week 3 Flashcards
1
Q
define primary and secondary thyroid disease
A
primary = disease affecting thyroid itself (goitre or non-goitrous)
Secondary - Hypothalamic or pituitary disease (No thyroid gland pathology)
2
Q
commonest cause of primary thyroid disease?
A
AI thyroid D most commonly
3
Q
why are diabetes patients with poor glycemic control more prone to infection?
A
they are IC - high BG causes WBC to stop working as effectively
4
Q
what thyroid hormones in inactive and when?
A
T4, always (free) until converted to T3
5
Q
what are some thyroid hormones (TH)?
A
TSH - Thyroid stimulating hormone/thyrotropin.
T4 - thyroxine (80% of TH secreted)
T3 - triiodothyronine (remaining 20%)
6
Q
how are T3/4 found in the body?
A
[>99%] bound to plasma proteins (TBG, albumin and pre-albumin)
7
Q
what is TBG
A
Thyroxine-binding globulin
8
Q
what is TSH release by and why?
A
thyrotroph cells in anterior pituitary in response to thyrotropin releasing hormone (TRH)
9
Q
what does TSH levels reflect?
A
Reflects tissue thyroid hormone action
10
Q
what is the Hypothalamic-pituitary-thyroid (HPT) axis
A
negative feedback system responsible for the regulation of metabolism..
senses low T3/T4 and releases TRH.
11
Q
bloods/biochemical PC of primary hypothyroidism
A
Free T3/4 low
TSH high
12
Q
bloods/biochemical PC of primary hyperthyroidism
A
Free T3/4 high
TSH low
13
Q
bloods/biochemical PC of secondary hyperthyroidism
A
Free T3/4 high TSH high (or ‘normal’)
14
Q
bloods/biochemical PC of secondary hypothyroidism
A
Free T3/4 low TSH low (or ‘normal’)
15
Q
define hypothyroidism
A
in insufficient secretion of thyroid hormones from the thyroid gland
16
Q
define Myxoedema
A
severe hypothyroidism and is a medical emergency
17
Q
what is Pretibial myxoedema? why does it occur?
A
it’s a rare clinical sign of Graves’ disease, an autoimmune thyroid disease which results in hyperthyroidism
18
Q
what are three risk factors for developing hypothyroidism
A
white ethnicity
female
area of high iodine intake
19
Q
causes of primary hypothyroidism
A
Goitrous:
Chronic thyroiditis, (Hashimoto’s thyroiditis), Iodine deficiency
[Drug-induced (e.g. amiodarone, lithium), Maternally transmitted (e.g. antithyroid drugs), Hereditary biosynthetic defects]
Non-goitrous:
Atrophic thyroiditis
[Post-ablative therapy (e.g. radioiodine, surgery)
Post-radiotherapy (e.g. for lymphoma treatment)
Congenital developmental defect}
Self-limiting
[Following withdrawal of antithyroid drugs
Subacute thyroiditis with transient hypothyroidism
Post-partum thyroiditis]
20
Q
what are the three commonest causes of primary hypothyroidism?
A
Chronic thyroiditis (Hashimoto’s thyroiditis)
Iodine deficiency
atrophic thyroiditis
21
Q
what are the causes of secondary hypothyroidism?
A
Diseases of the hypothalamus and pituitary gland (multiple!):
[Infiltrative Infectious Malignant Traumatic Congenital Cranial radiotherapy Drug-induced…]
22
Q
Chronic thyroiditis (Hashimoto’s thyroiditis): how common is it and what is it?
A
commonest cause of hypothyroidism in the Western world. (F>M, strong FHx)
Autoimmune destruction of thyroid gland and reduced thyroid hormone production
23
Q
what is Hashimoto’s thyroiditis characterised by?
A
Antibodies against thyroid peroxidase (TPO)
T-cell infiltrate and inflammation microscopically
24
Q
clinical features of Hypothyroidism? hair and skin
A
hair and skin = coarse/sparse hair, dull expressionless face, periorbital puffiness, pale skin cool and doughy to touch, vitiligo, hypercarotenaemia.
25
clinical features of Hypothyroidism? thermogenesis
intolerant to cold
26
clinical features of Hypothyroidism? fluid retention
pitting oedema
27
clinical features of Hypothyroidism? cardiac
Reduced heart rate
Cardiac dilatation
Pericardial effusion
Worsening of heart failure
28
clinical features of Hypothyroidism? metabolic
hyperlipidaemia.
decreases appetite
weight gain
29
clinical features of Hypothyroidism? GI
Constipation
(Megacolon and intestinal obstruction)
(Ascites)
30
clinical features of Hypothyroidism? resp?
Deep hoarse voice
Macroglossia (large tongue)
Obstructive sleep apnoea
31
clinical features of Hypothyroidism: neuro?
