Androgen stimulation of gross cystic disease fluid protein and carcinoembryonic antigen in patients with metastatic breast carcinoma.

Plasma levels of carcinoembryonic antigen (CEA) and the 15,000 molecular weight gross cystic disease fluid protein (GCDFP-15) were determined in 30 patients with metastatic breast carcinoma before, during, and after treatment with fluoxymesterone. Within 2 weeks after initiation of treatment, plasma levels of GCDFP-15 increased 50% above basal values in 15 (79%) of 19 patients. Similar increases in plasma CEA levels occurred in only 5 (23%) of 22 patients. Eight (33%) of 24 patients achieved increases in GCDFP-15 of 500% or more above basal levels after 14-336 days of therapy. Within 2 weeks of fluoxymesterone termination, 14 (93%) of 15 patients had a decrease in plasma GCDFP-15 levels, and in 12 (80%) the decrease exceeded 33% (the inverse of a 50% increase). Conversly, only 5 (33%) of 15 patients experienced a decrease in plasma CEA levels within 2 weeks of therapy termination, and in only 1 (6.7%) subject did the decrement exceed 33%. Nine (90%) of 10 patients who had 50% increases in plasma GCDFP-15 during initial androgen therapy also had significant decreases in plasma GCDFP-15 following termination of therapy. Data on 3 prospectively studied patients demonstrated that plasma GCDFP-15 rose within 24 hours of initiation of fluoxymesterone therapy and continued to rise for at least 6 days. Increased plasma levels of GCDFP-15 were reflected in increased urinary excretion of the glycoprotein.

Immunocytochemical analysis of estrogen receptors as a predictor of prognosis in breast cancer patients: comparison with quantitative biochemical methods.

Biochemical quantitation of estrogen receptors has been used to predict prognosis in breast cancer. Immunocytochemical analysis of estrogen receptors correlates with biochemical analysis but has very few follow-up studies in the literature to validate it as a prognostic indicator. 257 patients were followed for up to 10 years (median, 6.2 years) after primary surgical treatment. Estrogen receptor analysis using both biochemical and immunocytochemical techniques was performed on their tumor specimens. Patients with positive estrogen receptor values had longer survival than patients with negative values. This was demonstrated by both methods in the first 5 years of follow-up but only by immunochemistry after 5 years. The relationship between estrogen receptor status and disease-free interval was less strong than with survival. This study demonstrates that immunocytochemical estrogen receptor analysis was of prognostic significance.

Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors.

A monoclonal antibody to human estrogen receptor protein (H222 Sp gamma), amplified via immunoperoxidase techniques, was used in the analysis of estrogen receptor in 452 breast carcinomas, 100 endometrial carcinomas, and 15 melanomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining (HSCORE). Quantitative estrogen receptor content was determined by dextran-coated charcoal analysis and sucrose density gradient analysis. In all cases H222 Sp gamma localized in the nucleus of target cells. A semiquantitative correlation existed between HSCORE and biochemical assays for breast and endometrial tissues. The sensitivities and specificities for HSCORE as compared to the biochemical assays ranged from 80 to 95% and from 74 to 94%, respectively. HSCORE correlated with tumor grade for breast and endometrial carcinoma. Immunohistochemical evaluation showed no specific staining in melanomas. The data suggest that immunohistochemical receptor localization provides information complementary to standard biochemical assays in the tissues studied.

Iodine 131-labeled metaiodobenzylguanidine scintigraphy and biochemical analyses in suspected pheochromocytoma.

