Thyroid Conditions Flashcards
1
Q
What are differentiated thyroid cancer?
A
Differentiated thyroid cancer (DTC) refers to papillary and follicular variants
2
Q
Who is affected by DCTs?
A
Can affect any age group - childhood to elderly.
In females, rates increase from 15-40 then plateaus
In males, rates steadily increase with age
3
Q
Are DCTs associated with any diet or lifestyle risk factors?
A
- Not associated with diet, other proven malignancies, family history, smoking or other lifestyle factors
- Other than clusters associated with nuclear incidence, the overall incidence is constant at present
4
Q
What is papillary carcinoma?
A
- Derived from follicular epithelium
- Associated with Hashimoto’s
- Associated with ionising radiation
5
Q
What are the genetic associations with papillary carcinoma?
A
- Activation of MAP kinase pathway
- Rearrangements of RET or NTKR1
- Activating point mutation in BRAF
- Mutation of ras
6
Q
What is follicular carcinoma?
A
- Derived from follicular epithelium
- Higher incidence in females
- Higher incidence at 40-50 years
- Incidence slightly higher in regions of iodine deficiency
7
Q
What are the genetic associations with follicular carcinoma?
A
- Mutations in PI3K/AKT pathway
- Mutations in ras family
- Translocation involving Pax8 and PPAR𝛾1
8
Q
Describe the histology of papillary carcinoma.
A
- Can be multifocal
- Often cystic
- May be calcified - psammoma bodies
9
Q
Describe the histology of follicular carcinoma.
A
- Diagnosis depends on invasion of the capsule or vascular invasion
- Classed as minimally invasive or widely invasive
- Widely invasive: more solid architecture, less follicular architecture, more mitotic activity
- Minimally invasive: (most common) follicular architecture (well differentiated), may have part surrounding capsule, difficult to distinguish from adenoma
10
Q
What does this histology slide indicate?
A
Papillary Carcinoma
11
Q
What does this histology slide indicate?
A
Follicular Carcinoma
12
Q
Describe the spread of papillary carcinoma
A
- Papillary carcinomas tend to spread via lymphatics e.g. cervical lymph node metastases
- Haematogenous spread is uncommon but if occurs spread is usually to the lung, bone, liver and brain
13
Q
Describe the spread of follicular carcinoma.
A
- Rarely lymphatic spread, propensity for haematogenous spread (bones, lungs, liver)
- Uncommon to have multicentric disease
14
Q
What is the typical presentation of DTCs?
A
- Majority present with palpable nodules
- Small percentage are chance findings on histological section of thyroidectomy tissue
- Approx. 5% present with local or disseminated metastases
- Local effects e.g. hoarseness, dysphagia, cough suggest advanced disease
15
Q
What are the investigations for DTCs?
A
- TSH, US
- Confirmation: usually US-FNA, can involve excisional biopsy of lymph node
- No role for isotope thyroid scan (in diagnosis), CT or MRI
- Pre-operative laryngoscopy if vocal cord palsy suspected clinically
16
Q
Who are in the low risk group for surgical management of DTCs?
A
Age <50 years, tumour <4 cm
17
Q
What is the surgical management for the low risk DTCs?
A
Thyroid lobectomy + biopsy, thyroidectomy following biopsy results if needed
18
Q
Who is in the high risk group for DTCs?
A
Stage Thy3 or higher on FNA (atypical)
19
Q
What is the surgical management for someone in the high risk group of DTCs?
A
- Subtotal/total thyroidectomy
- Consider radioactive iodine
20
Q
Who gets a whole body iodine scan? and why?
A
- Used in patients who have undergone sub-total or total thyroidectomy
- Usually performed 3-6 months post-op
- Used to determine incomplete incision or present of occult metastases, and therefore inform need for further investigation/treatment
21
Q
Why is RAI ablation used?
