Thyroid dysfunction Flashcards
Define goitre.
Goitre = enlargement of the thyroid gland
Goitres may be be multi-nodular or consist of a solitary nodule
Nodules may be cystic, colloid, hyperplastic, adenomatous or cancerous
What can cause goitre?
- Iodine deficiency → most common cause of goitre worldwide
- Autoimmune conditions → Hashimoto’s thyroiditis and Grave’s disease
- Congenital hypothyroidism
- Medication → lithium and amiodarone
- Thyroid cancer
- Benign thyroid neoplasms
- Thyroid hormone insensitivity
Describe the pathology of goitre formation.
- Thyroid cell growth and function are mainly stimulates by TSH via the TSH receptor
- TSH activity is mediatedthrough the alpha subunit of stimulating G portein
- Signals from cell surface receptors are sensed by G proteins and transducer to cAMP
- Increased cAMP levels cause growth and excess function of thyrocytes
Describe the role of isotope scanning in the investigation of thyroid lesions.
- able to distinguish functioning toxic nodules and thyroid metastases from follicular and papillary carcinomas is best with iodine uptake studies
- low iodine uptake in a single palpable nodule gives a risk of malignancy fo 10-25%, falling to 1-3% if multiple nodules are demonstrated on the scan
Describe the role of fine needle aspiration in the investigation of thyroid lesions.
- should be performed in any thyroid nodule >1cm and in <1cm if there is any clinical or US suspicion of malignancy
- results of FNAC are very sensitive differential diagnosis of benign and malignant nodules
Describe the role of USS in the investigation of thyroid lesions.
- extremely sensitive for thyroid nodules and is used as a 1st line diagnostic procedure for detecting and characterising nodular thyroid disease
- USS features associated with malignancy:
(i) hypoechogenicity
(ii) microcalcification
(iii) absence of peripheral halo
(iv) irregular borders
(v) solid aspect
(vi) intranodular blood flow and shape - assess the status of lymph node chains
List the possible causes of thyroid enlargement in a euthyroid patient.
- Intrathyroidal hyperplastic/neoplastic:
- thyroid adenomas
- non-toxic multinoduular goitre (as a result of multiple colloid nodules/hyperplastic nodules/thyroif adenomas) - Intrathyroidal neoplastic (malignant):
- papillary, medullary, follicular, anaplastic thyroid tumours - Congenital/developmental/anatomical:
- thyroid cysts
- thyroglossal duct cysts - Infectious/inflammatory/autoimmune:
- acute suppurative thyroiditis (usually bacterial infection)
- subacute granulomatous thyroiditis (de Quervain’s thyroiditis)
- painless lymphocytic thyroiditis (initial hyperthyroid stage, followed by subsequent hyperthyroidism and then return to euthyroid state)
Describe the features of a benign thyroid adenoma and how it may present.
- Features:
- can be inactive or active (called a toxic adenoma in this case)
- will typically grow up to 3cm before symptoms develop, can grow as large as 10cm
- typically a solitary, spherical and encapsulated lesion
- almost all thyroid adenomas are follicular adenomas - Presentation:
- may be asymptomatic, with the mass as the only feature
- if active, patient will present with features of hyperthyroidism (heat intolerance, weight loss, agitation/anxiety, tachycardia etc.)
Describe the clinical features of papillary thyroid carcinomas.
- most common form of thyroid cancers (~70%)
- usually presents between 35-40 y/o and is 3 times more common in women
- usually presents when <1cm in size
- excellent long-term prognosis
- can spread locally to compress the trachea and recurrent laryngeal nerve
- can metastasise (usually to lung and bone)
Describe the clinical features of follicular thyroid carcinomas.
- second most common form of thyroid cancers (~10%)
- tends to occur in areas of low iodine
- 3 times more common in women, tends to present between 30-60 y/o
- greater propensity to metastasise to lung and bones than PTC
Describe the clinical features of medullary thyroid carcinomas.
- arises from the parafollicular calcitonin-producing C cells
- accounts for ~5-8% of all thyroid malignancies
- malignant C cells produce and secrete large amounts of CEA and calcitonin
- familial MTC arises as part of MEN2a/2b
Describe the clinical features of anaplastic thyroid carcinomas.
- most aggressive thyroid tumour
- arises from the follicular cells of the thyroid but does not retain any of the biological features of the original cells
- <2% of thyroid tumours, most commonly occurring between 60-70 y/o
- will usually develop form a pre-existing well-differentiated thyroid tumour
- ~50% of patients present with metastases (most lung, but also liver, bones + brain)
- mean overall survival <6 months regardless of treatment
Describe the treatment options for papillary thyroid cancer.
- Surgery:
- total thyroidectomy is most commonly performed
- can perform unilateral total lobectomy for low-risk patients (<1cm) - 131-I treatment:
- ablation of remnant thyroid tissue if tumour >4cm or in tumours <4cm with high-risk features - External beam radiotherapy:
- may be considered after complete resection and 131-I therapy if tumour is still large/ extracapsular spread/poor prognostic features
- can be used in palliative care - Targeted therapies:
- small molecule tyrosine kinase inhibitors (vandetanib, sorafenib, sunitinib)
Describe the treatment options for follicular thyroid cancer.
- Surgery:
- total thyroidectomy is most commonly performed
- can perform unilateral total lobectomy for low-risk patients (<1cm) - 131-I treatment:
- ablation of remnant thyroid tissue if tumour >4cm or in tumours <4cm with high-risk features - External beam radiotherapy:
- may be considered after complete resection and 131-I therapy if tumour is still large/ extracapsular spread/poor prognostic features
- can be used in palliative care - Targeted therapies:
- small molecule tyrosine kinase inhibitors (vandetanib, sorafenib, sunitinib)
Describe the treatment options for medullary thyroid cancer.
