What are the diagnostic steps for central hypothyroidism?

From the Guidelines

Diagnosing central hypothyroidism requires a comprehensive approach that includes clinical evaluation, laboratory testing, and imaging, with a key initial step being the measurement of low free T4 with inappropriately normal or low TSH, as indicated in the management of hypophysitis 1. To diagnose central hypothyroidism, the following steps should be taken:

• Measure thyroid hormone levels, specifically low free T4 with inappropriately normal or low TSH, to distinguish it from primary hypothyroidism, as suggested by the clinical presentation of hypophysitis 1.
• Perform additional testing to measure other pituitary hormones (such as ACTH, LH, FSH) to identify potential multiple pituitary hormone deficiencies, considering that central hypothyroidism often occurs alongside other hormonal deficiencies, as seen in hypophysitis 1.
• Conduct an MRI of the sella, with pituitary cuts, to identify structural abnormalities, which is a crucial step in diagnosing hypophysitis and its associated central hypothyroidism, as recommended for diagnostic confirmation 1.
• Check morning cortisol levels before initiating thyroid hormone replacement to avoid unmasking undiagnosed adrenal insufficiency, which can lead to an adrenal crisis, a consideration emphasized in the management of hypophysitis 1.
• Gather a thorough clinical history focusing on symptoms of pituitary dysfunction, head trauma, radiation exposure, or surgical interventions in the pituitary region to provide context for the diagnosis, as these factors can contribute to the development of central hypothyroidism. The diagnostic approach should prioritize the identification of pituitary hormone deficiencies and structural abnormalities, with strict criteria for diagnostic confirmation including ≥1 pituitary hormone deficiency (TSH or ACTH deficiency required) combined with an MRI abnormality, or ≥2 pituitary hormone deficiencies (TSH or ACTH deficiency required) in the presence of headache and other symptoms, as proposed for hypophysitis 1.

From the Research

Diagnostic Steps for Central Hypothyroidism

The diagnosis of central hypothyroidism can be challenging due to its rare and heterogeneous nature. The following steps can be taken to diagnose central hypothyroidism:

• Measure circulating levels of free T4 and TSH to determine if they are low or normal, respectively 2, 3, 4
• Use concomitant free T4 and TSH measurements for early detection, especially in congenital central hypothyroidism 3
• Avoid relying solely on TSH-reflex strategy, as it may miss cases of central hypothyroidism 2, 5
• Consider the clinical manifestations of central hypothyroidism, which are usually milder than those of primary hypothyroidism 2
• Be aware of potential pitfalls in diagnosis, such as methodological interference in free T4 or TSH measurements and concurrent systemic illness 2

Laboratory Tests

Laboratory tests play a crucial role in the diagnosis of central hypothyroidism. The following tests can be used:

• Free T4 (FT4) measurement to determine if levels are low 2, 3, 4
• TSH measurement to determine if levels are low or normal 2, 3, 4
• Total T4 or T3 measurements, although they may not be as accurate as free T4 measurements 2
• Other biochemical and hormonal parameters, such as reverse triiodothyronine (rT3) and sex hormone-binding globulin (SHBG), may also be useful in diagnosis 6

Challenges in Diagnosis

The diagnosis of central hypothyroidism can be challenging due to several factors, including:

• The rare and heterogeneous nature of the disorder 2, 3
• The similarity of clinical manifestations to those of primary hypothyroidism 2
• The potential for methodological interference in laboratory tests 2
• The need for concomitant measurement of free T4 and TSH to ensure accurate diagnosis 3, 5