Detection of abnormal catecholamine levels and localization of tumor mass are important factors in the diagnosis and treatment of pheochromocytoma. Iodine 131-labeled metaiodobenzylguanidine scintigraphy was performed in 64 patients with suspected pheochromocytoma if their urinary catecholamine levels were borderline or elevated, or if the clinical suspicion for pheochromocytoma was high in spite of normal urinary catecholamine determinations. The 131I-metaiodobenzylguanidine scans were evaluated for abnormal localization of tracer. Twenty-four-hour urine collections were analyzed for vanillylmandelic acid, homovanillic acid, dopamine, epinephrine, and norepinephrine. Thirty of the 64 patients had pheochromocytomas. The 131I-metaiodobenzylguanidine scan had a sensitivity and a specificity of 88%. The 24-hour urine vanillylmandelic acid and norepinephrine measurements had the best sensitivity (97%), while the vanillylmandelic acid and homovanillic acid measurements had the best specificity (91%). In patients in whom the vanillylmandelic acid measurement and the 131I-metaiodobenzylguanidine scan were normal, no pheochromocytomas were found. In patients in whom the vanillylmandelic acid measurement and 131I-metaiodobenzylguanidine scan were abnormal, a pheochromocytoma was always present. The 131I-metaiodobenzylguanidine scan often documents the presence or absence of a pheochromocytoma and provides localization of the tumor in the preoperative evaluation of these patients.

What is the clinical significance of bone loss in primary hyperparathyroidism?

To help determine the clinical significance of the bone loss associated with primary hyperparathyroidism, we studied the prevalence of vertebral fractures in a group of patients with this disorder. From a registry of parathyroidectomies, 206 cases were reviewed, and lateral chest roentgenograms were studied for the presence of fractures. All roentgenograms were interpreted by two of the investigators who were "blinded" to diagnoses. Comparisons of readings were made that assured interrater agreement. A group of patients who underwent cholecystectomy served as controls. Studied in a logistic regression analysis model, controlling for the effects of age, sex, and race, primary hyperparathyroidism was found to be significantly associated with vertebral fractures. Subgroup analyses performed on the patients with hyperparathyroidism failed to identify specific biochemical or clinical markers associated with fractures. Our results suggest that the bone loss of primary hyperparathyroidism is clinically significant, leading not only to decreased bone densities but also to an increased prevalence of fractures.

Parathyroid hormone secretion from dispersed human hyperparathyroid cells: increased secretion in cells from hyperplastic glands versus adenomas.

The in vitro secretion of PTH by dispersed human parathyroid cells was examined under conditions of low and high extracellular Ca+2 using tissue from patients with primary hyperparathyroidism and hyperparathyroidism resulting from chronic renal failure (CRF). The PTH secretion rate (nanograms of PTH per 10(5) cells/h) was lower in adenomatous tissues than in either primary hyperplastic cells or CRF cells under conditions of low (0.5 mM) or high (2.0-3.0 mM) extracellular Ca+2. Among the adenomas, a wide spectrum of degree of suppressibility of PTH secretion by high Ca+2 was found, ranging from 0% (completely nonsuppressible) to 98%. Suppression of the hyperplastic tissues in general was similar. The most suppressible adenomas demonstrated 2-fold greater PTH secretion rates in low Ca+2 conditions than the least suppressible adenomas, but in high Ca+2 conditions, the two groups had similar secretory rates. We conclude that the rate of PTH secretion by cells from adenomas was substantially lower than that of cells from tissues exhibiting either primary hyperplasia or hyperplasia resulting from CRF under these in vitro conditions. Thus, in adenomas, an increase in absolute cell number as well as alterations in the degree of calcium responsiveness may prove to be important etiological factors in the expression of hyperparathyroidism.

Stimulation of insulin secretion by a rapid intravenous calcium infusion in patients with beta-cell neoplasms of the pancreas.

