From the Guidelines
A referral to neurosurgery is strongly recommended for this patient despite normal dexamethasone suppression test (DST) and saliva cortisol results, as the clinical presentation and presence of a pituitary microadenoma suggest Cushing's disease, which is best treated surgically. The combination of elevated adrenocorticotropic hormone (ACTH) and cortisol levels, weight gain, poor response to metformin, and classic Cushing's syndrome features like purple striae strongly suggests ACTH-dependent hypercortisolism. Normal screening tests don't completely rule out Cushing's syndrome, as these tests can sometimes yield false-negative results, especially in mild or cyclic cases.
Key Considerations
- The presence of a 4mm pituitary microadenoma is a significant finding, as it could represent a corticotroph adenoma causing Cushing's disease, which is best treated surgically through transsphenoidal resection 1.
- The optimal treatment for Cushing's disease is surgical resection by selective removal of the adenoma, performed by a surgeon experienced in transsphenoidal surgery, as it maximizes the potential for normal pituitary tissue to remain in situ 1.
- Early intervention is crucial, as untreated hypercortisolism can lead to serious complications, including diabetes, hypertension, osteoporosis, and increased cardiovascular risk.
Next Steps
- A neurosurgical consultation would allow for proper evaluation of surgical candidacy and discussion of potential benefits versus risks.
- Additional specialized testing might be recommended by the neurosurgeon or endocrinologist, such as bilateral inferior petrosal sinus sampling to confirm the pituitary as the source of excess ACTH.
- The patient should be informed about the importance of lifelong follow-up after treatment, as recurrence of Cushing's disease can occur even after apparent surgical cure 1.
From the Research
Diagnosis and Treatment of Cushing's Syndrome
The patient's symptoms, including hypercortisolism, Cushingoid features, and a 4mm pituitary microadenoma, suggest Cushing's disease (CD) 2. However, the normal dexamethasone suppression test (DST) and saliva cortisol test results may indicate that the patient does not have overt hypercortisolism.
Referral to Neurosurgery
Despite the normal test results, the patient's symptoms and pituitary microadenoma suggest that CD is still a possible diagnosis. According to the study by 2, transsphenoidal surgery is the recognized first-line treatment of CD. The study by 3 also suggests that the initial therapy of choice for patients with CD is the selective transsphenoidal removal of the corticotroph adenoma.
Considerations for Referral
The following points should be considered when deciding whether to refer the patient to neurosurgery:
- The patient's symptoms, including weight gain, poor response to metformin, and purple striae, are consistent with Cushing's syndrome 2, 3.
- The presence of a 4mm pituitary microadenoma suggests that the patient may have a pituitary source of ACTH production 2, 3.
- The normal DST and saliva cortisol test results do not necessarily rule out CD, as the disease can be cyclic or episodic 4, 5.
- The patient may benefit from further evaluation, including MRI scan of the pituitary and CRH test, to confirm the diagnosis and determine the best course of treatment 2, 3.
Medical Therapies
If the patient is not a candidate for surgery or if surgery is unsuccessful, medical therapies may be considered. The following adrenally directed medical therapies are available:
- Ketoconazole
- Metyrapone
- Osilodrostat
- Mitotane
- Etomidate 6 These medications can inhibit adrenal steroidogenesis and reduce cortisol production. However, they require careful dose titration and patient monitoring to ensure safety and effectiveness.