management of thyroid disorders Flashcards
Name the physiological functions regulated by the thyroid hormones
- CNS (regulates brain function and mood)
- Sleep
- Cardiac function (heart rate and function)
- Lung function (affects breathing rate)
- GI function (affects rate of digestion)
- Increases lipid metabolism
- Increases uptake and utilization of glucose
- Musculoskeletal system and skin (affects muscle growth and strenght)
- Skin (affects skin dryness)
- Body temperature and basal metabolic rate (
- Menstrual cycles
Describe the HPT axis and the negative feedback involving it
Low levels of circulating thyroid hormones in blood –> hypothalamus increases secretion of TRH (thryrotropin releasing hormone) –> TRH stimulates the anterior pituitary to increase secretion of TSH (thyroid stimulating hormone/thyrotropin) –> TSH stimulates the thyroid tissues to increase secretion of thyroid hormones –> negative feedback to the hypothalamus and anterior pituitary
Describe the criteria for screening for thyroid hormone levels?
ALL pregnant women and pediatric population should undergo screening.
Otherwise, routine screening is generally not recommended, unless there is presence of compelling indications, such as: personal hx of autoimmune disease (e.g. T1DM, cystic fibrosis), first degree relative with autoimmune thyroid disease, psychiatric disorders, taking amiodarone/lithium, head/neck radiation therapy for maglinancies, symptoms of hyper/hypothyroidism
Describe the laboratory monitoring parameters/screening parameters for thyroid disease
Free T4 levels
TSH levels
Presence of autoantibodies:
- TRAb/TSI (thyrotropin receptor antibodies/thyrotropin stimulating immunoglobulin; specific and confirmatory for graves disease hyperthyroidism)
- ATgA (Anti-thyroglobulin antibodies)
- TPO (thyroperoxidase antibodies)
Describes the clinical manifestations of hypothyrodism (signs and symptoms + labs):
Signs and symptoms: fatigue/lethargy/weakness, weight gain, bradycardia, slow reflexes, intolerance to the cold, constipation, dry and coarse hair and skin, increased frequency of menstrual periods/bleeding, periorbital swelling, goiter
increased risk for atherosclerosis, myocardial infarction, miscarriage, impaired fetal cognitive development
labs:
low free T4
elevated TSH (if primary hypothyrodism) OR
low TSH (if central hypothyroidism)
(+) TPO and ATgA (if Hashimoto’s disease)
elevated LDL-C/TG
elevated CPK
List the pharmacological treatment options for hypothyroidism
Levothyroxine (synthetic T4), Liothyronine (synthetic T3)
Describe the properties of levothyroxine, including its indication, MOA, PK/PD characteristics, DDI, S/E and monitoring
indication: hypothyroidism
MOA: synthetic T4 (L-thyroxine)
Route: PO
Dosing:
healthy adults: 1.6mcg/kg/day -> usually start at 100mcg/day
elderly without CVD: 50mcg/day
with CVD: 12.5 to 25 mcg/day and titrate up
- to increase/decrease dose in 12.5-25mcg/day increments or 10%-15% of total weekly dose
PK/PD: conversion of T4 to T3 in liver, kidney, pituitary
DDI: absorption best on empty stomach (30-60 mins before meal, 4h after meal)
- not to be taken with polyvalent ions –> spaced out at least 2 hours from iron/calcium containing supplements and calcium/aluminium containing antacids
- not to be taken with PPI as absorption is affected by gastric pH
- dietary fibre may cause erractic absorption
S/E: anorexia, seizures (rare), cardiac abnormalities , e..g tachyarrhythmia, angina and MI (rare), increased risk of fractures, hyperthyroidism (diarrhoea, anorexia, insomnia)
Monitoring: assess TSH in 4-8 weeks, to target TSH: 0.4 to 4.0 mIU/L (can tolerate up to 6.9mIU/L for elderly >70 yo), assess for symptomatic relief in 2-3 weeks
*normalization of FT4 with consistently high TSH hints at non-adherance
Describe the properties of liothyronine, including its indication, MOA, PK/PD characterisitcs, DDI, S/E and monitoring
indication: used in combination with levothyroxine, for patients who are still symptomatic despite normalized TSH, can be considered if myxedema coma (IV)
