2. Endocrine Medications

What are the three hormones secreted by the thyroid gland?

T4 (L-thyroxine), T3 (L-triiodothyronine), and calcitonin

Which thyroid hormone is more potent?

T3

Which thyroid hormone is responsible for most systemic effects?

T3

How is T3 formed?

MIT + DIT = T3

How is T4 formed?

DIT + DIT = T4

What stimulates T4 secretion?

TSH

Where are MIT and DIT stored?

Bound to thyroglobulin in the thyroid gland

Where are thyroid hormone preparations metabolized?

Liver via enterohepatic recirculation

What is primary hypothyroidism?

Dysfunction of the thyroid gland causing ↓T3/T4 and ↑TSH

What is secondary hypothyroidism?

Inadequate TSH stimulation causing ↓T3/T4 and ↓TSH

Drug of choice for primary hypothyroidism

Levothyroxine (T4)

Drug of choice for secondary hypothyroidism

Levothyroxine (T4)

When should thyroid labs be checked after starting therapy?

4-6 weeks after initiation

What is the treatment goal for primary hypothyroidism?

Maintain TSH within the normal range (lower half of reference range)

How often should TSH be monitored during dose titration?

Every 2-3 months with dose adjustments every 6-8 weeks

What can excessive thyroid hormone replacement cause?

Hyperthyroidism

Patient education for ALL thyroid hormone replacement

Take every AM 30 minutes before breakfast, lifelong therapy, take missed dose ASAP unless close to next dose, DO NOT switch manufacturers, full effects take ~1 month, avoid heat exposure because it can inactivate the medication

What symptoms would be present if dose for hypothyroidism is too low?

Bradycardia, constipation, fatigue, lethargy

What symptoms would be present if dose for hypothyroidism is too high?

Diarrhea, heat intolerance, hyperthermia, irritability, tachycardia

Which thyroid replacement has the longest half-life?

Levothyroxine

What is the MOA of levothyroxine?

Replaces T4, increasing basal metabolic rate, gluconeogenesis, and DNA/protein synthesis

Examples of levothyroxine

Synthroid, Levoxyl, Unithroid

Drug class of levothyroxine

Thyroid hormone (T4)

Clinical uses of levothyroxine

Primary and secondary hypothyroidism

ADRs of levothyroxine

Tachycardia, hypertension, urticaria, alopecia, diarrhea, increased appetite, heat intolerance, tremor, rash, anxiety, hyperactivity

Contraindications of levothyroxine

Acute MI (without hypothyroidism) and thyrotoxicosis

Black Box Warning for levothyroxine

Avoid in treatment of obesity/weight loss

Drug interactions with levothyroxine

Bile acid sequestrants, iron salts, and antacids decrease absorption; estrogen decreases response; increases metabolism of antihypertensives and antiarrhythmics (especially digoxin)

Why is levothyroxine dosed once daily?

It has a long half-life

IV levothyroxine dose compared with oral

Half the oral dose

What is the MOA of liothyronine?

Replaces T3, increasing oxygen consumption and metabolism of carbohydrates, fats, and proteins

Drug class of liothyronine

Thyroid hormone (T3)

Brand names of liothyronine

Cytomel, Triostat

Clinical uses of liothyronine

Myxedema and short-term TSH suppression

How potent is liothyronine compared with natural T3?

Approximately 4 times more potent

ADRs of liothyronine

Tachycardia, hypertension, arrhythmias, urticaria, alopecia, diarrhea, increased appetite, heat intolerance, tremor, rash, anxiety, hyperactivity

Contraindications of liothyronine

Acute MI (without hypothyroidism) and thyrotoxicosis

Drug interactions with liothyronine

Increases metabolism of warfarin, insulin, oral hypoglycemics, antihypertensives, antiarrhythmics (especially digoxin); bile acid sequestrants decrease absorption

What is the most common cause of hyperthyroidism?

Graves disease

What is thyrotoxicosis?

Elevated circulating thyroid hormone levels causing accelerated metabolism

What laboratory findings are seen in overt hyperthyroidism?

Elevated free T3 or T4

What laboratory findings are seen in subclinical hyperthyroidism?

Suppressed TSH with normal T3/T4

What is thyroid storm?

A life-threatening form of severe thyrotoxicosis

Signs and symptoms of thyroid storm

Fever, atrial tachyarrhythmias, CHF, nausea, vomiting, diarrhea, seizures, altered mental status

Beta blocker of choice for thyroid storm

Propranolol

Why is propranolol preferred in thyroid storm?

It also inhibits peripheral conversion of T4 to T3

Monitoring for ALL antithyroid drugs

Monitor TSH and CBC for agranulocytosis during the first 3 months; monitor weight 2-3 times per week

Patient education for ALL antithyroid drugs

Seek medical care for unusual bleeding or jaundice; avoid iodine-rich foods (shellfish, shrimp, spinach) because they stimulate thyroid hormone production

Drug class of propylthiouracil (PTU)

Thioamide (antithyroid drug)

Clinical uses of PTU

Thyroid storm and hyperthyroidism during the first trimester of pregnancy

Why is PTU preferred in thyroid storm?

It more effectively inhibits peripheral conversion of T4 to T3

MOA of PTU

Inhibits thyroid hormone synthesis and peripheral conversion of T4 to T3

ADRs of PTU

Edema, hair loss, pruritus, rash, skin pigmentation, agranulocytosis, hepatitis, lupus-like syndrome, paresthesias

Drug interactions with PTU

Decreases metabolism of warfarin; monitor drugs with a narrow therapeutic index

Which antithyroid drug is preferred during the first trimester of pregnancy?

PTU

Drug class of methimazole

Thioamide (antithyroid drug)

Brand name of methimazole

Tapazole

Clinical uses of methimazole

Hyperthyroidism (drug of choice in nonpregnant patients)

MOA of methimazole

Inhibits thyroid hormone synthesis by preventing formation of T3 and T4

How often is methimazole administered?

Once daily (PTU is multiple x/day)

ADRs of methimazole

Edema, hair loss, pruritus, rash, skin pigmentation, loss of taste, agranulocytosis, hepatitis, lupus-like syndrome, peripheral paresthesias

Drug interactions with methimazole

Decreases metabolism of warfarin; monitor narrow therapeutic index drugs

Which antithyroid medication is the drug of choice for most nonpregnant adults?

Methimazole

Compare levothyroxine vs liothyronine

Levothyroxine is T4 with a long half-life and once-daily dosing; liothyronine is T3, more potent, faster acting, and more likely to cause arrhythmias.

Compare PTU vs methimazole

PTU inhibits thyroid hormone synthesis and T4→T3 conversion and is preferred in thyroid storm and first trimester pregnancy; methimazole is once daily and is preferred for most nonpregnant patients.

What are the primary hormones involved in calcium homeostasis?

Parathyroid hormone (PTH), calcitonin, and vitamin D (calcitriol)

What is the primary action of parathyroid hormone (PTH)?

Increases serum calcium and decreases serum phosphate.

What is calcitriol?

The active form of vitamin D (1,25-dihydroxyvitamin D3).

What are the major drug classes used to treat parathyroid disorders?

Calcimimetics and vitamin D analogs

Drug class of cinacalcet

Calcimimetic

Brand name of cinacalcet

Sensipar

Clinical uses of cinacalcet

Primary Hyperparathyroidism: Indication for parathyroidectomy BUT unable to obtain

Secondary Hyperparathyroidism: CKD on dialysis

Parathyroid Carcinoma

MOA of cinacalcet

Activates calcium-sensing receptors on the parathyroid gland, increasing sensitivity to extracellular calcium and decreasing PTH secretion.

What effect does cinacalcet have on serum calcium?

Decreases serum calcium.

ADRs of cinacalcet

Nausea, vomiting, diarrhea, dizziness, weakness, hypocalcemia, paresthesias, muscle spasms, QT prolongation secondary to hypocalcemia.

Contraindications of cinacalcet

Hypocalcemia (do not initiate if serum calcium is below normal).

Drug interactions with cinacalcet

CYP2D6 inhibitor; use caution with drugs metabolized by CYP2D6 and medications that prolong the QT interval.

Monitoring for cinacalcet

Monitor serum calcium, phosphorus, and PTH levels regularly.

Patient education for cinacalcet

Take with food or shortly after a meal; report muscle cramps, tingling, numbness, or seizures immediately.

What dietary implication is associated with cinacalcet?

High-fat meals DECREASE absorption

Which medication tricks the parathyroid gland into sensing higher calcium levels?

Cinacalcet

Drug class of calcitriol

Active vitamin D analog

Brand names of calcitriol

Rocaltrol, Calcijex

Clinical uses of calcitriol

Secondary hyperparathyroidism in chronic kidney disease

MOA of calcitriol

Increases intestinal absorption of calcium and phosphate while promoting normal bone mineralization.

What effect does calcitriol have on serum calcium?

Increases serum calcium.

ADRs of calcitriol

Hypercalcemia, hyperphosphatemia, weakness, headache, nausea, vomiting, constipation, polyuria.

Contraindications of calcitriol

Hypercalcemia, vitamin D toxicity.

Drug interactions with calcitriol

Thiazide diuretics increase hypercalcemia risk; magnesium-containing antacids increase hypermagnesemia risk in dialysis patients; digoxin toxicity risk increases with hypercalcemia.

Monitoring for calcitriol

Monitor serum calcium, phosphorus, and renal function.

Patient education for calcitriol

Avoid excessive calcium or vitamin D supplements unless prescribed; maintain recommended dietary intake.

Early signs of OD with calcitriol

Weakness, HA, N/V, constipation, muscle/bone pain, metallic taste

Later signs of OD with calcitriol

Polyuria, polydipsia, anorexia, somnolence, photophobia, rhinorrhea, pruritis, hallucinations, hyperthermia, HTN

Compare cinacalcet vs calcitriol

Cinacalcet lowers PTH and serum calcium by activating calcium-sensing receptors; calcitriol increases calcium absorption and raises serum calcium.

Which drug lowers serum calcium?

Cinacalcet

Which drug increases intestinal calcium absorption?

Calcitriol

Which anterior pituitary hormone stimulates linear growth?

Growth hormone (GH)

What hormone inhibits growth hormone secretion?

Somatostatin

Drug class of somatropin and somatrem

Growth hormone analogs (recombinant human GH)

Examples of growth hormone analogs

Somatropin, Somatrem