The effects of calcium on fasting plasma insulin and glucose levels were compared in 16 normal subjects and 11 patients with beta-cell neoplasms of the pancreas. Calcium was administered iv either as a rapid calcium infusion (RCI; 2 mg/kg in 1 min) or as a long calcium infusion (LCI; 12 mg/kg in 3 h). In normal subjects, the RCI produced a rise in mean plasma insulin from 11 +/- 1 (+/- SEM) microU/ml basally to a peak of 18 +/- 2 microU/ml (P less than 0.001). No consistent pattern of change in insulin levels occurred during the LCI, and plasma glucose levels did not change significantly with either test. In the patients with beta-cell neoplasms, the RCI resulted in a rapid increase in mean plasma insulin from 36 +/- 6 microU/ml to a peak level of 312 +/- 67 microU/ml (P less than 0.002). With the LCI, a more gradual rise in insulin from 35 +/- 11 to 92 +/- 36 microU/ml occurred (P less than 0.002). The mean increase in insulin in the patients with beta-cell neoplasms was significantly greater for the RCI than for the LCI (P less than 0.01). Pronounced increments in plasma insulin occurred in all 11 patients after the RCI, but in only 3 of 8 patients during the LCI. Plasma glucose levels declined significantly from 69 +/- 7 to 56 +/- 8 mg/dl during the RCI (P less than 0.05) and from 69 +/- 8 to 49 +/- 7 mg/dl during the LCI (P less than 0.005). Symptomatic hypoglycemia developed in 3 patients during the LCI but did not occur after the RCI. These data indicate that calcium is a more effective insulin secretagogue in patients with beta-cell neoplasms when administered as an RCI than as an LCI, and suggest that the RCI may be a useful test for the diagnosis of insulin-secreting tumors.

Intraluminal thrombus and bowel obstruction in acute leukemia due to bleeding Meckel's diverticulum.

Gastrointestinal bleeding from Meckel's diverticulum resulted in small bowel obstruction by thrombus in two patients with acute myelogenous leukemia during bone marrow aplasia and recovery from induction chemotherapy. Although gastrointestinal symptoms and complications are common in acute leukemia, these two cases are unique and describe a new syndrome that requires prompt recognition and surgical intervention. The complication of localized bowel obstruction by intraluminal thrombus is heretofore unreported.

Transplantation in miniature swine. II. In vitro parameters of histocompatibility in MSLA homozygous minipigs.

A selective breeding program based on serological techniques was used to establish three herds of miniature swine, each homozygous for a different allele at the major histocompatibility complex, termed MSLA. By selective immunization of these swine, high-titered antisera detecting the products of individual MSLA alleles were raised and used to confirm the genotype of offspring in these herds. Techniques for performing one-way mixed leukocyte cultures in these pigs were developed and demonstrated the presence of a strong mixed leukocyte culture locus (or loci) closely linked to the serologically defined MSLA locus. Cell-mediated cytotoxicity assays based on 51Cr release were developed to monitor the course of cellular immunity following allotransplantation and exhibited specificity identical to that predicted by the serological typing.

Transplantation in miniature swine. VI. Factors influencing survival of renal allografts.

Renal allografts were performed between and among animals from three herds of miniature swine that were selectively inbred to homozygosity at the major histocompatibility complex, MSLA. The results suggest several genetic factors which influence the survival of renal allografts in these animals. As expected, the major histocompatibility complex (MHC) was of dominant importance, and all MSLA-mismatched grafts were rejected promptly (12 +/- 3.7 days). Some MSLA-matched grafts were also rejected (30 +/- 15.0 days), indicating that non-MSLA loci also determine antigens which can lead to kidney rejection. Other MSLA-matched grafts were accepted indefinitely. At least one immune response gene that determined ability to reject kidneys across non-MSLA differences seemed to be segregating in our swine population. Animals that had accepted MSLA-matched renal grafts for extended periods demonstrated markedly prolonged survival of subsequent donor skin grafts compared to skin graft survival across the same non-MSLA difference in normal animals. This finding suggests that failure to reject kidneys across non-MSLA differences indicates systemic tolerance, and that there may be a relationship between the induction of such tolerance and the proposed immune response gene controlling rejection.

Initial experience with intraoperative PTH determinations in the surgical management of 130 consecutive cases of primary hyperparathyroidism.

