para>Myxedema coma: severe hypothyroidism characterized by change in mental status, hypothermia, respiratory failure, hemodynamic instability, and death. Precipitated by stress, sepsis, and trauma. �
Differential Diagnosis
- Other causes of hypothyroidism including thyroidectomy, radioiodine treatment, neck radiation, iodine, medications such as amiodarone and tyrosine kinase inhibitors, and pituitary/hypothalamic disorders
- Other causes of encephalopathy need to be ruled out to make the diagnosis of HE.
Diagnostic Tests & Interpretation
Initial Tests (lab, imaging)
- Initial screening with TSH is recommended. If TSH is abnormal, then check serum free thyroxine (FT4) (1)[A].
- Overt hypothyroidism: elevated TSH and decreased FT4
- Subclinical hypothyroidism: elevated TSH and normal FT4
- Hashitoxicosis: transient decrease in TSH and increase in FT4
- Silent or postpartum thyroiditis: Initially, patients present with thyrotoxicosis followed by hypothyroidism and eventually reach a euthyroid state after 3-6 months. Some patients progress to permanent Hashimoto hypothyroidism. Depending on the stage of illness, thyroid function results can vary.
- Consider checking TPO and TG antibodies in individuals with subclinical disease and silent or postpartum thyroiditis to determine risk of progression to overt hypothyroidism and need for thyroid hormone replacement (1,2).
- Ultrasound (US) of the gland can show diffuse, patchy hypoechoic areas (i.e., "leopard skin pattern"� or "moth-eaten appearance"�). US is not warranted for the diagnosis of HT. However, a US can be used to characterize thyroid nodules that can develop to HT.
- Consider evaluation for other autoimmune conditions (e.g., adrenal insufficiency) in patients with HT, as clinically indicated.
- Hypothyroidism can be associated with hyperlipidemia, hyperprolactinemia, and hyponatremia.
Follow-up tests & special considerations
- Gradual loss of thyroid function is noted in HT with subclinical disease progressing to overt hypothyroidism at a rate of 5% per year.
- 30-50% of individuals with silent or postpartum thyroiditis can progress to permanent hypothyroidism and/or goiter development.
- Therefore, monitor TSH in high-risk patients (i.e., history of silent/postpartum thyroiditis, other autoimmune disorders, family history, radiation exposure, etc.) and treat when abnormal TSH is noted (1)[A].
Diagnostic Procedures/Other
TSH is an independent predictor of thyroid malignancy with one study reporting prevalence as high as 30% in individuals with abnormal TSH levels. Individuals with HT can develop thyroid nodule, and a biopsy is recommended in these circumstances if the nodule is greater than 1 cm and meets sonographic characteristics. �
Test Interpretation
- Excluding other causes of hypothyroidism, an elevated TSH with low or normal FT4 is diagnostic of HT, although reversion of mild TSH elevation to normal is common, especially with "subclinical"� hypothyroidism. Repeat TSH testing at regular intervals in those with subclinical hypothyroidism is warranted.
- High TG and TPO antibodies titers can identify individuals at high risk for developing overt hypothyroidism or at risk for HE.
Treatment
General Measures
- The goal of treatment is to alleviate symptoms and to bring blood levels of TSH into the normal range.
- Oral thyroid hormone replacement should be considered in all patients with subclinical or overt HT. Thyroxine (T4), triiodothyronine (T3), or a combination of T4 and T3 can be prescribed (1)[A].
- IV thyroid hormone replacement (i.e., T4) is recommended for patients at risk for myxedema coma.
Medication
First Line
- Levothyroxine, synthetic T4, is recommended for the treatment of HT (1)[A].
- Patients with HT generally require smaller doses early in the disease process and progress to higher doses as the disease evolves.
- Starting doses of levothyroxine is between 25 and 75 μg/day based on age, weight, and comorbid conditions such as coronary artery disease.
- Levothyroxine 1.6 μg/kg/day estimates full replacement.
- Certain foods and medications including calcium supplements can affect levothyroxine absorption. For this reason, levothyroxine should be administered on an empty stomach and separate from other medications.
- Glucocorticoid treatment is recommended for HE (prednisone 50-150 mg/day for 3-6 months). Dose titrated by symptoms.
