Thyroid Autonomy

Thyroid autonomy is thyroid hormone production independent of thyroid stimulating hormone, from a solitary toxic adenoma or a toxic multinodular goitre. It ranges from subclinical (suppressed thyroid stimulating hormone with normal hormones) to overt hyperthyroidism.

It is a common cause of hyperthyroidism in older adults and in iodine deficient areas, and is more common in women. Autonomous nodules increase in number and size with age.

Causes are activating somatic TSHR variants (most common) and GNAS variants. Iodine excess can precipitate overt disease in an autonomous gland.

Pathophysiology.

Autonomous follicular cells synthesise hormone without thyrotropin stimulation. Rising output suppresses thyroid stimulating hormone, and the rest of the gland shuts down, giving a nodule that takes up radioiodine while the surrounding tissue does not.

Nodules enlarge slowly, and overt disease usually appears once a solitary adenoma exceeds about 3 cm.

• Palpitations, atrial fibrillation, weight loss, tremor, heat intolerance, anxiety and fatigue. Older adults may have apathetic thyrotoxicosis with weight loss and heart failure.
• A palpable nodule or multinodular goitre, with tracheal compression in large goitres. No eye disease.

Red flags.

• Atrial fibrillation or heart failure.
• Dysphagia, stridor or voice change (large goitre, or malignancy in a cold nodule).

• Thyroid stimulating hormone suppressed. Free thyroxine and free triiodothyronine raised (overt) or normal (subclinical).
• Thyrotropin receptor antibodies negative.
• Ultrasound for nodule size and number. Technetium or iodine scintigraphy shows focal uptake in one or more nodules with suppressed uptake in the rest of the gland.
• Fine needle aspiration of any cold nodule on the scan, because functioning nodules are rarely malignant.

Differential diagnosis.

• Graves disease (diffuse uptake, antibodies positive).
• Destructive thyroiditis (uptake low) and iodine induced hyperthyroidism.
• Thyroid cancer with nodule, and exogenous thyroid hormone.

• Overt disease: carbimazole 15 to 40 mg daily and propranolol 10 to 40 mg three to four times daily until euthyroid, then definitive therapy because antithyroid drugs do not cause remission.
• Definitive therapy: radioiodine (activity chosen from uptake and gland volume) for most patients, or surgery for large goitre, compression, suspected malignancy or a wish to avoid radiation. Hemithyroidectomy for a solitary adenoma.
• Subclinical disease: treat if thyroid stimulating hormone is persistently under 0.1 mU/L in a patient over 65 years or with atrial fibrillation, heart disease, osteoporosis or symptoms. Otherwise observe with checks every 6 to 12 months.
• Avoid iodine loads where possible.

Special groups. Pregnancy: radioiodine is not used. Control with the lowest effective antithyroid drug dose and consider surgery in the second trimester if needed.

Monitoring. Thyroid function every 4 to 6 weeks while on antithyroid drugs. After radioiodine or surgery check at 6 weeks, 3 months, then yearly for hypothyroidism.

Referral and escalation. Endocrinology for overt disease, atrial fibrillation or planned definitive therapy; surgery referral for compression or suspected cancer.