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Background: The incidence and risk factors of amiodarone-induced thyroid dysfunction are variable in the literature., Objective: The aim of this study was to investigate the clinical and biochemical features and risk factors of amiodarone-induced thyroid dysfunction in Taiwan., Setting: This study was conducted at a tertiary referral center for arrhythmia., Method: Retrospective analysis of patients treated with amiodarone during the years 2008-2009 was performed., Main Outcome Measure: Incidence and risk factors of amiodarone-induced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH) were assessed., Results: Of the 527 patients, 437 (82.9 %) remained euthyroid, 21 (4.0 %) developed AIT, and 69 (13.1 %) were affected with AIH. In univariate analysis, AIT was associated with younger age, and the risk factors for AIH included older age, higher baseline thyroid stimulating hormone (TSH) titer, lower baseline free T4 level, lower cumulative amiodarone dosage, and shorter amiodarone treatment duration. Cox regression analysis was performed to determine the different risk categories in the elderly population of age 65-74 (young-old), 75-84 (old-old), and ≥85 years old (oldest-old). Additionally increased risk of AIH was found in the groups of old-old (HR 2.09, 95 % CI 1.11-3.96) and oldest-old (HR 2.57, 95 % CI 1.21-4.75). In the multivariate analysis of risk factors for AIH, baseline TSH level (HR 1.38, 95 % CI 1.12-1.70) and cumulative amiodarone dosage (HR 0.95, 95 % CI 0.93-0.97) remained statistically significant., Conclusion: AIH was much more common than AIT in Taiwan, an area with sufficient iodine intake. Higher baseline TSH level was the predominant independent risk factor for the development of AIH.

Objectives: To identify mutations in the KAL1, the KAL2, and PROKR2/PROK2 genes and to characterize phenotypic features in 5 Chinese subjects with Kallmann Syndrome (KS) and 6 subjects with normosmic hypogonadotrophic hypogonadism (NHH) in Taiwan., Design and Patients: Five unrelated males (age range 22-52 yr) with clinical manifestations of KS and 6 unrelated males (age range 24-47 yr) with NHH were analyzed. In addition, 5 relatives of KS subjects were also evaluated. Genomic DNA extraction, PCR, and DNA sequence analyses were performed using standard procedures., Results: The 1st patient had a single missense mutation in his copy of the KAL1 gene, a T→G transversion in codon 134 that results in replacement of cysteine by gly cine. The 2nd affected subject had a single missense mutation in the KAL1 gene, a T→C transition in codon 163 that results in replacement of cysteine by arginine. The 3rd case was hemizygous for a nonsense mutation in codon 424 of exon 9 (c.CGA→TGA) of the KAL1 gene. This mutation predicts a markedly truncated protein. Two of the mutations (p.C134G and p.C163R) we identified in the KAL1 gene are novel., Conclusions: We identified 3 mutations, including 2 novel mutations, in the KAL1 gene in patients with KS in Taiwan. These data extend the variety of KAL1 gene mutations in KS and further define the role of the KAL1 protein in olfactory bulb development.

Multiple endocrine neoplasia type 1 (MEN1) is characterized by parathyroid, enteropancreatic endocrine and pituitary adenomas as well as germline mutation of the MEN1 gene. We describe 2 families with MEN1 with novel mutations in the MEN1 gene. One family was of Turkish origin, and the index patient had primary hyperparathyroidism (PHPT) plus a prolactinoma; three relatives had PHPT only. The index patient in the second family was a 46-yr-old woman of Chinese origin living in Taiwan. This patient presented with a complaint of epigastric pain and watery diarrhea over the past 3 months, and had undergone subtotal parathyroidectomy and enucleation of pancreatic islet cell tumor about 10 yr before. There was also a prolactinoma. Sequence analysis of the MEN1 gene from leukocyte genomic DNA revealed heterozygous mutations in both probands. The Turkish patient and her affected relatives all had a heterozygous A to G transition at codon 557 (AAG-->GAG) of exon 10 of MEN1 that results in a replacement of lysine by glutamic acid. The Chinese index patient and one of her siblings had a heterozygous mutation at codon 418 of exon 9 (GAC-->TAT) that results in a substitution of aspartic acid by tyrosine. In conclusion, we have identified 2 novel missense mutations in the MEN1 gene.