Thyroid

Question 1

Which gender are thyroid disease more common in?

Answer 1

women

Question 2

What joins the right and left lobe of the thyroid?

Answer 2

isthmus

Question 3

What is the histology of the thyroid?

Answer 3

follicle - simple cuboidal epithelium lining a central colloid filled lumen

Parafollicular cells or C cells (secrete calcitonin which reduces blood plasma Ca levels)

Question 4

What inhibits TSH?

Answer 4

dopamine
somatostatin
glucocorticoids
benzodiazepines

Question 5

What hormones does thyroid produce?

Answer 5

Thyroxine - T4 = pro-hormone

Tri-iodothyronine - T3 = active hormone

• 20% from thyroid gland
• 80% from peripheral conversion of T4 in liver, kidneys and muscle

T4 converted to T3 by deiodinases enzymes

Question 6

What is the ratio of T4:T3?

Answer 6

T4:T3 14:1

Question 7

What proportion of thyroxine is bound to protein?

Answer 7

99.95%

Question 8

What proteins can thyroxine be bound to?

Answer 8

thyroxine binding globulin - 70%
half life = 5 days

transthyretin- 20%
half life = 2 days

Albumin = 10%

Question 9

What does subclinical mean?

Answer 9

asymptomatic

Question 10

Subclinical hypothyroidism results

Answer 10

raised TSH
normal T4

• usually due to early autoimmune hypothyroidism
• usually do not treat unless TSH is very high (>10) or anti-TPO positive; treatment = normalize TSH

Question 11

Subclinical hyperthyroidism

• thyroid test results
• common causes
• what drugs could be causing it?

Answer 11

low TSH, normal T3 and T4

May be due to Graves, TMNG, or exogenous thyroxine ingestion

Also seen in patients with non-thyroidal illness, or on certain medications (amiodarone, glucocorticoids, anticonvulsants)

Amiodarone – high iodine content and direct toxic effect on thyroid follicular cells (inhibits T4 to T3 conversion).

Amiodarone-induced hypothyroidism occurs in 15% patients. Treatment: Levothyroxine and discontinuation of amiodarone if possible.

Amiodarone-induced thyrotoxicosis rare - <5% / treatment: ATD (+/- prednisolone), and discontinuation of amiodarone

SEEK cardio input

Increased risk of atrial fibrillation & osteoporosis

Question 12

Follicular adenoma

Answer 12

benign cause of solitary thyroid nodules

most non-functional

Question 13

Thyroid malignancy

• RF
• investigations

Answer 13

More likely if:
Patient is young (<20) or old (>60)
Nodule grows rapidly
Compressive symptoms – hoarse voice, difficulty breathing or swallowing
FH of endocrine malignancy
Cold nodule in patient with Grave’s disease

CT, MRI and RNI (radionuclide imaging) – staging thyroid malignancy

Question 14

What is the tumour marker for papillary/follicular thyroid cancer?

Answer 14

Tumour marker following treatment = thyroglobulin (Tg) – should remain undetectable following total thyroidectomy or ablative radioactive iodine.

Detectable levels suggests disease recurrence (metastasis)

Question 15

Papillary carcinoma

Answer 15

Most common thyroid cancer (75%)

Pupillae present in tumour tissue

Excellent prognosis

Total thyroidectomy with ablative dose of radioiodine

Require lifelong T4 replacement at supraphysiological dose

Aim: sublinical hyperthyroidism – with undetectable TSH level due to total suppression

TSH = growth factor for thyroid cells (including malignant cells) - Lifelong follow-up includes tests to Tg

Question 16

Follicular carcinoma

Answer 16

Well-differentiated follicular tumours – contain follicles with colloid

Good prognosis

Thyroid lobectomy recommended to assess malignancy

High-risk patients – complete thyroidectomy and ablative radioactive iodine recommended

Require lifelong T4 replacement at supraphysiological dose

Serum Tg = tumour marker

Question 17

Medullary carcinoma

Answer 17

Cancer of parafollicular ‘C’ cells – producing calcitonin
- Parafollicular cells = neuroendocrine - therefore produce other secretory products e.g. serotonin (5-HT) & can therefore lead to carcinoid syndrome (flushing, diarrhoea, abdominal pain, fast heart rate and bronchospasm).

