- Hyperthyroidism: sustained overproduction of thyroid hormones, e.g. Graves’ disease
- Thyrotoxicosis: physiological manifestations of elevated circulating free T3 and T4 reflecting a hypermetabolic state of target tissues.
- Prevalence: (Caucasians) 2-3% in women and 0.2-0.3% in men.
- Annual incidence: 0.8 per 1000 in women and less than 0.1 in men
- All thyroid diseases occur more frequently in females
- Graves disease – male-to-female ratio of 1:10
- Thyroid eye disease (Grave's ophthalmopathy) – more common in females
- Toxic multinodular goitre, toxic adenoma – male-to-female ratio of 1:2-4.
- Risk factors e.g. family history, high iodine consumption, smoking (especially associated with thyroid eye disease)
- Most common causes: Graves disease (60-85%), toxic multinodular goitre and hyperfunctional/toxic thyroid adenoma
- Other causes: subacute thyroiditis, hormone-secreting tumours e.g. thyroid carcinoma, TSHoma, teratoma and drugs e.g. amiodarone
- Weight loss (unintentional and/or despite an increased appetite)
- Heat intolerance
- Diaphoresis (excessive sweating)
- Lethargy, muscle weakness, fatigability
- Loss of libido
- Oligomenorrhoea or amenorrhoea
- Eye discomfort
- Enlarged thyroid gland
- Thyroid bruit
- Fine tremor
- Sweaty and warm peripheries
- Tachycardia (atrial fibrillation is a frequent presentation in the elderly)
- Eye signs such as exophthalmos and lid retraction*
- Thyroid acropachy*
- Pretibial myxoedema*
- Excoriations due to pruritus
- Proximal myopathy
- Brisk reflexes
(* only in Graves’ disease)
Figure 1. Thyroid enlargement
Figure 2. Thyroid eye disease - exophthalmos and lid retraction
- Serum TSH (↓) [unless in TSH hypersecretion – rare]
- Confirmatory: ↑ free T4, T3
- Autoantibodies most commonly found in Graves’ disease: antimicrosomal antibodies (against thyroid peroxidase), antithyroglobulin antibodies, TSH-receptor antibodies (not routinely measured)
- Thyroid ultrasonography
- Thyroid uptake scan: to identify any hot (overactivity) and cold (no activity) spots
3 main types of treatment: antithyroid medications, radioactive iodine and surgery
1. Antithyroid medications – carbimazole or propylthiouracil (must be aware of potential agranulocytosis – warn patients to seek medical attention if they have sore throat)
2. Radioactive iodine – may be given to patients of all ages but is contraindicated in pregnancy and during breastfeeding. Patients should be advised to avoid close contact with children and pregnant women. Hypothyroidism is a common complication (50-80%) and therefore patients will need long term LFTs follow-up.
- Subtotal/near total thyroidectomy (98% cure rate)
- Should be performed in patients who have suboptimal response to other therapies
- Complications: haemorrhage, hypoparathyroidism, laryngeal nerve palsy
- Beta-blockers or calcium-channel blockers for rapid symptomatic control (overactivity of sympathetic nervous system
- Specialist referral: e.g. Ophthalmology for thyroid eye disease
- Overall UK prevalence of 1% in women and less than 0.1% in men
- Lifetime prevalence: 9% in women, 1% for men
- Mean age of diagnosis: around 60 years old
- Commonest cause worldwide: iodine deficiency
- In areas without iodine deficiency: autoimmune and iatrogenic hypothyroidism are more common
- Other causes: antithyroid medications, radioactive iodine therapy, irradiation to the neck, tumour, TSH deficiency
- May produce many symptoms
- Classical description: dry, coarse hair, thick-skinned, deepened voice with cold intolerance, weight gain, bradycardia and constipation
- Other symptoms: malaise, poor libido, poor appetite and poor memory
- Other signs: myxoedema, slow-relaxing reflexes, loss of eyebrows, periorbital oedema, obesity
- Can be hard to diagnose in paediatric patients and young women (should exclude hypothyroidism in women presenting with menstrual complaints such as oligomenorrhoea)
- Signs can be hard to differentiate from normal ageing in the elderly
- Serum TSH (↑ in primary hypothyroidism)
- Free T4 (↓)
- Antithyroid peroxidase (anti-TPO) antibodies or anti-thyroglobulin antibodies present in 90-95% of patients with autoimmune thyroiditis
- Consider biochemistry and haematology: cholesterol, triglycerides, full blood count
- Ultrasound of the neck in asymmetrical goitre to appreciate the underlying architecture and rule out neoplastic lesions
Management of clinical hypothyroidism
- To achieve euthyroid status and restore normal metabolic states
- Replacement therapy with levothyroxine (100-150 micrograms for maintenance) and lower dose for elderly patients with ischaemic heart disease (25-50 micrograms initially).
