What are the symptoms and treatment options for hypothyroidism with low Thyroid-Stimulating Hormone (TSH) levels?

From the Guidelines

Hypothyroidism with low TSH levels, known as central or secondary hypothyroidism, requires prompt medical evaluation as it indicates a pituitary or hypothalamic problem rather than primary thyroid dysfunction. Symptoms of central hypothyroidism include fatigue, cold intolerance, weight gain, dry skin, hair loss, constipation, depression, muscle weakness, and menstrual irregularities in women. Unlike primary hypothyroidism where TSH is elevated, central hypothyroidism presents with low or inappropriately normal TSH alongside low thyroid hormone (T4) levels. Treatment typically involves levothyroxine (synthetic T4) replacement therapy, usually starting at 1.6 mcg/kg body weight daily, taken on an empty stomach 30-60 minutes before breakfast, as recommended by the USPSTF 1. The principal treatment for hypothyroidism is oral T4 monotherapy (levothyroxine sodium), and dosing cannot be guided by TSH levels, instead requiring monitoring free T4 levels, aiming for the mid to upper normal range 1. Additional hormone replacements may be necessary if other pituitary hormones are affected. The underlying cause of the pituitary or hypothalamic dysfunction should also be investigated and addressed, which may involve MRI imaging to check for tumors or other abnormalities. Regular follow-up appointments are essential to adjust medication dosage and monitor for proper hormone balance, typically every 6-8 weeks initially until stable, then annually. Some key points to consider in the management of hypothyroidism with low TSH include:

• The optimal screening interval for thyroid dysfunction is unknown 1
• Risk factors for a low TSH level include female sex, advancing age, black race, low iodine intake, personal or family history of thyroid disease, and ingestion of iodine-containing drugs, such as amiodarone 1
• Treatment is generally recommended for patients with a TSH level that is undetectable or less than 0.1 mIU/L, particularly those with overt Graves disease or nodular thyroid disease 1
• Long-term randomized, blinded, controlled trials of screening for thyroid dysfunction would provide the most direct evidence on any potential benefits of this widespread practice 1

From the FDA Drug Label

The general aim of therapy is to normalize the serum TSH level TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of pituitary-thyroid feedback. Failure of the serum T4 to increase into the upper half of the normal range within 2 weeks of initiation of levothyroxine sodium therapy and/or of the serum TSH to decrease below 20 IU per litre within 4 weeks may indicate the patient is not receiving adequate therapy

The symptoms of hypothyroidism with low TSH levels are not directly addressed in the drug label. However, hypothyroidism treatment options are provided, with the goal of normalizing the serum TSH level. In some cases, TSH may not normalize due to certain conditions. Treatment involves administering levothyroxine sodium and monitoring TSH and T4 levels to assess the adequacy of therapy 2. Key points to consider in treatment:

• Monitor TSH levels after any change in dosage
• Evaluate clinical and biochemical response every 6 to 12 months
• Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of levothyroxine sodium
• Monitor serum free-T4 levels in patients with secondary and tertiary hypothyroidism.

From the Research

Symptoms of Hypothyroidism with Low TSH

• Fatigue, lethargy, weight gain, and cold intolerance are common symptoms of hypothyroidism, although these symptoms are non-specific 3, 4
• Other symptoms may include dry skin, constipation, voice changes, and hoarseness 5, 3
• In some cases, hypothyroidism can be asymptomatic, especially in subclinical hypothyroidism 5, 3

Treatment Options for Hypothyroidism with Low TSH

• Levothyroxine monotherapy is the standard treatment for hypothyroidism, which is safe and inexpensive, and restores thyroid function tests to within the reference range 6, 3, 4
• The initial dose of levothyroxine is typically 1.5 to 1.8 mcg per kg per day, but may be lower for patients older than 60 years or with known or suspected ischemic heart disease 5, 3
• Adding triiodothyronine is not recommended, even in patients with persistent symptoms and normal levels of thyroid-stimulating hormone 6, 3
• Treatment monitoring is based mainly on blood TSH assay, and dose adjustment should only be considered after 6 to 12 weeks 5

Diagnosis and Management of Hypothyroidism with Low TSH

• Diagnosis is typically made on biochemical grounds through serum thyroid function tests, including TSH and free thyroxine levels 7, 3, 4
• There is no evidence that population screening is beneficial, and symptom relief and normalized thyroid-stimulating hormone levels are achieved with levothyroxine replacement therapy 3
• Patients with persistent symptoms after adequate levothyroxine dosing should be reassessed for other causes or the need for referral 3