ACTA ENDOCRINOLOGICA (BUC)

Central precocius puberty (CPP) is characterized by abnormalities in the setting up of the gonadotropin ?pubertal? release, which occurs earlier. The gonadotropin releasing hormone (GnRH) was used initially to test the pituitary regarding FSH and LH release in both precocious and delayed puberty. Various GnRH superagonists were used for the same purpose, including triptorelin. A triptorelin test was applied to 14 girls with premature thelarche by using the subcutaneous administration of 0.1 mg/sqm and blood sampling at 2, 3 and 4 hours for serum LH and FSH and at 24 hours for serum estradiol. Serum mean levels of LH were >7.8 mIU/ml at all intervals, suggesting a ?pubertal? type of LH release. As concerns the individual levels of LH, only 5 out of 14 girls showed a value greater than 8 mIU/ml, which is the cutoff limit for the diagnosis of precocious puberty. These girls also met the other clinical and radiological criteria necessary for the diagnosis of precocious puberty. It was concluded that soluble triptorelin may be useful in detecting ?pubertal? type of LH release in girls exhibiting premature thelarche. Regarding the FSH and estradiol levels, they were considered irrelevant for the diagnosis.

Vitamin D deficiency and insufficiency are common medical problems worldwide as they\r\nare quite prevalent in both healthy adults and individuals with osteoporosis, hospitalized patients\r\nand free-living and institutionalized elderly. The lack of serum 25-hydroxy-vitamin D (25OHD)\r\nassays standardization, variability of reference population, and the use of different cut-off points\r\nhave produced quite different prevalence reports from epidemiological studies.\r\nWe investigated the vitamin D status (deficiency, insufficiency, sufficiency) in 1048\r\nRomanian postmenopausal women with osteoporosis referred to our clinic for diagnosis and\r\ntreatment in the last three years. Most patients were untreated with osteoporosis drugs and nonsupplemented\r\nwith vitamin D. In our country dietary sources of vitamin D are scarce and there\r\nis no fortification of food with vitamin D. We found a high prevalence of both vitamin D\r\ndeficiency (25OHD < 10 ng/mL) - 22.23% and insufficiency (25OHD=10-30 ng/mL) - 61.26%.\r\nOur study also revealed a high prevalence of low vitamin D when using other cut-offs as reported\r\nin the literature. 83.49% had values lower than 30 ng/mL and 60.97% lower than 20 ng/mL. In\r\nthis study we identified a serum 25OHD concentration of 35 ng/mL above which serum\r\nparathyroid hormone (PTH) concentration attains a plateau at about 35 pg/mL. The relation\r\nbetween serum PTH and 25OHD concentration was non-linear and a log-log diagram showed a\r\nvery weak correlation. The prevalence of secondary hyperparathyroidism was 32.25% in the\r\nwhole population studied. It ranged from 40% in the subgroup of serum 25OHD less than 10\r\nng/mL to less than 15% in patients with 25OHD higher than 30 ng/mL.\r\nIn conclusion, in a representative osteoporosis population from Romania we found a very\r\nhigh prevalence of vitamin D deficiency and insufficiency whatever the cut-off used for\r\ndefinition.

Context. Graves' disease is the most prevalent cause of hyperthyroidism worldwide. Adiponectin, the most abundant adipokine, plays a significant role in a cluster of prevalent diseases connected to metabolic disorders. Objective. Although the association between adiponectin and Graves' disease has been studied, the existing data is inconsistent. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between adiponectin levels and Graves' disease. Methods. We performed a systematic electronic search on PubMed, EMBASE, Scopus and Cochrane Library using predefined keywords. We used the NHLBI quality assessment tools to assess the included studies. Results. There were 11 studies involving 781 subjects included in our qualitative synthesis, while 6 studies were included in our quantitative synthesis. We observed significantly increased adiponectin levels in Graves' disease patients compared to controls (MD 2.983 [95% CI 0.138– 5.828]) and hypothyroidism patients (MD 3.389 [95% CI 1.332–5.446]). Nevertheless, no significant MD was observed when comparing Graves' disease patients with and without Graves' ophthalmopathy (MD -27.124 [95% CI -88.893 – 34.645]). Conclusions. Adiponectin levels were significantly higher in patients with Graves' disease compared to controls and hypothyroidism patients. However, patients with and without Graves' ophthalmopathy did not present a significant mean difference in adiponectin levels.

