What is the next step for a 25-year-old female with elevated Adrenocorticotropic Hormone (ACTH) and cortisol levels, a suppressed Dexamethasone Suppression Test (DST) result, normal Corticotropin-Releasing Hormone (CRH) Stimulation test and 24-hour urine cortisol, a newly diagnosed 3mm pituitary adenoma, and symptoms of Cushing's syndrome?

From the Guidelines

The next step for this patient should be transsphenoidal surgery to remove the pituitary adenoma, as optimal treatment for Cushing's disease is surgical resection by selective removal of the adenoma, performed by a surgeon experienced in transsphenoidal surgery. Despite the patient's age and the presence of conflicting laboratory results, the diagnosis of Cushing's disease is suggested by the elevated ACTH and cortisol levels, and the presence of a pituitary adenoma on imaging. According to the consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence, selective adenomectomy is the first-line treatment of choice for Cushing's disease 1.

The patient's symptoms, such as cushingoid features, also support the diagnosis of Cushing's disease. While medical therapies, such as metyrapone or ketoconazole, can be used to reduce the cortisol burden in patients with Cushing's disease awaiting definitive surgery or the effect of pituitary radiotherapy 1, they are not recommended as a long-term treatment option due to their adverse effects.

The benefits of surgical removal of the adenoma, including the potential for normal pituitary tissue to remain in situ and low rates of post-operative hypopituitarism, outweigh the risks of the procedure 1. It is essential to perform the surgery at a center experienced in transsphenoidal surgery to minimize the risk of complications.

Key considerations for the patient's treatment plan include:

• The patient's age and the potential impact of Cushing's disease on growth and development
• The presence of a pituitary adenoma and the need for selective adenomectomy
• The potential benefits and risks of surgical removal of the adenoma
• The importance of lifelong follow-up for patients treated for Cushing's disease to monitor for recurrence or other complications.

From the FDA Drug Label

INDICATIONS AND USAGE SIGNIFOR is a somatostatin analog indicated for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative (1)

The patient has a newly diagnosed pituitary 3mm adenoma and Cushing's symptoms, but the DST of 0.6 suggests that the patient may not have Cushing's disease that is responsive to somatostatin analogs like pasireotide.

• The normal STIM test and 24 hour urine cortisol also do not provide clear evidence for the use of pasireotide.
• The patient's ACTH and cortisol levels are elevated, but the diagnosis of Cushing's disease is not clearly established. Given the lack of clear evidence for Cushing's disease, the next step would be to further evaluate the patient's condition, rather than initiating treatment with pasireotide 2.

From the Research

Next Steps for a 25-Year-Old Female with a Pituitary Adenoma

Given the patient's newly diagnosed 3mm pituitary adenoma, Cushing's symptoms, and laboratory results (ACTH of 66, cortisol of 33.1, DST of 0.6, normal STIM test, and 24-hour urine cortisol), the next steps should focus on managing the adenoma and assessing the hypothalamic-pituitary-adrenal (HPA) axis function.

• Surgical Intervention: Transsphenoidal surgery is often the preferred approach for pituitary adenomas 3. The goal is to remove the tumor while preserving pituitary function.
• Glucocorticoid Replacement Therapy: The patient's preoperative adrenal status and the potential impact of surgery on the HPA axis should be considered. Studies suggest that peri-operative glucocorticoid replacement therapy may be necessary, especially if there's evidence of impaired HPA function 4.
• Postoperative Assessment: Early morning cortisol levels can be used to predict short-term and long-term adrenal function after surgery 5, 6. However, the reliability of these measurements can vary, and follow-up testing is crucial to assess the need for ongoing glucocorticoid replacement.
• Monitoring for Adrenal Insufficiency: Given the risk of adrenal insufficiency post-surgery, close monitoring of the patient's clinical and biochemical status is essential. This includes regular assessments of cortisol levels and clinical evaluation for signs of adrenal insufficiency 7, 4.

Considerations for Management

• The size of the adenoma (3mm) and the patient's symptoms suggest the need for a thorough evaluation of the HPA axis function before and after surgery.
• The use of a standardized protocol for glucocorticoid replacement, based on postoperative cortisol levels, can help minimize unnecessary steroid exposure while ensuring patient safety 6.
• Long-term follow-up is necessary to assess the patient's adrenal function and adjust treatment as needed, considering the potential for delayed adrenal insufficiency 5.