Thyroid Flashcards
Which gender are thyroid disease more common in?
women
What joins the right and left lobe of the thyroid?
isthmus
What is the histology of the thyroid?
follicle - simple cuboidal epithelium lining a central colloid filled lumen
Parafollicular cells or C cells (secrete calcitonin which reduces blood plasma Ca levels)
What inhibits TSH?
dopamine
somatostatin
glucocorticoids
benzodiazepines
What hormones does thyroid produce?
Thyroxine - T4 = pro-hormone
Tri-iodothyronine - T3 = active hormone
- 20% from thyroid gland
- 80% from peripheral conversion of T4 in liver, kidneys and muscle
T4 converted to T3 by deiodinases enzymes
What is the ratio of T4:T3?
T4:T3 14:1
What proportion of thyroxine is bound to protein?
99.95%
What proteins can thyroxine be bound to?
thyroxine binding globulin - 70%
half life = 5 days
transthyretin- 20%
half life = 2 days
Albumin = 10%
What does subclinical mean?
asymptomatic
Subclinical hypothyroidism results
raised TSH
normal T4
- usually due to early autoimmune hypothyroidism
- usually do not treat unless TSH is very high (>10) or anti-TPO positive; treatment = normalize TSH
Subclinical hyperthyroidism
- thyroid test results
- common causes
- what drugs could be causing it?
low TSH, normal T3 and T4
May be due to Graves, TMNG, or exogenous thyroxine ingestion
Also seen in patients with non-thyroidal illness, or on certain medications (amiodarone, glucocorticoids, anticonvulsants)
Amiodarone – high iodine content and direct toxic effect on thyroid follicular cells (inhibits T4 to T3 conversion).
Amiodarone-induced hypothyroidism occurs in 15% patients. Treatment: Levothyroxine and discontinuation of amiodarone if possible.
Amiodarone-induced thyrotoxicosis rare - <5% / treatment: ATD (+/- prednisolone), and discontinuation of amiodarone
SEEK cardio input
Increased risk of atrial fibrillation & osteoporosis
Follicular adenoma
benign cause of solitary thyroid nodules
most non-functional
Thyroid malignancy
- RF
- investigations
More likely if:
Patient is young (<20) or old (>60)
Nodule grows rapidly
Compressive symptoms – hoarse voice, difficulty breathing or swallowing
FH of endocrine malignancy
Cold nodule in patient with Grave’s disease
CT, MRI and RNI (radionuclide imaging) – staging thyroid malignancy
What is the tumour marker for papillary/follicular thyroid cancer?
Tumour marker following treatment = thyroglobulin (Tg) – should remain undetectable following total thyroidectomy or ablative radioactive iodine.
Detectable levels suggests disease recurrence (metastasis)
Papillary carcinoma
Most common thyroid cancer (75%)
Pupillae present in tumour tissue
Excellent prognosis
Total thyroidectomy with ablative dose of radioiodine
Require lifelong T4 replacement at supraphysiological dose
Aim: sublinical hyperthyroidism – with undetectable TSH level due to total suppression
TSH = growth factor for thyroid cells (including malignant cells) - Lifelong follow-up includes tests to Tg
Follicular carcinoma
Well-differentiated follicular tumours – contain follicles with colloid
Good prognosis
Thyroid lobectomy recommended to assess malignancy
High-risk patients – complete thyroidectomy and ablative radioactive iodine recommended
Require lifelong T4 replacement at supraphysiological dose
Serum Tg = tumour marker
Medullary carcinoma
Cancer of parafollicular ‘C’ cells – producing calcitonin
- Parafollicular cells = neuroendocrine - therefore produce other secretory products e.g. serotonin (5-HT) & can therefore lead to carcinoid syndrome (flushing, diarrhoea, abdominal pain, fast heart rate and bronchospasm).
Calcitonin levels are used during follow-up to test for recurrence
Deposition of amyloid in thyroid & surrounding tissues (adjacent lymph nodes).
Can be sporadic or may be associated with MEN syndromes.
MEN II has to be excluded - as often presents with medullary thyroid cancer, and patients with MEN II will have other endocrine cancers.
MEN II = TAP - Thyroid, Adrenal, Parathyroid.
- Treated with total thyroidectomy and lymph node dissection.
Radioiodine is not used as C cells do not take up iodine
Suppressive thyroxine therapy not needed as C cells not controlled by TSH.
Histological features of MNG
- Cystically dilated follicles
- Cholesterol clefts
- Variably sized follicles
- Foamy macrophages
- Fibrous septae
Histological features of Graves disease
Clinical and biochemical diagnosis – not made on histology
Papillary architecture
Cells have a more columnar appearance
Histological features of Hashimoto’s
Associated with thyroglobulin and thyroid peroxidase antibodies
Lymphoid predominant inflammation
Lymphoid aggregates with germinal centre formation
Small lymphocytes
Follicular cell oncocytic change - Oncocytic epithelial cells
Variable degrees of gland destruction
Histological features of follicular adenoma
Completely encapsulated lesion
- Thick fibrous capsule
Made up of thyroid follicles
Clonal population but benign
If capsular or vesicular invasion then becomes follicular carcinoma
Graves - what are the antibodies against?
TSH receptor
Grave’s treatment
often with ATD first time round
- 12-18 course of tablets
- 60-70% chance of relapse
- block and replace - use very high dose of ATD, then replace thyroid hormones to avoid hypothyroidism
- titration - euthyroidism is achieved using ATDs then a low maintenance dose is given to keep patient euthyroid
RAI -I131 for recurrent graves
- may increase chance of graves eye disease
Surgery
- large goitre, personal preference, severe hyperthyroidism, intolerance to ATDs
- If over 50 years and have active eye disease
Is smoking bad in Graves
Yes - get worse eye disease
Will radioactive iodine affect graves eye disease?
