ENDOCRINOLOGY - HYPOTHYROIDISM Flashcards

1
Q

What’s the earliest biochemical abnormality of hypothyroidism?

A

Increase in serum TSH concentration with normal T4 and T3 followed by a decrease in serum T4 at which stage most patients have symptoms and require treatment (overt hypothyroidism)

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2
Q

Outline the epidemiology of hypothyroidism?

A

Increases with age is most common around the age of 60
Autoimmune is most common cause in UK
Iodine deficiency is the cause more commonly in mountainous areas

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3
Q

What’s the most common cause of hypothyroidism worldwide?

A

Iodine deficiency

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4
Q

What is hypothyroidism?

A

Results from insufficient secretion of thyroid hormones

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5
Q

What’s the severest form of hypothyroidism

A

Myxoedema - accumulation of mucopolysaccharides in the skin and other tissues, causing thickening of facial features and is associated with hypothermia, confusion and coma

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6
Q

What can cause primary hypothyroidism?

A

Hashimoto’s thyroiditis
Iodine deficiency
radio-iodine treatment, surgery, radiotherapy to neck i.e. treatment for hyperthyroidism
Drugs
Congenital defects e.g. absence of thyroid gland
Infiltration of the thyroid

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7
Q

What can cause secondary hypothyroidism?

A

Most commonly pituitary tumour

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8
Q

How does hypothyroidism present?

A

Tiredness
Intolerance to cold
Dry skin
Hair loss
Tongue enlargement
Slowing of intellectual activity e.g. poor memory and difficulty concentrating
Constipation
Decreased appetite and weight gain
Deep hoarse voice
Menorrhagia
Impaired hearing due to fluid in middle ear
Reduced libido
Bradycardia
Carpal tunnel syndrome
Serous cavity effusions
Slow relaxing reflexes
Features of other autoimmune diseases

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9
Q

What is Hashimotos disease?

A

An autoimmune disorder affecting the thyroid gland that can cause hypothyroidism

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10
Q

What is atrophied thyroiditis?

A

An extreme form of primary hypothyroidism in which the thyroid gland is severely atrophied by antibody attack - patients will be overt hypothyroidism

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11
Q

What is post partum thyroiditis?

A

Occurs in 7% of pregnancies within the first 6 months postpartum. Most women show complete remission but some may progress to permenant hypothyroidism

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12
Q

What is De quervains thyroiditis?

A

Aka subacute thyroiditis
A viral infection such as flu or mumps produces local symptoms and excquisite tenderness of the thyroid gland with modularity. Initially patients are thyrotoxic but later they become hypothyroid.

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13
Q

What is thyroid hormone resistance?

A

A rare genetic condition where some body tissues do not respond normally to thyroid hormones produced by the thyroid gland

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14
Q

What are thyroid hormone and TSH levels in thyroid hormone resistance?

A

Raised/ normal TSH
Raised T4 and T3

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15
Q

What are thyroid hormone and TSH levels in primary hypothyroidism?

A

Raised TSH
Lowered free T4
Lowered/normal fT3

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16
Q

What are thyroid hormone and TSH levels in secondary hypothyroidism?

A

Lowered/normal TSH
Lowered T4
Lowered/normal T3

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17
Q

What antibodies will be found in patients with autoimmune thyroiditis?

A

Anti-thyroid peroxidase antibodies
Anti-thyroglobulin antibodies

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18
Q

What is myxoedema coma?

A

an extreme complication of hypothyroidism in which patients exhibit multiple organ abnormalities and progressive mental deterioration.

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19
Q

What is subclinical hypothyroidism?

A

a condition where TSH levels are high, but T3 and T4 levels are within the normal reference range.

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20
Q

What are the common complications of hypothyroidism?

A

dyslipidaemia, metabolic syndrome, coronary heart disease and stroke, heart failure, neurological and cognitive impairments, and adverse maternal and fetal outcomes in pregnancy.

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21
Q

How should you manage a person with overt hypothyroidism?

A

Offer levothyroxine as first-line treatment Take it for life
Aim to maintain TSH levels within the reference range (may take up to 6 months to return to this range). Measure TSH every 3 months until stabilised and then once a year

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22
Q

What drugs can cause hypothyroidism?

