ACTA ENDOCRINOLOGICA (BUC)

Background. Hashimoto thyroiditis (HT) is an autoimmune disease and the most common cause of hypothyroidism. The widespread lymphocyte infiltration in the thyroid gland and intolerance of the body against its thyroid antigens leads to the destruction of thyroid cells and impaired thyroid function. Granulysin (GNLY) is a cytolytic antimicrobial peptide that has been associated with a wide range of diseases such as various infections, cancer, transplantation, and skin problems. However, there are a few studies investigating the relationship between HT and granulysin. Aim. Our study aims to investigate whether granulysin levels and GNLY gene polymorphism contribute to the damaged immune response leading to HT. Material and Methods. 100 unrelated patients diagnosed with HT and 140 healthy individuals were included in our study. Frequencies of GNLY rs10180391 and rs7908 gene polymorphisms were determined using PCR- RFLP method and serum granulysin levels were determined using ELISA. Results. There is no statistical significance between patient and control groups in terms of genotype and allele frequencies of GNLY gene polymorphisms and serum levels of granulysin. Conclusion. In conclusion, granulysin and GNLY gene polymorphisms do not appear to relate to HT disease.

Background: Published data sustain the participation of vascular renin angiotensin system (RAS) on alteration of pulmonary vessels reactivity during the allergic airway inflammation. Ghrelin is a growth hormone-releasing peptide involved in modulation of immune function.\r\nObjective: This study aims to investigate the interaction between ghrelin and local RAS from rat pulmonary vessels during ovalbumin ? induced allergic airway disease. Methods: The angiotensinogen (AGT) ? induced contractions were assessed on isolated pulmonary artery and veins from ovalbumin sensitized rats receiving either saline (OSR) or ghrelin (OSG) by endotracheal instillation. Experiments were performed in the absence or the presence of losartan, D-ALA7, chymostatin and Nω-nitro-L-arginine methyl ester (L-NAME).\r\nResults: The AGT contractile effects mediated by AT1 receptors were lower with at least 25% on vessels from OSG than from OSR. The D-ALA7 and L-NAME significantly increases the AGT ? induced contraction on OSG. The amount of nitric oxide released after stimulation with AGT is higher on OSG and it is blocked by D-ALA7.\r\nConclusion: Our results suggested that pulmonary delivery of ghrelin could modulate the local RAS from pulmonary vessels by promoted the angiotensin 1-7 mediated effects. These data sustained the existence of another possible way for ghrelin?s beneficial effects on the lung.

Despite several attempts to establish the role of QUS in clinical practice, issues such as definition of osteoporosis based on QUS, screening strategy and therapy efficacy for patients identified by QUS as having high risk of fracture remain a matter of debate. The present study aimed to evaluate the diagnostic agreement between two QUS techniques (heel QUS and proximal phalanges QUS) and DXA in an unselected population of Romanian women aged 24- 80 years, as well as to offer cut-off levels for QUS to distinct between women with or without osteoporosis identified by DXA. In women measured by both DXA and calcaneus QUS (c- QUS), bone mineral density (BMD) moderately correlated with stiffness index (SI) (L1-L4: r=+0.51, p<0.001; femoral neck: r=+0.53, p<0.001; hip: r=+0.57, p<0.001), while in women examined by both DXA and phalanx QUS (ph-QUS), BMD was positively related to amplitude-dependent speed of sound (Ad-SoS) (L1-L4: r=+0.47, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001) and ultrasound bone profile index (UBPI) (L1-L4: r=+0.44, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001). At a T-score cutoff level of -2.5SD, the high specificity but low sensitivity suggests a low false positive rate of c-QUS as a diagnostic test; still, several patients with the disease may not be correctly diagnosed. At the same cut-off level, ph-QUS showed higher sensitivity and lower specificity. Diagnostic agreement between DXA and QUS was poor, with k-scores ranging from 0.33 to 0.39 for c-QUS and from 0.14 to 0.29 for ph-QUS, respectively. Lowering c-QUS T-score cutoff for lumbar spine osteoporosis screening to -1.5SD and ph-QUS T-score cut-off to -1.9SD, respectively, improved sensitivity and had a minor effect on diagnostic agreement. Regardless of the evaluated site, neither c-QUS nor ph-QUS does represent an adequate predictor of BMD in Romanian women. Changing the diagnostic T-score threshold from -2.5 SD to -1.5 SD and -1.9 SD in subjects examined by c-QUS or ph-QUS, respectively, is followed by improved sensitivity and diagnostic agreement in the identification of patients with vertebral osteoporosis. Cut-off values may allow QUS to be used as a screening tool for spine and femur osteoporosis.

