Thyroid Flashcards
(138 cards)
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
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)
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
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
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
6
Q
Which hormones are routinely tested for in a px with suspected thyroid dysfunction?
A
1) TSH
2) Free T4
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
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)
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)
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
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)
12
Q
What are 4 causes of hyperthyroidism?
A
1) Grave’s disease
2) Hyperplasia
3) Nodular goitre
4) Neoplasms
13
Q
What are 2 causes of hypothyroidism?
A
1) Hashimoto thyroiditis
2) Congenital abnormalities
14
Q
Which thyroid conditions can lead to euthyroid?
A
1) Nodular goitre
2) Neoplasms
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
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
17
Q
How are thyroglossal duct cysts treated?
A
Complete excision
18
Q
What are 2 forms of abnormal development of thyroid glands?
A
1) Aplasia
2) Hypoplasia
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
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
21
Q
What is thyroid dyshormonogenesis?
A
Inherited defects in thyroid hormone synthesis leading to congenital hypothyroidism and goitre
22
Q
How does thyroid dyshormonogenesis present?
A
Mental and growth retardation
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)
24
Q
Multinodular goitre is a __________ from simple goitre.
A
Progression
- recurrent hyperplasia and involution
25
True or false: A simple goitre is a form of hyperthyroidism.
False.
Simple goitre is known as diffuse non-toxic (non-hyperfunctioning) goitre
26
What are the 2 morphological phases of diffuse goitre?
1) Hyperplastic stage
- Diffuse mild enlargement
- micro: crowded columnar cells, pseudopapillae
2) Colloid involution
- Micro: flattened cuboidal epithelium
- abundant colloid
27
Multinodular goitre is an evolution of _______ and shows extreme, irregular enlargement ± cystic change.
Multinodular goitre:
- progress from simple goitre
- extreme, irregular enlargement
- cystic change
28
True or false: Multinodular goitre is the most common cause of goitre
True
29
What are 2 complications of multinodular goitre?
1) Mass effects:
a) trachea → wheeze, stridor, hypoxia
b) oesophagus → dysphagia
c) recurrent laryngeal nerve → hoarseness
2) Toxic goitre → hyperthyroidism
30
What are 2 autoimmune conditions affecting the thyroid?
1) Hashimoto thyroiditis
2) Grave's disease (form of thyroid hyperplasia)
31
What are 2 examples of thyroiditides?
1) Granulomatous thyroiditis (DeQuervain thyroiditis)
2) IgG-4-related thyroiditis
3) Hashimoto's thyroiditis
32
What is the #1 cause of hypothyroidism where dietary iodine is sufficient?
Hashimoto’s thyroiditis
33
Hashimoto thyroiditis EPC:
(M/F)
Which age group
Familial clustering: _________
a/w other autoimmune conditions eg. _______
Hashimoto thyroiditis EPC:
F 10-20X > M
45-65 y/o
Familial clustering: HLA - DR3, DR5
a/w other autoimmune conditions eg. T1DM
34
Describe the pathogenesis of Hashimoto thyroiditis.
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
35
What are 3 clinical features of Hashimoto’s thyroiditis?
1) Painless goitre (diffuse>localised)
2) Hypothyroidism (T3/4 down, TSH up)
3) Anti-TPO, TSH, Tg Abs
4) Preceding transient thyrotoxicosis (hashitoxicosis)
36
What is the gross morphology of Hashimoto’s thyroiditis?
1) Pale, enlarged gland (diffuse > localised)
2) Pale, yellow firm cut surface (may be nodular)
37
What is the 3 microscopic features of Hashimoto’s thyroiditis?
1) Infiltrates: reactive lymphoid follicles, lymphocytes, plasma cells
2) Thyroid follicles - atrophic, Hurthle (oncocytic) cell change
3) Fibrosis
38
What are 3 complications of Hashimoto’s thyroiditis?
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)
39
What is the #1 cause endogenous hyperthyroidism?
Grave’s disease
40
Graves’s disease EPC:
(M/F)
Age group
Family Hx + genes ___________
a/w with other autoimmune conditions
Graves’s disease EPC:
Women 7x > Men
20-40 y/o
Family Hx + HLA-B8, DR3
41
Describe the pathogenesis of Graves’ disease.
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)
42
What are 6 clinical features of Graves’ disease?
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)
43
Describe the pathogenesis of ophthalmopathy in Graves’ disease.
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
44
What are 2 gross features of a thyroid gland afflicted with Grave’s disease?