Abstract Context. Autoimmune progesterone dermatitis (AIPD) is a rare, cyclical dermatosis, with variable clinical presentation, occurring exclusively or being aggravated during the luteal phase of the menstrual cycle, when levels of progesterone rise. Its pathogenesis is still unclear. AIPD is thought to occur as an autoimmune reaction to endogenous possibly modified progesterone, but it could also be triggered by exogenous progesterone exposure. AIPD is a diagnosis of exclusion. Usually there is no or limited response to oral H1 antihistamines and a partial response to steroids. Ovulation inhibitors represent the specific treatment. Case report. We report a case of AIPD in an 18-year-old nulliparous patient with no medical history of allergic diseases and no exposure to oral contraceptive pills. AIPD was suspected based on the clinical picture (recurrent cyclical eczematous eruption on the face and abdominal area) and confirmed by positive intradermal test and positive progesterone challenge. This diagnosis was supported by the result of the skin biopsy, which also helped to exclude other dermatoses with premenstrual aggravation. The rash responded satisfactorily to treatment with a combination of oral contraceptives, levonorgestrel and estrione, which is currently considered first line therapy. Conclusions. This case is of particular interest due to the lack of previous pregnancy or exposure to progesteron therapy. Recurrent, cyclical eruptions in fertile women should raise the suspicion of AIPD. If early recognized, the patient may benefit from non-invasive treatment that improves significantly the quality of life.

Background. Molecular defects in the SHOX gene including deletions, duplications or pathogenic point mutations are responsible for well-known pathologies involving short stature as a clinical manifestation: Léri–Weill dyschondrosteosis, Langer mesomelic dysplasia, Turner syndrome or idiopathic short stature. Duplications flanking the SHOX gene (upstream or downstream of the intact SHOX gene involving conserved non-coding cis-regulatory DNA elements - CNEs) have been described but their clinical involvement is still difficult to understand. Results. We describe two cases with short stature and normal GH-IGF1 status. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (arrayCGH) identified in both cases heterozygous duplications involving downstream regions of SHOX gene, within CNEs (CNE8, CNE9 and CNE4, CNE5, CNE6, ECR1, CNE8, CNE9 and surrounding areas, respectively). One of the cases showed a maternally inherited duplication. Although every case has several particularities, we consider that duplications in these non-coding regions of SHOX gene may explain the short stature phenotype. Conclusion. To our knowledge, these are the first Romanian-reported cases of ISS with a large duplication of downstream SHOX enhancers CNEs region. The spectrum of phenotypic consequences and the exact mechanism of the presumed clinical expression of these genetic alterations still needs to be evaluated and described.

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Leptin seems to play a significant role in the regulation of pituitary GH secretion. In GH deficient children serum leptin level is higher than in GH sufficient ones. Administration of rhGH resulted in a significant decrease in serum leptin in GH deficient but also in children displaying idiopathic growth delay, small for gestational age at birth, Prader-Willi syndrome and other obese. LBA is in fact the soluble form of leptin receptor. It was previously shown that GH deficient children are mostly hyperleptinemic and that GH induces a reduction in leptin level within 3 weeks of therapy. Such a reduction could serve as a valuable marker of the long term growth response. Twenty short children whose GH status was previously assessed through GH provocative tests and auxological evaluation were explored as concerns IGF I, leptin and LBA. According to these criteria they were classified as GH-deficient and GH-sufficient. Blood samples for the assay of serum leptin and LBA and IGF I were drawn at 8 a.m. A daily dose of 0.35 mg of rhGH was given subcutaneously at 8 pm in 12 of them and the same sampling was done 12 hours after the last injection. A therapy with GH with the same preparation and in comparable weekly dosage was started in all children and the height gain was evaluated after six months. Total serum leptin was assayed by a commercially available sandwich ELISA kit. LBA was assayed by a sandwich ELISA kit using a human IgG-Fc fragment of leptin receptor. IGF I determination was performed by the OCTEIA kit in a two-site immunoenzymometric assay (IEMA). The means and SEM before and after 10 days of GH administration in the whole group were of 3.4 ? 0.71 ng/ml and 1.7 ? 0.16 (p< 0.02) for leptin 0.27.1 ? 0.92 U/ml and 23.6 ?1.66 (ns) for LBA, 48.9 ? 10.65 ng/ml and 84.3 ? 17.61 for IGF I (p> 0.05, ns). Comparison between GH deficient (def) and GH sufficient (suf) subgroups resulted in significant differences as regards initial values for IGF I (20.2 ? 4.21 in def vs 77.6 ? 16.7 in suf, p< 0.02) but not in leptin, LBA, height and weight z scores. After ten days of therapy no significant differences were noted in subgroups for leptin, LBA and IGF I (absolute values), but a striking difference was noted in percentual rise of IGF I in def children. There was a significant positive correlation between leptin basal level and the growth rate in the subsequent 6 months of GH therapy. No similar correlation was noted for IGF I and LBA. It was concluded that hyperleptinemic GH deficient children seem to be particularly sensitive to the growth promoting effect of rhGH at least in the first six months of therapy.

