Treatment of thyroid disorders Flashcards
What is the main hormone released by the thyroid gland?
T4 (thyroxine)
How can T4 be converted to T3?
5’ deiodinase
Where is T4 converted to T3?
Kidney and liver
How much more active is T3 than T4?
5 - 10 x more active
What does T3 bind to?
Nuclear receptor on various different tissues
What does T3 binding to nuclear receptors result in?
- Gene transcription
- mRNA synthesis
- Protein synthesis
- Affects many tissues - increase in BMR
What are the main effects of the thyroid hormones?
- Increased soft tissue growth and bone maturation
- Increased maturation of CNS
- Increased Na/K+ ATPase
- Increased O2 consumption
- Increased Heat production
- Increased BMR
- Increased Glucose absorption
- Increased Glyogenolysis
- Increased gluconeogenesis
- Increased lipolysis
- Increased protein synthesis and degradation
- Increased cardiac output (ionotropic and chronotropic affects)
What are the main affects of hyperthyroidism?
- High BMR
- Increased temperature, sweating
- Nervousness, tremor, tachycardia, heat sensitivity and loss of weight
What are 2 common manifestations of hyperthyroidism?
- Diffuse toxic goitre
- Toxic nodular goitre
What is diffuse toxic goitre?
- Autoimmune disorder where antibodies to the TSH receptor stimulate thyroxine secretion
- Toxic nodular goitre is caused by benign neoplasm/adenoma
What are causes which lead to hyperthyroidism?
- Graves disease (LATS/TSI)
- Overtreatment with thyroxine
- Thyroid adenoma
- Transient neonatal thyrotoxicosis (mother with Graves disease)
What cells are affected by graves disease specifically?
Thyroid follicular cells
How can hyperthyroidism be diagnosed?
- Measure blood TSH, T3 and T4 levels
- Test for anti-thyroid antibodies (especially TSH receptor antibodies)
- Radionucleotide thyroid scan (123I - or 99mTcO4 - uptake) viewed by a gamma camera
What does an overactive part of the thyroid look like on a radionucleotide thyroid scaN?
Dark
What does the thyroid look like in thyroiditis on a radionucleotide thyroid scan?
Light - maybe nothing (hypothyroidism)
What are the 3 main treatments in thyroid disease?
- Anti-thyroid drugs
- Radioactive iodine
- Surgery
All have drawbacks
What is given to treat hyperthyroidism?
Oral radioiodine (131I)
How does radioiodine (131I) work?
- Selectively taken up by thyroid
- Damages cells - emits a short-range Beta radiation and affects only the follicle cells
- Hypothyroidism eventually occur which can be treated with replacement therapy
How is radioiodine (131I) given?
- Orally
- Given as single dose
- Lasts ~ 2 months
- Not to be given during pregnancy / lactation
What drugs are used to treat hyperthyroidism?
- Carbimazole (methimazole), Thioureylenes (thioamides)
- Iodine
- Beta blockers (propranolol)
- Calcium supplements
How do thioureylenes and carbimazole affect the thyroid?
- Decrease synthesis of thyroid hormones
- Inhibit thyroperoxidase so reducing the iodination of thyroglobulin. Acts over 3-4 weeks
How does iodine affect the thyroid?
Given orally in high doses and is converted to iodide and transiently reduces thyroid hormone secretion and vascularity of the gland
What is the purpose of prescribing calcium supplements in the treatment of hyperthyroidism?
To maintain normal bone density
What are the thioamides?
- Propylthiouracil
- Methimazole (Carbimazole is its pro-drug)
What group in thioamides is essential for antithyroid activity?
Thiocarbamide
What does hypothyroidism lead to in children?
Cretinism
What are the signs / symptoms of hypothyroidism?
- Low BMR
- Slow speech
- Deep hoarse voice
- Lethargy
- Bradycardia
- Sensitivity to cold
- Mental impairment
What can severe hypothyroidism be called?
Myxedema - can also be used to describe dermatological changes associated with hypothyroid and hyperthyroid conditions
What is hypothyroidism due to?
- Reduction removal ofthyroid hormones
- Preduction of antibodies that can break down the thyroid follicular cells
What other cells have TSH receptors on them?
Fibroblasts - can be stimulated in hypothyroidism
What is myxedema caused by?
- Accumulation of increased amounts of hyaluronic acid and chondroitin sulfate in the dermis in both lesioned and normal skin causing swelling/puffiness to the subcutaneous tissue
What % of patients with hyperthyroidism have symptoms limited to pretibial myxedema?
1 - 5% of patients (due to high levels of antibody)
What is Exophthalmos in Grave’s disease due to?
Depositing mucopolysaccaridies in the muscles at the back of the eye (antibody which does this not the high amounts of thyroid hormone)
What are the symptoms of hypothyroidism due to?
- Low levels of thyroid hormones and/or increased concentrations of TSH
When would TSH not be raised in hypothyroidism?
Pituitary problem (test with protirelin, synthetic analogue of TRH)
What can congenital hypothyroidism causes be?
- Hypoplasia (agenesis/dysgenesis of gland during development)
- Familial enzyme defects (dyshormonogenesis)
- Iodine deficiency (endemic cretinism, perchlorate)
- Intake of goitrogens during pregnancy
- Pituitary defects
- Idiopathic
Why is it extremely important to detect hypothyroidism in newborns / babies as quickly as possible?
- Longer the condition goes undetected the lower the IQ (also height)
- May have few or no clinical manifestations
What can be the causes of acquired hypothyroidism be?
- Iodine deficiency
- Auto-immune thyroiditis
- Thyroidectomy or RAI therapy
- TSH or TRH deficiency
- Medications (iodine and cobalt)
- Idiopathic
What is hashimoto’s disease?
- Enlarged, inflammed hypofunctioning thyroid (goite)
- Caused by antibodies attacking the thyroid gland causing it to atrophy
- Autoimmune lymphocytic thyroiditis
What are the anti-thyroid antibodies in hashimoto’s disease?
- Thyroglobulin Ab
- Microsomal Ab/Thyroid peroxidase (TPO) Ab
- TSH-R Ab (blocking antibodies)
Is hashimoto’s disease heritable?
Yes - it runs in families
What are the treatments for hypothyroidism?
- Levothyroxine - synthetic analogue of thyroxine - has all the actions of endogenous thyroxine. Standard T4 replacement therapy for hypothyroidism
- Liothyronine - synthetic analogue of tri-iodothyronine - has all the actions of endogenous tri-iodothyronne. Treatment of choice for myxedema coma
What is Myxedema coma (an extreme form of hypothyroidism compounded by some stressful state, such as infectio, MI or stroke) treated with?
Liothyronine (Synthetic T3)