```
Decreased intellectual and motor activities
Depression, psychosis, neuro-psychiatric
Muscle stiffness, cramps
Peripheral neuropathy
Prolongation of the tendon jerks
Carpal tunnel syndrome
(Cerebellar ataxia, encephalopathy)
Decreased visual acuity
```
32
clinical features of Hypothyroidism: reproductive?
Menorrhagia
Later oligo- or amenorrhoea
Hyperprolactinaemia - ↑TRH causes ↑ PRL secretion
33
lab investigations of primary hypothyroidism
↑TSH and ↓fT4/3 – cardinal abnormalities
```
Other abnormalities:
Macrocytosis (↑MCV)
↑Creatine kinase (CK)
↑LDL-cholesterol
Hyponatraemia -↓renal tubular water loss
Hyperprolactinaemia -↑TRH leads to ↑PRL (often mild)
```
34
diagnosis for AI hypothyroidism
anti-TPO antibody (anti-thyroglobulin)
35
management of hypothyroidism
thyroxine (levothyroxine) gradually until normal metabolic rate restored
check TSH 2 months after any dose change
once stabilised TSH should be checked 12-18 months
Secondary hypothyroidism: TSH unreliable (↓TSH production), Titrate dose of levothyroxine to the fT4 level
36
why must levothyroxine be given gradually?
Rapid restoration of metabolic rate may precipitate cardiac arrhythmias, also caution in Hx of IHD (lower dose, gradual).
37
drugs in management of hypothyroidism
levothyroxine mainly.
levothyroxine combination with T3 rarely given (some patients like as onset+ elimination quicker)
[take before breakfast without other medications]
38
pregnancy and hypothyroidism
inc dose 25%-50% of T4 (as there is inc in TBG)
39
myxoedema coma
elderly women with long standing but frequently unrecognised or untreated hypothyroidism
Mortality up to 60%
40
what findings are seen on myxoedema coma?
ECG: bradycardia, low voltage complexes, varying degrees of heart block, T wave inversion, prolongation of the QT interval
Type 2 respiratory failure: hypoxia, hypercarbia, respiratory acidosis
Co-existing adrenal failure is present in 10% of patients
41
treating myxoedema coma
ABCDE,
Passively rewarm: aim for a slow rise in body temperature
Cardiac monitoring for arrhythmias
Close monitoring of urine output, fluid balance, central venous pressure, blood sugars, oxygenation
Broad spectrum antibiotics
Thyroxine cautiously (hydrocortisone - adrenal failure)
42
define thyrotoxicosis
the clinical, physiological and biochemical state arising when the tissues are exposed to excess thyroid hormone
43
define hyperthyroidism
refers specifically to conditions in which overactivity of the thyroid gland leads to thyrotoxicosis
44
Thyrotoxicosis – symptoms and signs(cardiac)
```
Palpitation, atrial fibrillation (AF)
Cardiac failure (very rare)
```
45
Thyrotoxicosis – symptoms and signs (sympathetic)
tremor
| sweating
46
Thyrotoxicosis – symptoms and signs CNS
Anxiety, nervousness, irritability, sleep disturbance
47
Thyrotoxicosis – symptoms and signs GI
Frequent, loose bowel movements
48
Thyrotoxicosis – symptoms and signs -vision
```
Lid retraction (not specific to Graves’)
Double vision (diplopia)
Proptosis (Graves)
```
49
Thyrotoxicosis – symptoms and signs (hair and skin)
Hair change – brittle, thin hair
| Rapid fingernail growth
50
Thyrotoxicosis – symptoms and signs -reproductive
Menstrual cycle changes, including lighter bleeding and less frequent periods
51
Thyrotoxicosis – symptoms and signs muscles
Muscle weakness, especially in the thighs and upper arms
52
Thyrotoxicosis – symptoms and signs - metabolism + thermogenesis
weight loss and inc appetite
| intolerance to heat
53
causes of thyrotoxicosis associated with hyperthyroidism
Excessive thyroid stimulation:
Graves’ disease
Hashitoxicosis
Thyrotropinoma (THSoma, very rare)
Thyroid cancer (only very rarely cause thyrotoxicosis)
Choriocarcinoma (trophoblast tumour secreting hCG)
Thyroid nodules with autonomous function:
Toxic solitary nodule
Toxic multinodular goitre
54
key causes of thyrotoxicosis associated with hyperthyroidism
Graves' disease
Toxic solitary nodule
Toxic multinodular goitre
55
key causes of thyrotoxicosis not associated with hyperthyroidism
Subacute (de Quervain’s) thyroiditis
| Post-partum thyroiditis
56
causes of thyrotoxicosis not associated with hyperthyroidism
Thyroid inflammation (thyroiditis):
Subacute (de Quervain’s) thyroiditis
Post-partum thyroiditis
Drug-induced thyroiditis (e.g. amiodarone)
Exogenous thyroid hormones:
Over-treatment with levothyroxine
Thyrotoxicosis factitia
```
Ectopic thyroid tissue:
Metastatic thyroid carcinoma
Struma ovarii (teratoma containing thyroid tissue)
```
57
Graves' disease epidemiology
female, 20-50years, genetics susceptible (70%) and FHx in women strong. Smoking important.
