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Endocrine System > Thyroid > Flashcards

Thyroid Flashcards

1
Q

T4 and T4 are both taken up into cells but T__ is converted into T___ which binds to nuclear receptors and activates gene transcription.

A

T4→T3

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2
Q

What are 4 biological effects of thyroid hormones?

A

1) Brain development (perinatal period)
2) Growth (via GH production)
3) Thermogenic action (heat production)
4) Synthesis and effects of GH (Metab)

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3
Q

Describe the HPT axis in the regulation of thyroid hormone secretion.

A

Hypothalamus → TRH
Anterior pituitary → TSH
Thyroid → T3&4
- -ve feedback on both AP and Hypothalamus

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4
Q

What is not routinely tested for in thyroid disorders, why?

A

Free T3
i) very small titre
ii) very localised in tissues → hard to accurately measure
iii) very short T1/2

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5
Q

When is T3 tested for?

A

1) px is on thyroid replacement (if T4 is properly converting to T3)
2) suspected T3 toxicosis

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6
Q

Which hormones are routinely tested for in a px with suspected thyroid dysfunction?

A

1) TSH
2) Free T4

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7
Q

What are the 2 main clinical presentations of thyroid disease?

A

1) Goitre
- diffuse
- localised swelling/nodule

2) Functional derangement
- Hyperthyroidism/ Thyrotoxicosis
- Hypothyroidism

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8
Q

What are the symptoms, signs and biochemical findings in hyperthyroidism?

A

Symptoms:
1) Weight loss
2) Heat intolerance
3) Oligomenstrual
4) Diarrhoea
5) Irritable
6) ↑Appetite

Signs:
1) Thin
2) Staring gaze, lid lag, (exophthalmos in Grave’s)
3) Warm, sweaty skin
4) Tachycardia, Afib
5) Pretibial myxedema
6) Proximal myopathy

Biochemisty:
1) ↑Total T4
2) ↑T4
3) ↑T3
4) ↓TSH
5) ±autoantibodies (Grave’s, Early Hashimoto’s)

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9
Q

What are the symptoms, signs and biochemical findings in hypothyroidism?

A

Symptoms:
1) Weight Gain
2) Cold intolerance
3) Menorrhagia/oligomenstual
4) Constipation
5) Mental slowness
6) ↓Appetite

Sign:
1) Midly obese
2) Peaches and cream skin
3) Dry, cool skin
4) Bradycardia
5) Pericardial effusion
6) Proximal myopathy

Biochemical:
1) ↓Free T4
2) ↓T4
3) TSH (↑ in 1°, ↓ in 2°)
4) ±Autoantibodies (Hashimoto’s)

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10
Q

Which 4 thyroid conditions are associated with a diffuse goitre?

A

1) Grave’s disease
2) Hashimoto’s thyroiditis
3) DeQuervain thyroiditis
4) Simple goitre

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11
Q

Which 3 thyroid conditions are associated with a localised swelling/nodular goitre?

A

1) Nodular goitre
2) Neoplasms
3) Thyroiditis (Hashimoto’s, DeQuervain)

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12
Q

What are 4 causes of hyperthyroidism?

A

1) Grave’s disease
2) Hyperplasia
3) Nodular goitre
4) Neoplasms

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13
Q

What are 2 causes of hypothyroidism?

A

1) Hashimoto thyroiditis
2) Congenital abnormalities

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14
Q

Which thyroid conditions can lead to euthyroid?

A

1) Nodular goitre
2) Neoplasms

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15
Q

What are 4 congenital thyroid diseases?

A

1) Thyroglossal duct cyst
2) Abnormal development of thyroid gland (aplasia, hypoplasia)
3) Ectopic thyroid tissue
4) Thyroid dyshormogenesis

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16
Q

A Thyroglossal duct cyst is a embryonal vestige that occurs at (location) and can lead to (complications: 2).

A

Thyroglossal duct cyst:
- embryonal vestige
- midline neck cyst
- Cx: (i) Infection (ii) Malignant change

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17
Q

How are thyroglossal duct cysts treated?

A

Complete excision

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18
Q

What are 2 forms of abnormal development of thyroid glands?

A

1) Aplasia
2) Hypoplasia

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19
Q

What are 3 clinical presentations of abnormally developed thyroid gland?