A
- Ablate residual thyroid tissue in order to destroy occult microfoci
- Remove residual thyroid tissue which may be a source of Tg and therefore confound the levels during follow-up
- Permit predictively useful scanning in whole body scans and subsequent high dose therapy if required
- Small but significant incidence of acute myeloid leukaemia, no convincing evidence of increase in incidence of other solid tumours
22
Q
What follow up should be done for someone with DTCs?
A
- In both the low and high-risk groups, measure TSH and Tg every 6 months for first 5 years, then annually for next 5 years
- Consider discharge after 5 years if low risk
- To minimise risk of recurrence patients are treated with suppressive doses of levothyroxine (sufficient to suppress TSH below the normal range)
- For low-risk group, TSH should be kept in lower range of normal (0.4-4 mU/L), whereas in the high-risk group TSH should be kept <0.1 mU/L and fT4 below 25
- Thyroglobulin (Tg) is the protein precursor of T4/T3, made by thyroid follicular epithelial cell - can be used as ‘tumour marker’
23
Q
What is the management of recurrent DTCs?
A
- Can be detected clinically, by rising Tg, or by imaging
- Recurrence in cervical lymph nodes is more common in papillary cancer
- Haematogenous spread to lungs, bone or brain more common in follicular lesions
- Usually, patients undergo whole body scan to determine ability to take up iodine with a view to RAI
- Difficult group are those with rising Tg but negative whole body iodine scan - management options include PET scan to allow targeted treatment, and systemic anti-cancer therapy e.g., sorafenib and Lenvatinib
24
Q
What is thyrotoxicosis?
A
the clinical, physiological, and biochemical state arising when the tissues are exposed to excess thyroid hormone
25
What is hyperthyroidism?
refers specifically to conditions in which overactivity of the thyroid gland leads to thyrotoxicosis
26
What is the aetiology of hyperthyroidism?
**Graves’ disease**
- Accounts for 85% of cases
- Higher incidence in females - 10:1
- Usually presents between 20-40 years
- Interacting susceptibility genes plus environmental factors
**Other causes of thyrotoxicosis associated with hyperthyroidism**
*Excessive thyroid stimulation*
- Hashitoxicosis - transient hyperthyroidism caused by inflammation associated with Hashimoto's thyroiditis, patient will then develop hypothyroidism
- Thyrotropinoma - TSH secreting pituitary adenoma (very rare)
- Thyroid cancer - only very rarely cause thyrotoxicosis
- Choriocarcinoma - trophoblast tumour secreting hCG
*Thyroid nodules*
- Toxic solitary nodule
- Toxic multinodular goitre
27
What are the causes of thyrotoxicosis that are not associated with hyperthyroidism?
*Thyroid inflammation (thyroiditis)*
- Subacute (de Quervain's) thyroiditis
- Post-partum thyroiditis
- Drug-induced thyroiditis (e.g., amiodarone)
*Exogenous thyroid hormones*
- Over-treatment with levothyroxine
- Thyrotoxicosis factitia
*Ectopic thyroid tissue*
- Metastatic thyroid carcinoma
- Struma ovarii (teratoma containing thyroid tissue)
28
What is the pathophysiology of Graves' Disease?
- Involves auto-antibodies to TSH receptor, thyroid peroxisomes and thyroglobulin
- The anti-TSH receptor antibodies stimulate the thyroid resulting in increased function
- Some antibodies can inhibit function - may explain paradoxical episodes of hypofunction which can occur
29
What is the presentation of thyrotoxicosis?
- Weight loss despite increased appetite
- Frequent, loose bowel movements
- Sweating and heat intolerance
- Goitre - diffuse in Graves, goitre with firm nodules if toxic multinodular goitre
- Thyroid bruit - associated only with large goitres
- Reflective of hypervascularity of thyroid
- Auscultate over the thyroid
- Double vision
- Graves ophthalmopathy (see below)
- Increased pulse rate
- Palpitations, AF
- Rarely cardiac failure
- Fine tremor of the outstretched fingers
- Muscle weakness, especially in thighs and upper arms
- Increased nervousness and excessively emotional
- Sleep disturbance
- Depression
- Insomnia
- Hair change (thin, brittle hair)
- Rapid fingernail growth
- Menstrual cycle changes, including lighter bleeding and less frequent periods
30
What is the specific Graves' presentation?
