ChemPath: Thyroid ✔️ Flashcards
Thyroid physiology (SUMMARY) - how thyroxine is produced:
- TSH = produced by pituitary gland, it controls the uptake of iodine into the thyroid gland from GI tract
- Iodine taken up by GI tract, then converted to iodide
- Iodide is then taken up by the thyroid gland via Na+/K+ ATPase pump (active process)
- In the thyroid gland, iodide is converted into iodine using thyroid peroxidase
- Iodine is taken up by thyroglobulin
- Then iodine is converted into thyroxine (inside the thyroid gland, under the influence of thyroglobulin)
- Thyroxine stored inside thyroid gland, then secreted into capillary lumen as/when required
- In the peripheries, thyroxine (T4) is converted into T3
NOTE: therefore, you can measure TSH, T4, T3, thyroglobulin, thyroid peroxidase enzymes
What controls the uptake of iodine by thyroid follicular cells?
TSH
Which channel is important for the transport of iodine across the cell membrane?
Na+/K+ ATPase
Which enzyme converts iodide to iodine?
Thyroid peroxidase
How is thyroxine produced?
Iodination of tyrosine residues in thyroglobulin generates MIT and DIT which leads to the formation T3 and T4
What percentage of thyroxine is free active T4?
0.03%
The MAJORITY is bound to proteins in the blood
What does thyroxine bind to in the blood?
- Thyroxine binding globulin (TBG) –> majority is bound to this (70%) - TBG is based off albumin synthesis (so lacking albumin in the diet can lead to low TBG)
- Thyroxine-binding prealbumin (TBPA) –> 20% bound to this
- Albumin - 5% bound to this
Outline the hypothalamo-pituitary-thyroid axis (SUMMARY):
- The hypothalamus produces TRH which stimulates the release of TSH from the anterior pituitary
- TSH stimulates T4 production in the thyroid
- T4 is converted to T3 in the peripheries
- (Excess) T4 feeds back to the hypothalamus and pituitary as a negative feedback system (i.e. stops TRH & TSH production respectively)
List some causes of hypothyroidism:
PRIMARY (issue with the thyroid gland):
* Hashimoto’s thyroiditis (autoimmune)
* Atrophic thyroid gland
* Post-Graves’ disease (after treatment of Graves’ e.g. with RAI or surgery)
Less common causes:
* Post-thyroiditis
* Drugs (e.g. amiodarone, lithium)
Thyroid agenesis / dysgenesis
* Iodine deficiency
* SECONDARY cause: Pituitary disease
* Peripheral thyroid hormone resistance (receptors in tissues do not respond to thyroxine)
Symptoms of hypothyroidism:
- Metabolic: lethargy (low metabolic rate), poor appetite + weight gain, cold dry hands + feet
- CVS: bradycardia
- GI: thyroxine affects GI tract, so lack of thyroxine slows down GI tract –> constipation
- Resp: lower respiratory rate
- Reproductive: irregular periods / infertility
- Chem imbalances: hyponatraemia (are thyroxine is involved in Na+ transport in the kidneys, affecting Na+ reabsorption), normocytic / pernicious anaemia
NOTE: pituitary tumour –> visual issues; Graves’ disease –> goitre
NOTE: thyroid disease more subtle in elderly!
Outline the investigation findings that may be seen in hypothyroidism.
- High TSH
- Low T4
- Thyroid peroxidase antibodies
- Look out for other autoimmune conditions e.g. measure B12 for pernicious anaemia, look for IgA tTG for coeliac disease, adrenal hormones for Addison’s disease etc.
Why is it important to do an ECG in patients with suspected hypothryoidism?
If someone with hypothyroidism has underlying cardiovascular disease, giving them thyroxine may induce ischaemia (as thyroxine increases myocardial contractility)
NOTE: so you would start on a low dose of thyroxine and then escalate
How is hypothyroidism treated?
Levothyroxine - 50-150-200 µg/day, titrated to a normal TSH (depending on BMI)
What are some risks of overtreatment with thyroxine?
- Osteopaenia
- Atrial fibrillation
- Weight loss
What is a subclinical hypothyroidism?
- Normal T4 with high TSH
- Sometimes referred to as compensated hypothyroidism
Patients often do not have clinical signs / symptoms.
NOTE: if TPO antibodies are positive, the patient may go on to develop hypothyroidism
Why might there be some benefit to treating subclinical hypothyroidism?
- As they typically don’t present with symptoms, there are no symptoms that improve with treatment
- INSTEAD, hypothyroidism is associated with hypercholesterolaemia, which can improve with treating subclinical hypothyroidism
Outline how thyroid function changes in pregnancy.
- hCG has a similar structure to TSH so high hCG levels can cause hyperthyroidism
- Leads to slightly low TSH and slightly high free T4
- TBG level increases dramatically
NOTE: hCG level drops later on in pregnancy, TSH and T4 levels then normalise
NOTE 2: these changes are NORMAL in pregnancy and do NOT indicate thyroid disease
How is neonatal hypothyroidism diagnosed?
