Thyroid Pathology Flashcards
1
Q
List the 3 most common embryological abnormalities that affect the thyroid gland
A
Failure of descent – lingual thyroid
Excessive descent – retrosternal location in mediastinum
Thyroglossal duct cyst-
2
Q
How does a thyroglossal duct cyst present
A
localised lump in midline of neck
3
Q
How can the size of the thyroid gland be pathological
A
Enlargement can have many causes but has potential to cause local mass effects - most severe is complicating the airway
Atrophy can lead to reduced function
4
Q
What is a goitre
A
enlargement of thyroid for any reason
5
Q
What are the 2 most common autoimmune conditions that affect the thyroid
A
Grave’s disease - hyperfunction
Hashimoto’s thyroiditis - hypofunction
Both cause inflammation
6
Q
Does autoimmune thyroiditis have a genetic cause
A
There is susceptibitly associated with HLA haplotype
Incidence increased in family members
Associated with other autoimmune diseases - If you have one type then you are at higher risk of others
7
Q
What causes thyrotoxicosis
A
Excess of T3 and T4 85% due to Graves Tumours of the thyroid can cause excess production Thyroiditis Ectopic production Excessive intake of thyroid drugs
8
Q
Grave’s disease is an autoimmune condition - true or false
A
True
9
Q
What is the cause of symptoms in Grave’s disease
A
Auto-antibodies to TSH receptors - specific to Grave’s (TRAb)
They stimulate the thyroid gland (mimic TSH) to produce more hormones
This bypasses the feedback loop
Decreased TSH but increased free T4/3
10
Q
What are the clinical features in Grave’s
A
Hyperthyroidism with diffuse enlargement of the thyroid (can come with a bruit)
Eye changes - exophthalmos and inflammation
Pretibial myxoedema - bilateral plaques
Severe clubbing - thyroid acropachy
11
Q
What can cause hypothyroidism
A
Mostly Hashimoto's thyroiditis - autoimmune Iodine deficiency Certain drugs Post therapy Congenital abnormality IBEM
12
Q
What causes the hypothyroidism in Hashimoto’s
A
Autoantibodies (anti-TPO) attack enzymes involved in hormone production and damage the thyroid tissue
Gradual failure
Also causes inflammation so inflammatory cells and cytokines also cause damage
13
Q
Which age group tends to get Hashimoto’s
A
45-60
More common in women
14
Q
Which age group tends to get Grave’s
A
20-40
More common in women
15
Q
Which other conditions does Hashimoto’s increase your risk of
A
Other auto-immune conditions
B cell NHL - lymphoma
16
Q
Describe the presentation of a diffuse goitre
A
Usually euthyroid - functions normally
Get mass effects
T3 / T4 normal but TSH high
17
Q
What causes diffuse goitres
A
Ingestion of substances limiting T3/T4 production
Inborn errors of metabolism
Most cases – cause unknown
18
Q
What causes a multinodular goitre
A
Evolution from long standing simple goitre
Recurrent hyperplasia and involution
Enlargement
19
Q
What can multinodular goitres cause
A
Rupture of follicles, haemorrhage, scarring, calcification
Mass effects
20
Q
What are the 4 types of carcinoma that can affect the thyroid (from most common to least)
A
Papillary - 75-85%
Follicular -10-20%
Medullary - 5%
Anaplastic - <5%
21
Q
Describe adenomas of the thyroid
A
Discrete solitary mass
Benign
Encapsulated by a surrounding collagen cuff
Composed of neoplastic thyroid follicles
Usually non-functional but may secrete thyroid hormones
22
Q
Which age and sex are mostly affected by carcinomas
A
ANY age
Female predominance
23
Q
Which cells do thyroid carcinomas develop from
A
Folliuclar - Follicular epithelium
Papillary - papillary cells
Medullary - parafollicular C cells
Anaplastic - poorly differentiated so hard to tell
24
Q
What can lead to papillary thyroid carcinomas
A
Ionising radiation
Mutation in the RAS/ MAP kinase pathway
25
What can lead to follicular thyroid carcinomas
Iodine deficiency
Mutations in PI3K/ATK pathway
Variety of other mutations
26
What can lead to medullary thyroid carcinomas
Mutations in MEN2
27
What can lead to anaplastic thyroid carcinomas
```
Many mutations (similar ones to P and F)
p53 mutation
```
28
How do papillary carcinomas present
Usually solitary nodule in thyroid
Often cystic
May be calcified or multifocal
May have lymph node mets
Normal or slightly raised TSH
29
What are the main symptoms of papillary carcinoma
```
