What is the diagnosis and treatment for a patient with new Gastroesophageal Reflux Disease (GERD), hair loss, weight gain, and new freckles?

Diagnosis: Cushing's Syndrome, Not GERD

This patient's constellation of symptoms—new GERD, hair loss, weight gain, and new freckles (hyperpigmentation)—strongly suggests Cushing's syndrome rather than primary GERD, and requires immediate endocrine evaluation before treating the reflux symptoms.

Why This Is Not Simple GERD

The combination of symptoms points to a systemic endocrine disorder:

• Weight gain with GERD is atypical for primary reflux disease and suggests cortisol excess, which increases visceral adiposity and intra-abdominal pressure, secondarily causing reflux 1
• Hair loss is not a manifestation of GERD and indicates hormonal dysregulation consistent with hypercortisolism 2
• New freckles (hyperpigmentation) strongly suggests either ACTH-dependent Cushing's syndrome or Addison's disease, neither of which are related to primary GERD 2

Critical Diagnostic Workup Required

Before treating GERD, obtain:

• 24-hour urinary free cortisol or late-night salivary cortisol to screen for Cushing's syndrome
• 1 mg overnight dexamethasone suppression test as confirmatory testing
• Morning ACTH level if Cushing's is confirmed, to differentiate ACTH-dependent from ACTH-independent causes
• Complete metabolic panel and glucose to assess for diabetes and electrolyte abnormalities associated with hypercortisolism

Management of Secondary GERD

Once endocrine evaluation is underway, the GERD component can be addressed:

• Start omeprazole 20 mg once daily before meals for typical GERD symptoms, as this patient has heartburn/regurgitation 3
• Titrate to twice daily if inadequate response after 4 weeks 4, 5
• Lifestyle modifications: elevate head of bed, avoid meals 2-3 hours before bedtime, weight loss (though this will require treating underlying Cushing's) 1, 6

However, do not rely on PPI response to confirm GERD diagnosis, as symptom improvement may occur through non-acid mechanisms and does not confirm the diagnosis 2, 7, 4

When to Pursue Objective GERD Testing

• If symptoms persist after 8-12 weeks of twice-daily PPI therapy, proceed to upper endoscopy to evaluate for erosive esophagitis or alternative diagnoses 2, 7
• If endoscopy is normal and symptoms continue, perform 96-hour wireless pH monitoring off PPI (after 7-day washout) to objectively confirm pathologic reflux 2, 4
• Do not perform early reflux testing in this case since typical GERD symptoms are present alongside systemic disease 2, 4

Definitive Treatment Depends on Cushing's Etiology

• If pituitary adenoma (Cushing's disease): transsphenoidal surgery is first-line treatment
• If adrenal adenoma: unilateral adrenalectomy
• If ectopic ACTH: resection of ACTH-secreting tumor when possible
• Medical management with ketoconazole, metyrapone, or mifepristone may be needed if surgery is not feasible

The GERD will likely improve significantly once hypercortisolism is corrected, as excess cortisol contributes to increased intra-abdominal pressure and lower esophageal sphincter dysfunction 1

Common Pitfalls to Avoid

• Do not treat this as isolated GERD without investigating the systemic symptoms—missing Cushing's syndrome has significant morbidity and mortality implications 1
• Do not continue long-term PPI without objective confirmation of GERD once the endocrine disorder is treated 7, 4
• Do not assume PPI response confirms GERD as the primary diagnosis when systemic disease is present 2, 7
• Do not delay endocrine workup while empirically treating reflux symptoms—Cushing's syndrome requires prompt diagnosis and treatment to prevent cardiovascular, metabolic, and infectious complications 1