Thyroid Disorders Overview

Thyroid Disorders

• Thyroid hormones (T3 and T4) regulate body temperature, metabolism, and heart rate.
• Most T3 is protein-bound.
• Hyperthyroidism:
  • Two main types: Grave's Disease and Toxic Nodular Goiter.
  • Grave's Disease: Immune system produces antibodies mimicking TSH, causing overproduction of thyroid hormones. Unclear cause, likely genetic and environmental triggers. Most common cause of hyperthyroidism. Smoking worsens eye symptoms.
  • Toxic Nodular Goiter: Hyperfunctioning nodule develops in a goiter, leading to hyperthyroidism without eye problems.
  • Symptoms: Tremors, rapid heart rate (tachycardia), rapid breathing (tachypnea), heat intolerance, bulging eyes (exophthalmos), swelling of the shins (pretibial edema).
  • Hypermetabolic state.
• Hypothyroidism:
  • Most common cause is Hashimoto's thyroiditis (inflammation of the thyroid gland). Autoimmune disorder where the body attacks the thyroid. Other causes include viral infections, neck radiation, certain medications, pituitary/hypothalamus disorders, and surgery. Low-iodine diets are also a contributing factor. Postpartum thyroiditis may occur after pregnancy.
  • Symptoms: Lethargy, fatigue, weight gain, skin changes, cold sensitivity, constipation, high blood fats (hyperlipidemia), slow heart rate (bradycardia).
  • Hypometabolic state.
• Medications inducing thyroid dysfunction: Lithium, amiodarone, interferon.
• Treatment goals: Replace missing hormone, normalize TSH levels, with synthetic therapy primarily. Levothyroxine (T4) is the primary synthetic therapy. T4 converts to T3.
• Levothyroxine (T4)
  • Highly protein bound (97%).
  • Initial adult dose: 75-125 mcg (or ~1.6 mcg/kg/dl of ideal body weight).
  • Elderly dose: 75% or less than adult dose, start low and go slow.
  • Monitor for cardiac symptoms and adjust dose as needed.
  • 5-6 drug half-lives, testing interval 6-8 weeks after dose changes, then every 6-12 months for stable TSH.
• Absorption reducers: Proton pump inhibitors, calcium & iron supplements, aluminum-containing antacids.
• Warfarin interaction: Levothyroxine accelerates breakdown of Vitamin K-dependent clotting factors, so warfarin dosage may need adjustment.
• Insulin and digoxin needs may increase.
• Over-replacement symptoms: Similar to hyperthyroidism symptoms (fast heart rate, trouble sleeping, jittery feeling, sweating, anxiety, diarrhea, weight loss, bone loss).
• T3 therapy: May be used in some cases of persistent symptoms despite T4 therapy, but needs specialist consultation. T3 has short lifespan, multiple daily doses, and fluctuation risk of hyperthyroid symptoms.
• Black box warning: Do not use thyroid hormones for weight loss. Large doses in euthyroid patients can be toxic, especially with anorexic drugs.

Thyroid in Pregnancy and Lactation

• Thyroid hormones essential for fetal brain and nervous system development (fetus depends on mother's supply in first trimester).
• Fetus's thyroid starts working independently around 12 weeks but fully functional around 18-20 weeks,
• Pregnancy hormones (hCG and estrogen) increase measured thyroid hormone levels.
• Diagnosing in pregnancy can be difficult.
• Untreated hypothyroidism: Preeclampsia, anemia, miscarriage, low birth weight (LBW), heart failure (CHF).
• Untreated hyperthyroidism: Miscarriage, premature birth, LBW, preeclampsia, thyroid storm, CHF.
• Hypothyroidism in pregnancy: Levothyroxine is category A, first-line treatment. Dosage significantly increases; monitor serum TSH.
• Hyperthyroidism in pregnancy: Propylthiouracil (PTU) is often preferred due to lower transfer to the fetus. Both PTU and Methimazole are category D. Both are safe for breastfeeding.
• Screening: Postpartum depression suggests checking TSH; also check for thyroid dysfunction if symptoms are present. 5% of women have thyroid disorders postpartum.