1) Symmetrical diffuse enlargement
2) Soft, reddish meaty cut surface
45
What are 3 microscopic features of Grave’s disease?
1) Follicular cells (pseudopapillae: tall, columnar, crowded)
2) Colloid (pale, scalloped)
3) Lymphoid infiltrates, reactive lymphoid follicles
46
What is the pathogenesis of granulomatous thyroiditis (DeQuervain thyroiditis)?
Suggested:
Viral-induced Tc cell response to thyroid Ags lead to damage of follicular cells
47
True or false: Granulomatous (DeQuervain) thyroiditis is usually self-limiting
True
48
What are 5 clinical features of granulomatous (DeQuervain thyroiditis)?
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
49
What are 2 macroscopic features of Granulomatous (DeQuervain) thyroiditis?
1) Enlarged and firm gland (uni/bilateral)
2) Patchy, firm pale-yellowish areas w intervening normal parenchyma
50
What are 3 microscopic features of Granulomatous (DeQuervain) thyroiditis?
1) Destruction of follicles (w neutrophils, microabscesses)
2) Lymphocytes, plasma cells, histiocytes around damages follicles
3) Multinucleated giant cells, engulfing pools of colloid
51
IgG4-related thyroiditis mimics ______ clinically with progressive __________ and adherence to neck structures. It is the likely underlying pathology in “________”
IgG4-related thyroiditis mimics malignancy
Progressive fibrosis, enlargement
Likely underlying pathology in “Riedel thyroiditis”
52
IgG4-related thyroiditis:
Serology: ________
Treatment: _________
A/W: ______________
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)
53
What are 2 microscopic features of IgG4-related thyroiditis?
Microscopic features:
1) Lymphoplasmacytic infiltration (IgG4-producing plasma cells)
2) Fibrosis
3) Obliterative thrombophlebitis
54
Which of the thyroid neoplasms are associated with RAS mutations (PPARy/PAX8 rearrangments)?
1) Follicular adenoma (benign)
2) Follicular carcinoma (low grade malignant)
55
Which of the thyroid neoplasms are associated with BRAF mutations (RET/PTC rearrangements)?
Papillary thyroid carcinoma (low grade malignant)
56
Which of the thyroid neoplasms are associated with RET mutations?
Medullary carcinoma (C cells)
57
Which of the thyroid neoplasms are associated with general mutations/rearrangements & TERT, TP53 mutations?
High grade malignant:
1) Poorly differentiated thyroid carcinoma (PDTC)
2) Differentiated high grade thyroid carcinoma
Undifferentiated:
3) Anaplastic thyroid carcinoma (ATC)
58
What are 2 non-follicular cell origin thyroid neoplasms?
1) Medullary carcinoma
2) Lymphoma
59
What are 2 benign thyroid neoplasms of follicular cell origin?
1) Follicular adenoma
2) Oncocytic/Hurthle cell adenoma
60
What are 2 benign thyroid neoplasms of follicular cell origin?
1) Follicular adenoma
2) Oncocytic/Hurthle cell adenoma
61
What are 5 malignant thyroid neoplasms of follicular cell origin?
Low grade:
1) Papillary thyroid carcinoma
2) Follicular carcinoma
High grade:
3) Poorly differentiated thyroid carcinoma (PDTC)
4) Differentiated high grade thyroid carcinoma
Undifferentiated:
5) Anaplastic thyroid carcinoma
62
What is the clinical feature of benign thyroid neoplasms?
Solitary painless nodule
(Euthyroid)
63
What is the gross morphology of follicular adenoma and carcinoma (can look the same)?
1) Rounded, encapsulated
2) Well demarcated nodules
3) Intact capsule
4) Bulging from the cut surface
64
What is the microscopic appearance of benign thyroid adenomas?
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
What are 3 causes of malignant thyroid neoplasms?
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
What is the key difference between follicular carcinoma and adenoma?
Capsular and/or vascular invasion
(defined morphological)
- presence of vascular invasion is a worse prognostic factor
67
What genetic aberrations are a/w follicular carcinoma?
RAS family mutations: PPARy/PAX8 rearrangements
68
Follicular carcinoma presents as a (slow/fast) growing (painful/painless) cold nodule.
Prognosis: _______
Metastasises through ________
Follicular carcinoma:
- slow growing painless cold nodule
- excellent prognosis
- metastasises through bloodstream to lungs and bone
69
What are the 3 WHO subtypes of follicular carcinoma?
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
What are 5 variants of papillary carcinoma?
