L37, L38 Thyroid and its production Flashcards
1
Q
What type of gland is the thyroid and what does it secrete?
A
It is an endocrine gland that secretes T3 (triiodothyronine) and T4 (thyroxine) directly into the bloodstream.
2
Q
What are the main functions of thyroid hormones?
A
Regulate growth, development, and basal metabolic rate.
3
Q
Where is the thyroid gland located and how is it structured?
A
In the neck, butterfly-shaped with two lobes and a central isthmus.
4
Q
What do parafollicular (C) cells secrete and what is their function?
A
Calcitonin, which lowers blood calcium by inhibiting osteoclasts.
5
Q
What do follicular cells do?
A
Produce and store thyroid hormones (T3 and T4).
6
Q
What is the first step in thyroid hormone synthesis?
A
Iodide uptake via the sodium/iodide symporter (NIS).
7
Q
What protein helps iodide enter the follicular lumen?
A
Pendrin.
8
Q
What is thyroglobulin (Tg)?
A
A large glycoprotein that acts as a scaffold for thyroid hormone synthesis.
9
Q
What enzyme catalyses iodination and coupling of thyroglobulin?
A
Thyroid peroxidase (TPO).
10
Q
What are the end products of coupling reactions?
A
T3 (MIT + DIT) and T4 (DIT + DIT).
11
Q
How are T3 and T4 released into the bloodstream?
A
Via the MCT8 transporter after colloid is endocytosed and digested.
12
Q
What is the HPT axis?
A
Hypothalamus (TRH) → Pituitary (TSH) → Thyroid (T3/T4)
13
Q
How does negative feedback work in thyroid regulation?
A
High T3/T4 inhibits TRH and TSH production.
14
Q
What type of receptor is the TSH receptor (TSHR)?
A
A G-protein-coupled receptor (GPCR).
15
Q
What are the main pathways activated by TSH?
A
Gαs → cAMP/PKA, and Gαq → PLC/IP3/DAG.
16
Q
What are the effects of TSH on thyroid cells?
A
Stimulates iodide uptake, Tg and TPO expression, and thyroid hormone synthesis.
17
Q
What is the main source of active T3?
A
Peripheral conversion of T4 by deiodinases (mainly D2).
18
Q
What are the roles of D1, D2, and D3?
A
D1: Activates/inactivates; secondary T3 source.
D2: Main activator of T3.
D3: Inactivates T3 and T4.
19
Q
How are thyroid hormones transported in blood?
A
Bound to TBG(thyroxine-binding-globulin) (~70%), TTR(Transthyretin) (~15–20%), Albumin (~10–15%).
20
Q
What percentage of thyroid hormones are free and active?
A
Free T4 = 0.03%, Free T3 = 0.3%.
21
Q
What are developmental roles of thyroid hormones?
A
Essential for brain development and skeletal growth.
22
Q
How do thyroid hormones affect BMR?
A
Increase BMR via oxygen consumption and mitochondrial activity.
23
Q
What are metabolic effects of T3?
A
↑ Glycogenolysis & gluconeogenesis, ↑ lipid mobilisation, ↓ cholesterol.
24
Q
How does T3 affect the heart?
A
Increases heart rate and contractility.
25
What are thyroid hormone receptors (THRs)?
Nuclear receptors that bind T3 and act as transcription factors.
26
What are the main subtypes of THRs and their roles?
α1: Widespread (heart, muscle).
α2: Cannot bind T3, may suppress.
β1: Liver, kidney, brain.
β2: Pituitary, CNS – feedback.
27
What are non-genomic effects of thyroid hormones?
Rapid signalling via MAPK/PI3K and modulation of ion channels.
28
What are common thyroid disorders?
Hyperthyroidism, Hypothyroidism, Goitre, Thyroid cancer.
29
: What is Apparent Cortisone Reductase Deficiency (ACRD)?
A condition affecting cortisol/cortisone balance via a novel ER redox mechanism.
30
Describe the full synthesis of thyroxine (T4) in the thyroid gland.
1. Iodide Uptake:
Iodide enters thyroid follicular cells from blood via the sodium/iodide symporter (NIS) on the basolateral membrane.
2. Iodide Transport into Lumen:
Iodide passes into the follicular lumen via Pendrin on the apical membrane.
3. Thyroglobulin (Tg) Secretion:
Tg (a glycoprotein with 132 tyrosines) is secreted into the lumen and serves as a scaffold.
4. Iodination of Tg:
Catalysed by thyroid peroxidase (TPO) using H₂O₂.
Forms MIT (1 iodine) and DIT (2 iodines) on Tg tyrosines.
5. Coupling Reaction:
TPO couples two DIT molecules → T4.
Also couples MIT + DIT → T3.
6. Storage:
Iodinated Tg is stored as colloid in the lumen.
7. Release:
Upon TSH stimulation, colloid is endocytosed and digested in lysosomes to release free T3 and T4.
8. Secretion:
T3 and T4 exit via MCT8 transporters at the basolateral membrane into the bloodstream.
31
What is colloid and where is it found?
