Thyroid Research: A 5-Year Summary

From ThyroWorld Volume 3, No 1, Spring 2000.

This summary of recent thyroid research was presented by TFI's Medical Adviser, Dr. Robert Volpé at our 4th annual conference held in Pieria, Greece in May 1998. In conjunction with the research articles in this issue, numbers 7,8 and 10 may be of particular interest.

1. Thyrotoxicosis
   Vassart et at (JCEM 81:547, 1996) have determined the functional characteristics of three new germline mutations of the TSH receptor gene causing autosomal dominant toxic thyroid hyperplasia . This is a rare form of hyperthyroidism seen in infants due to an inherited mutation of the TSH receptor. The TSH receptor has an extracellular component, a transmembrane component and an intracellular component. It is in the extracellular component that these mutations have occurred. It may be added that manv cases of toxic nodular goitre in adults have been shown to be due to somatic mutations in the extracellular component of the TSH receptor, that is, occurring after birth, presumably in adult life.

2. Tuttle et al (Thyroid 5:243, 1995) have shown that treatment with propylthiouracil before radioactive iodine therapy is associated with a higher treatment failure rate than therapy with radioactive iodine alone in Graves' disease. Thus patients treated with PTU may require a greater radioactive iodine dose to ensure adequate treatment of their disease.

3. Toft et al (NEJM 334:220,1996) have shown that adding thyroxine along with an antithyroid drug does not improve the remission rate of Graves' disease when compared to the antithyroid drug alone. This is now the fourth such study and the whole idea that thyroxine would be helpful is now passing out of consideration.

4. Pinchera et al Pisa, Italy (NEJM) have now confirmed the studies of Tallstedt et al that radioactive iodine treatment for Graves' disease, given as primary therapy brings with it a risk of about 15%, that the eye disease will worsen following the treatment.

5. Shimojo et al (Proceedings of the National Academy of Science of the United States of America 93:11074,1996) have induced a disease much like Graves' disease in mice by immunizing them with fibroblasts transfected with the TSH receptor and a Class 11 molecule. Although this is an extremely interesting animal model which may be similar to Graves' disease, the thyroid cells may not be capable of presenting antigen as the fibroblasts seem to be capable of doing in this model. There is evidence that upregulating Class 11 expression on thyroid cells will not aggravate or precipitate Graves' disease and in fact will be protective instead.

6. Cho et al have shown a high prevalence of TSH receptor blocking antibodies which on the other hand, do not change with thyroxine or antithyroid drug therapy in patients with autoimmune thyroiditis.

7. Pop et al (JCEM 80:3561,1995) have shown that children of women with high titres of thyroperoxidase antibody and normal thyroid function in late gestation are at increased risk for impaired development. This interesting study has not yet been confirmed.

8. Wasserstrum et al (Clinical Endocrinology 42:353-1995) have shown that severe maternal hypothyroidism in early pregnancy frequently resulted in foetal distress during labour. Although near term, free thyroxine values were normal in these women, TSH levels were elevated throughout pregnancy. Early thyroxine therapy of patients is important because early deficits in the maternal thyroxine level may have permanent effects of a negative nature on the foetus.

9. Sawin et at (JAMA 276:285, 1996) have screened for mild thyroid failure at a periodic health examination for an analysis of decision making and cost effectiveness. The cost effectiveness of screening 35-year old patients with a serum TSH assay every five years was about $9000.00 US per quality adjusted life years for women and $22,000.00 US for men. Their conclusion was that screening for mild thyroid failure is as cost effective as other generally accepted preventive medical strategies. Measuring serum TSH levels in patients aged 35 years and older, especially elderly women, would be beneficial.

10. Reuss et al (NEJM 334:821,1996) have studied the relation of transient hypothyroxinaemia in pre-term infants to neurological development at two years of age. Many pre-term infants have transient hypothyroxinaemia which has generally been viewed as a condition with no long term sequelae and does not require thyroid hormone replacement. However, the possible link between hypothyroxinaemia in premature infants and subsequent motor and cognitive abnormalities was investigated in a historical cohort study. Drug thyroxine concentrations increased with gestational age for infants born after 29 weeks. The risk of disabling cerebral palsy was significantly increased for infants with severe hypothyroxinaemia when compared with those without hypothyroxinaemia after adjustment for gestational age. The mean development score at age two was 15 points lower for the infants with severe hypothyroxinaemia. Thus, this condition in preterm infants appears to be related to problems in neurological and mental development at age two. Studies of treatment to increase neonatal thyroxine concentrations could help determine whether the relationship is a causal one and whether treatment can prevent the neurological and development sequelae.

11. Fagin et al (JCEM 81:9, 1996) have studied the thyroid lesions in children and adolescents after the Chernobyl disaster. They have shown that malignant and benign thyroid tumours have appeared after a short latency period in a substantial number of children exposed to radiation after the Chernobyl disaster. The important factors in the development of malignant lesions appear to be exposure at an early age, and residence in the most contaminated regions.

12. Gharib and Mazzaferri (Annals of Internal Medicine 128:386,1998) have shown that patients with cytologically benign thyroid nodules are best followed without thyroxine treatment. Most benign nodules remain stable in size and remain benign when monitored over a long period of time. For nodules that increase in size, biopsy should be done again or surgery should be performed.