- Pretibial myxoedema (also occasionally seen in Hashimoto's thyroiditis)
- Thyroid acropachy - thickening of the extremities manifested by digital clubbing, soft tissue swelling of the hands and feet, and periosteal new bone formation
- Graves eye disease
- Autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, lid lag, swelling, erythema, conjunctivitis, and bulging eyes (exophthalmos)
- Occurs in ~20% of Graves' patients
- Results from autoimmune inflammation of the extra-ocular muscles as orbital fat and connective tissue TSH receptors
- Association with smoking (smoking cessation very important)
- Presentation can precede diagnosis of Graves'
- Can be unilateral
- Most disease is mild but can be severe and sight-threatening
- Diffuse goitre
31
What are the investigations of thyrotoxicosis?
**Thyroid hormones**
*Primary hyperthyroidism*
- TSH low
- Free T3/T4 high
*Secondary hyperthyroidism*
- TSH high
- Free T4 and T3 high (or 'normal')
**Thyroid autoantibodies in Graves' disease**
- Anti-TPO antibody - 70-80%
- Anti-thyroglobulin antibody - 30-50%
- TSH receptor antibody (stimulating) - 70-100%
**Scintiscan**
- Used in patients who are antibody negative to look for toxic nodular disease
32
What is the management of Grave's disease?
- Antithyroid drugs - carbimazole (first line), PTU (1st trimester of pregnancy)
- Gradual dose regimen lasts 12-18 months, block and replace regimen takes 6 months
- ~50% relapse rate
*Management of Graves' eye disease*
- Mild disease treated topically e.g., lubricants
- More severe disease: steroids, radiotherapy, surgery
33
What is the management of thyrotoxicosis?
**Antithyroid drugs such as carbimazole**
**β-blockers**
- Useful for immediate symptomatic relief of thyrotoxic symptoms
- CCBs can be used where β-blockers are contraindicated e.g., asthma
**Radioiodine**
- 1st choice treatment for relapsed Graves' disease and nodular thyroid disease
- High risk of hypothyroidism when used in Graves' disease (1:2)
**Thyroidectomy**
- Useful when radioiodine is contraindicated e.g., pregnancy
- Will leave a scar
- Surgical/anaesthetic risks:
- Recurrent laryngeal nerve palsy
- Hypothyroidism
- Hypoparathyroidism
34
What is thyroid storm?
- Rapid deterioration of hyperthyroidism with hyperpyrexia, severe tachycardia, extreme restlessness, cardiac failure and liver dysfunction
- Typically seen in hyperthyroid patient with an acute infection/illness or recent thyroid surgery
35
What is the management of thyroid storm?
- High dose carbimazole
- β-blockers (propranolol)
- Potassium iodide
- Hydrocortisone
- IV fluids +/- inotropes
- Treat precipitating cause e.g. MI, infection, PE
36
What is subacute thyroiditis?
Refers to a transient patchy inflammation of the thyroid
37
What is De Quervain's Thyroiditis?
Describes the presentation of a viral infection with fever, neck pain and tenderness, dysphagia and features of hyperthyroidism
38
What is the aetiology of subacute thyroiditis?
- Ages 20-50
- May be triggered by viral infection
39
What is the presentation of subacute thyroiditis?
- Painful, diffuse, firm goitre
- Fever and/or malaise may be present
- There is a hyperthyroid phase followed by a hypothyroid phase as the TSH level falls due to negative feedback
40
What are the investigations for subacute thyroiditis?
- Thyroid function tests
- May perform scintigraphy scan to rule out other causes of hyperthyroidism, will be low uptake throughout
41
What is the management of De Quervain's thyroiditis?