1) Classic PTC
2) Follicular variant:
a) infiltrative
b) invasive encapsulated
3) Encapsulated classic PTC (excellent Px)
4) Tall cell variant
71
Papillary carcinoma EPC:
Age group: ________
a/w: ____________
Papillary carcinoma EPC:
Age group: 20s-40s but can occur in children
a/w: ionising radiation
72
What are 3 clinical features of papillary carcinoma?
1) Painless nodule (cold)
2) Enlarged cervical lymph nodes
3) Hoarseness, cough, dysphagia (BAD)
73
True or false: Papillary carcinoma typically has a good prognosis.
True
10y survival >95%
74
True or false: Papillary carcinoma usually undergoes haematogenous metastasis.
False:
Metastasis if via lymph nodes
75
What are 4 gross features of a thyroid with papillary carcinoma?
1) Solitary/multifocal
2) Encapsulated but infiltrative
3) Whitish nodules
4) Cystic change, calcifications, fibrosis
76
True or false: The identification of papillae is essential in diagnosing papillary thyroid carcinoma microscopically.
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
What are the 3 defining nuclear features of Papillary Thyroid Carcinoma that is used for diagnosis?
Nuclear features:
1) Finely dispersed chromatin
- ground glass/ Orphan Annie eye nuclei (fine, powdery, open chromatin)
2) Nuclear grooves
3) Pseudoinclusions
78
What are 5 microscopic features of classic Papillary Thyroid Carcinoma?
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
jia yous
80
What are 2 similarities and 2 differences of the 2 subtypes of Follicular variant PTC?
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
What is NIFTP?
Non-invasive Follicular Thyroid Neoplasm with Papillary-like nuclear features
82
What are 3 characteristics of NIFTP?
1) Encapsulated/well-circumscribed (no capsular/vascular invasion)
2) Follicular architecture + some papillary nuclear features
3) Indolent behaviour after lobectomy
4) RAS mutations
83
Why is poorly differentiated thyroid carcinoma also known as insular carcinoma?
Growth pattern in large islands
84
How is poorly differentiated thyroid carcinoma diagnosed?
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
Poorly differentiated thyroid carcinoma usually shows:
- _______ pattern of growth
- (increased/decreased) mitotic counts/tumour necrosis
- grossly usually (invasive/encapsulated)
- gene mutations: _____________________
- Px: _________________
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
Which thyroid neoplasm has the worst prognosis?
Anaplastic carcinoma
- survival in months
87
Anaplastic carcinoma EPC:
- Age group: _______
- a/w: ____________
Anaplastic carcinoma EPC:
- Age group: mean=65y/o
- a/w: underlying
(i) MNG (50%)
(ii) Well-differentiated thyroid carcinoma (20-30%)
88
What are 3 clinical features of anaplastic thyroid carcinoma?
1) Rapidly enlarging, bulky mass
2) Compressive symptoms: (dyspnoea, dysphagia, hoarseness)
3) Often spread beyond thyroid (eg. metastasis to lungs)
89
What intervention improves the survival/prognosis of px with anaplastic thyroid carcinoma?
BRAF & MEFK inhibitors (for those with BRAF V600E mutant ATCs)
90
What are 3 microscopic features of anaplastic thyroid carcinoma?
Highly pleomorphic cells:
1) Giant tumour cells
2) Spindle cells (sarcomatoid features)
3) Small anaplastic cells
91
What is the pathogenesis of medullary thyroid carcinoma?
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
What are 4 clinical features of medullary thyroid carcinoma?
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
MEN2B associated medullary thyroid carcinoma is (more/less) aggressive than sporadic?
More
94
What are 5 microscopic features of medullary thyroid carcinoma?
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
What is the cellular origin of thyroid lymphoma?
B cells (B cell non-Hodgkin lymphoma, large B cell lymphomas, MALT)
96
Most thyroid lymphomas arise in the background of/are associated with _______________.
Hashimoto’s thyroiditis
97
What radioisotope is used for a thyroid scan?
Tc-99m pertechnetate
98
How do (i) Grave's disease (ii) Toxic nodular goitre (iii) thyroiditis differ on an RAI thyroid scan?
Graves: diffuse symmetrical increased uptake
Toxic nodular goitre: solitary/multiple nodules
Thyroiditis: no/poor uptake
99
Where can radioactivity be found in a px undergoing RAI 24hrs after administration?
1) Thyroid
2) Bowel
3) Liver
4) Urinary tract
100
Describe the process of T3/4 biosynthesis.
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
Describe the peripheral metabolism of thyroid hormones.
