The objective of this study was to present the long-term results of total adrenalectomy for Cushing's disease. Forty-four patients undergoing total adrenalectomy for Cushing's disease between 1953 and 1989 at Leiden University Medical Center, The Netherlands, were studied retrospectively. Remission was achieved in 42 patients (95%), with a mean duration of 19 years. Adrenal remnants were observed in 12 patients (27%), and were without clinical consequence in the majority of patients, but caused early recurrent disease in 2 patients. Nine patients (20%) experienced Addisonian crises up to 30 years following treatment. Nelson's syndrome developed in 10 patients (23%) 7-24 years following total adrenalectomy. Prior pituitary irradiation was a protective factor against Nelson's syndrome as it delayed its onset (p = 0.025). On the other hand, subnormal dose or noncontinuous glucocorticoid replacement therapy was associated with increased risk of development of Nelson's syndrome (p = 0.047). The incidence of Nelson's syndrome increased with prolonged follow-up, and female patients seemed to be at increased risk. Quality-of-life assessment showed less favorable scores on mental health and health perception scales, for which no explanation can be found except the long-lasting metabolic effects of Cushing's disease, even when successfully treated. In conclusion, total adrenalectomy remains the final treatment for Cushing's disease. The presence of adrenal remnants which can cause recurrent disease and the development of Nelson's syndrome during prolonged follow-up enhance the need for continued regular follow-up. Pituitary irradiation prior to total adrenalectomy delays the onset of Nelson's syndrome.

Plasma levels of o,p'-DDD were measured after ingestion of a single oral dose. At the onset of therapy o,p'-DDD was administered as commercially available tablets and granules and in milk, chocolate, and an oil emulsion to 9, 12, 14, 10, and 6 patients, respectively. Following administration in chocolate, emulsion, and milk significantly higher mean plasma levels were recorded in the first 5- and 10-h periods than after tablets. Granules gave significantly lower plasma levels than all other forms. Plasma levels were also measured during maintenance therapy, when a total of 200 g o,p'-DDD was administered to 22 patients with adrenocortical carcinoma. The plasma disappearance rate after termination of long-term therapy was found to be between 18 and 159 days. The recovery of o,p'-DDD from faeces was about five times higher after ingestion of tablets than after administration in oil emulsion and milk. As far as the rapid increase in plasma levels and patient compliance are concerned, the best results were obtained with the milk powder mixture.

Abstract. In 3 patients with adrenocortical carcinoma the effects of long-term mitotane therapy on the serum levels of three hormone-binding globulins and vitamin D-binding protein were studied. Within the first month of treatment cortisol-binding globulin increased two to three times, in close correlation with sex hormone-binding globulin. The rises in thyroxine-binding globulin and vitamin D-binding protein were considerably less. Elevated cortisol-binding protein appeared to be associated with increased binding of cortisol, whereas the binding of thyroxine and vitamin D remained below normal. Binding proteins returned to normal in 2 patients within a year after mitotane discontinuation. This phenomenon of hormone-binding protein enhancement invalidates the use of total serum hormone levels to monitor the effects of mitotane on endocrine function and could provide an explanation for the increased cortisol substitution requirement during mitotane therapy.

We describe a patient who suffered from ophthalmic trigeminal neuralgia as an isolated symptom of a noninvasive pituitary tumor. Bromocriptine appeared to provoke the attacks within hours. This provocation could be prevented by domperidone. After adenomectomy, both spontaneous and induced attacks disappeared. Acute transient cell swelling may be the mechanism by which bromocriptine induced the neuralgic attacks.

The distribution of o,p'-DDD in various body compartments of patients being treated for metastatic adrenocortical carcinoma was studied. A highly significant semilogarithmic relationship was found between plasma and adipose tissue concentrations during therapy and between plasma and brain at autopsy. A linear relationship was found at autopsy between concentrations in adipose tissue and those in various other tissues, such as tumour and brain. The semilogarithmic relationship can be explained by the assumption of two plasma pools for o,p'-DDD, one with low affinity and high capacity and one with high affinity and low capacity. Plasma concentrations must be carefully monitored to obtain an impression of the tumour concentration and to detect impending central nervous system intoxication.