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5.2 Surgery

Surgical technique is the subject of a separate chapter to which the reader can refer to.

Prolactinoma

Because medical treatment is cytostatic, for cases of microadenomas or well circumscribed small macroadenomas, surgery may be proposed as an alternative treatment because it is curative and avoiding possible side effects or the uncertainty of a long-term treatment .
In these specific forms, cure rates are about 90% for a low operative risk particularly anterior pituitary insufficiency (below 5%) 71. The few cases of resistance to medical treatment (5-10%)78 and GH-PRL microadenomas are also indicated for surgery. Surgery for micro-prolactinomas is delicate, requiring good pituitary surgical experience, like in Cushing’s disease.

For other macroadenomas, indications for surgery include : resistance to medical treatment observed in less than 10% of cases (tumor debulking restore sensitivity of dopamine agonists in the vast majority of cases59) and pituitary apoplexy (hemorrhagic softens tumor) with visual impairment. Sometimes the tumor destroys the osteodural membranes and resulting in a CSF fistula. Surgery for repair or better preventive surgery can be discussed, but in practice, this is rare. In cases of invasive tumors, the management of this risk of fistula can be made using a lower dose and leaving a non-compressive residual tumor, sealing the sella turcica.

Somatotropic Adenoma
Therapeutically, because of the morbidity and mortality associated with hypersecretion of GH, any acromegaly needs to be treated (management algorithm is summarized in Figure 4).

Surgery is discussed as the first line of treatment, as it is the only treatment that can cure the patient quickly and the decision will depend on the degree of cavernous sinus invasion. In the absence of cavernous sinus invasion surgery remains the "gold standard". If there is a doubt about the invasion, surgery should be proposed to the patient with the possibility of failure explained. Surgery is indicated when there are visual disturbances even with invasion of the cavernous sinus because medical therapies are long acting and reduction of tumor volume is less evident than that of prolactinomas treated with dopamine agonist. If obvious cavernous sinus invasion, the therapeutic attitude will depend on the tumor volume. If the tumor is of large volume (2-3 cm), it will be difficult to quickly control GH hypersecretion with medical treatment alone. Under these conditions a first volumetric reduction will be discussed because preoperative tumor reduction reduces the duration needed to control the disease.
For the surgeon, special attention will be paid to the course of the carotid arteries (C5 paraclinoid part) which tend to approach the midline ("Kissing arteries") resulting in additional vascular risk 27. Nasal anatomy is also important with hypertrophied and rigid structures. Resection of the middle turbinate may be required for « easier passage » and also to improve on the permeability of the nasal cavity and respiratory comfort in acromegaly patients.
The results of surgery inversely correlate with preoperative levels of GH, the tumor volume, cavernous sinus invasion and experience of the surgeon 7. Postoperative cure rates are around 80% for micro- or intrasellar macroadenomas, but drops to 40-50% for macroadenomas with intra and extrasellar extension 10.
The preoperative medical treatment can improve anesthesiologic conditions (difficult intubation, heart failure), but controversy remains about its utility to optimize the surgical cure rate57.

Corticotropic Adenoma

Therapeutically, the goal is to suppress corticotropic hypersecretion, even at the expense of an anterior pituitary insufficiency and treat complications.
Surgery is the first line treatment. Surgery should be performed by a neurosurgeon specialized in pituitary surgery and consist of an extended adenomectomy or hemi-hypophysectomy. To do this, the surgeon should excise the tumor and a juxtatumoral area of the anterior pituitary to ensure complete resection. This is the most demanding pituitary surgery that requires much experience. In almost one third of cases, the surgeon will operate without the tumor visible on preoperative MRI images68. A frozen section performed by an experienced pituitary pathologist can help the surgeon in resecting the tumor.
The best postoperative criterion for cure is corticotropic inertia that can last for several months or a year after surgery. Infact, after tumor removal, normal anterior pituitary cells which had been suppressed by cortisol hypersecretion remain quiescent for an unpredictatble period of time. Thus therapeutic education is essential, as the patient is in a state of corticotropic insufficiency during this period. Cure rate after transsphenoidal surgery is approximately 75-80% for microadenomas 68.
This postoperative phase is difficult for all patients already used to living in a state of excess cortisol; returning to a normal cortisol level is accompanied by severe asthenia and even depression. It is necessary to take preventive measures such as establishing psychological support and not to resort to higher doses of hydrocortisone.

Thyrotropic Adenoma

Controversy remains but schematically intra sellar forms without cavernous sinus invasion or forms with visual affection are surgical whereas other indications are debatable 76.

Non-secreting or nonfunctioning pituitary adenomas (gonadotrophin and "silent")

Therapeutically, there is no effective medical treatment. Surgical indication is unquestionable in the presence of visual disturbances which improve in 90% of the cases except atrophy consistent with a normal personal and professional life 50. Partial hypopituitarism is recovered in about 25% with a morbidity of about 15 % (13% of anterior pituitary insufficiency and less than 10% of diabetes insipidus) 50.
The indication of surgery is debatable in the presence of endocrine deficits without visual disturbances or in cases of incidentalomas (incidental finding): If the adenoma compromises the optic pathway, surgery is proposed to the patients but if there is no compromise, a control MRI at 6 months and annually is recommended to monitor tumor evolution and visual function. The decision is shared with the patient, keeping in mind that better results (from our experience) are obtained with early intervenetion especially in the absence of visual complications in patients with good preoperative functional status 51.
In case of residual tumor (20 to 30% of postoperative residual tumor) 50 or postoperative recurrence, the decision about the complementary treatment discussed during the Pituitary Multidisciplinary Meeting will be based on :

• Anatomical Criteria: volume and location of the residue. A persistent risk to the visual pathways, a significant volume or high expectations of a complete excision should allow for discussion on the possibility of reoperation via transcranial or transphenoidal route.
• Histological Criteria. If the adenoma is "atypical" or grade 2b according to recent classifications, complementary treatment will be discussed, especially if the patient is young.
• Age and the clinical setting. Certainly in young patients where the objective is the control of the residual tumor over decades, the tendency is to be more "aggressive" than in the elderly. Nevertheless it is certainly not appropriate to "rush" towards a decision for radiotherapy, particularly in the case of intra-cavernous residues. Infact many residual tumors remain stable or only increase after 4-5 years.

Pituitary carcinoma and Atypical Adenomas
The indications for repeated interventions be it at the site of the primary tumor or on the metastases are discussed on a case by case basis by the members of Pituitary Multidisciplinary Meeting.

Pituitary Apoplexy
The treatment of pituitary apoplexy remains controversial and was the subject of a consensus meeting by the English society of Endocrinology60. Referral to a pituitary reference center is the rule. The controversy concerns the question "indication for surgery or conservative treatment" because literature is confusing without a randomized study.
Schematically, the following will be considered for surgery via transphenoidal route :
On an Emergency basis : a patient with severe visual impairment (VA, VF) or disturbance of conscious level (hypothalamic compression or hydrocephalus), but the procedure can be delayed a few hours because it should be done by a experienced neurosurgeon.
In a semi-emergency setting, the patient with significant problems (VA, VF), and patients who are aggravating or remain stable after declining for a few days (maximum of eight days). Surgery can be discussed when faced with persistent and severe headache resistant to medical treatment. The analgesic effect of surgery is usually spectacular.
Oculomotor palsies are not indications for surgery in the absence of problems with the visual field or acuity

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