CG, a 22-year-old female presents to your ambulatory clinic regarding recently developed symptoms. She reports that she has been feeling like her Xanax has not been working for her anxiety anymore. After further interviewing, CG reveals her heart has been racing on occasion, which is making her fatigued.

Past medical history:

Generalized Anxiety Disorder: alprazolam 0.5mg TID PRN

Hypothyroidism: levothyroxine 88mcg QAM

CG’s laboratory findings and vitals are below:

Ht: 5’6”

Wt: 144 lbs

HR: 118 BPM

BP: 128/78

Temp: 99.0°F

TSH: 0.2 mIU/L (0.5-4.7 mIU/L)

Free T4: 4 nd/dL (0.8-2.7 ng/dL)

hCG: 0.1 mIU/mL (< 5 mIU/mL)

After confirming CG is taking her Synthroid correctly, what would be the best course of action to manage her new symptoms?

A. Decrease the levothyroxine dose to 75mcg PO every morning

B. Initiate propylthiouracil 50mg PO twice daily 

C. Increase levothyroxine dose to 100mcg PO every morning

D. Initiate methimazole 15mg PO once daily

Answer with rationale:

Hypo and hyperthyroidism are disorders of the thyroid gland that disrupt normal metabolic function. In hypothyroidism, the thyroid doesn’t produce enough hormones (T4/T3), causing symptoms like fatigue, weight gain, cold intolerance, and depression. Hyperthyroidism results in excess T4, leading to expectedly opposite effects: tachycardia, weight loss, heat intolerance, and anxiety. Think slowing down and speeding the whole metabolic system.

To understand the current therapies used to treat these disorders, one needs to understand the hypothalamic-pituitary-thyroid axis that regulates thyroid function through a feedback loop. High T4/T3 levels suppress the release of thyroid-stimulating hormone (TSH), whereas low T4/T3 levels promote TSH secretion. Levothyroxine is a synthetic form of T4, and is used to treat hypothyroidism by supplementing hormone levels, which in turn helps normalize TSH production.

Methimazole and propylthiouracil (PTU) are antithyroid medications used to treat hyperthyroidism by inhibiting thyroid hormone synthesis. An interesting thing about these medications is their roles in pregnant patients. PTU is the hyperthyroid drug-of-choice in the first trimester, while methimazole is preferred in the 2nd and 3rd trimesters. This is mainly due to the teratogenic risks that methimazole carries for early fetal development defects, including nasal and esophageal blockages. 

Answer A is correct. Levothyroxine is used to increase the amount of active thyroid hormone. When the T4 level increases, the TSH will react by lowering, as reflected in CG’s labs. If the levothyroxine dose is too high, the free T4 levels can become supratherapeutic and cause symptoms of hyperthyroidism. So, lowering the dose of levothyroxine would be appropriate to lower T4, increase TSH, and resolve symptoms of hyperthyroidism.

Answer B is incorrect. While PTU is appropriate in hyperthyroidism, especially the first trimester of pregnancy, this patient is 1) not pregnant, 2) not experiencing hyperthyroidism. The quantitative hCG levels indicating non-pregnancy are less than five, approaching 0, while the first trimester of pregnancy generally reads at 5-25 mIU/mL. CG is experiencing elevated thyroid levels and some corresponding symptoms, however it would be quite inappropriate to start antithyroid therapy when the baseline diagnosis is hypothyroidism and she is receiving too much levothyroxine that should be corrected. 

Answer C is incorrect. The patient is already dealing with elevated T4 and is showing signs and symptoms of too much active thyroid. Remembering that levothyroxine is synthetic T4, increasing the dose would only further increase the thyroid activity and risk worsening the unintended symptoms.

Answer D is incorrect. Methimazole is an antithyroid medication that blocks the synthesis of T3 and T4, preventing pro-thyroid hormonal effects. It can be used for hyperthyroidism in patients unable to receive surgery or radioactive iodine therapy, or for a short course in preparation for such treatments. While we are trying to lower T4 and avoid symptoms of hyperthyroidism, this is not appropriate for a patient who already is being treated for hypothyroidism and has been overtreated requiring levothyroxine dose adjustment. 

Brand/generics Covered:

Alprazolam (Xanax), Levothyroxine (Synthroid), Methimazole (previously Tapazole), Propylthiouracil or PTU (previously Propyl-Thyracil)

 Naplex Content Domains Covered

1.A.1 - Pharmaceutical science principles and concepts

• Pharmacology

3.C.1 - Patient health conditions, including special populations and medication-related factors

• Signs, symptoms , and findings of medical conditions, etiology of diseases, or pathophysiology

3.D - Therapeutic monitoring, plan development, evaluation, and modifications