A

1) Cretinism
- hypothyroidism in infancy or early childhood

2) Severe intellectual disability, short stature

3) Coarse facial features, protruding tongue, umbilical hernia

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20
Q

What are 3 common sites of ectopic thyroid tissue?

A

1) Upper GIT
2) Upper Respi Tract
3) Soft tissues of neck
4) CVS

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21
Q

What is thyroid dyshormonogenesis?

A

Inherited defects in thyroid hormone synthesis leading to congenital hypothyroidism and goitre

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22
Q

How does thyroid dyshormonogenesis present?

A

Mental and growth retardation

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23
Q

What is the pathogenesis of diffuse/multinodular goitre?

A

Due to abnormal iodine availability/usage → impaired synthesis of thyroid hormone:

1) Impaired synthesis of thyroid hormones:
i) endemic (iodine deficiency)
ii) sporadic (dyshormonogenetic goitre)

2) Compensatory ↑TSH
→ hypertrophy and hyperplasia of follicular cells
→ thyroid gland enlargement

3) Recurrent hyperplasia and involution → nodular enlargement (multinodular goitre)

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24
Q

Multinodular goitre is a __________ from simple goitre.

A

Progression
- recurrent hyperplasia and involution

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25
Q

True or false: A simple goitre is a form of hyperthyroidism.

A

False.
Simple goitre is known as diffuse non-toxic (non-hyperfunctioning) goitre

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26
Q

What are the 2 morphological phases of diffuse goitre?

A

1) Hyperplastic stage
- Diffuse mild enlargement
- micro: crowded columnar cells, pseudopapillae

2) Colloid involution
- Micro: flattened cuboidal epithelium
- abundant colloid

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27
Q

Multinodular goitre is an evolution of _______ and shows extreme, irregular enlargement ± cystic change.

A

Multinodular goitre:
- progress from simple goitre
- extreme, irregular enlargement
- cystic change

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28
Q

True or false: Multinodular goitre is the most common cause of goitre

A

True

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29
Q

What are 2 complications of multinodular goitre?

A

1) Mass effects:
a) trachea → wheeze, stridor, hypoxia
b) oesophagus → dysphagia
c) recurrent laryngeal nerve → hoarseness

2) Toxic goitre → hyperthyroidism

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30
Q

What are 2 autoimmune conditions affecting the thyroid?

A

1) Hashimoto thyroiditis
2) Grave’s disease (form of thyroid hyperplasia)

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31
Q

What are 2 examples of thyroiditides?

A

1) Granulomatous thyroiditis (DeQuervain thyroiditis)
2) IgG-4-related thyroiditis
3) Hashimoto’s thyroiditis

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32
Q

What is the #1 cause of hypothyroidism where dietary iodine is sufficient?

A

Hashimoto’s thyroiditis

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33
Q

Hashimoto thyroiditis EPC:
(M/F)
Which age group
Familial clustering: _________
a/w other autoimmune conditions eg. _______

A

Hashimoto thyroiditis EPC:
F 10-20X > M
45-65 y/o
Familial clustering: HLA - DR3, DR5
a/w other autoimmune conditions eg. T1DM

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34
Q

Describe the pathogenesis of Hashimoto thyroiditis.

A

CD4+ Sensitisation to thyroid Ags lead to:
1) CD8+ Tc cell-mediated cell death to thyrocytes

2) CD4+ Cytokine (IFN-y)-mediated cell death by recruitment and activation of macrophages

3) ADCC by production of autoAbs against (i) thyroglobulin (ii) TSHr (iii) Thyroid peroxidase/TPO

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35
Q

What are 3 clinical features of Hashimoto’s thyroiditis?

A

1) Painless goitre (diffuse>localised)
2) Hypothyroidism (T3/4 down, TSH up)
3) Anti-TPO, TSH, Tg Abs
4) Preceding transient thyrotoxicosis (hashitoxicosis)

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36
Q

What is the gross morphology of Hashimoto’s thyroiditis?

A

1) Pale, enlarged gland (diffuse > localised)

2) Pale, yellow firm cut surface (may be nodular)

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37
Q

What is the 3 microscopic features of Hashimoto’s thyroiditis?

