (0.29 ? 0.1 vs. 0.23 ? 0.1 ng/mL, p=ns). Total cholesterol and LDL-C were reduced after 12 months (p< 0.03), with no increase in triglycerides and at the same time body mass composition was unchanged.\r\nConclusions: Our results suggest that raloxifene reduces as early as three months the bone turnover in postmenopausal osteoporosis. It reduces bone turnover in premenopausal range after only six months of therapy, for the bone resorption (beta CrossLaps) and after 12 months for bone formation (osteocalcin). In addition raloxifene treatment has favorable effects on BMD and lipid profile, proving safety and a stable body mass composition.

Paget's disease of bone is a metabolic skeleton disorder with different epidemiological patterns: increased incidence up to 3% of the Northern Caucasian population over the age of 55 or a very rare occurrence as in Asia. We present a case of a 69 years old female patient with diffuse bone pain, suspected of osteoporosis after a DXA investigation of bones. She has developed progressive skull deformation over the last 17 years and bilateral sensoneural deafness. On admission in our hospital, she had alkaline phosphatase serum levels five times higher than the upper normal value and low values of 25 hydroxy vitamin D. Parathormone and calcium levels were in normal range. Radiologic findings confirmed the monostotic type of Paget's disease. Other biomarkers of bone remodeling: serum osteocalcin for bone formation and serum beta Cross Laps for bone resorption, showed moderately increased levels. High dose therapy with alendronate and alphacalcidol were given with the normalization of bone markers after 9 months of sustained treatment. The vitamin D deficiency of this patient is an independent, associated disease, producing a decrease of bone mineral density as shown by DXA measurement. The case presentation and the review of the medical literature on this subject are intended to remind clinicians of the importance of appropriate diagnosis and therapy in this disease, as well as the importance of establishing the prevalence of Paget's disease of bone in Romania.

Context. Thyroid fine-needle aspiration (FNA) cytology is the best tool for preoperative diagnosis of thyroid carcinoma; however, its learning curve is poorly described. Our aim was to assess the learning curve of a new thyroid FNA center involving unexperienced operator and pathologist. Methods. We retrieved from our tertiary endocrinology center database all thyroid FNA procedures done by a single operator (endocrinologist with no experience in FNA) between 2018 and 2021. Cytology was assessed by two pathologists with limited or no experience in thyroid cytology. We also got the corresponding sex, age, nodule diameter, EU-TIRADS score, Bethesda category and final pathology report. Results. There were 1872 FNA in 1618 patients. Proportion of Bethesda 1 nodules decreased significantly (p for trend=0.003) from 17% in the first 100 FNA procedures to 4% in the 401-500 group of procedures, and remained constant between 9% and 4% (p for trend=NS) for the rest of the study. Proportion of Bethesda 2 rose steady from 26% in the first 100 nodules to 80.1% in the last 241 nodules (p for trend<0.001). Indeterminate lesions (Bethesda 3 and 4) decreased significantly (p for trend=0.001) from 16% and 35% in the first 100 nodules to 2.5% and 5.8% in the last 241 lesions. Proportions of Bethesda 5+6 categories varied non-significantly over time. There were no time trends in the malignancy rate of surgically removed nodules. Conclusions. At least 300 procedures are needed to reach the standard performance. A steadily state for the whole center is obtained after about 500 procedures.

Osteoporosis (OP) is a disease predisposing postmenopausal women to fractures, and often accompanied by insulin resistance (IR) and metabolic syndrome (MetS). Previous studies provided contradictory results concerning prevalence of MetS in postmenopausal OP. To better understand the pathogenesis of IR, we reviewed cellular and molecular aspects and systematically reviewed studies providing homeostasis model assessment (HOMA) index. Bone is an active endocrine organ maintaining its integrity by orchestrated balance between bone formation and resorption. Both osteoblasts and osteoclasts contain receptors for insulin and insulin-like growth factor-1 (IGF-1) operating in skeletal development and in the adult life. Defects in this system generate systemic IR and bone-specific IR, which in turn regulates glucose homeostasis and energy metabolism through osteocalcin. Examination of genetic syndromes of extreme IR revealed intriguing features namely high bone mineral density (BMD) or accelerated growth. Studies of moderate forms of IR in postmenopausal women reveal positive correlations between HOMA index and BMD while correlations with osteocalcin were rather negative. The relation with obesity remains complex involving regulatory factors such as leptin and adiponectin to which the contribution of potential genetic factors and in particular, the correlation with the degree of obesity or body composition should be added.