BACKGROUND: Successful surgical management of primary hyperparathyroidism (1 degree HPT) historically has required bilateral neck exploration. The intraoperative parathyroid hormone (IO-PTH) assay allows a more limited procedure by confirming complete removal of hypersecreting tissue. METHODS: Plasma samples were obtained from 130 consecutive patients both before (preincision and preexcision baselines) and at approximately 5 and 10 minutes (and additional times) after removal of abnormal parathyroid tissue. Samples were assayed for IO-PTH by a rapid, two-site immunochemiluminescent assay (ICMA) with a 7-minute incubation at 45 degrees C. RESULTS: Plasma IO-PTH decreased by at least 50% in 126 of 130 cases; however, three of these cases were false positives. The four cases in which IO-PTH fell < 50% were classified as two true negatives and two false negatives. A single adenoma was removed in 125 cases, and two or three hyperplastic glands were removed in five cases. CONCLUSIONS: IO-PTH predicted the postoperative outcome in 125 of 130 cases (96.2%), including two of five cases in which multiple hyperplastic glands were removed, and 1 degree HPT was successfully treated in 97.7% (127/130) of the cases. The IO-PTH procedure can provide valuable confirmation to the endocrine surgeon; however, other sources of information must also be used to ensure that all hyperplastic glands are identified.

Function in athymic nude mice of parathyroid heterografts from patients with primary hyperparathyroidism and secondary hyperparathyroidism.

Heterotransplantation of adenomatous parathyroid glandular tissue from humans with primary hyperparathyroidism into athymic nude mice creates a unique animal model of this disease. The mice manifest high concentrations of both midregion/C-terminal human parathyroid hormone and biologically active intact human parathyroid hormone relative to either mice with no implants or mice that received normal human parathyroid tissue. Secretion of these substances is maintained in most mice for at least 9 to 13 months after implantation. In addition, animals that have experienced implantation exhibit other characteristics associated with human primary hyperparathyroidism including relative hypercalcemia and increased renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity. We also measured these parameters in a group of nude mice that received transplantation of a similar mass of hyperplastic parathyroid tissue that was obtained from patients with uremic secondary hyperparathyroidism. Although we hypothesized that the level of human parathyroid hormone secretion from these implants would fall over time in response to the normal host environment, hormone levels remained as high as those in recipients of adenomatous heterografts, even after 9 to 13 months. Moreover, similar biologic effect of the excess parathyroid hormone (i.e., relative hypercalcemia, hyperphosphatasemia, and increased 1,25-dihydroxyvitamin D biosynthesis) were detected. These animal models should prove extremely useful in supplementing our understanding of hyperparathyroid disorder in man.

Malignant teratoma in the thyroid gland of an adult: a case report and a review of the literature.

Teratomas in the neck are rare neoplasms. Most occur in the neonate and are benign. In contrast, cervical teratomas in adults are malignant and carry a poor prognosis. Fourteen adult cases have been reported in the world literature, and 11 of these were stated to have arisen in the thyroid gland. A case of a 27-year-old man who presented with a large goiter is reported. A preoperative diagnosis of a malignant thyroid mass was suggested by clinical examination, needle aspiration, and computerized tomography. The patient had a subtotal debulking thyroidectomy. The pathologic specimen confirmed a primary malignant teratoma of the thyroid gland. Despite a combination of radiotherapy and chemotherapy, which were well tolerated, the patient died 2 months after surgery.

Intraoperative parathyroid hormone monitoring during parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: The surgical management of secondary hyperparathyroidism by experienced surgeons is associated with excellent results. The presence of supernumerary glands and inadequate initial parathyroidectomy can lead to reoperations for recurrence. Intraoperative parathyroid hormone monitoring (qPTH), which has been described during parathyroidectomy for primary hyperparathyroidism, may be helpful in preventing or predicting the need for reoperation. This report describes the use of qPTH assays during parathyroidectomy in patients with secondary hyperparathyroidism. METHODS: Intraoperative parathyroid hormone (PTH) levels were determined in 13 patients with secondary hyperparathyroidism undergoing total parathyroidectomy with autotransplantation (n = 3) or subtotal parathyroidectomy (n = 10). Levels were determined using a modified immunochemiluminometric assay (qPTH). RESULTS: The average PTH levels before and after parathyroidectomy were 1599 pg/ml (620 to 2486 pg/ml) and 230.3 pg/ml (129 to 345 pg/ml), respectively. All patients had significant decreases in PTH levels after parathyroidectomy (mean, 84.6%). Symptoms were improved in all patients after operation. PTH levels at early follow-up were consistently below intraoperative levels. CONCLUSIONS: Intraoperative PTH monitoring reproducibly demonstrates the clinically relevant decrease in PTH levels after parathyroidectomy for secondary hyperparathyroidism similar to those previously documented in patients with primary hyperparathyroidism. Long-term follow-up and increasing numbers of patients are crucial in defining the role of qPTH monitoring during parathyroidectomy for secondary hyperparathyroidism.