A

1) Infiltrates: reactive lymphoid follicles, lymphocytes, plasma cells

2) Thyroid follicles - atrophic, Hurthle (oncocytic) cell change

3) Fibrosis

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38
Q

What are 3 complications of Hashimoto’s thyroiditis?

A

1) Primary Hypothyroidism (Low T3/4, high TSH)

2) Risk of other autoimmune diseases (eg. T1DM, SLE, Sjogren’s syndrome)

3) Higher risk of B cell lymphoma of thyroid (eg. MALT)

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39
Q

What is the #1 cause endogenous hyperthyroidism?

A

Grave’s disease

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40
Q

Graves’s disease EPC:
(M/F)
Age group
Family Hx + genes ___________
a/w with other autoimmune conditions

A

Graves’s disease EPC:
Women 7x > Men
20-40 y/o
Family Hx + HLA-B8, DR3

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41
Q

Describe the pathogenesis of Graves’ disease.

A

Breakdown in Th cell tolerance:

AutoAb to TSHr (TRAbs):
1) Thyroid stimulating immunoglobulin (TSI)
- 90% prevalence in px
- MOST SPECIFIC for Graves’
- binds to TSHr to stimulate release of T3/4 and increase growth of thyroid gland

2) TSH-binding inhibitor immunoglobulin (TBII)

3) Others (anti-TPO, anti-TGB)

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42
Q

What are 6 clinical features of Graves’ disease?

A

1) Thyrotoxicosis
2) Diffuse goitre +/- bruit
3) Opthalmopathy (exophthalmos), Dermopathy (pretibial myxedema)
4) Wide, staring gaze w lid lag (sympathetic overactivity)
5) Primary hyperthyroidism (High T3/4, low TSH)
6) Increased radioiodine uptake
7) AutoAbs (TSI, TBII, anti-TPO, anti-TGB)

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43
Q

Describe the pathogenesis of ophthalmopathy in Graves’ disease.

A

1) Cytokines from activated Th cells cause T cell infiltration and edema
2) Increased ECM and fatty infiltration lead to increase volume in extra-occipital muscles, retro-orbital tissue

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44
Q

What are 2 gross features of Grave’s disease?

A

1) Symmetrical diffuse enlargement
2) Soft, reddish meaty cut surface

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45
Q

What are 3 microscopic features of Grave’s disease?

A

1) Follicular cells (pseudopapillae: tall, columnar, crowded)

2) Colloid (pale, scalloped)

3) Lymphoid infiltrates, reactive lymphoid follicles

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46
Q

What is the pathogenesis of granulomatous thyroiditis (DeQuervain thyroiditis)?

A

Suggested:
Viral-induced Tc cell response to thyroid Ags lead to damage of follicular cells

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47
Q

True or false: Granulomatous (DeQuervain) thyroiditis is usually self-limiting

A

True

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48
Q

What are 5 clinical features of granulomatous (DeQuervain thyroiditis)?

A

1) Short Hx (weeks) + Self-limiting
2) Painful goitre
3) Mild hyper then hypo then euthyroid
4) Systemic symptoms: recent URTI
5) Women 4x > Men, 30-50 y/o

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49
Q

What are 2 macroscopic features of Granulomatous (DeQuervain) thyroiditis?

A

1) Enlarged and firm gland (uni/bilateral)
2) Patchy, firm pale-yellowish areas w intervening normal parenchyma

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50
Q

What are 3 microscopic features of Granulomatous (DeQuervain) thyroiditis?

A

1) Destruction of follicles (w neutrophils, microabscesses)

2) Lymphocytes, plasma cells, histiocytes around damages follicles

3) Multinucleated giant cells, engulfing pools of colloid

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51
Q

IgG4-related thyroiditis mimics ______ clinically with progressive __________ and adherence to neck structures. It is the likely underlying pathology in “________”

A

IgG4-related thyroiditis mimics malignancy

Progressive fibrosis, enlargement

Likely underlying pathology in “Riedel thyroiditis”

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52
Q

IgG4-related thyroiditis:
Serology: ________
Treatment: _________
A/W: ______________

A

IgG4-related thyroiditis:

Serology: Serum IgG4 raised

Treatment: Corticosteroid therapy

A/W: IgG-4 related fibrosclerotic disease (eg. retroperitoneal or mediastinal fibrosis, sclerosing cholangitis, lacrimal or salivary gland disease)

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53
Q

What are 2 microscopic features of IgG4-related thyroiditis?

