Age-related change in plasma concentration of 7B2 (a novel pituitary polypeptide) in normal humans

Using a specific radioimmunoassay, we measured concentrations of plasma 7B2 (a novel pituitary polypeptide) immunoreactivity (7B2-IR) in normal human subjects, patients with chronic renal failure and those with liver cirrhosis. Mean (+/- SEM) values of plasma 7B2-IR in normal healthy men and women were 55.8 +/- 1.2 pg/ml (n = 266) and 56.1 +/- 0.9 pg/ml (n = 408), respectively. The elevation of plasma 7B2-IR showed a relationship with age of the subjects, in both men (r = 0.39, t = 6.86, p less than 0.001) and women (r = 0.35, t = 7.44, p less than 0.001). Plasma 7B2-IR concentrations were elevated in patients with chronic renal failure (536 +/- 45 pg/ml, Mean +/- SEM, n = 10) as well as those in liver cirrhosis (95 +/- 10 pg/ml, Mean +/- SEM, n = 15) compared to values in normal subjects, suggesting that 7B2 is mainly eliminated through the kidney and is partly metabolized in the liver.     

Plasma levels of 7B2 (a novel pituitary polypeptide) and its molecular forms in plasma and urine in patients with chronic renal failure: possible degradation by the kidney

Plasma immunoreactive (IR)-7B2 was measured in patients with chronic renal failure (CRF), using a specific radioimmunoassay. The mean (+/- S.E.M.) concentration of plasma IR-7B2 in CRF patients under hemodialysis (502 +/- 36 pg/ml, n = 27) was significantly higher than that in normal subjects (men, 52.9 +/- 1.7 pg/ml (n = 179); women, 55.8 +/- 1.3 pg/ml (n = 198]. Significant correlations between plasma levels of IR-7B2 and those of blood urea nitrogen, creatinine and beta 2-microglobulin were evident in non-dialyzed CRF patients. In the analyses of pooled plasma and urine obtained from normal subjects on gel permeation chromatography, a major peak of IR-7B2 was observed at an apparent molecular weight of 20,000 in the plasma, and at a position of a smaller molecular weight in the urine. These results suggest that 7B2 is degraded mainly in the kidney and that measurement of plasma 7B2 may serve as an appropriate tool for assessing renal function.     

Plasma 7B2 (a novel pituitary protein) immunoreactivity concentrations in patients with various endocrine disorders

We have measured plasma 7B2 (a novel pituitary protein)-immunoreactivity (IR) concentrations in patients with various endocrine disorders. Mean (+/- SEM) basal plasma 7B2-IR concentrations (ng/L) in patients with acromegaly (81 +/- 14.6), Cushing's disease (57.2 +/- 8.5), prolactinoma (71.4 +/- 9.5), panhypopituitarism (50.6 +/- 7.6), isolated ACTH deficiency (47.9 +/- 11.6), hyperthyroidism (57.9 +/- 6.7) and hypothyroidism (60.8 +/- 9.4) were on the same levels as those in age-matched normal subjects. However, basal plasma 7B2-IR concentrations were increased to more than 100 ng/L in 5 out of 25 patients with acromegaly (20%). Mean basal plasma 7B2-IR concentrations in patients with medullary carcinoma of the thyroid and pheochromocytoma were 293 +/- 38.1 ng/L (range: 225.7-357.4 ng/L, n = 3) and 221 +/- 82.8 ng/L (range: 48.5-527.8 ng/L, n = 5), respectively, and significantly higher than those in age-matched normal subjects (P less than 0.001). These results suggest that plasma 7B2-IR may have some diagnostic value for acromegaly and may be useful as a marker for medullary carcinoma of the thyroid and pheochromocytoma.     

Plasma somatostatin in normal subjects and in various diseases: increased levels in somatostatin-producing tumors

