ENDOCRINE: Thyroid

Question 1

What are the physiological effects of thyroid hormone?

Answer 1

Increase HR and CO 
Increase bone resorption 
increases gut motility 
Increases gluconeogenesis 
Maintains normal hypoxic and hypercapnic drive

Question 2

Outline the normal thyroid hormone axis?

Answer 2

TRH released from hypothalamus–> TSH secreted from ant pit–> thyroid to release T3 and T4

Question 3

What is Graves disease?

Answer 3

A type of HYPERthryoidism where TSH-receptor stimulating antibodies cause excess T3/T4

Question 4

Apart from Graves disease, outline another autoimmune cause of thyrotoxicosis?

Answer 4

Nodular, either toxic nodule on the thyroid or a multiple nodules, secreting T3/T4

Question 5

What is thyroiditis?

Answer 5

Inflammation of the thyroid gland causing release of thyroxine (T4)

Question 6

What can cause thyroiditis?

Answer 6

Viral infection, medication (amiodarone) or following pregnancy

Question 7

What are the symptoms of hypothyroidism?

Answer 7

dry thick skin 
brittle hair 
macroglossia 
puffy face 
loss of lateral 1/3 eyebrow 
weight gain 
carpal tunnel syndrome 
peripheral neuropathy 
bradycardia

Question 8

What is a thyroid storm?

Answer 8

Severe form of thyroid disease.

Can occur in thyroxic patients who experience an acute stressor e.g. illness, trauma, surgery

Question 9

How do you treat a thyroid storm?

Answer 9

symptomatic treatment e.g. paracetamol
treatment of underlying precipitating event
HDU 
Strong dose of anti-thyroid medication e.g methimazole or propylthiouracil
Beta blockers (IV propranolol) 
Potassium iodide aka Lugol's iodine (to inhibit production of anymore thyroid hormone) 
High dose steroids: dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3

Propylthiouracil, B blocker and hydrocortisone/ steroids

Question 10

A 10 week pregnant patient comes in with heat intolerance and palpitation, upon further investigations it is found she has hyperthyroidism, what drug would you prescribe here?

Answer 10

Propylthiouracil as carbimazole crosses the placenta, therefore unable to use in first trimester of pregnancy

Question 11

Levothryroxine side effects?

Answer 11

• hyperthyroidism: due to over treatment
• reduced bone mineral density
• worsening of angina
• atrial fibrillation

Question 12

What is myxoedema coma?

Answer 12

extreme form of hypothyroidism
high mortality

Question 13

Clinical features of myxoedema coma?

Answer 13

• CVS: non-pitting oedema of hands and feet, bradycardia, hypotension refractory to vasopressors, reduced contractility, pericardial effusion
• RESP: respiratory depression, impaired respiratory muscle function, hypoxia and hypercapnia
• RENAL: bladder atony, urinary retention, urinary Na+ normal or high
• ELECTROLYTES: hyponatraemia from increased H2O reabsorption from high levels of ADH
• GI: macroglossia, anorexia, abdominal pain, constipation, ileus
• CNS: delayed tendon reflexes, slow mentation, depression -> psychosis, seizures

stupor
hypothermia
respiratory failure
confusion
coma
dry skin
sparse hair
hoarse voice
periorbital oedema

Question 14

Risk factors for myxoedema coma?

Answer 14

• hypothermia
• CVACHF
• infections
• drugs: anaesthetics, sedatives, narcotics, amiodarone, lithium
• GIH
• trauma
• electrolytes: hypoglycaemia, hyponatraemia
• acidosis
• hypoxaemia
• hypercapnia

Question 15

Inv and suspected findings in myxodema coma?

Answer 15

• TSH: markedly elevated in 95% of cases, 5% are caused by central TSH failure
• low free T4
• low T3
• hyponatraemia
• hypoglycaemia
• anaemia
• hypercholesterolaemia
• high LDH
• high CK

Question 16

Management for myxoedema coma?

Answer 16

RESUSCITATION
* admit to ICU because if high mortality and multi-faceted therapy
* may require intubation for various reasons (respiratory failure, airway obstruction from macroglossia, coma)
* ventilation may be required for several days -> weeks
* IV fluid resuscitation and vasoactive agents until thyroid hormone action begins
* warm patient and pre-empt vasodilation and hypotension

Acid-base and Electrolytes
* supportive care
* glucose
* hyponatraemia: cautious correction over time (<10mmol/L day)

Specific Therapy
* hydrocortisone 100mg Q 6hourly if adrenal or pituitary insufficiency suspected
* replacement of thyroid hormones (T4 or T3 is controversial):
* (1) T4 – loading dose = 500mcg IV -> 50-100mcg OD IV or orally
* (2) T3 – loading dose = 10mcg IV -> 10mcg Q4 hrly for 24 hours then every 6 hours

Underlying Cause
treat precipitant (withdraw drugs, treat infection…)

Question 17

Features of thyroid storm?

Answer 17

fever > 38.5ºC
tachycardia
confusion and agitation
nausea and vomiting
hypertension
heart failure
abnormal liver function test - jaundice may be seen clinically

Question 18

Causes of HYPOthryoidism?

