Written by Tristram Lesser
In 1907 Schloffer performed the first trans-sphenoidal removal of a pituitary tumour. To gain access, he split the nose in the midline and then removed the septum and turbinates to expose the sphenoid. His lead was quickly followed by other European surgeons, including Kocher, Hirsch (1911) and Chiari (1911). From 1909 to 1935 Harvey Cushing performed no fewer than 171 of these operations with the amazingly low mortality of 5.3%. In 1935, however, Cushing abandoned the trans-sphenoidal route and Dandy (1936) wrote a very forthright condemnation of the operation. Other neuro-surgeons such as Cairns (1936) and Henderson (1939) advocated its continued use in certain cases.
Nager’s Sermon Lecture in 1939 at the Royal Society of Medicine is a notable landmark in the operation’s history, in that he demonstrated Cushing’s and Dandy’s abandonment of the procedure to have been premature and ill advised. He presented the results of 39 operations, in most of which he was able to improve or preserve the patients eyesight.
After World War II, the discovery of antibiotics, cortisone and the operating microscope gave the operation a new impetus. Hamberger in particular realized the potential of these new weapons and was able to practise complete removal of the gland transantraily for endocrinological indications rather than just for the relief of pressure effects (Hamberger, Semon Lecturer 1960). Bateman (1963) and Angell-James (1967) have made outstanding contributions to the development of the operation.
The various techniques of trans-sphenoidal hypophysectomy developed over the last 70 years:
Transnasal (Schloffer 1907; Kocher 1909; Macbeth 1961)
Sublabial-transseptal (Cushing 1911)
Transseptal (Hirsch 1911; Cushing 1991; Bateman 1967)
Transantral (Hamberger 1960)
Transethmoidal (Chiari 1911; Nagger 1939; Angell-James 1967)
ln Cardiff between 1966 and 1988, 133 pituitary tumours were operated upon by the transethmoidal route for Acromegaly, Cushings disease, prolactinomas and other miscellaneous tumours.
In Acromegaly, the operation was performed where there was progressive clinical disease with a raised growth hormone (GH) level of 20 microml or more which was not suppressed after giving 50 g of oral glucose.
Patients with Cushing’s disease underwent surgery when there was clear cut clinical disease and the endocrinologist was satisfied that the disorder was pituitary in origin.
Operations were indicated for non-secreting tumours when there was clinical and radiological evidence or an expanding pituitary tumour with resectable parasellar extension.
The surgical technique employed in Cardiff is the transethmoidal procedure of Chiari (1911) as described and practised by Angell-James (1967), but with two modifications. First, exposure of the gland is enhanced by incising the dura with alligator scissors and creating dural flaps which are then retracted by means of stay sutures. Secondly, the pharyngeal pituitary is ablated as it is a possible extrasellar source of pituitary hormones. This is situated in the roof of the nasopharynx close to the vomerosphenoidal junction. Removal of this tissue achieved by excising a piece of mucoperiosteum, approximately 2 cm, with long-bladed scalpel. We have a found that this approach allows a wider exposure more than the restricted trans-septal route, and of the hypophysis, and that visual access is further improved by the invariable use of hypotensive anaesthesia. After removal of the ethmoid air cells, the sphenoid sinus is entered and the bone removed from the floor of the sella. After removal of the bone in the floor of the fossa, the dura is incised and the lateral lobes of the adenohypophysis are mobilised to allow comprehensive inspection of the surface of the gland. If the tumour was not readily identifiable on the surface of the gland, multiple incisions were made into the gland. Biopsy specimens of the adenoma were obtained, and if frozen sections confirmed the diagnosis, the part of the gland containing the tumour was removed. If the adenoma was near to the neurohypophysis the adjacent part of the neurohypophysis was excised. Similarly, the dura adjacent to the tumour was removed if possible.
