[Effects of adrenalectomy on the treatment of Cushing disease].

OBJECTIVE: To discuss the effects of adrenalectomy (ADX) on the treatment of Cushing's disease(CD). METHODS: Clinical data of 15 cases of CD between January 1980 and December 2005 were analyzed to evaluate operative indications, complications and the changes of hypercortisolism and hormone levels pre- and post- adrenalectomy. RESULTS: All the patients involved underwent transsphenoidal pituitary surgery previously. Repeated transsphenoidal surgery was performed in 4 cases. Pituitary radiotherapy was done in 4 cases. The average time from original transsphenoidal operation to ADX was 25.7 months. Pre- and post- adrenalectomy serum cortisol median level were 1156.4 nmol/L and 99.4 nmol/L, the 24 h urinary-free cortisol median level were 315.0 and 5.4 microg, respectively. Hormone replacement therapy was needed in all cases. Average follow-up period was 47 months (9-120 months). Nelson syndrome (NS) appeared in 5 cases (33.3%), while 10 cases showed no NS. CONCLUSIONS: ADX is an effective and symptomatic treatment to relieve hypercortisolism caused by CD but with the risk of NS. Longtime hormone replacement therapy and follow up are needed after ADX.

[Nelson's Syndrome: a case report]. / Síndrome de Nelson: relato de caso.

The aim of this article is to present and discuss several aspects of the pathogenesis, the clinical, hormonal, and imaging diagnosis, and the treatment of Nelson's syndrome, based on a typical patient's report, in whom several therapeutic approaches were shown to be ineffective.

Síndrome de Nelson: relato de caso / Nelson's Syndrome: a case report

O objetivo deste artigo é apresentar e discutir alguns aspectos da patogênese, do diagnóstico clínico, hormonal e radiológico e do tratamento da síndrome de Nelson, com base no relato de um paciente típico portador da doença, no qual várias abordagens terapêuticas mostraram-se ineficazes.

The aim of this article is to present and discuss several aspects of the pathogenesis, the clinical, hormonal, and imaging diagnosis, and the treatment of Nelson's syndrome, based on a typical patient's report, in whom several therapeutic approaches were shown to be ineffective.

Rosiglitazone for prevention or adjuvant treatment of Nelson's syndrome after bilateral adrenalectomy.

OBJECTIVE: To investigate the effect of Rosiglitazone in three patients treated with bilateral adrenalectomy followed by hyperpigmentation and hypersecretion of ACTH. PATIENTS AND METHODS: One patient had increasing ACTH after previous transsphenoidal surgery for Nelson's syndrome, and two patients without pituitary adenomas had recurrence of Cushing's disease after primary and repeated transsphenoidal surgery with need for bilateral adrenalectomy. The patients developed hyperpigmentation and increasing ACTH at nadir 2-4 h after morning hydrocortisone dose. ACTH during Rosiglitazone therapy (4 mg/day for 4 weeks and then 8 mg/day) was measured at regular intervals 24 h after the latest dose of hydrocortisone. RESULTS: In two patients there was a decrease in ACTH by 40% after 5 months. The first of these patients showed an escape with increasing ACTH to the initial value after 11 months. In the third patient no effect was observed. Tumour development or progression on magnetic resonance imaging was not observed. CONCLUSION: Rosiglitazone might represent an adjuvant therapy in patients with ACTH hypersecretion. Larger long-term studies are needed.

The long-term outcome after adrenalectomy and prophylactic pituitary radiotherapy in adrenocorticotropin-dependent Cushing's syndrome.

We have reviewed our experience of adrenalectomy performed as part of the management of 56 patients with ACTH-dependent Cushing's syndrome between 1946 and 1993. Forty-three patients were operated on at our institution. Surgery-related mortality did not occur, but complications developed in 14 (33%); these were minor in 12. Eleven patients (29%) of the 38 for whom long-term follow-up data were available and who did not have a proven ectopic source of ACTH subsequently developed Nelson's syndrome, diagnosed on the basis of clinical pigmentation and markedly elevated ACTH levels that were not normally suppressible with glucocorticoids. The effects of prophylactic pituitary radiotherapy were assessed in 38 patients who underwent adrenalectomy at our institution and 18 who underwent surgery elsewhere. Patients who had received prophylactic radiotherapy were less likely to develop Nelson's syndrome (5 of 20, 25%) compared to those who did not (18 of 36, 50%; P > 0.07), and there was a low incidence of radiotherapy-induced hypopituitarism. We conclude that total adrenalectomy has proved to be a safe and effective operation and still may be indicated in selected patients with ACTH-dependent Cushing's syndrome; because prophylactic pituitary radiotherapy reduces the incidence of subsequent Nelson's syndrome by 50%, it should always be considered in the management of these patients.

Adrenal autotransplantation after total adrenalectomy: delayed determined function.

Adrenal autotransplantation after bilateral total adrenalectomy has been utilized to eliminate the need for replacement therapy and to prevent the late occurrence of Nelson's syndrome in some patients with Cushing's disease. It is possible to follow these cases up closely today, owing to the highly developed hormonal evaluation and imaging techniques. In this study, two patients who underwent bilateral total adrenalectomy and cortex autotransplantation are presented. The autografts were found functional and the patients had not required any steroid replacement therapy.

Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease.

Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. Two of these received no further active treatment, one underwent successful pituitary surgery, one underwent a second course of low-dose external irradiation (as yet unsuccessful) and one has been treated with metyrapone for a total of 75 months. One of the 13 patients who did not respond received a further course of low-dose pituitary irradiation with prompt remission and two have received metyrapone for 41 months and 15 years without ill effect. One patient died from cerebrovascular disease. The remaining nine patients underwent bilateral adrenalectomy (one after unsuccessful pituitary surgery) with rapid resolution of hypercortisolism. Five of these patients have developed hyperpigmentation and elevated ACTH levels (range 505-1150 ng/l). A pituitary microadenoma has been demonstrated on CT scan in three and successfully removed by microadenomectomy. In the present series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy.