Neonatal screening for congenital hypothyroidism in an Italian Centre: a 5-years real-life retrospective study.

INTRODUCTION: Congenital hypothyroidism is an endocrine disease with a significant incidence in the general population (1:2000-1:3000 newborns in Italy) and a different geographical distribution, partially explained by endemic iodine deficiency, genetic traits and autoimmune thyroid diseases. OBJECTIVES: Aims of this study are: to evaluate the incidence of positive neonatal blood spot screening for CH in western Sicily, identified by the screening centre of the Children Hospital "G. Di Cristina", ARNAS, Palermo; to evaluate the impact of a lower TSH cutoff in the neonatal blood spot screening for CH. MATERIALS AND METHODS: The TSH threshold of the neonatal screening was established as ≥6 mU/L of whole blood. We analysed the screening centre data in the period January 2013-April 2018, for a total number of 85.373 babies (45.7% males; 54.3% females). RESULTS: 4.082 Babies (4.8%) required a second screening. Among these, 372 (0.44%) were out of range. The diagnosis of congenital hypothyroidism (CH) was confirmed in 182 babies (0.21%). 77/372 newborns (20.7%) with confirmed high TSH levels showed whole blood TSH levels ≥6 - < 7 mU/L. In synthesis, 48.9% of the out of range re-testing had a confirmed diagnosis of CH. CONCLUSION: The reduction of TSH cutoff to 6 mU/L allowed to identify 77/372 neonates (20.7%) with confirmed out of range TSH, otherwise not recruited by the previously employed TSH cutoff.

Reducing the False-Positive Rate for Isovalerylcarnitine in Expanded Newborn Screening: The Application of a Second-Tier Test

Abstract The isodecyl neopentanoate is an ingredient used in the cosmetic industry to prepare a nipple fissure balm. We report on 12 newborns that showed elevated C5-acylcarnitine levels upon newborn screening following treatment with balm. The first 3 neonates were immediately recalled for confirmatory tests and resulted negative for both isovaleric acidemia and short/branched chain acyl-CoA dehydrogenase deficiency. In the other 9 cases, the immediate recall was avoided by applying a new second-tier test able to confirm the presence of pivaloylcarnitine. The concentration of C5-acylcarnitine was measured in the days following the suspension of balm application. Abnormal concentrations of C5-acylcarnitine did not seem to be associated with free carnitine deficiency, probably due to the short time of exposure. A direct correlation between balm ingestion and the elevation in pivaloylcarnitine has been demonstrated in 10 adult volunteers. The commercial balm containing a pivalic acid derivative is causal of false-positive results during newborn screening, and it could have the potential to cause secondary carnitine deficiency when used chronically.

Expression of wild-type and variant estrogen receptor alpha in liver carcinogenesis and tumor progression.

Although estrogen receptors (ERs) are expressed in human hepatocellular carcinoma (HCC), several clinical trials have failed to demonstrate the efficacy of antiestrogen treatment in HCC patients. Recently, the identification of several ER splicing variants has enlightened the complex nature of estrogen signaling in peripheral tissues; this may help understanding estrogen role in either nontumoral or malignant nonclassical target organs, including liver. In this work we have investigated mRNA expression of wild-type and splice variants of ERα in nontumoral, cirrhotic, and malignant human liver, as well as in HCC cell lines, using an exon-specific reverse transcription polymerase chain reaction (RT-PCR). In particular, ERα66 was detected in nontumoral and, to a lesser extent, in cirrhotic liver tissues, whereas its expression decreased or became undetectable in HCC tissues and cell lines. The ERα46 splicing variant was detected ubiquitously in all samples; interestingly, however, the ERα36 variant was inversely expressed with respect to ERα66, being highest in HepG2 cells, intermediate in Huh7 cells, and lowest in HA22T cells. It is noteworthy that aromatase was correspondingly expressed with ERα36 and inversely related to ERα66. This observation suggests that a switch from ERα66 to a predominant expression of ERα36 may be associated with development and/or progression of human HCC.

Endocrine therapy in metastatic breast cancer: data from Breast Cancer Registry of Palermo, 1999-2005 .

This study compares the survival of breast cancer patients who are metastatic at diagnosis (DMBC) and of recurrent metastatic breast cancer (RMBC) patients. We analyzed retrospectively the population-based data of Breast Cancer Registry of Palermo and collected a total of 4459 breast cancer cases in the years 1999-2005. Survival analysis did not show statistically significant differences between DMBC and RMBC patients (P= 0.882). Endocrine manipulation is the treatment of choice in the case of hormone receptor-positive breast tumors. In 91 receptor-positive DMBC patients the endocrine treatment was associated with a prolonged overall survival (OS) (median survival 33.5 months compared to 29 months for receptor-positive patients who did not receive hormone treatment). Receptor-negative patients who underwent endocrine therapy (76% of cases) survived longer than receptor-negative patients who did not receive hormone treatment (median survival 28.5 months vs. 15 months, respectively). This evidence supports the concept that endocrine therapies impinging upon molecular targets other than hormone receptors may increase survival rates of breast cancer patients.