Lesion in thyroid or nodes
Hoarseness
Dysphagia
Cough
Dyspnoea
(resp features suggest advanced disease)
```
30
How does papillary carcinoma spread
Usually to lungs
| Haem spread uncommon
31
How are the survival rates for papillary carcinoma
Good
| 95% at 10 years
32
How does follicular carcinoma present
```
Usually single nodule
Slowly enlarging
Painless
Non-functional
Rarely presents with mets
Invasive growth pattern
Older age group
```
Normal or slightly raised TSH
33
How does follicular carcinoma spread
Through blood
Mets in bone, lungs and liver
Node spread is rare
34
What is the prognosis of follicular carcinoma
Depends on extent of invasion and stage at presentation
| Mortality 50% at 10 years
35
What is medullary carcinoma associated with
Multiple Endocrine Neoplasia II - if you have this genetic background then it can present very young
Familial medullary carcinoma - seen in adults
Amyloid deposition
36
How does medullary carcinoma present
Sporadic - single nodule
Familial case - bilateral or multicentric
Some form of thryoid mass
Calcitonin or CEA elevated
Composed of spindle or polygonal cells arranged in nests
Associated with amyloid deposition
37
What are the symptoms of medullary carcinomas
Neck mass with local effects (dysphagia, hoarseness, airway compromise)
Paraneoplastic syndromes: Diarrhoea due to VIP production or Cushings due to ACTH production
38
What is the treatment for medullary carcinoma
Total thyroidectomy
5 year survival 70-80%
May recur
39
List some good prognostic factors for medullary carcinoma
Young age
Female
Familial setting
Tumour size and if confined to the gland
40
Describe the presentation of anaplastic carcinoma
Undifferentiated and aggressive tumours
Usually older patients and those with history of thyroid cancer
Rapid growth and involvement of neck structures (airway issues, hoarseness) and death
41
How do you determine the likelihood of thyroid malignancy
```
Thyroid cytology - aspirate and analyse
Thy 1 – insufficient/uninterpretable
Thy 2 – benign
Thy 3 – atypia probably benign/equivocal
Thy 4 – atypia suspicious of malignancy
Thy 5 – malignant
```
42
What cells make up the parathyroid gland
Chief cells
round cells with moderate cytoplasm and bland round central nuclei
Secrete PTH
43
What can cause Hyperparathyroidism
Usually small adenoma
Hyperplasia
Secondary to renal failure, low Ca intake, Vit D deficiency (overactive to compensate)
It can become autonomous
44
What are the symptoms of hyperparathyroidism
```
Bone disease - pain, fracture, osteoporosis
Renal stones
Constipation, nausea
Gall stones
Depression
Lethargy, weakness and fatigue
Calcification of valves
```
45
What can cause hypoparathyroidism
Post-op
Rare congenital absence in Di George syndrome
Very rare
46
What are the symptoms of hypoparathyroidism
Tetany - muscle spasm
Altered mental state - anxiety, depression, confusion etc
Calcification of lens and cataract formation
Prolong QT interval in ECG
Basal ganglia calcification, Parkinsonian
47
what is a key sign of a thyroglossal cyst
It will move when you stick out your tongue
48
What is a potential complication of thyroglossal cyst
If it gets too large it can compress other structures such as airway
49
How does hypo/hyperthyroidism impact fertility
Reduced fertility
| Causes anovulatory cycles
50
How is the thyroid gland affected by pregnancy
increased demand during pregnancy - increased size and production
plasma protein binding increases
maternal thyroxine is important for foetal development - especially CNS
51
How do you manage pre-existing hypothyroidism in pregnancy
Increase dose of thyroixine by 25mcg as soon as pregnant
On average dose will be increased by 50%
regular testing is needed
52
What are the potential complications of not treating hypothyroidism in pregnancy
Increased abortion, preeclampsia, abruption, postpartum haemorrhage, preterm labour,
Affects foetal neuropsychological development
53
What impact does hCG have on thyroxine
Increased it secretion as needed in pregnancy
| Same affect as TSH as similar structure
54
What common pregnancy condition can mimic hyperthyroidism
Hyperemesis gravidarum - extreme morning sickness
| Raised hCG caused Gestational hCG-asscociated Thyrotoxicosis
55
How do you distinguish between Hyperemesis and Hyperthyroidism?