A

Microscopic features:
1) Lymphoplasmacytic infiltration (IgG4-producing plasma cells)
2) Fibrosis
3) Obliterative thrombophlebitis

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54
Q

Which of the thyroid neoplasms are associated with RAS mutations (PPARy/PAX8 rearrangments)?

A

1) Follicular adenoma (benign)
2) Follicular carcinoma (low grade malignant)

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55
Q

Which of the thyroid neoplasms are associated with BRAF mutations (RET/PTC rearrangements)?

A

Papillary thyroid carcinoma (low grade malignant)

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56
Q

Which of the thyroid neoplasms are associated with RET mutations?

A

Medullary carcinoma (C cells)

57
Q

Which of the thyroid neoplasms are associated with general mutations/rearrangements & TERT, TP53 mutations?

A

High grade malignant:
1) Poorly differentiated thyroid carcinoma (PDTC)
2) Differentiated high grade thyroid carcinoma

Undifferentiated:
3) Anaplastic thyroid carcinoma (ATC)

58
Q

What are 2 non-follicular cell origin thyroid neoplasms?

A

1) Medullary carcinoma
2) Lymphoma

59
Q

What are 2 benign thyroid neoplasms of follicular cell origin?

A

1) Follicular adenoma
2) Oncocytic/Hurthle cell adenoma

60
Q

What are 2 benign thyroid neoplasms of follicular cell origin?

A

1) Follicular adenoma
2) Oncocytic/Hurthle cell adenoma

61
Q

What are 5 malignant thyroid neoplasms of follicular cell origin?

A

Low grade:
1) Papillary thyroid carcinoma
2) Follicular carcinoma

High grade:
3) Poorly differentiated thyroid carcinoma (PDTC)
4) Differentiated high grade thyrid carcinoma

Undifferentiated:
5) Anaplastic thyroid carcinoma

62
Q

What is the clinical feature of benign thyroid neoplasms?

A

Solitary painless nodule
(Euthyroid)

63
Q

What is the gross morphology of follicular adenoma and carcinoma (can look the same)?

A

1) Rounded, encapsulated
2) Well demarcated nodules
3) Intact capsule
4) Bulging from the cut surface

64
Q

What is the microscopic appearance of benign thyroid adenomas?

A

Completely surrounded by an intact capsule:
- no capsular invasion
- no vascular invasion

Follicular adenoma:
a) uniform, microfollicles, distinct from the surrounding parenchyma
b) microfollicular/macrofollicular/mixed

Oncocytic (Hurthle cell) adenoma:
a) same as Follicular adenoma except cells show oncocytic damage

65
Q

What are 3 causes of malignant thyroid neoplasms?

A

1) Genetic abberations:
a) Follicular Ca: RAS family mutations, PPAR PAX8 rearrangements
b) Papillary Ca: RET/PTC rearrangements; BRAF mutation
c) Medullary Ca: MEN 2 syndrome (RET mutation)
d) Poorly differentiated and anaplastic carcinoma: TP53 mutations, TERT promoter mutations

2) Environmental (ionising radiation)

3) Longstanding Multinodular goitre

66
Q

What is the key difference between follicular carcinoma and adenoma?

A

Capsular and/or vascular invasion
(defined morphological)
- presence of vascular invasion is a worse prognostic factor

67
Q

What genetic aberrations are a/w follicular carcinoma?

A

RAS family mutations: PPARy/PAX8 rearrangements

68
Q

Follicular carcinoma presents as a (slow/fast) growing (painful/painless) cold nodule.

Prognosis: _______
Metastasises through ________

A

Follicular carcinoma:
- slow growing painless cold nodule
- excellent prognosis
- metastasises through bloodstream to lungs and bone

69
Q

What are the 3 WHO subtypes of follicular carcinoma?

A

1) Minimally invasive (capsular invasion only)
- very good prognosis, 10 year survival >90%

2) Encapsulated angioinvasive (vascular invasion)

3) Widely invasive (obvious gross extension into extra thyroidal tissues)
- moderate prognosis, 10 year survival 50-70%

70
Q

What are 5 variants of papillary carcinoma?

