| A patient who developed a pituitary tumor after adrenalectomy for Cushing's disease (Nelson's syndrome) is presented. The literature reviewed shows less than a 10 percent incidence of this disorder for which extremely elevated plasma ACTH levels are diagnostic. Special radiologic technics may be required to detect small pituitary tumors, but pituitary hormone levels may be elevated in the cerebrospinal fluid if there is suprasellar tumor extension. The different modalities available for treatment of Nelson's syndrome are discussed. ( info) |
12/52. A case of pseudo-Nelson's syndrome: cure of ACTH hypersecretion by removal of a bronchial carcinoid tumor responsible for Cushing's syndrome. It may sometimes be difficult to distinguish Cushing's disease from ectopic ACTH syndrome. A case is described here of a patient with a Cushing's syndrome and diagnostic difficulties. Initial features were consistent with a Cushing's disease (in particular metopirone test was positive). Because of relapse of hypercortisolism after mitotane therapy, total adrenalectomy was performed. Thereafter features occurred that evoked Nelson's syndrome, including high plasma ACTH levels and a pituitary mass syndrome. Pituitary reserve testings by vasopressin or corticotropin-releasing factor were positive, although inconstantly, in that plasma ACTH increased. A lung tumor was discovered about 20 yr after the first clinical signs of hypercortisolism. Its removal led to the discovery of a bronchial carcinoid tumor and was followed by normalization of plasma ACTH levels. An analysis of proopiomelanocortin-related peptides was performed postoperatively on the blood drawn before and after the tumor resection and on the tumor; the results of this study would have been contributive to the diagnosis of occult ectopic ACTH tumor. In conclusion this case demonstrates the limitations of the conventional procedures in the diagnosis of the ectopic ACTH syndrome. At contrast the newer biochemical procedures may be very useful in determining the type of hypercortisolism. ( info) |
13/52. Observations on the pathophysiology of Nelson's syndrome: a report of three cases. Nelson's syndrome is generally regarded as an unusual sequela of primary bilateral adrenalectomy when performed for Cushing's disease. It is classically defined by cutaneous hyperpigmentation, considerably elevated adrenocorticotropic hormone (ACTH) levels, and an enlarged sella turcica. In this report, we present three cases initially treated by transsphenoidal sellar exploration for Cushing's disease. In two of these cases, remission of hypercortisolism did not occur after the initial pituitary exploration. A microadenomectomy was performed in one case and, in the other, no microadenoma was found. In both, Nelson's syndrome occurred after adrenalectomy. A second transsphenoidal operation and radiotherapy were required to control tumor growth. In another case, transsphenoidal adenomectomy of an ACTH-secreting tumor initially led to a remission of hypercortisolism for 4 years, but recurrent Cushing's disease necessitated adrenalectomy, and again Nelson's syndrome occurred. The documentation of a pre-existing ACTH-secreting basophilic pituitary microadenoma before adrenalectomy, as seen in two of our cases, has not been previously reported, and these observations of "non-classical" courses have major implications for the pathophysiology of Nelson's syndrome. ( info) |
14/52. Adrenocorticotropin-dependent virilizing paraovarian tumors in Nelson's syndrome. A 35-yr-old woman with Nelson's syndrome presented with amenorrhea and virilization. serum testosterone (T) concentration was 605 ng/dl and fell to 33 ng/dl when dexamethasone was administered. The MCR of T fell from 1383 to 991 liters/day and the T production rate decreased by 96%. With administration of synthetic ACTH, T concentration rose to 338 ng/dl. plasma ACTH concentration paralleled T during repeated suppression testing, suggesting that T secretion was dependent on ACTH hypersecretion. Preoperative and intraoperative ovarian vein catheterization suggested that the predominant source of androgen production was from the right ovarian vein. Laporatomy revealed multiple paraovarian tumors in the right mesosalpinyx and mesovarium. Incubation of tumor slices and ovarian tissue with [3H]pregnenolone and [14C]17-hydroxyprogesterone demonstrated conversion of both precursors to T by the tumor and confirmed that the tumors were the source of androgen excess. The microscopic appearance of the tumors closely resembled the morphology of testicular and paratesticular tumors of men with congenital adrenal hyperplasia and Nelson's syndrome. The analogous dependency of the tumors on ACTH hypersecretion in men with paratesticular tumors and in this woman with paraovarian tumors suggests that the tumors may arise in both males and females from a common steroid-secreting cell of adrenogenital origin. ( info) |