Calcitonin levels are used during follow-up to test for recurrence

Deposition of amyloid in thyroid & surrounding tissues (adjacent lymph nodes).

Can be sporadic or may be associated with MEN syndromes.

MEN II has to be excluded - as often presents with medullary thyroid cancer, and patients with MEN II will have other endocrine cancers.

MEN II = TAP - Thyroid, Adrenal, Parathyroid.
- Treated with total thyroidectomy and lymph node dissection.

Radioiodine is not used as C cells do not take up iodine

Suppressive thyroxine therapy not needed as C cells not controlled by TSH.

Question 18

Histological features of MNG

Answer 18

• Cystically dilated follicles
• Cholesterol clefts
• Variably sized follicles
• Foamy macrophages
• Fibrous septae

Question 19

Histological features of Graves disease

Answer 19

Clinical and biochemical diagnosis – not made on histology

Papillary architecture

Cells have a more columnar appearance

Question 20

Histological features of Hashimoto’s

Answer 20

Associated with thyroglobulin and thyroid peroxidase antibodies

Lymphoid predominant inflammation

Lymphoid aggregates with germinal centre formation

Small lymphocytes

Follicular cell oncocytic change - Oncocytic epithelial cells

Variable degrees of gland destruction

Question 21

Histological features of follicular adenoma

Answer 21

Completely encapsulated lesion
- Thick fibrous capsule

Made up of thyroid follicles

Clonal population but benign

If capsular or vesicular invasion then becomes follicular carcinoma

Question 22

Graves - what are the antibodies against?

Answer 22

TSH receptor

Question 23

Grave’s treatment

Answer 23

often with ATD first time round

• 12-18 course of tablets
• 60-70% chance of relapse
• block and replace - use very high dose of ATD, then replace thyroid hormones to avoid hypothyroidism
• titration - euthyroidism is achieved using ATDs then a low maintenance dose is given to keep patient euthyroid

RAI -I131 for recurrent graves
- may increase chance of graves eye disease

Surgery

• large goitre, personal preference, severe hyperthyroidism, intolerance to ATDs
• If over 50 years and have active eye disease

Question 24

Is smoking bad in Graves

Answer 24

Yes - get worse eye disease

Question 25

Will radioactive iodine affect graves eye disease?

Answer 25

Yes, will make it worse

Question 26

Treatment in severe graves active eye disease

Answer 26

if severe - consider steroids - cyclosporine Otherwise management is with topical lubricants and selenium 200mcg daily

Question 27

what age is toxic multi nodular goitre seen most commonly?

Answer 27

50-70 years old - often 1 or more lumps will be overactive - rest of thyroid will be switched off as has no signal stimulating it to work

Question 28

What is the treatment for active thyroid nodules?

Answer 28

radioactive iodine if just one active nodule - may require ATD to make them euthyroid. Thyroidectomy

Question 29

What is thyroiditis? - what triggers it? - diagnosis - management

Answer 29

temporary overactivity of the thyroid - may be followed by period of underactivity Triggers - pregnancy, infection, drugs (amiodarone) Diagnosis - TFTs showing thyrotoxicosis, no uptake on technetium scan, inflammatory markers would be raised Management - self limited - beta blockers for symptoms relief - thyroxine may be required in hypothyroid phase

Question 30

Post-partum thyroiditis

Answer 30

occurs within 1 year of giving birth hyperthyroid phase within 4-6 months of delivery followed by a hypothyroid phase, then return to euthyroidism permanent hypothyroidism develops in 30%

Question 31

if you hear a bruit over a goitre - what is this almost always diagnostic of?

