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Hypothyroidism, Part 1

Heidi James, MD and Tania Gallant, MD

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Endocrinologist Tanya Gallant gives the endocrinologist's perspective on diagnosing and treating hypothyroidism.


  • 95% of patients with hypothyroidism have primary thyroid gland failure, often due to an autoimmune process.

  • The clinical presentation is often nonspecific; common initial symptoms are fatigue, myalgias, dry skin, constipation, and edema.

  • An elevated TSH is the best diagnostic test for primary hypothyroidism.

  • For younger patients with overt hypothyroidism, the usual initial dose of levothyroxine is 1.6 mcg/kg/day.

  • Gallant prefers levothyroxine to desiccated thyroid hormone for the treatment of hypothyroidism.  


  • What causes hypothyroidism?

    • 95% of cases are due to primary thyroid gland failure, most commonly due to autoimmune ( ashimoto’s) thyroid disease.

    • Iatrogenic causes comprise the 2nd most common etiologies and include:  

      • exposure to head or neck radiation and

      • medication side effects (such as amiodarone or lithium).

    • Central hypothyroidism is the least common cause, accounting for about 5% of cases.

      • Often due to hypothalamic or pituitary dysfunction resulting from tumors or radiation.

  • Hypothyroidism is commonly seen in connection with other medical conditions, so providers should have a heightened level of alertness for screening these patients.

    • Autoimmune diseases with a higher rate of thyroid dysfunction:  

      • 10% of patients with type 1 diabetes will eventually also develop hypothyroidism.

      • Other associated autoimmune diseases are Addison’s and celiac disease.

    • Genetic conditions that have an increased incidence are Down and Turner syndrome.

  • Hypothyroidism typically presents with symptoms that are nonspecific and varied.

    • Fatigue is one of the most common initial symptoms.

    • Other complaints include dry skin, constipation, myalgias, and peripheral edema.

    • Extreme cases may present with cognitive impairment.  A patient who has a significant decreased level of consciousness falls into the category of myxedema coma which requires emergent treatment.

    • Weight gain is not a common sequelae of run-of-the-mill hypothyroidism, although some studies have shown higher TSH levels in the morbidly obese.  

  • What physical exam findings are associated with hypothyroidism?

    • The most consistent sign is delayed relaxation of  deep tendon reflexes, although providers are rarely timing their DTR exam.

    • Skin coarseness, peripheral edema, and periorbital edema are often seen.

    • Proximal muscle weakness can be evident in long-standing cases where the diagnosis may have been delayed.

    • Diastolic hypertension is common.

  • Aside from an elevated TSH, what other lab abnormalities might one see with hypothyroidism?

    • The following lab values may be elevated with hypothyroidism:  CPK (rare), prolactin level, CRP (if the patient has an inflammatory cause of hypothyroidism), and LDL.

  • When the diagnosis is suspected, is the TSH alone an adequate screening test for hypothyroidism?  Usually.

    • The TSH is the best diagnostic test for primary hypothyroidism.

      • The only time the TSH is unreliable is in the setting of central hypothyroidism which affects the pituitary-hypothalamic axis.  In these settings, the TSH may be normal or low.  

    • The free T4 is automatically done by most labs if the TSH is abnormal.  

      • It is most helpful in confirming central hypothyroidism, as is the only reliable marker in these cases.  

      • This test is more useful in evaluating hyper- than hypothyroid patients.  Once the TSH is undetectable in a hyperthyroid patient, the T4 is the only measure of how hyperthyroid the patient is.  

    • The T3 is even less reliable than the T4 when evaluating hypothyroid patients.  It doesn’t correlate well with tissue levels of T3.  

    • Anti-TPO antibodies are useful for determining the cause of hypothyroidism.

      • These antibodies confirm an autoimmune, or Hashimoto’s, etiology.  

      • This test can also be helpful in a pregnant patient with past miscarriages where the TSH may be normal but anti-TPO antibodies elevated.  These women benefit from therapy.

    • Thyroglobulin levels are not useful in the hypothyroid setting.  

      • Thyroglobulin is a protein produced only by thyroid tissue.  As long as someone has a thyroid gland, this is not a useful measure.

      • Thyroglobulin levels are only helpful when confirming that a patient who had a thyroidectomy for thyroid cancer has no residual thyroid tissue.

  • How do you decide the proper initial dose of thyroid replacement when a patient is found to have an elevated TSH?

    • If the person is overtly hypothyroid and is younger, Gallant typically starts the patient on a full replacement dose, 1.6 micrograms/kg/day of levothyroxine.  This is best calculated using ideal (not total) body weight.  “Overt” hypothyroidism is defined as clinical symptoms with an elevated TSH with a low T4.

    • For elderly patients, Gallant starts with a lower dose to prevent adverse reactions which can be unmasked with full replacement therapy, such as tachycardia or angina.  Her usual starting dose is 25-50 micrograms per day. For patients who are tolerating the medication, she increases the dose every 4-6 weeks until the TSH is normal.

    • For patients who have subclinical hypothyroidism (no clinical symptoms, elevated TSH, normal T4), a lower starting dose can be considered.  A lower initial dose might be 25-75 micrograms per day, depending on the size of the patient.

  • Levothyroxine is most commonly prescribed for thyroid replacement.  What are the other pharmacologic options?

    • Desiccated thyroid extract (Armour thyroid) was the only available thyroid hormone before synthetically manufactured levothyroxine was developed.  Many patients will request this, though Gallant does not favor its use over levothyroxine.

      • It is ground up porcine thyroid.  When it was first produced, the medication was not well standardized and its effects were unreliable without predictable responses.  It is likely better standardized now.

      • The American Thyroid Association and the American Association of Clinical Endocrinologists do not recommend it in their guidelines.

      • Desiccated thyroid hormone should not be used in pregnancy as it has a higher percentage of T3 than T4.  Since it is the T4 that predominantly crosses the placenta, desiccated thyroid hormone can underdose the fetus.

      • A small randomized double-blind crossover study published in 2013  compared the use of desiccated thyroid extract (DTE) with levothyroxine for the treatment of hypothyroidism.  

        • 70 patients with primary hypothyroidism who were on a stable dose of levothyroxine for 6 months were randomized to either DTE or levothyroxine for 4 months.  Then they were all switched over to the other one for 4 more months.

        • The authors found that there was no difference in symptoms or quality of life between the two groups.  However, half of the patients preferred DTE and only about 20% preferred levothyroxine.  

        • The study also found that 15% of patients on DTE had hyperthyroid symptoms.  They also had about 3 pounds greater weight loss.

        • Hoang TD, et al. Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized,
          double-blind, crossover study. J Clin Endocrinol Metab. 2013 May;98(5):1982-90.PMID: 23539727

    • A combination of T4 and T3 treatment is another alternative to levothyroxine.  

      • This treatment has been well-studied; studies  show no significant difference compared with T4 alone.

      • A downside of T3 is that, compared with T4, it is very short-acting.  Therefore, it must be dosed twice a day.  For patients who miss a dose, they run the risk of being rendered hypothyroid until the next dose.

      • T3 is also about 4 times more potent than T4  and much more expensive that levothyroxine.

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Creme de la Thyroid Full episode audio for MD edition 180:16 min - 85 MB - M4AHippo Primary Care RAP July 2016 Summary 957 KB - PDF