58
Graves' disease lab findings
↓TSH and ↑fT4/3 – cardinal abnormalities
```
Other abnormalities:
Hypercalcaemia and ↑Alkaline phosphatase
Reflective of increased bone turnover
Graves’ associated with osteoporosis
Leucopenia (↓white cell count)
Often mild and related to the disease rather than treatment (ATD-induced agranulocytosis)
TSH receptor antibody (TRAb)
No need to image thyroid gland if raised titre found
```
59
Graves' disease diagnosis
TSH receptor antibody
| anti-TPO of present (70-80% and 40% anti-thyroglobulin)
60
clinical sign specific to Graves' disease
pretibial myxoedema
thyroid acropachy
thyroid bruit
graves' eye-disease
61
graves' ophthalmopathy/thyroid eye disease
smoking cessation important
TRAb driven pathophysiology
Most disease is mild but can be severe and sight-threatening (unilateral/bilateral. 20% get and 20% have before graves' diagnosis)
62
treatment of graves eye disease
Mild disease treated with topically (e.g. lubricants)
| More severe disease: steroids, radiotherapy (poor evidence base), surgery
63
nodular thyroid disease epidemology
```
Older patients
More insidious onset
Thyroid may feel nodular
Asymmetrical goitre
(smooth in Graves’)
```
64
tests for nodular thyroid disease
↑fT4/3, ↓TSH
Antibody negative (TRAb)
Scintigraphy: high uptake
Thyroid US
65
what is thyroid storm? common signs/sympotms? who is it commonly seen in?
Medical emergency, Severe hyperthyroidism,
Respiratory and cardiac collapse, Hyperthermia, Exaggerated reflexes, May require mechanical ventilation
Typically seen in hyperthyroid patients with an acute infection/illness or recent thyroid surgery
66
treatment for thyroid storm
Treatment: Lugol’s Iodine, glucocorticoids, PTU, β-blockers, fluids, monitoring
67
treatment of hyperthyrodism
antithyroid drugs (ATDs), BB, radioiodene, thyroidectomy
68
name two ATDs and their MOA
carbimazole - 1st line.
PTU/propylthiouracil - 1st line only in 3rd trimester.
MOA: inhibition of TPO thereby blocking thyroid hormone synthesis
69
difference between carbimazole and PTU?
once vs twice daily dosing. lower rate of side effects with carbimazole. PTU 10x less potent
70
which ATD carries risk of aplasia in early pregnancy and which drug has risk of liver disease?
PTU - liver
carbimazole - aplasia in pregnacy
71
side effects of ATDs?
Generally well tolerated drugs
1-5% will develop allergic type reactions – rash, urticaria, arthralgia
Cholestatic jaundice, ↑liver enzymes, fulminant hepatic failure (PTU)
Agranulocytosis (cannot be used again if have - 6 weeks=highest risk. 0.3% people - )
72
whitest be done when prescribing ATD's?
tell patient orally and in writing - stop drug and have urgent FBC checked in event of fever, oral ulcer or oropharyngeal infection
(Agranulocytosis)
73
BB: MOA, BB of choice, side effects in hyperthyrodism
Mechanism: β-adrenoceptor blockade, reduced activity of sympathetic nervous system (Useful for immediate symptomatic relief of thyrotoxic symptoms)
Propranolol is the drug of choice - Additional benefit of inhibition of DIO1
Use with caution in those with asthma as Risk bronchospasm - use CCB
74
radioiodene when is it used? contraindicated?
1st choice treatment for relapsed Graves’ disease and nodular thyroid disease. Safe, no increased risk of thyroid cancer
Contraindicated in pregnancy; Relatively contraindicated in active thyroid eye disease (can be used with steroid cover); Contact precautions (stay away from children/pregnant)
[High risk of hypothyroidism when used in Graves’ disease]
75
thyroidectomy when is it used? problems?
Useful when radioiodine is contraindicated,leaves Scar
Surgical/anaesthetic risks:
recurrent laryngeal nerve palsy
Hypothyroidism
Hypoparathyroidism
76
what is thyroiditis? causes of it?
inflammation of the thyroid
```
Hashimoto’s
De Quervain’s/subacute (viral)
Post-partum
Drug-induced (amiodarone, lithium)
Radiation
Acute suppurative thyroiditis (bacterial)
```
77
subacute thyroidits course
self-limiting - neck tenderness, fever, or other viral symptoms. (viral trigger)
78
amiodarone and the thyroid
TFTs anormal in half of patients (inhibition of DIO1- ↑fT4, ↓fT3, normal TSH). hypo in 13% (iodene rich areas) and hyper in 2% (iodine deficient areas)
79
subclinical thyroid disease is what?