| We present a case of Nelson's syndrome in which the clinical, radiographic, and surgical findings are indicative of a discrete microadenoma rather than of diffuse pituitary hyperplasia. Ultrastructural analysis reveals this to be the first example of a sparsely granulated lesion in Nelson's syndrome and only the second such adrenocorticotropic hormone-secreting tumor reported. Unfortunately, there do not seem to be any firm ultrastructural features that differentiate between hyperplasia and discrete adenoma. Separation of the two entities may be important in delineating the pathogenesis and treatment of Nelson's syndrome; these are discussed. ( info) |
16/52. Cortisol and androgen secretion in a case of Nelson's syndrome with paratesticular tumors: response to cyproheptadine therapy. Bilateral paratesticular tumors were observed in a 32-yr-old man 14 yr after he developed a pituitary tumor after adrenalectomy for Cushing's disease (Nelson's syndrome). plasma ACTH concentrations were markedly elevated (mean, 6350 pg/ml), but urinary free cortisol concentrations were low (27-31 micrograms/24 h). catheterization revealed a spermatic to peripheral venous gradient for cortisol consistent with secretion of this steroid by the tumor. This was confirmed by decreased cortisol excretion after tumor excision. serum androgen (testosterone, androstenedione, dihydrotestosterone, and dehydroepiandrosterone-sulfate) and progestin (progesterone and 17-hydroxyprogesterone) concentrations were decreased and did not decline further after tumor removal. These latter observations suggested that the paratesticular tumors did not secrete appreciable testosterone or any of its immediate precursors. serum gonadotropin levels were also low. cyproheptadine treatment resulted in a marked lowering of plasma ACTH concentrations (221-320 pg/ml). This was associated with an increase in both plasma LH and testosterone concentrations. These observations are consistent with the hypothesis that ACTH may directly affect LH and testosterone secretion. ( info) |
| Nelson's syndrome is rare and difficult to cure. The tumours in this condition may behave invasively and require multiple interventions. Two patients who had been followed up for nearly 20 years developed signs of cavernous sinus involvement, one with an empty sella. Long term follow-up for such patients is emphasized. ( info) |
18/52. The effect of the long-acting somatostatin analogue SMS 201-995 on ACTH secretion in Nelson's syndrome and Cushing's disease. Chronic therapy of a patient with Nelson's syndrome for 2 years with 300 micrograms SMS 201-995 per day resulted in a significant decrease in circulating ACTH levels, normalization of the visual field defect and of loss of visual acuity of one eye, and stabilization of tumour growth, without radiological evidence of shrinkage of the pituitary tumour. In two other patients with Nelson's syndrome, SMS 201-995 acutely inhibited circulating ACTH levels. This effect could be shown best if cortisol replacement was temporarily withheld. SMS 201-995 did not affect plasma ACTH and cortisol levels in three patients with untreated Cushing's disease. ( info) |
19/52. in vitro effects of ketoconazole on corticotrope cell morphology and ACTH secretion of two pituitary adenomas removed from patients with Nelson's syndrome. The direct effects of ketoconazole on the secretion of ACTH by human pituitary adenoma cells from 2 patient with Nelson's syndrome were studied in vitro. Stereologically quantified, intracellular changes affect the surface density of the endoplasmic reticulum (it decreased by 73%), the volume density of the secretion granules (it decreased by 49%), and the volume density of lysosomes (it decreased by 67%). The hormone released in the culture medium decreased depending on the doses of ketoconazole used; 10 mumol/l decreased ACTH levels by 31%. These data show that ketoconazole induce marked changes on corticotrope morphology and ACTH secretion in pituitary cells obtained from patients with Nelson's syndrome. ( info) |
20/52. Development of Nelson's syndrome in a patient with recurrent Cushing's disease. Analysis of secretory behavior of the pituitary tumor. A markedly cushingoid 32-year-old man presented to Queens Hospital Center with headache, hyperpigmentation, and visual field loss. Twelve years earlier, he had undergone subtotal adrenalectomy for Cushing's disease, but symptoms of hypercortisolemia promptly recurred. Workup revealed the presence of a large, expanding intrasellar mass, plasma ACTH levels between 3,000 and 10,000 pg/ml, and markedly elevated cortisol levels. The secretion of ACTH (mainly ACTH 1-39-like peptide) by the pituitary tumor showed neither diurnal periodicity nor response to a variety of pharmacologic agents known to affect ACTH secretion. The patient demonstrates a rarely observed presentation of Nelson's syndrome, with aggressive adrenotropic pituitary tumor growth even in the presence of chronic hypercortisolemia. ( info) |