1
Q
What releases TRH?
A
The paraventricular nuclei in the hypothalamus
2
Q
Where is TSH released from?
A
Thyrotrope cells in the anterior pituitary
3
Q
Is T3 or T4 more relevant?
A
T4 is more relevant because the thyroid releases T4 and T3 at a ratio of about 20:1 respectively, with T3 mainly being produced by peripheral conversion of T4
4
Q
Free T4 is roughly how much of total T4?
A
~1%
5
Q
What is T4’s half-life and what is the significance of this?
A
T4 has a half-life of about 1 week, therefore when monitoring the impact of an intervention, you need to wait several weeks before repeating LFTs
6
Q
List 10 clinical features of hypothyroidism
A
- Lethargy
- Weight gain
- Cold intolerance
- Constipation
- Hair loss
- Dry skin
- Depression
- Bradycardia
- Memory impairment
- Menorrhagia
7
Q
List 14 clinical features of hyperthyroidism
A
- Tachycardia
- Palpitations (atrial fibrillation)
- Hyperactivity
- Weight loss with increase appetite
- Heat intolerance
- Sweating
- Diarrhoea
- Fine tremor
- Hyper-reflexia
- Goitre
- Palmar erythema
- Onycholysis
- Muscle weakness and wasting
- Oligomenorrhea/ amenorrea
8
Q
List 7 clinical features of Grave’s Disease
A
- Exophthalmos/ proptosis
- Chemosis
- Diffuse symmetrical goitre
- Pretibial myxoedema (rare)
- Other autoimmune conditions
- Thyroid bruit
- Acropachy
9
Q
What would a raised TSH and a low T4 indicate?
A
Primary hypothyroidism
10
Q
What may a normal T4 in the context of a raised TSH suggest?
A
Sub clinical hypothyroidism (most commonly caused by an underlying autoimmune disease)
11
Q
List 7 causes of primary hypothyroidism
A
- Autoimmune thyroiditis (50%)
- Iodine deficiency or excess
- Thyroidectomy
- Therapy with radioactive iodine (treatment for hyperthyroidism)
- External radiotherapy
- Drugs
- Thyroid agenesis or dysgenesis
12
Q
What is primary hypothyroidism?
A
Reduced secretion of thyroid hormone from the thyroid gland itself
13
Q
What is secondary hypothyroidism?
A
Reduction in the hormones that stimulate the thyroid to produce thyroxine
14
Q
Is primary or secondary hypothyroidism more common?
A
Primary is more common (99%) vs secondary (1%)
15
Q
What would a normal/low TSH and a low T4 indicate?
A
Secondary hypothyroidism
16
Q
What are the two types of causes of secondary hypothyroidism?
A
Pituitary or hypothalamic (TRH is not measured as part of thyroid function tests as it is only released locally between hypothalamus and pituitary, therefore both structures are commonly grouped together into ‘secondary causes’ because an issue with TRH and TSH both show up as simply decrease TSH)
17
Q
List two pituitary causes of secondary hypothyroidism
A
- Pituitary adenoma (most common cause)
2. Pituitary surgery or radiotherapy
18
Q
List two hypothalamic causes of secondary hypothyroidism
A
- Hypothalamic or suprasellar tumour
2. Surgery or radiotherapy which damages the hypothalamic tissue
19
Q
What is primary hyperthyroidism?
A
Excessive production of T3 and T4 by the thyroid gland itself as a result of pathology within the thyroid gland itself
20
Q
What would a raised T3/T4 and a low TSH indicate?
A
Primary hyperthyroidism
21
Q
List 5 causes of primary hyperthyroidism
A
- Graves’ Disease (75% of all cases)
- Toxic multinodular goitre
- Toxic adenoma
- Iodine-induced (rare)
- Trophoblastic tumour (rare)
22
Q
What is secondary hyperthyroidism?
A
Stimulation of thyroid gland by excessive TSH
23
Q
What would a raised T3/T4 and a raised TSH indicate?
A
Secondary hyperthyroidism
24
Q
List 3 causes of secondary hyperthyroidism
A
- TSH-secreting tumour
- Chorionic-gonadotropin secreting tumour
- Thyroid hormone resistance (usually euthyroid) - TSH is resistant to T3/T4 negative feedback
25
In a patient with weight loss, which symptoms do you need to ask about in order to help you identify the cause?
Gastrointestinal symptoms (anorexia, abdominal pain, diarrhoea, symptoms of IBD, coeliac disease, peptic ulcer)
Symptoms of depression (low mood, loss of interest, sleep disturbance)
Symptoms of eating disorder (decrease food intake, self-induced vomiting, over-exercise)
Polyuria and polydipsia (T1DM)
Drug use (alcohol, cocaine, amphetamines, cannabis)
Night sweats or fever (malignancy, TB, HIV)
26
What can multinodular goitre result in?