A

Amiodarone
Ferrous sulphate, calcium carbonate and PPIs - interfere with thyroxine absorption

Rifampicin, phenytoin and carbamazepine - increases thyroxine turnover

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23
Q

What is sheehans syndrome?

A

postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive hemorrhage during or after delivery

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24
Q

What other autoimmune conditions are associated with hypothyroidism?

A

Type 1 diabetes
Autoimmune thyroid disorders
Addison’s disease
Coeliac disease
Pernicious anaemia

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25
How should you take levothyroxine?
Take it on an empty stomach and consider drug interactions
26
Why should you initiate levothyroxine treatment slowly with hypothyroid patients with cardiac dysfunction
As it can cause angina
27
Why should you increase the levothyroxine dose by 30-50% in pregnancy?
Lowers risk of miscarriage, preterm delivery, lower IQ in foetus
28
How do you manage subclinical hypothyroidism?
If TSH remains remains under 10 and symptoms are absent then management isn’t required
29
What is thyroid Wolff chaikoff effect?
iodine induced hypothyroidism an autoregulatory phenomenon, whereby a large amount of ingested iodine acutely inhibits thyroid hormone synthesis within the follicular cells, irrespective of the serum level of thyroid-stimulating hormone This is caused by down regulation of iodine receptors
30
What cells release TSH?
Thyrotropes
31
What are the 2 effects of TSH binding to follicular cells?
Production of thyroglobulin and thyroperoxidase
32
What 2 effects does thyroperoxidase have?
Converts iodine to iodide Combines iodide and thyroglobulin to produce iodinated thyroglobulin, of which T3 and T4 are cleaved off
33
What effect does T3 have on nucleated cells?
T3 binds intracellular receptors, activates genes and increases the expression of proteins - including Na+/K+ ATPase. Increasing expression of these proteins means we use more ATP which means we need to generate more ATP through glycogenolysis, lipolysis and glycolysis = increases metabolism
34
What effect do thyroid hormones have on the heart?
Increases beta adrenergic receptor sensitivity = increased HR and contractility They maintain vasomotor tone
35
What effect do thyroid hormones have on the bones?
Maintains balance between osteoclasts and osteoblasts Helps control development and maturation of skeletal system
36
What effect do thyroid hormones have on the sympathetic nervous system?
Increases SNS activity
37
What effect do thyroid hormones have on the GI system?
Increases GI motility and GI secretions
38
What effect do thyroid hormones have on the skin?
Increases blood flow to the skin, so is important for the growth of hair, skin and nails Regulates activity of sebaceous and sweat glands - increases both
39
What effect do thyroid hormones have on the reproductive system?
Helps with development and general function of this system It can regulate levels of sex hormone binding globulin TRH can affect LH and FSH
40
What effect do thyroid hormones have on the fibroblasts?
Controls production and degradation of glycosaminoglycans
41
What effect do thyroid hormones have on the muscle?
Controls development, regeneration of muscles Also controls muscle contraction by regulating activity of Ca2+ ATPase present on the sarcoplasmic reticulum
42
What are the autoantibodies in Hashimotos disease targeting?
Thyroperoxidase and thyroglobulin
43
What is post partum thyroiditis?
Hypothyroidism within 1 year of birth When you’re pregnant your immune system dials down. Post-partum the immune system ramps up again and creates antibodies against the thyroid This is acute so will resolve after some time
44
What are the autoantibodies present in post-partum hypothyroidism?
TPO and Thyroglobulin
45
What are the 3 drug induced causes of hypothyroidism?
Amiodarone Lithium Iodine 131
46
What is reidels thyroiditis
IgG4 antibodies activate fibroblasts around the thyroid gland which causes fibrosis of the gland. this reduces the ability to produce thyroid hormones.
47
How does iodine deficiency cause hypothyroidism?
You can’t make enough iodinated thyroglobulin so you cannot make functional thyroid hormones (Most common cause worldwide)
48
How does iodine excess cause hypothyroidism?
Wolf chaikoff effect - too much iodine inhibits TPO as too much thyroid hormones are created. This leads to decreased thyroid hormone synthesis
49
What is Sheehan syndrome?
