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Pharmacy Y3S1 > Thyroid > Flashcards

Thyroid Flashcards

1
Q

Where is the thyroid gland?

A

Infront of the trachea and cartilage

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2
Q

Which cells secrete T3 and T4? Describe these cells

A

Thyroid follicular cells

Thyroglobuilin filled follicular lumen - thyroglobulin contains iodide to supply thyroid hormones for 90 days

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3
Q

Which cells secrete calcitonin? Where are these?

A

Parafollicular C cells

Inbetween thyroid follicular cells

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4
Q

Describe the response to low temperature

A

Hypothalamus releases TRH
TRH stimulates anterior pituitary to produce TSH
TSH stimulates thyroid glands to secrete T3 and T4
T3 has actions on the body to increase metabolism and heat production

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5
Q

What effect does low T3 have on the pituitary thyrotropes?

A

Stimulates high TSH levels = thyroid enlargement and increased activity

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6
Q

What effect does high T3 have on the pituitary thyrotropes?

A

Stimulates low TSH levels = thyroid regression and reduced activity

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7
Q

How does TSH have an effect on the thyroid folicular cells?

A

Via TSH receptors
G-protein coupled (GPC) receptors
Activates adenylate cyclse to produce cAMP (intracellular messanger)

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8
Q

What roles does cAMP have in the thyroid cell?

A 
Activates:
Thyroglobulin synthesis
Iodine pumping
Iodination by throid peroxidase
Endocytosis, proteolysis and hormone release
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9
Q

How does iodid get into follicular cells?

A

Sodium/Iodide Symporter (NIS) - Na in against gradient brings I- basolateral membrane
Pendrin transports I- across apical membrane

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10
Q

What happens to I- once in the follicle lumen?

A

Oxidised to I by TPO

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11
Q

Which enzyme is responsible for iodination of thyroglobulin (Tg)?

A

Thyroid peroxidase (TPO) enzyme complex which spans the apical membrane

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12
Q

Which two complexes form when I is added to Tg?

A

Mono-iodotyrosine (MIT)

Di-iodotyrosine (DIT)

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13
Q

How do T3 and T4 form?

A

2 x DIT = T4

DIT + MIT = T3

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14
Q

Which method do the iodinated tyrosine residues get cleaved from the Tg by?

A

Proteolysis

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15
Q

How much of T3 and T4 is found in the blood?

A

90% T4

10% T3

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16
Q

How is T4 transported and why?

A

By specific binding proteins

Hydrophobic so is indoluble in serum

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17
Q

Why can liver disease affect T4 transport to peripheral tissues?

A

Binding proteins are synthesis in the liver

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18
Q

What are the three thyroid hormone binding proteins? How much T4 do they bind?

A

Albumin (5-10% T4)
Transthyretin (TTR) (30% T4 - CNS Delivery)
Thyroxine-binding globulin (70-75% T4 - prevents loss in urine)

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19
Q

Which of the throid hormone binding proteins bind T3 and T4?

A

TBG

Albumin

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20
Q

Which thyroxine hormones can enter cells and how?

A

Unbound T3 and T4 via specific transporters - MCT8, MCT10, OATP1c1

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21
Q

Are T3 and T4 biologically active?

A 
T3 = yes 
T4 = not really
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22
Q

How is T4 converted to T3?

A 
Iodothryonine deiodinases (DOI)
Selenium accepts iodide
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23
Q

Describe DIO1

A

Predominates liver, kidney, muscle (where highest blood supply)
Found in thyroid
Produces most circulating T3

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24
Q

Describe DIO2

A

Predominates CNSM pituitary thyrotropes
(skeletal muscle in some species)
Controls intracellular T3 conc
Important for feedback regulation