MOA: synthetic T3 (more potent)
Dosing:
healthy adults: 25mcg
elderly/CVD: 5mcg
S/E: high incidence of adverse effects
Describe the special notes for the use of levothyroxine in pregnancy
Pregnant women may require a 30-50% increase in dose of levothyroxine, due to their elevated levels of thyroxine binding globulin (TBG) in their plasma, which decreases the level of free unbound T4/T3
Targets for TSH are also different, as they require more TH, which crosses the placenta and plays essential roles in the fetus (fetus does not produce its own thyroid hormones in the first 12 weeks/first trimester)
- first trimester: TSH <2.0mIU/L
- second trimester: TSH <3.0mIU/L
- third trimester: TSH <3.5mIU/L
Define subclinical hypothyroidism and the indication for treatment and treatment regime
elevated TSH levels, but normal FT4 levels (often result of early Hashimoto’s disease) -> can cause complications such as elevated risk of HF in older adults (>7.0mIU/L) and CHD (>10.0mIU/L)
indication to treat:
- TSH > 10.0mIU/L
- TSH 4.5-10mIU/L if: symptomatic, positive for TPOAb or have existing cardiac disease
dose: 25-75mcg/day recommended
Describe the clinical manifestations of hyperthyroidism (signs and symptoms + labs)
tachycardia, sweating, anxiety, irritability, insomnia, intolerance to heat, diarrhoea, fine hair, weight loss, increased appetite, menstrual changes (oligomennorhea/amenorrhea), goiter, exophthalmus (Grave’s disease)
elevated T4
low TSH
positive TRAb/TSI (if Grave’s disease)
List the treatment options for hyperthyroidism (pharmacological and non-pharmacological)
surgical: surgical resection/thyroidectomy
radiation: radioactive iodine therapy (clear, oral capsules)
drugs to treat: thionamides, iodides
drugs for symptomatic management: non-selective beta blockers (usually given PRN; can also be given as a bridging treatment or for treatment of thyroiditis which is usually self limiting)
Describe the properties of the thionamides (carbimazole / propylthiouracil), including indication, MOA, dosing, PK/PD, DDI, S/E and monitoring
indication: hyperthyroidism
MOA: binds to and inhibits TPO (thyroperoxidase enzyme), thus inhibiting the iodination of tyrosine to produce thyroid hormones [inhibits thyroid hormone synthesis in the thyroid gland]
- propylthiouracil can additionally block the peripheral conversion of T4 to T3 but only at high doses
Route: PO
Dosing:
- carbimazole (first line):
initial:15-60mg TDD divided into 2-3 doses
maintenance: 5-15mg OD
- propylthiouracil:
initial: 50-150mg TDS
maintenance: 50mg TDS or BD
PK/PD: hepatic, CYP450 and FMO; carbimazole is converted to active metabolite, methimazole
S/E:
- rash, risk of SJS, hepatotoxicity/jaundice (FDA boxed warning for propylthiouracil), agranulocytosis early in therapy (rare, usually within 3 months), drug fever, joint pains, hypothyrodism
Monitoring:
- may take weeks to see effect (maximum effect takes 4-6 months)
- to monitor for T4 and TSH, but TSH may remain suppressed for months after therapy begins; early in therapy, total T3 may be a better marker for efficacy than free T4
Describe the special notes for using thionamides in pregnancy
1st trimester: PTU > Carbimazole due to increased risk of fetal malformations with carbimazole
2nd/3rd trimester: Carbimazole > PTU due to PTU having high hepatotoxicity
Describe the properties of iodides (Lugol’s solution of saturated potassium iodide), including indication, MOA, dosing, PK/PD, S/E and monitoring
Indication: hyperthyroidism, for prevention of thyroiditis mediated hyperthyroidism, treatment of thyroid storm, before surgery (7-10 days before to shrink the gland), after radioactive iodine ablation (3-7 days after to inhibit thyroiditis mediated release of stored TH; DO NOT use before ablative therapy as it may reduce the uptake of radioactive iodine)
MOA: inhibits the release of stored thyroid hormones (but loses effect after 7-14 days), shrinks the size of the thyroid gland and decreases its vascularity
