Cushing’s disease: pathobiology, diagnosis, and management

J Neurosurg 126:404–417, 2017

Cushing’s disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma. The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol.
The pathophysiological levels of cortisol are associated with hypertension, diabetes, obesity, and early death. Successful resection of the CD-associated ACTH-secreting pituitary adenoma is the treatment of choice and results in immediate biochemical remission with preservation of pituitary function.
Accurate and early identification of CD is critical for effective surgical management and optimal prognosis. The authors review the current pathophysiological principles, diagnostic methods, and management of CD.

Endoscopic radical hypophysectomy

endoscopic-radical-hypophysectomy

Acta Neurochir (2016) 158:2159–2162

Total hypophysectomy it is a classical procedure that currently has many indications especially in patients with Cushing syndrome without good endocrine control. Expanded endonasal endoscopic techniques grant us an alternative standpoint to the classic trans-sphenoidal microscopic approach and a comprehensive assessment of the process

Method The author provides technical nuances and describe step by step the radical endoscopic hypophysectomy. The study of cadaveric specimens adds clarifying dissections.

Conclusions Radical hypophysectomy is an easily replicable and safe procedure. The most important morbidity is the intraoperative cerebrospinal fluid (CSF) leakage, which is inherent to this technique and can be successfully prevented with a pedicled nasoseptal flap reconstruction.

Pure endoscopic transsphenoidal surgery for functional pituitary adenomas: outcomes with Cushing’s disease

Cushing's disease

This study was performed to examine patient outcomes following pure endoscopic transsphenoidal surgery (ETS) for Cushing’s disease (CD).

Method We studied 64 consecutive patients who underwent 69 endoscopic transsphenoidal procedures. Radiological evaluation comprised detailed examination of preoperative magnetic resonance images (MRI), including positron emission tomography (PET) for select cases. Inferior petrosal sinus sampling (IPSS) was not performed for any patient. Remission was defined by the presence of hypocortisolemia with requirement for steroid replacement therapy or eucortisolemia with suppression to <1.8 μg/dl after 1 mg dexamethasone on evaluation at least 3 months after surgery.

Results Preoperative MRI was abnormal in 87.5 % of cases and included 11 macroadenomas (17.2 %). PET was used to localize the adenoma in four cases. For microadenomas, operative procedures executed were as follows: selective adenomectomy (n=15), enlarged adenomectomy (n=21) and subtotal/hemihypophysectomy (n=17). Overall, pathological confirmation of an adenoma was possible in 58 patients (90.6 %). Forty-nine patients (76.6 %) developed hypocortisolemia (<5 μg/dl) in the early postoperative period. Mean follow-up was 20 months (range 6–18 months). Remission was confirmed in 79.7 % of the 59 cases followed up for >3 months and was superior for microadenomas (86.4 %) versus macroadenomas (55.6 %) and equivocal MRI adenomas (66.7 %). Postoperative CSF rhinorrhea occurred in five patients, and new endocrine deficits were noted in 17.1 % patients. A nadir postoperative cortisol <2 μg/dl in the 1st week after surgery was highly predictive of remission (p=0.001).

Conclusion ETS allows for enhanced intrasellar identification of adenomatous tissue, providing remission rates that are comparable to traditional microsurgery for CD. The best predictor of remission remains induction of profound hypocortisolemia in the early postoperative period.

Early promising results for the endoscopic surgical treatment of Cushing’s disease

Endoscopic treatment of Cushing's disease

Neurosurg Rev (2014) 37:105–114

High levels of endogenous cortisol due to Cushing’s disease cause significant mortality and morbidity. Treatment of Cushing’s disease is challenging. For many years, transsphenoidal microsurgical resection of the adenoma has been the treatment of choice. However, recently, neuroendoscope has taken its place in the neurosurgeon’s armamentarium, and the endoscopic transsphenoidal resection of pituitary tumors has become a familiar approach.

Our aim was to present the results of pure endoscopic surgery in the treatment of corticotropinomas for comparison with the results of previous endoscopic and microsurgical series.

We present a retrospective analysis of 90 patients with diagnosis of Cushing’s disease who were operated between 2006 and 2012. Among 90 patients, a total of 81 (90.0%) had a remission (28 out of 29 macroadenomas (96.6 %) and 53 out of 61 microadenoma patients (86.9 %)). Of note is that 66 out of 69 (95.7 %) primary patients (i.e., those who were operated in our center) and 15 out of 21 (71.4 %) patients previously operated in other centers reached a hypo/eucortisolemic state. A remission rate comparable with previous endoscopic series was achieved. In nine patients, it was not possible to achieve remission at all. On the other hand, only four of our cases (5.6%) had a recurrence, andwith reoperation, all of these patients entered a re-remission. To our knowledge, our series is the largest series studying endoscopically operated adrenocorticotropic hormone-secreting adenomas. Our results suggest that the endoscopic approach has opened a new avenue in the treatment of Cushing’s disease, previously a therapeutic challenge for both the clinician and the neurosurgeon.

Endoscopic approach in the treatment of Cushing’s disease is clearly better for patients because of its low morbidity rates and short duration of hospital stay. On the other hand, long-term follow-up of our patients will show whether these favorable observations will persist.