Most thyroid lumps are benign, but 5% are malignant and it is important to distinguish this sinister minority.

Benign thyroid lumps may include:

• Thyroid adenoma
• Thyroiditis
• Thyroid cysts
• Hyperplastic nodules

Pathogenesis

• Most thyroid nodules are adenomatous. Most are multiple and that is usually shown on ultrasound, scintigraphy and at surgery. The nodules are usually non-functioning (cold at scintigraphy), although a few may be hyper-functioning toxic adenomas (hot on scintigrams). They may also be a hyper-functioning adenoma in a multinodular goitre.
• When solid, the nodules are poorly encapsulated and not well-defined, and they merge into the surrounding tissue. Cystic adenomatous nodules are haemorrhagic, with irregular internal walls and particulate fluid content. Intratumoral calcification is occasionally seen.
• Follicular adenomas are the most common and arise from follicular epithelium. They are usually single, well-encapsulated lesions. On ultrasound, adenomas may be hyperechoic or hypoechoic solid nodules with a regular hypoechoic area surrounding ring called the halo sign. Rarely, a parathyroid adenoma has an ectopic intrathyroid location.
• Whether solitary adenomas transform into follicular carcinoma is uncertain. In particular, whether aneuploid cells, which are present in approximately 25% of follicular adenomas, represent carcinoma in situ is unclear.
• Follicular adenomas are further classified according to their cellular architecture and relative amounts of cellularity and colloid into fetal (microfollicular), colloid (macrofollicular), embryonal (atypical), and Hürthle (oxyphil) cell types.

Epidemiology

About 40% of the general adult population has a single nodule or multiple ones. They are more common in women. Most nodules are benign.

In most series, 8-65% of patients with clinically normal thyroid glands had one or more grossly visible nodules, whereas the incidence of malignancy was 2-4%.¹

Presentation

• Most patients with thyroid nodules are asymptomatic, and most nodules are found on clinical examination or self-palpation.
• Thyroid lumps are often asymptomatic and are noticed by family members or seen in the mirror.
• They may sometimes cause pain and rarely present with features of compression of the trachea.
• Ask about previous radiation.

Signs

• Ask the patient to drink some water and note the thyroid move as they swallow.
• Note enlargement or asymmetry.
• Stand behind a seated patient and use the 2nd and 3rd fingers of both hands to examine the gland as they swallow again.
• Note lumps, asymmetry, size and tenderness.
• Check for regional lymphadenopathy.

Differential diagnosis

• Non-toxic goitre - non-functioning nodules.
• Toxic nodular goitre - functioning nodules.
• Graves' disease - diffuse overactive thyroid gland.
• Hashimoto's disease - autoimmune destruction of the gland.
• Solitary thyroid nodule - 15-25% are cysts and can be aspirated.
• Thyroid carcinoma.
• Medullary cell carcinoma.
• Thyroid lymphoma - usually non-Hodgkin's.
• De Quervain thyroiditis - neck pain, fever and lethargy soon after an upper respiratory infection or a viral illness.
• Acute suppurative thyroiditis - results from bacterial or fungal infection causing abscess.

Investigations

• TFTs will show most patients to be euthyroid - refer those which are abnormal for endocrine opinion.²
• Ultrasound is useful to detect and characterise most thyroid nodules. It can show cystic lesions 2 mm wide and solid lesions 3 mm wide. Ultrasound examination is far more sensitive than clinical examination and only 4-7% of nodules detected by ultrasound are clinically palpable.
• Fine needle aspiration (FNA) gives tissue for cytology. It is performed under ultrasound guidance (for maximum accuracy) but for palpable nodules it can be performed with palpation. It is safe, inexpensive and provides direct information.
  FNA is best for uninodular lesions.³ Sensitivity is near 80% with specificity approaching 100%. False-negative and false-positive results occur in fewer than 6%. FNA is the first and, in the vast majority of cases after ultrasound, the only test required for the evaluation of a solitary thyroid nodule.^4,5
• Radionuclide imaging looks at iodine uptake by the thyroid:⁶
  • Normal is called 'warm'.
  • Lesions that take up excessive amounts of iodine are called 'hot' - 4% of hot nodules contain tumour.
  • Lesions that do not take up iodine are called 'cold' - 16% of cold nodules contain tumour.
  This makes radionuclide imaging unreliable to exclude or confirm cancer.
  