Hyperemeiss will have high hCG and low TSH
Wont be TRab antibody positive
Will resolve by 20 weeks
Treat for hyperthyroidism if it persists past this stage
56
What complications can hyperthyroidism cause in pregnancy
Infertility
Spontaneous miscarriage
Stillbirth
Thyroid crisis in labour - particularly in C section
57
What causes Transient Neonatal thyrotoxicosis
Thyroid receptor antibodies cross placenta and cause baby’s thyroid to become hyperactive – will go away eventually once the antibodies leave the system (baby doesn’t produce its own)
58
How do you manage hyperthyroidism in pregnancy
At first wait to see if it settles (around 20 weeks)
If it doesn't give B blockers if needed
Low dose anti-thyroid drugs - Propylthiouracil 1st trimester
- Carbimazole 2/3rd trimester
59
What are the risks of taking carbimazole in pregnancy
Can cause embryopathy in 1st trimeter
Scalp abnormalities
GI abnormalities
Choanal & Oesophageal atresia
60
What are the risks of taking propylthiouracil in pregnancy
Risk of liver toxicity
| Best avoided except possibly in 1st trimester, but then switch to CBZ
61
Describe Post Partum Thyroiditis
Thyroxine rises 6-8 weeks after delivery – becomes overactive
Then crashes after 4 months and becomes underactive - this is linked to post-partum depression
Usually corrects over time
62
How do you treat post-partum thyroiditis
Don’t give carbimazole in hyper phase as it makes the crash much worse
Do give thyroxine during hypo phase – if symptomatic
63
What is a primary thyroid disease
Disease affecting the thyroid gland itself
Can occur with or without a goitre
Autoimmune disease is the most common cause
64
What is a secondary thyroid disease
One with no thyroid gland pathology
Usually caused by hypothalamic or pituitary disease
Much rarer than primary
65
Describe the hormone levels in primary hypothyroidism
Free T3/4 low
| TSH high
66
Describe the hormone levels in primary hyperthyroidism
Free T3/4 high
| TSH low
67
Describe the hormone levels in secondary hypothyroidism
Free T3/4 low
TSH low (or ‘normal’)
TSH isn’t able to increase to counteract low T3/4
68
Describe the hormone levels in secondary hyperthyroidism
```
Free T3/4 high
TSH high (or ‘normal’)
Often a TSH secreting tumour of pituitary (extremely rare) so doesn’t respond to negative feedback and will continuously stimulate release of thyroid hormones
```
69
List some causes of Goitrous primary hypothyroidism
```
Chronic thyroiditis (Hashimoto’s thyroiditis)
Iodine deficiency
Drug-induced (e.g. amiodarone, lithium)
Maternally transmitted (e.g. antithyroid drugs)
Hereditary biosynthetic defects
```
70
List some causes of non-goitrous primary hypothyroidism
Atrophic thyroiditis
Post-ablative therapy (e.g. radioiodine, surgery)
Post-radiotherapy (e.g. for lymphoma treatment)
Congenital developmental defect
71
List some causes of self-limiting primary hypothyroidism
Following withdrawal of antithyroid drugs
Subacute thyroiditis with transient hypothyroidism
Post-partum thyroiditis
72
What are the hair and skin clinical features of hypothyroidism
```
Coarse, sparse hair
Dull, expressionless face
Periorbital puffiness
Pale cool skin that feels doughy to touch
Vitiligo may be present
Cold intolerance
Fluid retention - pitting oedema
```
73
What are the cardiac features of hypothyroidism
Bradycardia
Worsening of pre-existing heart failure
Cardiac dilatation
Pericardial effusion
74
What are the metabolic features of hypothyroidism
Hyperlipidaemia
Decreased appetite
Weight gain
Low metabolic rate
75
What are the GI features of hypothyroidism
Constipation
(Megacolon and intestinal obstruction)
(Ascites)
76
What are the respiratory features of hypothyroidism
Deep hoarse voice - uncommon
Macroglossia - enlarged tongue
Obstructive sleep apnoea
77
What are the neurological/ CNS symptoms of hypothyroidism
```
Decreased intellectual and motor activities
Depression, psychosis, neuro-psychiatric
Muscle stiffness, cramps
