Confirmation of hypothyroidism & differentiating between primary, central & subclinical hypothyroidism

• Measure serum TSH: Most sensitive test for detecting hypothyroidism
• Confirm w/ measurement of serum FT₄
• Primary hypothyroidism: High TSH & low FT₄
• Central hypothyroidism: Low/normal/mildly elevated TSH & low FT₄
• Subclinical hypothyroidism: High TSH & normal FT₄

Other tests

• Thyroid autoantibodies
  • Antithyroid peroxidase, antithyroglobulin autoantibodies

• Thyroid scan, ultrasonography (may do both)

• Subclinical hypothyroidism refers to the state of slightly increased serum TSH w/ normal serum FT₄ in patients who are usually asymptomatic

Other causes of elevated TSH that should be excluded

• Recent Levothyroxine dose adjustment wherein a steady state is not achieved
• Transient increase in TSH during recovery from severe illness or destructive thyroiditis
• Untreated primary adrenal insufficiency
• Administration of recombinant human TSH
• Presence of heterophilic antibodies against mouse proteins

Determination of Treatment for Subclinical Hypothyroidism:

Further Evaluation

• Thyroid antibodies detection (if positive, for treatment); if negative (TSH >10 mU/L, for treatment)
• Physical exam
• Lipid profile

Risk Assessment

• Higher risk of progression to overt hypothyroidism if TSH >10 mU/L, presence of thyroid antibodies, goiter, hyperlipidemia, pregnancy, ovulatory dysfunction w/ infertility
  • Treatment is recommended in higher risk patients
  • If patient is not at high risk, perform annual thyroid exam

Etiologies

Autoimmune Thyroiditis (Hashimoto’s Disease)

• Most common cause
• Diagnosis
  • Thyroid antibodies [anti-thyroid peroxidase (TPO)- in 95% or antithyroglobulin (TG) detection in 60%]
  • Careful history of radiation exposure, radioactive iodine therapy, neck surgery, recent viral infection, medications, pregnancy, change in diet
  • Presence of thyroid antibodies & absence of any of the above history confirms diagnosis of Hashimoto’s thyroiditis

Other Causes

• Congenital: Endemic iodine deficiency (Athyreosis, dyshormonogenesis), thyroid hormone resistance, TSH-receptor defect
• Acquired: Iodine deficiency, iatrogenic (post-thyroidectomy, thyroid irradiation, medications, radioactive iodine therapy)
• Transient: Subacute thyroiditis (de Quervain’s), lymphocytic thyroiditis (silent, postpartum & painless thyroiditis), neonatal hypothyroidism

Evaluation

• Thorough exam of the function of the hypothalamic-pituitary axis
• Determine adrenal status, if adrenal insufficient:
  • Thyroxine administration may increase metabolism & precipitate an adrenal crisis
  • Glucocorticoid should be replaced prior to thyroxine administration to avoid adrenal crisis

Etiologies 

• Central hypothyroidism is divided into secondary hypothyroidism (defect is in the pituitary gland) & tertiary hypothyroidism (defect is in the hypothalamus)
• Central hypothyroidism occurs due to failure of the hypothalamic-pituitary axis causing decreased TSH secretion or reduced TSH biological activity
• Pituitary: Tumor, vascular insufficiency, empty sella syndrome, infiltrating disease, infection, iatrogenic (surgery & radiotherapy)
• Hypothalamic: Tumor, infection, vascular insufficiency, thyrotropin-releasing hormone (TRH) deficiency, iatrogenic

• Correct diagnosis is imperative because critical illnesses are clinically similar to myxedema coma & can also present w/ altered thyroid function
  • If diagnosis is wrong, high doses of thyroid hormone is dangerous to the patient

Signs & Symptoms

• Severe hypothermia (<27°C)
• Bradycardia
• Respiratory failure & loss of consciousness
• Long-standing hypothyroidism

Precipitating Factors

• Infection
• CV event
• Exposure to cold