The plasma levels of somatostatin (SRIF) were studied in normal subjects and patients with various disorders by a sensitive and specific radioimmunoassay. In 45 normal subjects, the fasting plasma SRIF concentrations were 13.3 +/- 5.3 pg/ml (mean +/- SD). Very high concentrations of plasma SRIF, ranging from 125.0 pg/ml to 400.0 pg/ml, were found in all four patients with medullary carcinoma of the thyroid examined and the SRIF levels were changed in parallel with their clinical course after resection of the tumor. A case of pheochromocytoma also showed a relatively high SRIF concentration in plasma (47.0 pg/ml), but the plasma SRIF level decreased to 8.7 pg/ml after removal of the tumor. In normal subjects, plasma SRIF levels did not fluctuate during 2 hr-observation period in basal state. Glucagon (1 mg, iv) and secretin (3 CHRU/kg B.W., iv infusion over 30 min) had no effect on the SRIF levels in the peripheral blood plasma of normal subjects. On intravenous infusion of arginine (0.5 g/kg B.W.) over 30 min, all 6 normal subjects showed a significant increase in plasma SRIF 30-45 min after the start of the infusion (basal value, 11.6 +/- 1.5 pg/ml; peak value, 27.2 +/- 3.0 pg/ml; p less than 0.005). Two cases of medullary thyroid carcinoma showed exaggerated responses after the arginine administration (increases of 103 pg/ml and 157 pg/ml, respectively), suggesting that SRIF was released from the tumor. The findings indicate that plasma SRIF determination in the basal state and after arginine administration is useful for detecting and following up SRIF-producing tumors.     

Thyrotropin-releasing hormone and insulin in chemically induced pancreatic islet cell tumors in rats

Thyrotropin-releasing hormone (TRH) and insulin were measured by radioimmunoassay in acetic-acid extracts of 19 pancreatic islet cell tumors induced by streptozotocin and nicotinamide in rats. In addition, gel filtration properties of TRH-immunoreactivity and immunoreactive insulin (IRI) were examined in 5 and 14 tumors, respectively. TRH was demonstrated in 10 of 19 tumors, with a mean of 166 +/- 47 (SEM) pg/mg wet weight, whereas the concentration was less than 3 pg/mg wet weight in the other tumors. In contrast, all tumors contained IRI, with a mean of 11.0 +/- 1.6 micrograms/mg wet weight. Ten tumors in which TRH was demonstrated contained more IRI than those in which TRH was not detected (13.1 +/- 1.8 vs 6.5 +/- 1.7 micrograms/mg wet weight, P less than 0.02). After gel filtration, all TRH immunoreactivity was eluted at the same place as synthetic TRH in the 5 tumors. In addition, gel filtration elutes showed essentially the same pattern of IRI in the 14 tumors, with 3 peaks. The predominant IRI peak comigrated with marker insulin (95.7 +/- 0.8%), another prominent peak occurred coincident with proinsulin standard (3.3 +/- 0.5%), a third peak was present in the void volume (0.28 +/- 0.04%). These distributions of IRI were similar to those in extracts of normal pancreases. The present studies demonstrate TRH immunoreactivity in pancreatic islet cell tumors induced by streptozotocin and nicotinamide in rats. Chemically induced insulinomas can serve as a model for insulin storage which is analogous to islet B cells.     

Insulin and glucagon in rats with islet cell tumors induced by small doses of streptozotocin

Plasma insulin and glucagon responses to oral glucose loading were examined in rats with islet cell tumors induced by a single intravenous injection of streptozotocin (30 or 40 mg/kg body weight). Twenty-four macroscopic and six microscopic tumors occurred in 21 rats. In 15 of 21 tumor-bearing rats, there was exaggerated insulin release in response to oral glucose. Plasma glucose levels did not rise with the oral glucose load and were comparable to those seen in normal animals. Hence these rats are described as having "responsive tumors." In six rats with "nonresponsive tumors" there was no insulin response and the plasma glucose levels rose. No significant differences in plasma levels were observed between the two groups. Nonresponsive tumors as well as responsive tumors contained a significant amount of extractable insulin (17.68 +/- 8.60 and 35.07 +/- 10.05 mg/g wet weight, respectively) and detectable amounts of immunoreactive glucagon (1.47 +/- 0.61 and 2.24 +/- 0.67 micrograms/g wet weight, respectively). These results suggest that a small dose of streptozotocin produces two types of islet cell tumors. One is insulin producing and insulin secreting whereas the other is insulin producing but not insulin secreting.     

