1
Q
Primary vs Secondary thyroid disease
A
primary - Thyroid problem
Secondary - hypothalamus or pituitary problem
2
Q
Describe the thyroid axis
A
Hypothalamus - release TRH
Pituitary - release TSH
Thyroid - release T4 & T3
Bloodstream - T4 & T3 bound to proteins
Liver (& other organs) - T4 to T3 activation
** negative feedback
3
Q
State the expected T3/4 & TSH levels in
Primary hypothyroidism
Secondary hypothyroidism
Subclinical hypothyroidism
Primary hyperthyroidism
Secondary hyperthyroidism
Subclinical hyperthyroidism
A
Low T3/4 High TSH Primary hypothyroidism
Low T3/4 Low TSH Secondary hypothyroidism
Normal T3/4 High TSH Subclinical hypothyroidism
High T3/4 Low TSH Primary hyperthyroidism
High T3/4 High TSH Secondary hyperthyroidism
Normal T3/4 Low TSH Subclinical hyperthyroidism
4
Q
What is myxoedema
A
Severe hypothyroidism
5
Q
What is thyroid crisis
A
Severe hyperthyroidism
6
Q
What is sick euthyroid syndrome
A
Thyroiditis & abnormal thyroid function tests in unwell patients
7
Q
What is thyrotoxicosis vs hyperthyroidism
A
Thyrotoxicosis - excess T3 hormone tissue exposure
Hyperthyroidism - Overactive thyroid producing excess T3/4
8
Q
Primary hypothyroidism congenital aetiology
A
- Absent or underdeveloped thyroid gland
- Maternal transmission of anti thyroid drugs
- Dyshormogenesis (genetic defect in T3/4 synthesis)
- iodine deficiency in pregnancy
9
Q
Primary hypothyroidism acquired aetiology
A
- Hashimoto’s thyroditis (autoimmune)
- Iodine deficiency
- Iatrogenic - RI, surgery, amiodarone, lithium
- Atrophic thyroiditis (autoimmune)
10
Q
Primary hypothyroidism acquired self limiting aetiology
A
- Post partum thyroditis
- De Quervain’s thyroiditis (subacute thyroiditis with transient hypothyroidism)
11
Q
What is Hashimoto’s thyroiditis aka
A
Chronic lymphocytic thyroiditis
12
Q
What congenital hypothyroidism presents with a goitre
A
Dyshormogenesis
13
Q
Secondary & Tertiary hypothyroidism aetiology
A
Secondary - Pituitary disorder e.g. adenoma
Tertiary - Hypothalamic disorder
14
Q
Hashimoto’s thyroiditis pathophysiology
A
Anti-thyroglobulin (anti-TSH) & Anti-peroxidase (anti-TPO) =>
CD8+ cell mediated thyroid epithelial destruction =>
Cytokine mediated cell death =>
Interferon gamma release attracts macrophages =>
Macrophages cause further damage =>
May be preceded with transient hyperthyroidism (hashitoxicosis)
15
Q
Hashimoto’s thyroiditis histological features
A
- Follicle atrophy
- Prominent lymphoid infiltrate (lymphocytes & plasma cells)
- Reactive follicles with germinal centres
- Hurthle cells may be present
- Progressive fibrosis may also be present
16
Q
What are hurthle cells
A
Follicular cells with an abundant granular, eosinophilic cytoplasm. Can be present in Hashimoto’s disease, grave’s disease, hurthle cell adenoma & carcinoma
17
Q
Hypothyroidism clinical features (decreased metabolic rate related)
A
- Weight gain
- Constipation
- Tiredness
- Low mood
- Cold intolerance
- Sparse & thin hair
- Vitiligo
- Low HR
- Fluid retention
- Hyperlipidaemia
- Peripheral neuropathy
- Muscle weakness & cramps
- Menorrhagia, amenorrhoea
18
Q
What effect does hypothyroidism have on prolactin levels
A
(Primary) hypothyroidism can cause hyperprolactinaemia
Low T3/4 => High TSH => Prolactin release
This can cause menorrhagia & eventually amenorrhoea
19
Q
What skin autoimmune condition is closely linked to Hashimoto’s disease
A
Vitiligo
20
Q
If a kid had congenital hypothyroidism, what other features would you expect
A
Cretinism - dwarfism and limited mental functioning
21
Q
How can you differentiate between Hashimoto’s thyroiditis & atrophic thyroiditis
A
Hashimoto’s thyroiditis - goitre
Atrophic thyroiditis - atrophic thyroid
22
Q
Summarise clinical features of hypothyroidism
A
Decreased metabolic rate related symptoms
Generalised myxoedema related symptoms
Hyperprolactinaemia related symptoms
Goitre & related symptoms e.g. OSA
23
Q
What is myxoedema
A
Accumulation of mucopolysaccharides in subcutaneous tissue
24
Q
Myxoedema clinical features
A
Doughy skin texture, puffy face
Myxoedematous heart disease e.g. dilated cardiomyopathy
Periorbital oedema
Entrapment syndromes e.g. carpal tunnel syndrome
Macroglossia