Sex steroid receptor concentration in breast carcinoma tissue: effect of devascularization during mastectomy.

The accurate determination of sex steroid receptors at the time of mastectomy (MX) for breast carcinoma is important for the determination of subsequent therapy of patients who develop metastases in inaccessible sites. The estrogen (E) and progesterone (P) receptor (R) proteins are heat labile, and measured levels may be vulnerable to alterations once the tumor is devascularized. To evaluate potential differences in ER and PR determinations in tumor tissue acquired at biopsy as compared with tumor from the MX specimen, quantitative analyses of ER (21 patients) and PR (17 patients) were performed on dual samples acquired from the initial biopsy (BX) and the subsequent MX specimen. Receptor concentrations were determined both by sucrose density gradient analysis and titration analysis, and results were expressed as fmol/mg cytosol protein. ER values were classified as receptor-rich (greater than 10 fmol/mg), intermediate (3 to 10 fmol/mg), or receptor-poor (less than 3 fmol/mg); PR values greater than 3 fmol/mg were considered positive. ER BX values were found to be rich or intermediate in 18 patients. When compared with BX values, MX ER values were quantitatively unchanged in 11 patients, lower (MX less than BX) in four patients, and higher in three patients (MX greater than BX). In no patient was the BX ER rich or intermediate and the concomitant MX ER poor. In two patients the PR value was "positive" at BX but "negative" at MX. Accordingly, malignant tissue from a pre-MX biopsy specimen is preferred for receptor analysis although it is apparent that tumor tissue from a properly handled MX specimen is satisfactory for the determination of ER status for clinical purposes.

Circadian rhythms for calcium, inorganic phosphorus, and parathyroid hormone in primary hyperparathyroidism: functional and practical considerations.

We obtained serial serum and urine samples from 14 patients with primary hyperparathyroidism both before and 3 to 9 months after excision of their parathyroid adenomas to (1) determine whether the circadian rhythms for calcium, phosphorus, and parathyroid hormone (PTH) previously described in normal human beings are disturbed in this disorder; (2) gauge the effect of surgical treatment on the patterns observed before intervention; and (3) ascertain whether time(s) of blood sampling can be defined for optimal biochemical detection of the disease. Significant rhythms for serum phosphorus, ionized calcium, PTH, urine phosphorus, and urine calcium were observed in many but not all patients before and after surgery. Nonetheless, collective analysis revealed the following: (1) diurnal patterns for serum ionized calcium, phosphorus, urine calcium, and urine phosphorus in patients with primary hyperparathyroidism both before and after surgery, whereas a rhythm for serum PTH was uniquely observed after surgical treatment; and (2) no significant correlation between preoperative serum ionized calcium and PTH but restoration of the expected reciprocal relationship between these variables after surgery. Although variability in individual expression of the rhythm for PTH precludes precise definition of a sampling "window" when hormone levels are likely to be highest, collection of data at points throughout the day helped establish the diagnosis of primary hyperparathyroidism in several patients with borderline serum biochemistries.

The role of circulating N-terminal parathyroid hormone fragments in the early postparathyroid adenomectomy period.

