Thyroid disease Flashcards
What questions should be asked when a patient has unintentional weight loss?
Weight loss itself:
- How much weight?
- Time frame
- Changes in diet and appetite
- How the patient feels about the weight loss
- Stress
Other symptoms:
- GI: anorexia, abdominal pain, diarhoea, symptoms of IBD, coeliac disease, peptic ulcers
- Mental health: Low mood, loss of interest, sleep disturbance, decreased food intake, self-induced vomiting, over-exercise (eating disorders)
- Urinary: polyuria and polydipsia (T1DM)
- Drug use: alcohol, cannabis, cocaine, amphetamines
- B-symptoms: night sweats or fever (malignancy, tubercolosis, HIV)
What physical signs are seen in hyperthyroidism?
- Increased HR
- Increased BP
- Increased sewating
- Exophthalmos
- Lid lag
- Enlarged thyroid/goitre
- Agitation
- Tremor
- Onycholysis
- Acropachy
- Conjunctival oedema
- Opthalmoplegia
- Pretibial myxoedema
- Proximal myopathy
- Hyperreflexia
What TFTs are seen in primary hyperthyroidism?
- Elevated free T4
- Elevated free T3
- Suppressed TSH
Production of TSH is regulated by negative feedback from circulating free thyroid hormones, which is why it is suppressed
Which tissues do T3 and T4 target?
T3:
- Heart
- Liver
- Bone
- CNS
- Muscle
T4:
- Thyroid gland
- Liver
0 Musclw
What is the thyroid gland?
- Soft gland, lower neck
- Anterior to trachea
- Below thyroid cartilage of larynx
- Maxes thyroxine and T3
- 2 lobes and isthmus
What is the histology of the thyroid gland?
- Follicles filled with colloid
- Lined with columnar epithelium: thyroid follicular cells make thyroglobulin (protein that generates precursor of thyroid hormones)
- Interspersed C-cells makes calcitonin (bone mineral metabolism)
How are thyroid hormones made?
- Thyroid follicular cells make thyroglobulin (Tg) under the control of TSH
- TSH is activated by TSH receptor, and secrete it into the colloid
- Iodide is trapped by TFCs (sodium-iodide symporter, NIS) and is transported into the colloid
We now have iodide and Tg in the colloid
- Tg provides a source of tyrosines
- Thyroid peroxidase (TPO) on luminal membrane of TFCs iodinated tyrosines
(organfication of iodine) - TFCs endocytose Tg from the luminal border
- Endosomes/lysosomes:
Hydrolysis or Tg, release of T4 into blood - Transport in blood bound to binding proteins
Thyroid-binding globulin etc - Deiodination T4 -> T3: active intracellular hormone
- T3R is a nuclear hormone receptor, DBA binding, transcriptional effects
What is the basis of the pituitary-thyroid axis?
- Negative feedback of T4 and T3 on pituitary TSH and hypothalamic TRH
- Low T4 -> increased TSH
- High T4 -> suppressed TSH
What TFTs are seen in an overactive thyroid and in an underactive thyroid?
Overactive: High T4 and T3, low TSH
Underactive: Low T4
High TSH
What do we examine in Thyroid function tests?
- Total T4
- Free T4
- Total T3
- Free T3
- TSH
- Antibodies: TPO Abs, TSH-R Abs
What are some factors that can skew TFTs?
- Pregnancy raises TBG - use measurements of free thyroxine
- OCP raises TBG
Funny tests: - Antibodies
- Drugs: amiodarone
- Pituitary disease
- Wrong patient
How is Thyrotoxicosis managed?
- Observe clinical features and tests
- Check for thyroid eye disease (exophlamos, chemosis, peri-orbital oedema)
- Risks
Treatment options: - Beta blockers
- Antithyroid drugs
- Radioiodine
- Near total thyroidectomy
How is hypothyroidism managed?