Secretory protein 7B2. A novel tumor marker of medullary carcinoma of the thyroid

Mean plasma concentrations of 7B2 in three patients with medullary carcinoma of the thyroid (MCT) (294 +/- 38 pg/ml) were significantly higher than those in age-matched normal subjects (107.2 +/- 7.2 pg/ml, n = 11). The intravenous infusions of pentagastrin (0.5 microgram/kg) markedly increased the plasma concentrations of 7B2 as well as calcitonin in all three MCT patients but it caused no significant rise of the plasma 7B2 concentration in any healthy subjects. The peak times and rates of increase of plasma 7B2 concentrations were different from those of plasma calcitonin concentrations in MCT patients. The plasma 7B2 concentration in one of the patients with MCT showed a marked reduction and no further elevation from the pentagastrin infusion following a total thyroidectomy (preop. 226 pg/ml; postop. 112.1 pg/ml). The above evidence suggests that the increased levels of plasma 7B2 in MCT patients may be attributed to the release from parafollicular cells of thyroid. Therefore, 7B2 is considered to be clinically useful as a tumor marker of MCT.     

Fine needle aspiration cytology of endocrine neoplasms of the pancreas. Morphologic and immunocytochemical findings in 20 cases

OBJECTIVE: To analyze the role of fine needle aspiration (FNA) cytology in the preoperative diagnosis of pancreatic endocrine neoplasms. METHODS: Cytologic and histologic diagnoses of pancreatic endocrine tumors were reviewed. A total of 20 FNA cytologic procedures from 20 patients were selected. A false positive case, a retroperitoneal paraganglioma, was also reviewed. Two groups of patients were established: (1) those in whom a surgical biopsy with an immunohistochemical study was available (n = 13), and (2) those with a pancreatic tumor in which the diagnosis was confirmed by immunocytochemical studies (n = 7). In 13 cases the pancreatic tumor was aspirated, while in 7, liver metastases were studied. The immunoexpression of chromogranin and synaptophysin was evaluated in alcohol-fixed smears from 12 and 11 cases, respectively. RESULTS: One false negative and 1 false positive diagnosis were present. In the remaining 19 cases a cytologic diagnosis of pancreatic endocrine tumor was given. Main cytologic features were: (1) a prominent cellular dissociation with many single cells and small, poorly cohesive groups; (2) intermediate to large size cells with ill-defined cytoplasm, naked or eccentric nuclei, and frequent binucleation; and (3) variable nuclear pleomorphism with the characteristic finely granular distribution of the chromatin. Immunocytochemical evidence of endocrine differentiation (chromogranin or synaptophysin) was present in the 12 cases analyzed. CONCLUSION: FNA cytology offers the possibility of a precise preoperative, noninvasive diagnosis of pancreatic endocrine tumors. Cytologic features differ considerably from those of pancreatic adenocarcinoma, allowing differentiation from nonfunctioning endocrine neoplasms. In difficult cases immunocytologic studies are very helpful.     

Effect of age and sex on plasma total homocysteine in Taiwanese subjects

Plasma total homocysteine (tHcy) is now established as a clinical risk factor for coronary artery disease, as well as for other arterial and venous occlusive diseases. Therefore, we measured the plasma tHcy concentrations in 385 healthy Chinese subjects in Taiwan and in 40 patients with occluded coronary artery disease or maintenance hemodialysis. The plasma tHcy levels in Taiwanese male and female volunteers were found to increase gradually with age (age group: 20-29, 30-39, 40-49, 50-59, and >60; mean +/- SD 8.22 +/- 2.00, 8.51 +/- 2.67, 8.87 +/- 2.22, 11.41 +/- 2.50 and 13.28 +/- 2.31 microM for male volunteers and 6.49 +/- 1.75, 7.15 +/- 1.20, 7.40 +/- 1.30, 9.57 +/- 3.01 and 10.95 +/- 2.11 microM for female volunteers). At the same age, male volunteers were shown to have higher tHcy levels than female volunteers. In addition, the mean concentrations of plasma tHcy in occluded coronary artery disease (13.62 +/- 5.43 microM) or in maintenance hemodialysis (21.28 +/- 4.32 microM) were statistically higher than in age-matched normal subjects (11.02 +/- 2.85 microM). This study emphasizes the significance of age and sex-associated difference in the plasma tHcy levels, and underlines the importance of the range for plasma homocysteine in normal Taiwanese subjects.     