Thyrotoxicosis (hyperthyroidism)
27
Can Graves’ disease remit?
Maybe
28
Can multinodular goitre remit?
No
29
What causes Graves’ disease?
Antibody stimulation of TSH-receptor (molecular mimicry)
30
Name 2 drugs which can cause thyrotoxicosis
1. Interferon
| 2. Amiodarone
31
What is an important effect of thyrotoxicosis?
Cardiovascular effects (higher pulse and BP, atrial fibrillation)
32
What is thyroid eye disease?
A separate autoimmune disease which causes exophthalmos (proptosis), chemosis and peri-orbital oedema
33
What are the risks of thyroid eye disease?
Raise intraocular pressure causing optic nerve damage
Exposure
Corneal ulceration
34
What is the treatment for thyroid eye disease?
Steroids
Immunosuppression
Surgical decompression
Radiotherapy
35
Describe treatment options for thyrotoxicosis
1. Beta-adrenergic blockers
2. Anti thyroid drugs
- carbimazole (methimazole)
- propylthiouracil
3. Radioactive iodine
4. Surgery
- sub-total, near-total thyroidectomy
36
How often does carbimazole need to be administered?
Once daily
37
How often does propylthiouracil need to be administered?
Three times
38
For how long do most patients receive anti thyroid drugs?
6-24 months and then stopped as 50-60% remission at 1 year (mostly if patient has Graves’ disease)
39
What are the two drug regimens for anti thyroid medications? Which is contraindicated in pregnancy?
Titration and block-replace. Block-replace contraindicated in pregnancy
40
How long will the patient be on anti thyroid medication in the titration and block-replace drug regimens respectively?
18-24 months for titration
6 months for block-replace
41
What are possible side-effects of anti thyroid medications?
1. Rash, itching (3-5%)
2. Arthralgia
3. Nausea, vomiting
4. Mild leukopenia
5. Agranulocytosis
42
In what form is radioactive iodine administered in the treatment of hyperthyroidism?
Capsule or liquid format
43
What is sometimes given as pretreatment for radio iodine therapy?
Anti thyroid medications
44
What can worsen after radioiodine? What groups is especially at risk? How it is treated?
Eye disease
- often transient
- especially in smokers
- reduced by prednisolone
45
What are potential risks of thyroid surgery?
1. Parathyroid damage
2. Vocal cord paralysis
3. Bleeding
4. Keloid scars
46
Which clinical features are only found in hyperthyroidism due to Graves’ disease?
1. Exophthalmos
2. Pretibial myoxedema
3. Thyroid acropachy
4. Ophtalmoplegia
47
What is the thyroid composed of?
Follicles filled with colloid. The follicles are lined with columnar epithelium made up of thyroid follicular cells which make tyrosine bound to thyroglobulin (a T4 precursor). The thyroid also has interspersed C-cells which make calcitonin
48
What controls the production of thyroglobulin by thyroid follicular cells
TSH which activates TSHR
49
What iodinates tyrosines on the luminal membrane?
Thyroid peroxidase (TPO)
50
What antibodies relevant to the thyroid can be tested?
TPO abs
TSH-R abs
51
What important advice needs to be given to patients prescribed carbimazole?
Report signs of infection (especially a sore throat). The doctor would check their FBC to look for signs and symptoms of infection and stop treatment with carbimazole if white cell count is too low (due to risk of neutropenia and agranulocytosis)
52
What is the mechanism of neonatal hyperthyroidism?
Thyroid stimulating antibodies (in Graves’ disease) can cross placenta and stimulate the thyroid gland in the foetus
53
What is the thyroid gland attached to?
Thyroid cartilage and upper end of trachea (and so moves on swallowing)
54
Where is T4 deiodinated to T3?
In the peripheral tissues such as the liver and kidney
55
What is the role of thyroid hormones?
Important role in metabolism including oxygen consumption, cardiac output, heart rate, growth, brain development and sexual maturation
56
Which symptoms have the greatest ability to discriminate between euthyroidism and hypothyroidism?
Cold intolerance
Myalgia and muscle weakness
Constipation
Hoarse or deep voice
57
What is the most common cause of primary hypothyroidism in adults in the UK?
Chronic autoimmune thyroiditis (Hashimoto’s) - more common women and associated with other autoimmune diseases
58
Where is primary hypothyroidism due to iodine deficiency more common?
Places with endemic iodine deficiency e.g. South America - the problem is overcome in the population by use of iodised salt
59
If carbimazole is not sufficiently effective, what are possible treatment options?
1. Thyroidectomy
| 2. Radioactive iodine (possibly lower complication rate but contraindicated in pregnancy and breastfeeding)
60
How does radioactive iodine work?
