Hypothyroidism (E&M)

Question 1

Define hypothyroidism.

Answer 1

Clinical state resulting from underproduction of the thyroid hormones thyroxine (T4) and triiodothyronine (T3)

Question 2

What are some different types of hypothyroidism?

Answer 2

• primary
• secondary
• sub-clinical
• myxoedema coma

Question 3

Define primary hypothyroidism.

Answer 3

• most cases are due to primary hypothyroidism
• failure of the thyroid gland to produce thyroid hormone
• TSH concentrations above the reference range and free thyroxine concentrations below the reference range

Question 4

Define secondary hypothyroidism.

Answer 4

Underproduction of TSH by the pituitary gland

Question 5

Define sub-clinical hypothyroidism.

Answer 5

State of usually asymptomatic, mild thyroid failure, with normal levels of T4 and T3, and minimal elevation of TSH (may occur in intercurrent illness)

(Sub-clinical = not detected by usual clinical tests)

Question 6

Define myxoedema coma.

Answer 6

Rare severe form of hypothyroidism with multi-organ failure

Question 7

What are some congenital causes of hypothyroidism?

Answer 7

• thyroid dysgenesis
• inherited defects in thyroid hormone biosynthesis
• thyroid dysplasia / aplasia

Question 8

What are some acquired causes of hypothyroidism?

Answer 8

• Hashimoto’s thyroiditis (autoimmune): goitre due to lymphocytic and plasma cell infiltration
• primary atrophic hypothyroidism: diffuse lymphocytic infiltration of the thyroid –> atrophy, no goitre
• iatrogenic: post-thyroidectomy, radioiodine, hyperthyroid medication, amiodarone, lithium, iodine
• severe iodine deficiency (chief cause worldwide)
• iodine excess (Wolff-Chaikoff effect)
• thyroiditis: subacute temporary hypothyroidism after hyperthyroid phase (post-partum thyroiditis / de Quervain thyroiditis)

Question 9

What causes secondary hypothyroidism?

Answer 9

Pituitary disorders e.g. pituitary adenoma –> TSH deficiency

Question 10

What group does hypothyroidism occur more commonly in?

Answer 10

F > M

Question 11

What is the most common cause of hypothyroidism worldwide?

Answer 11

• iodine deficiency
• in developed countries where this is not an issue, Hashimoto’s thyroiditis

Question 12

What more serious condition is Hashimoto’s thyroiditis linked with?

Answer 12

MALT lymphoma

Question 13

What are some risk factors for hypothyroidism?

Answer 13

• iodine deficiency
• female sex
• middle age
• Fx of autoimmune thyroiditis
• autoimmune disorders
• treatment for thyroid disease
• post-partum thyroiditis
• Turner’s and Down’s syndromes
• radiotherapy to head and neck
• amiodarone/lithium use

Question 14

What are some non-specific symptoms of hypothyroidism? (4)

Answer 14

• weakness
• lethargy
• depression
• mild weight gain

Question 15

Describe symptoms/presentations seen in the history of a patient with hypothyroidism.

Answer 15

• insidious onset
• cold intolerance
• decreased sweating
• lethargy
• hoarse voice (due to Reinke’s oedema)
• cramps
• dry skin + hair loss
• weight gain, constipation, reduced appetite
• mental slowness, depression
• ataxia, paraesthesia
• menstrual disturbance (menorrhagia, irregular cycles)
• Hx of surgery or radioiodine therapy for hyperthyroidism
• personal/Fx of other autoimmune conditions (e.g. Addison’s, T1DM)

Question 16

What symptoms/presentations are seen in myxoedema coma?

Answer 16

• severe hypothyroidism usually seen in the elderly
• hypothermia
• hypoventilation
• hyponatraemia
• heart failure
• confusion
• coma

Question 17

What clinical features are seen on examination of a patient with hypothyroidism?

Answer 17

• hypertension due to decreased peripheral resistance
• hands - bradycardia, cold hands
• head/neck/skin - pale puffy face, goitre, oedema, hair loss, dry skin, vitiligo
• chest - pericardial effusion, pleural effusion
• abdomen - ascites
• neurological - slow relaxation of reflexes, signs of carpal tunnel syndrome

Question 18

What is a feature you would see in Hashimoto’s thyroiditis on examination?

Answer 18

Firm and non-tender goitre

Question 19

What is the 1st line investigation for hypothyroidism?

Answer 19

• serum thyroid-stimulating hormone (TSH)
• normal TSH range is 0.4 to 4.0 mIU/L and levels are elevated in primary hypothyroidism
• in sub-clinical disease levels are only mildly elevated - usually <20mIU/L or maybe <10mIU/L

Question 20

What other investigations do we consider for hypothyroidism (after conducting 1st line serum TSH)?

