Thyroid

• Thyroid gland anatomy:

  • Butterfly-shaped endocrine gland in the front of the neck
  • Responsible for synthesis, storage and release of the two thyroid hormones, T3 and T4
  • Hormones produce many physiological effects affecting every system in the body
• • Synthesis and secretion of T3 + T4 controlled by TSH, which is controlled by thyrotropin-releasing hormone
  • Creation of T3 and T4 requires iodide, thyroglobulin and tyrosine
  • Physiologic ratio of T4:T3 is 13:1
• Actions of T3 and T4:

  • Heart: chronotropic and inotropic
  • Adipose tissue: catabolic
  • Muscle: catabolic
  • Bone: developmental
  • Nervous system: developmental
  • Gut: metabolic
  • Other tissues: calorigenic
• Thyroid hormone release is regulated by a negative feedback loop. Hormone release promoted by TSH and inhibited by high circulating T3/T4 levels.
• Hyperthyroidism is a disease caused by excess synthesis and secretion of thyroid hormone.

  Common causes include:

  • toxic diffuse goiter (Graves disease)
  • toxic multi-nodular goiter (Plummers disease)
  • acute phase of thyroiditis
  • toxic adenoma
• Hyperthyroidism symptoms: Tremor in hands, Anxiety, Soft nails, Diarrhea, Hyperreflexia, Emotional lability, Heat intolerance, Atrial fibrillation, Insomnia, Unintentional weight loss, Increased perspiration, Hair loss, Weakness, Hyperactivity, Apathy, Tachycardia, Palpitations, Amenorrhea, + Hypertension
• Hyperthyroidism diagnosis/lab tests: Diagnosis based on clinical symptoms and lab tests including Serum TSH, Free T3, and Free T4
• Thioamides: Methimazole + Propylthiouracil are anti-thyroid drugs used for toxic diffuse goiter, toxic multi-nodular goiter, and pre-treatment before radioactive iodine.
• Thioamides serious SEs:

  • neutropenia + agranulocytosis - < 1500 neutrophils/uL (n), < 100 neutrophils/uL (a)
  • hepatotoxicity - in MMI caused by cholestatic jaundice, in PTU caused by allergic type hepatocellular damage
  • vasculitis - auto-immune process, damages vascular tissue causing inflammation + destruction of blood vessels
• side effects of thioamides - GI upset, rash, arthralgia, and abnormal taste + smell.
• Thioamides can interact with warfarin and digoxin
• Monitoring effectiveness of thioamides:

  • 1-4 weeks for symptom improvement
  • assess TSH, T3, and T4 every 4 - 6 weeks until stable then every 2 - 3 months got 6-12 months, then ever 4-6 months.
  • relapse most likely in first 3 months
• Monitoring safety of thioamides includes baseline CBCs and LFTs
• Methimazole has a faster onset of euthyroid in labs compared to propylthiouracil
• Propylthiouracil is more likely to cause side effects and toxicity compared to methimazole
• Beta-blockers can reduce symptoms of hyperthyroidism
• Radioactive Iodine 131 is a definitive treatment for hyperthyroidism compared to thioamides
• Radioactive Iodine 131 should not be given in pregnancy or lactation
• Pre-treatment with thioamides is recommended before Radioactive Iodine 131 to achieve euthyroid status
• Patients receiving Radioactive Iodine 131 should follow specific instructions to prevent exposure to others
• Surgery (thyroidectomy) is an option for hyperthyroidism treatment in specific cases
• Subclinical hyperthyroidism can lead to osteoporosis, cardiac abnormalities, and increased mortality
• Thyroiditis management includes symptomatic treatment with beta-blockers, NSAIDs, and steroids for severe cases
• Thyroid storm or thyrotoxicosis is a rare, life-threatening condition that requires immediate treatment
• Treatment for thyroid storm includes supportive care, anti-thyroid meds, beta-blockers, iodine, and steroids
• Hypothyroidism causes:

  • chronic autoimmune thyroiditis: Autoimmune disorder where antibodies form to thyroid cells + destroy them.
  • drug-induced: lithium + amiodarone
• Clinical presentation of hypothyroidism includes weight gain, fatigue, dry skin, and hypothermia
• Diagnosis of hypothyroidism involves serum TSH, free T3, and free T4 tests
• Subclinical hypothyroidism is characterized by elevated TSH levels and normal T3 and T4 levels
• Sub-clinical Hypothyroidism is when TSH range: 4.5 - 10 mIU/L with normal T3/T4 levels. Is asymptomatic.

  Increased risk of: Atherosclerosis, HF, MI, Depression, Low bone mineral density, Metabolic syndrome.

  Treat if patient develops symptoms, planning pregnancy, heart failure, very young patient
• Drugs that alter thyroid levels:

  • amiodarone: decreases TSH, decreases T4 to T3 conversion, decreases synthesis and release of T3/T4.
  • lithium: decreases synthesis and release of T3/T4.
• Hypothyroidism Treatment Options:

  • Desiccated thyroid
  • Liothyronine
  • Levothyroxine
  • Combined T3/T4
• Desiccated Thyroid

  • Contains T3 and T4
  • Causes high peak T3
  • Not well standardized batch to batch
• Liothyronine Treatment:

  • Contains T3, no effect on T4
  • Short half-life causes wide fluctuations in serum levels
  • Higher incidence of cardiac adverse effects
  • Considered when some patients do not respond to other treatments
• Levothyroxine Treatment:

  • Analogue of T4
  • Half-life of 7 days
  • Dosage/administration depends on age, weight, cardiac status, severity, and duration of hypothyroidism
• Levothyroxine Dosage/Administration:

  • Recommend starting low and titrating up if: Any CVD, Rhythm disorders, >50 years old, or Severe, long-standing hypothyroidism.
  • 1.6 mcg/kg/day or 12.5 mcg to max. wt based
  • can give 100 mcg empirically to young, healthy pts
  • Start low (12.5-25mcg) and titrate up by 12.5 – 25mcg q4-6 weeks
• Levothyroxine Side-effects:

  • Hyperthyroidism symptoms
  • Increased cardiac risk
  • Aggravation of existing CVD
  • BMD reduction if dosed too high
• Levothyroxine Drug Interactions:

  • Absorption reduction with: Antacids/H2 blockers/PPIs, Iron, Calcium/mineral supplements, Cholestyramine/colestipol
  • Manage by spacing levothyroxine 2-4 hours away from these meds
  • Raloxifene -> space by 12h
  • Potent CYP inducers increase thyroid hormone metabolism: Ciprofloxacin (short term), Phenytoin, Carbamazepine, Rifampin
  • TCAs increase the risk of arrhythmias
• TSH Hypothyroid levels:

  • Aim for low normal TSH value (< 2.5 mIU/L) - lower values can increase the risk of cardiac toxicity
  • Free T4 should be normal to slightly elevated
  • Free T3 should be normal
  • Symptoms should improve in 2 to 3 weeks, with maximum effect in 4 to 6 weeks
  • Once stable and symptom-free, monitor TSH q 6 + 12 + 24 m
• Reasons for levothyroxine failure:

  • Decreased bioavailability
  • Poor adherence
  • Malabsorption
  • Improper administration
  • Increased need
  • Other conditions like Addison’s disease, altered hypothalamic-pituitary-thyroid axis, insufficient peripheral conversion of T4 to T3