Introduction: Obesity, a disease whose morphological background has as main problem the “dysfunctional” adipocyte, continues to raise scientific interest for the completion of the existing data and the verification of the hypothetic ones. Material and method: We determined insulinemia and glycemia within the oral glucose tolerance test (OGTT), and we analyzed the relation between the fat mass and cortisolemia in a group of 50 obese patients aged between 4 months –18 years. In 19 obese patients, between 5 ½ -17 ½ years old, we determined the basal leptin and resistin serum levels, comparatively to a control group of 19 normal weight children. In 14 obese and 10 normal weight controls, we determined the number of androgenic and estrogenic adipocyte receptors, which we correlated with the degree of obesity, the Tanner stage and respectively the testosterone, progesterone and estradiol serum levels. We studied the cellularity, morphohistochemical and ultrastructural features of the adipose tissue in 42 obese and 20 normal weight controls. Leptin and resistin were determined by ELISA. The measurement of the fat mass was done by bioelectric impedance. For the study of the adipose tissue we took 1g of tissue from the retro-trochanterian area. We identified the estrogenic (ER) and androgenic (AR) receptors by LSAB2 technique. We interpreted the data statistically by the linear regression analysis and variance test “t” for two unequal parameters using Microsoft Excel 2002. Results: A positive correlation was demonstrated between glycemias and insulinemias for the entire group (r=0.927, p=0.002), as well as between cortisolemia and fat mass excess (r=0.917; p=0.001). Serum leptin levels were significantly high in the obese (mean values: 81.07 ng/ml) comparatively to normal weight individuals (mean values: 4.17 ng/ml). Resistin serum levels did not show significant differences between the obese and normal weight individuals. We cannot talk about the existence of any correlation between resistin and leptin.

Atherosclerotic Cardiovascular Diseases are the leading cause of death worldwide. Aim. To estimate the prevalence of cardiovascular risk (CVR) categories in the adult population (aged 40-79 years) of Romania. Design. The present study was part of the epidemiological, cross-sectional PREDATORR study (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania). Subjects and Methods. Exclusion criteria: age <40/ or>79 years old and diagnosis of ischemic vascular disease. The CVR was evaluated using charts developed by the World Health Organization/ International Society of Hypertension (WHO/ISH) available for Europe B (epidemiological subregion where Romania was included). The CVR was divided into 5 categories: <10%, 10-20%, 20-30%, 30-40%, > 40%. Results. A total of 1631 subjects (57.0±10.7 years, 45.1% males) were included in the present study. The age and sex-adjusted prevalence of CVR >40% was 2.9% (95%CI 2.8-3.1%), CVR 30-40% was 1.85% (95%CI 1.8-1.9%), CVR 20-30% was 5.8% (95%CI 5.6- 6.0%) and 13.0% (95%CI 12.8-13.3%) of the adult Romanian population has a 10-20% CVR, these CVR categories being more frequent in male and older age. Diabetes, overweight/ obesity and smoking were associated with high CVR categories. Conclusion. Romania is one of the countries with high CVR, requiring CVD prevention measures.