• Hypothyroidism is the most common hormone deficiency condition and involves insufficient amounts of thyroid hormones produced by the thyroid gland, namely thyroxine (T4) and triiodothyronine (T3).
• Hypothyroidism is more common in women and the incidence increases with age.
• The majority of hypothyroidism cases (~95%) are due to primary hypothyroidism which involves failure of the thyroid gland to produce thyroid hormones.
• Central (secondary or tertiary) hypothyroidism accounts for the remaining 5% of cases and involves impaired secretion of thyroid-stimulating hormone (TSH) from the pituitary gland (secondary hypothyroidism) or impaired secretion of thyrotropin-releasing hormone (TRH) from the hypothalamus (tertiary hypothyroidism).
• Many patients with central hypothyroidism also have deficiencies in other pituitary gland hormones.

• Due to the nonspecific and variable clinical features of hypothyroidism (Table 1), diagnosis is based on laboratory testing.

Initial Investigation: TSH

• Serum TSH is the first laboratory investigation to order in patients with signs or symptoms of hypothyroidism.

If TSH is elevated:

• Repeat serum TSH measurement
• Measure serum T4:
  • If TSH is still elevated and T4 is below the reference range:
    • Clinical/overt primary hypothyroidism is suspected
    • Initiate thyroid hormone replacement therapy
  • If TSH is still elevated and T4 is within the reference range:
    • Subclinical/mild primary hypothyroidism is suspected
    • Initiation of thyroid hormone replacement therapy on a case-by-case basis

If TSH is normal or low:

• Repeat serum TSH measurement
• Measure serum T4:
  • If TSH is inappropriately normal or low and T4 is below the reference range:
    • Central (secondary or tertiary) hypothyroidism is suspected.
    • Further investigation and imaging required.

Investigations for Suspected Central Hypothyroidism

• Visual Field defects on exam.
• Suspect if low Free T₄and inappropriately low, normal or slightly increased TSH. A delayed TSH response to TRH (TRH stimulation test) supports the diagnosis.
• MRI or Computed Tomography (CT) with coronal views through the pituitary gland (done by consultant).
• Evaluation of other hypothalamic-pituitary-end organ hormones (estradiol, prolactin, gonadotropins, testosterone) in patients with sellar mass lesions on MRI.
• ACTH stimulation test to assess pituitary-adrenal function and adrenal insufficiency.

Thyroid Hormone Replacement

• Initiate levothyroxine (synthetic T4) at a weight-based dose of 1.6 mcg/kg/day in young and otherwise healthy patients.
• Initiate levothyroxine at a lower dose (25 – 50 mcg/day) in patients of older age, with cardiovascular disease, or unknown duration of hypothyroidism.

• Admit if hemodynamically unstable, altered mental status, hypothermic, or vulnerable patient.
• If stable to discharge, refer to Internal Medicine, endocrine if no family physician.

Pregnant Patients

• Pregnant women with pre-existing hypothyroidism should increase their dose of levothyroxine by ~30%.
• Pregnant women with newly diagnosed primary hypothyroidism should start levothyroxine at a dose of 1.6 mcg/kg/day to achieve a euthyroid state as soon as possible.
• Endocrine or internal medicine referral.

Untreated Adrenal Insufficiency

• Administration of levothyroxine to patients with untreated adrenal insufficiency may precipitate an adrenal crisis.
• Patients with evidence of central hypothyroidism and other pituitary hormone deficiencies should have pituitary-adrenal function assessed before administering levothyroxine therapy.

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