Abnormal TSH with normal thyroid hormone levels.
80
subclinical hypothyroidism
Risk of progression to overt hypothyroidism
Higher risk if strongly TPO antibody positive
Treatment generally advised if TSH >10
Always treat in pregnancy to maintain normal TSH
81
Subclinical hyperthyroidism
Risk of progression to overt hyperthyroidism
Often seen in multinodular goitre
Association with osteoporosis and atrial fibrillation
Treatment generally advised if TSH <0.1 (or if co-existing osteoporosis/fracture or AF)
82
non-thyroidal illness/sick euthyroid syndrome
Commonly encountered in the unwell, hospitalised patient
Refers to the impact of intercurrent illness (e.g. severe infection) on the HPT axis
TSH typically suppressed initially then rises during recovery
Avoid checking TFTs in unwell patients unless clinical suspicion of thyroid disease
83
```
68 yr old lady
Tiredness
Weight gain
Slowness
Goitre
```
TSH 42 mU/L
Free T4 4 pmol/L
primary hypothyroidsim
84
normal ranges of TSH and free t4
TSH 0.4-4.0 mU/L
| Free T4 9.8-18.8 pmol/L
85
68 yr old lady
Family history of thyroid disease
Tiredness
Goitre
TSH 12 mU/L
Free T4 11 pmol/L
TPO Antibodies 200 (elevated)
Subclinical hypothyroidism
86
```
52 yr old male
Headache
Visual field defect
Dizziness/weakness
Poor libido/loss of erections
TSH 0.20 mU/L
Free T4 6 pmol/L
```
Pituitary tumour causing secondary hypothyroidism
87
```
32 yr old lady
Weight loss and tremor
Feels tired
Sleep disturbance
TSH <0.01 mU/L
Free T4 54 pmol/L
```
Graves’ disease
| do additional antibody tests
88
```
70 yr old lady
Diagnosed with atrial fibrillation
No symptoms
TSH <0.01 mU/L
Free T4 26 pmol/L
```
Toxic multinodular goitre
89
```
32 yr old
Sore throat and febrile illness
Tired, weight loss, poor sleep
GP blood tests:
TSH<0.01, T4 36 pmol/L
Seen in clinic 6 weeks later
TSH 12 mU/L, Free T4 9 pmol/L
```
Subacute thyroiditis
90
solitary thyroid lump. how many people have them? how many benign?
5% female population has them, 95% benign
91
what can cause a benign Solitary Thyroid Nodule
Cyst
Colloid Nodule
Benign Follicular adenoma
Hyperplastic Nodule
92
what can cause a malignant Solitary Thyroid Nodule
```
PAPILLARY THYROID CARCINOMA – 80%
Follicular Thyroid Carcinoma
Medullary Thyroid Carcinoma
(Lymphoma)
(Poorly Differentiated)
```
93
how can you tell if a lump in the neck in a solitary thyroid nodule?
moves on swallowing? (invested in pre-trchela fascia).
pain is an uncommon feature (usually caused by bleed into a cyst causing pain)
94
Hx, exam, investigation of solitary thyroid nodule
neck irradiation, FHx of thyroid Cancer
LN, hoarseness
TSH, USS-FNA
95
treatment for malignant solitary thyroid nodule
lobectomy or thyroidectomy (consider radioactive iodine)
96
Follow up of a Differentiated Thyroid Cancer
TSH lower level of normal (0.4-4 mU/l)
Thyroglobulin – protein precursor of T4/T3; made by thyroid follicular epithelial cell - Use Tg as a tumour cell marker for follow up of patient
Get TSH/Tg measured every 6 months for first 5 years then annually for next 5 years
97
which thyroid cancer speads by LNs?
papillary (commonest 80%)
98
what investigation is good at showing is LN involvement?
USS
99
follicular thyroid carcinoma (how common and prognosis)
10%, diagnosis depends on invasion of the capsule or vascular invasion (minimally to wide invasive) - surgery usually sufficient
100
how do follicular thyroid carcinomas spread?
Haematogenous spread
101
treatment of FTC (follicular)
most are minimally invasive and treated with lobectomy - if significant vascular involement then thyroidectomy
102
thyroid lymphoma clinical picture
long-standing (AI) hypothyroidism, 70-80 female, rapid growth
103
what is needed to diagnoses thyroid lymphoma
core biopsy
104
treatment of thyroid lymphoma
steroids if actually unwell, radio/chemotherapy. goodish prognosis
105
medullary thyroid carcinoma arrises from which cell? why is this important?
rare tumour of the parafollicular cells which secrete CALCITONIN – can be used as a tumour cell marker
106
how can medullary thyroid carcinoma be diagnosed? what should also be check once diagnosed with MTC?
