Long‐term Results of Total Adrenalectomy for Cushing's Disease

Abstract

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.

Nelson's syndrome

“…For some tumours (although not microadenomas), pre-TBA urinary cortisol serves as a useful marker of corticotrophinoma tumour size and functionality, and may be a useful predictor of the subsequent Nelson's syndrome development (3,33,40). However, the evidence is not conclusive, and a correlation between urinary cortisol levels and the risk of subsequent development of Nelson's syndrome has not been demonstrated in some studies (13,30,32).…”

“…Suboptimal or absent steroid replacement therapy post TBA may increase the risk of developing Nelson's syndrome (41,42) or even result in transformation of a pre-existing adenoma into a more aggressive tumour subtype (3,26). However, most studies have not shown this (3,13,32).…”

“…Nelson's syndrome can develop up to 24 years following TBA (30,33,38,61). It has also been demonstrated that patients with invasive corticotrophinomas (shown on TSS-derived samples) are at greater risk of subsequent (and earlier) development of Nelson's syndrome (62) compared with less aggressive forms (3,31). Although corticotrophinoma aggressiveness is an important concept when considering Nelson's syndrome aetiology, other factors may also be implicated.…”

“…Nelson's syndrome can develop up to 24 years post TBA, with mean development at 15 years post TBA (3). In the first published series of patients with Nelson's syndrome, mortality was 12% (6), although mortality rates have been much lower in the subsequent series (including absent mortality in two series (7,8)), probably due to earlier diagnosis and improved management.…”

“…Although generally out of favour (12), laparoscopic TBA can be useful when a corticotrophinoma is undetectable, surgically unresectable or there is recurrence following TSS. In these cases, TBA offers 85-100% success rate in controlling hypercortisolaemia (3,11) and is particularly useful in patients with life-threatening manifestations of hypercortisolism (13). Although TBA is usually a definitive form of treatment for refractory Cushing's disease with immediate control of hypercortisolaemia, a limitation is the potential for the subsequent development of Nelson's syndrome (14).…”