Pharm - Thyroid Flashcards
[Men/Women] are more likely to suffer from a thyroid condition
Women – 5-8x more likely
[Younger/Older] are more likely to suffer from hypothyroidism
Older – 17% of women by age 60 have hypothyroid conditions
What is the active metabolite form of thyroid hormone?
T3
What is the pro-hormone form of thyroid hormone?
T4 – Thyroxine
Where are the 3 deiodinases (D1, D2, D3) expressed?
D1 = liver, kidney D2 = CNS, pituitary, thyroid, heart, brown fat, skele muscle D3 = brain, skin, placenta, tissue in disease states (tumors)
Which deiodinase has inactivating function?
D3 – inactivates T3 by converting to T2 and reverse T3
Which deiodinase contributes the most to circulating T3?
D2 – contributes ~60% of T3 converted from T4
—-D1 only contributes ~ 24%
What happens in Hashimoto’s Thyroiditis?
Autoantibodies against symporter affecting iodide transport
High TSH, Low T4
What thyroid state?
Primary Hypothyroidism – No feedback inhibition of TSH production
Low TSH, Low T4
What thyroid state?
Secondary Hypothyroidism – low TSH made in anterior pituitary is primary cause, leading to no T4 made in thyroid
Low TSH, High T4
What thyroid state?
Hyperthyroidism – Thyroid uses up normally made amounts of TSH to make lots of T4
Associated w/ [hyper/hypo] thyroidism:
- -Goiter
- -Cold Sensitivity
- -Heat Intolerance
- -Exopthalmos
- -Excessive sweating
- -Tachycardia
- -Constipation
- -Weight gain
- -Dry/brittle hair
- -Goiter = HypO
- -Cold Sensitivity = HypO
- -Heat Intolerance = HypER
- -Exopthalmos = HypER
- -Excessive sweating = HypER
- -Tachycardia = HypER
- -Constipation = HypO
- -Weight gain = HypO
- -Dry/brittle hair = HypO
How is most circulating T3 generated?
Peripheral conversion from T4 (80%) – 20% is direct secretion
Adult onset (especially older women) severe form of hypothyroidism is called ___
Myxedema
Infant/childhood hypothyroidism that causes mental retardation and Dwarfism is called ___
Cretinism
The first synthetic thyroid hormone is called ___ and is specifically the ___ form.
Levothyroxine Sodium – T4 replacement
T3 form synthetic thyroid hormone is called ___
Liothyronine Sodium
Synthetic thyroid hormone that is a mixture of T3/T4 called ___ has more ___ form by weight.
Liotrix —4:1 ratio of T4:T3
Patients with what condition have difficulty converting T4 to T3?
Chronic Fatigue Syndrome
In what patient population should Levothyroxine be initiated with lower doses?
Patients w/ Angina Pectoris
Half life and time to peak theraputic effect of Levothyroxine?
Half life = 6-7days
Time to Peak theraputic = 3-4weeks
Longer half life compared to Liothyronine
Half life and time to peak theraputic effect of Liothyronine?
Circulating half life = 1day
Reaches peak levels in 2-4hr after oral administration
How do you treat acute emergency hypothyroid conditions (like Myxedema Coma)?
IV formulation of Liothyronine
[Levothyroxine/Liothyronine] is more potent by weight
T3 Liothyronine is 4x more potent on mcg for mcg basis
Heart palpitations Nervousness Heat intolerance Excessive sweating Insomnia Tremors Frequent bowel movments Excessive weightloss Are all symptoms of what?
Thyroid hormone overdose – similar to hyperthyroidism symptoms
What is the most common preventable cause of mental handicap in the world?
Iodine deficiency –> goiter (hypothyroidism)
What area is referred to as the “goiter belt”?
Great Lakes and Northwestern region of US
What are 3 common causes of primary and secondary hypothyroidism?
Primary: Hashimoto’s, Iodine Deficiency, Thyroid Ablation
Secondary: Pituitary adenoma, pituitary surgery, radiotherapy
What is the most common cause of hyperthyroidism and who does it most often affect?
Grave’s disease – autoimmune thyroid-stimulating antibodies activating thyrotropin receptor on thyroid cells
Most often affect women 20-40 y/o
What are the 4 common causes of hyperthyroidism?
- Grave’s disease
- Nodular goiter –older age 90% of nodules are benign
- Thyroiditis – inflammation–> excess release
- Thyroid cancer
Mechanism of action of antithyroid drugs?
Inhibit Thyroid Peroxidase activity – prevent organification of iodide and coupling of iodotyrosine
Which antithyroid drug also reduces deiodination of T4 to T3 by inhibiting D1 deiodinase activity?
Propylthiouracil
What are 3 severe side effects of antithyroid drugs (Methimazole, Propylthiouracil, Carbimazole)
- Agranulocytosis (granulocyte less than 500/mm3)
- Hepatitis
- Lupus-like syndrome
**These are absolute contraindications for further antithyroid drug therapy
Propylthiouracil vs. Methimazole
- -Longer half life
- -Faster excretion
- -Relatively less transplacental passage
- -Higher Concentration in breast milk
- -Higher Agranulocytosis risk
- -Longer half life = Methimazole
- -Faster excretion = Propylthiouracil
- -Relatively less transplacental passage = Propylthiouracil
- -Higher Concentration in breast milk = Methimazole
- -Higher Agranulocytosis risk = Propylthiouracil
Mechanism of action of Radioactive Iodine?
131 I = thyroid specific Iodine isotope destroys sufficient thyroid tissue to restore euthyroid
- -Emits beta particles and gamma rays
- -5 day half-life
Indications and contraindications for radioactive Iodine therapy?
Indication: relapsed hyperthyroidism after antithyroid drug therapy
Contraindications: pregnancy, breast-feeding (passes to breast milk)
Why are B-blockers used for hyperthyroid therapy?
Control symptoms – tremor, anxiety, palpitations
