Salvo: Thyroid Dysfunction and Pharmacotherapy

primary hypothyroidism

inadequate secretion of thyroid hormones from the thyroid gland

secondary hypothyroidism

pituitary or hypothalamic failure

hypothyroidism s/s

· Weight gain

· Dry skin

· Cold intolerance/sensitivity

· Constipation

· Myalgias

· Bradycardia

· Weakness

· Depression

· Fatigue

· Coarse skin and hair

· Hoarse voice

· Slowed speech

hyperthyroidism s/s

· Nervousness

· Anxiety

· Irritability

· Heat intolerance

· Palpitations

· Easily fatigued

· Weight loss (with increased appetite)

· Warm, smooth, moist skin

· Fine tremor

· Increased frequency of bowel movements

· Fine hair

5 causes of primary hypothyroidism

o Hashimoto's disease

o Iodine deficiency

o Surgical removal of all or part of the thyroid

o Thyroid gland ablation with radioactive iodine

o Medications

what is the cause of secondary hypothyroidism

pituitary failure

what are the causes of hyperthyroism

all considered thyrotoxicosis

o Graves' disease

o Iodine-induced (excess intake, exposure to radiographic contrast media)

o Medications (Excessive doses of levothyroxine)

lab values in hypothyroidism

HIGH TSH

low total T3, total T4, and free T4

lab values of hyperthyroidism

LOW TSH

high total T3, total T4, and free T4

2 parts of hyperthyroidism diagnosis

high free T4 and low TSH

Biotin impact on thyroid labs

biotin > 5000mcg/day can falsely increase T3 and T4 and falsely decrease TSH

hold biotin for 24-48 hours before testing

3 goals of thyroid disease therapy

· Resolution of signs and symptoms

· Safe and effective medication use

· Medication adherence

brand names of levothyroxine

synthroid, levoxyl, levothroid, unithroid

what is levothyroxine

synthetic L-isomer of T4/thyroxine

when should follow-up/monitoring be done with levothyroxine

at 6 weeks (full effect seen)

what is considered the most sensitive and clinically relevant measurement of thyroid function

TSH

why should we try to keep patients on the same thyroid product/brand of medication

FDA’s current determination of bioequivalence provides no guarantee that a patient’s effectively absorbed dose will remain constant enough to stabilize TSH levels if patient is switched from product to product

LT4/levothyroxine dosing in age >12 without cardiac disease

1.6-1.7 mcg/kg/day

levothyroxine/LT4 dosing in older adults with known cardiac disease

1 mcg/kg/day (use IBW in obese pts)

or start 12.5-25mcg/day and titrate to full replacement dose

IV: PO conversion of levothyroxine

0.75:1

doses of levothyroxine

doses usually increase by 12-25 mcg

pregnancy dosing of levothyroxine

Will need an increased dose

after delivery, adjust to pre-pregnancy dose

TSH goals in 1st vs 2nd and 3rd trimester of pregnancy

§ 1st trimester <2.5mIU/L

§ 2nd and 3rd trimester: < 3 mIU/L

what drugs can cause decreased absorption of levothyroxine (need a dose increase)

Aluminum hydroxide, calcium, ferrous, dietary fiber, espresso, bile acid sequestrants, PPIs, H2Ras

what diseases can cause decreased absorption of levothyroxine (need a dose increase)

§ Mucosal disease (i.e. celiac disease, gastric bypass)

what drugs can cause increased clearance of levothyroxine (need a dose increase)

rifampin, carbamazepine, phenytoin, and phenobarbital

what 2 factors can cause a decreased conversion of T4 to T3 and will need an increased dose of levothyroxine

amiodarone, selenium deficiency

what 3 factors may need a dose decrease with levothyroxine

-increasing age

-post-delivery of a baby

-withdrawal of an interacting product

how to to titrate LT4 when monitoring TSH levels

adjust dose by 10-20%

consider available strengths

what does euthyroid mean

TSH levels in the normal range

monitoring frequency once a patient is euthyroid

monitor q 6-12 months

over treatment risks with levothyroxine

o HF, AF, angina, MI

o Osteoporotic effects (in postmenopausal women)

under treatment risks with levothyroxine

o Continued symptoms of hypothyroidism

o Depression

o Obstetric complications

when to take levothyroxine (pt counseling)

· Take 30 mins before food (and other meds)

o Or 2 hours after food/interacting products

o Or at bedtime

what should levothyroxine not be taken within 4 hours of?