Background. Skull metastasis has not been reported from mixed medullary follicular thyroid carcinoma (MMFTC). Objective. To present a patient with expansile lytic skull metastasis. Case report. A 61 year lady is presented with goiter for 7 years and 8 cm diameter painful swelling over frontal bone for 18 months, aspiration from which revealed sheets and clusters of polygonal cells, similar to aspiration from hypoechoic nodule in right thyroid lobe. Serum calcitonin (569pg/mL) and carcinoembryonic antigen (11.2ng/mL) were elevated. Histopathology of 3.8×3.1cm nodule in thyroidectomy specimen revealed irregular islands of small polygonal tumor cells with extracellular amyloid deposits (suggesting medullary thyroid carcinoma (MTC)), intermingled with thyroid follicular cells showing capsular and vascular invasion (follicular thyroid carcinoma (FTC)). Immunohistochemistry of the thyroid tumor was negative for calcitonin and for thyroglobulin. Post-operative serum calcitonin and stimulated thyroglobulin were respectively 97 pg/mL and 11.5 ng/mL. I131 whole body scan revealed intense uptake in region of the skull metastasis with small uptake in thyroid bed. She received 150 mCi of I131with resolution of pain, heaviness, throbbing, reduction in swelling size, and lack of disease progression. Conclusions. Skull metastasis was the presenting feature of MMFTC which improved with I131 therapy. Patients with lytic skull metastasis should be evaluated for occult thyroid malignancy.

Context. Ghrelin, in both its acylated and desacylated forms, and leptin can modulate fetal energy balance and development. Objective. The aim of our study is to assess desacylated ghrelin (DAG) and leptin values and influence on intrauterine and postnatal growth in infants with intrauterine growth restriction. Design, subjects and methods. We performed a prospective study on 39 infants recruited over five months, 20 appropriate - for - gestational - age (AGA) infants and 19 small-for-gestational-age (SGA) infants, in which we measured DAG and leptin in the umbilical cord blood and we compared their respective values between the two groups, along with auxological parameters at birth and at 10 months of postnatal age. Results. Our results show that both DAG and leptin have lower values in SGA infants and correlate with most of the anthropometrical parameters at birth. Both hormones correlate with weight at 10 months in SGA infants, but this correlation lacks in AGA infants. Whereas DAG in the cord blood can be considered a predictor for weight at 10 months (β=0.207, p=0.001), the same cannot be stated about leptin (β=0.078, p=0.195). Conclusion. DAG and leptin are involved in both intrauterine and postnatal development, but the extent of their role is still to be determined.

There are no new national growth references for the Romanian population and the current recommendations for short stature evaluation is the use of the Swiss growth charts developed based on a longitudinal study. The aim of the present paper is to present the new synthetic growth references for Romanian children. Material and methods. We used local Romanian data from 9 studies with information on height and weight obtained between 1999 and 2016. Based on their plausibility and methodology six studies were selected for generating the National Synthetic Growth References for Romanian Children based on the specific methodology described previously. The selected studies included 8407 subjects measured in schools/kindergartens. Age is reported in years covering a range from 3-18 years. Height and weight were measured at a precision of 0.1 cm and 0.1 kg. All children were measured at normal temperature, in light clothes, without footwear. Results. We present the charts and tables with the common centiles for height, weight and body mass index for boys and girls. Conclusion. We suggest synthetic growth references based upon recent growth data from 6 different Romanian regions as new National Growth Charts for Romanian children.