- Observe clinical features and tests
Treatment: - T4 and T3
What are the causes of thyrotoxicosis?
Graves’ Disease
- Antibody stimulation of TSH-receptor
- ‘Molecular mimicry’
- Autoimmune mechanism,, may remit
Multinodular goitre
- Autonomous multiple thyroid nodules
- Uncertain pathogenesis, won’t remit
Solitary toxic nodule
- Solitary benign adenoma
- ?TSH receptor activating mutation
Drugs
- Interferon
- Amiodarone
What is the epidemiology of thyrotoxicosis, and what are its effects?
Thyrotoxicosis:
- Common
- 2% in women, 0.2% in men
- Graves/ disease - autoimmune: possible remission
- Multinodular goitre
- Solitary nodule
Cardiovascular effects:
- Higher pulse and BP, heart function
- Atrial fibrillation - 3x risk in 60+yrs
What are the signs and symptoms of thyrotoxicosis?
Thyrotoxicosis
- Weight loss + good appetite
- Tachycardia - palpitations, AF
- Sweating, heat intolerance
- Irritability, mood swings
- Frequent bowel action
- ?goitre
- Eye signs: lid retraction
Thyroid eye disease:
- Exophthalmos (proptosis_
- Chemosis
- Peri-orbital oedema
Tests:
- fT4 raised (Normally: 10-22pmol/L)
- TT3 raised (Normally: 1.1-3.0nmol/L)
- TSH suppressed (Normally 0.2-3.0mU/L)
What are the risks and treatment for thyroid eye disease?
Risks: (consequences)
- Intraocular pressure
- Optic nerve damage exposure
- Corneal ulceration
Treatment:
- Steroids
- Immunosuppression
- Surgical decompression
- Radiotherapy
What are the treatment options for thyrotoxicosis?
- Beta-adrenergic blockers
Anti-thyroid drigs:
- Carbimaxole (methimazole)
- Propylthiouracil
- Radioactive iodine
Surgery
- sub-total, near-total thyroidectomy
How are antithyroid drugs used?
Carbimazole
- Single daily doses OK
Propylthiouracil (PTU)
- Shorter half-life, thrice daily doses (150mg = 40mg CBZ)
Most UK patients received one of the above initially, for 6-24 months
Remission after stopping: 50-60% at 1y
40% at 10y
- No reliable markers for predicting remission
(Large gotire, severe toxicosis, high TSAb = worse risk)
What are the side-effects of anti-thyroid drugs?
Side effects:
- Rash, itching (3-5%)
- Arthralgia
- Nausea, vomiting
- Mild leucopaenia
Agranulocytosis
- 0.1-0.5% risk of significant infection
- Screening not normally done in UK
- Written warning leaflets advised
- Hospitalisation, antibiotics
Why do we avoid block-replace therapy in pregnancy?
Block replace:
- Provide antithyroid drugs, then replace with thyroxine
- The ATD get through to the foetus but the thyroxine does not
- Puts foetus at risk of hypothyroidism
What is radioactive iodine?
Radioactive iodine
- Thyrotoxicosis treatment
- Beta and gamma emitter (131-iodine)
- Capsule or liquid
Dose:
- low hypothyroid rates from low doses = high failure rates
ATD pretreatment:
- Sometimes used to prevent thyroid crisis
- Should stop 5-7 days before iodine
Problems:
- KILLS thyroid follicular cells
- High risk of hypothyroidism
- 25% of patient hypothyroid within 5 years
- Does not cause cancer
- No overall excess risk
- Vigilance needed - younger age groups now treated
DOES NOT CAUSE INFERTILITY!
But avoid pregnancy for 6mo due to radiation issue
What is the practical advice for patients on radioiodine?
Depending on dose, there are limitations placed on the patient for up to 3 weeks:
- No close contact with children and pregnant women (1m)
- Only less than 15mins contact
- No adult in same bed
- Avoid being on public transport for more than 1 hour
What is the relationship between radioiodine and eye disease?