FNA – presence of amyloid or Calcitonin positive stains
Should always Check 24 hour urinary metanephrines and genetics
107
what genes can be associated with medullary thyroid cancer?
MEN2a and MEN2b (familial)
[can also be sporadic or non-MEN familial]
108
MEN2a(b) gene gives increased incidence of what conditions? why is it important to identify MEN2a link?
Medullary TC, Phaeochromocytoma, Hyperparathyroidism
prophylactic thyroidectomy as child possible
109
what to do if suspect a multi-nodular goitre?
Assess Function
Assess Structure – what is being squashed (symptoms of stridor or choking lying flat)?
TSH
CT scan
110
in a multi nodular goitre what are the results of the investigations?
TSH – usually normal or slightly suppressed; occasionally needs antithyroid drugs (Radioactive iodine/RAI)
CT scan:
Retrosternal Extension
Tracheal Compression
111
treatment of multi nodular goitre
Most can leave alone
RAI if significant hyperthyroidism
Surgery if structural problem (or significant retrosternal extension)
112
who is surgery offered to with retrosternal goitres?
Lifestyle interfering symptoms
Possibility of cancer
Significant tracheal compression (?<7 mm)
Tracheal Flow Loops if other respiratory potential causes of orthopnoea/breathing difficulties
? Audible Stridor
113
when is a flow volume loop done concerning goitres??
if there is another potential cause for breathlessness.
114
what does the thyroid gland secrete?
Thyroxine (T4)
Tri-iodothyronine (T3)
Calcitonin
115
structure of the thyroid gland
bow tie (2 lobes with isthmus)
116
blood supply to the thyroid gland
highly vascular organ,
sup and inferior thyroid arteries (branch of external carotid +/- thyroidea ima).
Three pairs of veins drain- superior/ middle thyroid vein > internal jugular, inferior thyroid vein> brachiocephalic veins
117
where is the thyroid located?
5th cervical- 1st thoracic vertebrae/ 2-4th tracheal rings
118
innervation of the thyroid
autonomic nerve supply (Parasympathetic from vagus nerves, and sympathetic fibers from superior, middle, and inferior ganglia of the sympathetic trunk
119
what is the posteromedial aspect of the thyroid gland is attached by
berry's ligament
120
cells of the thyroid
follicle made up of follicular cells (Colloid is enclosed by follicular cells, colloid is a tyrosine-containing thyroglobulin)
parafolicular C cells (secrete calcitonin)
121
Release of Thyroid Hormones.
Iodine ions travel from blood supply through follicular cell to colloid thyroglobulin with T3 and T4. pinocytosis then occurs in and binds to lysosomes in follicular cell with causes T3 and T4 to be released and then diffuse into bloodstream
122
what the the pyramidal lobe of the thyroid
extra lobe
123
Synthesis and Storage of T3 and T4?
iodine taken up by follicle cells, then done attached to tyrosine residues on thyroglobulin to form MIT and DIT. coupling of MIT-DIT or DIT x2 occurs to form T3/T4 respectively. They are stored in colloid thyroglobulin until required.
124
what is Inhibited by CARBIMAZOLE & PROPYLTHIOURACIL used to treat hyperthyroidism
iodine attached to tyrosine residues on thyroglobulin to form (MIT) & (DIT)
125
thyroid hormones. which is secreted more, which is more potent? where does conversion take place?
T4 = 90%, T3 is more potent.
T4 made to T3 in liver and kidney (T3 is major biologically active thyroid hormone)
126
why do T3 and T4 bind to plasma proteins?
hydrophobic/ lipophillic
127
which plasma proteins do T3/4 bind to?
thyroxine binding globulin (TBG) ~70%
Transthyretin (TTR) (thyroxine binding prealbumin) ~20%
Albumin (~5%)
[unbound in biologically active form]
128
what does T3 do once converted from T4?
enters nuclear receptor of target cell → mRNA →proteins → biological resp
129
effects of thyroid hormones on basal metabolic rate
Thyroid hormones inc basal metabolic rate
Increase number & size of mitochondria
Increase oxygen use and rates of ATP hydrolysis
Increase synthesis of respiratory chain enzymes
130
effects of thyroid hormones on thermogenesis
inc thermogenesis
131
effects of thyroid hormones on metabolism
Carbohydrate metabolism:
inc blood glucose – due to stimulation of glycogenolysis and gluconeogenesis.
inc insulin-dependent glucose uptake into cells
Lipid metabolism :
Mobilise fats from adipose tissue
inc fatty acid oxidation in tissues
Protein metabolism
inc protein synthesis
132
Thyroid Hormone Effects-
| Growth and Development
Growth:
Growth hormone releasing hormone (GHRH) production & secretion requires thyroid hormones
Glucocorticoid-induced GHRH release also dependent on thyroid hormones (permissive action)
GH/somatomedins require presence of thyroid hormone for activity (permissive action).
