The patient tells you that she has had classical thyrotoxic symptoms for 8–10 weeks and had lost approximately two stone in weight over 4 months. She first noticed the lump in her neck about 6 months ago and does feel that it has become more noticeable. She has a PMH of post-menopausal osteoporosis for which she takes alendronate weekly. She has no relevant family history.

On examination you note that she is tremulous with moist palms. She has a regular tachycardia (120 bpm) with no evidence of heart failure. She has no signs of active thyroid eye disease. The thyroid is moderately and diffusely enlarged with a palpable nodule within the right lobe of the thyroid which is non-tender and mobile. There is no cervical lymphadenopathy.

The overriding issue at this stage is to treat this patient’s hyperthyroidism and the symptoms related to this. Anti-thyroid medication such as carbimazole 40 mg od along with a beta-blocker (propranolol 80–160 mg bd) would be the initial treatment option. Longer term management will vary significantly depending on the final diagnosis and so further investigation is warranted at this stage. A thyroid radionuclide uptake scan will indicate if the nodule is “hot” or “cold” and provide useful information to aid the diagnosis. Thyroid function tests (TFTs) should be repeated 4–6 weeks after commencing treatment and reviewed in clinic with the results of the uptake scan.

In her follow up visit, the patient reports an improvement in her symptoms and her weight loss has plateaued. Her repeat TFTs are as follows:
The thyroid radionuclide uptake scan is reported:

The nodule within the right lobe of the thyroid does not take up the radio-isotope, whereas within the remainder of the thyroid tissue there is increased uptake.

The picture is consistent with Graves’ disease with a non-functioning nodule within the right lobe of the thyroid (Fig. 4.1).

The diagnosis is now suggestive of Graves’ disease with an indeterminate thyroid nodule that requires further investigation.

The presence of thyroid nodules in the general population is common, with a prevalence of around 5 %, which can increase to 30–40 % when ultrasound is used to visualise the thyroid, and which is consistent with autopsy studies [1]. The causes of thyroid nodules are shown in Table 4.1. Thyroid cancer is rarer than nodules and accounts for 1–2 % of all cancers. The link between Graves’ disease, thyroid nodules and thyroid cancer has been the subject of much debate. Palpable nodules are present in 10–15 % of Graves’ disease patients, two to three times higher than in the general population [1], and nodules may also develop de novo during the course of the disease [2]. In terms of malignancy and Graves’ disease, the overall risk is approximately 5 % [3–5]; however, this risk is greatly increased in the presence of cold, palpable nodules, ranging from 15 to 48 % [3, 4, 6]. The malignancy rate of palpable nodules within the general population is around 5 %, suggesting that thyroid nodules associated with Graves’ are at increased risk of developing differentiated thyroid carcinoma than nodules within euthyroid individuals. Malignant nodules also appear more aggressive in Graves’ disease, presenting at a more advanced staged and associated with a worse outcome than tumours in matched euthyroid individuals [7, 8].