Plasma kisspeptin is raised in patients with gestational trophoblastic neoplasia and falls during treatment

Kisspeptin is a 54-amino acid peptide, encoded by the anti-metastasis gene KiSS-1, that activates G protein-coupled receptor 54 (GPR54). The kisspeptin-GPR54 system is critical to normal reproductive development. KiSS-1 gene expression is increased in the human placenta in normal and molar pregnancies. Circulating kisspeptin is dramatically increased in normal pregnancy, but levels in GTN have not previously been reported. The present study was designed to determine whether plasma kisspeptin levels are altered in patients with malignant GTN. Thirty-nine blood samples were taken from 11 patients with malignant GTN at presentation during and after chemotherapy. Blood was also sampled from nonpregnant and pregnant volunteers. Plasma kisspeptin IR and hCG concentrations were measured. Plasma kisspeptin IR concentration in nonpregnant (n = 16) females was <2 pmol/l. Plasma kisspeptin IR in females was 803 +/- 125 pmol/l in the first trimester of pregnancy (n = 13), 2,483 +/- 302 pmol/l in the third trimester of pregnancy (n = 7), and <2 pmol/l on day 15 postpartum (n = 7). Plasma kisspeptin IR and hCG concentrations in patients with malignant GTN were elevated at presentation and fell during and after treatment with chemotherapy in each patient (mean plasma kisspeptin IR: prechemotherapy 1,363 +/- 1,076 pmol/l vs. post-chemotherapy <2 pmol/l, P < 0.0001; mean plasma hCG: prechemotherapy 227,191 +/- 152,354 U/l vs. postchemotherapy 2 U/l, P < 0.0001). Plasma kisspeptin IR strongly positively correlated with plasma hCG levels (r(2) = 0.99, P < 0.0001). Our results suggest that measurement of plasma kisspeptin IR may be a novel tumor marker in patients with malignant GTN.     

Effect of different insulin administration modalities on vitamin D metabolism of insulin-dependent diabetic patients

The vitamin D status of IDDs was studied in 3 groups of patients who were treated for several months with (i) conventional insulin therapy (group I, n = 17, HbA1 = 10.1 +/- 0.5%); (ii) continuous subcutaneous insulin infusion (CSII, group II, n = 11, HbA1 = 8.9 +/- 0.6%); and (iii) continuous intraperitoneal insulin infusion (CPII, group III, n = 13, HbA1 = 8.0 +/- 0.4%). In all patient groups the plasma concentration of vitamin D metabolites were within normal range. However plasma 25 OH D (ng/ml) was significantly lower in groups I (13.0 +/- 0.8, P less than 0.01) and II (12.5 +/- 1.5, P less than 0.02) than in group III: 22.1 +/- 2.3 (normal range 7-27). Plasma 24,25-(OH)2D (ng/ml) was positively correlated to plasma 25 OH D and was significantly decreased in groups I (1.5 +/- 0.2, P less than 0.05) and II (1.4 +/- 0.2, P less than 0.05) compared with group III: 2.3 +/- 0.3. No significant differences were found in plasma 1,25-(OH)2D between the three groups of diabetics. Plasma PTH was similar in the three groups. The same differences in plasma 25 OH D were observed between the patients treated with CPII and 15 subcutaneously treated patients matched for diabetic control (HbA1 less than 10 per cent). The present results seem to indicate that insulin might have a stimulatory effect on the hepatic 25 hydroxylase activity.     

Ectopic growth hormone-releasing hormone (GHRH) syndrome in a case with multiple endocrine neoplasia type I

A 36-yr-old man with multiple endocrine neoplasia (MEN) type I had an ectopic growth hormone-releasing hormone (GHRH) syndrome due to a GHRH-secreting pancreatic tumor. The immunoreactive (IR)-GHRH concentration in his plasma ranged from 161 to 400 pg/ml (299 +/- 61 pg/ml, mean +/- SD; normal, 10.4 +/- 4.1 pg/ml), and a significant correlation was found between his plasma IR-GHRH and GH (r = 0.622, p less than 0.02). After removal of the pancreatic tumor, the high plasma GH concentration returned to nearly the normal range (42.2 +/- 31.3 to 9.6 +/- 3.8 ng/ml). These changes paralleled the normalization of his plasma IR-GHRH (16.1 +/- 3.8 pg/ml) and some of his symptoms related to acromegaly improved. However, plasma GH (7.7 +/- 1.3 ng/ml) and IGF-I (591 +/- 22 ng/ml) concentrations were high at 12 months after surgery, suggesting adenomatous changes in the pituitary somatotrophs. Before surgery, exogenous GHRH induced a marked increase in plasma GH, and somatostatin and its agonist (SMS201-995) completely suppressed GH secretion, but not IR-GHRH release. No pulsatile secretion of either IR-GHRH or GH was observed during sleep. An apparent increase in the plasma GH concentration was observed in response to administration of TRH, glucose, arginine or insulin, while plasma IR-GHRH did not show any fluctuation. However, these responses of plasma GH were reduced or no longer observed one month and one year after surgery. These results indicate that 1) a moderate increase in circulating GHRH due to ectopic secretion from a pancreatic tumor stimulated GH secretion resulting in acromegaly, and evoked GH responses to various provocative tests indistinguishable from those in patients with classical acromegaly, and 2) the ectopic secretion of GHRH may play an etiological role in the pituitary lesion of this patient with MEN type I.     