Development of foetal & neonatal brain
Myelinogenesis & axonal growth require thyroid hormones
Normal central nervous system activity:
Hypothyroidism - slow intellectual functions
Hyperthyroidism – nervousness, hyperkinesis & emotional lability
133
Thyroid Hormones Permissive Sympathomimetic Action
increase responsiveness to adrenaline & sympathetic NS neurotransmitter, noradrenaline, by increasing numbers of receptors
cardiovascular responsiveness also increased due to this effect – increased force and rate of contraction of heart
(BB like propranolol used to treat symptoms)
134
how are thyroid hormones regulated?
TRH=THYROTROPHIN RELEASING HORMONE
TRH release from hypothalamus stimulates TSH release form anterior pituitary.
135
inc TSH does what to t3/t4 secretion?
inc TSH = stimulates T3/4 release
136
t3/4 effect on TRH?
negative feeback (inc T3/4 reduce TRH)
137
TSH receptor is found where?
thyroid folicular cell
138
what external factors can regulate thyroid hormones conc?
low temp (inc TRH/TSH), stress(inhibits TRH/TSH), circadian rhythm (low in morning, highest late at night)
139
what are DeIodinase Enzymes? what do they do?
Subfamily of 3 enzymes (type 1, 2 and 3) important in the activation and deactivation of thyroid hormone (tissue regulation)
add/remove an iodine atom.
140
3 types of DeIodinase Enzymes another locations?
Type I (D1) is commonly found in the liver and kidney
Type II (D2) is found in the heart and skeletal muscle, CNS, fat, thyroid, and pituitary
Type III (D3) found in fetal tissue and placenta and brain (except pituitary)
141
what is the main determinant of T3?
D2 (activates T4->T3 in tissues)
142
what are the four different thyroid hormone recpetors? why is this useful?
Thyroid hormone receptor alpha – TRα1, TRα2
Thyroid hormone receptor beta –TRβ1. TRβ2
(different effect/sensitivity per tissue)
143
what occurs if person is Resistant to thyroid hormone alpha (RTHα)
delayed bone development
chronic constipation
bradycardia
impaired neurological development
144
what occurs if person is Resistant to thyroid hormone beta (RTHβ)
```
impaired HPT axis
goitre
affected colour vision
abnormal cochlea
tachycarida
impaired neurological development
```
145
deficiency of thyroid hormones cause by what? are the conditions goitrous or not?
Primary (gland) failure – may be associated
with enlarged thyroid (goitre)
Secondary to TRH or TSH (no goitre)
Lack of iodine in diet (may be associated with goitre)
146
what are the symptoms of hypothyroidism?
```
Reduced BMR
Slow pulse rate
Fatigue, lethargy, slow response times and mental sluggishness
Cold-intolerance
Tendency to put on weight easily
```
147
what is myxoedema (hypothyroidism in adults) signs
puffy face, hands & feet
148
what is cretinism (hypothyroidism in kids) signs
dwarfism & limited mental functioning due to deficiency of thyroid hormones present at birth
149
symptoms of hyperthyroidism
```
Increased BMR
Very fast pulse rate
Increased nervousness and excessively emotional.
insomnia
Sweating & heat intolerance
Tendency to lose weight easily
```
150
condition commonly causing hyperthyroidism? signs?
Graves' disease.
Autoimmune disease – Thyroid stimulating immunoglobulin (TSI) acts like TSH but unchecked by T3 & T4.
Exophthalmos
Goitre – enlarged thyroid gland
151
why does Exophthalmos occur?
bulging eyes due to water retaining carbohydrate build up behind eyes.
152
whiter the 5 types of thyroid cancer?
papillary, follicular, medullary, anaplastic, other (lymphoma...)
153
what makes up differentiated thyroid cancer/DTC?
papillary, follicular.
refers to histology, most cancer cells take up Iodine and secrete Thyroglobulin, DTC are TSH driven - good prognosis (95% after 10 years)
154
what do most DTC present with?
palpable nodule (thyroid or LN)
5% with local/disseminated mets
155
who does DTC occur in?
white adults with radiation exposure.
156
papillary thyroid cancer. how common, spread and associations
commonest, LN, spread to lungs, bone, liver, brain; associated with hashimoto's thyroiditis
157
follicular thyroid cancer. how common, spread and associations
2nd commonest, haematogenously spread. incidence inc in regions of relative iodine deficiency
158
investigation of potential DTC
US guided FNA (+excision biopsy of LN).
159
what do to if suspect DTC and vocal cord palsy?
pre-operative laryngoscopy
| [make sure of no recurrent laryngeal nerve injury]
160
clinical predictors of malignacy in thyroid nodule?
```
<20 or >50
Nodule increasing in size
> 4cm in diameter
History of head and neck irradiation
Vocal cord palsy
```
161
treatment for DTC?
surgery +/- RAI
162
what are the three types of surgery for DTC and which is preferred?