T4: binds to serum proteins → T1/2: 6-8days
- converted by:
i) Inner ring deiodinase → rT3 (inactive)
ii) Outer ring deiodinase → T3 (active)
102
What is the half-life of T3/4?
T4: 6-8days
T3: 1 day
103
Describe the hepatic metabolism of thyroid hormones.
Non-deiodinative degradation:
- T4/3 conjugated to glucuronic acid (glucuronide conjugation) and sulfuric acids (sulphate conjugation)
- excreted in bile
104
What is the Wolff-Chaikoff effect?
Autoregulation of thyroid secretion in the presence of excess iodine
- via transient inhibition of thyroid peroxidase
105
What are the drugs used to treat hypothyroidism?
1) Levothyroxine (T4)
2) Liothyronine (T3)
106
When is Liothyronine preferred over Levothyroxine?
When rapid onset is needed (eg. myxedema coma)
107
_____________ should be monitored _______ after initiation/change of levothyroxine dose.
TSH
6-8 weeks
108
When would TSH levels be persistently high after levothyroxine therapy?
1) Inadequate dosing
2) Poor compliance
3) Malabsorption
4) Drug/food interaction
109
After prescription, when should a px be advised to take levothyroxine?
30-45min before breakfast on an empty stomach
- avoid with antacids, coffee, supplements
110
In px with estrogen hormone replacement treatment, how would the levothyroxine treatment be affected?
↑ dose
- due to ↑thyroxine-binding globulin levels
111
How would hypothyroidism management differ in an older patient?
Start levothyroxine @ lower dose then slowly titrate upwards until euthyroidism
- reduce risk of precipitating severe angina/MI/osteoporosis
112
How would hypothyroidism management differ in an IHD patient?
Start levothyroxine @ lower dose then slowly titrate upwards until euthyroidism
- reduce risk of precipitating severe angina/MI
113
How would hypothyroidism management differ in a pregnant patient?
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
What are 3 differences between Levothyroxine and Liothyronine?
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
How is levothyroxine administered?
Oral
116
How is liothyroxine administered?
Oral but usually IV in myxedema due to edema of gut impairng absorption
117
What are 5 medications used to treat hyperthyroidism?
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
What is the moa of thioamides?
Inhibit thyroid peroxidase (TPO) enzyme → inhibit iodination to form MIT/DIT
PTU (Propylthiouracil) also inhibits deiodination of T4 to T3
119
True or false: Carbimazole is administered in its biologically active form.
False.
Carbimazole converted to active metabolite Thiamazole after absorption
120
What are 4 indications for thioamides?
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
What are 4 AEs of thioamides?
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
How does thioamide Rx differ in pregnant px?
1st tri: PTU, 2nd onwards: Carbimazole
Thiamazole a/w fetal abnormalities but propylthiouracil has maternal AE of hepatotoxicity.
123
How are thioamides administered?
Oral
124
What are 2 main differences between Propylthiouracil and Carbimazole?
1) PTU (75mins) T1/2 shorter than Carbimazole (4-6hrs, Thiamazole 5-13hrs)
2) PTU hepatotoxicity > Carbimazole
125
PTU should be reserved for px who:
i)_____________________
ii)____________________
iii)____________________
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
What is the moa of I- in the treatment of hyperthyroidism?
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
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.
Thyrotoxicosis
128
What are 4 indications of Lugol's solution/KI?
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
When is high conc. I- contraindicated?
Pregnant px
130
Lugol's solution is administered (Oral/IV) has a ____hr onset of action and excreted ______.
Oral
24-48hr onset of action
Renal clearance
131
What are 4 AEs Lugol's solution/KI?
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
What is the moa of RAI used in hyperthyroidism?
1) RAI trapped by thyroid Na+/I- transporter
2) Destructive ß-particles act on follicular tissues → pyknosis and necrosis of gland
## Footnote
y radiation quantifiable by radiology
133
What are 3 AEs of RAI in treating hyperthyroidism?
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
When is RAI contraindicated?
Pregnant women
- concentration of RAI in fetal thyroid
- exposure to fetal tissues to RAI
135
What are 2 indications for RAI?
1) Grave's disease
2) Toxic nodular goiter
- px need to stop thioamide at least 3 days before RAI
136
What 2 main differences between I131 and I123?
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
What are 5 medications used to treat a thyrotoxic storm?
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
What are 4 treatment options for Grave's disease?
1) ß-blockers
2) Antithyroid drugs
3) RAI
4) Thyroidectomy