Answer 20

Bedside:

• fasting blood glucose (may be elevated in T1DM - associated with hypothyroidism)

Bloods:

• TFTs - primary hypothyroidism (high TSH low T3/T4) vs secondary hypothyroidism (low TSH low T3/T4)
• antithyroid peroxidase antibodies - elevated in most patients with autoimmune thyroiditis, not routinely ordered
• FBC - normocytic anaemia associated with hypothyroidism
• serum cholesterol - often elevated –> high CVD risk
• U&Es - may show low sodium

Question 21

What may TFT results be during normal pregnancy?

Answer 21

• normal TSH, fT4 and fT3 but raised total T3 and T4
• due to high concentration of thyroid-binding globulins

Question 22

If we suspect pituitary insufficiency in a patient with hypothyroidism, what do we do next?

Answer 22

MRI

Question 23

What antibody is present in Hashimoto’s thyroiditis?

Answer 23

Anti-TPO

Question 24

What electrolyte can be affected in hypothyroidism?

Answer 24

Sodium - can get euvolaemic hyponatraemia

Question 25

What do you see in sick euthyroid syndrome?

Answer 25

Low T3/T4 and normal TSH with acute illness

Question 26

What is the diagnostic criteria for hypothyroidism?

Answer 26

- TFTs - clinical

Question 27

What are some differential diagnoses for (primary) hypothyroidism?

Answer 27

- secondary hypothyroidism - with/without other symptoms of hypopituitarism e.g. hypogonadism and secondary adrenal insufficiency, papilledema and visual field deficits, low TSH, MRI - depression - Alzheimer's - cognitive dysfunction in hypothyroidism responds to thyroid replacement therapy - anaemia - hypothyroid and anaemic patients often have fatigue and dyspnoea on exertion, associated with concurrent autoimmune conditions e.g. pernicious anaemia, TSH

Question 28

What is the 1st line treatment for primary hypothyroidism in healthy patients <65?

Answer 28

Levothyroxine - 1.6mg/kg/day orally adjust dose in increments of 12.5 to 25mg to normalise TSH - 50-100mg/day - adjust dose to TFTs but do not suppress - important to rule out underlying adrenal insufficiency before starting thyroid replacement therapy - can precipitate Addisonian crisis - lifelong

Question 29

What is the 1st line treatment for primary hypothyroidism in patients with pre-existing coronary artery disease or age >65?

Answer 29

Low-dose levothyroxine (25-50mg orally once daily, adjust dose in increments of 12.5 to 25mg every 4-6 weeks) (Levothyroxine therapy may exacerbate angina in patients with CAD)

Question 30

What is the 1st line treatment for sub-clinical hypothyroidism with TSH>10mIU/L? (and TSH 5.5-10)

Answer 30

Low-dose levothyroxine (50-75mg/day, adjust dose in increments of 25-50mg to normalise TSH) Repeat TFTs in 3-6 months In patients >65/asymptomatic - observe and repeat TFTs in 6 months In subclinical hypothyroidism with TSH 5.5-10mU/L: offer patients <65 a 6 month trial of levothyroxine if TSH remains at that level on 2 separate occasions 3 months apart and they have hypothyroidism symptoms

Question 31

What should be checked regularly in hypothyroid patients receiving levothyroxine?

Answer 31

TSH should be checked annually - poor compliance = raised TSH and normal T4

Question 32

How is levothyroxine dose affected in pregnancy?

Answer 32

Should be increased up to 50% as early as 4-6 weeks into pregnancy

Question 33

What risk does overreplacement with thyroxine have?

Answer 33

Increased risk of osteoporosis (/ iatrogenic hyperthyroidism)

Question 34

How do we advise patients taking levothyroxine who also are taking iron/calcium supplements?

Answer 34

Take iron/calcium 4 hours apart from levothyroxine as they can reduce levothyroxine absorption

Question 35

What do we give patients with amiodarone-induced hypothyroidism?

Answer 35

Give levothyroxine and can continue amiodarone

Question 36

How do we treat myxoedema coma?

Answer 36

- oxygen - rewarming - rehydration - IV T4 (levothyroxine) and T3 (liothyronine - faster onset of action) - IV hydrocortisone - treat underlying cause e.g. infection

Question 37

What are some side effects of levothyroxine therapy? (4)

Answer 37

- hyperthyroidism (due to over-treatment) - reduced bone mineral density - worsening of angina - atrial fibrillation

Question 38

What are some complications of hypothyroidism?

Answer 38

- **myxoedema coma** - older untreated patients with multiple comorbidities, mortality rate 80% - angina - high initial dose of levothyroxine in patients with CAD - over-treatment --> AF, osteoporosis - complications in pregnancy e.g. pre-eclampsia, perinatal mortality, recurrent miscarriage, foetal neurological maldevelopment - Hashimoto's thyroiditis --> MALT lymphoma

Question 39

What is the prognosis for patients with hypothyroidism?

Answer 39

- lifelong levothyroxine required - myxoedema coma has mortality rate of 80%