An unusual sellar mass--solitary plasmacytoma.

OBJECTIVE: To describe a case of solitary intrasellar plasmacytoma in a patient with a preoperative diagnosis of a nonfunctioning pituitary adenoma. METHODS: A case of a solitary intrasellar plasmacytoma is presented, in which the clinical and laboratory findings are detailed and the response to treatment is discussed. Pertinent reports from the literature are reviewed. RESULTS: A 53-year-old woman came to the neurology clinic with complaints of frontal headaches and intermittent blurry vision. Physical examination showed no remarkable findings. Computed tomography revealed an enhancing sellar and suprasellar mass, with extension into the sphenoid and cavernous sinuses. The patient had a preoperative diagnosis of a clinically nonfunctioning pituitary adenoma and underwent transsphenoidal resection. The biopsy specimen was heavily infiltrated with abnormal plasma cells, which stained exclusively for lambda light chain immunoglobulins. An extensive investigation failed to show evidence of multiple myeloma. In view of these findings, the diagnosis of solitary extramedullary plasmacytoma was made. Postoperatively, the patient received radiotherapy to the pituitary and has remained free of disease for 7 years. Review of the world literature disclosed only 17 previous reports of patients in whom a solitary plasmacytoma or multiple myeloma first appeared as a sellar mass. In each case, the plasmacytoma mimicked a clinically nonfunctioning pituitary adenoma. CONCLUSION: Parasellar plasmacytomas are often mistaken for a nonfunctioning pituitary adenoma. The diagnosis is difficult to make in the absence of overt systemic myeloma. Nevertheless, normal pituitary function associated with severe destruction of the pituitary fossa, cranial neuropathies, and diabetes insipidus are clues that the primary lesion is outside the pituitary gland itself. The current patient is unique in terms of prolonged survival in the absence of systemic myeloma. Perhaps those patients with progression of disease did not have extramedullary tumors because such lesions rarely progress to overt myelomatous disease.

Comparison of albumin excretion rate obtained with different times of collection.

This study was undertaken to assess the usefulness of different techniques for determination of albumin excretion rate (AER). Ninety patients with type I (insulin-dependent) diabetes mellitus and 45 with type II (non-insulin-dependent) diabetes mellitus, with AER/24 h of less than 200 micrograms/min, were included. All patients were free of major systemic complications of diabetes and overt kidney disease (mean serum creatinine 1.1 +/- 0.1 mg/dl, range 0.4-1.2 mg/dl). We compared timed day, night, and 24-h specimens, as well as timed spot specimens during water-induced diuresis. Most patients with type I (75 of 90) and type II (30 of 45) diabetes had AER less than 20 micrograms/min and showed significant differences in AER that were dependent on the collection time. Differences were diminished or absent with AER less than 20 micrograms/min. Sensitivity, specificity, and prediction rates of AER in different specimens were evaluated against 24-h AER. Use of albumin concentrations and albumin-creatinine ratios did not improve test performance in comparison with AER. Sampling time and the overall rate of AER influenced measurement of urinary albumin excretion. Day or 24-h AER is most useful to determine the presence of abnormal AER. AER and albumin concentration in spot samples are of limited use for initial screening and frequently require day or 24-h specimens of AER for confirmation. Day or 24-h AER should be used for long-term follow-up of the diabetic patient.

Immunoregulation of anti-islet cell antibody in insulin-dependent diabetes: failure to detect anti-idiotypic antibody following seroconversion.

A search was made for the presence of spontaneous auto-anti-idiotype in sera of three insulin-dependent diabetics when they converted from islet cell antibody positive to islet cell antibody negative states. Rabbit anti-idiotype specific for islet cell antibody was used as the positive control. Using an enzyme-linked immunoabsorbent assay, binding of the rabbit anti-idiotype to idiotype-coated plates could not be inhibited by islet cell antibody negative sera. Using this same assay, there was no significant difference in the binding of islet cell antibody positive or negative sera to either idiotype-coated or normal IgG-coated plates. Binding of islet cell antibody to pancreatic sections could not be inhibited by islet cell antibody negative sera in an immunofluorescent assay. Network regulation by auto-anti-idiotype does not seem to play a role in the decline or absence of islet cell antibody in the early phases of insulin-dependent diabetes mellitus.