There have been 8 cases of transitory CSF rhinorrhoea and 10 of meningitis but they have not been troublesome features and have resolved rapidly. The space left after excision of the gland was packed with a muscle graft and the dural incision sutured. Antibiotic cover was given during the operation and for seven days postoperatively. All patients (except one who required urgent surgery) underwent full endocrinological assessment prior to surgery using standard tests of hypothalamic-pituitary and target gland function.
One patient had a temporary quadrantic visual defect but this resolved rapidly leaving no permanent disability. Two patients had persistent diabetes insipidus. There were no persistent cerebrospinal fluid leaks and no III, IV or VI nerve palsies.
One postoperative death occurred in the total series of 133 hypophysectomy cases. The patient, a woman, aged 32 years, with gigantism associated with acromegaly, had a large tumour and severe hypertension. She died 72 hours after operation from a subarachnoid haemorrhage confirmed at autopsy.
Acromegaly: In 2 patients out of the total, post-operative clinical assessment was not possible — one being the patient who died in the immediate post-operative period and another patient died of carcinoma of the bladder two months after operation. A third patient was found to have an invasive tumour and removal was not possible due to extensive scar tissue formation from previous yttrium and gold implants. All remaining patients had excellent sustained clinical remission of disease. The GH estimations were carried out and pre- and post-operative levels were measured by the same laboratory. The patients in the series have now been followed up for five years or more and it is of interest that the values remain well down, and for the most part are still below the upper limit of normal.
Cushing’s disease: Out of 28 cases of Cushing’s disease, 24 had a complete clinical remission which has been sustained up to the present time. Prolactinomas and stalk compression adenomas were clearly identified in 33 patients, but in two cases no lesion was found and further surgery was abandoned. Altogether, 13 patients had microadenomas (<10 mm) and 20 had macroadenomas (10 mm). 19 had presented with galactorrhoea, three with decreased libido, three with headache, and one with a visual field defect; these symptoms were all alleviated by surgery. All of the 20 women in this group who had complained of amenorrhoea achieved regular menses, and ovulatory cycles were restored biochemically in at least 13 of them; most importantly, nine normal pregnancies occurred in seven women, including four who had previously complained of infertility.
35 clinically non-secretory pituitary adenomas treated surgically by the trans-ethmoidal approach:
Most patients had symptoms and signs of either hypopituitarisim or visual disturbance. Five patients presented initially with the clinical picture of hypothyroidism, and investigations subsequently showed a pituitary origin. Three patients presented with extreme prostration due to hypoadrenalism; one other had an acute Addisonian crisis associated with the sudden onset of headache, vomiting and diplopia, ie pituitary apoplexy (infarction of the gland was confirmed on histology). One patient was found incidentally to have an enlarged pituitary fossa, which was seen on a radiograph taken for cervical spondylosis. These tumours present later than hormone secreting tumours: 90% were over 2 cm in diameter at operation. 71% of patients had impaired vision and 89% had hypopituitarism. Surgical treatment relieved or significantly improved visual fields in 79% of patients with impaired vision. 91% required permanent hormone replacement.
Ten patients were electively treated with a radical course of postoperative radiotherapy after primary trans-sphenoidal surgery. The indications were either doubt about the completeness of excision and/or an aggressive histological picture. This approach to the sella was also found to be a very practical method of getting biopsy material in one patient with a primary squamous cell carcinoma and in patients with metastatic deposits in the pituitary region.
We have found that very close supervision by both surgeon and endocrinologist are necessary for many months after surgery, and have established a monthly joint clinic for pre- and post-operative assessment of patients. This has proved to be of great benefit to all concerned, and we would recommend its adoption by those who undertake this work.
Transethmoidal microsurgery for pituitary tumours is a relatively safe procedure, and there is much room for improvement in the technique of this operation, such as the development of small needle holders, clip applicators, and micro coagulators. Pituitary tumours are so slow-growing that we must think in terms of ten to fifteen years follow up before true assessment can be made. Finally, the potential for partial and selective removal has been explored, with the more detailed knowledge of the endocrine function and malfunction of various parts of the gland.