Thyroid disorders

Question 1

Explain the process of Thyroid Hormone Synthesis

Answer 1

1) Organification of iodide: Iodide → Iodine → condensed onto tyrosine residues → mono or di-iodinated tyrosine
2) Coupling reaction: 2 DIT molecules → T4
3) Release of the T3 and T4 from the thyroid gland
4) Major production of T3 occurs outside of the thyroid gland by peripheral conversion from T4

Question 2

Explain the hypothalamo-pituitary-thyroid axis

Answer 2

Question 3

Are primary or secondary disorders of thyroid gland more common?

Answer 3

Primary

Question 4

Are thyroid diseases more common in women or men

Answer 4

Women

Question 5

What are autoimmune thyroid disorders commonly associated with?

Answer 5

Other autoimmune diseases e.g. T1 DM, autoimmune adrenal insufficiency

Question 6

Is T3 or T4 more more biologically active

Answer 6

T3

Question 7

What is Hyperthyroidism?

Answer 7

Over-production of thyroid hormone by the thyroid gland

Question 8

What is Thyrotoxicosis?

Answer 8

Abnormal and excessive quantity of thyroid hormone in the body

Question 9

Most common cause of Hyperthyroidism?

List 4 other common causes of thyrotoxicosis

Answer 9

Graves’ Disease ☆

1. Iatrogenic,
2. Toxic adenoma,
3. Toxic multinodular goitre
4. Thyroiditis
5. Iodide excess

Question 10

What is Graves disease? Incl the pathophysiology

Answer 10

Autoimmune condition where TSH receptor antibodies cause a primary hyperthyroidism.

These TSH receptor antibodies (TSHRAb) mimic TSH and stimulate TSH receptors on the thyroid

Question 11

What is subclinical hyperthyroidism?

Answer 11

Low levels of TSH but normal levels of T3 and T4

Question 12

List 4 symptoms of hyperthyroidism

Answer 12

1. Anxiety and irritability
2. Weakness and fatigue
3. Palpitations
4. Sweating and heat intolerance
5. Dyspnoea
6. Frequent loose stools (hyperdefecation)
7. Insomnia
8. Poor concentration
9. Menstrual abnormalities and sexual dysfunction

Question 13

List 4 signs of hyperthyroidism

Answer 13

1. Weight loss
2. Proximal myopathy
3. Tachycardia, arrythmias
4. Warm, moist skin
5. Tremor
6. Eye conditions (stare, lid lag, lid retraction)
7. Emotional lability
8. Hyperactive deep tendon reflexes with shortened relaxation time

Question 14

What is a Thyroid storm?

Answer 14

Exaggerated typical signs and symptoms, fever, jaundice, changes in neurologic function

Question 15

Clinical features/presentation specific to Graves disease

Answer 15

1. Diffuse goitre (without nodules)
2. Graves eye disease
3. Bilateral exophthalmos
4. Pretibial myxoedema

Question 16

Pathophysiology behind Graves’ Ophthalmopathy?

Answer 16

Antibodies to TSH receptor also target retroorbital tissues

• T-cell inflammatory infiltrate → fibroblast growth
• Severe: exposure keratopathy, diplopia, com-pressive optic neuropathy

Strong link with tobacco and seen in 50% of Graves Disease

Question 17

Pathophysiology behind Graves’ Myxedema (thyroid dermopathy)

Answer 17

Activation of fibroblasts → increased hyaluronic acid and chondroitin sulfate

Asymmetric, raised, firm, pink-to-purple, brown plaques of nonpitting edema

Occurs In <5% of Graves disease

Question 18

What is Thyroid acropachy?

List the 3 characteristic findings on imaging which comprise this

Answer 18

Rare complication of autoimmune thyroid disease

1. Digital clubbing
2. Soft tissue swelling of hands and feet
3. Periosteal bone formation

Occurs in 0.1-1 % and almost always in patients with myxedema and ophthalmopathy

Question 19

Laboratory findings indicative of primary hyperthyroidism?

Answer 19

Suppressed TSH (<0.05 uU/ml)

Elevated Free T4 and/or Free T3

Question 20

Ddx in a patient with hyperthyroidism for the follow values of T3:T4

• T3:T4 > 20
• T3:T4 < 20

Answer 20

T3:T4 > 20:

• Graves’ Disease
• Toxic MN Goiter

T3:T4 < 20:

• Non-thyroid illness
• Thyroiditis
• Exogenous thyroxine

Question 21

List 3 other investigations for hyperthyroidism

Answer 21

1. Thyroid radioiodine uptake
2. TSH receptor antibodies: Grave’s
3. US thyroid: hypoechogenic in untreated diffuse toxic goitre

Question 22

What would iodine uptake show on nuclear scintigraphy for the following:

1. Toxic multinodular
2. Graves
3. De Quervain’s thyroiditis

Answer 22

1. TMG: Patchy uptake
2. Graves: diffuse, homogenous, increased uptake
3. DQ thyroiditis: globally reduced uptake of iodine-131

Question 23

List 4 complications of hyperthyroidism

Answer 23

1. Atrial Fibrillation
2. Osteoporosis
3. Heart failure
4. Thyroid Storm

Question 24

List 4 treatments of thyrotoxicois?

Answer 24

1. Antithyroid medications: Carbimazole and Propylthiouracil
2. β- blockers for symptom control (Propranolol preferred)
3. Radioactive iodine
4. Surgery

Question 25

List 2 dangers/ side effects of Antithyroid medications

Answer 25

Carbimazole and Propylthiouracil can cause Agranulocytosis, and or hepatotoxicity (PTU)

Question 26

What is hypothyroidism?