Peripheral neuropathy
Prolongation of the tendon jerks
Carpal tunnel syndrome
Decreased visual acuity
```
78
What are the gynae/reproductive symptoms of hypothyroidism
Menorrhagia - heavy periods
Later oligo- or amenorrhoea - missed periods
Hyperprolactinaemia - ↑TRH causes ↑ PRL secretion
79
Describe the typical biochemical picture of primary hypothyroidism
```
Increased TSH
Decreased free t3/4
Increased mean cell volume
Increases creatinine kinase
Increased LDL cholesterol
Hyponatraemia
Hyperprolactin
```
80
How do you treat hypothyroidism
Younger patients: start levothyroxine at 50-100 μg daily
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 every change and then every 12-18 months
81
What is a myxoedema coma
Severe and often a first presentation of untreated hypothyroidism - causes a coma
Typically affects elderly women
High mortality
82
What are the symptoms of a myxoedema coma
Bradycardia, heart block, T wave inversion, prolonged QT
Type 2 respiratory failure - hypoxaemia and hypercapnia
Hypothermia
Also get very oedematous - hold onto water, become hyponatraemic and may get pleural effusions
83
How do you treat myxoedema coma
Intensive care, remember – A, B, C!
Passively rewarm
Cardiac monitoring
Antibiotics - broad spectrum
Close monitoring of BP, urine output, oxygen
Give thyroxine
Can give T3 if you have it as it has a more rapid onset
84
What is thyrotoxicosis
clinical, physiological and biochemical state arising when the tissues are exposed to excess thyroid hormone
Caused by hyperthyroidism
85
What are the cardiac symptoms of thyrotoxicosis
Palpitation, atrial fibrillation (AF)
Increased CO - force and rate
Cardiac failure (very rare)
86
What are the CNS symptoms of thyrotoxicosis
```
Tremor
Sweating
Anxiety and irritability
Sleep disturbance
heat Intolerance
```
87
What are the GI symptoms of thyrotoxicosis
Frequent, loose bowel movements
88
What are the eye symptoms of thyrotoxicosis
```
Lid retraction (not specific to Graves’)
Double vision (diplopia)
Proptosis (Graves’)
```
89
What are the hair and skin symptoms of thyrotoxicosis
Hair change – brittle, thin hair
| Rapid fingernail growth
90
What are the reproductive symptoms of thyrotoxicosis
menstrual cycle changes - lighter and less frequent
| loss of libido
91
What are the muscle symptoms of thyrotoxicosis
Muscle weakness - especially in thighs and upper arms
92
What are the metabolic symptoms of thyrotoxicosis
weight loss
increased appetite
due to increase in metabolic rate
93
How does thyrotoxicosis affect thermogenesis
Intolerance to heat
94
What conditions associated with hyperthyroidism can cause thyrotoxicosis
```
Excessive thyroid stimulation
Graves’ disease
Hashitoxicosis
Thyrotropinoma (very rare)
Thyroid cancer
Thyroid nodules with autonomous function
```
95
What is hashitoxicosis
early stage of hashimotos where they get temporary hyperthyroid before their gland failure and they go hypo
96
What conditions NOT associated with hyperthyroidism can cause thyrotoxicosis
Thyroid inflammation (thyroiditis)
- Subacute (de Quervain’s)
- Post-partum thyroiditis
- Drug-induced (e.g. amiodarone)
Exogenous thyroid hormones
- Over-treatment with levothyroxine
- Thyrotoxicosis factitial
Ectopic thyroid tissue
- Metastatic thyroid carcinoma
- Struma ovarii (teratoma containing thyroid tissue)
97
What causes a thyroid bruit
Hypervascularity of thyroid
Seen in Grave's
Associated with large goitres
98
Is smoking related to Grave's disease
YES
| very significant - must encourage cessation
99
describe nodular thyroid disease
seen in older patients and has insidious onset
thyroid may feel nodular, often assymterical
Get high fT3/4 and low TSH
100
What is a thyroid storm
Medical emergency
Most severe presentation of overactive thyroid - rare
Get respiratory and cardiac collapse, hyperthermia and exaggerated reflexes
Typically seen in hyperthyroid patients with an acute infection/illness or recent thyroid surgery
Has a high mortality
