INTRODUCTION

The overwhelming majority of patients who have hypothyroidism have thyroid disease (primary hypothyroidism). Central hypothyroidism refers to thyroid hormone deficiency due to a disorder of the pituitary, hypothalamus, or hypothalamic-pituitary portal circulation. Pituitary thyrotropin (TSH) production is regulated in part by thyrotropin-releasing hormone (TRH), which is secreted from the paraventricular nucleus in the hypothalamus. TRH is released into portal blood vessels and transported to the anterior pituitary gland where it regulates the synthesis, glycosylation, and release of TSH (figure 1). TSH stimulates the synthesis and secretion of triiodothyronine (T3) and thyroxine (T4). (See "Thyroid hormone synthesis and physiology".)

Hypothalamic-pituitary tumors can cause central hypothyroidism by compression of the hypothalamus or pituitary, which results in a decrease in TRH or TSH secretion, or by disrupting signalling between the hypothalamus and pituitary. Other causes of central hypothyroidism include lymphocytic hypophysitis, Sheehan syndrome, traumatic brain injury, subarachnoid hemorrhage, and infiltrative disorders. Patients with central hypothyroidism frequently have other pituitary hormone deficiencies.

The clinical features, diagnosis, and treatment of central hypothyroidism will be reviewed here. The approach to patients with primary, subclinical, and congenital hypothyroidism is reviewed separately. (See "Diagnosis of and screening for hypothyroidism" and "Treatment of hypothyroidism" and "Subclinical hypothyroidism" and "Clinical features and detection of congenital hypothyroidism" and "Treatment and prognosis of congenital hypothyroidism".)

ETIOLOGY

Central hypothyroidism is a rare cause of hypothyroidism, estimated to occur in 1:20,000 to 1:80,000 in the general population [1]. The causes of central hypothyroidism are the same as the causes of hypopituitarism (table 1) [2,3]. (See "Causes of hypopituitarism".)

Pituitary mass lesions, especially pituitary adenomas, are the most common cause of central hypothyroidism [4]. Pituitary tumors can cause hypothyroidism by compression of pituitary thyrotrophs, interruption of the hypothalamic-pituitary portal blood flow, or rarely by acute hemorrhage or infarction resulting in pituitary apoplexy [2,3]. Other mass lesions that can cause central hypothyroidism include cysts and abscesses, meningiomas and dysgerminomas, metastatic tumors, and craniopharyngiomas, which may enter the sella or remain suprasellar.