- Self-limiting condition - supportive treatment with NSAIDs for pain and inflammation and beta-blockers for symptomatic relief of hyperthyroidism is usually all that is necessary
- Short course of steroids may be needed
42
What is the aetiology of drug-induced thyroiditis?
- Drugs which can induce thyroiditis include amiodarone and lithium
- Amiodarone inhibits DIO1 - increased free T4, decreased free T3, normal TSH
- Hypothyroidism occurs in 13% - tends to occur in iodine rich areas
- Hyperthyroidism occurs in 2% - tends to occur in iodine deficient areas, split into type 1 (similar to Graves', type 2 (destructive thyroiditis) or mixed
43
What is the management of drug-induced thyroiditis?
- Resolves without treatment in many cases
- Steroid therapy may be necessary with some drugs
44
What is hypothyroidism?
Results from any disorder that results in insufficient secretion of thyroid hormones from the thyroid gland
45
What is the aetiology of congenital hypothyroidism?
- Absent or under-developed thyroid gland
- Dyshormogenesis - genetic defects in the synthesis of thyroid hormones, resulting in hypothyroidism with goitre
- Iodine deficiency during pregnancy
- Maternal transmission of antithyroid drugs
46
What is the aetiology of acquired hypothyroidism?
*Primary hypothyroidism:*
Insufficient thyroid hormone production:
- Hashimoto's thyroiditis (chronic lymphocytic thyroiditis)
- Most common cause of hypothyroidism in iodine-sufficient regions
- Affects middle aged women (45-60 years)
- Associated with family history of autoimmune thyroiditis or other autoimmune diseases
- Associated with HLA - DR3 and DR5
- Iodine deficiency - most common cause worldwide, particularly in iodine-deficient regions
- Iatrogenic e.g., post-ablative therapy (e.g., radioiodine, surgery)
- Others: atrophic thyroiditis (autoimmune), de Quervain's thyroiditis and post-partum thyroiditis
*Secondary hypothyroidism*
- Pituitary disorders (e.g., pituitary adenoma) resulting in TSH deficiency
*Tertiary hypothyroidism*
- Hypothalamic disorders resulting in TRH deficiency
47
What is the pathophysiology of Hashimoto's thyroiditis?
- Gradual failure of thyroid function due to autoimmune destruction of thyroid tissue
- Characterised by anti-thyroglobulin and anti-peroxidase antibodies which, when bound, cause antibody dependent cell mediated cytotoxicity
- CD 8+ cells may mediate destruction of thyroid epithelium
- Cytokine mediated cell death
- 𝛾 interferon from T cell activation recruits’ macrophages that may damage thyroid follicles
- May be preceded by transient hyperthyroidism (Hashitoxicosis)
48
Describe the histology of Hashimoto's thyroiditis?
- Thyroid may be diffusely enlarged.
- Prominent lymphoid infiltrate - lymphocytes, plasma cells and reactive follicles with germinal centres
- Thyroid follicles atrophy
- Follicular cells have abundant eosinophilic cytoplasm (Hurthle cells)
- May see progressive fibrosis within the gland
49
What is the presentation of hypothyroidism?
- Tiredness/malaise
- Weight gain, despite decreased appetite
- Cold intolerance
- Decreased sweating
- Coarse, sparse hair, brittle nails and cold, dry skin
- Constipation
- Bradycardia - slow pulse
- Hypothyroid myopathy - myalgia, stiffness, cramps
- Delayed relaxation of deep tendon reflexes
- Hyperlipidaemia - xanthelasma
- Hypercarotenaemia
Deep hoarse voice
- Goitre (in Hashimoto thyroiditis) or atrophic thyroid (in atrophic thyroiditis)
- Impaired cognition, depression
- Vitiligo may be present
- Obstructive sleep apnoea - macroglossia or the presence of a goitre can inhibit breathing during sleep
50
What are the investigations of primary hypothyroidism?