Peripheral neuropathy
Deep hoarse voice
Myxoedema coma
25
Hypothyroidism investigations
TSH & T3/4 levels
Anti-TPO & Anti-TSH antibodies
26
Hypothyroidism blood test findings (apart from TFTs)
Macrocytosis
Raised creatinine kinase
Hyperlipidaemia
Fluid retention & associated hyponatraemia
Hyperprolactinaemia
27
Hypothyroidism treatment
T4 Levothyroxine tablets
Take every morning before breakfast
Start low, gradually increase dose (avoid cardiac arrhythmia)
28
What is checked every year in patients with hypothyroidism
TSH - in primary hypothyroidism
T4 - in secondary hypothyroidism (should be higher end of normal)
29
Why is Levothyroxine gradually increased when treating hypothyroidism
rapid restoration of metabolic rate may precipitate cardiac arrhythmias
30
A complication of severe (prolonged & untreated) hypothyroidism is myxoedema coma & myxoedematous heart disease. How would this present on an ECG
“myxedema heart” consists of an enlarged sluggish heart with low electrical voltages and flattened or inverted T waves on the electrocardiogram, changes which are reversible with the administration of thyroid hormone
- Bradycardia
- Low voltage complexes
- varying degrees of heart block
- inverted T waves
- prolonged QT interval
31
Why does myxoedema cause type 2 respiratory failure
Myxedema impairs the central nervous system's ability to detect high CO2 levels, leading to a reduced respiratory drive and inadequate breathing
This will present as Type 2 respiratory failure (hypoxia, hypercarbia, respiratory acidosis)
32
Autoimmune hypothyroidism increases your risk of what cancer
B cell NHL of the thyroid gland
33
Myxoedema coma management
- 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
34
What is de quervians thyroditis
Describes the presentation of a viral infection with fever, neck pain and tenderness, dysphagia and features of thyroid disease
35
De Quervain's thyroiditis clinical presentation
- Painful, diffuse, firm goitre
- Fever and/or malaise may be present
- Recent viral infection
- Initial hyperthyroid phase
- Followed by a hypothyroid phase (negative feedback)
36
De Quervain's thyroiditis investigations
TFTs
Possibly scintigraphy to rule out other causes of hyperthyroidism
37
De Quervain's thyroiditis management
- Self limiting - NSAIDs & beta blockers
- rarely may need steroids
38
What two drugs can induce thyroiditis
amiodarone and lithium
39
How would amoidarone-induced thyroiditis present on TFTs
Amiodarone inhibits DIO1 - increased free T4, decreased free T3, normal TSH
40
How does hypo- and hyperthyroidism affect fertility
Hypo- and hyperthyroidism causes anovulatory cycles - reduced fertility
41
What part of neonatal development requires thyroxine
Maternal thyroxine important for all neonatal development but especially CNS
42
What happens to thyroid levels during pregnancy
- Increased demand on thyroid during pregnancy
- Increase in size
- Increased T4 production to maintain normal levels
- Increased plasma binding proteins
43
What happens to patients with pre-existing hypothyroidism who get pregnant & how is this managed
Patients who are already on thyroxine will have a relative thyroid deficiency as thyroid cannot meet increased demands. They should increase their thyroxine dose by 25g as soon as pregnancy is suspected & check TFTs monthly, increasing dose to aim for TSH <3 mU/l
44
Untreated hypothyroidism in pregnancy complications
Increased rate of abortion,
Preeclampsia, postpartum haemorrhage,
Placental abruption, preterm labour
Impacts on foetal neurophysical development
45
What is the effect of excess hCG in pregnancy & why is this a problem when interpreting TFTs
hCG increases thyroxine & so suppresses TSH
This means it presents the same as hyperthyroidism
46
How would you distinguish gestational hCG-associated thyrotoxicosis from hyperthyroidism
hCG-associated thyrotoxicosis would:
- Not be TRab antibody positive
- Resolve by 20 weeks gestation
& so only treat if no improvement by >20 weeks
47
Hyperthyroidism complications in pregnancy
- Infertility/ammenorhoea
- Spontaneous miscarriage, Stillbirth
- Thyroid crisis in labour
- Transient neonatal thyrotoxicosis (TRAb antibodies can cross the placenta)
