Approach
Hypothyroidism is caused by a deficiency of thyroid hormones (thyroxine [T4] and triiodothyronine [T3]) and generally presents with cold intolerance, fatigue, depression, and generalised weakness. The diagnosis of central hypothyroidism requires low serum free T4 and low, normal, or slightly elevated thyroid-stimulating hormone (TSH).[4][32]
History
Clinical features of central hypothyroidism are similar to those of primary hypothyroidism but may be milder.[1] Manifestations may include weakness, fatigue, lethargy, headaches, cold intolerance, hearing impairment, constipation, muscle cramps, modest weight gain, galactorrhoea, decreased memory, and depression.
Features in the history that support central, rather than peripheral, hypothyroidism include symptoms consistent with deficiency or excess of other pituitary hormones including prolactin, adrenocorticotrophic hormone, growth hormone, luteinising hormone (LH), and follicle-stimulating hormone (FSH). Symptoms of diabetes insipidus may indicate concomitant posterior pituitary dysfunction. A history of headaches, diplopia, or diminished peripheral vision may indicate a sellar or suprasellar mass. A past medical history of brain or metastatic cancer, haemochromatosis, sarcoidosis, recent pregnancy, or pituitary surgery or radiation may indicate a possible aetiology. A family history of central hypothyroidism may suggest a genetic disorder in rare cases.
Physical examination
The examination findings in patients with central hypothyroidism are similar to those found in primary hypothyroidism. Patients may have dry, coarse skin, impassive facial expression, bradycardia, reduced body and scalp hair, and delayed relaxation of deep tendon reflexes. Physical examination findings that support a central rather than peripheral hypothyroidism include findings consistent with a deficiency or excess of other pituitary hormone(s), such as atrophic breasts, galactorrhoea, buffalo hump, moon facies, or acromegaly.
Laboratory evaluation
If hypothyroidism is suspected, serum TSH and free T4 should be ordered. Central hypothyroidism is characterised by a low free T4 in association with discordant TSH (usually low or normal, but also could be elevated). Non-thyroidal illness is an important differential diagnosis that must be excluded. Urgent referral to an endocrinologist is advised for further assessment of pituitary function. Appropriate baseline endocrine investigations include a serum cortisol, prolactin, gonadotrophins (FSH, LH), and a total testosterone. Low/normal serum gonadotrophins in post-menopausal women and low serum gonadotrophins in combination with a low serum total testosterone in men indicate hypogonadotrophic hypogonadism. Genetic analyses are recommended in congenital cases, and in cases of onset during childhood or at any age when central hypothyroidism remains unexplained.[3]
Imaging
Large pituitary tumours are common in the setting of central hypothyroidism. Thus, imaging of the pituitary is essential. Magnetic resonance imaging (MRI) is the single best imaging procedure for sellar masses. If MRI is unavailable, a computed tomographic scan with coronal views through the pituitary is a reasonable alternative.[33][34][35]
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