*Thyroid hormones*
- TSH high
- Free T4 and T3 low
*Other abnormalities*
- Macrocytosis (↑ MCV)
- ↑ creatinine kinase
- ↑ LDL cholesterol
- Hyponatraemia
- ↓ renal tubular water loss
- Hyperprolactinaemia
*Thyroid antibodies in autoimmune hypothyroidism*
- Anti-TPO antibody - 95%
- Anti-thyroglobulin - 60%
- TSH receptor antibody (blocking) - 10-20%
51
What are the investigations for secondary hypothyroidism?
- TSH low (or 'normal')
- Free T4 and T3 low
52
What is the management of primary hypothyroidism?
- Younger patients: start levothyroxine at 50-100 µg daily and gradually increase
- In the elderly with a history of IHD: start levothyroxine at 25-50 µg daily, adjusted every 4 weeks according to response
- Check TSH 2 months after any dose change
- Once stabilised within the normal range, TSH should be checked every 12-18 months
53
What is the management of secondary hypothyroidism?
Titrate dose of levothyroxine to the tT4 level - should be higher end of normal (TSH unreliable due to low TSH production)
54
What are the complications of hypothyroidism?
**Myxoedema coma**
- Typically affects elderly women with long standing but frequently unrecognised or untreated hypothyroidism
- Mortality up to 60% despite early diagnosis and treatment
**Long-term complications of autoimmune hypothyroidism**
- Increases risk of developing other auto-immune diseases
- Increased risk of developing B-cell NHL in the affected gland
55
What are the investigations for myxoedema coma?
- ECG: bradycardia, low voltage complexes, varying degrees of heart block, T wave inversion, prolongation of the QT interval
- ABGs: type 2 respiratory failure (hypoxia, hypercarbia, respiratory acidosis)
- Co-existing adrenal failure present in 10% of patients
56
What is the management of myxoedema coma?
- Passively rewarm - aim for slow rise in body temperature
- Cardiac monitoring for arrhythmias
- Close monitoring of urine output, fluid balance, central venous pressure, blood sugars, oxygenation
- Broad spectrum antibiotics
- Thyroxine cautiously, hydrocortisone if adrenal failure
57
What is subclinical hypothyroidism?
- ↑TSH, normal fT4/3
- Risk of progression to overt hypothyroidism
- Higher risk if strongly TPO antibody positive
- Treatment generally advised if TSH > 10
- Always treat in pregnancy to maintain normal TSH
58
What is subclinical hyperthyroidism?
- ↓TSH, normal fT4/3
- Risk of progression to overt hyperthyroidism
- Often seen in multinodular goitre
- Association with osteoporosis and atrial fibrillation
- Treatment generally advised if TSH <0.1% (or if co-existing osteoporosis/fracture or AF)
59
What is the aetiology of solitary thyroid nodules?
- Very common; affect 5% of women
- Vast majority (95%) are benign
- Malignant thyroid nodules can affect any age group; there is a higher incidence in females after childhood and before older age
60
What are the classifications of benign solitary thyroid nodules?
- Cyst
- Colloid nodule
- Benign follicular adenoma
- Hyperplastic nodule
61
What are the features of benign solitary thyroid nodules?
- Family history autoimmune disorders
- Family history benign nodules/goitre
- Associated hormonal disturbance
- Pain/tenderness
- Soft, smooth, mobile
62
What are the types of malignant solitary thyroid nodules?
- Papillary thyroid carcinoma (80%)
- Medullary thyroid carcinoma (3%)
- Lymphoma - primary (5%) or secondary
- Anaplastic - poorly differentiated, aggressive and associated with worse outcomes
63
What are the features of malignant solitary thyroid nodules?
- <20 and >50 years old
- Male
- FHx of thyroid cancer
- Dysphagia/dysphonia
- Previous neck irradiation
- Firm, hard, immobile
- Cervical lymphadenopathy
- Nodule increasing in size
- Lesion >4cm
64
What is the presentation of a solitary thyroid nodule?