48
Hyperthyroidism in pregnancy management
1. Check TRAb antibodies - if present alert neonatologist
2. Wait & see!
- If due to excess hCG/ hyperemesis, will settle by week 20
- If due to graves, may settle as pregnancy suppresses autoimmunity
3. If no improvement after week 20 - low does anti thyroid drugs (wait as late as possible due to side effects on foetus)
- Propylthiouracil 1st trimester
- Carbimazole 2/3rd trimester
49
What is post-partum thyroiditis
After delivery, the mother develops transient over-active thyroid, classically at around 6 weeks
& then at around 3 months has an underactive thyroid which can persist up to 1 year post partum
50
Post partum thyroiditis clinical features
- Occurs within 6 months of giving birth
- Initial hyperthyroidism & then hypothyroidism
- Small, diffuse, non-tender goitre
51
Post partum thyroiditis investigations
- Thyroid function tests
- Thyroid antibody tests
- Scintigraphy scan
52
Post partum thyroiditis
- No treatment for hyperthyroid phase
- If symptomatic hypothyroid phase treat with thyroxine
- If hypothyroidism persist after 1 year, will likely need thyroxine long term
53
When would you treat someone with subclinical hypothyroidism
If TSH > 10 or if pregnant
54
When would you treat for subclinical hyperthyroidism
If TSH <0.1% or if co-existing osteoporosis/fracture or AF
55
What is subclinical thyroid disease
Abnormal TSH with normal thyroid.
Risk of progression to hyper/hypothyroidism
56
What two conditions are associated with subclinical hyperthyroidism
Osteoporosis/ fractures
AF
57
Hyperthyroidism aetiology
Autoimmune
- Graves’ disease
- Hashitoxicosis
Malignancy
- Thyrotropinoma - TSH secreting pituitary adenoma (rare)
- Thyroid cancer
- Choriocarcinoma - trophoblast tumour secreting hCG
Nodular
- Toxic solitary nodule
- Toxic multinodular goitre
58
Thyrotoxicosis without hyperthyroidism aetiology
Subacute 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)
59
Grave’s disease pathophysiology
- Involves auto-antibodies to TSH receptor, thyroid peroxisomes and thyroglobulin
- The anti-TSH receptor antibodies stimulate the thyroid resulting in increased function
60
Hyperthyroidism clinical features
Weight loss, increased appetite, diarrhoea
Heat intolerance, hyperhidrosis
Anxiety, irritability
Tremor, muscle weakness & cramps
Tachycardia, palpitations, atrial fibrillation
Sparse, thin hair, rapid nail growth
Menstrual cycle changes
Double vision & Graves opthalmopathy
Goitre & thyroid bruit (in large goitres)
61
What is pretibial myxoedema
It typically occurs in grave’s disease but may occasionally occur in hashimoto’s thyroiditis
It is a form of diffuse mucinosis where there is an accumulation of excess mucopolysaccharides in the dermis & cutis of the skin of the lower leg
It causes swelling & thick, scaly plaques on the lower leg
62
What is thyroid arcropachy
Associated with Graves’ disease.
