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Highlights from the European Thyroid Association Annual Meeting, September 15-18, 2018, Newcastle-upon-Tyne, UK

Highlights from the European Thyroid Association Annual Meeting, September 15-18, 2018, Newcastle-upon-Tyne, UK
  • Endocrinology and metabolism
  • Thyroid disorder

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International meeting
ETA
genetics
thyroid cancer
LT-4 bioequivalence

This 4-day event was a great scientific and medical success, attended by approximately 1100 participants and supported by 15 European sponsors. The meeting presented the latest developments in clinical and experimental thyroid research.

Thyroid update

The symposium “Thyroid update” provided an insight into three clinically relevant topics in thyroidology. Professor Pilar Santisteban (President of the ETA, Spanish National Council of Research, Institute of Biomedicine Alberto Sols of Madrid, Spain), introduced the audience to the “Genomic profiles of thyroid cancer”. Progress has been made in decoding the thyroid cancer genome, which has revealed the breadth of genetic mutations across the spectrum of thyroid neoplasia. 

Professor Colin Dayan (Secretary of the ETA, Department of Clinical Diabetes and Metabolism, Cardiff University School of Medicine, UK) discussed the recently described condition of immune reconstitution thyroiditis. The first demonstration of immune reconstitution autoimmune thyroid disease (AITD) was in patients with multiple sclerosis who had received lymphocyte-depleting alemtuzumab antibody treatment. Of these, 20–30% developed TSH-R-antibody positive Graves’ disease. A similar pattern of AITD has been observed in patients with HIV who have received effective, highly active antiretroviral therapy and in bone marrow transplant patients, with hyperthyroidism developing as CD4 lymphocyte count increases. 

Professor Tomasz Bednarczuk (Treasurer of the ETA, Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Poland) offered an overview on “iodinated contrast media-induced hyperthyroidism”, a poorly defined medical problem arising in daily practice. Indeed, iodinated contrast media exposure is associated with subsequent development of thyroid dysfunction in 1–10% of cases.

Pharmacokinetics and bioequivalence of L-T4 compounds

Thyroid hormones are a critical component in the regulation of metabolic rate. Insufficient production of thyroid hormones influences every tissue of the body, causing diverse and non-specific effects. The treatment of choice is the synthetic thyroid hormone, levothyroxine (L-T4), which substitutes for endogenously produced T4. L-T4 is chemically identical to the naturally secreted T4: it increases metabolic rate, decreases thyrotropin production from the anterior lobe of the pituitary gland, and in peripheral tissues, is converted to T3. Often considered a drug with a narrow therapeutic window, small changes in dose may have significant clinical effects in sensitive patients. Therefore, dosing of L-T4 must be carefully tailored to age, sex, clinical condition and body weight, and requires regular fine-tuning, depending on the clinical course. 

Levothyroxine sodium tablets are manufactured with a shelf-life of up to 36 months and at the standard shelf-life specification of 90–110% of the label claim. However, following adjustments to the potency specifications in the revised United States Pharmacopoeia (USP) monograph for L-T4 tablets, and the request by Agence Nationale deSécuritédu Medicament et des Produits de Santé (ANSM) for all companies to adopt this specification, increasingly authorities are adopting tighter potency specification requirements for L-T4. To meet the more stringent potency criteria from various national regulatory bodies – the most stringent of which being 95.0–105.0% at release and over the envisaged shelf-life – the tablets have been redeveloped, with changes to the quantitative composition of excipients. Other agencies have been less stringent in their revisions, such as the Medicines and Healthcare Products Regulatory Agency (MHRA), which recommends 90.0–105.0%.

A number of European countries have faced several issues regarding the interchangeability of L-T4 products over the past years. Although it is not possible to ascertain what proportion of these health issues are biologically related to the formulation change, the issues include increased prevalence of non-specific side- effects. Biochemical signs of potential inadequate dosing may follow since testing bioequivalence does not guarantee continued euthyroidism after a formulation change of L-T4 and, as a consequence, enhanced healthcare consumption and healthcare expenses may arise. In line with this, a joint statement on the interchangeability of L-T4 products in European countries on behalf of the European Thyroid Association and Thyroid Federation International has been recently posted on the website of the ETA

Professor Hans-Peter Lipp, (Department of Clinical Pharmacy, Tübingen University, Germany) introduced the pharmacologic terms: pharmacokinetics, bioequivalence, pharmacovigilance, shelf-life, 95%-105% potency specification and dosage form proportionality to the audience and specified the requirements of the European Medicine Agency (EMA) for L-T4 products. Subsequently, Professor James Hennessey (Department of Clinical Endocrinology, Harvard University, Boston, USA) discussed the requirements of the Food and Drug Administration (FDA), the current standards in the US, and compared the FDA with the EMA policy.

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