What is the diagnosis and treatment for central hypothyroidism (reduced production of thyroid-stimulating hormone (TSH) by the pituitary gland)?

From the Guidelines

Central hypothyroidism should be treated with thyroid hormone replacement therapy, and the diagnosis should involve evaluating TSH and FT4 levels, with low TSH and low FT4 indicating central hypothyroidism, as per the guidelines 1. The treatment approach for central hypothyroidism involves thyroid hormone supplementation, with the goal of achieving normal FT4 levels, as TSH levels cannot be used to monitor treatment adequacy due to the underlying deficiency of TSH production.

• The initial evaluation should include checking TSH and FT4 levels, with low TSH and low FT4 consistent with central hypothyroidism, as indicated in the guidelines for managing immune-related adverse events in patients treated with immune checkpoint inhibitor therapy 1.
• For symptomatic patients, thyroid hormone supplementation should be prescribed, and TSH levels should be monitored every 6-8 weeks while titrating hormone replacement to goal, with FT4 used to help interpret ongoing abnormal TSH levels on therapy, as suggested in the guidelines 1.
• In cases of severe symptoms or life-threatening consequences, ICPi should be held until symptoms resolve to baseline with appropriate supplementation, and endocrine consultation should be sought to assist with rapid hormone replacement, as recommended in the guidelines for grade 3-4 symptoms 1.
• Regular monitoring is essential, with free T4 measurements every 6-12 months once stable, to ensure that the treatment is effective and to make any necessary adjustments to the hormone replacement therapy.
• It is also important to consider comprehensive pituitary function testing at diagnosis, as central hypothyroidism often occurs with other pituitary hormone deficiencies, and to evaluate for potential causes of the condition, such as damage to the pituitary or hypothalamus from tumors, surgery, radiation, inflammation, or congenital defects.

From the FDA Drug Label

Levothyroxine sodium tablets are a L-thyroxine (T4) indicated in adult and pediatric patients, including neonates, for: • Hypothyroidism: As replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism (1)

The diagnosis of central hypothyroidism is based on reduced production of thyroid-stimulating hormone (TSH) by the pituitary gland. The treatment for central hypothyroidism is replacement therapy with levothyroxine sodium tablets, which are indicated for secondary (pituitary) hypothyroidism 2. Key considerations for treatment include:

• Starting dose depends on a variety of factors, including age, body weight, cardiovascular status, and concomitant medications
• Peak therapeutic effect may not be attained for 4 to 6 weeks
• Adequacy of therapy determined with periodic monitoring of TSH and/or T4 as well as clinical status

From the Research

Diagnosis of Central Hypothyroidism

• Central hypothyroidism is diagnosed based on a confirmed decrease in the level of free T4 with a low or normal level of TSH 3
• The diagnosis can be difficult due to the non-typical clinical picture and frequent combination with impaired function of other pituitary hormones 3
• Measurement of concomitant free T4 and TSH is essential for early detection and preventing neurological sequelae, particularly in congenital central hypothyroidism 4
• Exploration of the circadian TSH cycle, determination of TSH response after a TRH test or recombinant TSH injection, estimation of TSH index, or evaluation of peripheral indexes of thyroid hormone metabolism may be required to establish a diagnosis in patients with early-stage or moderate central hypothyroidism 5

Treatment of Central Hypothyroidism

• The standard treatment for central hypothyroidism is monotherapy with levothyroxine, which allows to restore the euthyroid state in most patients 3
• Levothyroxine treatment is essential for correcting hormonal imbalances and improving quality of life, though caution is needed to avoid overdosing, especially in vulnerable populations 4
• The criterion for the effectiveness of therapy is to maintain the level of T4 free in the upper half of the reference norm interval 3
• Hormone objectives during follow-up need to be precisely determined in order to reduce cardiovascular risks and to improve the quality of life of patients 5
• Personalized treatment and continuous monitoring are emphasized to ensure the best clinical outcomes and promote optimal quality of life 4