Causes thickening of extremities:
- digital clubbing
- hand & feet soft tissue swelling
- periosteal new bone formation
63
What causes graves eye disease
Autoimmune inflammation of the extra-ocular muscles, orbital fat and connective tissue due to the presence of TSH receptors
64
What are the clinical features of graves eye disease
Upper eyelid retraction
Lid lag
Swelling & erythema
Conjunctivitis
Bulging eyes (exopthalmos)
65
What 4 specific signs of Graves’ disease in a patient presenting with hyperthyroidism
- Pretibial myxoedma
- Thyroid arcropachy
- graves eye disease
- diffuse goitre
66
Graves’ disease treatment
First line - carbimazole (or PTU)
Symptomatic relief - beta blockers (or CCBs)
Relapsed graves - Radioiodine
Radioidodine contraindicated - thyroidectomy
67
Risks of radioiodine use in Graves’ disease
Hypothyroidism
68
Risks of thyroidectomy
- Recurrent laryngeal nerve palsy
- Hypothyroidism
- Hypoparathyroidism
69
Graves eye disease management
Smoking cessation! (Association with smoking)
Mild - lubricant
Severe - steroids/ radiotherapy/ surgery
70
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
71
Thyroid storm treatment
- High dose carbimazole
- β-blockers (propranolol)
- Potassium iodide
- Hydrocortisone
- IV fluids +/- inotropes
- Treat precipitating cause e.g. MI, infection, PE
72
What is a goitre
Enlarged palpable thyroid gland, which moves on swallowing
73
Goitre pathophysiology
- 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
74
Diffuse goitre aetiology (PAIN)
- Physiological - puberty, pregnancy
- Autoimmune - Hasimoto's thyroiditis, Grave's thyrotoxicosis
- Inflammation - acute (de Quervain's) thyroiditis
- Nutritional - iodine deficiency
75
Diffuse goitre clinical presentation
Entire thyroid gland swells and is smooth to the touch
Compression effects (SOB, dysphagia)
Symptoms of thyroid hormonal imbalance (though usually euthyroid)
76
Multi-nodular goitre Pathophysiology
Variation of response of follicular cells to external stimuli
=> Recurrent hyperplasia and involution
=> varying degree of fibrosis, haemorrhage and calcification
77
Multi nodular goitre presentation
Irregular enlarged thyroid due to nodule formation - thyroid feels bumpy on palpation
If toxic - S&S of hyperthyroidism, If active - euthyroid, no S&S
78
Multi nodular goitre investigations
- 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 symptoms
- Thyroid isotope scan:toxic or non-toxic
79
Multi nodular goitre management
- Usually can leave alone
- If toxic - radioiodine
- If structural problem/ significant extension - surgery
80
Solitary thyroid nodule aetiology
Benign
- Cysts
- Colloid nodule
- Follicular adenoma
- Hyperplastic nodule
Malignant
- Papillary thyroid carcinoma (80%)
- Medullary thyroid carcinoma
- Lymphoma
- Anaplastic
81
Solitary thyroid nodule red flags
- FHx of thyroid cancer
- Dysphagia/dysphonia
- Previous neck irradiation
- Firm, hard, immobile
- Cervical lymphadenopathy
- Nodule increasing in size
- Lesion >4cm
82
If it is a thyroid nodule would you expect it to move on swallowing
Yes - It is invested in pretracheal fascia
83
Why might a benign thyroid nodule be painful?
Pain is usually caused by intra-thyroidal bleed into a cyst
84
Solitary thyroid nodule investigations
- Thyroid function tests
- USS-FNA (ultrasound fine needle aspiration) - diagnostic!
- Thyroid scan (scintigraphy) - functioning or non functioning!
