From the Guidelines
A liver granuloma can potentially be a source of ectopic Adrenocorticotropic Hormone (ACTH) production, even when MRI of the pituitary and adrenal CT scans are normal, and a normal Dexamethasone Suppression Test (DST) result does not rule out this possibility. In a 33-year-old female with suspected Cushing's syndrome, this presents a diagnostic challenge. Ectopic ACTH syndrome accounts for approximately 10-20% of ACTH-dependent Cushing's syndrome cases, and while bronchial carcinoids and small cell lung cancers are the most common sources, hepatic neuroendocrine tumors or granulomas can occasionally produce ACTH 1.
Key Considerations
- The normal DST result is unusual for ectopic ACTH production, which typically shows resistance to dexamethasone suppression, suggesting either a false-negative test result or an atypical presentation.
- Further evaluation should include bilateral inferior petrosal sinus sampling (BIPSS) to definitively distinguish between pituitary and ectopic sources of ACTH, as it is considered the gold standard to reliably exclude ectopic ACTH production 1.
- Additional imaging such as a whole-body CT, MRI with contrast of the liver, or nuclear medicine studies like somatostatin receptor scintigraphy (Octreoscan) or gallium-68 DOTATATE PET/CT may be necessary to locate the ectopic source, with 68Ga-DOTATATE PET/CT being particularly useful in guiding clinical management 1.
- Liver biopsy of the granuloma would be required for definitive diagnosis, with immunohistochemical staining for ACTH.
Diagnostic Approach
- A combination of three or four tests, specifically CRH and desmopressin stimulation plus MRI, followed by whole-body CT if diagnosis is equivocal, may correctly diagnose Cushing's disease in approximately half of patients, potentially eliminating the need for IPSS 1.
- A positive CT scan despite negative CRH/desmopressin stimulation and MRI had a negative predictive value of 100%, suggesting that a non-invasive approach using a combination of laboratory and imaging testing may be useful in distinguishing between pituitary and ectopic ACTH-secreting tumors 1.
From the Research
Ectopic Adrenocorticotropic Hormone (ACTH) Production
- Ectopic ACTH production is a rare clinical condition resulting from dysregulated ACTH secretion by neuroendocrine tumors 2.
- The overall incidence of endogenous Cushing's syndrome is 0.7-2.4 per million people annually, with children accounting for only 10% of new cases each year 2.
Liver Granuloma as a Source of Ectopic ACTH Production
- There is no direct evidence in the provided studies to suggest that a liver granuloma can be a source of ectopic ACTH production.
- However, ectopic Cushing's syndrome can be caused by various neuroendocrine tumors, and the diagnosis can be challenging due to the heterogeneity of the condition 2.
Diagnostic Challenges
- Normal pituitary Magnetic Resonance Imaging (MRI) and adrenal Computed Tomography (CT) scan do not exclude Cushing's syndrome 3.
- A normal Dexamethasone Suppression Test (DST) may not rule out ectopic ACTH production, as some cases may have intermittent or cyclic hypercortisolism 2.
Treatment Options
- Medical therapy, including steroidogenesis inhibitors such as ketoconazole, metyrapone, and etomidate, can be effective in managing hypercortisolism in patients with Cushing's syndrome 4, 5, 6.
- However, the treatment of ectopic ACTH-producing tumors often requires surgical intervention, and the choice of treatment depends on the underlying cause and severity of the condition 2, 4.