An 18 years old, tall man presented for circumoral numbness, paresthesias, and hypocalcaemia, without carpopedal spasm or seizures. Previous medical history revealed bilateral cataract and osseous cysts on limbs at the age of 12. Hypocalcaemia resistant to calcium treatment and mild increased TSH levels were present. At diagnosis, we noticed a normal phenotype with tall stature, moderate hypocalcaemia (5.8 mg/dL), hyperphosphatemia (5.08 mg/dL) and significantly higher than normal intact parathormone (PTH) levels (518 pg/mL), in the presence of normal serum levels of 25-hydroxy vitamin D (53.56 ng/mL). The mother and the family members have been found in good health. All these data strongly suggested sporadic pseudohypoparathyroidism type Ib (PHP-Ib), but with some features of PHP - type Ia, like the osseous cysts. We were not able to perform molecular genetic tests. The nearly complete recovery of clinical and biochemical signs (normalization of PTH, calcaemia, phosphatemia, and a normal DXA osteodensitometry) after 2 years of chronic treatment with activated 1,25- dihydroxycholecalciferol (2.00-0.75 &#956;g/day) indirectly, but strongly confirmed the diagnosis of pseudohypoparathyroidism. The patient may have resistance to TSH evidenced by high TSH\r\n(range 4.8-7.5 mIU/L), with normal thyroid hormone levels, absence of goiter and normal TPO antibodies. The TRH test (400 &#956;g i.v.) showed a response of TSH, and also of serum thyroxine and triiodothyronine in a range that did not clarify the diagnosis. This association of the resistance to TSH with type Ib PHP was relatively recently reported by two groups (17,20) and before them it was reported only in PHP-Ia. Our patient also showed mild thrombocytopenia, with normal bleeding time, indicating also a possible Gs&#945; deficiency in platelets. In conclusion, our patient with sporadic pseudohypoparathyroidism without clinical phenotype of Albright hereditary osteodystrophy is highly suggestive for the type Ib PHP. A possible resistance to TSH and thrombocytopenia associated are features related to the genetic mechanisms found also in type Ia PHP. It is tempting to suggest that this case is one of the new variants of pseudohypoparathyroidism-Ib, recently reported.

Introduction: There is a large agreement about the positive effect of GH therapy in patients with panhypopituitarism. Objective: We investigated the potential psychological effect of GH replacement in hypopituitary patients secondary to surgery + radiotherapy for pituitary tumors. The study design was prospective, non-placebo controlled.\r\nPatients and methods: after informed consent, we enrolled 14 subjects with pituitary tumor, submitted to transfrontal (FS) or transsphenoidal (SS) surgery and with GH < 1 ng/mL after insulin-induced hypoglycemia. Our subjects were aged 50.2 + 14 years, 11 men, 3 women, with craniopharyngioma (n=3, all postfrontal surgery=post FS), nonfunctioning pituitary adenoma (n=10, 6 post FS, 4 post SS) and 1 macroprolactinoma (post FS). Seven subjects were submitted to radiotherapy. GH (Norditropin) was provided by Novonordisk, in 5 mg vials, self-administered by a specific device (pen) provided by manufacturer in a dose of 0.01 mg/kg/day. GH and IGF 1 were assayed monthly, using a commercial kit. Quality of Life (QoL) was assessed monthly by a 22 item questionnaire provided by Novonordisk, which measures a total QoL score, as well as subscores for depression, anxiety, personal well being and self perceived sense of energy. A statistically significant improvement of QoL score is indicative of positive effect of therapy. Fasting glucose and tumoral dimensions were monitorised every 3 months; 2 patients were excluded from study after diabetes mellitus occurrence; one additional patient discontinued therapy for fears of tumoral outgrowth.\r\nResults: a positive effect could be noticed concerning QoL total score and subscores, concerning auto-perceived level of energy and personal well being. Prior radiotherapy tends to blunt this beneficial effect. IGF 1 increased first 2 months, then we noticed a significant and sustained increase of IGF 1 with frequent upper normal values, especially in more obese and in men rather than in women. Adiposity and BMI decreased during therapy, which favorably influence QoL.\r\nConclusions: patients benefit psychologically from GH therapy. We found an unexpected high rate of metabolic complication (2 out of 14 subjects drop out study because of diabetes mellitus). Prior radiotherapy might blunt the psychological effect of GH.

Objectives. The objective of this study was to assess the impact of endometriosis on the quality of life. Patients and methods. Study group of 205 women, aged between 18-45 years old, hospitalized in the “Cuza-Voda” Hospital of Iasi, between 2013-2015. We used the Fertility Problem Inventory, the Endometriosis Health Profile and the Beck Depression Inventory. Results. We first realized a descriptive analyses of patients’ health related quality of life - 60% of women reported higher infertility distress associated with relationship issues caused by difficulties to conceive. The descriptive analysis over the quality of life in patients with endometriosis suggests that the high level of stress related factors, are: the loss over the control of the symptoms, dyspareunia and altered emotional status. Regarding the sexual aspect of life, almost a quarter of the women complained about an altered sexual status, due to both fear of failing in conceiving and dyspareunia caused by the endometriosis. The descriptive analysis over the infertility related stress suggests that the factors associated with a high level of stress are: sadness, pessimism, feeling of failure, irritability, lack of confidence, self-hatred and fatigue. Conclusions. Patients with endometriosis are dealing daily with a large spectrum of symptoms, including pain, dyspareunia, emotional instability and high levels of stress, which have a negative impact upon the quality of life, by lowering it on different levels. Also, within the present study we showed a significant presence of high infertility stress in patients of all ages that lead to depression and social anxiety.