Cushing's disease. Treatment by pituitary implantation of radioactive gold or yttrium seeds.
Fifty-seven patients with Cushing's disease (pituitary-dependent Cushing's syndrome), and four with Nelson's syndrome following adrenalectomy, have been treated by implantation of 198Au or 90Y seeds into the pituitary gland. Fifty-five of the Cushing's disease patients have been fully followed up with steroid tests for 1½ to 12 years after implant. They have been categorized according to the X-ray appearance of the fossa before implant, which was the most important factor in predicting the outcome. The results were as follows:

1. Cushing's disease without evidence of pituitary tumour on X-ray (31 patients). One year after implant, 65 per cent of these patients were in complete remission and a further 16 per cent in partial remission—a total of 81 per cent improved, without any other treatment. Only 34 per cent required replacement corticosteroids, and 30 per cent replacement thyroxine. 52 per cent needed no replacement hormone treatment. Only one patient had relapsed more than 2 years after implant.

2. Cushing's disease with possible pituitary tumour on X-ray (10 patients). One year after implant, five of these were in complete and one in partial remission. These remissions were maintained. 60 per cent required replacement steroids or thyroxine.

3. Cushing's disease with definite X-ray evidence of pituitary tumour (14 cases). In only two of these was permanent remission obtained by implant alone, despite the use of higher radiation doses in most of them. In four the tumour showed X-ray or clinical evidence of local invasion after implant, and three subsequently needed surgical hypophysectomy. A combination of implant, adrenalectomy, hypophysectomy, or external irradiation was needed to control the disease in most of these patients; 10 required surgery of pituitary or adrenals. Some degree of hypopituitarism occurred in them all and 64 per cent required replacement hormones as a result of pituitary or adrenal ablation.

In the whole series of 61 patients implanted for either Cushing's or Nelson's syndrome, there were six who developed serious problems from local invasion by pituitary tumours despite various forms of treatment of the pituitary. This invasion contributed to the deaths of four.

4. In all four cases of Nelson's syndrome, clinical remission of pigmentation was evident within a year of implant. One patient later required external pituitary irradiation and craniotomy to control his pituitary tumour, but survived 13 years. The others have been followed for three, four, and nine years without recurrence.

5. Pituitary implant for Cushing's disease appears to be at least as effective in producing remission as other treatments directed at the pituitary, and is as effective in restraining growth of pituitary tumours. It is much more effective than external irradiation. Though the cure of the Cushing's syndrome is not as certain as with adrenalectomy, the proportion of patients requiring replacement hormone therapy is approximately half, and the procedure of implant is a smaller surgical undertaking. The technical complications of implants, particularly cerebrospinal fluid rhinorrhoea, are minimal (5 per cent) and readily treatable.