ACTA ENDOCRINOLOGICA (BUC)

Background. If not diagnosed at birth, congenital hypothyroidism (CH) can cause deleterious, irreversible neurodevelopmental sequels. The importance of thyroid newborn screening (NBS) is therefore well established. Objective. To evaluate the efficacy of NBS for CH in North-East Romania. Methods. Retrospective, descriptive study involving 271662 newborns screened between 2010 and 2019 for CH and phenylketonuria in maternities from six Romanian NorthEastern counties by measuring neonatal TSH (neoTSH) in the whole blood extracted from the heel between days 3 and 5 after birth. Values found higher than a cut-off level of 10 mIU/L were followed by serum evaluation of TSH and fT4 for the confirmation of CH. Thyroid ultrasound was further performed at children found with CH. Results. NeoTSH was found elevated in 417 newborns, but CH was subsequently confirmed in only 57 cases (1/4766 newborns). Mean age at the time when diagnosis was communicated was of 37.2 ± 15 days (between 9 and 157 days). Mean age when therapy was started was of 44.2 ± 17.9 days (between 13 and 160 days) with a mean delay of one week from diagnosis (between 0 and 62 days). Thyroid ultrasound revealed athyreosis in only 3 cases, atrophic thyroid gland in other 10 cases, whereas the thyroid was described as present in the remnant 44 cases. The number of first year follow-up visits greatly varied from 0 to 5, with an average of 2. Conclusions. NBS allowed rapid diagnosis of CH in North East Romania. The communication of diagnosis to families and therapy onset were however often delayed. Diagnosis and therapy onset before the age of two weeks, as well as a tighter follow-up should be assured by the healthcare system. Etiological diagnosis should be more accurate, for a better prognosis of disease severity, as well as the possibility of genetic advice in selected cases.

Nodular thyroid disease (NTD) is represented by palpable thyroid nodules (solitary, multiple) and thyroid incidentalomas (identified by means of thyroid ultrasonography). The discussed entities carry the same risk of malignancy (about 5 %). The main objective in evaluating NTD is represented by the exclusion of malignancy by means of corroborated investigations, focused on the value of a panel of IHC markers.\r\nMaterial and methods. We included in the study 27 cases of NTD, evaluated by means of: clinical investigation, ultrasonography of the thyroid, cytological examination, morphological analysis and IHC. The used panel of IHC markers comprised: Ki-67, PCNA, CK 19 and c-erbB2 (DAKO LSAB method)\r\nResults. From the total of cases, 8 presented positivity with Ki-67 and 17 with PCNA. Regarding CK 19, the majority of PTC cases stained ++ and diffusely, but not papillary hyperplasia (focal positivity).c-erbB2 diffuse and intense positivity (+++) was noticed in PTC.The case with a follicular tumor of uncertain malignant potential stained weakly only with c-erbB2.\r\nConclusions. From the used panel of IHC markers, CK 19 presented the best value, being able to differentiate FVPTC from FTC and PTC from papillary hyperplasia.

Various clinical and experimental studies indicate that gonadal hormones exert\r\nmodulatory effects on nociception and analgesia.\r\nThe aim of the present study was to investigate the role of gonadal hormones in the\r\nresponse by male and female rats to thermal nociceptive stimulation.\r\nMaterials and Methods. 7 week old albino (Wistar) rats were used in our study.\r\nAnimals were randomly divided into control, sham and ovariectomised or orchidectomised\r\ngroups. Thermal pain threshold was measured through tail immersion test before and 10, 20\r\nor 40 days after gonadectomy. The pain threshold was measured as the time required to elicit\r\na flick of the tail called analgesia time. Serum testosterone, estradiol, progesterone or\r\nprolactin levels were measured simultaneously.\r\nThe results showed that analgesia time was higher in female (5.11 min) than in male\r\n(4.93 min) intact animals (p<0.05) indicating sex difference in response to thermal\r\nnociception. Serum testosterone, estradiol or progesterone level as well as analgesia time\r\nwere not significantly reduced 10 days after gondectomy. In male animals, analgesia time\r\nwas significantly decreased (p<0.01) 20 or 40 days after orchidectomy (2.25 or 2.14 min,\r\nrespectively) compared with control rats (4.93 min). Serum testosterone concentration was\r\nsignificantly reduced (p<0.05) 20 or 40 days after orchidectomy (0.08 or 0.09 ng/mL,\r\nrespectively) compared with control serum testosterone level (2.14 ng/mL). In female rats,\r\nanalgesia time was significantly decreased (p<0.001) 20 or 40 days after ovariectomy (2.87\r\nor 2.66 min, respectively) compared with control rats (5.11 min). Serum estradiol\r\nconcentration was significantly reduced (p<0.001) 20 or 40 days after ovariectomy (3.17 or\r\n0.87 ng/mL, respectively) compared with control serum estradiol level (19.95 ng/ml). Serum\r\nprogesterone level was also decreased (p<0.001) 20 or 40 days after orchidectomy (5.27 or\r\n0.55 ng/mL, respectively) compared with control serum estradiol level (17.66 ng/mL).\r\nSerum prolactin level was not significantly enhanced during experiment indicating that there\r\nwas not heat stress influencing the procedure.\r\nConclusively, our findings clearly indicate that depletion of gonadal hormones 20 or 40 days\r\nafter gonadectomy modulates the pain-induced behavioral responses related to thermal nociception.

