Endocrine Abstracts

Case history: A 28-year-old gentleman was referred with symptoms of memory fog, difficulty with concentration, mood disturbance and fatigue. His thyroid function tests had been stable but abnormal for over 8 years, with a normal FT4 between 17–19 pmol/l (12–22 pmol/l), FT3 5.6 pmol/l (3.1–6.8 pmol/l) and an elevated TSH between 12–16 mu/l (0.27–4.2 mu/l). He had no family history of thyroid disease. He was clinically euthyroid. His weight had remained stable over the years and he had a pulse rate of 70 bpm. Clinical examination of his thyroid was normal.

Investigations: Further investigations showed that his thyroid peroxidase antibody titre was negative, and his SHBG concentration and anterior pituitary function tests were normal. A differential diagnosis of assay interference or thyroid hormone resistance was considered. A sample was sent to the reference laboratory at Addenbrooke’s Hospital, Cambridge.

Results and Treatment: Blood results from Addenbrooke’s Hospital showed good agreement with local assay methods, however, there was low PEG recovery in the DELFIA assay indicating the possible presence of macro (antibody-bound) TSH. There was a comment that TSH results may be unreliable in this patient. This fitted with the clinical impression, and he was discharged with a recommendation that his FT4/FT3 should be used to assess his thyroid status if there was any future concern. Alternative causes for his symptoms were explored.

Conclusion and points for discussion: This patient’s raised TSH was due to assay interference from macro-TSH. Macro-TSH is caused by combinations of TSH and anti-TSH autoantibodies forming macrocomplexes. It has low bioactivity. Macrocomplexes as a cause of assay interference have been best described with respect to prolactin (macroprolactin). This phenomenon is less familiar with TSH, but is not that uncommon. Estimates of prevalence range from 0.6% in a study of 463 samples sent for routine analysis and found to have a TSH>10 mu/l, to 1.62% in 681 samples from patients with subclinical hypothyroidism. As TFTs (particularly TSH) are checked in many millions of the UK population annually, this is probably an under-recognised phenomenon. It is important to be aware of macro-TSH to prevent patients undergoing inappropriate investigations and treatment.