F.H. Doyle

The mediastinum in portal hypertension

Summary The radiological features of the mediastinum in portal hypertension have been analysed. A method of measurement of the diameter of the azygos vein using tomography is described. In thirty-six patients with portal hypertension, the mean diameter of the azygos vein, corrected to a standard patient weight of 140 lb., was 18 mm. (standard deviation 3 mm.). In a group of forty-eight patients without portal hypertension or any lesion known to cause azygos vein enlargement, the mean diameter of the weight standardised azygos vein was 14·2 mm. (standard deviation 2·6 mm.). There was no good correlation between the size of the azygos vein and the extent of the collateral circulation assessed by splenic venography or the size of the oesophageal varices demonstrated by barium swallow. There was no correlation between the clinical features of ascites, encephalopathy or gastro-intestinal bleeding and the size of the azygos vein. The width of the left paravertebral shadow was measured in forty patients with portal hypertension and in fifty-four control subjects. The width of the shadow is increased on the average in patients with portal hypertension, but it is not a reliable indication of the size of the hemiazygos veins. A very wide paravertebral shadow in a patient with fluid retention may be due to mediastinal oedema. Attention is drawn to the occurrence of other abnormal mediastinal shadows in patients with portal hypertension. Recognition of this is important in avoiding diagnostic errors.

Intravenous urography and renal function

Sixty-four intravenous pyelograms using varying doses of diatrizoate have been carried out in 39 patients. The subjects investigated represented a wide range of renal function, and this was studied by measuring the glomerular filtration rate by the clearance of 57 Co. vitamin B12. The fate of the contrast medium was followed by means of radioisotope labelling, and findings in plasma and urine have been related to renal function. It has been confirmed that diatrizoate is excreted by glomerular filtration, and that its concentration in the urine is therefore a function of plasma level, glomerular filtration rate, and urine flow rate. Studies on the mechanism of water handling of individuals given a large solute load were carried out, and we suggest that in patients with adequate renal function there is on average no improvement in urinary contrast concentration with doses larger than 1 ml. Urografin 60%/kg. body weight. The increase in urinary concentration achieved by 1 ml. contrast/kg. over ½ ml. contrast/kg. was not statistically significant; attention is drawn to the great variability in dehydration state in the same individual on different days. In patients with impaired renal function, urinary contrast concentrations sufficient to produce useful urograms may be achieved by using up to 2 ml. Urografin 60%/kg. body weight.

Serum growth hormone levels and size of pituitary tumour in untreated acromegaly

Serum levels of growth hormone were measured in 84 untreated acromegalic patients. The range of mean level during a glucose tolerance test was 8 to 1,860 ng./ml. and was lognormally distributed. Mean level was reproducible and correlated moderately well with maximum sellar area on lateral tomography. The hormone level was more responsive to oral glucose and insulin-induced hypoglycaemia in patients with smaller tumours. Attention is drawn to limitations of plain radiographs in assessing the size of a pituitary tumour. Suprasellar tumour extensions may be present in patients without visual field defects.

TREATMENT OF CUSHING'S DISEASE IN JUVENILES WITH INTERSTITIAL PITUITARY IRRADIATION

Nine juvenile patients (five boys and four girls aged 10–18) with Cushings disease were treated with pituitary implantation of 198 Au and/or 90Y. No patient had any surgical complication from the procedure. At the latest assessment, 3 months to 17 years after operation, Cushings disease was in remission in all the patients; the response time following operation was a few days to 3 months. Radiology of the pituitary fossa at time of pituitary implantation was normal in all patients and remains so. The final height in six patients is 149–172 cm (59–67.5 inches) and three patients who continue to grow have increased by 13, 6 and 3 cm since implantation. Only one patient required full pituitary hormone replacement therapy, and he had been previously treated by external irradiation, and one other patient failed to complete puberty. In all the other seven sexual maturation is normal and one has fathered two children. We conclude that pituitary implantation with interstitial irradiation is a satisfactory form of treatment for Cushings disease in juveniles.