Answer 26

Inadequate output of thyroid hormones by the thyroid gland

Question 27

List 4 populations at risk of hypothyroidism

Answer 27

1. Women 2. History of Graves disease or postpartum thyroid dysfunction 3. Elderly 4. Other autoimmune disease 5. Family history of thyroid disease, pernicious anemia, type I DM

Question 28

Is primary or secondary hypothyroidism more common? What is the difference between these

Answer 28

1^o → Thyroid gland insufficiency (more common) 2^o → Pituitary pathology

Question 29

What defines subclinical hypothyroidism?

Answer 29

Normal free T4 concentration in the presence of an elevated TSH concentration

Question 30

What is the treatment of choice for hypothyroidism?

Answer 30

Levothyroxine (needs to be titrated)

Question 31

List 4 causes of Hypothyroidism

Answer 31

1. Hashimoto's thyroiditis 2. Thyroiditis 3. Congenital hypothyroidism 4. Drug induced 5. Post radiation 6. Thyroid surgery

Question 32

List 4 clinical features of hypothyroidism

Answer 32

1. Weight gain 2. Fatigue 3. Dry skin 4. Coarse hair and hair loss 5. Fluid retention (oedema, pleural effusions, ascites) 6. Heavy or irregular periods 7. Constipation

Question 33

What is a Myxedema coma? How does it present?

Answer 33

Medical emergency - end stage of untreated/insufficiently treated hypothyroidism Presents with: 1. hypothermic 2. hypotensive 3. hypoventilation 4. bradycardic 5. Impaired sensorium

Question 34

What is cretinism and why does it occur? List 3 clinical features

Answer 34

Lack of thyroxine from birth or before birth (severe and irreparable) From lack of thyroid gland or lack of iodine in mother 1. Mental defects 2. Stunted growth 3. Reduced growth and function of many organs

Question 35

Typical clinical picture of a Myxedema Coma?

Answer 35

1. Elderly obese female 2. Becoming increasingly withdrawn, lethargic, sleepy and confused 3. Slips into a coma

Question 36

List 4 physical findings of Myxedema Coma

Answer 36

1. Comatose or semi comatose 2. Hypothyroid features: dry coarse skin, hoarse voice, thin dry hair 3. Delayed reflex relaxation time 4. Hypothermia 5. Pericardial, pleural effusions, ascites

Question 37

Typical history of a Myxedema Coma?

Answer 37

1. Previous thyroid surgery 2. Radioiodine 3. Default thyroid hormone therapy

Question 38

List 4 things which may precipitate a Myxedematous Coma

Answer 38

1. Infections 2. Trauma (incl surgery) 3. Exposure to cold 4. CVS problems 5. Drugs

Question 39

Management of Myxedema?

Answer 39

1. ICU admission - ventilatory support and IV meds 2. Parenteral thyroxine 3. Electrolytes - water restriction for hyponatremia, avoid fluid overload 4. Avoid sedation 5. Glucocorticoids - Hydrocortisone

Question 40

List 4 factors which may reduce levothyroxine effectiveness

Answer 40

1. Malabsorption Syndromes ie. celiac disease 2. Drugs that ↑ clearance ie. rifampin 3. Factors that ↓ T4 to T3 clearance ie. amiodarone 4. ↓absorption ie. ferrous sulfate 5. Other Mechanisms ie. sertraline

Question 41

What is Hashimoto’s Thyroiditis?

Answer 41

Autoimmune inflammation of the thyroid gland. Initially it causes a goitre after which there is atrophy of the thyroid gland.

Question 42

List 2 antibodies which are associated with Hashimoto’s Thyroiditis

Answer 42

1. antithyroid peroxidase (anti-TPO) antibodies 2. antithyroglobulin antibodies

Question 43

a) What is the most common cause of hypothyroidism in the **developed** word b) What is the most common cause of hypothyroidism in the **developing** world

Answer 43

a) Hashimoto’s Thyroiditis b) Iodine Deficiency

Question 44

All treatments for **hyper**thyroidism have potential to cause hypothyroidism, list 4 of these

Answer 44

1. Carbimazole 2. Propylthiouracil 3. Radioactive iodine 4. Thyroid surgery

Question 45

List 2 other medications which can cause hyperthyroidism

Answer 45

1. **Lithium** - inhibits production of thyroid hormones in the gland, can cause a goitre and hypothyroidism 2. **Amiodarone** - interferes with thyroid hormone production and metabolism, can cause both hypothyroidism and thyrotoxicosis

Question 46

What findings on a thyroid function test would be indicative of a primary vs secondary cause of hypothyroidism?

Answer 46

1^o → low T3 & T4, high TSH 2^o → low TSH, low T3 & T4

Question 47

What is secondary hypothyroidism?

Answer 47

Where the pituitary gland is failing to produce enough TSH. ## Footnote Often associated with a lack of other pituitary hormones ie. ACTH - known as 'hypopituitarism'

Question 48

List 4 causes of secondary hypothyroidism

Answer 48

1. Tumours 2. Infection 3. Vascular (e.g. Sheehan Syndrome) 4. Radiation

Question 49

What is Sheehan Syndrome?

Answer 49

Hypopituitarism caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth Also known as postpartum pituitary gland necrosis