Aetiology

The majority of thyroid cancers are sporadic. Other risk factors include radiation exposure (papillary carcinoma), genetic (e.g. MEN2 with medullary carcinoma, FAP with papillary carcinoma) and endemic goitre (follicular carcinoma).

Presentation

Common presentation is with an enlarging solitary nodule. Cervical lymphadenopathy is common with medullary, papillary and anaplastic carcinoma. Local invasion can lead to symptoms of hoarseness of the voice and dysphagia. Anaplastic carcinoma has an aggressive growth with local invasion and rapid growth which can lead to stridor.

Evaluation

Evaluation includes clinical examination and assessment for thyrotoxicosis which is rare in cancer. Initial investigations include thyroid function tests and FNA of the lesion. Biopsy may be indicated for lymphoma and anaplastic carcinoma and hemithyroidectomy is indicated for all follicular lesions. MRI is the preferred imaging to assess local invasion (Figure 17.1) as the use of iodine containing contrast can cause thyroid stunning which may prevent effective use of radioiodine for at least three months subsequently.

Figure 17.1 Axial (A) and coronal (B) view of MRI scan in anaplastic carcinoma of thyroid.

Staging

Box 17.1 shows the TNM staging system. The TNM and MACIS (Box 17.2) have been shown to be the best predictors of outcome in differentiated thyroid cancer.

Management

Well-differentiated cancer

Surgery is the definitive treatment of all malignancies except lymphoma. The majority of patients need total or near total thyroidectomy. In low-risk patients (<1 cm papillary cancer with no nodes, <2 cm follicular cancer in women aged less than 45 years and <1 cm follicular cancer with minimal capsular invasion) lobectomy is adequate. Patients with high-risk disease (male >45 years, tumour >4 cm and extracapsular spread) are at risk of level VI nodal involvement and hence elective central node dissection is indicated. Patients with proven neck node metastases are treated with modified radical neck dissection. All patients should have serum calcium postoperatively to rule out transient hypocalcaemia. Serum thyroglobulin (TG), the tumour marker, is estimated 6 weeks postoperatively which should be undetectable in patients who had total thyroidectomy and have no residual disease. Patients after total thyroidectomy are started on triiodothyronine (T3) 20 mg thrice daily which is subsequently changed to T4. T4 is started with a dose of 100 mcg daily and increased by 25 mcg every 6 weeks until TSH levels are below 0.1 MiU/L.

Radioablation

Postoperative radioiodine ablation is recommended for all patients except for those who had total thyroidectomy for a well-differentiated unifocal tumour of <1 cm with no vascular or extracapsular invasion. Informed consent should be obtained and instruct female patients not to get pregnant prior to and up to 12 months after treatment (Box 17.3). T4 is substituted with T3 4–6 weeks before radioablation and T3 is withdrawn 2 weeks before ablation. 3–3.7 GBq of radioiodine is administered orally. In patients with a history of myxoedema psychosis, severe cardiac disease and high volume disease, T3 withdrawal can be dangerous and hence recombinant human TSH (0.9 mg IM daily for 48 hours before radioablation) is used. Patients are admitted to and remain in a specialist facility with appropriate shielding and sanitation. Isolation is continued until safe levels of radiation are measured by a medical physicist. Patients are advised to keep well-hydrated, empty the bladder frequently and to take prescribed laxatives to avoid constipation and these measures are aimed at minimizing the absorbed dose of radiation. An uptake scan is done 3–10 days after radioiodine to assess residual thyroid tissue. In patients with elevated TG and positive uptake scans, either further surgery or repeat dose of radioiodine (5.5 MBq) is indicated. Further management afterwards is shown in Figure 17.2.

Box 17.3
Side effects of radioablation

Early effects

• Sialoadenitis and taste changes

• Nausea

• Neck pain and swelling

• Radiation cystitis, gastritis

• Symptoms of hypothyroidism for 4–6 weeks

Late effects

• Dry mouth and taste changes

• Dry eyes due to lachrymal gland dysfunction

• Increase in miscarriage rate in first year after treatment

• Pulmonary fibrosis

• Male infertility

• Risk of 2nd malignancy

Figure 17.2 Management of well-differentiated thyroid cancer.

Some patients do not have a take-up of radioiodine when external beam radiotherapy to the entire thyroid bed has been carried out, and level III–VI nodes (60 Gy in 30 fractions) is indicated if there is gross residual disease, extranodal disease and in patients >60 years with T4 disease.

Introduction

Adrenocortical carcinoma (ACC) is a rare malignancy with heterogeneous manifestations and a poor prognosis. In adults it peaks at 57 years of age. There are no proven aetiological factors. ACC is rarely reported in multiple endocrine neoplasia I (MEN I), Li–Fraumeni and Wiedemann–Beckwith syndromes.

Presentation

Approximately 60% patients present with features of adrenal steroid hypersecretion. Rapidly progressing Cushing’s syndrome with or without virilization is the most common presentation. Other presenting symptoms include virilization in women and gynaecomastia and testicular atrophy in men, hypertension and hypokalaemia.

Non-secreting tumours present with abdominal discomfort or back pain due to mass effect. Rarely patients can present with fever, weight loss and anorexia.

Diagnosis

Initial investigations include hormonal workup and imaging with CT chest and abdomen (Figure 17.3). MRI is also useful in identifying invasion of adjacent organs and the inferior vena cava, and hence in planning surgery. Biopsy of an adrenal tumour is controversial because of the theoretical risk of needle tract metastases. However, it may be acceptable if primary surgical management is not feasible and diagnosis cannot be established with non-invasive measures.

Figure 17.3 CT scan in adrenocortical carcinoma. On CT scan adrenocortical carcinoma is typically more than 4 cm with central necrosis with heterogeneous enhancement and may show calcification (30%) and invasion into adjacent structures.

Staging

WHO (2004) staging for adrenocortical carcinoma is as follows:

Management

Complete removal of tumour offers best chance for cure in patients with stage I–III tumours. Radiotherapy has an established role in the palliation of bone and brain metastases. Mitotane (o,p’-DDD) is a specific drug for the treatment of adrenocortical cancer which leads to an objective response of 25% of cases. The main side effects are vomiting, diarrhoea, lethargy, somnolence, depression, and adrenal insufficiency. All patients need high-dose gluococorticoid replacement (e.g. 50 mg hydrocortisone daily) which helps to minimize mitotane-induced side effects.

Combination chemotherapy with mitotane with streptozocin has yielded a response rate (partial and complete) of 36%.

The commonly used combination regimes used are cisplatin, etoposide and doxorubicin (EDP) with mitotane (Berruti Regime) and EDP with streptozocin (Khan Regime). The ongoing FIRM-ACT trial is comparing efficacy of these two combination regimes in patients with inoperable stage III–IV disease.

Outcome

The reported 5-year survival is 60% for stage I, 58% for stage II, 24% for stage III and 0% for stage IV. Median survival of stage IV patients is less than 12 months. Cortisol secreting tumours are associated with worse prognosis, partially attributable to morbidity associated with Cushing’s syndrome.