A male patient with a craniopharyngioma involving the hypothalamus develops diabetes insipidus, central hypogonadism, and hypothyroidism. The TSH level is low-normal and free T4 is low. This pattern of central hypothyroidism is due to:

• A Excessive somatostatin tone from the hypothalamus suppressing TSH glycosylation
• B Direct autoimmune destruction of thyrotrophs by tumour-infiltrating lymphocytes
• C High dopamine output from the tumour inhibiting TSH release
• D Loss of hypothalamic TRH pulsatility, producing biologically inactive glycoforms of TSH with normal immunoreactivity ✓

Explanation

In central (secondary/tertiary) hypothyroidism caused by hypothalamic disease, TRH pulsatility is lost. TRH is required not only for TSH release but also for proper glycosylation (addition of terminal sialic acid and sulphate residues) that confers TSH biological activity. Without adequate TRH, TSH molecules secreted are immunologically detectable (normal or low-normal TSH on immunoassay) but biologically inactive, resulting in low free T4. This explains the apparently paradoxical picture of low-normal TSH with low free T4 in tertiary hypothyroidism. The other options are not the primary mechanism.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.