85
Why is thyroid scan (scintigraphy) helpful when investigating a thyroid nodule
Can be useful in distinguishing between functioning (hot) or non-functioning (cold) nodules
** Hot nodule is only rarely malignant
86
Describe the USS classification for thyroid nodules & how it guides investigations
- U2 - benign
- U3 - atypical → U3 and above do FNA
- U4 - probably malignant
- U5 - malignant
87
What is a follicular adenoma
A benign encapsulated tumour of the thyroid gland that arises from the follicular cells & is surrounded by a thin fibrous capsule
88
Is a follicular adenoma typically functioning or non functioning
Non-functioning
89
Describe the histological appearance of a follicular adenoma
neoplastic thyroid follicles encapsulated by a surrounding collagen cuff
90
Is an USS-FNA adequate to diagnosis a follicular adenoma
No - FNA can’t distinguish between a follicular adenoma & carcinoma. Must carry out a lobectomy with biopsy to diagnose
91
Describe papillary & follicular carcinomas
Differentiated thyroid cancer (DTCs) derived from follicular epithelium
92
What is the most common type of thyroid cancer
Papillary carcinoma
93
What is papillary carcinoma associated with
Hashimotos
Ionising radiation
94
What is follicular carcinoma loosely associated with
Iodine deficiency
95
Describe the histological features of papillary carcinoma
Differentiated follicular epithelial cells
Often cystic & may be calcified
96
Where do papillary carcinomas tend to spread
Nearby lymphatics e.g. cervical lymph nodes
97
Where do follicular carcinomas tend to spread
Haematogenous spread (bones, liver, lungs)
98
Papillary & Follicular carcinoma clinical features
Palpable nodule on thyroid (moves as swallow)
Metastasis symptoms & local effects
Swollen cervical lymph node (papillary carcinoma)
99
Papillary & Follicular carcinoma investigations
TFTs
USS-FNA (usually diagnostic)
May also involve excisional biopsy of lymph node
100
Papillary & Follicular carcinoma treatment
Subtotal/total thyroidectomy +/- Radioactive iodine
101
Papillary & Follicular carcinoma treatment follow up
Whole body iodine scanning, ~3-6 months post op
Regular TSH & Tg monitoring
102
What can be used as a tumour marker in Papillary & Follicular carcinoma
Thyroglobulin (Tg)! - Is the protein precursor of T4/T3, made by thyroid follicular epithelial cell
103
Describe anaplastic thyroid carcinoma
Undifferentiated and aggressive tumours derived from follicular epithelium
104
Anaplastic thyroid carcinoma clinical presentation
- Thyroid nodule, rapid growth
- Features of local infiltration/compression
- Cervical lymphadenopathy
- Signs of distant metastases
- History of differentiated thyroid cancer
105
Anaplastic thyroid carcinoma investigations
- Bloods: TSH
- Ultrasound scan
- US-FNA or biopsy: to confirm
106
Anaplastic thyroid carcinoma treatment
- Total thyroidectomy if resectable
+/- adjuvant radiochemotherapy as needed
- Do not respond to RAI!
107
Describe medullary carcinoma
Tumour of the parafollicular cells which secrete calcitonin (C-cells)
108
What genetic condition is medullary thyroid carcinoma associated with
Multiple Endocrine Neoplasia Type 2a (MEN2a)
109
Medullary carcinoma histological features
- Composed of spindle or polygonal cells arranged in nests, trabeculae or follicles
- Associated amyloid deposition (abnormally folded calcitonin)
110
Medullary carcinoma clinical features
- Neck mass with local effects
- dysphagia, hoarseness, airway compromise
- Paraneoplastic syndrome
- Diarrhoea - VIP production
- Cushings - ACTH production
111
Medullary carcinoma investigations
- Bloods:
- Measure serum base calcitonin
- 24 hour urinary metanephrines (phaeochromocytoma)
- Imaging:
- Neck USS and FNA (diagnostic)
- Further imaging to detect localised/advanced disease
- Genetics:
- check genetics for MEN
112
Medullary carcinoma investigations
- Bloods:
- Measure serum base calcitonin
- 24 hour urinary metanephrines (phaeochromocytoma)
- Imaging:
- Neck USS and FNA (diagnostic)
- Further imaging to detect localised/advanced disease
- Genetics:
- check genetics for MEN
113
Medullary carcinoma treatment
Localised disease
- Total thyroidectomy - curative
- Local recurrence in 35% of patients
Advanced disease
- May involve tyrosine kinase inhibitors (RET gene mutation)
Endocrine
flashcards
Decks in class (23)
# Cards
-
Hypopituitarism & Panhypopituitarism21
-
Endocrine Investigations10
-
Genetics2
-
Parathyroid Disorders28
-
Ovulation Physiology16
-
Male Hypogonadism & Gynaecomastia23
-
Ovulation Disorders & PCOS23
-
Adrenal Gland69
-
Acromegaly10
-
Hyperprolactinaemia & Prolactinoma8
-
Diabetes Insipidus8
-
Hormones & Receptors46
-
Hormone Summary32
-
Sodium & Water Balance32
-
Endocine Pancreas34
-
Obesity6
-
Physiology Of The Thyroid23
-
Physiology Of The Adrenal Gland9
-
Diabetic Drugs59
-
Diabetes58
-
Diabetic Emergencies23
-
Diabetic Complications27
-
Thyroid113
