Endocrine Abstracts

Case: A 31-year-old female presented to Gynaecology abroad with a three-month-history of secondary amenorrhoea in 2011. Thyroid function checked and TSH was high with normal free T4 (FT4) and free T3 (FT3). She was commenced on Levothyroxine with gradual dose titrations up to a maximum dose of 75 micrograms daily. Despite variations in levels and some response, TSH never normalised, and she stopped Levothyroxine in 2015. She moved to the UK in 2016 and was referred to our Service in 2020 with “abnormal thyroid function” and TSH ranging between 32 and 59 mU/l (normal reference range 0.35-5 mU/l). FT4 and FT3 were normal on serial testing with negative TPO antibodies. Pituitary function was checked with normal cortisol, prolactin and gonadotrophins. Patient was taking no regular medication, except supplements of vitamin C, zinc and occasional use of bone complex. She reported occasional cold intolerance but no other symptoms of thyroid dysfunction. Her mother had normal TSH; her father and brother had never been tested. Her TFTs were repeated and sent to another lab to exclude assay interference; TSH confirmed to be high at 39.9 mU/l in our lab and 17.43 mU/l in external lab. Given she had experienced some response to the raised TSH with Levothyroxine, she was diagnosed with subclinical hypothyroidism, advised to restart Levothyroxine and discharged. She went back to Sweden and returned to the UK in 2024 at 24 weeks of her first pregnancy. She had been tested for interference of macro-TSH and confirmed in Sweden. Her thyroid function tests were repeated with us, and further tests were sent to Addenbrooke’s Hospital where interference with macro-TSH was confirmed. TSH on Atellica was 34.16 mU/l with borderline recovery with polyethylene glycol (PEG) precipitation. The best estimate of bioactive TSH was 5.5-16.3 mU/l.

Discussion: Macro-TSH is a rare finding, caused by binding of TSH to other plasma proteins, commonly immunoglobulins, resulting in falsely elevated TSH measurement. The biochemical profile mimics subclinical hypothyroidism and if not identified early, can result in inappropriately high Levothyroxine doses. Due to assay interference, TSH is not a reliable indicator of thyroid status. Clinical judgement and monitoring of FT4 and FT3 is recommended to guide management. Our patient remained clinically and biochemically euthyroid for the duration of her pregnancy and did not require any treatment. As macro-TSH can cross the placenta and interfere with the heel-prick test, further neonatal testing might be indicated.