- If lump moves on swallowing, it is in the thyroid - invested in pretracheal fascia
- Majority are painless
- Pain is usually caused by intra-thyroidal bleed into a cyst
- Signs of malignancy include enlarged neck lymph nodes and hoarseness
- Can be toxic or non-toxic - if toxic may be signs of hypothyroidism
65
What are the investigations for solitary thyroid nodules?
- Thyroid function tests
- US scan
- USS-FNA (ultrasound fine needle aspiration)
- Thyroid scan (scintigraphy) - can be useful in distinguishing between functioning (hot) or non-functioning (cold) nodules
- Hot nodule is only rarely malignant
- FNA has largely replaced isotope scans in the diagnosis of thyroid nodules
66
How are solitary thyroid nodules classified?
*FNA Bethesda classification - Thy1-5*
- Thy1 - inadequate
- Thy2 - benign
- Thy3 - atypical
- Thy4 - probably malignant
- Thy5 - malignant
67
What is follicular adenoma?
A benign encapsulated tumour of the thyroid gland that is surrounded by a thin fibrous capsule
68
What is the aetiology of follicular adenoma?
- More commonly found in women
- Increases in incidence with increasing age
- Increased incidence in regions of iodine deficiency
69
What are the genetic factors associated with follicular adenoma?
- <20% have a mutant ras or PIK3CA
- Functional adenomas have an activating mutation in the TSHR signalling pathway → increased cAMP
- N-ras and K-ras mutations have been implicated in the evolution of follicular adenoma to follicular carcinoma
70
What is the pathophysiology of follicular adenoma?
- Usually, non-functional
- Around 1% develop into a toxic adenoma - produces thyroid hormone autonomously
- FA histology shows neoplastic thyroid follicles encapsulated by a surrounding collagen cuff
71
What is the presentation of follicular adenoma?
- Discrete solitary mass in an otherwise normal thyroid gland
- May be incidental finding
- Patients with larger tumours may present with local symptoms e.g., dysphagia
72
What are the investigations of follicular adenoma?
- US scan
- FNA - cannot distinguish between follicular adenoma and follicular carcinoma
- Serum TSH
73
What is the management of follicular adenoma?
Lobectomy with biopsy is required for treatment and definitive diagnosis as FNA cannot distinguish between follicular adenoma and follicular carcinoma
74
What is anaplastic carcinoma?
Undifferentiated and aggressive tumours derived from follicular epithelium
75
What is the aetiology of anaplastic carcinoma?
- Can arise de novo or be due to dedifferentiation of another carcinoma
- Usually, older patients
- Similar genetic features to papillary carcinomas and follicular carcinomas as well as p53 and β-catenin mutations
76
What is the pathophysiology of anaplastic carcinoma?
- May occur in people with a history of differentiated thyroid cancer
- Rapid growth and involvement of neck structures and death
77
What is the presentation of anaplastic carcinoma?
- Thyroid nodule
- Features of local infiltration/compression
- Cervical lymphadenopathy
- Signs of distant metastases
78
What are the investigations for anaplastic carcinoma?
- TSH, US
- Confirmation: US-FNA or biopsy
79
What is the management of anaplastic carcinoma?
- Total thyroidectomy if resectable +/- adjuvant radio chemotherapy as needed
- Do not respond to RAI
80
What are medullary carcinoma?
Tumour of the parafollicular cells which secrete calcitonin (C-cells)
81
What is the aetiology of medullary carcinoma?
- Can be:
- Sporadic (70%) - seen in adults (40s-50s)
- Medullary carcinoma associated with Multiple Endocrine Neoplasia Type 2a (MEN2a) can arise in very young patients
- MTC associated with phaeochromocytoma and hyperparathyroidism in these patients
- Consider prophylactic thyroidectomy as child
- Familial non-MEN seen in adults (40s-50s)
**Genetic features**
- Germline RET mutations
82
What is the morphology of medullary carcinoma?
