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Thyroid Hormone Replacement TSH free T4

last modified on: Fri, 03/15/2024 - 16:19

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  1. General
    1. Thyroid hormone (T4 and T3)
      1. Controls about 25% of the basal metabolism in most tissues
      2. It helps maintain thermogenic and metabolic hemostasis in the adult
    2. Thyroid Simulating Hormone (TSH)
      1. It is the most useful physiologic marker of the thyroid hormone action
      2. Secreted by the thyrotrope cells of the anterior pituitary
      3. Plays a pivotal role in the control of the thyroid feedback loop
      4. TSH is a marker used for the diagnosis of Hyperthyroidism (low TSH) and Hypothyroidism (high TSH)
    3. Thyroid Feedback Loop
      1. Feedback loops or "circuits" are the basis of most control mechanisms in your body to regulate the secretion of hormones
        1. One type of feedback loop is negative feedback
          1. Negative feedback is seen when the output of a pathway inhibits the inputs into the pathway
          2. For example, the heating system in your home is a negative feedback loop
            1. When your furnace produces enough heat to elevate the temperature above the set point of your thermostat, the thermostat is triggered and shuts off the furnace.
            2. If there is a problem with the thermostat, the furnace will continue to work causing the room to get too hot. The broken thermostat doesn't send "feedback" to the furnace to shut off after the room reaches the set temperature.
      2. Example of Thyroid's Negative Feedback Loop:
        1. Thyroid Releasing Hormone (TRH) secreted by the Hypothalamus stimulates the anterior pituitary production of TSH, which in turn stimulates thyroid hormone (T4 and T3) synthesis and secretion.
          1. TRH (Hypothalamus) -> (Anterior Pituitary) TSH -> T4 and T3
        2. When thyroid hormone (T4 and T3) are at normal or high levels, they negatively feedback to inhibit TRH and TSH production

Clinical Relevance

  1. Disorders of the thyroid gland can trigger an overproduction of thyroid hormone (hyperthyroidism) or cause glandular destruction and hormone deficiency (hypothyroidism)​
  2. TSH Level Thyroid Hormone Level (T4) Disorder
    Low High Hyperthyroidism
    High Low Hypothyroidism
  3.  Hypothyroidism (Low T4, High TSH)
    1. Onset is usually subtle and patients may only become aware of symptoms only when normal TSH level (euthyroidism) is restored. 
    2. Causes: (1) Iodine deficiency, (2) Iatrogenic - after thyroidectomy, radioactive iodine treatment, radiation exposure to head and neck, and/or certain medications.
    3. Symptoms: tiredness/weakness, dry skin, feeling cold, hair loss, difficulty concentrating, poor memory, constipation, weight gain with poor appetite.
  4. Hyperthyroidism (High T4, Low TSH)
    1. Causes: Autoimmune disorders (i.e. Graves Disease), multi-nodular goiters, viral infections, ingestion of excessive amounts of thyroid hormone
    2. Symptoms: Sweating, weight loss/gain, anxiety, palpitations, heat intolerance, irritability menstrual irregularity

Laboratory Analysis

  1. TSH
    1. Glycoprotein
    2. Released from anterior pituitary gland via hypothalamohypophyseal portal system
    3. Stimulates thyroid gland to secrete the hormones T4 and T3
    4. Production of TSH is controlled by TRH
  2. Free T4 (Thyroxine)
    1. T4 is bound to plasma proteins including thyroxine-binding globulin, transthyretin, and albumin.
    2. Numerous factors such as illness, medications, and genetics can influence protein binding of T4. Therefore, it is reasonable to measure the free or "unbound" T4 hormone levels
  3. T3 (Triiodothyronine)
    1. Most T3 in the body comes from the conversion of T4 to T3 by deiodination in peripheral tissues.
    2. T3 has a very short life span in the body compared to T4
  4. Lab Timing
    1. Post-operative TSH measurement is completed for all patients who underwent a thyroid lobectomy or a total thyroidectomy, at least 6wk after surgery, and followed by 6mo and 12mo after surgery.
    2. A previously normal TSH level should be rechecked at least biannually in an asymptomatic patient post-thyroid lobectomy or total thyroidectomy.
    3. A previously abnormal TSH level should be rechecked in, at minimum, 7 weeks or 2 month intervals until levels stabilize.

