Thyroid

Question 1

Factors contributing to low TSH

Answer 1

• Glucocorticoids
• Dopamine

Question 2

Factors contributing to low T3

Answer 2

• High cortisol levels
• Circulating inhibitors of deiodinase activity e.g. free fatty acids
• Drugs which inhibit deiodinase - propranolol, amiodarone
• Cytokines

Question 3

Factors contributing to low T4

Answer 3

• Reduced hormone binding protein
• Reduced binding to binding proteins

Question 4

Drugs that cause hyperthyroidism

Answer 4

• Interleukin 2
• Amiodarone
• Interferon alpha
• Iodine

Question 5

Drugs that cause low TBG

Answer 5

• Danazol
• Androgens
• Danazol
• Glucocorticoid

Question 6

Drugs that cause high TBG

Answer 6

• Estrogens
• Tamoxifen
• Raloxifen
• Methadone

Question 7

What is the most specific test for Grave’s disease

Answer 7

TSH receptor antibody

Question 8

Role of colestyramine in thyroid storm

Answer 8

• Increases T4 clearance
• Dexamethaone and PTU prevent conversion of T4 → T3

Question 9

Alemtuzumab and autoimmune thyroid disease

Answer 9

• Seen in nearly half of patients on alemtuzumab
  
  • Grave’s disease (75%)
  • Subacute painless thyroiditis
  • Hashimoto’s thyroiditis
• Thyroid receptor antibodies - TRAB
  
  • Mainly stimulating - hence hyperthyroidism, can also be blocking (can also alternate leading to alternating thyroid status)
• Treatment → high rate of remission either spontaneously or with treatment
• Anti-thyroid drugs first line
• Spontaneous hypothyroidism can occur too

Question 10

Autoimmune manifestations of Alemtuzumab

Answer 10

• Grave’s disease
• ITP
• Haemolytic anaemia
• Anti-GBM glomerulonephritis

Notes on alemtuzumab:

• Humanised anti-CD52 monoclonal antibody
• Depletes autoreactive lymphocytes → immune suppression, followed by immune reconstitution → B cell mediated autoimmunity

Question 11

Role of biotin in interpreting thyroid function tests:

Answer 11

• Need to stop and reassess thyroid function in 3-4 weeks
• TSH/Thyrotropin assay → excess biotin occupies streptavidin binding sites → low thyrotropin signal antibody detected yielding a falsely low thyrotropin level and falsely elevated T4 level

Question 12

Effect of biotin on blood tests

Answer 12

1. TSH/T4 - hyperthyroid (falsely)
2. Falsely elevated vitamin D
3. Falsely low troponin

Question 13

Effects of amiodarone on thyroid function

Answer 13

• Both hypothyroidism and hyperthyroidism
• Inhibits 5’-monodeiodination of T4-T3, decreasing T3 production (spurious result)
• Direct toxic effect on thyroid follicular cells (destructive thyroiditis - type 2 AIT)
• Beta blockade - masks symptoms of thyrotoxicosis

Question 14

Distinguishing between AIT Type I and Type II

Answer 14

Type I

• More common in early phase post amiodarone commencement
• Autoantibodies may be positive
• Normal vascularity on doppler ultrasound
• Slow response to carbimazole/steroids

Type II

• More common
• More common in late phase or following discontinuation
• Vascularity reduced on Doppler ultrasound
• Rapid response to steroid

Question 15

Effect of CTLA4 inhibitors and immune checkpoint inhibitors on thyroid function

Answer 15

• CTLA4 inhibitors (ipilimumab) - hypophysitis, central hypothyroidism
• PD-1 inhibitors (pembrolizumab, nivolumab) → primary hypo- or hyperthyroidism
• Stopping immune checkpoint inhibitors generally not required
• Thyroid function improves in nearly half of people if stopped

Question 16

Effect of lithium on thyroid function (and other endocrinopathies)

Answer 16

• Hypothyroidism (goitre)
• Parathyroid hyperplasia (hypercalcaemia)
• Nephrogenic diabetes insipidus
• Not related to therapeutic range
• Predisposing factors:
  
  • Female
  • >40 years of age
  • Presence of TPO antibodies
  • Duration of use

Question 17

Causes of primary hyperthyroidism

Answer 17

1. Grave’s disease
2. Toxic multinodular goitre
3. Toxic adenoma
4. Thyroiditis (early stages)
5. Drugs - biotin, amiodarone, immune checkpoint inhibitors, alemtuzumab
6. Excess iodine, thyroxine
7. Pregnancy related - hyperemesis gravidarum, hydatidiform mole

Question 18

Features suggesting Grave’s disease

Answer 18

• More common in females (8:1)
• Peak onset 40-60 years
• Pathognomic signs - diffuse goitre, thyroid eye disease (bilateral proptosis, lid retraction, scleral injection, periorbital oedema), pretibial myxoedema, clubbing
• Thyroid uptake scan → uniform normal or diffuse high uptake
• Antibodies - TSH-R Ab positive, TPO Ab often mildly positive

Question 19

Features of toxic multinodular goitre

Answer 19

• More common in women
• 50+ years
• Nodularity present for years
• Normal or elevated multifocal uptake with suppression of surrounding thyroid on thyroid uptake scan
• TSH-R Ab negative, TPO Ab low titre or absent

Question 20

Features of toxic adenoma

Answer 20

• Female > male
• 30-50 years
• Slow growing, solitary thyroid nodule
• Thyroid uptake scan → elevated focal uptake with suppression of surrounding thyroid
• TSH-R Ab negative
• TPO Ab low titre or absent

Question 21

MEN 1 Features

Answer 21

• Pituitary adenomas
• Parathyroid tumour
• Pancreatic adenomas

Question 22

MEN 2A Features

Answer 22

• Phaechromocytoma
• Medullary thyroid cancer
• Parathyroid adenomas

Question 23

MEN 2B Features

Answer 23

• Phaechromocytomas
• Medullary thyroid cancers
• Mucosal neuromas
• Marfanoid habitus

Question 24

Causes of subclinical hypothyroidism

Answer 24

Transient

• Non-thyroidal illness recovery
• Poor adherence with thyroxine
• Malabsorption of thyroxine
• Drugs (amiodarone, lithium)

Persistent

• Physiological - aging (TSH <7- 10)
• Obesity (TSH <7-10)
• Assay interference
• TSH or TRH resistance (rare)
• Adrenal insufficiency

Question 25

Absolute indication for treating subclinical hypothyroidism

Answer 25

• Pregnancy

Question 26

What is the first line agent for treating hyperthyroidism in pregnancy after the first trimester

Answer 26

• Carbimazole

Generally use Proplythiouracil in first trimester

Question 27

Causes of normal T4/T3, low TSH

Answer 27

• Subclinical hyperthyroidism
• Recent treatment of hyperthyroidism
• Drugs (steroids, dopamine)
• Assay interference

Question 28

Significance of subclinical hyperthyroidism and when to treat

Answer 28

• Progression to overt hyperthyroidism can occur → especially when TSH <0.1
• Can be A/W cardiovascular disease (AF, CHF, CAD), bone loss, fractures, dementia → particularly in > 65 years with severe disease
• Data lacking re when to treat - but generally in >65 years, and post-menopausal women, especially when TSH <0.1