postpartum hypopituitarism caused by necrosis of the pituitary gland due to infarction Can cause hypothyroidism as it impairs TSH release
50
What are the additional features of congenital hypothyroidism? (7Ps)
Pot belly Pale Puffy face Protuberant tongue Protruding umbilicus Poor brain development Prolonged neonatal jaundice
51
What are some reasons for goitre in hypothyroidism?
Not releasing thyroid hormones Damage of thyroid gland leads to hypertrophy
52
Why does hypothyroidism cause weight gain and decreased appetite?
Because metabolism slows so lipids and glycogen are not broken down for ATP production
53
Why do you get sensitivity to cold/low body temp?
Heat is a by-product of metabolism so less metabolism = less heat
54
Why does hypothyroidism cause bradycardia?
Less thyroid hormone = decreased beta 1 adrenergic receptor sensitivity
55
Why does hypothyroidism cause hypertension?
Less thyroid hormone increases vasoconstriction = decreased diameter = increased resistance = increased bp
56
Why does hypothyroidism cause short stature?
Low thyroid hormones leads to poor bone growth and maturation
57
Why does hypothyroidism cause depression, fatigue and memory loss?
Low thyroid hormones causes decreased sympathetic NS activity
58
What is Woltmans sign?
a delayed relaxation phase of an elicited deep tendon reflex
59
Why does hypothyroidism cause constipation?
Low thyroid hormones cause decreased gut motility and decreased gut secretions
60
Why does hypothyroidism cause proximal myopathy?
Low thyroid hormone reduces muscle growth and regeneration. this damage leads to CK spilling out of muscles - cannot be repaired It also causes decreased expression of calcium ATPase so decreased muscle contraction control
61
Why does hypothyroidism cause hair loss, brittle nails and dry skin?
Low thyroid hormones cause decreased blood flow to the skin and decreased activity of sebaceous and eccrine sweat glands
62
Why does hypothyroidism cause hypercholesterolaemia and hypertriglycerolaemia?
Low thyroid hormones cause reduced LDL and triglyceride receptors = LDL and triglycerides built up in blood
63
Why does hypothyroidism cause infertility, decreased libido, gynaecomastia, erectile dysfunction, oligomenorrhoea, amenorrhoea and galactorrhoea?
Low thyroid hormones causes stimulation of hypothalamus to release TSH but there’s also an increase in prolactin. prolactin inhibits FSH and LH production = inhibits production of testosterone and oestrogen
64
What is Queen Anne's sign?
A thinning or loss of the outer third of the eyebrows, and is a classical sign of hypothyroidism or atopic dermatitis, but it can also be detected in lepromatous leprosy.
65
Why does hypothyroidism cause pretibial myxoedema, periorbital oedema and carpal tunnel syndrome?
Low thyroid hormones causes decreased degradation of glycosaminoglycans. Lots of GAGs pulls water out causing oedema GAGs typically accumulate in the dermis of tibia, around the eyes and near the carpal tunnel
66
What would TFTs show in primary hypothyroidism?
Low free T4 high TSH
67
What would TFTs show in secondary hypothyroidism due to a hypothalamus cause?
Low free T4 Low TSH Low TRH
68
What would TFTs show in secondary hypothyroidism due to a pituitary cause?
Low free T4 Low TSH
69
How can you differentiate between hypothalamic and pituitary causes of secondary hypothyroidism?
MRI
70
How can you determine Hashimoto’s thyroiditis?
Check for positive TPO and TG antibodies elevated serum TG because injury to thyroid gland causes thyroglobulin to leak out Biopsy - definitive diagnosis
71
How can you determine post partum thyroiditis?
<1 year from birth Check if TPO and TG antibodies positive Should be acute and so should return to euthyroid
72
How can you determine drug induced thyroiditis?
Take a drug history - amiodarone, lithium or had iodine 131 recently
73
How can you determine reidels thyroiditis?
Check for hard and painless thyroid (because of fibrous tissue) Do they have dysphasia, dyspnoea, hoarseness of voice? - compressive symptoms Biopsy - to determine if its cancer or this type
74
How can you determine subacute granulomatous thyroditis?
Check for elevated ESR Do they have flu -like symptoms? Do they have a painful and tender thyroid
75
What are some associated labs that may suggest hypothyroidism?
Increased LDL and triglycerides (because of LDL receptor uptake) Increased creatinine kinase (because of muscle damage) Hypoglycaemia (because of reduced gluconeogenesis) Hypotonic hyponatraemia (low thyroid hormones stimulate ADH production = increased water resorption = dilute Na+ in blood)
