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YEAR 5: Chemical Pathology PM > ChemPath: Thyroid > Flashcards

ChemPath: Thyroid Flashcards

1
Q

What controls the uptake of iodide by thyroid follicular cells?

A

TSH

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2
Q

Which transporter is important for the transport of iodine across the cell membrane?

A

Na+/I- symporter

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3
Q

Which enzyme converts iodide to iodine?

A

Thyroid peroxidase

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4
Q

How is thyroxine produced?

A
  • TPO iodinates of tyrosine residues in thyroglobulin to generate monoiodotyrosine (MIT) and diiodotyrosine (DIT)
  • MIT and DIT combine to form triiodothyronine (T3)
  • Two DIT combine to form tetraiodothyronine (T4)
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5
Q

What percentage of total T4 is free T4?

A

0.03%

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6
Q

What does T4 bind to in the blood and how is it distributed?

A
  • Thyroxine binding globulin (TBG) - 75%
  • Thyroxine-binding prealbumin (TBPA) - 20%
  • Albumin - 5%
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7
Q

Outline the hypothalamo-pituitary-thyroid axis.

A
  • The hypothalamus produces TRH which stimulates the release of TSH from the anterior pituitary
  • TSH stimulates T4 production
  • T4 negatively feeds back to the hypothalamus and pituitary
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8
Q

List some causes of hypothyroidism.

A
  • Hashimoto’s thyroiditis (autoimmune)
  • Atrophic thyroid gland
  • Post-Graves’ disease (after treatment)
  • Iodine deficiency
  • Postpartum thyroiditis
  • Drugs (e.g. amiodarone, lithium)
  • Pituitary disease
  • Peripheral thyroid hormone resistance
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9
Q

Outline the investigation findings that may be seen in hypothyroidism.

A
  • High TSH
  • Low T4
  • Thyroid peroxidase antibodies

(Look out for other autoimmune conditions)

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10
Q

What are some clinical features of hypothyroidism?

A
  • Weight gain with poor appetite
  • Cold intolerance
  • Constipation
  • Fatigue
  • Hyponatraemia
  • Normocytic anaemia (unless pernicious anaemia)
  • Myxoedema
  • Goitre

Clinical features often subtle in elderly

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11
Q

Why is it important to do an ECG in patients with suspected hypothryoidism?

A

If someone with hypothyroidism has underlying cardiovascular disease, giving them thyroxine may induce ischaemia

NOTE: so you would start on a low dose of thyroxine and then escalate

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12
Q

How is hypothyroidism treated?

A

Levothyroxine (T4) - 50-125-200 µg/day titrated to a normal TSH

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13
Q

What are some risks of overtreatment with levothyroxine?

A
  • Osteopaenia
  • Atrial fibrillation
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14
Q

What is a subclinical hypothyroidism?

A
  • Normal T4 with high TSH
  • Sometimes referred to as compensated hypothyroidism
  • If TPO antibodies are positive, the patient may go on to develop hypothyroidism
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15
Q

Why might there be some benefit to treating subclinical hypothyroidism?

A

Hypothyroidism is associated with hypercholesterolaemia

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16
Q

Outline how thyroid function changes in pregnancy.

A
  • hCG has a similar structure to TSH so high hCG levels can cause hyperthyroidism
  • Free T4 levels rise slightly
  • TBG level increase dramatically

NOTE: hCG level drops later on in pregnancy

17
Q

How is neonatal hypothyroidism diagnosed?

A

Guthrie test

18
Q

Why is the timing of the Guthrie test important?

A

It needs to be done at least 48-72 hours after birth to make sure maternal TSH is no longer in the baby

19
Q

What is sick euthyroid?

A
  • Alteration in the pituitary thyroid axis in non-thyroidal illness
  • In other words, when you are very sick, your thyroid will shut down to try and reduce your basal metabolic rate
20
Q

What are the TFT findings in sick euthyroid?

A
  • Low T4 and T3
  • Normal/high TSH

NOTE: these patients do not have symptoms of hypothyroidism

21
Q

What are the three main causes of hyperthyroidism?

A
  • Graves’ disease (40-60%)
  • Toxic multinodular goitre (30-50%)
  • Single toxic adenoma (5%)

Others: subacute thyroiditis, post-partum thyroiditis

22
Q

What is post-partum thyroiditis?

A
  • Autoimmune disease that occurs up to 1 year postpartum
  • Anti-thyroid antibodies destroy thyroid follicles resulting in the release of T3 and T4
  • Leads to hyperthyroidism
23
Q

What is struma ovarii?

A

A rare form of ovarian dermoid tumour (teratoma) that contains >50% thyroid tissue and produces thyroid hormones

24
Q

List some investigation findings of hyperthyroidism.

A
  • Low TSH
  • High T4 and T3
  • Technetium scan
  • Thyroid antibodies (thyroid microsomal)
25
Q

Outline the management of hyperthyroidism.

A
  • Beta-blocker - to treat adrenergic symptoms (palpitations, tremor)
  • Thionamides (e.g. carbimazole)
  • Radioiodine
26
Q

What is a major risks of radioiodine treatment for hyperthyroidism?

A
  • Can precipitate thyroid storm
  • Can result in hypothyroidism
27
Q

List some features of Graves’ disease.

A
  • Diffuse goitre
  • Thyroid-associated ophthalmopathy
  • Pretibial myxoedema
  • Thyroid acropachy
    (other autoimmune disease)
28
Q

What is the mechanism of action of thionamides?

A

Inhibits TPO thus preventing the conversion of iodide to iodine as well thyroid hormone synthesis

29
Q

What is a rare but important side effect of thionamides?

A

Agranulocytosis

NOTE: patients should be advised to stop treatment if they develop a sore throat or fever

30
Q

What kind of dosing regimes can be used for thionamdes?

A
  • Can be titrated to achieve normal T4 levels
  • Block and replace - high dose is given to block the thyroid gland and then given thyroxine replacement
31
Q

Which drug can be given to hyperthyroid patients prior to surgery to block uptake of iodide?

A

Potassium perchlorate

32
Q

What is the definitive treatment of Grave’s and TMG?

A

Radioiodine

33
Q

What is the long-term treatment of thyroiditis?

A

Thyroid hormone replacement

34
Q

What are the two most common forms of thyroid cancer?

A
  • Papillary thyroid cancer
  • Follicular thyroid cancer
35
Q

How is thyroid cancer treated?

A

Total thyroidectomy

NOTE: radioiodine treatment may also be given

NOTE: high dose thyroxine may be given to suppress TSH levels to prevent TSH from stimulating any remaining cells

36
Q

Which cells do medullary thyroid cancer arise from?

A
  • Calcitonin-producing C cells
37
Q

What genetic condition is medullary thyroid cancer associated with?

A

MEN2

38
Q

Name two tumour markers used for medullary thyroid cancer?

A
  • Calcitonin
  • CEA
39
Q

What is thyroglobulin used to monitor?

A

Disease reoccurance in differentiated thyroid cancer (papillary or follicular)

YEAR 5: Chemical Pathology PM (27 decks)

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