Thyroid Physiology: what does TSH influence what blocks TSH?
TSH influences:
- Iodine through membrane via Na/K ATPase
- Iodide → iodine by TPO
- iodine taken up by thyroglobulin in colloid and into thyroxine
- tyrosine residues iodinated in thyroglobulin → MIT and DIT → TIT, rTIT and T4
- T4 (thyroxine) produced, stored in thyroid gland (and secreted into lumen when required
- in periphery, T4 → T3
TSH is blocked by perchlorate
Thyroid hormone transport
Majority T4 bound to protein (TBG) when secreted
- minority is active thyroxine (fT4)
- if lacking albumin, TBG levels go down
T4 can also bind to thyroxine-binding pre-albumin (TBPA) and albumin
4 types of thyroiditis
Grave’s disease (low TSH, high T4/T3) → hyperthyroid, anti-TSH-R ABs, anti-TPO ABs
Hashimoto’s thyroiditis/chronic lymphocytic thyroiditis (high TSH, low T4) → hypothyroid, anti-TPO ABs, anti-TG ABs
Reidel’s thyroiditis (high TSH, low T4) → hypothyroid, IgG4-related disease
Viral thyroiditis/subacute (De Quervain’s) (high TSH, low T4) → hyperthyroid to hypothyroid (no antibodies)
4 types of thyroiditis
Grave’s disease (low TSH, high T4/T3) → hyperthyroid, anti-TSH-R ABs, anti-TPO ABs
Hashimoto’s thyroiditis (autoimmune)/chronic lymphocytic thyroiditis (high TSH, low T4) → hypothyroid, anti-TPO ABs, anti-TG ABs
Reidel’s thyroiditis (high TSH, low T4) → hypothyroid, IgG4-related disease
Viral thyroiditis/subacute (De Quervain’s) (high TSH, low T4) → hyperthyroid to hypothyroid (no antibodies)
HPT Axis
Hypothalamus releases TRH → stimulated TSH production from pituitary gland → T4 production
- T4 → T3 in peripheries (activate component of thyroxine)
Too much T4 → feedback to hypothalamus to prevent it from producing too much TRH
- low T4 → high TRH and high TSH (hypothyroidism)
NB: hCG and TSH have similar structures, and so can stimulate same actions
- string on neck pregnancy test in Africa (hCG → goitre)
HPT Axis
Hypothalamus releases TRH → stimulated TSH production from pituitary gland → T4 production
- T4 → T3 in peripheries (activate component of thyroxine)
Too much T4 → feedback to hypothalamus to prevent it from producing too much TRH
- low T4 → high TRH and high TSH (hypothyroidism)
NB: hCG and TSH have similar structures, and so can stimulate same actions
- string on neck pregnancy test in Africa (hCG → goitre)
What are causes of hypothyroidism?
Most are PRIMARY hypothyroidism
Causes:
- Hashimoto’s thyroidits (AI)
- atrophic thyroid
- Post-Graves’ disease (radioactive iodine natural hx or thionamines)
- other minor causes = post-thyroiditis, postpartum, thyroid genesis or dysgenesis, drugs (amiodarone, lithium), iodine deficiency and dyshormonogenesis, 2o hypothyroidism (pituitary disease) → LOW TSH LOW T4, peripheral thyroid hormone resistance e
Clinical features of hypothyroidism
- reduced BMR → weight gain
- bradycardia
- constipation
- laboured breathing
- oligomenorrhoea
- other = poor appetite, hyponatraemia, cold/dry hands/feet, normocytic anaemia (unless pernicious anaemia), depression, myxoedema, goitre, subtle in the elderly
What is myxoedema coma?
In very rare cases, a severe underactive thyroid may lead to a life-threatening condition called myxoedema coma. This is where the thyroid hormone levels become very low, causing symptoms such as confusion, hypothermia and drowsiness. Myxoedema coma requires emergency treatment in hospital.
Ix for hypothyroidism
High TSH and LOW T4 in 1o hypothyroidism
TPO autoantibodies (suggests autoimmune hypothyroidism/Hashimoto’s thyroiditis)
remember to consider any other AI conditions the patient also may have (e.g. pernicious anaemia, coeliac disease, Addison’s disease)
Tx for hypothyroidism
ECG
- co-cardiac failure alongside, giving levothyroxine will exacerbate myocardial ischaemia and MAY worsen HF → start at VERY low dose and titrate
Levothyroxine (T4), 50-125-200 mcg/day → titrated to a normal TSH
Liothyronine (T3)
NO evidence base for over-treating patients with T4
- lose weight BUT osteopenia and AF
NO evidence base for giving T3 rather than T4
What is subclinical hypothyroidism (SH)? ‘compensated hypothyroidism’
- T4 level is NORMAL but TSH is HIGH
- Pituitary gland senses T4 and thinks the thyroid is NOT producing enough thyroxine so it produces more TSH
- If TPO antibodies are positive, it suggests that the patient may go on to develop thyroid disease
- Subclinical hypothyroidism is UNLIKELY to be the cause of their presenting symptoms
- Hypothyroidism is associated with hypercholesterolaemia (may be only benefit of treating SH)
Hypothyroidism after radio iodine treatment
- Most patients with this condition will become hypothyroid within 1 year of receiving radioiodine treatment
- However, it may take many years in some patients (up to 15) → 50% of patients
Thyroid function in pregnancy
hCG similar structure to TSH
rise in hCG in 1TM → free T4 levels increase slightly (this is normal)
- so normal ranges of TSH and T4 in pregnancy different
TBG levels increase in pregnancy (under control of oestrogen)
later in pregnancy, hCG levels drop → T4 level drop and TSH levels will rise slightly
Neonatal hypothyroidism
- Diagnosed in the Guthrie test – done at 6 days old and the TSH detected comes from the baby (not mother)
- It is important to capture hypothyroidism at the correct time – if you measure it too early, TSH levels may be erroneously high because of the presence of maternal TSH in the blood
What is sick euthyroidism?
