Central hypothyroidism (CH) is a rare cause of
hypothyroidism, generally due to either pituitary or hypothalamic defects. On the basis of its etiology, it is possible to distinguish acquired and hereditary forms. Hereditary CH can be isolated or associated with
combined pituitary hormone deficiency (CPHD). In the former case, alterations of only two genes, TSHbeta and the
TRH receptor, have so far been described as responsible for the disorder. In hereditary CH associated with CPHD, inactivating mutations of different pituitary
transcription factors (HESX1, PROP-1, POU1F1) have been found involved in the pathogenesis of the disease. Finally, an association between CH and
severe obesity has been described in patients with
leptin receptor (
Leptin-R) mutations. The clinical consequences of CH in adult life vary greatly depending on the etiology, the severity of the thyroid impairment, the extent of the associated
hormone deficiencies, and the age of the patient at the time of the onset of the disease. In general, acquired CH is less severe than the congenital form because of the constitutive activity of the wild-type
TSH-receptor. Symptoms and signs of thyroid insufficiency are usually milder than those of
primary hypothyroidism, and
goiter is always absent. In CPHD, most patients have other endocrine manifestations of the disease (growth failure,
delayed puberty,
adrenal insufficiency,
diabetes insipidus) that lead them to seek medical attention before the
hypothyroidism becomes severe. Early diagnosis of the congenital form by neonatal screening for
hypothyroidism is strongly recommended in order to avoid
cretinism. Replacement
therapy with
L-thyroxine administration has to be established as soon as possible.