OUDE Hypoforum

Program Number 9
Autoimmunity Thursday Poster Clinical
RISK OF COEXISTING AUTOIMMUNE DISEASES IN 3286 INDEX CASES WITH AUTOIMMUNE THYROID DISEASE AND THEIR PARENTS

K. BOELAERT1, P. NEWBY1, M. SIMMONDS1, R. HOLDER2,
J. CARR-SMITH1, J. HEWARD1, A. ALLAHABADIA3,
M. ARMITAGE4, K. CHATTERJEE5, J. LAZARUS6, S. PEARCE7,
B. VAIDYA8, S. GOUGH1, J. FRANKLYN1
1Department of Medicine, University of Birmingham, Birmingham,
United Kingdom; 2Statistics, University of Birmingham, Birmingham,
United Kingdom; 3Departments of Endocrinology and Endocrine
Surgery, Sheffield Teaching Hospitals NHS Trust and Division of
Clinical Sciences University of Sheffield, Sheffield, United Kingdom;
4Department of Medicine, Royal Bournemouth Hospital,
Bournemouth, United Kingdom; 5Department of Medicine,
Addenbrooke’s Hospital, Cambridge, United Kingdom; 6Department
of Medicine, University of Wales College of Medicine, Cardiff, United
Kingdom; 7Institute of Human Genetics, Newcastle University,
Newcastle upon Tyne, United Kingdom; 8Department of Medicine,
Royal Devon and Exeter Hospital, Exeter, United Kingdom

Autoimmune thyroid diseases (AITD), Graves’ disease (GD), and Hashimoto’s thyroiditis (HT) are common, but there is limited  information on the prevalence of coexisting autoimmune diseases (AID).
We investigated a prospectively collected cohort of 3286 patients with AITD and determined prevalences of associated AID in
index cases and parents.
Of those with GD (n¼2791), 9.67% had another AID, with a higher frequency in HT (14.3%, p¼0.005).
Rheumatoid arthritis was the commonest coexisting AID (in GD:
3.15%; in HT: 4.24%).
In GD, prevalences of type 1 diabetes mellitus, pernicious anemia, and vitiligo were between 1% and 2%, with similar findings in HT apart from more frequent pernicious anemia (4.04% versus 1.4%, p¼0.004) and a 10-fold higher prevalence of Addison’s disease (1.41% versus 0.11%, p<0.001).
Relative risks (RR) were increased for almost all of the AID examined with RR >10 for pernicious anemia, SLE, Addison’s disease, celiac disease, vitiligo, and myasthenia gravis; higher RRs were evident for pernicious anemia and Addison’s disease in HT than in GD.
There was relative ‘‘clustering’’ of GD in the index case with parental hyperthyroidism and of HT in the index case with parental hypothyroidism.
Mothers of index cases with either GD or HT had a reported history of thyroid dysfunction in 17.5% and 23.6% of cases, respectively.
Fathers of index cases had thyroid dysfunction in 3.1% (GD) and 5.7% (HT) of cases.
RRs for other autoimmune disorders were increased among
parents of index cases, being >10 for rheumatoid arthritis and pernicious anemia in parents of either GD or HT cases. Because of its unprecedented size and power, this study allows, for the first time, accurate quantification of the risk of other AID in subjects with AITD and their parents.
Associations were common to GD and HT, but there were specific differences, reflecting either different susceptibility genes or  different environmental triggers.