Yes, will make it worse
Treatment in severe graves active eye disease
if severe - consider steroids - cyclosporine
Otherwise management is with topical lubricants and selenium 200mcg daily
what age is toxic multi nodular goitre seen most commonly?
50-70 years old
- often 1 or more lumps will be overactive - rest of thyroid will be switched off as has no signal stimulating it to work
What is the treatment for active thyroid nodules?
radioactive iodine
if just one active nodule - may require ATD to make them euthyroid.
Thyroidectomy
What is thyroiditis?
- what triggers it?
- diagnosis
- management
temporary overactivity of the thyroid
- may be followed by period of underactivity
Triggers - pregnancy, infection, drugs (amiodarone)
Diagnosis - TFTs showing thyrotoxicosis, no uptake on technetium scan, inflammatory markers would be raised
Management
- self limited
- beta blockers for symptoms relief
- thyroxine may be required in hypothyroid phase
Post-partum thyroiditis
occurs within 1 year of giving birth
hyperthyroid phase within 4-6 months of delivery followed by a hypothyroid phase, then return to euthyroidism
permanent hypothyroidism develops in 30%
if you hear a bruit over a goitre - what is this almost always diagnostic of?
Graves
Grave’s eye signs
redness gritty sensation pain on eye movement swelling around eye proptosis (eye appears to be pushed forward) double vision loss of colour vision lagopthalmos (inability to close eye lid)
Eye sign that may be seen in any cause of overactive thyroid
lid retraction (eyelid drawn back) and lid lag (look up and follow, eyelids dont follow movement)
Anti-thyroid drugs
- examples
- mechanism of action
- SE
Carbimazole (CBZ) and propylthiouracil (PTU)
- Decrease production of thyroid hormone
- Inhibits thyroid peroxidase -> decrease hormone production
SE: Rash, pruritis (itching) & arthralgia (joint pain)
- Can use antihistamines
Rare SE: agranulocytosis (<1/1000) – CBZ and PTU
Leucopenia (low WBC count)
- Usually occurs during first few months of treatment
- Must immediately report: high temp, sore throat, mouth ulcers
Risk of hepatotoxicity (PTU)
2 regimens:
Titration: euthyroidism is achieved using ATDs, then low maintenance dose given to keep the patient euthyroid (12-18 month course).
‘Block and replace’: a very high dose of ATD is used and once hyperthyroidism is under control L-thyroxine (T4) is added to avoid hypothyroidism (may be useful for people with poor compliance and/or difficult to control with ATD dose titration).
Repeat TRAb levels taken near the end of treatment
Remission is likely if normal, and relapse is likely if TRAbs remain elevated. Once treatment is stopped, chances of remission are about 30-40%.
When should ATD not be used?
Not for thyroiditis (high T4 levels due to release of hormone store from damaged gland, but gland is not actually overactive)
Hyperthyroidism - what could you prescribe to someone who has tremor and increased HR?
When would this be contra-indicated?
propranolol for significant adrenergic symptoms
NO if asthma, or severe COPD
When is radioactive iodine contraindicated?
Contraindicated: children/ pregnant / breastfeeding / vomiting or incontinent of urine/ active thyroid eye disease
Risk of thyroid eye disease flaring up after I131
Precautions with radioactive iodine
Avoid pregnancy/breastfeeding for 6 months
Restrict close contact with children under 12 and pregnant women for 12 days and avoid extended periods (>15mins a day) or close contact for 25 days
Don’t share bed with partner for 4 days
Men should not father children for 4 months after treatment
Wear disposable gloves for first 14 days when prepping food
Before thyroidectomy, what needs to be achieved in the patient?
euthyroidism
Results in primary hypothyroidism
High TSH
low T4 and normal/low T3
subclinical hypothyroidism
high TSH
Normal T4 and T3
Secondary hypothyroidism
low/normal TSH
low T4
Low or normal T3
What is the effect of iodine deficiency on thyroid function?
hypertrophic effect on thyroid normally
- so in deficiency - cannot make hormones normally
- T4 goes down, TSH goes up
Hashimoto’s thyroiditis
TPO antibodies - thyroid peroxidase
Congenital hypothyroidism screening
heel prick
- 1 in 4,000 in UK
- if untreated may lead to cretinism (stunted physical and mental growth)
- at risk if mother is iodine deficient in pregnancy
Drug induced causes of hypothyroidism
lithium
amiodarone
Thyroid hormone replacement treatment
- aim
- half life
Aim: normalise TSH
half life: 7 days
No further investigations needed for hypothyroidism if TSH increases (scans do not change management)
Takes several weeks for TSH to normalise
Some drugs may impair T4 absorption
- what are these drugs?
PPIs
H2 antagonists - ranitidine
some antacids
Iron, Ca, aluminium
leave 4 hour gap before taking T4
Increased T4 requirement with what drugs
OCP; HRT - due to estrogen
anti-convulsants (epilepsy)
Hypothyroidism in pregnancy
- when does the fetus need T4?
from 4-5/40
uses maternal T4 exclusively up to 10/40 and partially thereafter
Check TFTs each trimester
untreated overt hypothyroidism during pregnancy is associated with:
infertility, miscarriage
pre-eclampsia
premature delivery
increased foetal mortality, impaired neurological development