- Once stabilised, check TSH annually and free T4 in secondary hypothyroidism
- Common, autopsy data indicate a 50% prevalence of thyroid nodules greater than 1cm in patients without clinical evidence of thyroid disease
- Warrant removal if symptomatic or concern for malignancy
- Majority are asymptomatic, with 5-10% of nodules being malignant
- Benign thyroid lumps include thyroid adenoma, thyroiditis, thyroid cysts and hyperplastic nodules
- Low iodine consumption (incidence of malignancy rises from 5% to as high as 40%)
- Risk of malignancy increases with age, radiation exposure and where benign thyroid disease has existed.
- Family history of thyroid cancer
- Often asymptomatic but may sometimes present with features of compression of the trachea
- Inspection: enlargement or asymmetry, ? moves with deglutition
- Palpation: note size, asymmetry, tenderness and any regional lymphadenopathy
- Auscultation: ? bruit
- Nodules are more like to be neoplastic if (1) solitary or, (2) in younger patients or, (3) in males or, (4) in patients with history of previous radiation to the head and neck region.
- Concern for malignancy increases if (1) nodules larger than 4cm in size (19.3% risk of malignancy) or, (2) firmness to palpation or, (3) fixated or, (4) cervical lymphadenopathy or, (5) vocal cold immobility
- Goitre (non-toxic or toxic)
- Thyroiditis (e.g. Graves’, Hashimoto’s, De Quervain’s)
- Thyroid cysts
- Thyroid neoplasms (benign or malignant)
- Non-thyroid lumps (e.g. lymph nodes, branchial cyst, thyroglossal cyst)
- Laboratory studies: TFTs (most patients are euthyroid), serum calcitonin (reserved) if positive family history of medullary thyroid carcinoma, multiple endocrine neoplasia (MEN)-2a or -2b, phaechromocytoma or hyperparathyroidism
- Imaging studies:
- Ultrasonography – imaging study of choice; allows detection of non-palpable nodules, lymphadenopathy, provides measurements and allows characterisation of nodules.
- Radioisotope scanning – to determine if a thyroid nodule is functioning (does not provide an accurate measurement of size), 80-85% of thyroid nodules are cold (non-functional) and only 10% of these represent a malignancy, likelihood of malignancy is less than 1% in hot nodules; sensitivity for the diagnosis of thyroid cancer is 89-93% with specificity of 5% and positive predictive value of malignancy is 10%
- CT or MRI scans: to detect local and mediastinal spread and regional lymph nodes.
- Histopathological studies: fine needle aspiration cytology (FNAC) is performed under ultrasound guidance and is best for uni-nodular lesions. Sensitivity is about 80% with specificity approaching 100%.
- The British Thyroid Association (BTA) recommends patients with non-palpable nodules smaller than 1cm that are discovered incidentally and with no worrying features can be managed in primary care
- Lumps with red flag symptoms should be referred urgently for specialist opinions.
Figure 4. FNAC of a neck lump
Figure 5. Scintiscanning - multinodular toxic goitre.
Hot nodules on the apex of the left lobe and on the middle of the right lobe.
Cold nodules on the right lobe and on the isthmus.
- Most common endocrine cancer
- Differentiated carcinomas derive from thyroid epithelium: papillary or follicular carcinoma
- Undifferentiated carcinomas: anaplastic carcinoma
- Arise from calcitonin-producing C cells: medullary carcinoma
- 1.5% of adult cancers
- Female predominance (2-3 fold higher)
- Strong association with exposure to radiation and family history (10-20% of malignancy has a positive familial component e.g. MEN)
- Papillary carcinoma (>85%)
- Follicular carcinoma (5-15%)
- Medullary carcinoma (5%)
- Anaplastic (undifferentiated) carcinoma (<5%)
- Majority present with palpable nodules
- Approximately 5% present with local or disseminated metastases
- Commonest histological type and often presents as an asymptomatic nodule
- Features of advanced disease: hoarseness, dysphagia or dyspnea
- Majority spread via lymphatics
- Excellent prognosis: 10-year survival rate 95%
- Peak incidence between 40 – 60 years of age (present at an older age than do papillary carcinomas)
- More commonly seen in areas with iodine deficiency
- Presents as slowly growing, painless nodules
- Haematogenous spread is common
- Prognosis largely depends on the extent of invasion (e.g. minimally invasive follicular carcinoma has 10-year survival rate greater than 90%)
- Often presents as a mass in the neck and can be associated with compressive effects such as dysphagia
- May also present with manifestations of a paraneoplastic syndrome
- Despite elevated calcitonin levels, hypocalcaemia is not a prominent feature.
