Catalina Poiana

Quantitative Ultrasound in the Management of Osteoporosis: The 2007 ISCD Official Positions

Dual-energy X-ray absorptiometry (DXA) is commonly used in the care of patients for diagnostic classification of osteoporosis, low bone mass (osteopenia), or normal bone density; assessment of fracture risk; and monitoring changes in bone density over time. The development of other technologies for the evaluation of skeletal health has been associated with uncertainties regarding their applications in clinical practice. Quantitative ultrasound (QUS), a technology for measuring properties of bone at peripheral skeletal sites, is more portable and less expensive than DXA, without the use of ionizing radiation. The proliferation of QUS devices that are technologically diverse, measuring and reporting variable bone parameters in different ways, examining different skeletal sites, and having differing levels of validating data for association with DXA-measured bone density and fracture risk, has created many challenges in applying QUS for use in clinical practice. The International Society for Clinical Densitometry (ISCD) 2007 Position Development Conference (PDC) addressed clinical applications of QUS for fracture risk assessment, diagnosis of osteoporosis, treatment initiation, monitoring of treatment, and quality assurance/quality control. The ISCD Official Positions on QUS resulting from this PDC, the rationale for their establishment, and recommendations for further study are presented here.

The Expression of the F-Box Protein Skp2 is Negatively Associated with p27 Expression in Human Pituitary Tumors

The CDK inhibitor p27 plays a pivotal role in controlling cell proliferation during development, and has been implicated in tumorigenesis. Previous studies have demonstrated changes in p27 protein expression, but not in mRNA levels, in human pituitary tumors. It seems probable that the fall in p27 is due to increased degradation through the ubiquitin-proteasome pathway. Skp2 (S-phase kinase-interacting protein) is a specific F-box protein that allows the recognition and binding of phosphorylated p27 to the ubiquitin complex. The aim of our study was thus to investigate the possible role of Skp2 in pituitary tumorigenesis.A total of 59 human pituitary samples, 7 normal and 52 adenomas, were assessed for transcriptional expression of Skp2; 51 pituitary samples were assessed for protein expression. Real-time RT-PCR was performed on cDNA of reverse-transcribed mRNA for relative quantification of the Skp2 transcript. Immunostaining was performed using mouse monoclonal anti-Skp2 antibody.Skp2 mRNA and protein was detectable in every sample studied. Our results showed no significant difference between the pituitary tumors and normal pituitary tissue in Skp2 mRNA or nuclear protein expression. Individual tumor types had similar mRNA expression and variable protein expression. However, samples with high p27 protein expression showed significantly less Skp2 expression than samples with low p27 staining.Our data suggest that increased p27 degradation through the ubiquitin-proteasome pathway could be regulated in pituitary tumors by changes in Skp2 expression, although other factors probably also play a role.

Immature ovarian teratoma with unusual gliomatosis

This study aimed to investigate an unusual case of immature ovarian teratoma with onset of mature glial cells implanted on the contralateral ovary, a challenge in the diagnosis of the second ovarian tumor. We report the case of a 31- yr-old woman, who developed at the age of 16 an immature teratoma in the right ovary that was surgically removed. Six years later mature glial implants were present on the left ovary and six months later at the level of peritoneum that relapsed after other six months. The patient suffered three surgical resections after the initial one. Paraffin sections and immunohistochemical examinations using antibodies against glial and neuronal antigens were performed. In the teratoma, the neuroectodermal tissue expressed Glial fibrillary acidic protein (GFAP), S100 protein, Epithelial membrane antigen (EMA) and Cytokeratin 34 beta E12 (Ck34beta E12), wheares the implants expressed only GFAP and S100 protein. The immature teratoma is the rarest type of ovarian teratomas. Gliomatosis peritonei is an exceptional finding, expecially with onset on the contralaterally ovary. The implant of the mature glial cells has a high risk of relapse, as seen in our case, thus close follow-up of the patient is necessary.

Virilising Sertoli-Leydig cell tumour associated with thyroid papillary carcinoma: case report and general considerations.

We present a case of a Sertoli–Leydig cell tumour manifested with progressive hirsutism, frontal alopecia and secondary amenorrhea in a 46-years-old female, evolving for 6 years until presentation. Serum testosterone level was 8.01 ng/ml and gonadotropic hormones were LH 8.57 mIU/ml and FSH 9.52 mIU/ml. Computed tomography revealed a dense, solid, heterogeneous mass of 3.5/2.8 cm in the right ovary. Bilateral ovariectomy and hysterectomy were performed. The histopathological report mentioned a Sertoli-Leydig cell tumor with intermediate grade of differentiation. Immunohistochemical stains showed positive reaction for α-inhibin, calretin and for progesterone receptor. The testosterone levels dramatically decreased after surgery (0.31 ng/ml) while levels of gonadotropes increased: LH 40.98 mIU/ml and FSH 50.41 mIU/ml. At 6 months follow-up the diagnosis of a left lobe thyroid nodule leaded to fine needle aspiration biopsy with suspicion of papillary carcinoma. Total thyroidectomy established the diagnosis of thyroid papillary carcinoma (2.17/2.18 cm) T2N0M0, stage II, followed by radioiodine administration. This is to our knowledge the first presented case of ovarian Sertoli–Leydig cell tumour associated with papillary thyroid carcinoma. This could suggest a common genetic background.