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25
DIO3
Produces inactive rT3 | Prevents thyroid hormone access to specific tissues e.g. during pregnancy
26
What happens to T3 once in the nucleus?
Binds to thyroid receptor Binds to Thyroid response element (TRE) Functions as a transcription factor Increases/inhibits gene transcription
27
Describe the Thyroid hormone receptors
TRA and TRB Found in the nucleus Heterodimer with retinoid X receptor
28
The feedback of T3 on the anterior pituitary can cause:
Increased growth hormone Reduced prolactin Reduced alpha and beta subunits of TSH
29
What are the 5 biological actions of thyroid hormones?
``` Control of metabolic rate Growth Foetal development Cardiovascular effects Musculoskeletal effects ```
30
How does the thyroid control basal metabolic rate?
Increase in metabolic proteins = Na+K+ATPase, mitochondrial and respiratory enzymes, other enzymes and proteins, proteins for tissue growth and maturation. Need an increase in oxygen (input CO2 and substrates) which causes an increase in metabolic rate (output)
31
How do thyroid hormones have a role in growth regulation?
Synergise with other hormones Deficiencies = abnormal growth, development, reproduction, behavior, metabolism Effects on all organs and tissues throughout life
32
What is the role of thyroid hormones in foetal development?
Neural and skeletal systems | Loss of T4 supply to foetus = irreversible mental impairment and congenital iodine deficiency syndrome
33
What are the effects of iodine deficiency on a foetus?
``` Miscarriage Stillbirth Congenital abnormalities Perinatal morbidity & mortality Congenital iodine deficiency syndrome ```
34
What are the effects of iodine deficiency on a neonate?
Neonatal goiter Neonatal hypothyroidism Impaired mental function
35
What are the effects of iodine deficiency on a child and adolescent?
Goiter (subclinical) hypothyroidism Impaired mental function Impaired physical development
36
What overall effect do the thyroid hormones have on the cardiovascular system?
``` T3 increases: cardiac contraction and output heart rate oxygen supply to tissues CO2 removal from tissues ```
37
What direct effects does T3 have on the cardiovascular system?
Increases myocardial Ca2+ uptake Increases expression of a-myosin heavy chain and reduces beta Increases expression of RYR in SR
38
What indirect effects does T3 have on the cardiovascular system?
Increases metabolism = thermogenesis = vasodilation | Increases sensitivity to catecholamines
39
What musculoskeletal effects does T3 have?
Potent stimulatory effect on bone turnover = increases formation and resorption Increases linear bone growth after birth Increases rate of muscle relaxation
40
What causes hypothyroididm?
Autoimmune disease Previous treatment for hyperthyroidism Iodine imbalance Congenital hypothyroidism
41
What are the symptoms of hypothyroidism
``` Lethargic Weak Dry scaly skin Sensitive to cold Depression Hair loss Memory loss Weight gain Constipation Puffy face and gruff voice if untreated ```
42
What is done to test thyroid function?
TFT's Thyroid peroxidase antibody used Hypo = High TSH but Low unbound T4
43
How is hypothyroidism managed in non-pregnant adults?
High TSH and low T4 = Levothyroxine Low TSH and Low T4 = Look if symptoms Yes = levothyroxine 6 months and see if it resolves No = measure TPO antipody
44
What is the initial hypothyroisism treatment for adults UNDER 50?
Initially 50-100mcg levothyroxine daily | Adjust by 25-50mcg every 3-4 weeks (to response)
45
What is the initial hypothyroisism treatment for adults OVER 50 and in heart disease?
Initially 25mcg daily | Adjust by 25mcg
46
What is the initial congenital hypothyroisism treatment?
Initially 10-15 mcg/kg for neonates (max 50mcg) | Adjust 5mcg/kg
47
After initial treatment with levothyroxine, when should TSH be measured?
After 8-12 weeks
48
What is the usual maintenance dose of levothyroxine?
Adults: 100-200mcg Children: 50-200 mcg depending on age
49
On maintenance of levothyroxine, how often should TSH be measured?
Adults: Yearly Children: every 4-6 months
50
What patient counselling should be given with levothyroxine?
``` Lifelong treatment Single daily dose Do not take at the same time as calcium or iron preparations or caffeine beverages Three strengths Monitoring Medical exemption certificate ```