- Often associated with MEN-2 (those in the context of MEN-2B are generally more aggressive than those occurring in MEN-2A)
- Local invasion or metastatis is frequent
- Responds poorly to treatment
- Patient’s family should be screened for endocrine neoplastic conditions
- More commonly found aged 50-60
- Usually presents as a rapidly enlarging neck mass
- Metastases are common at initial presentation (commonly metastasize to lungs)
- Symptoms of local, compressive effects such as dysphagia. Dyspnea and hoarseness are common
- No effective treatment and does not respond to radioactive iodine
- Death commonly occurs within a year
- Refer to investigations of thyroid lumps
- Urgent referral to specialists
- Surgery is treatment of choice (thyroid lobectomy with isthmusectomy, sub-total thyroidectomy or total thyroidectomy)
- Radioactive iodine is given 4-6 weeks to ablate residual cancerous tissue after surgical excision
- Lifelong thyroxine replacement (also monitor TSH because 15-20% of cancers respond to TSH)
- Palliative external beam radiotherapy if indicated
- Annual life-long follow-up is recommended.
Kronenberg H, Melmed S, Polonsky K, Larsen R. Williams textbook of endocrinology. 11th ed. Philadelphia: Saunders Elseviers; 2008.
Kumar V, Abbas A, Fausto N, Aster J. Robbins and Cotran pathologic basis of disease. 8th ed. Philadelphia: Saunders Elseviers; 2010.
Rubin R, Strayer D. Rubin’s pathology: clinicopathologic foundations of medicine. 5th ed. USA: Lippincott Williams & Wilkins; 2008.
Kumar P, Clark M, editors. Kumar & Clark’s clinical medicine. 7th ed. Edinburgh: Elesevier; 2009.
Lee S, Ananthakrishnan S. Hyperthyroidism [homepage on the Internet]. No date [last updated 2011 Oct 27; cited 2012 Feb 11]. Available from: http://emedicine.medscape.com/article/121865-overview
Rull G. Hyperthyroidism [homepage on the Internet]. No date [last updated 2010 Jul 10; cited 2012 Feb 13]. Available from: http://www.patient.co.uk/doctor/Hyperthyroidism-%28Thyrotoxicosis%29.htm
Rull G. Hypothyroidism [homepage on the Internet]. No date [last updated 2009 Jun 15; cited 2012 Feb 13]. Available from: http://www.patient.co.uk/doctor/Hypothyroidism.htm
Willacy H. Thyroid carcinoma [homepage on the Internet]. No date [updated 2009 May 19; cited 2012 Feb 17]. Available from: http://www.patient.co.uk/doctor/Thyroid-Carcinoma.htm
Willacy H. Benign thyroid tumours [homepage on the Internet]. No date [updated 2012 Feb 06; cited 2012 Feb 17]. Available from: http://www.patient.co.uk/showdoc/40026199/
British Thyroid Association. Guidelines for the management of thyroid cancer [homepage on the Internet]. c2007 [cited 2012 Feb 17]. Available from: http://www.british-thyroid-association.org/news/Docs/Thyroid_cancer_guidelines_2007.pdf
Konturek A, Barczyński M, Nowak Wojciech, Richter P. Prognostic factors in differentiated thyroid cancer – a 20-year surgical outcome study. Langenbecks Arch Surg [serial on the Internet]. 2012 [cited 2012 Feb 17]; Epub ahead of print. Available from: http://www.springerlink.com/content/j7g7q77j8lq475x3/fulltext.html
Bomeli S, LeBeau S, Ferris R. Evaluation of a thyroid nodule. Otolaryngol Clin North Am [serial on the Internet]. 2010 [cited 2012 Feb 17]; 43(2):229-38. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879398/?tool=pubmed
(Figure 1) Texas Tech University Health Sciences Center. Bilateral exophthalmos and lid retraction due to thyroid eye disease [homepage on the Internet]. No date [cited 2012 Feb 13]. Available from: http://www.ttuhsc.edu/som/ophthalmology/eyeatlas/Orbit/bilateral_exopthalmos_and_lid_retraction_due_to_thyroid_eye_disease.aspx
(Figure 2). Leeds Student Medical Practice. Hypothyroidism/hyperthyroidism [homepage on the Internet]. No date [cited 2012 Feb 13]. Available from: http://www.leeds.ac.uk/lsmp/healthadvice/hypothyroidism/hypothyroidism.html
(Figure 3) Medchrome: Medical and health articles. Hypothyroidism : Clinical featues, diagnosis and treatment [homepage on the Internet]. c2010 [last updated 2010 Dec 18; cited 2012 Feb 13]. Available from: http://medchrome.com/major/medicine/endocrinology/hypothyroidism-clinical-featues-diagnosis-and-treatment/
(Figure 4) Chee G. Common ENT investigations [homepage on the Internet]. c2005 [cited 2012 Feb 17]. Available from: http://www.gcheeent.com/investigations.htm
(Figure 5) Multinodular goiter [homepage on the Internet]. c2004 [cited 2012 Feb 17]. Available from: http://www.thyroidimaging.com/scint_multinod1.htm