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Yew Wen Yap, Steve Ball and Zubair Qureshi

Summary

The coexistence of primary hypothyroidism and thyroid-stimulating hormone (TSH)-stimulating pituitary macroadenoma can be a rare occurrence and can make diagnosis very challenging. We describe a case of a 44-year-old female with a history of fatigue, poor concentration, weight gain and amenorrhoea together with biochemical evidence of primary autoimmune hypothyroidism. Her initial TSH levels were elevated with low normal free thyroxine (T4) levels. Levothyroxine treatment was initiated and the dose was gradually titrated to supraphysiologic doses. This led to the normalisation of her TSH levels but her free T4 and triiodothyronine (T3) levels remained persistently elevated. This prompted a serum prolactin check which returned elevated at 2495 µ/L, leading onto pituitary imaging. A MRI of the pituitary gland revealed a pituitary macroadenoma measuring 2.4 × 2 × 1.6 cm. Despite starting her on cabergoline therapy with a reduction in her prolactin levels, her TSH levels began to rise even further. Additional thyroid assays revealed that she had an abnormally elevated alpha subunit at 3.95 (age-related reference range <3.00). This corresponded to a thyroid-secreting hormone pituitary macroadenoma. She went on to have a transphenoidal hypophysectomy. Histology revealed tissues staining for TSH, confirming this to be a TSH-secreting pituitary macroadenoma. This case highlighted the importance of further investigations with thyroid assay interferences, heterophile antibodies, alpha subunit testing and anterior pituitary profile in cases of resistant and non-resolving primary hypothyroidism.

Learning points:

  • Levothyroxine treatment in primary hypothyroidism can potentially unmask the presence of a latent TSH-secreting pituitary macroadenoma, which can make diagnosis very challenging.

  • A high index of suspicion should prompt clinicians to further investigate cases of primary hypothyroidism which despite increasing doses of levothyroxine treatment with normalisation of TSH, the free T4 and T3 levels remain persistently elevated.

  • Clinicians should consider investigating for adherence to levothyroxine, thyroid assay interference, heterophile antibodies, TSH dilution studies, alpha subunit and anterior pituitary profile testing to further clarity the diagnosis in these patients.

  • Although coexistent cases of TSHoma with primary hypothyroidism are rare, it should always be in the list of differential diagnoses in cases of unresolving primary hypothyroidism.