51
What causes hyperthyroidism?
Autoimmune disease (Grave's) Toxic nodules Antibodies to TSH receptor stimulate the gland and increase the production of thyroid hormones
52
What are the symptoms of hyperthyrodism?
``` Anxious Palpitations Tremor Weight loss Tachycardia Goitre Heat intolerance Warm moist skin Difficulty sleeping Diarrhoea ```
53
What is the expected outcome of a thyroid function test for hyperthyroidism?
Low TSH and High free T4
54
How does drug therapy stop hyperthyroidism?
Intereferes with thyroid hormone synthesis by inhibiting thyoperocidase activity in the follicular lumen
55
What is the regime for Carbimazole?
15-40mg daily Maintain until TFTs normal (1-8 weeks) Maintain for 12-18 months - reduce by 25-30% monthly until 5-15mg
56
What is a blocking-replacement regimen with carbamazole?
40-60mg for approx 4 weeks THEN add thyroxine 50-100mg (treat up to 18 months) Make temporarily hypothyroid
57
Why should a blocking-replacement regimen not be used in pregnancy?
Only carbimazole can cross the placenta making foetus hypothyroid
58
Can carbimazole be used in pregnancy?
Only consider after benefit-risk assessment at the lowest effective dose without any additional administration of thyroid hormones
59
How much Propylthoiuracil should be given and when is it used?
Initially 200-400mg daily (3 doses) Then 50mg TDS maintenance Use in pregnancy or carbimazole intolerance
60
How do carbimazole and Propylthoiuracil cause drug-induced agranulocytosis?
Cause bone marrow suppression | Reduce white cell count = infection
61
What patient counselling should be given for carbimazole and Propylthoiuracil?
Carbimazole = OD Propylthoiuracil = TDS Duration and tapering to maintenance Report agranulocytosis signs: sore throat, mouth ulcer, bruising Report hepatic dysfunction (Propylthoiuracil): pruritis, jaundice, dark urine Advise on contraception (contraception) Need for regular reviews/tests Hyper=NOT entitled to medical exemption certificate
62
What is radioactive iodine preferred for?
``` First-line treatment except for mild disease or if radioactivity unsuitable If no response to drug treatment If relapse after drugs Comorbid cardiac disease Toxic nodular goitre ```
63
What is surgery preferred for?
Oesophageal obstruction Intolerance to drug treatment Young adults
64
Before iodide or surgery, why should the patient be made euthyroid?
To prevent thyrotoxic crisis due to dangerously high levels of T4 released into system
65
What is an adjuvant therapy in hyperthyroism
Beta-blockade | Propanolol, Nadolol
66
How does Iodine induce thyroid disease?
Overdose: Acute - inhibits T3/T4 release Prolonged - suppresses T3/T4 production
67
How does Amiodarone induce thyroid disease?
Contains organic iodine Hypo: inhibits synthesis and release of T3/T4 (start replacement therapy) Mild hyper: Blocks T4 to T3 conversion (increases TSH and T4) Severe hyper: increased production of T4 (do to iodine content) - stop/carbimazole
68
How does Lithium induce thyroid disease?
Hypo: inhibits iodine uptake and prevents T3/T4 release (replace T4) Hyper:rare
69
Give examples of Ca2+ homeostasis diseases
``` Primary hyperparathyroidism Secondary hyperparathyroidism Osteoporosis Rickets Calcium Stones Receptor mutations Paget's disease ```
70
What are the two types of cells in the parathyroid gland?
Chief calls | Oxyphil cells
71
Which cells produce parathyroid hormone?
Chief cells
72
What is the function of parathyroid cells?
Increase blood Ca2+ conc when it gets too low
73
How is low Ca2+ detected?
By G-protein coupled Ca2+ sensing receptors (CaSR)
74
How does PTH work?
Raises blood Ca2+: Indirectly stimulates osteoclasts to release more Ca from bone (resorption) Increased renal Ca reabsorption Increased Vit D production (stimulates Ca uptake from intestine and above)
75
How is PTH regulated?
Negative feedback | Increase in blood Ca decreases PTH and increases bones formation
76
How does calcitonin work?
Reduces blood Ca2+ | Reduces osteoclast activity to reduce bone resorption and allows rapid bone deposition by osteoblast
77
How is calcitonin regulated?
Negative feedback | Decrease in blood Ca decreases calcitonin secretion and reduces bone formation
78
Which diseases are caused by calcitonin?
None

Pharmacy Y3S1 (14 decks)

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