TSH-Secreting Pituitary Adenoma

TSH-secreting pituitary adenoma is a thyrotroph tumour causing central hyperthyroidism, in which thyroid stimulating hormone is raised or inappropriately normal while thyroid hormones are raised.

It is rare, about 1 in 1,000,000 people each year, and under 1% of pituitary adenomas. Most are macroadenomas at diagnosis, and many co-secrete growth hormone or prolactin.

It is often misdiagnosed as Graves disease, and patients may have had thyroid ablation before the correct diagnosis, which allows tumour growth.

Pathophysiology.

Tumour thyrotrophs secrete thyroid stimulating hormone autonomously and are resistant to negative feedback from thyroid hormones. The alpha subunit is often raised.

Thyroid stimulating hormone drives the gland, causing goitre and thyrotoxicosis, usually of mild to moderate degree.

• Goitre, palpitations, weight loss, tremor, heat intolerance and anxiety, often milder than expected for the hormone levels. No eye disease or pretibial myxoedema.
• Headache and visual field loss from mass effect, and features of acromegaly or hyperprolactinaemia if co-secretion occurs.

Red flags.

• Visual loss or apoplexy.
• Atrial fibrillation or heart failure.
• Rising thyroid stimulating hormone after thyroid ablation with new headache or visual change.

• Raised free thyroxine and free triiodothyronine with thyroid stimulating hormone not suppressed (normal or raised), repeated on two occasions.
• Exclude assay interference: repeat on a different platform, check for heterophile antibodies, and stop biotin for at least 2 days.
• Exclude thyroid hormone resistance: family testing and THRB sequencing. Sex hormone binding globulin is raised and the alpha subunit to thyroid stimulating hormone molar ratio is over 1 in many tumours.
• Pituitary MRI with contrast, visual fields, prolactin, IGF-1 and the other pituitary axes. A thyrotropin releasing hormone test (blunted response) or triiodothyronine suppression test supports a tumour.

Differential diagnosis.

• Thyroid hormone resistance beta.
• Familial dysalbuminaemic hyperthyroxinaemia and assay interference.
• Drug effects (amiodarone, heparin), recovery from non-thyroidal illness and thyroid hormone treatment adjustment.
• Graves disease and toxic nodular goitre (thyroid stimulating hormone is suppressed in both, which separates them).

• Transsphenoidal surgery is first line. Do not ablate the thyroid before pituitary treatment.
• Before surgery restore euthyroidism with a somatostatin analogue: octreotide long acting 20 mg intramuscularly every 4 weeks or lanreotide 90 to 120 mg deep subcutaneously every 4 weeks. Antithyroid drugs (carbimazole 15 to 40 mg daily) and beta blockers (propranolol 10 to 40 mg three to four times daily) are used short term, and thyroid stimulating hormone may rise with antithyroid drugs.
• Remission: normal free thyroxine with thyroid stimulating hormone not suppressed (it often becomes low after cure). Stereotactic radiotherapy for residual tumour.
• Treat co-secreted hormones (growth hormone, prolactin) and hypopituitarism.

Monitoring. Thyroid function 2 weeks and 3 months after surgery. MRI at 3 to 6 months, then yearly.

Referral and escalation. Pituitary multidisciplinary team at diagnosis; urgent review for visual loss.