Thyroid lobectomy with isthmusectomy
Sub-total thyroidectomy
Total thyroidectomy
Sub-total thyroidectomy
163
why is a Sub-total thyroidectomy operation of choice for DTC?
leave on 5% in situ so chance of recurrence low
leaving decreases chance of complications (vocal cord palsy, parathyroid destruction)
164
what happens post-op to DTC patients?
risk assessed by AMES(age, mets, extent and size of primary tumour). - basically low and high risk groups made depending on how advanced cancer was before surgery
165
treatment for low and high risk groups post surgery for DTC?
low -TSH-supression via thyroxine
high- RAI
166
when whole body iodine scan done? what preparations are necessary?
Usually performed 3-6 months post-op.
use rhTSH is far better as no need to stop T3/T4 - as need high TSH for scan
167
why is a high TSH needed for a whole body iodine scan?
as sensitivity is determined by ensuring that TSH is elevated
inc TSH helps cancer cells to recognise iodine and uptake it - making results clearer
168
what is TRA/Thyroid Remnant Ablation?
rhTSH and high dose of RAI given - patient kept in lead room for 2/3 days (inpatient)
169
side effects of RAI?
few, patients usually well, sore salivary glands/throat possible
170
how is TRA followed up?
patient maintained on T4 to suppress TSH. this reduced recurrence rates (suppress long-term = extra protection)
thyroglobulin (Tg) can be used as tumour marker, should be undetectable. (very sensitive test)
171
what is thyroglobulin. why can it be used as a tumour marker? what happens if positive?
a protein produced by thyroid cells and (most) thyroid cancers.
with most of thyroid cells and cancer destroyed in successful treatment, level should be nothing and if increases then shows cancer still there.
if + = do whole body iodine scan
172
what do to if patient with PMHx of DTC has positive Tg but negative whole body iodine scan? how to treat?
PET scan. positive means cancer has changed an become anaplastic.
use biologics (Sorafenib and Lenvatinib)
173
recurrence of DTC: when? where? rate?
<2 years after op.
LN>thyroid
30% rate but if it uptakes iodine then is curable (via TRA)
174
what does TRA increase risk of?
AML (acute myeloid leukaemia). highest at 15 years post-treatment [no other cancer risk or is to fertility/offspring.]
175
how does cold exposure cause a release of thyroxine?
hypothalamus (TRH), ant pituitary (thyrotropin), thyroid (thyroxine)
176
(paired) hormones from ant pit?
```
ATCH - cortisol
TSH - thyroxine
Lh/FSH - Testosterone/estradiol
GH - IGF1
Prolactin
```
177
post pituitary hormones?
vasopressin, OXT
178
what is the difference between micro/macroademona?
≤ 1cm: Microadenoma
| > 1cm: Macroadenoma
179
what are the complications of a non-functioning pit ademona?
Compression on optic chiasma (Bitemporal hemianopia)
Compression on other structures eg cranial nerve 3,4,6
Hypoadrenalism
Hypothyroidism
Hypogonadism
(Diabetes Insipidus)
GH deficiency
180
what are the benign causes of a raised prolactin?
Physiological - breast feeding - pregnancy - stress - sleep
Drugs - Dopamine antagonists eg metoclopramide - Antipsychotics eg phenothiazines - antidepressants eg TCA, SSRIs - other, estrogens, coccaine
181
what are the pathological causes of a raised prolactin?
Hypothyroidism
Stalk lesions: iatrogenic, road accident
Prolactinoma
182
signs and symptoms of raise prolactin in female
```
EARLY presentation
Galactorrhoea
30-80%
Menstrual irregularity
Ammenorrhoea
Infertility
```
183
signs and symptoms of raise prolactin in male
```
LATE Presentation
Impotence
Visual field abnormal
Headache
Ant pit malfunction
```
184
investigating prolactinoma
```
prolactin conc,
MRI pituitary (tumour, pit stalk, optic chiasma)
visual fields (bitemproal hemianopia)
pit tests (other Hormones affected?)
```
185
treatment of prolacitnoma
Cabergoline (twice oral per week) - dopamine agonists (work very well)
186
what is acromegaly?
GH excess
187
acromegaly sings and symptoms
```
giant,
thickened soft tissues - skin, large jaw, sweaty, large hands
Hypertension (heart), cardiac failure
Headaches (vascular)
Snoring/Sleep apnoea
Diabetes mellitus
Local pituitary effects - visual fields, hypopituitarism
Early CV Death
Colonic polyps and colon cancer
```
188
how is acromegaly diagnosed? other tests that are important to consider?
IGF1
GTT (GH not suppressed)
Visual field
CT or MRI pituitary scan
Pituitary function tests ie the “other hormones
189
treatment for acromegaly
Pituitary surgery
(+/-External radiotherapy to pituitary fossa)
Retest GTT (if too high need drug therapy)
190
what drugs can be used in acromegaly?