A

1) Classic PTC
2) Follicular variant:
a) infiltrative
b) invasive encapsulated
3) Encapsulated classic PTC (excellent Px)
4) Tall cell variant

71
Q

Papillary carcinoma EPC:
Age group: ________
a/w: ____________

A

Papillary carcinoma EPC:
Age group: 20s-40s but can occur in children
a/w: ionising radiation

72
Q

What are 3 clinical features of papillary carcinoma?

A

1) Painless nodule (cold)
2) Enlarged cervical lymph nodes
3) Hoarseness, cough, dysphagia (BAD)

73
Q

True or false: Papillary carcinoma typically has a good prognosis.

A

True
10y survival >95%

74
Q

True or false: Papillary carcinoma usually undergoes haematogenous metastasis.

A

False:
Metastasis if via lymph nodes

75
Q

What are 4 gross features of a thyroid with papillary carcinoma?

A

1) Solitary/multifocal
2) Encapsulated but infiltrative
3) Whitish nodules
4) Cystic change, calcifications, fibrosis

76
Q

True or false: The identification of papillae is essential in diagnosing papillary thyroid carcinoma microscopically.

A

False

The diagnosis of PTC is based on these nuclear features even in the ABSENCE of papillae

Nuclear features:
1) Finely dispersed chromatin
- ground glass/ Orphan Annie eye nuclei (fine, powdery, open chromatin)
2) Nuclear grooves
3) Pseudoinclusions

77
Q

What are the 3 defining nuclear features of Papillary Thyroid Carcinoma that is used for diagnosis?

A

Nuclear features:
1) Finely dispersed chromatin
- ground glass/ Orphan Annie eye nuclei (fine, powdery, open chromatin)
2) Nuclear grooves
3) Pseudoinclusions

78
Q

What are 5 microscopic features of classic Papillary Thyroid Carcinoma?

A

1) Branching well formed papillae w fibrovascular cores

2) Cells:
- uniform, cuboidal
- Nuclear features:
a) Finely dispersed chromatin
- ground glass/ Orphan Annie eye nuclei (fine, powdery, open chromatin)
b) Nuclear grooves
c) Pseudoinclusions

3) Psammoma bodies

4) Fibrosis, Calcifications

5) Lymphatic invasion

79
Q

What are 5 microscopic features of classic Papillary Thyroid Carcinoma?

A

1) Branching well formed papillae w fibrovascular cores
2) Cells:
- uniform, cuboidal
- Nuclear features:
3) Psammoma bodies
4) Fibrosis, Calcifications
5) Lymphatic invasion

80
Q

What are 2 similarities and 2 differences of the 2 subtypes of Follicular variant PTC?

A

Similarities:
1) Follicular architecture
2) Diagnostic PTC nuclear features:
a) Finely dispersed chromatin
- ground glass/ Orphan Annie eye nuclei (fine, powdery, open chromatin)
b) Nuclear grooves
c) Pseudoinclusions

Differences:
Infiltrative follicular variant PTC
1) Non-encapsulated, infiltrative growth pattern
2) BRAF V600E mutation, RET translocations

Invasive encapsulated FVPTC
1) Encapsulated/circumscribed, with capsular/vascular
invasion
2) RAS mutations, PPARG/PAX8 rearrangements
3) DDx: Follicular carcinoma

81
Q

What is NIFTP?

A

Non-invasive Follicular Thyroid Neoplasm with Papillary-like nuclear features

82
Q

What are 3 characteristics of NIFTP?

A

1) Encapsulated/well-circumscribed (no capsular/vascular invasion)

2) Follicular architecture + some papillary nuclear features

3) Indolent behaviour after lobectomy

4) RAS mutations

83
Q

Why is poorly differentiated thyroid carcinoma also known as insular carcinoma?

A

Growth pattern in large islands

84
Q

How is poorly differentiated thyroid carcinoma diagnosed?

A

Turin criteria:

1) solid/trabecular/insular growth pattern
2) absence of nuclear features of papillary carcinoma
3) at least one of the following three features:
i) mitotic index ≥3/10 high power fields (HPFs)
ii) necrosis
iii) convoluted nuclei

85
Q

Poorly differentiated thyroid carcinoma usually shows:
- _______ pattern of growth
- (increased/decreased) mitotic counts/tumour necrosis
- grossly usually (invasive/encapsulated)
- gene mutations: _____________________
- Px: _________________

A

Poorly differentiated thyroid carcinoma usually shows:
- trabecular/insular pattern of growth in large islands
- increased mitotic counts/tumour necrosis
- grossly usually invasive
- gene mutations: TP53, TERT promoter mutations, RAS mutations
- Px: between low grade and anaplastic thyroid carcinoma

86
Q

Which thyroid neoplasm has the worst prognosis?