Self-regulation in individuals with type II diabetes.

A model for self-regulation of diabetes was tested which proposed that individuals monitor their disease status by comparing their current state with their standard of well-being. When a discrepancy is experienced and associated with a change in blood glucose, action is taken to relieve the symptom and thereby regulate blood glucose. Two variables of the self-regulatory process (symptom-associating and action-taking) were tested through semi-structured interviews of 173 subjects who had Type II diabetes. Most (85%) subjects associated their symptoms with a change in blood glucose levels. Of subjects who associated symptoms with elevated blood glucose, 77% took action; of subjects who associated symptoms with lowered blood glucose, 89% took action. Only sex and insulin use were related to symptom associating and action taking. There was no relation between metabolic control measured by glycosylated hemoglobin and symptom association and action taking.

Endocrine studies in a male patient with choriocarcinoma and gynecomastia.

Sex hormone profiles were studied in serum and tumor extracts of a man with pulmonary choriocarcinoma and gynecomastia. Although levels of serum estrogens were elevated as expected, serum androgen levels were uncharacteristically quite high. Tumor extract contained increased quantities of both androgens and estrogens when compared with surrounding normal lung tissue, but lacked the enzymes necessary for androgen biosynthesis while retaining aromatase activity. It is concluded that unlike the usual male patient with choriocarcinoma, the tumor-derived beta-human chorionic gonadotropin stimulated testicular androgen production. These androgens were in turn concentrated by the tumor and converted in part to estrogens. Furthermore, gynecomastia can occur even in the face of high serum androgen concentrations provided total estrogen levels are also disproportionately elevated.

Androblastomas and thyroid disease in postmenopausal sisters.

Androblastomas are virilizing ovarian tumors found predominantly in premenopausal women. Reported are two postmenopausal sisters with androblastomas, the first such occurrence in the literature. An association has been proposed between the familial occurrence of these tumors and thyroid adenomas or nontoxic goiter. Of the two patients studied, one had a history of Graves disease and the other had thyroid cancer. The authors conclude that the associated thyroid pathology in the families described and in the studied patients is inconsistent and does not represent a unique multiple endocrine neoplasia syndrome.

Immune abnormalities in diabetic patients not requiring insulin at diagnosis.

Islet cell antibodies (ICA), complement fixing islet cell antibodies, immune complexes and thyro-gastric autoantibodies were studied in newly diagnosed diabetic patients not requiring insulin at diagnosis. Particular attention was focussed on that minority of patients who are initially treated with diet or oral agents but show ICA in their serum. One hundred and six non-insulin-requiring patients were studied at clinical diagnosis. Seventeen who had ICA in their serum were compared with a control group of 89 who did not. The 17 ICA-positive diabetic patients were followed serologically for approximately 1 year from diagnosis. Patients were followed clinically for 3 years. Forty-seven percent of ICA-positive and 19% of ICA-negative patients had immune complexes in their serum. Eleven of the 17 ICA-positive patients also had serum complement fixing islet cell antibodies. Thyro-gastric antibodies were found in 29% of ICA-positive and 18% of ICA-negative diabetic patients. ICA, complement fixing antibody and immune complex positivity declined with time. Ten of the 7 ICA-positive and two of the 89 ICA-negative patients required insulin within 3 years of diagnosis. There was a positive trend for the presence of complement fixing islet cell antibodies at diagnosis to be associated with the early development of insulin dependency. The type of diabetes in ICA-positive patients not requiring insulin at diagnosis has strong immunological and clinical similarities to classical Type 1 (insulin-dependent) diabetes.

Monoclonal antibodies defined abnormalities of T-lymphocytes in type I (insulin-dependent) diabetes.

