What are the pathophysiology, clinical manifestations, and lab values associated with hypothyroidism and hyperthyroidism, including the emergent condition of thyroid storm, according to medical references such as Medscape and Merck Manual?

Pathophysiology, Clinical Manifestations, and Laboratory Values in Thyroid Disorders

Pathophysiology of Hypothyroidism

Hypothyroidism results from inadequate thyroid hormone production, most commonly caused by primary thyroid gland dysfunction. In industrialized nations, Hashimoto's disease (chronic autoimmune thyroiditis) is the most frequent cause, while worldwide, iodine deficiency remains the leading cause 1. The condition involves decreased production of thyroid hormones (T3 and T4), leading to reduced metabolic rate and multiple systemic effects. The hypothalamic-pituitary-thyroid axis attempts to compensate through increased TSH production, which is a key diagnostic marker 1, 2.

Clinical Manifestations

Hypothyroidism

• Fatigue and muscle cramps, which worsen with disease progression 1
• Cold intolerance that persists despite environmental temperature changes 3
• Constipation that can be severe and resistant to conventional treatments 1, 3
• Hair loss and dry skin that may not improve with moisturizers 3
• Weight gain accompanied by intellectual slowness and voice changes 1

Hyperthyroidism

• Tachycardia out of proportion to other clinical findings, a hallmark sign 1
• Heat intolerance and hyperthermia, often with excessive sweating 4
• Tremors and neuropsychiatric symptoms including anxiety and restlessness 1
• Gastrointestinal disturbances including diarrhea and vomiting 1
• Cardiac manifestations including atrial fibrillation and heart failure symptoms 1

Emergent Conditions

Thyroid Storm (Hyperthyroidism Emergency)

Thyroid storm is a life-threatening condition characterized by exaggerated signs of hyperthyroidism with evidence of multiorgan decompensation. It typically occurs in patients with untreated or inadequately treated hyperthyroidism when triggered by an acute stressor such as infection, trauma, or surgery 4, 5.

Key features include:

• Fever and extreme tachycardia disproportionate to fever 1
• Altered mental status ranging from agitation to coma 1, 4
• Gastrointestinal dysfunction with vomiting and diarrhea 4
• Cardiovascular collapse that may progress to shock 1, 4
• Without prompt treatment, mortality approaches 10% even with modern care 5

Myxedema Coma (Hypothyroidism Emergency)

Myxedema coma represents the most extreme manifestation of severe hypothyroidism with deteriorating mental status, hypothermia, and multiple organ system abnormalities. This condition typically affects elderly patients with long-standing untreated hypothyroidism 6, 7.

Key features include:

• Hypothermia that may be severe and resistant to warming 6
• Decreased mental status progressing to coma 6, 7
• Hypoventilation with risk of carbon dioxide retention 6
• Hyponatremia and other electrolyte disturbances 6
• Cardiovascular manifestations including bradycardia and hypotension 7

Laboratory Values in Thyroid Disorders

Normal Laboratory Values

• TSH: 0.4-4.0 mIU/L
• Free T4: 0.8-1.8 ng/dL
• Free T3: 2.3-4.2 pg/mL

Laboratory Findings in Hypothyroidism

• TSH: Elevated (often >10 mIU/L) in primary hypothyroidism 1
• Free T4: Low (below normal range) 1
• Free T3: Low or low-normal 2

Laboratory Findings in Hyperthyroidism

• TSH: Suppressed or undetectable (<0.1 mIU/L) 1
• Free T4: Elevated (above normal range) 1
• Free T3: Elevated, often disproportionately higher than T4 5

Important Clinical Considerations

• Beta-blockers may mask symptoms of thyroid dysfunction, making diagnosis challenging 3
• In patients with both adrenal insufficiency and hypothyroidism, steroids must be started before thyroid hormone replacement to prevent precipitating adrenal crisis 3
• Laboratory values alone cannot diagnose thyroid storm or myxedema coma; these are clinical diagnoses based on presentation 4, 7
• Thyroid function tests are recommended in all patients presenting with heart failure due to the potential contribution of thyroid dysfunction 1

Treatment Approaches

Thyroid Storm Management

• Immediate multimodal therapy including beta-blockers (unless severe heart failure present), thionamides, iodine solutions, and steroids 4, 5
• Supportive care including cooling measures, fluid resuscitation, and treatment of precipitating factors 4
• Consideration of plasma exchange or thyroidectomy in refractory cases 5

Myxedema Coma Management

• Thyroid hormone replacement (typically intravenous levothyroxine) 6
• Glucocorticoid administration until adrenal insufficiency is ruled out 6
• Supportive care addressing hypothermia, hypoventilation, and electrolyte abnormalities 6, 7

Remember that both thyroid storm and myxedema coma are clinical diagnoses that require prompt recognition and treatment to reduce mortality 4, 6.