SERIAL CHANGES OF LIVER FUNCTION TESTS BEFORE AND DURING METHIMAZOLE TREATMENT IN THYROTOXIC PATIENTS

OBJECTIVE Overt hyperthyroidism and methimazole (MMI) treatment are frequently associated with abnormal liver function tests (LFTs). We describe the serial changes of LFTs in MMI-treated hyperthyroid patients. METHODS We retrospectively analyzed all 77 patients presenting with newly diagnosed overt hyperthyroidism (59 Graves diseases, 11 toxic nodular goiters, 4 toxic adenomas, 3 amiodarone-induced thyrotoxicosis) between 2012 and 2014. All patients started MMI at 10 to 60 mg/day that was gradually tapered. We measured thyroid-stimulating hormone, free thyroxine, alanine aminotransferase (ALT) and aspartate aminotrasnferase (AST) at baseline and at 6 weeks, 4.5 months and 10 months after starting the MMI treatment. The concomitant medication was stable during MMI treatment. RESULTS At baseline, 25 patients (32.5%) had abnormal LFT, of which 5 had ALT or AST levels >2× the upper limit of normal (ULN). In most patients with baseline abnormal LFT, MMI treatment resulted in a normalization of serum ALT and AST. Thirteen patients with normal baseline LFT had <2× the ULN elevations of LFT sometime during treatment. There was a case of significant hepatotoxicity. During treatment, there were no significant differences in LFT levels between patients with initially normal or abnormal LFT. In a Cox proportional hazard regression model, abnormal LFT at baseline, abnormal thyroid function at the last evaluation, and MMI dose were not predictors of abnormal LFT at the final evaluation. CONCLUSION MMI treatment can induce insignificant LFT elevation, <2× the ULN. MMI can be safely administered in hyperthyroid patients with abnormal LFT, and normalization of increased AST and ALT levels should be anticipated. ABBREVIATIONS ALT = alanine aminotransferase AST = aspartate aminotransferase fT4 = free thyroxine HCV = hepatitis C virus LFT = liver function test LOCF = last observation carried forward MMI = methimazole PTU = propylthiouracil TSH = thyroid-stimulating hormone ULN = upper limit of normal.

Plasma free metanephrine and normetanephrine levels are increased in patients with chronic kidney disease.

OBJECTIVE Patients with impaired renal function, particularly those on dialysis, frequently exhibit high blood pressure and hemodynamic instability, which often lead to pheochromocytoma assessment. Our objective was to assess plasma free metanephrine (MN) and normetanephrine (NMN) in chronic kidney disease patients (CKD) with or without dialysis. METHODS In this prospective observational study we performed enzyme-linked immunosorbent assays (ELISAs) to evaluate plasma free MN and NMN in 48 CKD patients (15 with stage 3-5 CKD without dialysis, 26 on hemodialysis [HD], and 7 continuous ambulatory peritoneal dialysis [CAPD]), 30 patients with histologically proven pheochromocytoma, and 43 hypertensive patients. Adrenal masses were ruled out by abdominal computed tomography (CT) scans in all CKD and control hypertensive patients. RESULTS All 3 CKD groups (HD, CAPD, and CKD without dialysis) had significantly higher plasma free MN and NMN levels than the control hypertensive group (P<.0055). HD and CAPD patients had significantly lower plasma free NMN (P<.0055), but free MN levels were not significantly different than those observed in pheochromocytoma patients. In patients with HD, CAPD, and CKD without dialysis, plasma free MN and NMN were higher than manufacturers upper limits of normal in 57.7% and 28.5%, 13.3% and 61.5%, and 85.7% and 26.6%, respectively. Regression models showed that the number of dialysis years was significantly correlated with plasma free MN (r = 0.615, P<.001) but not free NMN. CONCLUSION Plasma free MN and NMN levels are frequently elevated in CKD patients, particularly in those on dialysis. Plasma free MN levels significantly overlap with the range in pheochromocytoma patients and correlate with the number of years on dialysis.

Galactocele and prolactinoma - a pathogenic association?

