Thyroid disease Flashcards
(52 cards)
1
Q
What questions should be asked when a patient has unintentional weight loss?
A
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)
2
Q
What physical signs are seen in hyperthyroidism?
A
- Increased HR
- Increased BP
- Increased sewating
- Exophthalmos
- Lid lag
- Enlarged thyroid/goitre
- Agitation
- Tremor
- Onycholysis
- Acropachy
- Conjunctival oedema
- Opthalmoplegia
- Pretibial myxoedema
- Proximal myopathy
- Hyperreflexia
3
Q
What TFTs are seen in primary hyperthyroidism?
A
- 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
4
Q
Which tissues do T3 and T4 target?
A
T3:
- Heart
- Liver
- Bone
- CNS
- Muscle
T4:
- Thyroid gland
- Liver
0 Musclw
5
Q
What is the thyroid gland?
A
- Soft gland, lower neck
- Anterior to trachea
- Below thyroid cartilage of larynx
- Maxes thyroxine and T3
- 2 lobes and isthmus
6
Q
What is the histology of the thyroid gland?
A
- 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)
7
Q
How are thyroid hormones made?
A
- 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
8
Q
What is the basis of the pituitary-thyroid axis?
A
- Negative feedback of T4 and T3 on pituitary TSH and hypothalamic TRH
- Low T4 -> increased TSH
- High T4 -> suppressed TSH
9
Q
What TFTs are seen in an overactive thyroid and in an underactive thyroid?
A
Overactive: High T4 and T3, low TSH
Underactive: Low T4
High TSH
10
Q
What do we examine in Thyroid function tests?
A
- Total T4
- Free T4
- Total T3
- Free T3
- TSH
- Antibodies: TPO Abs, TSH-R Abs
11
Q
What are some factors that can skew TFTs?
A
- Pregnancy raises TBG - use measurements of free thyroxine
- OCP raises TBG
Funny tests: - Antibodies
- Drugs: amiodarone
- Pituitary disease
- Wrong patient
12
Q
How is Thyrotoxicosis managed?
A
- 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
13
Q
How is hypothyroidism managed?
A
- Observe clinical features and tests
Treatment: - T4 and T3
14
Q
What are the causes of thyrotoxicosis?
A
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
15
Q
What is the epidemiology of thyrotoxicosis, and what are its effects?
A
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
16
Q
What are the signs and symptoms of thyrotoxicosis?
A
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)
17
Q
What are the risks and treatment for thyroid eye disease?
A
Risks: (consequences)
- Intraocular pressure
- Optic nerve damage exposure
- Corneal ulceration
Treatment:
- Steroids
- Immunosuppression
- Surgical decompression
- Radiotherapy
18
Q
What are the treatment options for thyrotoxicosis?
A
- Beta-adrenergic blockers
Anti-thyroid drigs:
- Carbimaxole (methimazole)
- Propylthiouracil
- Radioactive iodine
Surgery
- sub-total, near-total thyroidectomy
19
Q
How are antithyroid drugs used?
A
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)
20
Q
What are the side-effects of anti-thyroid drugs?
A
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
21
Q
Why do we avoid block-replace therapy in pregnancy?
A
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
22
Q
What is radioactive iodine?
A
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
23
Q
What is the practical advice for patients on radioiodine?
A
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
24
Q
What is the relationship between radioiodine and eye disease?
A
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
25
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
26
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
27
Which clinical features are only seen in Graves' Disease hyperthyroidism?
- Exopthalmos
- Thyroid acropachy
- Pretibial myxoedmea
- Opthamoplegia
28
What are the serious side-effects of carbimazole?
Neutropaenia and agranulocytosis
29
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
30
What is the mechanism for neonatal hyperthyroidism?
- Thyroid stimulating antibodies (in Graves') can cross the placenta and stimulate the thyroid gland of the foetus
31
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
32
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
33
Which symptoms would suggest hypothyroidism over euthyroidism?
- Constipation
- Myalgia and muscle weakness
- Hoarse or deep voice
- Cold intolerance
34
What is the most common cause of primary hypothyroidism in adults in the UK?
Chronic autoimmune thyroiditis (Hashimoto's)
35
What is secondary hypothyroidism?
Secondary hypothyroidism:
- Due to TSH deficiency due to pituitary/hypothalamic disease
- Low free T4 and low TSH
36
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+
37
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)
38
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+
39
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
40
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
41
How do we know if a dose of thyroxine is sufficient?
- Resolution of symptoms
| - TSH within reference range
42
What are the side-effects of thyroxine over-replacement?
- Atrial fibrillation
| - Osteoporosis
43
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
44
What initial investigations would we do for a suspected thyroid cancer?
- History and exam
| - USS followed by fine need aspiration of the lump
45
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
46
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
47
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)
48
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)
49
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
50
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
51
How do we evaluate thyroid nodules?
USS + FNA
52
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)
