Background: Thymus transplantation is undertaken for conditions associated with severe immunodeficiency. These comprise a number of genetic and syndromic associations including 22q deletion syndrome, CHARGE association, diabetic embryopathy, and other rarer conditions. Autoimmune thyroid dysfunctions (Hashimoto's thyroiditis and Graves' Disease) are described in the literature as the most common autoimmune disease after thymic transplant.
Objective: To determine the frequency and aetiology of thyroid dysfunction following thymus transplantation at a tertiary center.
Case Series: Total 33 patients (age 2 months-2 years, 20 male) from the UK and 13 European centres underwent thymus transplantation between 2009-2018. The underlying diagnoses included 22q11.2 (n=18, 1 with a phenotype only of 22q11.2), CHARGE association (n=10), diabetic embryopathy (n=2), FOXN1 mutation (n=2), and TBX1 mutation (n=1).
24 patients (72.2%) were assessed for thyroid status prior to transplant. Pre-transplant thyroid function test (TFT) abnormalities were found in 5 patients. Secondary hypothyroidism n=2 (Typical DiGeorge and TBXMUT mutation). Persistently raised TSH with normal FT4 n=1 (CHARGE). Transiently raised TSH with normal FT4 n=2.
Post-transplant TFT results were available for 16 patients (48.49%). Of these, 3 patients had normal thyroid function, and 3 had pre-existing thyroid dysfunction prior to transplant. 10 patients (62.5 %) developed post-thymic transplant thyroid dysfunction. Autoimmune thyroid disease (positive anti-TPO antibodies) were found in 5 patients (31.2 % of total cohort). Of these, 3 were found to have a raised TSH with Low FT4 at time and were commenced on levothyroxine treatment. T4 assay interference on post-mortem samples was confirmed in 1 patient, who had an undetectable T4. 1 patient has normal thyroid function to date with positive anti TPO antibodies. Transiently raised TSH (normalization within 6 months) was seen in 3 patients.
Thyroid dysfunction was observed as early as Day 8 post-transplant to 2-years post-transplant. The mean time to develop autoimmune thyroid disease was 1.2 years after transplant (7 month- 2 years).
Conclusion: This case series highlights the variability of thyroid dysfunction in patients undergoing thymus transplantation. This vulnerable cohort is at significant risk of thyroid dysfunction. Assay interference should be considered while analyzing TFT post-thymic transplant.
The lack of standardized evidence-based guidelines for the investigations and management of these patients has important implications for morbidity, mortality and healthcare costs.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology