Thyroid + Disorders Flashcards
(86 cards)
1
Q
Anatomy of thyroid?
A
- 2 lobes, sometimes 3rd pyramidal lobe
- Rich blood supply, more blood per unit weight than kidney
- Inferior thyroid artery from thyrocervical trunk of subclavian artery
- Superior thyroid artery as branch of external carotid artery
2
Q
Functional unit of thyroid tissue?
A
roughly spherical follicles
3
Q
How are follicular cells arranged?
A
in layer around colloid (a protein rich storage material, contains a lot of hormones available for release)
4
Q
What does colloid contain?
A
thyroglobulin - protein synthesised by follicular cells + contains tyrosine residues, which get combined with iodine which allow the formation of thyroid hormones
5
Q
Role of follicular cells?
A
- synthesise + secrete TH
- release into colloid
- take them back up from colloid when there is need for release
6
Q
What’s between follicles?
A
capillaries, with basal membrane of follicular cells facing capillary + apical membrane facing the colloid
7
Q
Role of calcitonin?
A
involved in calcium regulation
8
Q
What are thyroid hormones derived from?
A
2 iodinated tyrosine molecules
9
Q
What’s T4?
A
major form released to blood, less active (prohormone)
10
Q
What’s T3?
A
active form, converted in target cells
11
Q
Role of TSH?
A
pituitary hormone thyrotrophin (thyroid stimulating hormone which stimulates active uptake of iodide - control point for hormone synthesis
12
Q
Describe TH synthesis
A
-stimulated by TSH
-active uptake of iodide across basolateral membrane, against conc + electrical gradient by Na/I symporter (NIS)
-iodide diffusion across apical membrane via pendrin exchanger (PDS)
-iodide is oxidized -> I2 +covalently bound to tyrosine residues within thyroglobulin (TG) macromolecule at
extracellular apical membrane
-requires thyroid peroxidase (TPO) + H2O2
-tyrosine residues iodinated in 1 (mono-iodotyrosine, MIT) or 2 (DIT) positions
-coupling of iodotyrosine residues (catalysed by TPO) produces T4 (DIT-DIT) + smaller amount of T3 (MIT-DIT)
13
Q
Describe TH secretion
A
-using TSH
-colloid droplets consisting of thyroid hormones within thyroglobulin molecules taken back up into follicular cells by pinocytosis
-fusion of colloid droplets with lysosomes causes hydrolysis of thyroglobulin + release of T3 and T4
-10% of T4 undergoes mono-deiodination to T3 before secreted
-released iodide reutilized
-several-fold more iodide is reused than is taken from the blood each day but in states of iodide excess there is loss from thyroid
-100 μg TH secreted daily:
(90% T4 + 10% T3). Secretion probably relies on membrane transporter MCT8
14
Q
How do thyroid hormones circulate?
A
99% bound to plasma protein:
thyroid-binding globulin (~70%), transthyretin (10-20%), albumin (10-20%)
15
Q
Features of TH receptors (TRs)?
A
Belong to nuclear receptor superfamily Ligand-activated transcription factors High affinity for T3 DNA binding domain lies upstream to target genes Hormone binding region Regulatory region
16
Q
How’s TH receptors (TRs) activated?
A
requires dimerization with another TR or retinoid X receptor (RXR)
17
Q
How’s TH receptors (TRs) encoded?
A
by two genes: TR α + TR β
18
Q
What’s retinoid X receptor (RXR)?
A
heterodimer partner that binds with other nuclear receptors to DNA response elements
19
Q
Role of deiodinases?
A
Family of 3 enzymes that activate or inactivate TH
Vital for TH homeostasis
Tissue specific (via varying expression of deiodinases) of way of regulating amount of T3 available to bind with the receptor
20
Q
What are the inactive metabolites of T3/T4?
A
T2, rT3
21
Q
What are the transporters required to help TH across membrane?
A
MCT8, OATP1C1
22
Q
What’s MCT8 mutation?
A
mutations in gene discovered to underlie an X-linked condition, Allan–Herndon–Dudley syndrome, which is associated with psychomotor retardation
highly expressed in brain
23
Q
Functions of TH?
A
-Increase metabolic rate: number + size of mitochondria enzymes in metabolic chain Na/K ATPase activity positive inotropic + chronotropic effects on heart synergizes with sympathetic -Energy metabolism partially antagonizes insulin signalling gluconeogenesis, lipolysis -Growth and development
24
Q
How TH increases metabolic rate?
A
Number + size of mitochondria Enzymes in metabolic chain Na/K ATPase activity Positive inotropic + chronotropic effects on heart Synergizes with sympathetic
25
How TH does energy metabolism?
Partially antagonizes insulin signalling
| Gluconeogenesis, lipolysis
26
Role of hypothalamic-pituitary-thyroid axis?
- Negative feedback control of thyroid hormone synthesis + secretion via hypothalamo-pituitary axis
- Hypothalamic neurosecretory cells release thyrotrophin-releasing hormone (TRH) into portal capillaries
- TRH stimulates thyrotrophs of anterior pituitary to secrete thyroid stimulating hormone (TSH)
27
Role of thyrotrophin-releasing hormone (TRH)?
stimulates thyrotrophs of anterior pituitary to secrete thyroid stimulating hormone (TSH)
28
Describe negative feedback control of TH synthesis + secretion
- stress + cold
- hypothalamic neurosecretory cells release thyrotrophin-releasing hormone (TRH) into portal capillaries
- TRH stimulates thyrotrophs of anterior pituitary to secrete thyroid stimulating hormone (TSH)
- targets thyroid gland
- T3, T4 released
- increases metabolic rate, CVS, development
- HIGH T3, T4 --> reduce hypothalamic + anterior pit
29
Possible congenital hypothyroidism in neotatal needle prick if...?
high TSH because no thyroid hormones to do negative feedback
30
Features of TSH receptor?
-G protein coupled receptor
-7 transmembrane spanning domains
-A pathway:
via G proteins activating adenyl cyclase -> cAMP -> PKA
31
Actions of TSH?
Increases iodine uptake
Stimulates other reactions involved in TH synthesis(TPO)
Stimulates uptake of colloid
Induces growth of thyroid gland --> goitre
32
Define euthyroid
normal thyroid function
33
Define hyperthyroidism
TH excess
Primary: problem is thyroid gland itself
Secondary: problem is pituitary regulation
34
Define hypothyroidism
TH deficiency
35
What would you expect from primary hyperthyroidism?
- high T3, T4
- lots of negative feedback
- strong inhibition of hypothalamus + anterior pit
- low TSH
36
What would you expect from primary hypothyroidism?
- low T3, T4
- less negative feedback
- no inhibition of hypothalamus + anterior pit
- high TSH
37
What would you expect from secondary hyperthyroidism?
- anterior pit pumps too much TSH
| - stimulates high T3, T4
38
Features of Grave’s disease: primary hyperthyroidism?
```
Autoimmune
High circulating TH, low TSH
Weight loss, tachycardia, fatigue
Diffuse goitre (TSH receptor stimulation)
Opthalmopathy
```
39
Features of Grave’s disease: primary hyperthyroidism?
```
Autoimmune
High circulating T3, T4, low TSH
Weight loss, tachycardia, fatigue
Diffuse goitre - TSH receptor stimulation
Opthalmopathy
```
40
Describe how Grave’s disease arises
- develop antibodies to TSH receptor
- antibodies act as agonist
- activate TSH recepetor
- stimulate T3, T4
41
Features of Hashimoto’s: primary hypothyroidism?
```
Autoimmune
Low circulating T3, T4, high THS
Lethargy, intolerance to cold
Lack of growth and development
Diffuse goitre
```
42
How's monoiodotyrosine (MIT) made?
Tyrosine + Iodine
43
How's diiodotyrosine (DIT) made?
monoiodotyrosine + iodine
44
How's T3 made?
MIT + DIT
45
How's T4 made?
DIT + DIT
46
What's diffuse goitre?
uniformly swollen
47
What's nodular goitre?
lumpy
48
Symptoms/signs of hyperthryoidism?
- Weight loss despite increased appetite
- Anxiety
- Palpatations
- Diarrhoea
- Hyperactivity
- Tremor
- Eye signs
- Tachycardia
- Exopthalamos (bulging eyes)
(more common in women, less prevalent/noticeable in the elderly)
49
Causes of thyrotoxicosis?
autoimmune so Grave’s disease, toxic multinodular goitre, (toxic adenoma, thyroiditis, TSHoma, follicular thyroid cancer)
50
Symptoms of Graves Disease?