Cellular hypersensitivity to human pancreatic B-cell clone in diabetes mellitus and its relationship to the presence of islet cell antibodies

A leukocyte migration inhibition test on the human pancreatic B-cell clone (JHPI-1) was performed in 13 IDDM patients with islet cell cytoplasmic antibody (ICCA) and/or islet cell surface antibody (ICSA), 15 IDDM patients without ICCA or ICSA, 34 NIDDM patients and 17 healthy controls. The mean values for the migration index (M.I. %) in each group were 85.4 +/- 6.9, 89.1 +/- 10.9, 98.3 +/- 7.9 and 100.0 +/- 8.5. The M.I. values were significantly decreased in IDDM patients than in NIDDM patients and controls irrespective of whether or not there were islet cell antibodies in the patients' sera. When M.I. values less than 0.83 (Mean-2 S.D.) were taken as indicative of inhibition, the percentage of IDDM and NIDDM patients with migration inhibition were 32% and 0% respectively. And the decreased M.I. values in IDDM patients proved not to be due to non-specific migration inhibition by normal M.I. values, with the human fetal lung fibroblast cells (W 138) as antigen. Our data suggested that the lymphocytes of IDDM patients might be sensitized by pancreatic B-cell antigen(s) present in the JHPI-1 cells, which promoted leukocyte migration inhibition. No correlation between the migration indices and duration of diabetes mellitus in IDDM patients was observed (r = 0.254, Y = 84.9 + 0.49 X). LMT to JHPI-1 seems to be useful in detecting the abnormal cell-mediated immunity even in patients with longstanding IDDM.     

Physiological plasma concentrations of cholecystokinin stimulate pancreatic enzyme secretion and gallbladder contraction in man

The present study was undertaken to determine whether infusion of cholecystokinin (CCK) to plasma concentrations comparable to those found after a meal stimulates pancreatic enzyme secretion and gallbladder contraction. Plasma CCK concentrations were measured by radioimmunoassay using antibody T204, which binds to all carboxyl-terminal CCK-peptides containing the sulfated tyrosine region. Ingestion of a standardized test meal in 7 normal subjects induced significant increases in plasma CCK from 2.0 +/- 0.2 pmol/l to levels between 4.6 +/- 0.6 and 7.3 +/- 1.0 pmol/l (p less than 0.05-p less than 0.0005). Infusion of 2.5 pmol/kg X h CCK 33 resulted in significant increases in plasma CCK from 2.0 +/- 0.2 to 3.9 +/- 0.3 pmol/l (p less than 0.0005). This infusion of CCK induced significant increases in trypsin secretion from 0.5 +/- 0.1 to 1.4 +/- 0.2 KU/15 min (p less than 0.005) and in bilirubin output from 1.6 +/- 0.7 to 30.3 +/- 8.0 mumol/15 min (p less than 0.05). It is concluded that physiological plasma concentrations of CCK stimulate pancreatic enzyme secretion and gallbladder contraction in man.     

A radioimmunoassay for plasma dehydroepiandrosterone sulphate incorporating placental steroid sulphatase as a hydrolysing reagent

We describe a method for the measurement of plasma dehydroepiandrosterone sulphate (DHAS) which incorporates a Triton X-100 solubilised preparation of human placental steroid sulphatase as a hydrolysing agent and a direct radioimmunoassay of liberated DHA using a specific antiserum. The hydrolysis procedure is carried out at 50 degrees C for 1 h and an assay run can be completed in 4 h. As determined by the method, plasma concentrations of DHAS in 32 normal adult men (ages 23-58 yr) had a mean value +/- SD of 5.5 +/- 1.89 mumol/l. For 30 normal adult cyclic women (ages 22-35 yr) the mean plasma concentration of DHAS +/- SD was 3.1 +/- 1.35 mumol/l which was significantly lower (P less than 0.01) than found for men. Plasma DHAS concentration were also measured in 50 hirsute female patients. The mean value +/- SD was 5.03 +/- 2.52 mumol/l which was significantly higher (P less than 0.01) than the value for the normal female group. Some 42% of the hirsute patients had DHAS concentrations above the upper 95% probability limit of the normal range for premenopausal women.     

