From the Guidelines
Pituitary adenoma Cushing syndrome is best treated with selective adenomectomy as the first-line treatment of choice, as it offers the highest potential for normal pituitary tissue to remain in situ and minimizes the risk of post-operative hypopituitarism. This approach is supported by a strong recommendation with moderate-quality evidence from the 2024 consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence 1. The optimal treatment involves surgical resection by selective removal of the adenoma, performed by a surgeon experienced in pediatric transsphenoidal surgery.
Key considerations for treatment include:
- Selective removal of the adenoma to maximize the potential for normal pituitary tissue to remain in situ 1
- Low rates of post-operative hypopituitarism have been reported in several large studies in children with Cushing's disease 1
- Early post-operative remission is associated with identification of the adenoma at surgery, whilst long-term remission correlates with a younger age, a smaller adenoma, and the absence of cavernous sinus or dural invasion 1
- Repeat surgery for pediatric Cushing disease resulted in early biochemical remission in 93% of 27 patients, highlighting the importance of considering repeat surgery for persistent or recurrent disease 1
Lifelong follow-up is essential for children treated for Cushing disease, as recurrence can occur up to 15 years after apparent surgical cure, even in individuals with very low or undetectable post-operative cortisol levels 1. Regular cortisol testing and temporary glucocorticoid replacement after successful surgery until the hypothalamic-pituitary-adrenal axis recovers are crucial components of post-operative care.
From the Research
Pituitary Adenoma and Cushing Syndrome
- Cushing's disease (CD) is caused by a corticotroph, adrenocorticotropic-hormone (ACTH)-secreting pituitary adenoma, resulting in significant morbidity and mortality 2.
- Transsphenoidal surgery is the initial treatment of choice in almost all cases, with remission rates for microadenomas ranging from 65-90% and lower rates for macroadenomas 2, 3.
Treatment Options
- Medical treatment can temporarily suppress excessive cortisol production and ameliorate its clinical manifestations while more definitive therapy becomes effective 4.
- Drugs used to suppress cortisol secretion are mostly inhibitors of steroidogenesis, including ketoconazole, fluconazole, aminoglutethimide, metyrapone, mitotane, and etomidate 4, 5.
- Pituitary-directed therapy with new multireceptor ligand somatostatin analogs (e.g., pasireotide) and second-generation dopamine agonists are also being explored as treatment options 2.
Surgical Outcomes
- Early, post-operative remission rates >80% are expected for patients with a microadenoma (≤ 10 mm) visible on magnetic resonance (MR) imaging 3.
- Macroadenoma and tumor invasion beyond the pituitary and sella are associated with failure to obtain remission with the initial transsphenoidal surgery and greater likelihood of late recurrence 3.
- A team-based approach, in a specialized pituitary center, can lead to initial and durable, long-term remission in patients with CD 3.
Diagnostic Evaluation
- The diagnostic algorithm employed in the patient with suspected CD is complex and includes consideration for inferior petrosal sinus sampling (IPSS) 6.
- IPSS can confirm central origin of hypercortisolemia and indicate the side of the pituitary adenoma 6.
- Endoscopic endonasal approach for extracapsular resection of the ACTH-secreting pituitary adenoma is the preferred operative strategy 6.