Measurement of the liver iron concentration in transfusional iron overload by MRI R2* and by high-transition-temperature superconducting magnetic susceptometry.

PURPOSE: To compare measurement of the liver iron concentration in patients with transfusional iron overload by magnetic resonance imaging (MRI), using R2*, and by magnetic susceptometry, using a new high-transitiontemperature (high-Tc; operating at 77 K, cooled by liquid nitrogen) superconducting magnetic susceptometer. METHODS: In 28 patients with transfusional iron overload, 43 measurements of the liver iron concentration were made by both R2* and high-Tc magnetic susceptometry. RESULTS: Measurements of the liver iron concentration by R2* and high-Tc magnetic susceptometry were significantly correlated when comparing all patients (Pearson's r = 0.91, p < 0.0001) and those with results by susceptometry >7 mg Fe/g liver, dry weight (r = 0.93, p = 0.006). In lower ranges of liver iron, no significant correlations between the two methods were found (0 to <3.2 mg Fe/g liver, dry weight: r = 0.2, p = 0.37; 3.2 to 7 mg Fe/g liver, dry weight: r = 0.41; p = 0.14). CONCLUSION: The lack of linear correlation between R2* and magnetic susceptibility measurements of the liver iron concentration with minimal or modest iron overload may be due to the effects of fibrosis and other cellular pathology that interfere with R2* but do not appreciably alter magnetic susceptibility.

Vitamin K deficiency bleeding after NICE guidance and withdrawal of Konakion Neonatal: British Paediatric Surveillance Unit study, 2006-2008.

OBJECTIVE: To survey vitamin K deficiency bleeding (VKDB) and document vitamin K (VK) prophylaxis practice, and compare with findings predating withdrawal of Konakion Neonatal and guidance from the National Institute of Health and Clinical Excellence (NICE), both occurring in 2006. DESIGN: Two-year surveillance of VKDB (2006-2008) using British Paediatric Surveillance Unit methodology. Postal questionnaire to consultant-led maternity units. SETTING: UK and Irish Republic. PATIENTS: All newborns and infants under 6 months with suspected VKDB. MAIN OUTCOME MEASURES: VKDB incidence and predisposing factors, VK prophylaxis recommended/received. RESULTS: Eleven cases of VKDB were found: six (55%) babies received no VK prophylaxis, in five (45.5%) because parents withheld consent; three (27.5%) babies with late VKDB received intramuscular (IM) Konakion MM (two had biliary atresia, and one was delivered preterm); two (18%) babies received incomplete oral prophylaxis. Nine babies (82%) were breast fed. Three (27%) babies had liver disease; four (36%), including all those with liver disease, were jaundiced at presentation after 21 days. Four (36%) babies had intracranial haemorrhage, two probably suffering long-term morbidity. VK prophylaxis practice was defined in 236 (100%) units. All units recommended prophylaxis for every newborn: 169 (72%) IM, 19 (8%) oral, and 48 (20%) offered parental choice. All units that recommended IM prophylaxis used Konakion MM. Oral prophylaxis always involved multidose regimens for breastfed babies; 61 (91%) units used Konakion MM, and six (9%) used unlicensed products suitable for administration by parents. CONCLUSIONS: IM Konakion MM is efficacious, but parents withholding consent for recommended IM prophylaxis reduces effectiveness. Reappraisal of NICE guidance would be appropriate. Prolonged jaundice demands investigation. Late VKDB occasionally occurs after IM prophylaxis.

Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation.

OBJECTIVE: Nonautoimmune hyperthyroidism (NAH), a rare autosomal dominantly inherited condition characterized by nonremitting thyrotoxicosis and the absence of features of autoimmune thyrotoxicosis, can result from activating germline mutations in the thyrotropin receptor (TSHR) gene. We report clinical and genetic features of a new family with NAH, and highlight that premature delivery and low birth weight are important characteristics of this condition. PATIENTS AND METHODS: Thyrotoxicosis was diagnosed in two children at the ages 20 months and 4 years and in their father at the age of 9 years. Both children were born prematurely by Caesarian section at 33 and 30 weeks following early rupture of the membranes. Their birth weights were 1750 g (27th centile) and 790 g (< 3rd centile), respectively. Mutation analysis of the TSHR gene was performed in both children and their parents by direct DNA sequencing. RESULTS: A heterozygous germline mutation of the TSHR gene resulting in the substitution of serine (AGC) by asparagine (AAC) at codon 505 (S505N) was found, which co-segregated with thyrotoxicosis in the family. A review of all previously reported cases of NAH due to an activating TSHR germline mutation showed that the mean duration of gestation in these patients was significantly lower than in patients with inactivating TSHR mutations causing congenital hypothyroidism (35.8 weeks vs. 39.4 weeks, P = 0.003). In addition, the mean birth weight in patients with activating TSHR mutations was lower than in patients with inactivating TSHR mutations (2338 g vs. 3470 g, P = 0.004). CONCLUSIONS: Premature delivery and low birth weight are consistent features of NAH due to activating TSHR germline mutations. This suggests a possible role for the fetal thyroid axis in the regulation of the timing of delivery and possibly fetal growth.