Endocrinology · Thyroid Disorders
The facts most likely to be tested
Hashimoto thyroiditis is the most common cause of primary hypothyroidism in iodine-sufficient areas and is characterized by anti-thyroid peroxidase (anti-TPO) antibodies.
The most sensitive screening test for primary hypothyroidism is an elevated serum TSH level.
Clinical presentation often includes fatigue, weight gain, cold intolerance, dry skin, bradycardia, and delayed relaxation of deep tendon reflexes.
Levothyroxine is the standard of care for hormone replacement, requiring monitoring of TSH levels every 6 to 8 weeks after dose adjustments.
Myxedema coma is a life-threatening complication presenting with altered mental status, hypothermia, and hypoventilation, requiring emergent intravenous levothyroxine and glucocorticoids.
Patients with hypothyroidism may exhibit hypercholesterolemia and hyponatremia on routine metabolic panels.
Subclinical hypothyroidism is defined as an elevated TSH with a normal free T4 level and is typically treated if TSH is >10 mIU/L or if the patient is symptomatic or pregnant.
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A 45-year-old woman presents to the clinic complaining of persistent fatigue, weight gain, and constipation over the last six months. She reports feeling cold even when others are comfortable. Physical examination reveals dry, coarse skin, non-pitting edema of the lower extremities, and delayed relaxation of the ankle jerks. Laboratory studies demonstrate a TSH of 12.5 mIU/L and a low free T4.
What is the most appropriate initial management for this patient?
Initiation of levothyroxine therapy
The patient presents with classic signs of primary hypothyroidism, and the elevated TSH with low free T4 confirms the diagnosis, necessitating thyroid hormone replacement.
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Etiology / Epidemiology
Most common cause in US is Hashimoto thyroiditis; globally, iodine deficiency prevails. Affects women > men with peak incidence in middle age.
Clinical Manifestations
Presents with fatigue, weight gain, cold intolerance, and myxedema. Look for delayed relaxation of deep tendon reflexes.
Diagnosis
Gold standard is TSH; primary hypothyroidism shows elevated TSH and low free T4.
Treatment
First-line is Levothyroxine. Caution in elderly/CAD due to risk of angina or arrhythmias.
Prognosis
Generally excellent with adherence. Myxedema coma is a life-threatening emergency requiring IV thyroid hormone.
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Epidemiology & Etiology
Autoimmune destruction via Hashimoto thyroiditis is the leading cause in iodine-sufficient regions. Iatrogenic causes include radioactive iodine ablation or thyroidectomy. Increased risk in patients with other autoimmune conditions like Type 1 Diabetes or Celiac disease.
Pertinent Anatomy
The thyroid gland produces T4 and T3, regulated by the hypothalamic-pituitary-thyroid axis. Peripheral conversion of T4 to T3 occurs in tissues via deiodinase enzymes. Dysfunction leads to systemic metabolic slowing.
Pathophysiology
Decreased thyroid hormone production leads to a loss of negative feedback on the pituitary, causing elevated TSH. Reduced metabolic rate results in accumulation of glycosaminoglycans in the interstitial space, causing myxedema. This manifests as generalized slowing of organ system function.
Clinical Manifestations
Patients present with bradycardia, dry skin, coarse hair, and non-pitting edema. Classic findings include delayed relaxation of deep tendon reflexes and goiter. Myxedema coma presents with altered mental status, hypothermia, and respiratory depression.
Diagnosis
The TSH level is the most sensitive screening test. Primary hypothyroidism is confirmed by TSH > 10 mIU/L and low free T4. Anti-thyroid peroxidase (TPO) antibodies are positive in the majority of Hashimoto cases.
Treatment
Initiate Levothyroxine at a weight-based dose. Monitor TSH every 6 weeks until euthyroid. In patients with known coronary artery disease, start at a lower dose to avoid precipitating myocardial ischemia.
Prognosis
Lifelong replacement is usually required. Subclinical hypothyroidism (elevated TSH, normal T4) requires treatment if TSH > 10 or if the patient is symptomatic/pregnant. Failure to treat leads to hyperlipidemia and increased cardiovascular risk.
Differential Diagnosis
Sick Euthyroid Syndrome: abnormal thyroid labs in non-thyroidal illness
Subclinical Hypothyroidism: elevated TSH with normal free T4
Central Hypothyroidism: low TSH and low free T4
Depression: mimics fatigue and psychomotor slowing
Anemia: mimics fatigue and pallor