Colloid is a protein-rich substance containing iodinated thyroglobulin, stored in the follicular lumen of the thyroid gland.
32
What are the three shapes of follicular cells and what do they indicate?
Cuboidal: Normal activity
Columnar: Stimulated (active hormone synthesis)
Squamous: Inactive or suppressed thyroid function
33
What is the role of the sodium/iodide symporter (NIS)?
Transports iodide into follicular cells from the bloodstream against its concentration gradient; located on the basolateral membrane.
34
What does Pendrin do in the thyroid gland?
Transports iodide into the follicular lumen across the apical membrane.
35
What is the role of MCT8 in thyroid hormone physiology?
Transports T3 and T4 from follicular cells into the bloodstream and into peripheral tissues.
36
Where is Deiodinase 1 (D1) expressed and what is its function?
Found in liver and kidney; activates and inactivates thyroid hormone and contributes to circulating T3 levels.
37
Where is Deiodinase 2 (D2) found and what does it do?
Found in the CNS, pituitary, heart, placenta, and skeletal muscle; converts T4 to active T3 for local tissue use and serum contribution.
38
What is the role of Deiodinase 3 (D3) and where is it found?
Found in CNS and placenta; inactivates T3 and T4, regulating hormone excess and protecting tissues.
39
Why are thyroid hormones mostly protein-bound in circulation?
Binding prolongs half-life, prevents renal clearance, and maintains a reservoir of hormone.
40
Why is iodine important for thyroid health?
It is essential for thyroid hormone synthesis; deficiency can lead to goitre and hypothyroidism.
41
What is the effect of iodine deficiency during pregnancy?
It can cause severe developmental problems in the foetus, including cretinism and intellectual disability.
42
What is the most likely diagnosis in a young woman with low TSH and raised T4/FT3, weight loss, palpitations, and anxiety?
Graves’ disease (autoimmune hyperthyroidism).
43
What is the most common cause of hyperthyroidism in the UK?
Graves’ disease.
44
What is the underlying mechanism of Graves’ disease?
Autoantibodies (TRAb) stimulate the TSH receptor, causing excess thyroid hormone production.
45
List 5 classic symptoms of hyperthyroidism.
Weight loss, palpitations, anxiety, heat intolerance, tremor.
46
What eye signs are associated with Graves’ disease?
Exophthalmos (bulging eyes), lid lag, periorbital oedema.
47
What menstrual irregularity is often seen in hyperthyroidism?
Oligomenorrhoea or amenorrhoea.
48
What are the typical thyroid function test (TFT) results in Graves’ disease?
Suppressed TSH, raised free T4 and T3.
49
What is the role of TRAb testing in hyperthyroidism?
Confirms autoimmune cause (Graves') as they're the reason why thyroid is overstimualated by mimickinng TSH
50
What is the first-line antithyroid medication used in Graves’ disease in the UK?
What is a major and potentially life-threatening side effect of carbimazole?
Carbimazole.
Agranulocytosis (drop in white cells → risk of infection).
51
What advice should be given to a patient on carbimazole who develops a sore throat or fever?
Stop the drug and seek urgent blood tests (FBC) to check for agranulocytosis.
52
What medication is used to manage palpitations and tremor in hyperthyroidism?
Beta-blockers, e.g. propranolol.
53
What are the long-term treatment options for Graves’ disease?
Continued antithyroid drugs, radioiodine therapy, or thyroidectomy.
54
Why is carbimazole use in pregnancy controversial?
It is teratogenic, especially in the first trimester.
| means it can cause birth defects
55
What is the preferred antithyroid drug in early pregnancy?
Propylthiouracil (PTU), due to a better safety profile in the first trimester.
56
Why should radioiodine therapy be avoided in pregnancy?
It can damage the fetal thyroid gland.
57
What is toxic multinodular goitre (TMG)?
Hyperthyroidism caused by autonomous hormone production from thyroid nodules, often in an enlarged thyroid, independent of TSH.
58
What is thyroiditis and how does it present?
Inflammatory destruction of thyroid tissue causing a temporary release of preformed hormone. Often painless or mildly painful and self-limiting.
59
What imaging can help differentiate Graves’ disease from thyroiditis?
Radioactive iodine uptake (RAIU) scan – increased uptake in Graves’, low uptake in thyroiditis.
60
Which antibodies are often positive in Graves' disease?
TSH receptor antibodies (TRAb – positive in ~99%) and thyroid peroxidase antibodies (TPO Abs – ~75%).
61
When is a thyroid ultrasound indicated?
To assess nodules or goitre, especially if malignancy is suspected.
62
How does carbimazole work?
It inhibits thyroid peroxidase, blocking iodination and coupling of thyroglobulin, thus reducing thyroid hormone synthesis.
63
How long is the typical course of antithyroid drugs for Graves’?
12–18 months with regular TFT monitoring.
64
What lab test is needed before starting antithyroid drugs?
Full blood count (FBC) and liver function tests (LFTs).
65
What are signs of thyroid storm?
High fever, tachycardia, delirium, hypotension – it’s a medical emergency.