alteration in pituitary thyroid axis in non-thyroidal illness
- Can occur in any severe illness that affects the HPT axis – if you are very sick, the thyroid may shut down to try and reduce the basal metabolic rate to conserve energy (however, there are NO hypothyroid symptoms)
- Biochemistry
- Low T4 and T3 (and reduced T3 action)
- Normal/high TSH (later decreased)
Hyperthyroidism T4 and TSH, causes
High T4, low TSH
Causes:
- Graves’ disease = autoantibodies on thyrotropin/TSH-R (40-60%)
- toxic multi nodular goitre (Plummers) (30-50%)
- Single toxic adenoma (5%)
- subacute thyroiditis/viral thyroiditis/de Quervain’s thyroiditsm
- postpartum thyroiditis
Rare causes:
- silent thyroiditis (AI, amiodarone)
- TSH-induced
- trophoblastic tumour and Struma ovary (high hCG production)
- factitious thyroiditis
- thyroid cancer induced
Graves’ disease features
Diffuse goitre
Thyroid-associated ophthalmopathy (TSH-R in eye muscles)
- RI tx can make Graves’ eye disease worse
Thyroid-associated dermoathy (pretibial myxoedema)
Thyroid acropachy
Other autoimmune conditions (or FH)
Ix for hyperthyroidism
- LOW TSH, HIGH T3 AND T4
- technetium scan may show high or low uptake
- thyroid autoantibodies (thyroid microsomal)
Clinical features of hyperthyroidism
- weight loss
- tachycardia
- diarrhoea
- tachypnoea
- osteopenia and osteoporosis
- irregular periods
Management of hyperthyroidism
- b-blocker if pulse >100bpm
- eye drops for eye disease
- topical steroids for dermopathy
- other AI conditions (coeliac, Addison’s)
- ECG
- BMD
Radioactive iodine = taken up by thyroid gland → releases radiation to destroy thyroid gland
- I-131 used → can precipitate thyroid storm and make thyroid gland underactive
- stop thiamine if using radioactive iodine
- side effects: ophthalmopathy/tracheal compression
Thionamides (e.g. carbimazole, PTU)
- prevent iodide → iodine via TPO
- s/e = rash, agranulocytosis
- patients should STOP tx if develop sore throat or fever → seek medical attention
- titration regime or ‘block and replace’ (high dose thionamide then thyroxine to maintain normal)
Mechanism of action of potassium perchlorate and thionamides
- Potassium perchlorate can be given to hyperthyroid patients before surgery to block the uptake of iodide by the thyroid cells
- Thionamides inhibit thyroid peroxidase, thereby preventing the conversion of iodide to iodine
Types of thyroiditis: silent, viral, postpartum
Types:
- Silent (painless) thyroiditis (most have some pain in the neck)
- Viral / sub-acute thyroiditis
- Post-partum thyroiditis (tx for viral or post-partum thyroiditis is different to hyperthyroidism)
With thyroiditis, you initially get inflammation of the thyroid gland resulting in release of thyroid hormone
Then, eventually the thyroid hormone will stop working completely
- Thyroiditis patients are likely to present at the stage where their TSH is high and their T4/T3 is low
Long-term treatment of thyroiditis is thyroid hormone replacement
Types of Thyroid Cancer (most common ones)
pathology of papillary
PFMA
- papillary (pathology = Psammoma body)
- follicular
- medullary carcinoma of thyroid
- anaplastic
slow-progressing cancer
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1: Calcium Metabolism45
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7. Brief Lipid Update21
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3. Sodium and Fluid Balance33
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4: Potassium handling and electrolytes19
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8: Pituitary21
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5: Diabetes Clinical Cases17
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6: Adrenal disease25
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1s: uric acid metabolism10
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2s: Lipoproteins16
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3s: Acid-Base20
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4s: Liver CPC49
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5: Diabetes Cases21
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11: LFTs and Cases42
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5s: Metabolic Disorders21
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6s: Metabolic Disorders 223
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9s: Thyroid43
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7s: Paediatric Clinical Chemistry24
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10s: Nutrition49
