Patients with low thyroid peroxidase antibodies (anti-TPO) and increased TSH-receptor antibodies (TRAb) at diagnosis of Graves' disease (GD) have been suggested to have an increased risk to develop Graves' ophthalmopathy (GO). The aim was to evaluate if GO development can be predicted.This is an observational study with registration of possible GD and GO risk factors.399 patients with GD were registered 2003-2008 in Malmö, Sweden and out of these 310 were retrospectively followed up to 6 years. The main outcome measures were anti-TPO titer, TRAb titer, smoking habits, radioiodine treatment and GO development.TRAb was assessed with a third generation assay at GD diagnosis in 231 patients. The proportion of patients with GO increased above the median 6.3 IU/L both at diagnosis of GD (p=0.001) and at follow-up (p=0.0001).The distribution of GO patients anti-TPO above or below 20 kIU/L at diagnosis of GD was similar between groups (p=0.239). However at follow-up anti-TPO<20 kIU/L was associated with an increased proportion of newly developed GO as compared to the cohort with anti-TPO>20 kIU/L (p=0.018).87% of patients who developed GO after GD diagnosis had TRAb above 6.3 IU/L and/or anti-TPO below 20 kIU/L. The proportion of GO was doubled in GD patients treated with radioiodine but could not explain the described findingsAnti-TPO<20 kIU/L and/or TRAb>6.3 IE/L at the time of GD diagnosis were associated with an increased risk to develop GO after diagnosis of GD.

Objective: The aim was to compare the vitamin D levels in patients with Graves disease (GD) with the general population and to correlate the vitamin D levels with laboratory and clinical parameters in GD. Moreover, we examined the genetic variation in genes involved in the vitamin D metabolism and their association with GD. Methods: The levels of vitamin D were compared in 292 patients with newly diagnosed GD and 2,305 controls. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR), vitamin D binding protein (DBP), and 1-α-hydroxylase (CYP27B1) were examined for association with GD and/or Graves ophthalmopathy (GO) in 708 patients and 1,178 controls. Results: Patients with GD had significantly lower vitamin D levels compared to controls (55.0 ± 23.2 vs. 87.2 ± 27.6 nmol/L, p < 0.001). In patients with GD (n = 219), there was no association between the levels of vitamin D at diagnosis and free thyroxine (fT₄), free triiodothyronine (fT₃), thyrotropin receptor antibodies (TRAb), GO at diagnosis, or relapse after terminating treatment with antithyroid drugs. Two SNPs in VDR were associated with GD: rs10735810 (OR = 1.36, 95% CI: 1.02–1.36, p = 0.02) and rs1544410 (OR = 1.47, 95% CI: 1.03–1.47, p = 0.02). There was no difference in the mean vitamin D level between genotypes in either rs10735810 or rs154410. Conclusions: Patients with GD had lower vitamin D levels compared to the general population; however, the vitamin D levels did not affect the laboratory or clinical parameters of GD. SNPs in the VDR influenced the risk of GD through mechanisms other than reducing the vitamin D levels.

BackgroundThe standard treatment of hypothyroidism is levothyroxine (LT-4). However, there are several controversies regarding treatment of hypothyroid patients.AimTo investigate the Swedish endocrinologists’ use of thyroid hormones in hypothyroid and euthyroid individuals.MethodsPhysician members of the Swedish Endocrine Society (SEF) were invited by e-mail to participate in an online survey investigating this topic.ResultsOut of the eligible 411 members, 116 (28.2%) responded. The majority (98.9%) stated that L-T4 is the treatment of choice. However, around 50% also prescribed liothyronine (L-T3) or a combination of L-T4+L-T3 in their practice. Combination therapy was mostly (78.5%) used in patients with persistent hypothyroid symptoms despite biochemical euthyroidism on L-T4 treatment. Most respondents prescribed L-T4 tablets and did not expect any major changes with alternative formulations such as soft-gel capsules or liquid formulations in situations influencing the bioavailability of L-T4. In euthyroid patients, 49.5% replied that treatment with thyroid hormones was never indicated, while 47.3% would consider L-T4 for euthyroid infertile women with high thyroid peroxidase (TPO) antibody levels.ConclusionThe treatment of choice for hypothyroidism in Sweden is L-T4 tablets. Combination therapy with L-T4+L-T3 tablets was considered for patients with persistent symptoms despite biochemical euthyroidism. Soft-gel capsules and liquid solutions of L-T4 were infrequently prescribed. Swedish endocrinologists’ deviation from endocrine society guidelines merits further study.