Guthrie test
Why is the timing of the Guthrie test important?
It needs to be done at least 48-72 hours after birth to make sure maternal TSH is no longer in the baby
What is sick euthyroid?
- Alteration in the pituitary thyroid axis in non-thyroidal illness
- In other words, when you are very sick (e.g. septic), your thyroid will shut down to try and reduce your basal metabolic rate
- During severe illness, this leads to low T4 and high / normal TSH in response
- Later, the TSH decreases and T3 also decreases, all of which to lower BMR
These patients do NOT have hypothyroidism / subclinical hypothyroidism as this is the body’s mechanism to preserve BMR and not an actual hypothyroid condition
What are the TFT findings in sick euthyroid?
- Low T4 and T3
- Normal/high TSH
NOTE: these patients do NOT have symptoms of hypothyroidism
What are the three main causes of hyperthyroidism?
High uptake on radio iodine scan:
* Graves’ disease
* Toxic multinodular goitre
* Single toxic adenoma
Low uptake on radio iodine scan:
* Subacute thyroiditis
* Post-partum thyroiditis
Others: silent thyroiditis (immune & amiodarone), factitious thyroiditis (e.g. overmedicating with thyroxine for weight loss), TSH-induced, thyroid cancer induced, struma ovarii
What is struma ovarii?
A rare form of ovarian tumour (usually a teratoma) that contains mostly thyroid tissue and produces thyroxine
What is post-partum thyroiditis?
During pregnancy, the body may produce antibodies that stimulate the thyroid gland
Clinical features of Graves’ disease:
- Diffuse goitre
- Exophthalmos (TSH can act on receptors on the eye)
- Pretibial myxoedema
- Thyroid apropachy (affects fingers)
NOTE: NO radioactive iodine treatment for Graves’ disease with eye involvement, as radioiodine can make Graves’ eye disease worse
Clinical features of thyroiditis:
Inflammation of the thyroid gland, so often have:
- Painful thyroid
- Fever
RARE - painless/silent thyroiditis
Clinical signs of thyrotoxicosis:
- Metabolic: increased BMR = weight loss
- CVS: tachycardia / palpitations, AF
- GI: diarrhoea (thyroxine stimulates peristalsis)
- Resp: tachypnoea
- Skeletal: osteopenia / osteoporosis (thyroxine affects osteoclasts)
- Reproductive: irregular periods, infertility
Thyrotoxicosis diagnostic tests and management:
Diagnosis:
* Blood tests: High T4, low TSH (+/- thyroid autoantibodies)
* Radioiodine uptake scan
Other Ix:
* ECG
* Bone mineral density
Mx:
* Beta-blocker if pulse >100bpm
* Radioactive iodine –> taken up by thyroid gland, after which radiation slowly destroys thyroid gland (Complications: precipitation of thyroid storm, hypothyroidism after treatment)
* Thionamides e.g. carbimazole, propylthiouracil –> typically used to treat Graves’ disease
What is a major risk of radioiodine treatment for hyperthyroidism?
- Can precipitate thyroid storm
- Can result in hypothyroidism
How do thionamides work?
What is a rare SE of thionamides?
E.g. Carbimazole, propylthiouracil
Works by targeting thyroid peroxidase and prevents conversion of iodide to iodine
Thionamide can be titrated over 18 months OR can be used for the block & replace method
SEs:
* Rash
* Agranulocytosis - RARE SE: neutropenia –> STOP MEDICATION if patient has a sore throat or fever and check FBC
What kind of dosing regimes can be used for thionamdes?
- Can be titrated to achieve normal T4 levels
- Block and replace - high dose is given to block the thyroid gland and then given thyroxine replacement
Which drug can be given to hyperthyroid patients prior to surgery to block uptake of iodide?
Potassium prechlorate - prevents uptake of iodide prior to surgery
What is the long-term treatment of thyroiditis?
Thyroid hormone replacement
NOTE: this is because although thyroiditis presents with hyperthyroidism initially (as infection / inflammation damages the follicular cells leading to excess release of stored thyroxine), it later develops into hypothyroidism after the thyroid is damaged and no longer producing thyroxine
What are the two most common forms of thyroid cancer?
- Papillary thyroid cancer
- Follicular thyroid cancer
NOTE: medullary thyroid cancer = RARE
How is thyroid cancer treated?
- Total thyroidectomy
- +/- adjuvant radioiodine treatment
- +/- high dose thyroxine to suppress TSH levels to prevent TSH from stimulating any remaining cells*
What is a thyroid tumour marker to check is the thyroid cancer treatment has been successful?
- Thyroglobulin - indicates functioning thyroid tissue
NOTE: thyroglobulin levels are not affected by stimulated/suppressed TSH
Which cells do medullary thyroid cancer arise from?
Calcitonin-producing C cells
NOTE: it is part of MEN2
Name two tumour markers used for medullary thyroid cancer?
- Calcitonin
- Carcinoembryonic antigen (CEA)
