Elevated Serum ACTH Levels Research Articles

HPA Axis Function as Biomarker for Atypical and Melancholic Depression

HPA Axis Function as Biomarker for Atypical and Melancholic Depression

Outcomes in pituitary surgery in Nelson's syndrome--therapeutic pitfalls.

Nelson's syndrome (NS) is a rare clinical syndrome caused by an enlarging, aggressive corticotroph pituitary adenoma that can occur following bilateral adrenalectomy performed in the treatment of refractory Cushing's disease (CD). Such tumours respond poorly to currently available therapeutic options, which include surgery, radiotherapy, pharmacotherapy, and chemotherapy. They are a challenging problem in neurosurgical practice. The aim of this work was to evaluate the early and long-term results of microsurgery in a single surgeon's series of patients with NS. During the period from January 2000 to December 2005, 10 patients with NS underwent surgery. The authors analysed surgical outcomes in the NS group of seven women and three men with the mean age of 47.99 years (range 39-66, SD ± 8.47 years). NS was diagnosed based on clinical signs and symptoms, especially hyperpigmentation of the skin, elevated serum ACTH levels, and pituitary tumour growth. Parasellar extension of the adenomas was assessed in both groups according to Knosp's and Hardy-Wilson classifications. Pituitary function and radiographs were evaluated in the early postoperative period, 30 days after the operation, and during follow-up. Histological examination was based on the WHO (2004) criteria. According to the criteria for Nelson's syndrome remission, five patients (50%) were cured. No perioperative mortality was reported. Three patients developed pituitary insufficiency and two patients developed diabetes insipidus. There was one case of postoperative cerebrospinal fluid leakage. One patient was diagnosed with pituitary carcinoma. Transsphenoidal microsurgical removal of pituitary adenomas is a safe and effective treatment of Nelson' syndrome.

Nelson’s syndrome after bilateral adrenalectomy for Cushing’s disease

Presentation and outcome of Nelson's syndrome after bilateral adrenalectomy is variable. Clinical records of 39 patients who underwent bilateral adrenalectomy for primary or recurrent Cushing's disease during a 15-year period were analyzed for frequency and evolution of Nelson's syndrome. The study included 32 females and 7 males with a mean age of 31 years; 20 patients had a hypophysectomy as the initial procedure, and 19 had an adrenalectomy. Of the group, 17 patients received prophylactic radiation therapy to the pituitary gland. A total of 11 patients, none of whom had received prophylactic radiation therapy, developed Nelson's syndrome (determined by skin hyperpigmentation, elevated serum ACTH levels, and enlargement of a previous pituitary tumor or development of a new tumor in patients with no previous pituitary abnormality) over a mean follow-up period of 53 months. Treatment for Nelson's syndrome included valproic acid, radiation therapy, and hypophysectomy as monotherapy or combined therapy. Of the remaining 28 patients, 10 (7 without prophylactic radio therapy) developed skin hyperpigmentation and increased ACTH levels without a tumor. Nelson's syndrome is a frequent complication after bilateral adrenalectomy in the absence of prophylactic radiotherapy (28%). The syndrome can be successfully controlled by medical treatment and or radiotherapy; patients rarely require hypophysectomy.

Large and Invasive Silent Corticotroph-cell Adenoma with Elevated Serum ACTH: A Case Report

Background A silent corticotroph-cell adenoma (SCCA) is defined as evidence of immunoreactive ACTH in tumor cells of a pituitary adenoma that is not associated with symptoms of Cushing’s disease. Most previous reports have discussed the etiology of this unique entity; however, the precise mechanisms of its “silence” are not clear yet. We discuss the pitfalls of endocrinological diagnosis and surgical management of SCCA. Methods A 63-year-old man, without the symptoms of Cushing’s disease, demonstrated elevated serum levels of ACTH, but normal levels of cortisol. ACTH was measured by newly developed immunoradiometric assays (IRMA), which are more specific for biologically active ACTH than conventional radioimmunoassay (RIA). The tumor was more than 3 cm in diameter and invaded both the cavernous sinus and the sphenoid sinus. Results Two different types of IRMAs revealed elevated serum ACTH levels. The tumor was removed successfully by staged operations. The high levels of serum ACTH were normalized after the second operation. Conclusion The cause of the silence of SCCA is not clear yet. The elevated serum ACTH levels in the present case were not attributable to “Big ACTH.” We suggest one possibility: the cause of the silence might be a minor variant of ACTH, detected by IRMA, leading to less biological activity of ACTH. This type of adenoma is invasive in nature and can potentially grow large because it is free of endocrinological symptoms. We emphasize the appropriate surgical strategy to normalize the serum levels of ACTH in case of SCCA.

Present status and future aspects of radioimmunoassay of tumor markers

BackgroundA silent corticotroph-cell adenoma (SCCA) is defined as evidence of immunoreactive ACTH in tumor cells of a pituitary adenoma that is not associated with symptoms of Cushing’s disease. Most previous reports have discussed the etiology of this unique entity; however, the precise mechanisms of its “silence” are not clear yet. We discuss the pitfalls of endocrinological diagnosis and surgical management of SCCA.MethodsA 63-year-old man, without the symptoms of Cushing’s disease, demonstrated elevated serum levels of ACTH, but normal levels of cortisol. ACTH was measured by newly developed immunoradiometric assays (IRMA), which are more specific for biologically active ACTH than conventional radioimmunoassay (RIA). The tumor was more than 3 cm in diameter and invaded both the cavernous sinus and the sphenoid sinus.ResultsTwo different types of IRMAs revealed elevated serum ACTH levels. The tumor was removed successfully by staged operations. The high levels of serum ACTH were normalized after the second operation.ConclusionThe cause of the silence of SCCA is not clear yet. The elevated serum ACTH levels in the present case were not attributable to “Big ACTH.” We suggest one possibility: the cause of the silence might be a minor variant of ACTH, detected by IRMA, leading to less biological activity of ACTH. This type of adenoma is invasive in nature and can potentially grow large because it is free of endocrinological symptoms. We emphasize the appropriate surgical strategy to normalize the serum levels of ACTH in case of SCCA.