GALACTORRHOEA, HYPERPROLACTINAEMIA AND PITUITARY TUMOURS IN THE FEMALE

A series of sixty‐two women with pituitary tumours, but having neither acromegaly nor Cushings disease, has been analysed with respect to mode of presentation. Thirty‐six (58%) presented with amenorrhoea and galactorrhoea and a further fifteen (24%) presented with amenorrhoea only. Pretreatment prolactin levels were available in thirty‐four of these patients and in twenty‐seven (79%) hyperprolactinaemia was found, this occurring in the absence of a history of galactorrhoea in four out of ten cases.

Treatment of Nelson's syndrome by pituitary implantation of yttrium-90 or gold-198.

Eight patients with Nelsons syndrome were treated with a pituitary implant of yttrium-90 or gold-198 four to 16 years after adrenal surgery. All had considerable pigmentation. One already had cranial nerve abnormalities and visual field defects and had had both a craniotomy and deep x-ray treatment. Radiographs showed that the pituitary fossa was abnormal in seven patients. A biopsy performed in six cases showed mucoid (or basophil) adenoma in all. In the four specimens examined ACTH was identified by electron microscopy or immunofluorescence, or both. Patients were followed up after pituitary implantation for three months to 12 years. All showed decreased pigmentation, and six became normal. Four patients regained normal ACTH levels and the other two studied had decreased levels. In no case did new cranial nerve disease or further sellar expansion develop since operation, and two patients showed remodelling of the sella. Complications were temporary leakage of cerebrospinal fluid and diabetes insipidus in one patient and gonadotrophin deficiency in another.

Successful treatment of Cushing's disease using yttrium-90 rods

Interstitial irradiation using yttrium-90 (90Y) rods implanted by needle into the pituitary gland was used as primary treatment in 16 patients with pituitary dependent Cushings disease. Clinical and biochemical remission was observed within three or six months in 13 and in the remaining three after a supplementary implant. There was no perioperative morbidity. Follow-up from the time of definitive operation ranged from six to 123 months (mean 39). No recurrence has been observed. The return of a normal diurnal cortisol rhythm has been observed in 10/12 patients studied after remission. Some form of long-term pituitary hormone replacement therapy was required in only the six patients who had received the largest irradiation dose. Implantation of 90Y is safe and effective treatment for patients with Cushings disease, comparing favourably with selective trans-sphenoidal pituitary surgery.

THE EFFECT OF YTTRIUM-90 IMPLANTATION ON ENDOCRINE FUNCTION AND VISUAL FIELDS IN PATIENTS WITH ‘FUNCTIONLESS’ PITUITARY TUMOURS, WITH BIOPSY AND RADIOLOGICAL FINDINGS

Thirty patients with symptoms from ‘functionless’ * pituitary tumours were treated by yttrium‐90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62.5%, and reduced in 12.5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre‐implant.

Pituitary ablation by yttrium-90 implantation: Some post mortem and clinical observations

Abstract The pituitary gland was examined at autopsy from 21 patients who had had 90 Y implantation, 20 with the aim of total pituitary ablation. By placing coronal histological sections on a millimetre-squared grid, areas of necrotic, damaged and normal pituitary tissue were measured and the volume and proportion of necrosis produced by a known radiation dose were calculated. A method for measuring the distance from the yttrium rod to a point of radiation damage was also developed, utilizing the same measuring grid and correcting for obliquity of yttrium rods in relation to the section by a mathematical method based on measurements of radiographs of the sphenoid bone with the pituitary in situ . An average of 90 per cent necrosis resulted from the 300 krad dose plan (range 70–100%). About 90% necrosis was required to effect a subnormal 48 h neck uptake of 131 I. The mean threshold radiation dose for pituitary necrosis was 184 (range 85–346) krad. Similar thresholds were found for the cells in bone and for smooth muscle of the carotid artery; no structural defects had occurred in bone or artery.

Sellar reconstitution and serum levels of growth hormone in acromegaly before and after pituitary implant.

Radiographs of the pituitary fossa of 35 acromegalic patients have been studied for evidence of sellar reconstitution after treatment by pituitary implant. Partial reconstitution of the sella was demonstrated in 20% of patients. The mean lateral area of fossae which showed reconstitution was similar to that of fossae whic hwere unchanged. Patients in whom sellar reconstitution occurred had significantly higher serum levels of growth hormone before treatment, and significantly greater reduction in growth hormone as a result of implant. It is postulated that these patients had more active, cellular pituitary tumours which responded more completely to irradiation than those patients whose sellae showed no change after implantation.