  Low ¹²³I uptake in a single palpable nodule gives a risk of malignancy of 10-25%, falling to 1-3% if multiple nodules are demonstrated on the scan.
• CT scans and MRI scans are valuable to detect local and mediastinal spread and regional lymph nodes.

Management

General measures

• Solitary benign disease can be observed.
• New thyroid lumps that have been growing over a period of months, or patients with a sudden onset of pain in a nodule (which is usually due to a bleed into a cyst), should be referred to a specialist thyroid clinic with provisions for ultrasound and fine needle aspiration (FNA) assessment, where they should be seen within four weeks of referral.²
• Urgent referral to secondary care is necessary when:⁷
  • There is a solitary nodule increasing in size.
  • There is history of neck irradiation.
  • There is a thyroid nodule or goitre in a child or teenager.
  • A family history of an endocrine tumour exists.
  • Unexplained hoarseness or voice changes are noted.
  • There is cervical lymphadenopathy (usually deep cervical or supraclavicular).
  • The patient is aged 65 years or older.
  • There has been enlargement of a painless thyroid mass over a period of weeks (may be indicative of thyroid cancer).

Pharmacological

• Biochemical abnormalities of TFTs need to be treated in the usual way. Betablockers may be needed to control symptoms in some severely toxic patients.
• Patients with benign solitary thyroid nodules may have suppression therapy with thyroxine:⁶
  • Thyroxine is given for 6-12 months to shrink the nodule.
  • If successful, the medication is stopped, with follow-up examination of the thyroid nodule in 3-6 months.
  • If a benign solitary thyroid nodule increases in size, a repeat trial of thyroxine and repeat FNA may be undertaken but growth of a thyroid nodule during therapy is a strong indication for surgery.
  • There is currently little evidence to support the practice.⁸

Surgical

Solitary thyroid nodules that are malignant, suspicious, or indeterminate on FNA require removal. There is controversy about which operation, with advocates for thyroid lobectomy, total or subtotal thyroidectomy.

Complications

Both surgery and alcohol injection can cause recurrent laryngeal nerve palsy, which should occur in fewer than 5% of procedures.² With alcohol injection it is usually transient with full recovery within 1-3 months. The primary disease can cause nerve damage in both benign and malignant conditions.

Prognosis

After exclusion of anaplastic carcinoma, prognosis for thyroid disease is excellent.

Document references

1. Dean DS, Gharib H; Epidemiology of thyroid nodules. Best Pract Res Clin Endocrinol Metab. 2008 Dec;22(6):901-11. [abstract]
2. Guidelines for the management of thyroid cancer, British Thyroid Association (2007)
3. Gharib H; Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations, and effect. Mayo Clin Proc. 1994 Jan;69(1):44-9. [abstract]
4. Ross DS; Evaluation of the thyroid nodule. J Nucl Med. 1991 Nov;32(11):2181-92. [abstract]
5. Mazzaferri EL, de los Santos ET, Rofagha-Keyhani S; Solitary thyroid nodule: diagnosis and management. Med Clin North Am. 1988 Sep;72(5):1177-211. [abstract]
6. Kelley DJ; Thyroid, Evaluation of Solitary Thyroid Nodule, Medscape, Oct 2008
7. Neck lump, Clinical Knowledge Summaries (February 2010)
8. Helling TJ; Thyroid-hormone-suppressive therapy in benign thyroid nodules. Lancet. 2003 Mar 29;361(9363):1137.