Could It Be Addison’s? Top 5 Diseases Mimicked by the Great Pretender

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Hypoadrenocorticism (ie, Addison’s disease) can be challenging to recognize. Both glucocorticoid deficiency and mineralocorticoid deficiency cause nonspecific and highly variable clinical signs that may wax and wane (see Clues that Raise Clinical Suspicion for Hypoadrenocorticism).1,2

Clues that Raise Clinical Suspicion for Hypoadrenocorticism1-3

History

Physical Examination

Clinicopathologic Findings

Treatment

Waxing and waning episodes of nonspecific disease

Sudden collapse related to a stressful event

Anorexia

Lethargy

Vomiting

Depression

Weakness

Trembling

Bradycardia in the face of hypovolemic shock

Lack of stress leukogram in a sick patient

Reverse stress leukogram (ie, eosinophilia, lymphocytosis)

Hyperkalemia

Hyponatremia

Low Na:K ratio

Unexpectedly rapid response to symptomatic fluid therapy or corticosteroid therapy 

In addition, none of the clinicopathologic changes often associated with Addison’s disease are pathognomonic.1,2 Even the classic electrolyte changes associated with hypoadrenocorticism (ie, hyperkalemia, hyponatremia, low Na:K ratio) can be found with other diseases (eg, severe GI, kidney, or liver disease) and are absent with atypical hypoadrenocorticism.1,2 These challenges may lead clinicians to place other, more common diseases at the top of their differentials list when encountering hypoadrenocorticism, earning the disease its nickname “the great pretender.”2,3

The following are the top 5 diseases hypoadrenocorticism imitates.

1. Recurrent Gastrointestinal Disease

In the absence of glucocorticoids, as seen with hypoadrenocorticism, GI integrity is compromised, causing chronic GI signs.1 Anorexia, vomiting, diarrhea, regurgitation, and weight loss are some of the most common historical findings in Addisonian patients,1,2 with melena and hematemesis being possible as well.2

Symptomatic treatment (eg, fluid therapy, corticosteroids) can significantly improve clinical signs, but without addressing the underlying hypoadrenocorticism, clinical signs will inevitably recur.1,2 These episodic GI issues can be easily misdiagnosed as any number of diseases with deceivingly similar presentations (eg, protein-losing enteropathy, intestinal neoplasia, food sensitivities).2-4 Hypoadrenocorticism should be considered in any patient with chronic, poorly controlled GI disease and ruled out before proceeding to invasive diagnostics (eg, endoscopy, biopsy).1,2

2. Acute Renal Failure

Mineralocorticoid deficiency and its electrolyte changes, which occur with hypoadrenocorticism, can mimic renal failure.2,3 Hyponatremia alters the kidney’s ability to resorb water, resulting in polyuria and compensatory polydipsia.1,2 Over time, dehydration and hypovolemia ensue.1 The combination of polyuria, polydipsia, and azotemia from dehydration can trick clinicians into suspecting renal disease.2,3 Urine specific gravity typically remains decreased, making prerenal azotemia difficult to differentiate from renal azotemia.1,2 Other clinicopathologic features similar to renal disease (eg, hyperphosphatemia, hypercalcemia) further complicate the diagnosis.1,2,5 Because acute renal failure has a much graver prognosis than hypoadrenocorticism, differentiating between them is important.1,2

3. Liver Disease

When a sick patient has both elevated liver enzymes and changes suggestive of poor liver function (ie, hypoglycemia, hypocholesterolemia, hypoalbuminemia), liver disease usually tops the differential list; however, hypoadrenocorticism can cause all these same changes.1,2,6

Glucocorticoid deficiency causes hypoglycemia by reducing gluconeogenesis and increasing insulin sensitivity.1,7 Hypoglycemia may be found in as many as one-third of Addisonian patients.1 Hypoadrenocorticism is an important cause of hypocholesterolemia and is thought to be related to reduced fat absorption in the GI tract.1

When a sick patient has both elevated liver enzymes and changes suggestive of poor liver function, liver disease usually tops the differential list; however, hypoadrenocorticism can cause all these same changes.

Hypoalbuminemia is fairly common in Addisonian patients as well and has multiple contributing causes, including reduced protein synthesis, impaired protein absorption, and protein loss.1 Meanwhile, liver enzyme (ALT, AST) elevations are typically mild to moderate, occur in ≈30% of Addisonian patients, and are potentially the product of poor liver perfusion.1,2

4. Toxic Ingestion

The acute nature of an Addisonian crisis in a patient believed to be otherwise healthy may raise suspicion for a toxic ingestion. Depending on the presenting clinical signs, any variety of toxins may be implicated. GI signs like vomiting and diarrhea are seen with many toxins (eg, NSAIDs, chocolate), and polyuria and polydipsia may be seen with renal toxins (eg, grapes, raisins, ethylene glycol). Hypoglycemic seizure, a rare but documented presentation of hypoadrenocorticism, may mimic xylitol toxicity.1,2,7

When historical evidence for toxic ingestion is lacking, other causes of sudden collapse, including hypoadrenocorticism, should be considered.

5. Megaesophagus

Although a rare comorbidity of hypoadrenocorticism, megaesophagus can develop in Addisonian patients.1,2,8,9 The etiology is poorly understood.1 Neuromuscular dysfunction from electrolyte imbalance or muscle weakness from cortisol deficiency have both been proposed.1 In Addisonian patients, megaesophagus may be reversible once hypoadrenocorticism is controlled.2,9 The possibility of curative treatment should prompt investigation for the underlying cause before megaesophagus is presumed idiopathic.

Conclusion

Left undiagnosed and untreated, hypoadrenocorticism can become problematic for a variety of reasons1,2: hypovolemic shock associated with an Addisonian crisis can be life-threatening and requires emergency stabilization; misdiagnoses may appear more grave, potentially leading owners to choose euthanasia; and recurrent disease and unnecessary tests and treatments may cause emotional fatigue and financial limitations for owners.

Early recognition and diagnosis are essential to prevent serious complications and control this treatable disease. Keeping reasons to raise clinical suspicion of hypoadrenocorticism top of mind may help clinicians ensure that a diagnosis is never missed (see Clues That Raise Clinical Suspicion for Hypoadrenocorticism).

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