Pituitary Surgery for Cushings Disease

In this article, the present status of neurosurgical operations for Cushing’s disease is briefly reviewed. Transsphenoidal surgery is considered the treatment of choice in most patients with Cushing’s disease once the diagnosis has been established. In a considerable proportion of patients, even sophisticated imaging does not directly depict the tiny micro adenoma. The search for the tumor is technically difficult, particularly when the sella turcica is small, the dura vascularized and the sphenoid sinus poorly pneumatized. Thus, even in expert hands, microadenomas cannot always be identified intraoperatively. Usually, a selective adenomectomy is attempted, preserving pituitary functions. There is a huge variation of surgical outcomes reported. As an estimate, a remission rate of some 75% can be expected 5 years after surgery. Almost all data available to date derive from microsurgical operations. Unfortunately, even in patients who initially remit, recurrences may occur. Low postoperative serum cortisol levels and a long-lasting adrenocortical insufficiency seem to be factors associated with a favorable long-term outcome. When no distinct microadenoma can be identified intraoperatively, partial or even total hypophysectomy has been suggested. However, the outcome of these procedures is less favorable than with selective resecPublished online: September 10, 2010 Michael Buchfelder Department of Neurosurgery, University of Erlangen-Nürnberg Schwabachanlage 6, DE–91054 Erlangen (Germany) Tel. +49 9131 853 4566, Fax +49 9131 853 447 E-Mail michael.buchfelder @ uk-erlangen.de © 2010 S. Karger AG, Basel 0028–3835/10/0925–0102$26.00/0 Accessible online at: www.karger.com/nen D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /2 2/ 20 17 7 :1 2: 55 P M Pituitary Surgery for Cushing’s Disease Neuroendocrinology 2010;92(suppl 1):102–106 103 tumors escape radiological detection because of their minute size. The aim of this article is to briefly review the present status of neurosurgical operations for Cushing’s disease. The authors used selected pertinent literature which they comment with some personal bias which results from their own experience. Indications for Surgery When the diagnosis of ACTH-dependent hypercortisolism is established, one assumes that an ACTH-secreting pituitary adenoma is the source of hypercortisolism. Ideally, a visible lesion in the sellar region is identified. To date, the standard imaging procedure is MR imaging and minimal requirements would be coronal and sagittal T1weighted sections through the sella before and after contrast enhancement [4] . If endocrine tests are not perfectly conclusive, most neurosurgeons, including ourselves, feel more comfortable to attack an inconspicuous pituitary if selective catheterization of the inferior petrosal sinus has unequivocally demonstrated a central-peripheral ACTH gradient [5, 6] . Intensive care facilities should be available for these patients. Operative Techniques There are basically two types of operations available for pituitary adenomas. The most frequently used that is suitable for the majority of patients with Cushing’s disease is the transsphenoidal (transnasal) route. Only exceptionally is a craniotomy (transcranial operation) needed. Transsphenoidal Surgery There are many possible variations starting with positioning of the patient. While some surgeons, like ourselves, prefer to operate on a patient in the supine position [7, 8] with the head slightly extended, others favor a semisitting position [2] . Radiofluoroscopic control is still the most commonly used, but some surgeons prefer to use a navigation system. The operation can be performed with and without dissection of the septal mucosa. Either a sublabial or medial nasal incision may be used. The medial nasal mucosa is detached unilaterally from the cartilaginous and osseous nasal septae, respectively. A nasal speculum is inserted to keep the mucosal tunnel open. Alternatively, a direct endonasal approach to the sphenoid sinus can be chosen. The vomer, which serves as an excellent midline orientation, is exposed and opened with forceps and drill. The septations of the sphenoid sinus are resected. Usually, now the sellar floor is already visualized through the sphenoid sinus. Incomplete pneumatization of the sphenoid requires extensive drilling. Once the sellar floor is resected, the basal dura of the pituitary fossa may be incised and the gland and adenoma visualized. The content of the sella can only be visualized properly via the transsphenoidal approach and then either sectioning of the gland, adenomectomy or a variant of hypophysectomy can be performed. Both the operating microscope and the endoscope allow an adequate visualization of the intrasellar content [7] . Selective Adenomectomy In microadenomas, the tumor is mostly embedded within the pituitary. It can now be selectively released from the normal gland [2] . In larger adenomas, the dural opening allows a soft tumor to protrude through this opening. Currettes and microforceps are used to loosen and resect the tumor. The normal pituitary is identified by its yellowish color, firmer consistency and vascular surface structure. As much of it as possible is preserved. The extent and radicality of tumor resection can be estimated by inspection and palpation of the tumor cavity, visualization of the cavernous sinus bilaterally and, in larger tumors with suprasellar extension, by the arachnoid that descends into the intrasellar space. In small microadenomas which escape radiological detection, the gland must be sectioned multiply in order not to miss the tiny tumor [2, 3, 7] . This is a specific surgical problem encountered in Cushing’s disease. The normal size of the gland, the vascularization of the basal dura and the proximity of the cavernous sinus and carotid arteries make it a technically demanding enterprise. Even with utmost experience and optimal technical equipment there are still large and invasive pituitary adenomas that cannot be resected completely [9] . Very rarely, microadenomas can be found entirely outside of the sella, e.g. within the cavernous sinus. Whether they should be called ‘ectopic’ is a matter of definition [3, 10] . Hypophysectomy The high density of ACTH-secreting pituitary cells in the medial portion of the gland, and his observation that many of these tiny tumours lie in the midline led Hardy [2] to suggest a partial ‘central core’ hypophysectomy in patients in whom he could not identify a distinct microadenoma intraoperatively. With the availability of ACTH gradients from bilateral cavernous sinus catheterization, Oldfield et al. [5] suggested that half of the pituitary is resected at the side with the higher ACTH concentraD ow nl oa de d by : 54 .7 0. 40 .1 1 11 /2 2/ 20 17 7 :1 2: 55 P M Buchfelder/Schlaffer Neuroendocrinology 2010;92(suppl 1):102–106 104 tions, as determined during preoperative petrosal sinus catheterization. Hypophysectomy is an ultimate option and means that one attempts to resect the entire gland [2, 3] . Unfortunately, it is also not possible to cure all patients with Cushing’s disease [9] . Transcranial Surgery The decision to perform transcranial surgery is made more and more restrictively. However, to date a suprasellar tumor that has no or only a minor intrasellar component is still being operated upon using transcranial surgery. Either a pterional or subfrontal approach can be used. The frontolateral or frontotemporal craniotomies are usually preferred. Essentially, brain protection is achieved by a basal bone flap and CSF drainage. The visual pathways and the major arteries of the anterior cerebral circulation are dissected and the tumor is then resected stepwise through corridors either medially between the optic nerves or laterally between the optic nerve and the carotid artery [7] . Perioperative Management Routine prophylaxis with antibiotics is started before the operation. Flitsch et al. [11] have suggested perioperative measurements of ACTH, equating an impressive drop in levels with successful tumor resection. This requires a laboratory within reach of the operating theater or means a prolongation of the operating time. Different regimens of corticosteroid substitution have been proposed [4] . In an earlier publication, we recommended to put the patient on replacement therapy when an adenoma was found and resected intraoperatively [3] . We have now changed to wait and determine cortisol on the first postoperative day [8] . Depending on these cortisol levels, substitution therapy is then initiated, if needed. If early reoperations are considered in the patients without initial remission, an early documentation of remission or persistent disease is required.