A

Anaplastic carcinoma
- survival in months

87
Q

Anaplastic carcinoma EPC:
- Age group: _______
- a/w: ____________

A

Anaplastic carcinoma EPC:
- Age group: mean=65y/o
- a/w: underlying
(i) MNG (50%)
(ii) Well-differentiated thyroid carcinoma (20-30%)

88
Q

What are 3 clinical features of anaplastic thyroid carcinoma?

A

1) Rapidly enlarging, bulky mass
2) Compressive symptoms: (dyspnoea, dysphagia, hoarseness)
3) Often spread beyond thyroid (eg. metastasis to lungs)

89
Q

What intervention improves the survival/prognosis of px with anaplastic thyroid carcinoma?

A

BRAF & MEFK inhibitors (for those with BRAF V600E mutant ATCs)

90
Q

What are 3 microscopic features of anaplastic thyroid carcinoma?

A

Highly pleomorphic cells:
1) Giant tumour cells
2) Spindle cells (sarcomatoid features)
3) Small anaplastic cells

91
Q

What is the pathogenesis of medullary thyroid carcinoma?

A

Parafollicular C cell origin:
- 70% sporadic (40-50y)
- 30% hereditary (younger, multiple tumours)
- MEN2A/2B

Molecular:
- mutations in RET proto-oncogene (in MEN syndrome & in 50% sporadic)

92
Q

What are 4 clinical features of medullary thyroid carcinoma?

A

1) Mass (familial: multiple tumours), may have extrathyroidal extension

2) Grey-white infiltrative mass

3) Paraneoplastic syndromes:
i) VIP secretion: diarrhoea
ii) ACTH secretion: Cushing’s

4) Raised serum calcitonin, +/- CEA

93
Q

MEN2B associated medullary thyroid carcinoma is (more/less) aggressive than sporadic?

A

More

94
Q

What are 5 microscopic features of medullary thyroid carcinoma?

A

1) Epithelioid or spindled cells
2) Salt and pepper chromatin
3) Nest, trabeculae, follicles in architecture
4) Amyloid (Congo Red staining) background
5) C cell hyperplasia (esp in MEN/familial MTC)

95
Q

What is the cellular origin of thyroid lymphoma?

A

B cells (B cell non-Hodgkin lymphoma, large B cell lymphomas, MALT)

96
Q

Most thyroid lymphomas arise in the background of/are associated with _______________.

A

Hashimoto’s thyroiditis

97
Q

What radioisotope is used for a thyroid scan?

A

Tc-99m pertechnetate

98
Q

How do (i) Grave’s disease (ii) Toxic nodular goitre (iii) thyroiditis differ on an RAI thyroid scan?

A

Graves: diffuse symmetrical increased uptake

Toxic nodular goitre: solitary/multiple nodules

Thyroiditis: no/poor uptake

99
Q

Where can radioactivity be found in a px undergoing RAI 24hrs after administration?

A

1) Thyroid
2) Bowel
3) Liver
4) Urinary tract

100
Q

Describe the process of T3/4 biosynthesis.

A

Thyroid follicular cell:
1) I- trapping by Na+/I- symporter into thyroid follicular cells from bloodstream
(Na+ gradient maintained by Na+/K+ ATPase)

2) Transport of I- into follicular colloid by Pendrin

3) Thyroglobulin formed by RER and exocytosed into follicular colloid

Follicular colloid:
4) Oxidation of iodide to iodine by Thyroid Peroxidase (TPO)

5) Iodination of tyrosyl residues on thyroglobulin → DIT/MIT residues by TPO

5) Coupling of 2DIT or 1DIT/1MIT to form T4/3

6) Endocytosis of iodinated thyroglobulin into follicular cells

Thyroid follicular cell:
7) Fusion of iodinated thyroglobulin with lysosome → proteolysis and release of T4, T3, DIT, MIT

8) Release of T4/3 into circulation

101
Q

Describe the peripheral metabolism of thyroid hormones.

