Can weakness be a sign of Addison's disease or hypothyroidism?

Weakness is a Common Symptom in Both Addison's Disease and Hypothyroidism

Weakness is a significant clinical sign of both Addison's disease and hypothyroidism, and should be thoroughly investigated for either condition when present, especially when accompanied by other characteristic symptoms.

Weakness in Addison's Disease

Weakness is a cardinal symptom of adrenal insufficiency (Addison's disease) and is specifically mentioned as one of the key symptoms to monitor for during steroid weaning 1. The Endocrine Society recognizes fatigue and weakness as primary indicators of adrenal insufficiency that require close monitoring, particularly in patients at risk 1.

The pathophysiology behind weakness in Addison's disease involves:

• Insufficient cortisol production leading to decreased energy metabolism
• Electrolyte disturbances (particularly decreased sodium and increased potassium)
• Hypotension causing reduced tissue perfusion

Weakness in Addison's disease is often accompanied by:

• Fatigue
• Dizziness
• Nausea
• Weight loss
• Hypotension
• Hyperpigmentation of skin and mucous membranes 2

Weakness in Hypothyroidism

Weakness is also a common manifestation of hypothyroidism. The FDA drug label for levothyroxine specifically lists muscle weakness as an adverse reaction when transitioning from hypothyroidism to hyperthyroidism during treatment, indicating that weakness is a recognized symptom of thyroid dysfunction 3.

In hypothyroidism, weakness typically presents as:

• Generalized muscle weakness
• Muscle cramps or spasms
• Slowed movement and reflexes
• Exercise intolerance

Diagnostic Considerations

When evaluating weakness as a potential sign of either condition:

1. Laboratory Testing:

   • For Addison's disease: Morning serum cortisol and ACTH levels are the gold standard initial tests 1

     • Morning cortisol <110 nmol/L (<4 μg/dL) suggests adrenal insufficiency
     • High ACTH + Low cortisol indicates primary adrenal insufficiency
     • Electrolyte abnormalities (low Na, high K) are common

   • For Hypothyroidism: TSH and free T4 levels

     • Elevated TSH with normal or low free T4 indicates hypothyroidism

2. Important Clinical Caveat: Thyroid hormone increases metabolic clearance of glucocorticoids. Initiating thyroid hormone therapy prior to treating adrenal insufficiency can precipitate an acute adrenal crisis 3. This critical interaction is specifically mentioned in the FDA levothyroxine label.

Autoimmune Polyglandular Syndrome Consideration

A crucial clinical consideration is that both conditions can coexist, particularly in autoimmune polyglandular syndrome type 2 4. In such cases:

• Treating hypothyroidism without addressing adrenal insufficiency can precipitate an adrenal crisis 4, 5
• Steroid replacement in patients with both conditions may normalize thyroid function in some cases 6

Clinical Algorithm for Evaluating Weakness

1. Assess for characteristic features of each condition:

   • Addison's: Hyperpigmentation, salt craving, postural hypotension, weight loss
   • Hypothyroidism: Cold intolerance, constipation, dry skin, bradycardia, weight gain

2. Order appropriate testing:

   • Morning cortisol and ACTH
   • TSH and free T4
   • Electrolytes (sodium, potassium)

3. If both conditions are suspected:

   • Always treat adrenal insufficiency first with glucocorticoid replacement
   • Only after adequate steroid replacement, address hypothyroidism with levothyroxine

4. Monitor for symptom improvement:

   • Weakness should improve with appropriate treatment of the underlying condition
   • Persistent weakness may indicate inadequate treatment or comorbid conditions

Common Pitfalls to Avoid

1. Missing the coexistence of both conditions - Always consider autoimmune polyglandular syndrome when one endocrine disorder is diagnosed

2. Treating hypothyroidism before addressing adrenal insufficiency - This can precipitate a life-threatening adrenal crisis 3, 4

3. Attributing weakness solely to hypothyroidism without considering adrenal function - Some cases initially diagnosed as hypothyroidism may actually be Addison's disease or a combination of both 5

4. Overlooking the possibility that steroid replacement alone may normalize thyroid function in some patients with both conditions 6