Central hypothyroidism — a neglected thyroid disorder

Abstract

Central hypothyroidism is a rare and heterogeneous disorder that is characterized by a defect in thyroid hormone secretion in an otherwise normal thyroid gland due to insufficient stimulation by TSH. The disease results from the abnormal function of the pituitary gland, the hypothalamus, or both. Moreover, central hypothyroidism can be isolated or combined with other pituitary hormone deficiencies, which are mostly acquired and are rarely congenital. The clinical manifestations of central hypothyroidism are usually milder than those observed in primary hypothyroidism. Obtaining a positive diagnosis for central hypothyroidism can be difficult from both a clinical and a biochemical perspective. The diagnosis of central hypothyroidism is based on low circulating levels of free T in the presence of low to normal TSH concentrations. The correct diagnosis of both acquired (also termed sporadic) and congenital (also termed genetic) central hypothyroidism can be hindered by methodological interference in free T or TSH measurements; routine utilization of total T or T measurements; concurrent systemic illness that is characterized by low levels of free T and normal TSH concentrations; the use of the sole TSH-reflex strategy, which is the measurement of the sole level of TSH, without free T, if levels of TSH are in the normal range; and the diagnosis of congenital hypothyroidism based on TSH analysis without the concomitant measurement of serum levels of T. In this Review, we discuss current knowledge of the causes of central hypothyroidism, emphasizing possible pitfalls in the diagnosis and treatment of this disorder.

2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism

“…Several conditions are associated with increased thyroid hormone requirements through different mechanisms. In comparison with primary hypothyroidism, there is a higher frequency for such conditions because of the persistent impact from rhGH (reviewed in [63]). Estrogen therapy is also known to impact thyroid replacement, and this is even more so when medicallyassisted fertility treatments are used [64], but these effects are generally transient in most patients [25,65].…”

MANAGEMENT OF ENDOCRINE DISEASE: Pitfalls on the replacement therapy for primary and central hypothyroidism in adults

“…As matter of fact, FT4 levels are higher in patients with primary hypothyroidism adequately treated based on TSH levels, comparing with euthyroid controls, suggesting that the level of FT4 needs to be higher than that in the normal population to maintain an euthyroid state (136). Based on these data from primary hypothyroidism patients, the recommendation to keep FT4 levels in the middle upper level of the normal reference range as a target for CH patients receiving LT4 seems to be appropriate (128,129,131,136). Because LT4 determines a peak concentration 2-4 h after ingestion, it is recommended to perform blood tests before the ingestion of LT4 tablets, to avoid the peak concentration (128,129,134).…”

“…CH can be isolated or combined with other pituitary hormone deficiencies. Congenital or acquired defects causing functional or anatomic disorders of the pituitary gland and/or hypothalamus can lead to CH (128,129). It is a rare cause of hypothyroidism, affecting 1 of 1000 patients with hypothyroidism (130).…”

“…The aim of CH treatment is to restore euthyroidism (128,129,130,131,132). Levothyroxine is considered the standard treatment as it is inexpensive, worldwide available, has a long half-life of 7 days, lead to more stable serum levels comparing with LT3, enabling the administration of a single daily dose (134).…”

“…Based on these data from primary hypothyroidism patients, the recommendation to keep FT4 levels in the middle upper level of the normal reference range as a target for CH patients receiving LT4 seems to be appropriate (128,129,131,136). Because LT4 determines a peak concentration 2-4 h after ingestion, it is recommended to perform blood tests before the ingestion of LT4 tablets, to avoid the peak concentration (128,129,134). TSH levels are usually low (<0.5 mU/L) in more than 80% of patients receiving LT4 (137).…”