Program Number 10
Autoimmunity Thursday Poster Clinical
VITAMIN D DEFICIENCY IS A RISK FACTOR FOR OPHTHALMOPATHY IN PATIENTS WITH GRAVES’ HYPERTHYROIDISM

B. WISE, H. TJIANG, H. LAHOOTI, J. WALL
Medicine, University of Sydney, Penrith, Australia

Apart from its role in bone metabolism, there is good evidence that
vitamin D (VitD) plays a role in immune function, cancer prevention,
and autoimmunity. VitD deficiency (serum level <25 nmol=L)
and insufficiency (25–50 nmol=L) are very common in the West
Sydney area. We have addressed a possible relationship between
VitD deficiency=insufficiency and ophthalmopathy or isolated chronic
upper eyelid retraction (UER) in patients with Graves’ disease (GD)
and Hashimoto’s thyroiditis (HT).
We studied 37 patients with GD and 69 with HT at the first visit before any VitD replacement. Overall, 70% of patients with GD and 76% of those with HT were VitD deficient or insufficient. Sixty-one percent of patients with GD who were VitD deficient had ophthalmopathy (CAS >2) and=or UER compared
to 75% who were VitD insufficient and 27% who were VitD replete
(w2-test vs. replete; p<0.01 and p<0.01, respectively). Twelve percent of patients with HT who were VitD deficient had mild ophthalmopathy (one patient) or isolated UER (seven patients), and 88% had no eye signs, compared to 22% and 78%, respectively, who were VitD
insufficient and 20% and 80%, respectively, who were VitD replete
(vs. replete; all p¼NS). There was no significant relationship between VitD status and positive calsequestrin or collagen XIII antibodies in patients with GD or HT.
Overt ophthalmopathy is common in patients with GD, while UER, with or without generally mild ophthalmopathy,
is found in about 25% of patients with HT. The observed relationship between VitD deficiency=insufficiency and  ophthalmopathy, but not UER, suggests that the pathogenesis of the two disorders is different.
While the significance of the findings needs to be addressed in prospective studies before and after VitD replacement, it is clear that VitD deficiency is another risk factor for ophthalmopathy
in patients with Graves’ hyperthyroidism.

Program Number 53
Thyroid Diseases Thursday Poster Clinical
METFORMIN THERAPY DECREASES SERUM TSH LEVELS IN PATIENTS SUBMITTED TO L-THYROXINE TREATMENT

F. ARTURI1, C. CLORO2, E. SUCCURRO1, T. BUCCINNA’1,
G. COSTANTE1
1Dipartimento di Medicina Sperimentale e Clinica, University of
Catanzaro, Catanzaro, Italy; 2Unita` Operativa di Cardiologia,
UTIC-Riabilitazione Cardiologia, I.N.R.C.A, Cosenza, Italy

Although metformin has been widely used for several decades, the
possibility that this drug could modify thyroid hormone economy has
never been considered. A recent report has described four hypothyroid patients in whom metformin appeared to suppress serum thyroid-stimulating hormone (TSH) to subnormal levels.
Aim of this prospective study was to evaluate the effect of metformin administration on free triiodothyronine (T3) and TSH levels in a group (n¼32) of patients submitted to levo-thyroxine therapy (L-T4) for primary hypothyroidism or multinodular goiter. The results were

Program Number 52
Thyroid Diseases Thursday Poster Clinical
BONE AND MINERAL METABOLISM IN RESISTANCE TO THYROID HORMONE

Program Number 92
Autoimmunity Friday Poster Clinical
PATIENTS OF HASHIMOTO’S DISEASE WITH 590CC GENOTYPE IN THE IL4 GENE WOULD DEVELOP HYPOTHYROIDISM

M. WATANABE1, T. NANBA1, T. AKAMIZU2, Y. IWATANI1
1Division of Health Sciences, Department of Biomedical Informatics,
Osaka University Graduate School of Medicine, Suita, Japan;
2Translational Research Center, Kyoto University Hospital, Kyoto
University School of Medicine, Kyoto, Japan

Program Number 93
Autoimmunity Friday Poster Clinical
EYE AND UPPER EYELID ABNORMALITIES ARE COMMON
IN PATIENTS WITH HASHIMOTO’S THYROIDITIS

J. WALL, H. TJIANG, B. WISE, H. LAHOOTI
Medicine, University of Sydney, Penrith, Australia