A galactocele is a rare form of cystic, benign lesion of the breast, appearing when a mammary duct becomes obstructed and over filled with milk. It is usually found in postpartum women, either lactating or not. There are only a few cases reported that are not immediately linked to the lactation, as seen in postmenopausal women or in men. Furthermore, the relationship to overproduction of prolactine, a growth factor for the breast epithelium is not very well defined at this moment. We present such an unusual case of a 37-year-old female patient who has no history of birth or abortion. She was diagnosed with both microprolactinoma and galactocele whose dimensions seemed to be related to the evolution of the pituitary tumor and serum prolactine. Because no other etiology could be found in the young patient for the mammary galactocele, the prolactine excess is the most probable cause. Even considering the rarity of the association it is important to point the hormonal role in changing the anatomy of the breast.

New Clues that May Link Osteoporosis to the Circulating Lipid Profile

Bone Mineral Density (BMD) is a gold standard for the diagnosis of osteoporosis and is also important in the assessment of fracture risk. Other risk factors have been identified that together make up fracture risk assessment tools such as FRAX. Another potential factor, circulating lipids, has been suggested because of reports linking statins to fracture risk reduction. We analyzed the lipid profile in a cohort of women diagnosed with postmenopausal osteoporosis based on bone density determination: 610 women with osteoporosis (mean lumbar spine T-score −3.16±0.81, mean yrs. since menopause 15.79±8.9) were grouped according to age at evaluation (< 50 years, 51–60 years, 61–70 years, > 70 years), the presence/absence of a history of a fragility fracture, statin and/or antiresorptive drug use. There was no correlation between BMD and Body Mass Index (BMI: P>0.05, r2<0.02). However, when BMD was correlated with both BMI and the lipid profile (Triglycerides, Cholesterol, LDLc, HDLc), significant correlations were found in 5 cohorts: 51–60 years with fractures (n=61, r2=0.14, P<0.01), 61–70 years (n=201, r2=0.09, P<0.01) with fractures (n=88, r2=0.14, P<0.01) or without fractures (n=113, r2=0.24, P=0.02) and over 70 years (n=247, r2=0.11, P<0.01).

Branched-Chain Amino Acid Database Integrated in MEDIPAD Software as a Tool for Nutritional Investigation of Mediterranean Populations

Branched-chained amino acids (BCAA) are essential dietary components for humans and can act as potential biomarkers for diabetes development. To efficiently estimate dietary intake, we developed a BCAA database for 1331 food items found in the French Centre d’Information sur la Qualité des Aliments (CIQUAL) food table by compiling BCAA content from international tables, published measurements, or by food similarity as well as by calculating 267 items from Greek, Turkish, Romanian, and Moroccan mixed dishes. The database embedded in MEDIPAD software capable of registering 24 h of dietary recalls (24HDR) with clinical and genetic data was evaluated based on archived 24HDR of the Saint Pierre Institute (France) from 2957 subjects, which indicated a BCAA content up to 4.2 g/100 g of food and differences among normal weight and obese subjects across BCAA quartiles. We also evaluated the database of 119 interviews of Romanians, Turkish and Albanians in Greece (27–65 years) during the MEDIGENE program, which indicated mean BCAA intake of 13.84 and 12.91 g/day in males and females, respectively, comparable to other studies. The MEDIPAD is user-friendly, multilingual, and secure software and with the BCAA database is suitable for conducting nutritional assessment in the Mediterranean area with particular facilities for food administration.

A 2018 Italian and Romanian Survey on Subclinical Hypothyroidism in Pregnancy

Objectives: Pregnancy induces changes in thyroid function, and thyroid dysfunction during gestation is associated with adverse outcomes. We examined the management of subclinical hypothyroidism and chronic autoimmune thyroiditis in pregnancy among Italian and Romanian endocrinologists. Methods: Members of the Associazione Medici Endocrinologi (AME) and Romanian Society of Endocrinology (RSE) were invited to participate in a web-based survey investigating the topic. Results: A total of 902 individuals participated in the survey, 759 of whom completed all sections. Among the respondents, 85.1% were aware of the 2017 American Thyroid Association guidelines about thyroid disease and pregnancy, and 82.9% declared that thyroid-stimulating hormone (TSH) screening at the beginning of pregnancy should be warranted. In a patient negative for peroxidase antibodies, 53.6% considered 2.5 mIU/L and 26.2% considered 4.0 mIU/L as the upper normal limit of TSH, and 50% would treat a patient with TSH 3.5 mIU/L with levothyroxine. About 20% did not suggest iodine supplementation. Isolated hypothyroxinemia detected in the first trimester would be treated by 40.8%. In patients undergoing ovarian stimulation, a TSH < 2.5 mIU/L would be targeted by 70%. Conclusions: Respondents globally appeared well informed about the management of thyroid autoimmunity and subclinical hypothyroidism in pregnancy. A more aggressive attitude in implementing iodine supplementation would be desirable. Most endocrinologists were convinced about an evident association between mild thyroid impairment and adverse outcomes in pregnancy, thus using a TSH value of 2.5 mIU/L as the threshold for diagnosing hypothyroidism and starting levothyroxine in pregnant women.