Second Line
- Liothyronine sodium (Cytomel) is a synthetic preparation of T3. It can be given alone or in combination with T4. It has a shorter onset and duration of action than T4.
- Desiccated thyroid preparations (Armour Thyroid, Nature-Thyroid, Westhroid) are animal-derived thyroid hormone products containing both T3 and T4 and generally not recommended.
- Majority of studies have failed to show benefit of combined T4 plus T3. More research is needed to identify if any subgroups of patients with HT benefit from this combination.
- Potential cardiac complications noted with treatment (i.e., arrhythmias) limit the use of these agents.
AlertGeriatric Considerations
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AlertPregnancy Considerations
Euthyroid pregnant women with high TPO antibodies titers
Increased risk for fetal loss, perinatal mortality, and large for gestational age infants. Thyroid hormone replacement may improve miscarriage rates.
Increased risk for subclinical hypothyroidism in the 1st trimester and thyroiditis in the postpartum period. Recommend universal screening of all pregnant women at risk for HT in the 1st trimester and postpartum period. Treatment started if appropriate.
Replacement doses of thyroid hormone increases by as much as 50% during pregnancy. TSH should be monitored every 4 weeks until target goals are achieved and then at least once per trimester. The goal of therapy is to keep TSH <2.5 mU/L during 1st trimester, <3 mU/L during 2nd trimester, and <3.5 mU/L during 3rd trimester. After delivery, thyroid hormone replacement doses can generally be reduced to prepregnancy doses (2)[A].
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Alert
In patients with HT, always consider coexisting autoimmune adrenal insufficiency. Thyroid hormone replacement can trigger adrenal crisis. Therefore, adrenal insufficiency needs to be ruled out prior to thyroid hormone replacement and stress steroids started in individuals at high risk for underlying adrenal insufficiency.
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Issues for Referral
Endocrine consultation should be considered for myxedema coma, in pregnancy, and if difficulty achieving TSH target goal. �
Surgery/Other Procedures
Thyroidectomy can be considered for goiter associated to compressive symptoms (i.e., dysphagia, dysphonia, dyspnea). �
Inpatient Considerations
Admission Criteria/Initial Stabilization
- Severe hypothyroidism/myxedema coma is an endocrine emergency and requires admission to the intensive care unit.
- Treatment consists of IV levothyroxine and corticosteroids together with hemodynamic support.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- TSH can be monitored every 4-6 weeks and dose titrated to achieve target goals.
- Once target goal is achieved, then TSH should be monitored yearly or based on symptoms.
Diet
Optimal iodine content is recommended. �
Patient Education
- Education should focus on the importance of patient compliance, as it relates to frequency and manner of dosing (i.e., empty stomach).
- Maternal hypothyroidism especially in the 1st trimester has been linked to impaired psychomotor/cognitive deficits in the child. Therefore, women of childbearing years with or at risk for HT need to notify their physician when planning pregnancy and when they become pregnant so that timely monitoring of labs and T4 dose adjustments can occur.
Prognosis
Prognosis is excellent with early diagnosis and treatment. However, mortality rates can be as high as 50% in myxedema coma. �
Complications
Untreated, HT can lead to severe hypothyroidism, including myxedema coma. �
References
1.Garber �JR, Cobin �RH, Gharib �H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012; 22(12):1200-1235. �
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2.Stagnaro-Green �A, Abalovich �M, Alexander �E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011; 21(10): 1086-1125. �
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Codes
ICD09
- 245.2 Chronic lymphocytic thyroiditis
- 244.9 Unspecified acquired hypothyroidism
- 240.9 Goiter, unspecified
ICD10
- E06.3 Autoimmune thyroiditis
- E03.9 Hypothyroidism, unspecified
- E04.9 Nontoxic goiter, unspecified
SNOMED
- 21983002 Hashimoto thyroiditis (disorder)
- 40930008 Hypothyroidism (disorder)
- 3716002 Goiter (disorder)
Clinical Pearls
- HT progresses from asymptomatic to overt hypothyroidism. Thyroid hormone replacement is recommended for both overt and subclinical Hashimoto hypothyroidism.
- Pregnant women who are at risk for HT should have TSH checked in the 1st trimester and postpartum period. Thyroid hormone replacement started and monitored to maintain TSH goal of <2.5 mU/L in pregnancy.