76
How is congenital hypothyroidism screened for?
Within 24-48 hours post birth TSH must be checked (if high then order a free T4)
77
What is levothyroxine?
T4 (MOA is the same.., gets converted to T3 and does all the physiological effects)
78
How can you know if you are giving the correct dose of levothyroxine?
Check TSH - this is how we monitor hypothyroidism If giving too little then TSH will be high in response to low thyroid hormones If giving too much then TSH will be low in response to high thyroid hormones
79
How does being on an oral contraceptive affect dosage of levothyroxine?
Oral contraceptives increas oestrogen which causes an increase in thyroxine binding globulins which binds more T4 so there is less circulating T4 This means you may need to increase the dose
80
How does being on an corticosteroids affect dosage of levothyroxine?
Corticosteroids decreased thyroxine binding globulin so less T4 is bound and there is more circulating free T4 This means you should reduce the dose
81
What are triggers for myxoedema coma? And why?
Infection, surgery, trauma and extreme cold - these want to increase sympathetic drive by hypothyroidism diminishes this response making their effects more pronounced than usual
82
How does myxoedema coma present?
Severe bradycardia, decreased bp/shock, altered mental status/coma, severe hypothermia Because metabolism is significantly affected
83
How do you treat myxoedema coma?
IV levothyroxine and synthetic T3 IV fluids if hypotensive IV hydrocortisone (until we rule out adrenal failure as these present the same so we should treat it as adrenal failure until we know it isn’t that)
84
Who is at higher risk of hypothyroidism?
Perimenopausal Post partum Babies - always check After treatment for hyperthyroidism Down’s syndrome T1 diabetes (and maybe other autoimmune diseases) Those recieving amiodarone or lithium
85
What are the 4 phases of De Quervain’s thyroiditis?
Phase 1 lasts 3-6 weeks - hyperthyroidism, painful goitre, raised ESR Phase 2 lasts 1-3 weeks - euthyroid Phase 3 lasts weeks-months - hypothyroidism Phase 4 - thyroid structure and function goes back to normal
86
How is De QUervains thyroiditis treated?
It’s usually self limiting Aspirin or other NSAIDs can be offered Steroids can be used in severe cases
87
What can interact with thyroid drugs’ absorption?
iron and calcium salts absorption of levothyroxine reduced so give at least 4 hours apart
88
What does it suggest if TSH is high but free T4 is normal?
Subclinical hypothyroidism Or poor compliance with thyroxine medication for hypothyroidism
89
Why can amiodarone induce hypothyroidism?
Amiodarone has a high iodine content, and this can lead to inhibition of thyroxine production due to high iodine levels.
90
What is Hashimoto’s thyroiditis associated with?
other autoimmune conditions e.g. coeliac disease, type 1 diabetes mellitus, vitiligo Hashimoto's thyroiditis is associated with the development of MALT lymphoma
91
What type of goitre does de Quervains thyroiditis cause?
Painful
92
What is sick euthyroid syndrome?
‘Non thyroidal illness syndrome’ common in unwell, elderly patients it is often said that TSH, thyroxine and T3 is low. In the majority of cases however the TSH level is within the >normal range (inappropriately normal given the low thyroxine and T3). Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed.
93
What are the 2 forms in which Hashimoto’s thyroiditis can present?
Goitrous: characterised by a firm and rubbery goitre Atrophic: characterised by an atrophic gland
94
What is amiodarone-induce hypothyroidism?
Taking amiodarone can cause hypothyroidism The effects of amiodarone are dependent on whether there is pre-existing thyroid disease: Pre-existing autoimmune disease: hypothyroidism may occur secondary to the Wolff–Chaikoff effect - a phenomenon in which raised iodine intake results in reduced levels of thyroid hormone. Normal thyroid gland: those with a normal gland may also develop hypothyroidism, frequently affecting T3.
95
What screening test is used for congenital hypothyroidism? What is this to prevent?
Guthrie screen Prevent cretinism which can be caused by congenital hypothyroidism
96
What are the 2 outcomes of congenital hypothyroidism?
Dyshormonogenesis Abnormal gland development
97
What are the side effects of levothyroxine?
hyperthyroidism: due to over treatment reduced bone mineral density worsening of angina atrial fibrillation