Testosterone Deficiency

• Primary: Testicular origin; Secondary: Hypothalamus-pituitary dysfunction.
• Common in men >45 years old, increasing due to aging population.
• Diagnosis: Total testosterone <300 ng/dL after two separate early morning measurements, combined with symptoms/signs.
• Causes: Aging, injury, infection, loss of testicles, cancer treatment, genetic abnormalities, hormone treatments for prostate cancer, corticosteroids.
• Additional testing considerations: Unexplained anemia, bone density loss, diabetes, chemotherapy/radiation exposure, HIV/AIDS, chronic narcotic use, male infertility, pituitary dysfunction, and chronic corticosteroid use in the absence of symptoms.
• Reproductive evaluation before testosterone therapy for men with testosterone deficiency who are interested in fertility.
• Measured hemoglobin/hematocrit before therapy, and PSA in men over 40.
• Uncertain impact of therapy on cardiovascular events.
• Comorbidities: Metabolic syndrome, diabetes, cardiovascular disease, hypertension, COPD, autoimmune diseases.
• Black box warning: Secondary virilization in children, avoid contact with topical testosterone application sites. Blood pressure increases and may increase risk of major adverse CV events and pulmonary microembolism reactions.
• Risks and benefits of therapy: Improved quality of life (libido, mood, bone/muscle mass). Limited well-controlled studies. May lower blood sugar in diabetics.
• Adverse effects: Worsening sleep apnea, gynecomastia, acne, accelerated male pattern baldness, erythrocytosis, prostate cancer, metastatic progression, decreased spermatogenesis, fertility issues, increased cardiovascular risk.
• Contraindications: Prostate/breast cancer.
• Warnings/Precautions: Long-term use risk of breast cancer (if parenteral). May alter serum lipid profiles (use caution with history of MI within 3 months or coronary artery disease.) Avoid in patients with cardiovascular disease.
• Testing: Measure testosterone every 6-12 months.

Erectile Dysfunction

• Persistent inability to maintain and sustain an erection for sexual intercourse.
• Occasional ED is normal, frequent occurrences may signal underlying health issues.
• Often a combination of emotional and physical factors.
• Risk marker for cardiovascular disease.
• Measurement of morning total testosterone to rule out low testosterone.
• Conditions associated with ED: Cardiovascular disease, high blood pressure, obesity, low testosterone/hormone imbalances, age, stress, anxiety, depression.
• Erection mechanism: Sexual stimulation releases nitric oxide, dilating blood vessels in corpus cavernosum. Accumulation of cyclic GMP dilates vessels. Enzyme PDE5 breaks down cGMP leading to erection resolution.
• Treatment: Primarily pharmacological (PDE5 inhibitors).
• PDE5 Inhibitors:
  • Relaxation of smooth muscle, inflow of blood, increasing corpus cavernosum dilation.
  • Reduce smooth muscle, endothelial cell proliferation, nerve activity, increase smooth muscle relaxation and tissue perfusion of the prostate and bladder. - Possible adverse effects: Headache, dyspepsia, flushing, gastritis, priapism, myalgias, abnormal vision, elevated LFTs. - Metabolism: CYP450 system (CYP3A4). Caution with other CYP3A4 substrates (grapefruit juice). - Potential drug interactions: Potentiate hypotensive effects of nitrates, alpha-blockers, and other antihypertensives. CYP3A4 inhibitors increase plasma levels, and CYP3A4 inducers (like rifampin) reduce levels. - Contraindications: Concurrent use of nitrates. - Precautions: Cardiovascular disease.
  • Patient education: Take 1 hr before intercourse, maximum once-daily use. Not affected by alcohol (although alcohol can cause ED).
  • Enhanced with testosterone therapy (when low testosterone is a factor.)

Benign Prostatic Hyperplasia

• Enlarged prostate gland, common in aging males.
• Urinary symptoms: Frequent/urgent urination, increased nighttime urination (nocturia), difficulty starting urination, weak or interrupted urine stream, dribbling.
• Severity doesn't correlate with size.
• Some potential stabilization or symptom improvement over time.
• Treatments:
  • Medications, minimally invasive therapies, or surgery.
  • Alpha-1 blockers: Relax bladder, neck, and prostate muscles, making urination easier.
    • Tamsulosin (Flomax) is a common example.
    • Quick effect in men with smaller prostates (improvement in 48 hours to one week).
    • Symptom relief for up to 4 years if used alone, doesn't shrink the prostate
    • Adverse effects: Hypotension, fatigue, prolonged erection, atrial fibrillation
  • 5-alpha-reductase inhibitors: (blocking dihydrotestosterone); shrink the prostate, increase urine flow
    • Takes 3-6 months.
    • Adverse effects: Impotence (4%), allergic reactions, breast or high-grade prostate cancer, decreased libido, abnormal ejaculation; gynecomastia, dizziness or lightheadedness.