Answer 31

Graves

Question 32

Grave's eye signs

Answer 32

``` redness gritty sensation pain on eye movement swelling around eye proptosis (eye appears to be pushed forward) double vision loss of colour vision lagopthalmos (inability to close eye lid) ```

Question 33

Eye sign that may be seen in any cause of overactive thyroid

Answer 33

lid retraction (eyelid drawn back) and lid lag (look up and follow, eyelids dont follow movement)

Question 34

Anti-thyroid drugs - examples - mechanism of action - SE

Answer 34

Carbimazole (CBZ) and propylthiouracil (PTU) - Decrease production of thyroid hormone - Inhibits thyroid peroxidase -> decrease hormone production SE: Rash, pruritis (itching) & arthralgia (joint pain) - Can use antihistamines Rare SE: agranulocytosis (<1/1000) – CBZ and PTU Leucopenia (low WBC count) - Usually occurs during first few months of treatment - Must immediately report: high temp, sore throat, mouth ulcers Risk of hepatotoxicity (PTU) 2 regimens: Titration: euthyroidism is achieved using ATDs, then low maintenance dose given to keep the patient euthyroid (12-18 month course). ‘Block and replace’: a very high dose of ATD is used and once hyperthyroidism is under control L-thyroxine (T4) is added to avoid hypothyroidism (may be useful for people with poor compliance and/or difficult to control with ATD dose titration). Repeat TRAb levels taken near the end of treatment Remission is likely if normal, and relapse is likely if TRAbs remain elevated. Once treatment is stopped, chances of remission are about 30-40%.

Question 35

When should ATD not be used?

Answer 35

Not for thyroiditis (high T4 levels due to release of hormone store from damaged gland, but gland is not actually overactive)

Question 36

Hyperthyroidism - what could you prescribe to someone who has tremor and increased HR? When would this be contra-indicated?

Answer 36

propranolol for significant adrenergic symptoms NO if asthma, or severe COPD

Question 37

When is radioactive iodine contraindicated?

Answer 37

Contraindicated: children/ pregnant / breastfeeding / vomiting or incontinent of urine/ active thyroid eye disease Risk of thyroid eye disease flaring up after I131

Question 38

Precautions with radioactive iodine

Answer 38

Avoid pregnancy/breastfeeding for 6 months Restrict close contact with children under 12 and pregnant women for 12 days and avoid extended periods (>15mins a day) or close contact for 25 days Don’t share bed with partner for 4 days Men should not father children for 4 months after treatment Wear disposable gloves for first 14 days when prepping food

Question 39

Before thyroidectomy, what needs to be achieved in the patient?

Answer 39

euthyroidism

Question 40

Results in primary hypothyroidism

Answer 40

High TSH | low T4 and normal/low T3

Question 41

subclinical hypothyroidism

Answer 41

high TSH | Normal T4 and T3

Question 42

Secondary hypothyroidism

Answer 42

low/normal TSH low T4 Low or normal T3

Question 43

What is the effect of iodine deficiency on thyroid function?

Answer 43

hypertrophic effect on thyroid normally - so in deficiency - cannot make hormones normally - T4 goes down, TSH goes up

Question 44

Hashimoto's thyroiditis

Answer 44

TPO antibodies - thyroid peroxidase

Question 45

Congenital hypothyroidism screening

Answer 45

heel prick - 1 in 4,000 in UK - if untreated may lead to cretinism (stunted physical and mental growth) - at risk if mother is iodine deficient in pregnancy

Question 46

Drug induced causes of hypothyroidism

Answer 46

lithium | amiodarone

Question 47

Thyroid hormone replacement treatment - aim - half life

Answer 47

Aim: normalise TSH half life: 7 days No further investigations needed for hypothyroidism if TSH increases (scans do not change management) Takes several weeks for TSH to normalise

Question 48

Some drugs may impair T4 absorption | - what are these drugs?

Answer 48

PPIs H2 antagonists - ranitidine some antacids Iron, Ca, aluminium leave 4 hour gap before taking T4

Question 49

Increased T4 requirement with what drugs

Answer 49

OCP; HRT - due to estrogen anti-convulsants (epilepsy)

Question 50

Hypothyroidism in pregnancy | - when does the fetus need T4?

Answer 50

from 4-5/40 uses maternal T4 exclusively up to 10/40 and partially thereafter Check TFTs each trimester

Question 51

untreated overt hypothyroidism during pregnancy is associated with:

Answer 51

infertility, miscarriage pre-eclampsia premature delivery increased foetal mortality, impaired neurological development