101
How do you treat a thyroid storm
Lugol’s Iodine - shocks the gland to buy you time
Glucocorticoids
PTU
β-blockers
Lithium can also be used - reduces T4 to T3 conversion
May give muscle relaxants to reduce tremor and heat production
May need ICU for fluids, ventilation monitoring
102
Describe the use of carbimazole
```
1st line drug
Once daily dosing
Lower rate of side effects compared to PTU (14 vs 52%)
Risk of aplasia cutis in early pregnancy
Treats hyperthyroidism
```
103
Describe the use of propylthiouracil
```
1st line only in 1st trimester of pregnancy
Twice daily dosing
10x less potent compared to carbimazole
Inhibits DIO1 (↓T4 to T3 conversion)
1:10,000 risk of liver failure
```
104
What are the side affects of anti-thyroid drugs
Generally well tolerated
allergic type reaction - rash, urticaria etc
PTU can cause jaundice and liver failure
Agranulocytosis
105
How are B blockers used in treatment of hyperthyroidism
Propranolol is the drug of choice
| Useful for immediate symptomatic relief - slows heart
106
How is radioiodine used in treatment of hyperthyroidism
1st choice for relapsed Grave's and nodular thyroid disease
Cant use in pregnancy
Easy to give but must avoid other people until radioactivity has decreased
High risk of hypothyroidism when used in Graves’ disease
107
How is thyroidectomy used in treatment of hyperthyroidism
Used when radioiodine is contraindicated
Leaves you with a scar
Comes with the surgical/anaesthetic risk
108
What is thyroiditis
inflammation of the thyroid
109
What can cause thyroiditis
```
Hashimoto’s
De Quervain’s/subacute (viral)
Post-partum
Drug-induced (amiodarone, lithium)
Radiation
Acute suppurative thyroiditis (bacterial)
```
110
Describe subacute thyroiditis
Ages 20-50 years
May be triggered by viral infection
May be associated with neck tenderness, fever, or other viral symptoms
Usually self limiting
111
What is sick euthyroid syndrome
Non-thyroid based illness
Occurs in unwell, hospitalised patietns
Severe infection, sepsis or recent surgery can lead to abnormal thyroid function
Will give abnormal test results at the time but no real issue
112
Describe typical hormone levels in someone with Grave's disease
High T4
T3 either high or normal
Low TSH
113
What causes exophthalmos in Grave's disease
Water build up and retroorbital swelling
Collagen fibres may also be deposited
Eyes become pushed forward and may have difficulty with eye movement and redness
114
What are toxic multinodular goitres
Functioning autonomous nodules that secrete large amounts of thyroid hormones
2nd most common cause of hyperthyroidism
115
Describe de Quervain's thyroiditis
Caused by acute inflammatory process - usually viral
Cause of hyperthyroidism
Get usual symptoms as well as fever, malaise and local tenderness
116
Describe the appearance of Grave's disease on Thyroid scintigraphy
If the thyroid is enlarged and has high uptake across whole gland it is graves
117
Describe the appearance of thyroiditis on Thyroid scintigraphy
Homogenously reduced tracer uptake
118
Describe the appearance of a multi-nodular goitre on Thyroid scintigraphy
Focal uptake
| One large area of increased uptake (black)
119
What structure can be damaged by thyroid surgery
Recurrent larygeal nerve hooks around the back so can be damaged - will lead to a hoarse voice
120
How can amiodarone cause a thryoid abnormality
It contains a lot of iodine which can then be used in the production of thyroid hormone
121
List primary thyroid causes of hyperthyroidism
Graves
Toxic adenomas
Multinodular goitres
Thyroiditis
122
How can you measure thyroid hormones
Blood test for T4 and T3 and TSH levels
T3 and T4 are measured as free hormones rather than the total including those bound to other proteins as only the free is physiologically active
123
Why does radioactive iodine not affect other organs when given
Thyroid is the only gland which uses iodine so can give it safely without affecting other organs