Take orally and rapidly taken up by the thyroid gland. From there the radiation is released and destroys the tissue over a period of 6-18 weeks
61
What are early complications of radioactive iodine?
Neck discomfort and precipitation of Graves’ opthalmopathy
62
What are long term complications of radioactive iodine?
Progressive incidence of hypothyroidism (most patients require treatment with thyroxine after several years)
63
What are the possible side effects of over replacement of thyroxine?
Atrial fibrillation and osteoporosis
64
In a patient presenting with a lump in their thyroid gland, what red flags should you look out for?
Anything indicating possible malignancy: dysphagia, neck pain, hoarseness, history of radiation to the neck, family history of thyroid cancer
65
What is the investigation of choice for a thyroid lump?
Ultrasound with fine needle aspiration
66
What is the investigation of choice for a thyroid lump?
Ultrasound followed by a fine needle aspiration
67
What are the main histological types of thyroid carcinoma?
```
Papillary carcinoma (70%)
Follicular carcinoma (20%)
Medullary cell carcinoma (5%)
Anaplastic carcinoma (3%)
Lymphoma (2%)
```
68
Where are papillary and follicular carcinomas derived from?
Follicular epithelium
69
What is the prognosis for papillary and follicular carcinomas?
Good prognosis as well differentiated
70
Where do medullary cell carcinomas arise from?
Calcitonin-producing C-cells
71
In which age group do papillary carcinomas usually arise?
Middle-aged women
72
What is the most common site of papillary carcinoma metastasis?
Local lymph nodes in neck
73
How is thyroid cancer treated?
Surgery (total thyroidectomy or lobectomy)
Post-operative radioactive iodine treatment in some cases
Thyroid hormone suppression (to suppress TSH so that tumour growth is not stimulated)
74
What is Hashimoto’s thyroiditis?
Autoimmune disease causing T-cell infiltration (autoantibodies to TPO and Tg) leading to destruction of thyroid tissue, resulting in hypothyroidism
75
What can Hashimoto’s cause in early stages?
Firm goitre
76
In what population is Hashimoto’s most commonly seen?
Women over 40
77
In women with hypothyroidism, other condition may result from their heavy periods?
Iron deficiency anaemia
78
How is hypothyroidism treated?
Thyroxine T4 (once daily dose)
79
What is a problem with thyroxine medication?
Iron can interfere with the absorption of T4
80
In a patient with hypothyroidism treatment with T4 but who is still tired despite normal TSH, what might you consider?
Potentially a case for administering T3 too?
Addison’s disease?
Anaemia?
Other associated diagnosis?
81
List 4 causes of diffuse goitre
Graves’ disease
Hypothyroidism (Hashimoto’s)
Colloid goitre (euthyroid)
Iodine deficiency (drugs e.g. lithium)
82
Other than thyroid status, what else should you look out for in a patient with goitre?
Pressure symptoms: mobility, skin tethering, lymphadenopathy, recurrent laryngeal nerve palsy
83
A patient returns to her GP for a review. She has been taking 50mcg of thyroxine daily for 8 weeks. Her constipation has resolved but she is still feeling tired. Her thyroid function tests show a normal T4 but a raised TSH. What dose of thyroxine should her GP prescribe?
Increase dose to 75mcg daily - TSH is elevated and the patient still has symptoms of hypothyroidism. BNF recommends the dose of thyroxine is increased in 25mcg steps
84
Martin Kelly is a 75 year old man who presents with a lack of energy. He has a history of myocardial infarction and his week angina attacks. His thyroid function tests so a low T4 and a high TSH. What dose of thyroxine should Martin Kerry be prescribed?
Elderly patients and those with known ischemico heart disease with severe hypothyroidism should be prescribed thyroxine in a low dose of 25mcg daily which can be increased in 25mcg steps every 4 weeks. This is because higher doses of thyroxine may worsen angina or precipitate myocardial infarction
85
Susan Preston has noticed a lump in the left side of her neck for the last few weeks. When her GP examines her, he detects a solid lump 2cm in diameter in the left lobe of her thyroid and also enlarged left sided cervical lymph nodes. Susan volunteers that her brother had one adrenal gland removed last year due to a tumour. What is the most likely diagnosis?
Medullary cell carcinoma is the most likely due to the family history. It can be an inherited condition and is associated with phaechromocytoma (adrenal tumour) and hyperparathyroidism
86
Louise Reed is a 28 year old lady who delivered a healthy baby boy 10 weeks ago. She had a difficult time after delivery. She suffered post-partum haemorrhage and required a blood transfusion. Since the delivery, Louise has felt exhausted and was disappointed that she was unable to breast feed as she couldn’t produce any milk. Her thyroid function tests show low T4 and low TSH. What is the most likely diagnosis?