Calcium or iron supplement or bile acid sequestrant

liothyronine brand name

cytomel

what is liothyronine

synthetic T3

starting and usual dose of liothyronine (cytomel)

starting: 25 mcg/day

usual dose: 25-75 mcg/day

dosing of liothyronine (cytomel) in those with cardiac disease or elderly

5 mcg PO QD

liotrix

o Combination of synthetic T4 and T3 in a ratio of 4:1

o High cost and lack therapeutic rationale

desiccated thyroid (thyroid USP)

o Contains T3 and T4

o Animal protein-derived

what are the 3 treatment options for hyperthyroidism

· Antithyroid medications (thionamides)

· Radioactive iodine

· Surgery

methimazole (MMI) brand name

tapazole

dose forms and frequency of methimazole (tapazole)

5mg and 10 mg tablets

administered 2-3 x day

what is the preferred thioamide

methimazole

methimazole use in pregnancy

·      Use in 2nd and 3rd trimesters of pregnancy with lowest effective dose

when is the max effect of methimazole seen

4-8 weeks

propylthiouracil (PTU) MOA

inhibits conversion of T4 to T3

propylthiouracil dose forms and frequnecy

50 mcg tablet

admin 3-4 times/day

use of propylthiouracil in pregnancy

·      Preferred treatment in 1st trimester of pregnancy, in thyroid storm, and in those unable to tolerate MMI

what is a concern with propylthiouracil

possible hepatotoxicity

monitoring timing of MMI and PTU

· Assess thyroid function in 4-6 weeks --> improvement should be noted

· Once stable/euthyroid, monitor thyroid function q 2 months

· Continue treatment for a minimum of 12-24 months

o After remission occurs, follow up every 6 to 12 months

what 2 things should be monitored with MMI and PTU

CBC and LFTs

major ADRs of thionamides (MMI and PTU)

o Agranulocytosis (usually within first 3 months)

§ Flu-like symptoms (fever, malaise)

§ Granulocyte count (< 200-500/mm^3)

§ Do NOT use other thionamide

o Hepatotoxicity

lab values for agranulocytosis

granulocyte count (<200-500/mm^3)

minor ADRs of thionamides (MMI and PTU)

o Rash (maculopapular)

o Arthralgias

o GI intolerance

o Fever

o Benign transient leukopenia (WBC < 4000/mm^3)

§ Cross-sensitivity ~50%

iodide MOA

blocks release of thyroid hormone and thyroid hormone synthesis and decreases gland size and vascularity

what are the 3 uses of iodide

· prepare Graves' disease patient for surgery, quickly achieve euthyroid, or following radioactive iodine

symptoms improve in 2-7 days

MOA of radioactive iodine (131 I)

· Concentrates in the thyroid and disrupts hormone synthesis

when is radioactive iodine the agent of choice (3 circumstances)

· Graves' disease, toxic autonomous nodules, and toxic MNGs

contraindication of radioactive iodine

pregnancy

when to withdraw/start thionamide with radioactive iodine use

withdraw the thionamide 4-6 days before use

restart 4 days after radioactive iodine treatment

surgery for hyperthyroidism requirement

·      Must be euthyroid before undergoing

o   Can use meds

pros/cons of surgery for hyperthyroidism

· Rapid onset and highest efficacy

· Most invasive and costly

· Surgical complications are low

beta blockers in hyperthyroidism

· Symptomatic relief

· Adjunct treatment with thioamides, iodides, I-131, or in preparation for surgery

which beta blocker is used for hyperthyroidism? dose?

propanolol 20-40 mg QID