Thyroid Hormone Preparation

  1. Synthetic T4
    1. Is identical to that produced in the human thyroid gland
    2. T4 has higher serum levels, slower metabolic clearance, and a longer half-life than T3
    3. Example: Levothyroxine sodium tablets
      1. Dosage forms: 25, 50, 75, 88, 100, 112, 137, 150, 175, 200, 300mcg
      2. Absorbed in the gastrointestinal tract. Absorption is increased in a fasting state.
      3. Half-life is about 6-7 days (euthyroid), 3-4d (hyperthyroid), 9-10d (hypothyroid)
      4. Liver is the major site of degradation (CYP450)
      5. Eliminated primarily by the kidneys (urine), but ~ 20% is eliminated in the stool.
      6. Caution used in patients with cardiovascular disease and elderly patients
  2. Synthetic T3
    1. Liothyronine sodium tablets
      1. Onset of activity is rapid, occuring within a few hours.
      2. Short half-life is about 2 1/2 days
      3. May lead to unpleasant symptoms due to the several high/low points of thyroid hormone during day
  3. Synthetic T3 & T4 Combinations
    1. Nature-Thyroid Tablets, Westhroid Tablets, Thyrolar
      1. Produce much more T3 than is usually produced naturally within the body
      2. Can have same side effects as Synthetic T3 supplements
  4. Medication Timing
    1. Best time to take thyroid hormone is first thing in the morning on an empty stomach
      1. If patients are unable to take their thyroid hormone replacement in the morning, the best thing is to be consistent and take the medication at the same time and same way everyday.
      2. It may take several weeks before patients notice an improvement in symptoms
      3. If a days dose was missed, just resume taking the medication the next morning.

Goals of Therapy

  1. Clinically Euthyroid State (Normal TSH)
    1. Normal TSH levels for non-thyroid cancer patients varies by hospitals and clinics, but it is generally between 0.3 to 4.5 uIU/mL.
    2. Initial dose is carefully selected based on the patient's weight, age, and other medical conditions.
    3. The medication dose may need to be adjusted by a physician to keep the thyroid function within normal range.
    4. Problem: "I am continuing to have an elevated TSH even after taking thyroid supplements."
      1. Indicates under replacement with thyroid hormone (i.e. thyroid supplements, Levothyroxine sodium)
      2. *Confirm medication compliance prior to changing medication dose*
      3. To treat an elevated TSH, the Levothyroxine sodium (Synthetic T4) dose is increased to suppress the TSH back to a normal state (euthyroid)
  2. TSH Suppression
    1. Reasoning
      1. Regularly performed in patients after completing treatment for thyroid cancer
      2. This has the effect of turning off one of the "signals" in the Thyroid Feedback Loop
      3. This prevents thyroid tissue to be stimulated, thus stopping the growth of microscopic thyroid cancer cells or residual thyroid cancer that is left in the body despite best efforts to remove all thyroid or cancerous tissue.
    2. TSH Suppression varies by hospitals but is generally between 0.2 to 0.5 uIU/mL
      1. A reasonable goal is to suppress TSH as much as possible without subjecting the patients to unnecessary side effects

Complications of Treatment

  1. Inducing symptoms of hyperthyroidism
  2. Cardiac
    1. Arrhythmias, atrial fibrillation, heart failure, or angina
    2. Over treatment with thyroid hormone replacements may have adverse cardiovascular effects
    3. Patients with cardiovascular disease or elderly patients need to be initiated a lower replacement doses compared to the recommended doses given to younger patients or patients without a history of cardiovascular disease.
  3. Osteoporosis
    1. Long-term thyroid hormone replacement can cause a small loss of bone density, particularly in postmenopausal women.
    2. Patients at risk for osteoporosis are advised to have periodic bone density testing
  4. Other
    1. Lipids
    2. Psychiatric disorders, depression, anxiety


American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper, D.S., et al. (2009). Revised american thyroid association management guideliens for patients with thyroid nodules and differentiated thyroid cancer. Thyroid: Official Journal of the American Thyroid Association, 19(11), 1167-1214.

Brassard, M., et al. (2011). Long-term follow-up of patietns with papillary and follicular thyroid cancer: A prospective study on 715 patients. The Journal of Clinical Endocrinology and Metabolism, 96(5), 1352-1359.

Fauci, A.S., Braunwald, E., & Loscalzo, J. (2008). Harrison's principles of internal medicine. (17th edition), New York, NY, USA: McGraw-Hill Professional Publishing.

Johner, A., et al. (2011). Detection and management of hypothyroidism following thyroid lobectomy: Evaluation of a clinical algorithm. Annals of Surgical Oncology, 18(9), 2548-25554.

McPhee, S.J., Papadakis, M.A., & Tierney, L.M. (2007). Current medical diagnosis and treatment 2010. Blacklick, OH, USA: McGraw-Hill Medical Publishing Division.