Dopamine Agonist -Cabergoline
Somatostatin Analogues - octreotide, sandostatin LAR, lanreotide.
GH Antagonist -
Pegvisomant
191
what is cushion's syndrome caused by??
excess cortisol
192
what occurs in cushing's syndrome due to excess cortisol?
```
Protein loss
Myopathy; wasting
Osteoporosis; fractures
Thin skin; striae, bruising
Altered Carbohydrate/Lipid metabolism; Diabetes mellitus, Obesity
Altered psyche; psychosis, depression
```
193
what occurs in cushing's syndrome due to excess mineralocorticoid
hypertension, oedema
194
what occurs in cushing's syndrome due to excess androgen
Virilism
Hirsutism
Acne
oligo/amenorrhoea
195
what does cushion's cause to be in excess?
cortisol, mineralocorticoid, androgen
196
what is cushion's characterise (compared to obesity? )
```
Thin Skin
Proximal myopathy
Frontal balding in women
Conjunctival oedema (chemosis)
Osteoporosis
buffalo hump, moon face
```
197
what is the diagnostic test for cushing's?
screening = overnight Dexamethasone suppression test
definitiative = 2day Dexamethasone suppression test
198
what is the difference between cushings disease and syndrome?
Pituitary (majority) = Cushing’s Disease
ALL others are Cushing’s Syndrome: Adenoma of adrenal (B/M), ectopic (thymus, lung, pancreas), pseudo (steroid meds, alcohol, depression)
199
DD of cushing's: blood results pituitary cause (disease)
abn - low dose dexa test
<300 - ACTH
suppress by 50% - high dose exam suppression
200
DD of cushing's: blood results ectopic cause
abn - low dose dexa test
>300 - ACTH
nil- high dose exam suppression
201
DD of cushing's: blood results adrenal cause
abn - low dose dexa test
<1 - ACTH
nil - high dose exam suppression
202
treatment of pituitary Cushing's disease
hypophysectomy +/-radiotherapy (recurrance); bilateral adrenalectomy
203
treatment of adrenal Cushings syndrome
Adrenalectomy
204
treatment of ectopic Cushings syndrome
remove source
| OR bilateral adrenalectomy
205
drugs used in the treatment of cushings?
Metyrapone - if other treatments fail - while waiting for radiotherapy to work
- S/E common
Ketoconazole (hepatotoxic)
Pasireotide: (new somatostatin analogue; receptor 2 and 5 blocked)
206
pan Hypopituitarism causes what?
```
Anterior Pitutary
Growth Hormone; growth failure
TSH; hypothyroidism
LH/FSH; Hypogonadism
ACTH; hypoadrenal
Prolactin; none known
```
Posterior Pituitary
Diabetes Insipidus
207
causes of Hypopituitarism (many)
```
Pituitary Tumours
Secondary metastatic lesions
Local brain tumours
Granulomatous diseases
(TB, sarcoidosis)
Trauma(road accidents, skull fractures)
Hypothalamic diseases
(Syphilis, meningitis)
Iatrogenic; surgery
Autoimmune;Sheenan – post pregnancy infarction
Infection; meningitis
```
208
Symptoms and signs of anterior hypopituitarism
```
Menstrual irregularities (F)
Infertility, impotence
Gynaecomastia (M)
Abdominal obesity
Loss of facial hair (M)
Loss of axillary and pubic hair (M&F)
Dry skin and hair
Hypothyroid faces
growth retardation (children)
```
209
treatment of pan Hypopituitarism
```
Thyroxine
Hydrocortisone
ADH
GH
Sex Steroids: HRT/Oest/prog pill for female + Testosterone for males
```
210
GH in adults
```
Improves well being and Quality of life
Decreases abdominal fat
Increases muscle mass, strength, exercise capacity and stamina
Improves cardiac function
Decreases cholesterol and increases LDL
Increases bone density
Given by daily SC injection
```
211
Testosterone Replacement in hypopituitarism
```
IM injection every 3-4 weeks (sustanon)
Skin gel (testogel, tostran)
Prolonged IM injection 10-14 wks (nebido)
(Oral tablets (restandol))
```
212
risks of testosterone replacement
Prostate Enlargement. Does NOT cause prostate cancer but may make it grow - monitor PR exam and PSA at start
Polycythaemia - monitor FBC
Hepatitis (only for oral tablets) - monitor LFTs
213
causes of cranial D.insipidus
familail (DIDMOAD = DI, DM, optic atrpohy, deaf)
acquired (idiopathic and trauma (RTA/sugery/skull #))
Rare (tumour, sarcoid, irradtions, meningitis )
214
how is DI diagnosed?
Water Deprivation test
215
why do DI occur?
reduced ADH/vasopressin
216
how is DI treated?
desmopressin (oral, inhale, injection)