Pancreastatin-like immunoreactivity in human carcinoid disease

Pancreastatin-like immunoreactivity has been demonstrated in human carcinoid tumors by immunohistochemistry and radioimmunoassay, employing antisera raised to a synthetic C-terminal fragment of porcine pancreastatin. Immunohistochemistry revealed intense immunoreactivity in all tumors. By radioimmunoassay, high concentrations of pancreastatin-like immunoreactivity were measured in carcinoid tumors arising from the fore-gut (mean +/- S.D. and range: 369 +/- 955 and 9.4-3670 pmol g-1, respectively, n = 14), mid-gut (mean +/- S.D. and range: 1354 +/- 1538 and 337-3978 pmol g-1, respectively, n = 5) and in metastases associated with mid-gut tumors (mean +/- S.D. and range: 684 +/- 739 and 31-2255 pmol g-1, respectively, n = 7), compared to corresponding normal tissues (less than 1.4 pmol g-1). Individuals with hepatic metastases and carcinoid syndrome had elevated circulating levels of pancreastatin-like immunoreactivity (mean +/- S.D. and range: 770 +/- 1249 and 42-4120 pmol l-1; n = 12), significantly above the normal, fasting range (mean +/- S.D. and range: 14.9 +/- 7.5 and 4-37.5 pmol l-1, respectively, n = 42). However, patients with non-metastatic carcinoid tumors (n = 4), who had been clinically cured after primary tumor resection, had plasma levels within the normal range. Chromatographic analysis of extracts of primary lung and ileal tumors, hepatic metastases from ileal tumors and plasma from individuals with carcinoid syndrome revealed molecular heterogeneity of pancreastatin-like immunoreactivity.     

Effect of thyroid hormone therapy on plasma insulin-like growth factor I levels in normal subjects, hypothyroid patients and endemic cretins

The effect of thyroid hormone therapy (L-T4 or L-T3) on plasma immunoreactive insulin-like growth factor I (somatomedin C, Sm-C) concentrations was studied in 8 normal controls, 14 primary hypothyroid subjects and in 7 patients with endemic cretinism. In normals basal levels of Sm-C (1.56 +/- 0.77 U/ml) increased to (2.46 +/- 1.0 U/ml; L-T4) and to (2.9 +/- 0.95 U/ml; L-T3). Plasma Sm-C basal levels were significantly lower in primary hypothyroid subjects (0.81 +/- 0.48 U/ml) and increased to 2.54 +/- 1.43 U/ml (L-T4) and to 2.16 +/- 0.83 U/ml (L-T3). A significant and positive correlation (r = 0.56) was found between Sm-C and serum T4 and T3 concentrations. Plasma Sm-C concentrations in endemic cretinism were initially normal in 4 patients, but low in the remaining 3 (mean +/- SD: 1.18 +/- 0.63 U/ml) and did not increase after 12 months (1.34 +/- 0.61 U/ml) or 18 months (1.01 +/- 0.43 U/ml) of L-T4 and L-T3 therapy. Plasma T4 levels and free T4 increased considerably in EC after therapy with a significant decrease in the previously elevated plasma TSH concentrations. The subnormal response of plasma Sm-C during effective thyroid thyroid hormone therapy could be an additional factor involved in growth failure of endemic cretins.     