Answer 18

Primary:
* Hashimotos Thyroiditis
* Subacute Thyroiditis
* Riedel Thyroiditis
* Post- thyroidectomy
* Drug therapy e.g. lithium, amiodarone
* Dietary iodine deficiency

Secondary:
* due to Pit failure
* associated conditions: Downs syndrome, Turners syndrome and coeliac disease

Question 19

What is Hashimotos Thryoiditis?

Answer 19

• most common cause of hypothyroid
• autoimmune disease
• may cause transient thyrotoxicosis in the acute phase
• 5-10 time more common in women

Question 20

What other diseases is Hashimotos associated with?

Answer 20

• IDDM
• Addisons
• Pernicious anaemia

Question 21

Inv for ?hypothyroid

Answer 21

• Bedside: ECG, BM
• Bloods: FBC (anaemia), WCC (infection), CRP (infection), Vit D (deficiency), U&Es (rule out any electrolyte abnormalities), LFTs (if yellowish tinge to skin)
• Other: change in bowel habit consider stool sample

Question 22

Management of hypothyroidism?

Answer 22

• patients should be started on a dose of 50-100mcg od
• patients with cardiac disease, severe hypothyroidism or patients over 50 years the initial starting dose should be 25mcg od with dose slowly titrated.
• following a change in thyroxine dose thyroid function tests should be checked after 8-12 weeks
• the therapeutic goal is ‘normalisation’ of the thyroid stimulating hormone (TSH) level
• TSH aim: 0.5-2.5 mU/l
• women with established hypothyroidism who become pregnant should have their dose increased ‘by at least 25-50 micrograms levothyroxine’ due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value

Question 23

What is subclinical hypothyroidism?

Answer 23

• elevated TSH
• Normal T4

Question 24

How does subclinical hypothryoidism present?

Answer 24

• usually asymptomatic
• mild symptoms incl fatigue, weight gain and cold intolerance

Question 25

Managaement of subclinical hypothyroidism?

Answer 25

* TSH is > 10mU/L and the free thyroxine level is within the normal range: consider offering levothyroxine if the TSH level is > 10 mU/L on 2 separate occasions 3 months apart * TSH is between 5.5 - 10mU/L and the free thyroxine level is within the normal range: if < 65 years consider offering a 6-month trial of levothyroxine if: the TSH level is 5.5 - 10mU/L on 2 separate occasions 3 months apart, and there are symptoms of hypothyroidism in older people (especially those aged over 80 years) follow a 'watch and wait' strategy is often used if asymptomatic people, observe and repeat thyroid function in 6 months

Question 26

What is De Quervain's thyroiditis?

Answer 26

* post viral infection * typically presents with hyperthyroidism

Question 27

Phase of De Quervain's thyroiditis?

Answer 27

There are typically 4 phases; * phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR * phase 2 (1-3 weeks): euthyroid * phase 3 (weeks - months): hypothyroidism * phase 4: thyroid structure and function goes back to normal

Question 28

Inv for ?De Quervain's thyroiditis?

Answer 28

* Thyroid scintigraphy: globally reduced uptake of iodine- 131

Question 29

Management for De Quervains?

Answer 29

* self limiting- usually no treatment * thyroid pain may respond to aspirin or other NSAIDs * more severe cases esp if hypothryoid is present- steroids

Question 30

What other manifestations of Graves disease may patients have?

Answer 30

30% of pts will have extrathyroidal manifestations * orbitopathy * acropachy * pretibial myxoedema

Question 31

RF for Graves disease?

Answer 31

* +ve fhx * Female * Smoking (tobacco increases risk of orbitopathy)

Question 32

Associations of Graves disease?

Answer 32

* T1DM * Addisons disease * Pernicious anaemia

Question 33

Clinical features of Graves disease?

Answer 33

**General hyperthyroidism signs and symptoms:** * Metabolic: Heat intolerance: due to increased metabolism leading to higher body temperature. Weight loss: caused by higher metabolic rate and accelerated metabolism. Increased appetite: in 90% this is in the absence of weight gain. Excessive sweating: must be differentiated from ‘hot flushes’ due to oestrogen deficiency in post-menopausal women. * Cardiac: Palpitations: this includes atrial fibrillation (20%) or other supraventricular tachycardias, especially in older patients. Tachycardia Atrial fibrillation: a cause of palpitations, especially in older patients. Hypertension Heart failure: thyrotoxic cardiomyopathy, especially in the elderly. * Excessive nervous stimulation: Anxiety: a feeling of nervousness and trembling. Tremor: usually fine. * Other: Palpable thyroid: smooth, diffusely and uniformly enlarged thyrotoxic (excess production of thyroid hormone) goitre. Oligomenorrhoea **Extrathyroidal manifestations specific to Graves’ disease:** * Eye disease (30%): upper eyelid retraction, exophthalmos, ophthalmoplegia, eye pain, tearing, diplopia, photophobia, blurred vision. * Pretibial myxoedema (3%): waxy, discoloured induration of the skin on the anterior aspect of the lower legs. * Thyroid acropachy (1%): clubbing of fingers and toes with soft tissue swelling due to sub-periosteal formation of new bone.