A

T4: binds to serum proteins → T1/2: 6-8days
- converted by:
i) Inner ring deiodinase → rT3 (inactive)
ii) Outer ring deiodinase → T3 (active)

102
Q

What is the half-life of T3/4?

A

T4: 6-8days
T3: 1 day

103
Q

Describe the hepatic metabolism of thyroid hormones.

A

Non-deiodinative degradation:
- T4/3 conjugated to glucuronic acid (glucuronide conjugation) and sulfuric acids (sulphate conjugation)
- excreted in bile

104
Q

What is the Wolff-Chaikoff effect?

A

Autoregulation of thyroid secretion in the presence of excess iodine
- via transient inhibition of thyroid peroxidase

105
Q

What are the drugs used to treat hypothyroidism?

A

1) Levothyroxine (T4)
2) Liothyronine (T3)

106
Q

When is Liothyronine preferred over Levothyroxine?

A

When rapid onset is needed (eg. myxedema coma)

107
Q

_____________ should be monitored _______ after initiation/change of levothyroxine dose.

A

TSH
6-8 weeks

108
Q

When would TSH levels be persistently high after levothyroxine therapy?

A

1) Inadequate dosing
2) Poor compliance
3) Malabsorption
4) Drug/food interaction

109
Q

After prescription, when should a px be advised to take levothyroxine?

A

30-45min before breakfast on an empty stomach

  • avoid with antacids, coffee, supplements
110
Q

In px with estrogen hormone replacement treatment, how would the levothyroxine treatment be affected?

A

↑ dose
- due to ↑thyroxine-binding globulin levels

111
Q

How would hypothyroidism management differ in an older patient?

A

Start levothyroxine @ lower dose then slowly titrate upwards until euthyroidism
- reduce risk of precipitating severe angina/MI/osteoporosis

112
Q

How would hypothyroidism management differ in an IHD patient?

A

Start levothyroxine @ lower dose then slowly titrate upwards until euthyroidism
- reduce risk of precipitating severe angina/MI

113
Q

How would hypothyroidism management differ in a pregnant patient?

A

Need 30-50% increase in dose
- thyroid hormone insufficiency → impaired neuropsychological development in offspring, miscarriage, premature birth, low birth weight
- need reduction of dose after pregnancy

114
Q

What are 3 differences between Levothyroxine and Liothyronine?

A

Levothyroxine:
1) Must take on empty stomach
2) Longer T1/2
3) Drug of choice for chronic replacement

Liothyronine:
1) Can take whenever
2) Shorter T1/2
3) Better for acute situations (eg. myxedema coma)

115
Q

How is levothyroxine administered?

A

Oral

116
Q

How is liothyroxine administered?

A

Oral but usually IV in myxedema due to edema of gut impairng absorption

117
Q

What are 5 medications used to treat hyperthyroidism?

A

Thioamides:
1) Carbimazole
2) Propylthiouracil

Iodine/Iodide:
3) Lugol’s solution (I-)
4) Potassium iodide (KI)

Radioactive iodine/Sodium iodide isotopes:
5) I131 (I123 used for diagnosis)

118
Q

What is the moa of thioamides?

A

Inhibit thyroid peroxidase (TPO) enzyme → inhibit iodination to form MIT/DIT

PTU (Propylthiouracil) also inhibits deiodination of T4 to T3

119
Q

True or false: Carbimazole is administered in its biologically active form.

A

False.
Carbimazole converted to active metabolite Thiamazole after absorption

120
Q

What are 4 indications for thioamides?

A

1) Grave’s disease (expected to improve within 3-6 weeks of treatment)
2) Thyroid storm (PTU > Carbimazole as PTU additionally blocks peripheral T4→T3 conversion)
3) Overactive thyroid gland (MNG)
4) To attain euthyroid state to prep for radioiodine therapy or thyroidectomy

121
Q

What are 4 AEs of thioamides?

A

1) **Agranulocytosis → infection
- stop and have FBC
- reversible upon discontinuation + both thioamides auto contraindicated

2) Hepatotoxicity
- PTU > Carbimazole

3) Jaundice

4) Mild, purpuric, urticarial papular rash (subsides spontaneously w/o interrupting treatment)

122
Q

How does thioamide Rx differ in pregnant px?