Increased plasma plant sterol levels in heterozygotes with sitosterolemia and xanthomatosis

Plasma sterol levels in a family of sitosterolemia and xanthomatosis were determined by a high performance liquid chromatography. Three affected siblings manifested marked xanthomatosis including subcutaneous soft tissues and generalized atherosclerosis. Two other siblings as well as children of the patients did not show such clinical symptoms and signs. Plasma levels of cholesterol, sitosterol, campesterol, and cholestanol in three affected subjects were 190 +/- 18.5, 25.9 +/- 11.6, 16.1 +/- 7.8, 1.84 +/- 0.92 mg/dl (mean +/- SD), respectively. Four daughters of the affected subjects, who should be considered as obligatory heterozygotes, showed moderately increased levels of these sterols (195 +/- 41.7, 1.33 +/- 0.44, 1.56 +/- 0.69, 0.80 +/- 0.28 mg/dl), which were significantly higher than those of normal subjects. Treatment with cholestyramine had little effect on the increased plasma plant sterol levels, but markedly decreased plasma cholestanol concentrations in two affected siblings. This report presents the clinical features of the patients with sitosterolemia and xanthomatosis and also demonstrates that heterozygotes with this disorder have increased plasma levels of plant sterols as well as cholestanol, and suggests that this rare disease might be inherited as an autosomal co-dominant trait in certain cases. The data also indicate that cholestyramine administration was not effective in this family for treatment of sitosterolemia.     

Plasma cortisol and corticosteroid-binding globulin in essential hypertension

Plasma concentration of cortisol, total CBG-binding capacity, and blood pressure were measured in control subjects (n = 171), patients with essential hypertension (EH; n = 210) and their first-degree normotensive (NR; n = 84) or hypertensive (HR; n = 66) relatives. Mean (+/- SD) plasma cortisol was significantly (p less than 0.001) decreased in EH (10.1 +/- 4.3 g/dl) patients and HR (11.7 +/- 4.1). Plasma cortisol in NR did not differ from control values (14.3 +/- 4.5) but the distribution of individual values covered the entire control-EH (14.6 +/- 5.5) range. Mean (+/- SD) CBG-binding capacity was significantly (p less than 0.001) lower in EH (14.4 +/- 3.0), NR (17.5 +/- 2), HR (17.6 +/- 2.2) as compared to controls (20.9 +/- 2.1), indicating that the decline in EH and in most relatives was mainly in plasma CBG-bound cortisol. The plasma CBG-binding capacity for cortisol was significantly negatively correlated with mean arterial pressure (MAP) in both controls (p less than 0.001) and NR (p less than 0.01) but not in either HR (r = 0.02) or never-treated EH patients. Total afternoon plasma aldosterone was higher (p less than 0.01 vs. controls) in 93 untreated EH patients (11.2 +/- 4.8 ng/dl) than in either 161 first-degree relatives (8.1 +/- 3.4 ng/dl) or 117 controls (7.6 +/- 3.5 ng/dl). The respective aldosterone-binding globulin (ABG) binding capacities for aldosterone were 21.2 +/- 6.7, 20.1 +/- 9.3 and 9.8 +/- 4.0%. In all these subjects taken together, there was a positive correlation between MAP and ABG-binding capacity (r = 51; p less than 0.001). The association of reduced plasma cortisol and decreased CBG binding capacity in EH may be closely related to altered steroid metabolism, which may be partly explained by an abnormality resembling a relative deficiency in adrenal 17 alpha- and 11 beta-hydroxylation. In some EH patients, hypertension may be the result of the ineffectiveness of plasma cortisol in preventing slightly elevated endogenous ACTH levels leading to an increase in ACTH-sensitive steroids.     

Islet cell tumor of the pancreas: increasing diagnosis after instituting ultrasonography-guided fine needle aspiration

OBJECTIVE: To review the clinical and cytomorphologic features of pancreatic islet cell tumors (ICT). STUDY DESIGN: Computer search identified patients with pancreatic ICT diagnosed by fine needle aspiration biopsy (FNAB) between January 1995 and December 2003. Clinical, radiographic, and cytomorphologic findings were reviewed. RESULTS: Thirty-eight patients (19 men, 19 women; median age 60 years, range 30-82) with ICT were identified; 30 were diagnosed through endoscopic ultrasonography (EUS)-FNAB and 8 through computed tomography (CT)-guided FNAB. Smears of 37 specimens had adequate cellularity. Most were highly cellular with bloody backgrounds. No major differences were observed between specimens obtained by EUS-FNAB or CT-FNAB. Radiographically, 20 tumors measured 1-5 cm, 7 were > 5 cm and 4 < 1 cm. Twenty-two patients underwent tumor resection. CONCLUSION: Newer radiography and biopsy techniques to detect and examine smaller pancreatic masses have increased the number of pancreatic ICT diagnoses at our institution. The distinctive cytomorphologic features of pancreatic ICT make it reliably diagnosable by FNAB.