```
present with smooth goitre + exopthalamos.
eye signs :
-Periorbital oedema
-Chemosis (swelling)
-Lid retraction/lid lag
-Proptosis (exophthalmos)
-Opthalmoplegia (paralysis)
```
51
Investigation of hyperthyroidism?
-Assays of fT4, TSH
-Autoantibody assays - TPO, TSH receptor
-Imaging:
ultrasound
nuclear medicine
52
Other features of Graves?
Diabetes, Vitilligo, Onycholysis, Dermopathy, Acropachy
53
MRI of Graves' ophthalmopathy?
Coronal : muscles appear white, enormously enlarged, especially in the left eye
Transverse : rnlarged muscles (appearing dark against light fat signal), exophthalmos is apparent
54
How to diagnose hyperthyroidism in patients older than 70 years?
Classical S/S may be lacking
Goitre may be absent
Anorexia with wasting
AF or congestive heart failure may be predominant manifestations
55
Diagnosis of hyperthyroidism?
-Suppressed TSH
-Measurement of FT3 will be necessary in patient with
C/F of hyperthyroidism
-Normal FT4 (T3 toxicosis seen in MNG)
-Isotope uptake studies
-Thyroid USS
-Thyroid antibody assays in selected cases only
Patient without opthalmopathy, iodine31 uptake scan establishes cause of thyrotoxicosis:
- increased uptake = hyperthyroidism
- lack of uptake = thyroiditis + iodine ingestion
- in MNG defines functional characteristics of gland
56
Treatment of hyperthyroidism?
REFERRED TO SPECIALIST AT DIAGNOSIS
Antithyroid drugs (ATD)
Radioiodine (131I)
Subtotal Thyroidectomy (surgery)
57
Factors to consider after hyperthyroidism diagnosis?
Age
Size of goitre
Presence of co-existing condition
58
eg of antithyroid drugs (ATD)?
Carbimazole, Methimazole, Propylthiouracil block TPO (thyroid perioxidase) enzyme
59
Why do β-blockers help hyperthyroidism patients feel better?
effects of high thyroid are like there's high adrenaline - temporary relief while other medications work.
60
Effect of antithyroid drugs (ATD) on pregnanacy + breast feeding?
Drugs safe in pregnancy
No contraindication to breast feeding
Association of carbimazole with fetal aplasia cutis
Physicians may substitute PTU for CMZ in pregnancy
PTU excreted less in breast milk
Patients receiving CMZ 20mg or less need not be changed to PTU
61
Treatment regimens + outcome?
-CMZ starting dose 15-40mg daily
-PTU starting dose 100-600mg 2x daily
-Titrate treatment against serum T4 concentrations at 4-6 weeks to a maintenance dose
-Follow up at 3-4 months interval
-For the aim of remission treatment has to be used 12-24 months
-Long term remission can be achieved in 50-60% of cases
-Long term treatment with 5-10mg CMZ is safe + option for patients with relapsed Graves’ disease, toxic nodular goitre
-No specific markers for long term remission
-Patients unlikely to undergo remission:
large goitre, positive TSH receptor antibodies, F/H of thyroid disease, opthalmopathy, smoking
62
Radio-iodine indications for hyperthyroidism?
- Safe + appropriate treatment especially in elderly
- Contraindicated in children, pregnancy, breast feeding
- Women of childbearing age should wait for 4 months after 131I before becoming pregnant
- Should be used with caution in patients with opthalmopathy
- Use prophylactic steroids + avoid hypothyroidism
- Patient info sheet should be supplied
- Patient should sign a consent form
- Amount of 131I given should be sufficient to achieve euthyroidism
- In 2-3 months:
- moderate rate of hypothyroidism 15-20% at 1st yr
- 1-3% yearly subsequently
- ablative dose of 131I with higher rate of hypothyroidism is acceptable
63
In patients with hyperthyroidism + low 131I uptake which therapies are indicated?
- Thyroiditis generally resolves spontaneously
- β-blocker sufficient to control the symptoms of hyperthyroidism
- NSAIDs
- Steroids
64
Surgery indications for hyperthyroidism?
```
Large goitre
Failed medical treatment
Non compliance
Side effects
Patient preference
Multinodular goitre
```
65
What's subclinical hyperthyroidism?