A

1st tri: PTU, 2nd onwards: Carbimazole
Thiamazole a/w fetal abnormalities but propylthiouracil has maternal AE of hepatotoxicity.

123
Q

How are thioamides administered?

A

Oral

124
Q

What are 2 main differences between Propylthiouracil and Carbimazole?

A

1) PTU (75mins) T1/2 shorter than Carbimazole (4-6hrs, Thiamazole 5-13hrs)
2) PTU hepatotoxicity > Carbimazole

125
Q

PTU should be reserved for px who:
i)_____________________
ii)____________________
iii)____________________

A

PTU should be reserved for px who:
i) px w thiamazole allergy
ii) px in whom RAI therapy and surgery are not appropriate
iii) 1st trimester pregnant women

126
Q

What is the moa of I- in the treatment of hyperthyroidism?

A

High [I-]:
1) suppress iodination of tyrosine and coupling of DIT/MIT → T4/3 synthesis
2) ↓thyroid gland size and vascularity when given over 1-2 weeks
3) Temporarily inhibit T4/3 release into circulation (useful in thyroid storm)

127
Q

As the effect of high [I-] conc. would not be maintained upon discontinuation, severe exacerbations of _________ when the gland “escapes” the iodide block may occur.

A

Thyrotoxicosis

128
Q

What are 4 indications of Lugol’s solution/KI?

A

1) Preparation for thyroidectomy (↓thyroid hormone synthesis and release + size and vascularity)
- may need ß-blockers to ↓risk of thyroid storm

2) Thyrotoxicosis crisis

3) After RAI exposure to block uptake of RAI uptake by thyroid and ↓cancer risk

4) Endemic goitre

129
Q

When is high conc. I- contraindicated?

A

Pregnant px

130
Q

Lugol’s solution is administered (Oral/IV) has a ____hr onset of action and excreted ______.

A

Oral
24-48hr onset of action
Renal clearance

131
Q

What are 4 AEs Lugol’s solution/KI?

A

1) GI intolerance and bitter/metallic taste
- take with juice or milk to protect against irritation

2) Allergic like rxn (angioedema, laryngeal edema → suffocation and rashes)

3) Chronic intoxication (iodism)
- soreness of teeth and gums w ↑salivation, irritation of eyes, lacrimation and rhinorrhoea + severe headache
- disappear after administrate of iodide

132
Q

What is the moa of RAI used in hyperthyroidism?

A

1) RAI trapped by thyroid Na+/I- transporter
2) Destructive ß-particles act on follicular tissues → pyknosis and necrosis of gland

y radiation quantifiable by radiology

133
Q

What are 3 AEs of RAI in treating hyperthyroidism?

A

1) Delayed hypothyroidism (need lifelong levothyroxine replacement)
2) Cancer risk in tissues with Na+/I- transporter (eg. stomach, kidney, breast)
3) Worsening Grave’s ophthalmopathy

134
Q

When is RAI contraindicated?

A

Pregnant women
- concentration of RAI in fetal thyroid
- exposure to fetal tissues to RAI

135
Q

What are 2 indications for RAI?

A

1) Grave’s disease
2) Toxic nodular goiter
- px need to stop thioamide at least 3 days before RAI

136
Q

What 2 main differences between I131 and I123?

A

I131:
1) ß particles, y rays
2) Therapeutic use (thyroid destruction)
3) Longer T1/2: 8days

I123:
1) y rays
2) Diagnostic/imaging
3) short T1/2: 13hrs

137
Q

What are 5 medications used to treat a thyrotoxic storm?

A

1) Antithyroid drugs (Thioamides)
- ↓T4/3 production (+ T4→T3 peripheral conversion by PTU)

2) Inorganic iodine (KI)
- ↓release of T4/3

3) Bile acid sequestrants (Cholestyramine)
- ↓circulating thyroid hormones

4) ß-blockers (propanolol)
- ↓peripheral effects of T3

5) Glucocorticoids (hydrocortisone, dexamethasone)
- ↓peripheral T4→T3 conversion

6) Paracetamol
- ↓fever

138
Q

What are 4 treatment options for Grave’s disease?

A

1) ß-blockers
2) Antithyroid drugs
3) RAI
4) Thyroidectomy

Endocrine System (9 decks)

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