Question 34

Inv for ?Graves disease?

Answer 34

Thyroid dysfunction: * TSH * fT4 * fT3 Specific tests for Graves: * TSH receptor antibodies- present in graves * Technetium scan of thyroid gland- consider if receptor antibodies are negative

Question 35

A pt has confirmed Graves disease, what further inv would you like to do?

Answer 35

If there is a discrete thryoid nodule * USS- assess size, vascularity and presence of nodules. In graves an englarged hypervascular thyroid is seen w nodules in 15% of graves pts * Radioactive iodine scane- uneven uptake indicates presence of nodule, diffuse and high uptake suggests graves , low uptake suggests thyroiditis

Question 36

What does a radioactive iodine scan show?

Answer 36

* uneven uptake indicates presence of nodule * diffude and high uptake: Graves * low uptake: thyroiditis

Question 37

How to assess for thyroid eye disease?

Answer 37

* Examine visual fields, acuity and eye movement s * MRI or CT scans can confirm the diagnosis esp if subclinical

Question 38

TFT results in Graves disease?

Answer 38

* TSH: low * fT4: high * fT3: high

Question 39

Ddx for Graves disease?

Answer 39

**Toxic nodular goitre** * Similarities: hyperthyroidism. * Differences: palpable nodular goitre, absence of extrathyroidal manifestations and thyroid receptor antibodies. **Subacute thyroiditis (de Quervain)** * Initial transient hyperthyroidism followed by hypothyroidism, usually resolving in a few months. * Similarities: hyperthyroidism. * Differences: systemic febrile illness, painful thyroid, raised C-reactive protein, absence of thyroid receptor antibodies. **Gestational hyperthyroidism** * During the first trimester, high levels of hCG stimulate the TSH receptor. * Similarities: hyperthyroidism. * Differences: usually subclinical but can be overt (more likely if hyperemesis gravidarum), absence of thyroid receptor antibodies. **TSH-producing pituitary adenoma** * Similarities: hyperthyroidism. * Differences: MRI shows pituitary tumour, absence of thyroid receptor antibodies, normal or raised TSH. **Iodine-induced hyperthyroidism** * Following iodine exposure (e.g. radiographic contrast, amiodarone). * Similarities: hyperthyroidism. * Differences: history of iodine exposure, absence of thyroid receptor antibodies. **Inflammatory eye conditions, myasthenia gravis** * Similarities: proptosis, ophthalmoplegia, photophobia, diplopia. * Differences: clinically euthyroid, often unilateral eye signs. **Postnatal thyroiditis** * An initial transient hyperthyroid period usually followed by a transient hypothyroid period. * Similarities: hyperthyroidism (in the initial phase). * Differences: absence of thyroid receptor antibodies. **Thyrotoxicosis factitia** * Ingestion of exogenous thyroid hormone (mistaken ingestion of excess, or a symptom of Munchausen syndrome). * Similarities: hyperthyroidism. * Differences: goitre usually absent, no thyroid receptor antibodies.

Question 40

Managment of Graves diease?

Answer 40

**Beta blockers** * for rapid control of symtpoms incl tachycardia, palpitations, anxiety and heat intolerance **Radioactive iodine** * first line definitve treatment * unsuitable in pregancy, attempting to conceive in next 4-6 months, presence of active eye disease, concerns about compression or malignancy * pts often become hypothryoid and need replacement **Antithyroid drugs** * Offer a 12-18 month course as first-line definitive treatment if it is likely to achieve remission, or if radioactive iodine and surgery are unsuitable. * Examples include carbimazole (first-line) and propylthiouracil. **Surgery** * Total thyroidectomy if concerns of compression or malignancy or radioactive iodine or antithryoid drugs are unsuitable * If antithyroid drugs have been tried but hyperthyroidism has replapsed * Risk: recurrent laryngeal nerve samage, hypoparathryoidism * become hypothyroid and need replacement

Question 41

Where should Graves disease pts be managed?

Answer 41

* Secondary care with primary care starting antithyroid durgs and B blockers whilst waiting

Question 42

early complications of Graves?

Answer 42

Early complications include: * Atrial fibrillation More likely over 40 years and may be the presenting feature of hyperthyroidism. Can result in thromboembolic events and stroke. * Pregnancy-related issues These include miscarriage, pre-term birth, thyroid dysfunction in the foetus, poor foetal growth, pre-eclampsia and maternal heart failure. * Sight-threatening orbitopathy Problems include corneal ulcers and optic neuropathy. Rare and usually occurs within one year of diagnosis.

Question 43

Later complications of Graves?

Answer 43

* Osteoporosis The degree of bone mineral loss is proportional to the duration in which the hypothyroidism is left untreated. * Congestive heart failure Occurs more frequently in the elderly. High-output failure can occur due to thyrotoxic cardiomyopathy.