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Objective. In postmenopausal period, changes in bone turnover markers (BTM), vitamin D3, cytokines and parathyroid hormone (PTH) are frequently observed. The study was to assess bone mineral density (BMD) and bone metabolism index (IBM) in the perimenopausal women. Design years: 2013-2014. Subjects and Methods. One hundred and thirteen women were divided into four groups: group I (35 not menstruating 50 - 60 years old with osteoporosis), II (23 not menstruating 50 - 60 years old without osteoporosis), III (30 menstruating 40 - 49 years old with osteoporosis), IV (25 menstruating 40 - 49 years old without osteoporosis). The following parameters were measured: IL-1β, IL-6, TNF-α, hormone oestradiol (E2), PTH, FSH, TSH, calcium (Ca2+), phosphates (P), alkaline phosphatase (bALP), C-terminal telopeptide of type I collagen alpha 1 chain (α1CTX), osteocalcin (OC), BMD, IBM. Results. IBM and BMD were significantly lower in premenopausal than in postmenopausal women. The concentration of OC, CTX, 25OH D3 and PTH levels differed significantly between group I vs. II, group I vs. III and group II vs. IV. Conclusions. The levels of BTM, D3, PTH differed significantly between groups. This study demonstrated that bone metabolism depended mainly on processes related with menopause state and changes in D3, PTH and cytokines levels.

Context. Different polymorphisms of the endothelial nitric oxide synthase gene (NOS3) have been related to diabetic kidney disease. Objective. To evaluate the association between advanced diabetic chronic kidney disease (ACKD) and the rs1799983 and rs2070744 poymorphisms of NOS3 in a population from the Gran Canaria island. Design. Cross-sectional case-control study. Subjects and methods. Polymorphisms were genotyped in 152 subjects with ACKD secondary to type 2 diabetes [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2], 110 subjects with type 2 diabetes for 20 or more years since diagnosis without ACKD (eGFR ≥45 mL/ min/1.73m2 and albumin/creatinine ratio <300 mg/g and/or 24-h urinary albumin excretion <300 mg) and 292 healthy controls. Association between both polymorphisms and established coronary heart disease (CHD) was also analyzed in both groups with diabetes. Results. A greater proportion of homozygous individuals for the risk allele C of rs2070744 was found among subjects with ACKD. Association between ACKD and rs2070744 was observed in a recessive genetic model, both for comparison to subjects with diabetes but no ACKD [OR 2.17 (95% CI: 1.17-4.00), p=0.014] and for comparison to healthy controls [OR 1.61 (1.03-2.52), p=0.036]. The frequency of the C allele was significantly higher among subjects with CHD, but only in the group with ACKD. No associations were found for rs1799983. Conclusions. NOS3 rs2070744 is associated with ACKD in population with type 2 diabetes from Gran Canaria. A link between this genetic variant and CHD in Canarian subjects with type 2 diabetes could be restricted to cases with ACKD.