66
What is the treatment for thyroid storm?
High-dose antithyroid drugs (e.g. PTU), beta-blockers, corticosteroids, supportive ICU care.
67
What is the hypothalamic-pituitary-thyroid (HPT) axis?
TRH from the hypothalamus stimulates TSH from the pituitary, which stimulates T3 and T4 release from the thyroid. T3/T4 then suppress TRH and TSH (negative feedback).
68
What is the difference between T3 and T4?
T3 is the active hormone; T4 is a prohormone converted to T3 by deiodinases.
69
What features suggest malignancy in a thyroid nodule?
Rapid growth, firmness, fixation, lymphadenopathy, microcalcifications, hypoechogenicity, irregular margins.
70
What are the four main types of thyroid cancer?
Papillary (PTC) – Most common (85%), spreads via lymphatics.
Follicular (FTC) – Spreads haematogenously.
Medullary (MTC) – From C-cells, linked to MEN2.
Anaplastic (ATC) – Rare and aggressive.
71
What is the gold standard for assessing thyroid nodules?
Fine Needle Aspiration Cytology (FNAC).
72
What does a “cold” nodule on a radionuclide scan suggest?
Higher risk of malignancy.
73
What TFT pattern suggests primary hypothyroidism?
↑ TSH, ↓ free T4.
74
What TFT pattern suggests secondary (central) hypothyroidism?
↓ TSH, ↓ free T4 (both low, pituitary cause).
75
What does elevated TSH and normal T4 indicate?
Subclinical hypothyroidism.
76
What happens to thyroid hormone requirements during pregnancy?
They increase — levothyroxine doses usually need to be increased.
77
What is postpartum thyroiditis?
Transient hyperthyroidism followed by hypothyroidism, often resolves spontaneously.
78
What do deiodinase enzymes do in thyroid physiology?
D1/D2: Convert T4 to active T3.
D3: Converts T3 and T4 into inactive forms (e.g. reverse T3). 001882056790
79
Where is D2 especially active?
Brain, pituitary, placenta, brown adipose tissue.
80
Which proteins bind thyroid hormones in the blood?
Thyroxine-binding globulin (TBG) – ~70%
Transthyretin (TTR) – ~15–20%
Albumin – ~10–15%
Only free T3/T4 are biologically active.
81
What antibodies are commonly found in Hashimoto’s?
TPO antibodies and anti-thyroglobulin antibodies.
82
What does Hashimoto’s look like histologically?
Lymphocytic infiltration, fibrosis, and follicular cell destruction.
83
What safety advice should be given when prescribing carbimazole?
Warn about symptoms of agranulocytosis (e.g. sore throat, fever) and advise immediate medical review if these occur.
84
When is surgery preferred over other hyperthyroidism treatments?
Large goitre, pregnancy with drug intolerance, severe eye disease, patient choice.
85
What are the key tests used to diagnose thyroid conditions and what does each test tell us?
1. TFTs (Thyroid Function Tests)
What:
TSH
Free T4
Free T3
Why:
First-line test to assess thyroid function.
Helps determine whether a patient is hyperthyroid, hypothyroid, or euthyroid.
Interpretation Examples:
↓ TSH, ↑ T3/T4 = Primary hyperthyroidism
↑ TSH, ↓ T4 = Primary hypothyroidism
↓ TSH, ↓ T4 = Secondary (central) hypothyroidism
🧫 2. Thyroid Autoantibodies
Tests:
TSH Receptor Antibodies (TRAb)
Thyroid Peroxidase Antibodies (TPO Abs)
Anti-thyroglobulin (Tg) antibodies
Why: TRAb: Positive in ~99% of Graves’ disease — diagnostic marker.
TPO Abs: Present in 75–90% of Graves’ and ~90% of Hashimoto’s.
Helps confirm autoimmune origin of disease.
☢️ 3. Radioactive Iodine Uptake (RAIU) Scan
What: Measures iodine uptake by the thyroid.
Why: Differentiates causes of hyperthyroidism.
Interpretation:
High uptake → Graves’, toxic nodular goitre
Low uptake → Thyroiditis, factitious thyrotoxicosis
📸 4. Thyroid Ultrasound (USS)
What:
Imaging using high-frequency sound waves.
Why:
- First-line imaging for nodules or goitre.
- Assesses size, vascularity, solid/cystic composition, and suspicious features.
Findings Suggestive of Malignancy:
- Irregular margins, microcalcifications, hypoechogenicity, taller-than-wide shape.
💉 5. Fine Needle Aspiration Cytology (FNAC)
What:
Aspiration of thyroid tissue for cytological examination.
Why:
Gold standard for assessing thyroid nodules for malignancy.
Interpreted using Bethesda classification (I–VI).
🧪 6. Other Supportive Tests
Thyroglobulin levels: Can be used in monitoring thyroid cancer.
Calcitonin: Marker of medullary thyroid carcinoma.
CT/MRI: For large goitres with retrosternal extension or compressive symptoms.
Barium swallow/flow loops: If trachea or oesophagus is compressed.