- Persistently suppressed TSH with normal FT4 + FT3 in a patient with no symptoms
- No consensus whether such patients should be treated
- Significant morbidity via higher risk of AF in patients over 60 + decreased BMD in postmenopausal women
66
What's hypothyroidism?
non specific, appear insidiously and often attributed to aging
67
Clinical features of hypothyroidism?
- Fatigue
- Cold intolerance
- Weight gain
- Bradycardia
- Constipation
68
Signs + symptoms of hypothyroidism?
```
SLUGGISH
S = sleepy, fatigue, lethargy
L = loss of memory, trouble conc
U = unusually dry, coarse skin
G = goitre
G = gradual personality change, depression
I = increase in weight, bloating, puffiness (oedema)
S = sensitivity to cold
H = hair loss
```
69
Classic features of myxoedema?
```
Nonpitting odema
Periorbital odema
Hoarseness
Sinus bradycardia
Decrease in body temperature
Delayed relaxation of ankle jerks
```
70
Types of hypothyroidism?
Primary hypothyroidism
Central or secondary hypothyroidism
Central or tertiary hypothyroidism
71
How does primary hypothyroidism arise?
From thyroid destruction
72
How does central or secondary hypothyroidism arise?
Deficient TSH secretion due to sellar lesions such as pituitary tumor or craniopharyngioma
Infrequently is congenital
73
How does central or tertiary hypothyroidism arise?
Deficient TSH stimulation above level of pituitary
Lesions of pituitary stalk or hypothalamus
less common than secondary hypothyroidism
74
Investigations of hypothyroidism?
```
Serum assays - fT4, TSH
Autoantibody assays - TPO, Thyroglobulin
Imaging:
ultrasound
nuclear medicine
-check for angina + ecg
```
75
Laboratory investigations of hypothyroidism?
- Increased TSH
- It antedates a decline in FT4
- Presence of antibodies will confirm autoimmune thyroiditis as the cause
- Occur in association with other autoimmune disorders, pernicious anemia or Addisons’
- Mild anemia
- Increased CK
- Abnormal lipids with high total + LDL cholesterol
76
Treatment of hypothyroidism?
Thyroxine - aiming to normalise the serum TSH concentration
77
Thyroxine dosage for hypothyroidism?
- Initial dose : 50-100ug
- Measurement of TSH after 6 weeks
- Adjust the dose by 25-50ug
- Older patients especially those with IHD, initial dose : 25ug increased every 4 weeks by 25ug
- Dose of thyroxine in patients treated for thyroid carcinomas should suppress TSH below normal<0.05
78
TSH range?
0.4 – 5.5 mU/L
79
Variation in thyroxine dosage for hypothyroidism?
- Once the appropriate dose is established it remains constant in most patients
- In pregnancy increase dose by 50ug daily to maintain normal TSH concentration
- TSH should be measured in each trimester
80
Mild Hypothyroidism + Pregnancy?
- TSH testing in 1st trimester
- To maintain euthyroid state, LT4 dose increased during pregnancy
- Maternal hypothyroidism during gestation --> variety of fetal complications
81
Consequences of Mild Hypothyroidism Fetal Brain Development?
Children have:
Averaged 7 points lower on IQ testing
Had a sig percentage (19%) of IQ <85
82
When do you test for hypothyrodism?
-Regular testing in patients on amiodarone which may be difficult to detect clinically:
can result in hypothyroidism or hyperthyroidism
-Testing recommended in patients with deteriorating cardiac function or weight loss
-Early specialist referral is advised in view of difficulties in interpreting biochemical abnormalities
83
Typical thyroid hormone levels in hypothyroidism vs hyperthyroidism?
HYPOTHYROIDISM:
high TSH, low T4, low T3
HYPERTHYROIDISM:
low TSH. high T4, high T3
84
Signs + symptoms of thyroid disease?
```
Depend on thyroid function:
-euthyroidism
-hypothyroidism
-hyperthyroidism
Size of goitre:
-dysphagia
-dysphonia
-dyspnoea
```
85
What are thyroid tumours?
```
Papillary Thyroid carcinoma
Follicular carcinoma
Anaplastic carcinoma
Medullary thyroid carcinoma
Lymphoma
```
86
Investigation of thyroid tumours?
FNA cytology
