A 60 year old lady was diagnosed with thyrotoxicosis in 1985 (aged 28) five months postpartum. She underwent partial thyroidectomy in 1990 (age 32). Thyroid tests remained abnormal and in 1992, she underwent radio-iodine treatment requiring post-treatment. She remained under endocrine supervision and the TSH was found to be persistently elevated with normal free thyroid hormone levels (whilst on Levothyroxine). Issue with compliance and assay interference were considered. She was referred to our unit for an opinion and advice on best management. Her mother also had abnormal thyroid status and her sister has been referred for genetic testing, which we presume was secondary to abnormal thyroid function tests. She denied any long bone fractures, however reported worsening symptoms of feeling hot and sweaty with occasional palpitations over 12 months. She was on Tibolone which was changed to alendronic acid for osteoporosis identified on DEXA scan.
TPO-abs: 35 (060 mIU/L)
Anti -Thyroglobulin Abs <15 (060 mIU/L)
TSH-R abs: <0.9 (IU/L)
Normal FSH, LH and serum prolactin from 2014.
SHBG: 49 (1469 mmol/L)
Cortisol: 611 nmol/L (610 am: 133537 nmol/L; 48 pm: 68327 nmol/L)
Vitamin D 122 nmol/L
Anti-Tissue transglutaminase Ab: 0.3 (0-7)
Negative smooth muscle antibody, anti-nuclear antibody, anti-mitochondrial antibody, gastric parietal cell antibodies and negative Liver/kidney microsomal antibodies. Pituitary MRI showed a small Rathkes cleft cyst of the pituitary gland with no serial change over two years. Given the family history and repeated elevated TSH level and free T4, she had diagnostic testing for thyroid hormone resistance once assay interference was ruled out. Fluorescent sequencing analysis detected a heterozygous base change c.272>T, in exon 7 of the THRbeta gene. This pathogenic variant is predicted to result in an abnormal THRbeta protein and has been previously associated with thyroid hormone resistance. Reviewing the history it is likely that prior to surgery and RAI that free hormone levels were elevated with non-suppressed TSH (data unavailable). There is no current clinical or serological evidence of Graves or AITD. Understanding that there is THR helps with management of the case. We have been titrating thyroxine against clinical symptoms, measuring free hormones and SHBG. The patient feels most well with a generous TSH, and there may be differential tissue sensitivity to the exogenous thyroxine.