Diagnostic Complexities in determining the cause of Secondary Hyperthyroidism
Dr S Clarke, Dr M Oldfield, Miss F Davidson
TSHomas are extremely rare, accounting for <1% of all pituitary adenomas (Kienitz et al, 2007). Characterised by autonomous TSH secretion, they result in secondary hyperthyroidism. The main differential diagnosis is thyroid hormone resistance (RTH), an autosomal dominant condition associated with variable end organ resistance to thyroid hormone, ineffective negative feedback and resultant increased TSH secretion by the pituitary gland.
We present the case of a 25 year old patient who attended with polyathralgia three weeks following elective tonsillectomy and who was found serendipitously to have elevated thyroid hormones (fT4 47.7 pmol/L and TSH 7.11 mU/l). On endocrine enquiry he admitted to long standing low weight, and mild tremor, but no symptoms of overt thyrotoxicity. He denied headaches or visual problems. Clinical examination revealed a tall, slim man with small goitre and resting tachycardia.
T3 suppression with 80mcg o.d for 10 days failed to supress his TSH (TSH 5.32 mU/l pre T3, 5.06 mU/l post T3) and subsequent TRH stimulation showed a flat response (Time 0 mins - TSH 3.08 mU/l, time 30 mins 4.96 mU/l, time 60 mins - TSH 3.89 mU/l). Alpha subunits were not raised (0.35 units). Genetic analysis for RTH was negative. Pituitary MRI revealed a microadenoma and the patient underwent excision. Post surgery the patient reported increased weight, resolution of his tachycardia and improvement in bowels and general well being. Thyroid function returned to normal (TSH 0.41 mU/l). Pituitary histology stained TSH in keeping with a TSHoma.
This complex case provided a diagnostic challenge and required a combination of biochemistry, radiology and histopathology to determine the cause of the patient's presentation.
Thyroid hormone resistance was suggested by the patient's lack of clinical features consistent with thyrotoxicosis, along with negative alpha subunits. However, his flat response to TRH stimulation, along with the absence of genetic mutations, and findings of a TSH staining adenoma confirmed the diagnosis of TSHoma. This case clearly raises the question of how to reliably differentiate between RTH and TSHoma in patients with secondary hyperthyroidism.