- Sporadic cases - solitary nodule
- Familial cases - bilateral/multicentric
- C cell hyperplasia
- Composed of spindle or polygonal cells arranged in nests, trabeculae or follicles
- Associated amyloid deposition (abnormally folded calcitonin)
83
What are the prognostic factors of medullary carcinoma?
*Good prognostic factors*
- Young age, female
- Smaller tumour rise, confined to thyroid, no metastases
*Negative prognostic factors*
- Necrosis
- Many mitosis
- Squamous metaplasia
- Small cell morphology
- <50% cells calcitonin positive
- Type of RET mutation
- Some familial forms have more aggressive potential (MEN2B)
84
What is the presentation of medullary carcinoma?
- Neck mass with local effects - dysphagia, hoarseness, airway compromise
- Paraneoplastic syndrome
- Diarrhoea - VIP production
- Cushing's - ACTH production
85
What are the investigations of medullary carcinoma?
- Neck USS and FNA
- Measure serum base calcitonin
- 24 hour urinary metanephrines
- Further imaging to detect localised/advanced disease
- Check genetics for MEN
86
What is the management of medullary carcinoma?
**Localised disease**
- Total thyroidectomy - curative
- Local recurrence in 35% of patients
**Advanced disease**
- May involve tyrosine kinase inhibitors
87
What is thyroid lymphoma?
Lymphoma that arises from the thyroid gland
88
What is the aetiology of thyroid lymphoma?
- Background of auto-immune hypothyroidism
- Females aged 70-80 years
89
What is the presentation of thyroid lymphoma?
Rapid onset mass in thyroid
90
What is the investigation for thyroid lymphoma?
Core biopsy
91
What is the management of thyroid lymphoma?
- Chemotherapy (R-CHOP), radiotherapy or steroids
- Does not respond to RAI
92
What is a goitre?
Enlarged palpable thyroid gland, which moves on swallowing
93
What is the aetiology of a goitre?
May be a benign disorder but is also associated with several thyroid diseases, including iodine deficiency, Hashimoto’s thyroiditis, and some of the causes of hyperthyroidism
94
What is the pathophysiology of a goitre?
- Reduced T3/T3 production causes a rise in TSH, stimulating gland enlargement
- This may maintain euthyroid state or if compensation fails there will be goitrous hypothyroidism
95
What is the aetiology of a diffuse goitre?
- Physiological goitre - puberty, pregnancy
- Autoimmune thyroid disease - Hashimoto's thyroiditis, Grave's disease thyrotoxicosis
- Endemic - iodine deficiency +/- ingestion of goitrogens (chemicals which exaggerate the effects of iodine deficiency)
- Inflammation - acute (de Quervain's) thyroiditis
- Sporadic
- 4:1 female, usually during puberty/YA
- Most cases have no clear cause
- Some associated with ingestion of substances limiting T3/T4 production or inborn errors of metabolism (dyshormonogenesis)
96
What is the presentation of a diffuse goitre?
- Entire thyroid gland swells and is smooth to the touch
- Usually euthyroid, if not may be symptoms of hyper/hypothyroidism
- Present with mass effects
- Cosmetic
- Compression of the trachea → exertional dyspnoea and, in severe cases, stridor or wheezing
- Compression of the oesophagus → dysphagia
- In children dyshormonogenesis may cause cretinism
97
What are the investigations for a goitre?
Thyroid function tests - T3/T4 normal, TSH high or upper limit of normal
98
What is the management of a diffuse goitre?
- Treat underlying cause if appropriate (iodine deficiency, autoimmune thyroid disease)
- Usually no further treatment needed (unless causing obstructive symptoms - surgery)
99
What is the aetiology of a multi-nodular goitre?
Develops from a long-standing simple sporadic goitre
100
What is the pathophysiology of a multi-nodular goitre?