Purpose. To correlate the volume of parathyroid adenomas with the hormonal and metabolic profile at patients diagnosed with primary hyperparathyroidism (pHPTH). Patients and Methods. Cross-sectional multicentric study, enrolling 52 patients with pHPTH from two medical institutions. Serum calcium and PTH were evaluated in all patients before surgery, whereas 25OHD3 was measured only in the 33 patients recruited form one medical unit. The volume of parathyroid adenoma was measured by using the formula of a rotating ellipsoid. Results. We observed a significant correlation of the volume of parathyroid adenomas with PTH at patients from the two units and in the whole group (p < 0.0001), but not with serum calcium (p = 0.494). Twenty-five out of the 33 patients at whom 25OHD3 was measured had levels in the range of deficiency. 25OHD3 was not correlated with PTH or calcium levels, but was negatively correlated to the adenoma volume and positively to the PTH/volume ratio (p = 0.041 and p = 0.048, respectively). Conclusions. The volume of parathyroid adenoma seems to be related to preoperative PTH and 25OHD3, but not to calcium level. Vitamin D deficiency is frequently found at patients with pHPTH and may contribute to particular disease profiles, including larger parathyroid adenomas.

Background. The research evidence have suggested that ghrelin, a neuropeptide containing 28 amino acids, plays an\r\nimportant role in glucose homeostasis and its concentration is increased in diabetes.\r\nObjective. To investigate the relationship between the serum levels of ghrelin, insulin, fasting glucose and glycated hemoglobin in patients with type 2 diabetes mellitus.\r\nMaterials and Methods. Fasting glucose, insulin, ghrelin and glycated hemoglobin were measured after a 12-14 hours overnight fasting in 48 adult males with type 2 diabeties. Pearson correlations were used to establish the relationship\r\nbetween ghrelin concentration and other variables. P-value of less than 0.05 was considered statistically significant.\r\nResults. There were no correlations between serum ghrelin and Systolic and diastole blood pressure and body mass index (p<0.05). Serum ghrelin is weakly associated with glycated hemoglobin (p=0.076, R=0.19). Serum ghrelin concentrations were positively correlated with fasting glucose (p=0.005, R=0.40). In addition, ghrelin correlated negatively with\r\nserum insulin (p=0.013, r=-0.36).\r\nConclusion. Our data demonstrate that high ghrelin concentration is accompanied with increase in blood glucose\r\nin type 2 diabetic patients, and support this hypothesis that this neuropeptide plays a pathophysiological role in this disease.

Introduction: During the past thirty years bone biopsy has been used as an invasive diagnostic and research investigation of bone structure and metabolism. Quantitative bone histomorphometry parameters offer information on both bone mass and bone quality.\r\nObjectives: This study aimed to establish the value of routine qualitative bone biopsy evaluation in subjects with unexplained primary osteoporosis. Patients in whom low bone mineral density was not adequately explained by risk factors or patients in whom therapy\r\nwas not followed by BMD changes according to evidence-based data on treatment of osteoporosis were referred to bone biopsy. One-hundred seventy patients (73 men and 97 women), aged 54.29?0.95 years, were included in the study. The diagnosis was based on clinical data, lumbar spine and hip dual X-ray absorptiometry (DXA) evaluation and routine laboratory measurements. Bone biopsy was performed by horizontal approach, using an electric drill. Qualitative bone biopsy evaluation was performed in one single department by trained pathologists. Quantitative bone histology assessment (histomorphometry) was not available.\r\nResults: Of the 170 bone samples, secondary causes of low bone mineral density were identified in 19 patients (mastocytosis, multiple myeloma, myeloproliferative syndrome, sarcoidosis and osteomalacia). In 21 subjects with osteoporosis as defined by WHO criteria qualitative histological evaluation found no pathological changes. Accelerated bone resorption as expressed by the daily urinary levels of deoxypyridinoline (D-Pyr) and longterm sodium fluoride therapy were associated with relevant osteoidosis as assessed by qualitative evaluation of bone samples. Bone biopsy changes were not related to serum thyroid hormone, parathyroid hormone or 25-hydroxyvitamin D3 levels.\r\nConclusions: Qualitative bone biopsy evaluation may offer valuable information in the diagnosis of metabolic bone diseases in subjects with unexplained causes of low bone mineral density or in non-responders to anti-fracture agents. Despite of lack of quantitative information on bone mass and the degree of mineralization of bone tissue, few patients with osteoporosis may benefit from this diagnostic routine procedure.