Peripheral T-lymphocytes subsets have been investigated in 36 patients with type I (insulin-dependent) diabetes of varying duration, 18 patients with type II (non-insulin-dependent) diabetes, and in 23 healthy subjects, using six different monoclonal antibodies. At the time of diagnosis of type I diabetes, there was evidence of an increase in cytotoxic T-lymphocytes, a decrease in suppressor T-lymphocytes, but a normal proportion of helper/inducer T-lymphocytes. In six of seven newly diagnosed cases studied, there was evidence of an increased number of activated T cells. An increase in activated T-cells was also found in 5 of 10 genetically susceptible islet cell antibody positive unaffected siblings in type I diabetic probands. In type I diabetes of long standing, the total T-cell population was decreased, largely due to a marked decrease in helper/inducer T-lymphocytes. Type II diabetic patients showed no abnormalities in T-lymphocyte subsets, making it unlikely that hyperglycemia was responsible for the changes observed. These results suggest that an imbalance of T-lymphocyte regulation is an important feature of type I diabetes and lend support for an immunologic role in its early pathogenesis.

Specific immunoregulation abnormality in insulin-dependent diabetes mellitus.

We evaluated antigen-nonspecific (Con A) and antigen-specific (islet cell) activation of suppressor cell function in 11 IDD patients. Compared with healthy controls, IDD was associated with both antigen-specific (n = 11, p less than 0.01) and nonspecific (n = 6, p less than 0.03) suppressor cell hypofunction. The specific defect was not present in NIDD patients and correlated negatively with the duration of the disease (r = -0.6, p less than 0.05). No relationship was found between the degree of specific suppressor cell dysfunction and diabetic control as assessed by glycosylated hemoglobin, plasma glucose values, insulin-binding capacity, or C-peptide determinations. Plasma from IDD lacked anti-suppressor cell activity. Low levels of circulating immune complexes were detected in IDD patients whose disease duration was 1 month or less. Specific suppressor cell hypofunction and/or enhanced helper cell activity in early stages of IDD could be contributing to the formation of islet cell autoantibodies, immune complexes, islet cell injury, and the diabetic state.

Neuroblastoma, pheochromocytoma, and renal cell carcinoma. Occurrence in a single patient.

A 26-year-old woman had a neuroblastoma during infancy; an extra-adrenal pheochromocytoma at age 16 years, with hepatic recurrences during the next ten years; and multifocal renal cell carcinoma. Neuroblastoma and pheochromocytoma, despite their common embryologic origin, to our knowledge have not been previously reported as separate tumors in the same patient. Although many attributes of the patient's tumors suggest a hereditary disorder, thorough investigation disclosed no evidence of heritable conditions associated with any of these tumors in the patient or her family members. Long-term observation of persons surviving after treatment of neuroblastoma will be necessary to determine whether this case represents a previously unidentified tumor predisposition or a sporadic occurrence.

Metabolic responses to plasma concentrations of theophylline.

We investigated the effect of intravenous infusions of aminophylline on plasma glucose, insulin (IRI), glucagon (IRG), growth hormone (HGH), cortisol, and free fatty acid (FFA) levels in healthy young subjects. Six received an intravenous loading dose of aminophylline (6.0 mg/kg over 20 min) followed by a maintenance dose (0.9 mg/kg/hr) for 100 min. Another 7 subjects initially received smaller loading (3.0 mg/kg) and maintenance (0.45 mg/kg/hr) doses, and after 60 min they received a second loading dose (3.0 mg/kg) followed by a larger maintenance dose (0.9 mg/kg/hr) over 120 min. In these fasting volunteers, infusion of aminophylline, which produced theophylline levels in the usual therapeutic range (10 to 20 microgram/ml) caused small increases in plasma glucose levels without changing IRI, IRG, HGH, or cortisol. There were rapid, pronounced, and prolonged rises in FFA associated with the aminophylline infusion. Increases in FFA paralleled the rise in theophylline levels. It is concluded that routine therapeutic doses of theophylline, i.e., doses that achieve serum levels normally encountered in treatment for bronchial asthma, cause a marked rise in FFA and a slight rise in glucose (8 +/- 3 mg/dl) without changing levels of IRI, IRG, HGH, or cortisol.