- Variation of response of follicular cells to external stimuli - recurrent hyperplasia and involution
- Mutations of TSH signalling pathway
- There will be a varying degree of fibrosis, haemorrhage and calcification
101
What is the presentation of a multi-nodular goitre?
- Irregular enlarged thyroid due to nodule formation - thyroid feels bumpy on palpation
- Enlargement can be impressive
- Presents with mass effects
- Can be inactive or toxic
- Toxic multinodular goitres are responsible for ~35% of cases of hyperthyroidism
- Toxic nodules have an increased risk of malignant transformation
102
What are the investigations of a multi-nodular goitre?
- Thyroid function tests - TSH usually normal or slightly suppressed, fT3/T4 normal if inactive or increased if toxic
- US scan - sensitive method for delineating nodules and can demonstrate whether they are cystic or solid
- FNA - to assess cancer risk for prominent palpable and suspicious nodules
- CT scan - may detect retrosternal extension and tracheal compression in patients with a very large goitre or clinical symptoms
- Thyroid isotope scan - toxic or non-toxic
- Flow volume loops if considering other potential causes of breathlessness
103
What is the management of a multi-nodular goitre?
- Most can leave alone
- Antithyroid drugs if toxic
- Radioactive iodine if significant hyperthyroid
- Surgery if structural problem or significant retrosternal extension
104
What is the management of pre-existing hypothyroidism in pregnancy?
- Unable to compensate for increased demand
- Increase thyroxine dose by 25mcg as soon as pregnancy suspected
- Check TFTs monthly for first 20 weeks then 2 monthly until term
- The average dose increase is by 50% by 20 weeks
- Aim for TSH <3 mU/l
105
What are the complications of pre-existing hypothyroidism in pregnancy?
- Increased abortion, preeclampsia, abruption, postpartum haemorrhage, preterm labour
- Impacts on foetal neurophysical development - average of 7 IQ points less in children of untreated hypothyroid mother's vs normal mothers
106
What are the causes of hyperthyroidism in pregnancy?
- Most common cause in this age group (fertile women) is Graves' disease
- Other causes include TMNG, toxic adenoma and thyroiditis
107
What are the complications of hyperthyroidism in pregnancy?
- Infertility/amenorrhoea
- Spontaneous miscarriage
- Stillbirth
- Thyroid crisis in labour
- Transient neonatal thyrotoxicosis
108
What is the management of hyperthyroidism in pregnancy?
- Wait and see (supportive management)
- If hyperemesis, will settle
- Graves may settle as pregnancy suppresses autoimmunity
- Check TRAb antibodies - if present alert neonatologist as TRAb antibodies can cross the placenta and cause neonatal transient hyperthyroidism
- β-blockers if needed
- LOW DOSE antithyroid drugs - wait as late as possible due to side effects on foetus
- Propylthiouracil 1st trimester
- Carbimazole 2/3rd trimester
109
What is the aetiology of post-partum thyroiditis?
- Affects 5% postpartum women (25% in T1DM)
- Occurs within 6 months of giving birth
- In the postpartum phase there is exacerbation of all autoimmune diseases
110
What is the presentation of post-partum thyroiditis?
- After delivery, the mother develops transient over-active thyroid, classically at around 6 weeks, and then at around 3 months has an underactive thyroid
- Will develop small, diffuse, nontender goitre
- Hypothyroid phase associated with neonatal depression
- Can persist up to 1-year post-partum
- 25-50% will have persistent hypothyroidism beyond 1 year
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What are the investigations for post-partum thyroiditis?
- Thyroid function tests
- Thyroid antibody tests
- Scintigraphy scan
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What is the management of post-partum thyroiditis?
- No treatment for hyperthyroid phase, if symptomatic hypothyroid treat with thyroxine
- Should eventually be able to stop thyroxine but if patient is still on thyroxine after a year it is likely they will need it long term
