Hyperthyrotrophinaemia during thyroxine replacement therapy

During the follow-up of 224 cases of treated hypothyroidism, 14 clinically euthyroid patients were found to have elevated serum thyrotrophin and normal total thyroxine concentrations. Closer observation of these patients during the following 27 months resulted in the serum thyrotrophin levels returning to normal spontaneously in 8 patients (Group 1) whilst remaining elevated in 6 (Group 2), despite no significant differences in thyroid hormone levels between the two groups. Serum thyrotrophin in Group 2 patients remained high until an additional 50 micrograms/day thyroxine was prescribed although only 2 patients noted any benefit. Non-compliance or inadequate dosage of thyroxine are the probable causes of this sub-clinical hypothyroidism. Thyroid hormone estimations fail to differentiate the two conditions and we recommend a period of closer observation before making any thyroxine dosage adjustments in order to detect non-compliance.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.