Secondary hypothyroidism - this is a typical presentation of secondary hypothyroidism due to pituitary infarction post-partum (Sheehan’s syndrome). The patient is likely to also be deficiency in ACTH, gonadotrophins and prolactin.
87
A 28-year-old man presents to his GP with a 4cm mobile anterior neck mass. A fine needle aspirate is performed which reveals cells with ‘orphan Annie eye’ nuclei and psammoma bodies.
What is the most likely diagnosis?
Papillary carcinoma
'Orphan Annie eye' nuclei are pathognomonic for papillary carcinoma. Although clinically a thyroglossal duct cyst is likely, the histology finding indicate papillary carcinoma.
88
What is the most common type of thyroid carcinoma?
Papillary carcinoma
89
Which of the following features is NOT typical for Graves disease?
1. Hyperplasia of the follicles
2. Scalloping of the colloid
3. Irregular shaped follicles
4. Infiltration of mononuclear cells into retro-orbital connective tissues
5. Extensive infiltration of the mononuclear cells into the thyroid parenchyma
Extensive infiltration into the parenchyma is typically seen in Hashimoto's thyroiditis. All other features are typical of Graves disease. In Graves disease IgG TSH-like autoantibodies cause stimulation of the TSH receptor causing hyperplasia of the follicles. These follicles are irregular shape and display scalloping of the colloid.
90
A 37-year-old woman presents to the clinic with 2 days of sudden onset pain in the anterior neck radiating to the jaw. She is otherwise well having reported a full recovery from a ‘cold’ a week ago.
What findings are NOT consistent with her diagnosis?
1. Dense fibrosis of the thyroid gland
2. Neutrophilic infiltration of the thyroid
3. Formation of micro-abscesses
4. Multi nucleated giant cells encapsulating colloid fragments
Dense fibrosis of the thyroid gland is usually seen in Riedel's thyroiditis, a rare form of thyroiditis showing fibrosis of the thyroid, neck structures and sometimes other areas of the body. The clinical picture of sudden onset neck pain radiating to the facial region, including the ears, in a 30-50 year old female following a upper respiratory tract infection indicates subacute thyroiditis, also called de Quervain’s thyroiditis.
91
A 62-year-old gentleman presents to the clinic with a 5cm painless neck mass as well as diarrhoea for the past 3 months. A biopsy is taken and he is subsequently diagnosed with medullary carcinoma.
Which of the following features is consistent with a medullary carcinoma?
1. Grossly soft and tender mass
2. Diagnosis of MEN-1 syndrome
3. Haematologic metastatic spread
4. High levels of calcitonin
5. Localised amyloid deposits
High level of calcitonin. Malignant cells in an amyloid stroma is a typical feature of medullary carcinoma. It is associated with MEN-2 syndrome, local and lymphatic spread and high levels of calcitonin are seen due the proliferation of parafollicular C-cells (which produce calcitonin). Clinically the mass is usually firm and painless.
92
Which of the following features is NOT consistent with follicular carcinoma?
1. Malignant proliferation of follicular cells
2. Follicular carcinomas are diagnosed via fine needle aspiration
3. More common in women than men
4. Commonly have PI-3K/AKT signally pathway mutations
5. Uniform cells forming small colloid containing follicles
A major differentiating feature between follicular carcinoma and follicular adenoma is the carcinomas ability to break through the follicular capsule. This is unable to be distinguished via fine needle aspiration because the needle breaks through the capsule. All other features are descriptive of follicular carcinoma, with approximately 1/3rd having PI-3K/AKT pathway mutations.
93
A 46-year-old female presents to the preadmission clinic and is found to have a 3cm anterolateral firm painless neck mass along with a minor decrease in calcium serum levels.
What is the most likely diagnosis?
Medullary carcinoma is the proliferation of parafollicular C cells which produce calcitonin. Calcitonin decreases serum calcium, however it should be noted that this is not a prominent feature in medullary carcinoma.
94
Which of the following features are NOT consistent with anaplastic carcinoma?
1. Large, pleomorphic giant cells
2. Occasional osteoclast-like multinucleated giant cells
3. Spindle cells
4. Poor prognosis
5. Positive thyroglobulin markers
Anaplastic carcinomas are highly anaplastic, undifferentiated cells and are usually negative for any markers of thyroid differentiation such as thyroglobulin.
95
An 18-year-old female presents with a painless 1cm mass in the anterior neck region. A biopsy is taken revealing fluid contained within pseudostratified columnar epithelium.
What is the most likely diagnosis?
Thyroglossal ducts are cystic dilations of thyroid duct remnant. The thyroid gland embryologically develops at the base of the tongue and then migrates to the anterior neck, a thyroglossal duct cyst may develop at any stage if the duct fails to close.
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