Eye disease may worsen after radioiodine, but:
- Often transient
- Especially smokers
- May related to T-cell activation after RAI
- Reduced by prednisolone
Best treatment of Graves’ with TED is still anti-thyroid drugs, but leaves risk of relapse
Good case now to use radioactive iodine with steroids
Radioiodine can be used with care in selected patients
How is a thyroidectomy used to treat thyrotoxicosis?
Near-total thyroidectomy:
- Remnant tissue less than 2g
- Patient takes T4 post-op
- Relapse rate less than 2%
Complication rates
- Operator dependent, experience dependent
(Prefer 20+ cases per year)
Risks
- Should be low for 1st operation:
- Permanent parathyroid damage 2-4%
- Vocal cord paralysis less than 1%
- Bleeding less than 2%
- Keloid scars
- Hypothyroidism inevitable
What are the 2 commonest causes of hyperthyroidism?
Toxic multinodular goitre
- 2 or more autonomously functioning nodules secrete thyroid hormones
- Second commonest cause of hyperthyroidism in the UK
Solitary toxic adenoma
- May account for up to 5% of cases of hyperthyroidism
Graves’ Disease
- Commonest cause (60-80%)
- Autoimmune process
- Produces more antibodies that stimulate TSH receptors
- Mimic effect of TSH and stimulate the thyroid gland to produce thyroid hormones
- 50% of patients experience opthamopathy
- Related to activation of T cells - autoimmune disease of retroorbital tissues
Which clinical features are only seen in Graves’ Disease hyperthyroidism?
- Exopthalmos
- Thyroid acropachy
- Pretibial myxoedmea
- Opthamoplegia
What are the serious side-effects of carbimazole?
Neutropaenia and agranulocytosis
What advice must be given when carbimazole is prescribed?
- Report signs of infection, especially sore throat
- Doctor should check FBC if there are signs or symptoms of infection
- Stop treatment is WCC is low
What is the mechanism for neonatal hyperthyroidism?
- Thyroid stimulating antibodies (in Graves’) can cross the placenta and stimulate the thyroid gland of the foetus
How does radioactive iodine work?
- Taken orally
- Rapidly uptaken by thyroid
- Release of radiation destroys tissue over 6-18 weeks
Complications:
- Neck discomfort
- Precipitation of Graves’ Opthalmology
- Incidence of hypothyroidism
What are the treatment options for patients with hyperthyroidism who relapse after carbimazole?
Thyroidectomy:
- Recommended for patients with large goitre or severe hyperthyroidism
- Patient preference
Radioactive iodine:
- Contraindicated in pregnancy or in women who are breast feeding
- Complication rate may be lower than in surgery
Which symptoms would suggest hypothyroidism over euthyroidism?
- Constipation
- Myalgia and muscle weakness
- Hoarse or deep voice
- Cold intolerance
What is the most common cause of primary hypothyroidism in adults in the UK?
Chronic autoimmune thyroiditis (Hashimoto’s)
What is secondary hypothyroidism?
Secondary hypothyroidism:
- Due to TSH deficiency due to pituitary/hypothalamic disease
- Low free T4 and low TSH
What is Hashimoto’s thyroiditis?
Hashimoto’s
- Chronic lymphocytic thyroiditis
- 1st immune disease
- T-cell infiltration, destruction of thyroid tissue -> hypothyroidism
- May cause firm goitre in early stages
- Autoantibodies to TPO and Tg
- More common in women (10:1), age 40+
What are the features of hypothyroidism?
Hypothyroidism (Myxoedma)
- Weight gain
- Lethargy ++
- Cold intolerance
- Cool, dry skin
- Dry, brittle hair, nail changes
- Constipation
- Menorrhagia
- Muscle cramps
Tests:
- T4 low
- TSH raised
- T3 unhelpful (often low or normal)
What is subclinical hypothyroidism?