- Surgery:
- all patients should have a total thyroidectomy
- only potentially curative intervention
- + central and ipsilateral neck node disseciton - External beam radiotherapy:
- post-op for macroscopic remnant to maximise local control
- may cause inoperable tumour to become operable - Chemotherapy:
- doxorubicin first line
Describe the treatment options for anaplastic thyroid cancer.
- Surgery:
- usually inoperable at presentatino
- if operable: total thyroidecromy and therapeutic node dissection - External beam radiotherapy:
- consider in post-op for the small number of patients whose tumour are completely resected
- more frequently used with palliative intent for the local control of inoperable tumour - Chemotherapy:
- doxorubicin first line
- potential for dacarbazine combination therapy
What are the causes of hypothyroidism?
- Primary:
- autoimmune: Hashimoto’s and atrophic thyroiditis
- iatrogenic: radio-iodine treatment, surgery, radiotherapy to the neck
- iodine deficiency
- drugs
- congenital defect: absence of thyroid gland, dyshormonogenesis
- infiltration of the thyroid: amyloidosis, sarcoidosis, haemochromatosis - Secondary:
- isolated TSH deficiency
- hypopituitarism: neoplasm, infiltative, infection + radiotherapy
- hypothalamic disorders: neoplasms + trauma - Transient:
- withdrawal of thyroid suppressive therapy
- postpartum thyroiditis
- subacute/chronic thyroiditis with transient hypothyroidism
What are the symptoms of hypothyroidism?
- tiredness, lethargy, intolerance to cold
- dry skin and hair loss
- slowing of intellectual activity (poor memory, difficulty concentrating)
- constipation
- decreased appetite and weight gain
- deep hoarse voice
- menorrhagia and later oligomennorhoea or amenorrhoea
- impaired hearing due to fluid in middle ear
- reduced libido
What are the signs of hypopituitarism?
- dry coarse skin, hair loss and cold peripheries
- puffy face, hands and feet (myxoedema)
- bradycardia
- delayed tendon reflex relaxation
- carpal tunnel syndrome
- serous cavity effusions (pericarditis or pleural effusions)
- loss of hair on the outer parts of the eyebrows
What problems can hypothyroidism cause in relation to the eyes?
- swelling around the eyes
- protruding eyeballs
- visual disturbance
What results in TFTs would you expect to find in:
(a) Thyroid hormone resistance
(b) Primary hypothyroidism
(c) Secondary hypothyroidism
(a) Raised/normal TSH
- Raised free T4
- Raised free T3
(b) Raised TSH
- Lowered free T4
- Lowered or normal free T3
(c) Lowered or norma TSH
- Lowered free T4
- Lowered or normal free T3
How should clinical hypothyroidism be managed?
- levotyroxine (50-100 micrograms) once daily
- usual maintenance dose is 100-200 micrograms once daily
- once stabilised, check TSH annually
- drugs such as ferrous sulfate, calcium supplements, rifampicin and amiodarone can interfere with T4 absorption
How should subclinical hypothyroidism be managed?
- some patients may benefit from levothyroxine (TSH >10 mU/L)
- treat patients with a history of radio-iodine treatment or +ve thyroid antibody (this subgroup will almost always progress to overt hypothyroidism
- also treat if there has been previous history of Grave’s disease, or other organ-specific autoimmune disease
- if none of the above is present, then monitor every 6-12 months
List the causes of hyperthyroidism.
- Grave’s disease → most common cause
- Toxic nodular goitre
- Solitary thyroid nodule
- de Quervain’s thyroiditis
- Self-medication (OTC iodine)
- Follicular carcinoma of the thyroid gland
- Drugs (amiodarone, lithium, exogenous iodine)
- Ovarian teratomas
- TSH-secreting pituitary adenoma
- Pituitaru resistance to thyroid hormones
What are the symptoms of hyperthyroidism?
- weight loss (despite increased appetite)
- weight gain
- increased or decreased appetite
- irritability
- weakness and fatigue
- diarrhoea ± steatorrhoea
- sweating
- tremor
- mental illness
- heat intolerance
- loss of libido
- oligomenorrhoea or amenorrhoea
What are the signs of hyperthyroidism?
- palmar erythema
- sweaty and warm palms
- fine tremor
- tachycardia (may be AF and/or heart failure)
- hair thinning or diffuse alopecia
- urticaria, pruritis
- brisk reflexes
- goitre
- proximalmyopathy
- gynaecomastia
- lid lag
What are the typical symptoms of thyroid crisis/storm?
- hyperthermia
- mental disturbance
What usually precipitates a thyroid storm?
- withdrawal of anti-thyroid drugs, radio-iodine therapy, infection and surgery
How should a thyroid storm be managed?
- IV fluids
- B blockers
- anti-thyroid drugs
- steroid
(also important to look for the presence of Addison’s disease)
What is the mortality rate in thyroid storms; what usually causes death?
Mortality rate 20-30%
Cause; arrhythmias and hypothermia
What are the definitive treatments for hyperthyroidism?
- Antithyroid drugs
- Radio-iodine
- Surgery
What drugs are used in hyperthyroidism? What must the patients be warned of?
- Carbimazole → most patients euthyroid within 4-8weeks and dose reduced to the lowest effective dose
- Propylthiouracil → can cause severe liver failure (reserved for use in pregnancy and thyroid storm)
Warn patients: if they develop a sore throat (will need FBC as anti-thyroid drugs can cause bone marrow suppression
When is surgery indicated in hyperthyroidism?
If there is subotpimal response to anti-thyroid drugs or radio-iodine
