From the Guidelines
Weight loss in Addison's disease is primarily caused by cortisol deficiency, leading to impaired glucose metabolism, increased protein breakdown, and reduced fat storage, as well as aldosterone deficiency, resulting in sodium loss and dehydration, all of which contribute to a negative energy balance and progressive weight loss. The pathophysiology of weight loss in Addison's disease involves multiple factors, including:
- Cortisol deficiency, which impairs the body's ability to maintain normal glucose levels, leading to decreased appetite and inadequate caloric intake 1
- Increased protein breakdown and reduced fat storage, contributing to muscle wasting and overall weight loss
- Aldosterone deficiency, leading to sodium loss and dehydration, further reducing body weight through fluid loss
- Gastrointestinal symptoms, such as nausea, vomiting, and abdominal pain, which can significantly decrease food intake Treatment with hormone replacement therapy, including hydrocortisone and fludrocortisone, addresses these underlying hormonal deficiencies and typically reverses the weight loss, with monitoring of glucocorticoid replacement relying on clinical assessment, including symptoms and signs of over-replacement, such as weight gain, and under-replacement, such as lethargy, nausea, poor appetite, weight loss, and increased pigmentation 1. Key considerations in managing weight loss in Addison's disease include:
- Adjusting glucocorticoid dosages based on clinical assessment, rather than plasma ACTH and serum cortisol levels
- Monitoring for signs of over-replacement and under-replacement
- Fine-tuning daily hydrocortisone dosage based on patient symptoms, energy levels, and pigmentation changes
- Considering serum or salivary cortisol day curve monitoring in cases of suspected malabsorption to guide dosing 1.
From the Research
Causes of Weight Loss in Addison's Disease
- Weight loss in Addison's disease is a common symptom, often accompanied by other symptoms such as malaise, anorexia, diarrhea, joint and back pain 2.
- The disease is characterized by glucocorticoid and mineralocorticoid deficiency, which can lead to a range of symptoms including weight loss 2, 3.
- The exact mechanism of weight loss in Addison's disease is not fully understood, but it is thought to be related to the hormonal deficiencies and resulting metabolic changes 4, 5.
- Studies have shown that patients with Addison's disease often experience impaired health-related quality of life (HRQoL) and increased mortality, despite treatment with glucocorticoid and mineralocorticoid replacement therapy 5, 6.
- Weight loss in Addison's disease can be significant, with one case report describing a patient who lost 7 Kg in four weeks 3.
Hormonal Deficiencies and Weight Loss
- The hormonal deficiencies in Addison's disease, including cortisol and aldosterone, can lead to changes in metabolism and appetite, contributing to weight loss 4, 2.
- The deficiency of adrenal androgens, such as dehydroepiandrosterone (DHEA), may also play a role in weight loss, although the evidence for this is weak 4, 5.
- Replacement therapy with glucocorticoids and mineralocorticoids can help to alleviate symptoms, but may not fully restore normal hormonal balances and metabolic function 5, 6.
Clinical Presentation and Diagnosis
- Weight loss in Addison's disease is often accompanied by other symptoms such as fatigue, anorexia, and hyperpigmentation of the skin and mucosal surfaces 2, 3.
- Diagnosis of Addison's disease is typically made through a combination of clinical presentation, laboratory tests, and imaging studies 2, 3.
- Early diagnosis and treatment of Addison's disease are critical to preventing long-term complications and improving patient outcomes 3.