Subclinical hypothyroidism
- Early thyroid failure
- Raised TSH, maintained T4 and T3
- May be symptomatic, but can be nonspecific and difficult to judge
- More common in women 40+
How do we use TSH as a test?
TSH > 2mU/L increases risk of hypothyroidism in the enxt 20 years
- Positive TPO Abs increases risk further
- TSH >2 is within lab ranges, but range is skewed (includes people predisposed to thyroid failure!)
- TSH >2 indicates disturbance of HPT axis - implication for T4 replacement therapy
How do we treat hypothyroidism?
Thyroxine (T4)
- 50-150μg, mostly 100-125μg per day
OD
No S/E
Monitor dose with TFTs - NB long half life of T4
- Issues of compliance, interference with absorption (iron)
T3 hardly used, nor all tissues equally able to convert T4 to T3
Claims for T3 supplements remain unproven
Doing both:
- Risks of transient over-replacement
- Risks of suppressed TSH
- Worries of predisposing to AF
How do we know if a dose of thyroxine is sufficient?
- Resolution of symptoms
- TSH within reference range
What are the side-effects of thyroxine over-replacement?
- Atrial fibrillation
- Osteoporosis
What are the red flag symptoms with regards to thyroid cancer?
- Lump that has been growing
- Dysphagia
- Neck pain
- Hoarseness
- History of radiation to the neck
- Family history of thyroid cancer
What initial investigations would we do for a suspected thyroid cancer?
- History and exam
- USS followed by fine need aspiration of the lump
What are the main histological types of thyroid cancer?
- Papillary carcinoma (70%)
- Follicular carcinoma (20%)
- Anaplastic carcinoma (3%)
- Lymphoma (2%)
- Medullary cell carcinoma (5%)
Papillary and follicular carcinomas are derived from the follicular epithelium, are well differentiated, and ave a good prognosis
Medullar cell carcinomas arise from the calcitonin-producing C cells in the thyroid
What are psammoma bodies?
Seen in papillary carcinoma or the thyroid
- Cells of neoplasm often have nuclei with a central clear appearance from fixation
Papillary tumours are indolent, with a long survival, even with metastases
- Most common metastasis is to the local lymph nodes in the neck
How is thyroid cancer treated?
- Surgery (total thyroidectomy or lobectomy)
- Post-operative radioactive iodine treatment
- Thyroid hormone suppression (to suppress TSH so that tumour growth is not stimulated)
What are goitres?
Goitre
- Enlarged thyroid
- Must assess thyroid status (toxic, hypo, euthyroid…))
- Are there compression symptoms?
Diffuse:
- Graves’ Disease
- Hypothyroidism (Hashimoto’s)
- Colloid goitre (euthyroid)
- Iodine deficiency; drugs (lithium etc)
What are thyroid nodules?
Thyroid nodules
- Solitary lumps
- Common, increase with age
- 30-60% of normal thyroids have nodules at autopsy
- May be part of multinodular disease
- Palpation: 5-20% (>1cm)
- USS: 15-50% (>2mm)
- Thyroid cancer is rare
What clinical signs should we observe with regards to thyroid lumps?
- Age
- Duration
- Iodine status
- Radiation exposure
- Thyroid status
- Presence of solitary nodule vs goiture
- ?multinodular disease
- Pressure symptoms
- Mobility
- Skin tethering
- Lymphadenopathy
- RLN palsy
How do we evaluate thyroid nodules?
USS + FNA
How do we classify cytology of thyroid nodules?
Thy1 - Non-diagnostic (inadequate cellularity: 5-20%)
Thy2 - benign (colloid nodules: 70%)
Thy3 - indeterminate (follicular lesion, could be adenoma or carcinoma: 10-20%)
Thy4 - suspicious of malignancy (30% will be malignant)
Thy5 - diagnostic of malignancy (clear features of papillary, follicular, medullary or other carcinoma; lymphoma, metastasis)