We report the case of a 6.6 years old boy, born to healthy unrelated parents, from a normal pregnancy, admitted for severe growth retardation. His height was 71 cm\r\n(-9.3 SD), with a weight of 6.6 kg and he presented a triunghiular face, mycrognatia, proeminent nose and hypertelorism resulting in a ?bird headed? profile. He associated clinodactyly of the 5th finger and a slightly longer left leg. Tanner stages were P1 G1. The\r\nbiochemical panel was normal, but he presented mild hypocromic anemia. The thyroid function was normal, and the IGF1 low. The karyotype was 46 XY and the bone age 4.5\r\nyears. The pituitary computed tomography revealed empty sella. Based on the clinical picture, the possible diagnosis of Seckel syndrome was suspected. A short course of treatment with Metandienonum 0.04 mg/kg/day for 3 months was recommended, without success (growth speed of 6 cm/year - -0.14 SD)

Background. Advances in imaging techniques have led to increasing discovery of\r\nadrenal and pituitary &#8220;incidentalomas&#8221;, tumors with normal endocrine function and no\r\ncompression mass effects. We evaluated the age at diagnosis (AD) in patients with benign\r\nnon-functioning adrenal incidentalomas, as compared to pituitary non-functioning tumors,\r\nin a series of patients from a national center of endocrinology. Methods. From 2,123\r\nconsecutive patients with adrenal and pituitary tumors hospitalized between 1977 - 2009,\r\n2,069 patients were analysed. The study groups included: group A - 137 patients with\r\nadrenal incidentalomas (AI), group B - 534 patients with pituitary incidentalomas (PI).\r\nControl groups included 1,398 patients: group C1 147 patients with adrenal carcinomas or\r\nbenign hormone-secreting adrenal tumors, and group C2, 1,251 patients with pituitary\r\nsecreting adenomas or large non-functioning pituitary macroadenomas (NFA). Imaging was\r\ndone by computed tomography and/or magnetic resonance after 1981 and by skull X-ray or\r\npneumoencephalography before 1981. Results. Mean age AD is more advanced in patients\r\nwith AI (53 ? 11.9 years, range 21 - 78 yr) than in patients with PI (36.8 ? 13.1 years, range\r\n10 - 81 yr), p < 0.01. AD was higher in AI than in patients with secreting adrenal tumors,\r\nbut similar in patients with adrenal malignancy. There is an age-related increase in the\r\nproportion of AI among patients with adrenal tumors, and of NFA, but not of PI, among\r\npatients with pituitary tumors. In patients aged over 65 years, 74% of patients with adrenal\r\ntumors have AI, while only 18% of patients with pituitary tumors have PI and 42% have\r\nNFA. AD in NFA (49.3 ? 13.1 yr, range 12 - 79 yr) was more advanced than in PI (p < 0.01).\r\nAD does not correlate with tumor size. Tumor growth occurred in 24% of AI (follow-up 3.0\r\n? 2.8 yr) and only in 0.7% of PI, p<0.01 (follow-up 3.1 ? 2.5 yr).\r\nConclusions. Adrenal non-functioning benign tumors show a clear association with ageing,\r\nin contrast with pituitary incidentalomas. It seems unlikely that most pituitary incidentalomas in\r\nyoung patients become large NFA, whose development seems to be also age-related. It is tempting\r\nto suggest that pituitary tumorigenesis starts earlier than adrenal tumorigenesis.