Hyperthyroidism Flashcards
What is hyperthyroidism?
Overabundance of TH, mimics effect of activated sympathetic nervous system
Describe the changes in primary hyperthyroidism
High levels of TH secretion of thyroid gland (function independently)
=> Low TSH, high TH
List the possible causes of hyperthyroidism
- Grave’s disease - TRAb (thyrotropin receptor ab) mimics TSH & stimulates TH production
- Pituitary adenomas
- Toxic adenomas (hot nodule) - nodule secretes T3
- Toxic multi-nodular goiter (plummer’s disease) - nodules secrete T3
- Drug induced (amiodarone, lithium) - affect TH levels
- Subacute thyroiditis (may be due to infection, drug induced, early hashimoto) - inflamed thyroid bursts and release stored TH (result in hypothyroidism later on)
What are the signs and symptoms of hyperthyroidism?
- Weight loss, increased appetite (incr metabolism)
- Heat intolerance
- Goiter (due to nodules)
- Fine hair
- Heart palpitations, tachycardia
- Nervousness, anxiety, insomnia, tremor (*think sympathomimetic and CV effects)
- Menstrual disturbances (lower levels of E, higher levels of P, lighter and more infrequent menstruation, amenorrhea)
- Sweating, warm, moist skin
- Exophthalmos (bulging eyes) in Grave’s
- Fatigue
- Diarrhea
- Irritability
- Insomnia
Explain the diagnosis of hyperthyroidism
- Signs and symptoms
- Labs
- Radioactive iodine uptake (RAIU)
- Biopsy
- Signs and symptoms
- Labs
- Elevated FT4 concentrations
- Suppressed TSH concentrations (except in TSH-secreting adenomas, or secondary to excess TRH or TSH)
- Positive autoantibodies (TRAb, ATgA, TPO)
- Radioactive iodine uptake (RAIU)
- Uptake is elevated if gland is actively secreting TH (e.g., Grave’s toxic adenoma, multinodular goiter, TSH-secreting adenoma)
- Uptake is suppressed in disorders caused by thyroiditis or cancers (thyroiditis - thyroid gland burst, cancer - cancer cells proliferate and produce TH without iodine uptake)
- Biopsy (invasive)
What are the goals of hyperthyroidism therapy?
- Minimize or eliminate symptoms, improve QoL
- Minimize long-term damage to organs (heart disease, arrhythmia, sudden cardiac death, bone demineralization, fracture)
- Normalise FT4 and TSH concentrations
What are the 4 types of treatment options for hyperthyroidism?
- Surgical resection
- able to get rid of root cause (e.g., nodule)
- often results in hypothyroidism
- Radioactive iodine (RAI) ablative therapy
- colorless, tasteless liquid in a capsule that will concentrate in thyroid tissue and destroy overactive thyroid cells
- often results in hypothyroidism
- Thyroidectomy
- remove whole thyroid gland
- hypothyroidism - need to be on lifelong Levothyroxine
- Antithyroid Pharmacotherapy
- Thionamides
- Iodides
- Non-selective BBs
Antithyroid pharmacotherapy is last line in hyperthyroidism treatment
What are the situations in which antithyroid pharmacotherapy is considered?
- Those awaiting ablative therapy or surgical resection
- Antithyroid pharmacotherapy can be used to deplete stored hormones to minimize risk of post-ablative hyperthyroidism as a result of thyroiditis (thyroid gland burst)
- E.g., BB as bridging therapy, iodides to shrink gland before surgery, thionamides before surgery
- Those that cannot undergo ablative therapy or surgical resection
- RAI ablation is an absolute contraindication in pregnancy - risk of RAI entering fetus
- Pregnant ladies, young children, elderly may be unsuitable
- People who cannot isolate after RAI ablation (radioactive material ingested - potential exposure to others)
- Those who failed to normalize thyroid despite ablative or surgical intervention
- Mild disease / small goiter / low or negative antibody titers / women
- Limited life expectancy
What is the MOA of thionamides (carbimazole and propylthiouracil)
Inhibit iodination and synthesis of thyroid hormones via inhibiting thyroid peroxidase (TPO)
*TPO - oxidizes I- to active iodide, and attaches iodide to tyrosine within thyroglobulin (Tg) molecule to give MIT + DIT (precursors to T3 and T4)
PTU can additionally block T4 to T3 conversion in the periphery at high doses
Describe the absorption of Carbimazole
Oral, once daily dosing (FYI: initially 15-60mg daily in 2-3 divided doses, once euthyroid, can reduce to 5-15mg once daily)
Converted into active methimazole in serum after absorption
Describe the distribution of Carbimazole
Methimazole
- clinical effects last a day because it concentrates in the thyroid
- no binding to plasma protein
- produces >90% inhibition of thyroid organification of iodine (into thyroglobulin) within 12h
Describe the metabolism of Carbimazole
Metabolised in the liver by CYP450 and FMO enzymes
*FMO: flavin-containing monooxygenase
Describe the elimination of Carbimazole
Metabolites mainly excreted in urine ~90% and feces ~10%
What are the adverse effects of Thionamides (Carbimazole, PTU)
- Hepatotoxicity risk (Carbomazole can cause jaundice, PTU has Black Box Warning)
- Rash - risk for SJS
- Agranulocytosis (low WBC) early in therapy, usually within 3 months
- Fever
Others:
- Joint pain
- Nausea
- Overtreatment - hypothyroidism (thus dose should be decreased once euthyroid)
Describe the efficacy of Thionamide therapy
EFFICACY:
Slow onset in reducing symptoms - weeks
=> Clinical response may take 3-6w after initiating
Maximal effect may take up to 4-6 months
*Why? T4 has long half-life and the thyroid stores of hormone need to be depleted
