Endocrine Abstracts

Background: Hyperthyroxinaemia with non-suppressed TSH, due to resistance to thyroid hormone (RTH) or TSH-secreting pituitary tumour (TSHoma), can be difficult to diagnose, particularly with coincident autoimmune thyroid disease (AITD).

Methods: To determine presentation patterns of AITD coincident with RTH or TSHoma, we analysed our cohort of cases with dual diagnoses.

Results: Nine patients with RTH had AITD. Six had Graves’ disease (GD); RTH was suspected when anti-thyroid drug treatment led to unexpected TSH increase despite hyperthyroxinaemia (e.g. initial TSH <0.03 mU/l, TT₄ 300 nmol/l; post carbimazole TSH 6 mU/l, TT₄ 150 nmol/l (NR 50–150)) or when hyperthyroxinaemia was associated with incompletely suppressed TSH (e.g. FT₄ 89.6 pmol/l, FT₃ 26.7 pmol/l, TSH 0.04 mU/l during GD flare-up, with baseline TSH 1.7 mU/l, FT₄ 27.9 pmol/l, FT₃ 16.7 pmol/l). Three had autoimmune hypothyroidism with elevated TSH levels but high-normal TH (e.g. TSH 29.8 mU/l, FT₄ 20.8 pmol/l, FT₃ 7.2 pmol/l) and positive anti-TPO antibody titres.

Two patients with TSHoma had coincident AITD; the first presented with an elevated TSH and concomitant mild hyperthyroxinaemia (TSH 35.2 mU/l, FT₄ 22.2 pmol/l), the second presented with failure to suppress TSH after levothyroxine for presumed primary hypothyroidism (TSH 5.9 mU/l, FT₄ 25 pmol/l, on 50 μg of levothyroxine). Both had raised TPO antibody titres.

20% of our genetically heterogeneous RTH cohort (n=160) without known AITD, are anti-TPO antibody positive, but all are anti-TSHR antibody negative.

Conclusion: Resistance within the HPT axis (RTH) or inappropriate TSH secretion (TSHoma) should be suspected in i) autoimmune hypothyroidism where physiological dose thyroxine replacement fails to correct elevated TSH, ii) thyrotoxic patients with incompletely suppressed TSH especially when normalisation of TH levels in response to anti-thyroid drug treatment results in exaggerated TSH rise and iii) patients with elevated TSH but high-normal TH concentrations. Lastly, the increased prevalence of positive thyroid autoantibodies in RTH suggests these patients may be at greater risk of developing AITD.