Calcium metabolism and hormonal control after parathyroid adenomectomy are poorly understood. During the first postoperative hours, biologically active intact parathyroid hormone (PTH) (hPTH 1-84) levels are subnormal and, in spite of down-regulation of PTH peripheral receptors (caused by hypercalcemia before surgery), total and ionized calcium concentrations are maintained in the normal range. Serum samples from 20 patients with primary hyperparathyroidism were collected in the immediate preoperative period and 4 and 48 hours after excision of one parathyroid adenoma. Total and ionized calcium, intact (iPTH), midregion (mrPTH) specific PTH (hPTH 53-68), and N-terminal PTH (N-PTH) serum concentrations were determined. Levels of N-PTH were obtained with a radioimmunoassay by a modified reverse immunoextraction procedure that measures N-PTH fragments after exclusion of the interfering iPTH. No significant correlation was found between ionized and total calcium, mrPTH, and iPTH. However, total and ionized calcium levels correlated well with N-PTH (r = 0.9999, p = 0.0054, and r = 0.9993, and p = 0.0226, respectively). The data suggest that the relatively moderate decrease in calcium levels, in spite of marked decrease in circulating iPTH during the first postoperative hours, may be attributable to the minimal decrease of the bioactive N-PTH epitope concentrations. We would hypothesize that hPTH (1-34) fragments may play a significant role in regulating serum calcium levels in the early postoperative period.

The role of resection in the management of melanoma metastatic to the adrenal gland.

Melanoma metastatic to the adrenal gland diagnosed before death was exceedingly rare before the development of computed tomographic (CT) scanning. The records of 28 patients with melanoma metastatic to the adrenal gland seen since 1975 were reviewed. Eighteen patients were men and 10 were women. Twenty-three patients had unilateral disease. Four patients were diagnosed only at autopsy, leaving 24 for analysis of treatment and survival. Twenty-one patients had received specific active immunotherapy, four had received chemotherapy (dacarbazine, lomustin, bleomycin, and vincristine), and three had received both before the diagnosis of their adrenal disease. Adrenal metastases were diagnosed by CT scanning in 14 patients with symptoms, 10 (91%) of whom had pain. Ten patients were diagnosed by CT before entry into a chemotherapy protocol. Of eight patients who underwent resection of all known disease, five underwent unilateral adrenalectomy, two underwent unilateral adrenalectomy and bowel resection, and one underwent bilateral adrenalectomy. Two patients underwent partial resection of large unilateral tumors. Fourteen patients with adrenal metastases and disease elsewhere were initiated or continued with chemotherapy or were treated symptomatically. Mean survival in the group that underwent resection for cure was 59 months (3 to 112 months), whereas survival in the group with unresectable tumors was 15 months (1.5 to 132 months). Four of eight patients who underwent resection for cure lived more than 5 years after detection of adrenal metastasis, whereas in only one of 14 patients with unresectable tumors was the same true. Patients with metastatic melanoma localized to one or both adrenal glands may benefit from early detection and surgical intervention.

Quantitative analysis of the calcium-sensing receptor messenger RNA in parathyroid adenomas.

BACKGROUND: In primary hyperparathyroidism, hypercalcemia fails to suppress adequately secretion of parathyroid hormone by the parathyroid gland, which may result from failure of the cell-surface calcium receptor (CaR) to sense calcium correctly. Quantification of mRNA concentrations should provide important information on the role of expression of Call in primary hyperparathyroidism. METHODS: We have developed a quantitative reverse transcriptase-polymerase chain reaction assay with a competitive template (CaR-M). Amplified cDNAs for CaR and CaR-M are quantified, and the concentration of CaR mRNA is determined from the ratio of CaR-M/CaR versus known CaR-M concentrations. RESULTS: In parathyroid adenomas (n = 12) the CaR mRNA was 19.2 +/- 2.4 (mean +/- SE) fg/ng total RNA (range, 7.4 to 32.8 fg/ng). Extracellular ionized calcium levels ranged from 1.38 to 1.74 mmol/L (normal 1.19 to 1.31 mmol/L) and parathyroid hormone from 69 to 345 pg/ml (normal, 14 to 65 pg/ml). In spite of the wide variability in CaR expression in the various adenomas, there was no correlation between mRNA and either extracellular ionized calcium (r2 = 0.013) parathyroid hormone levels (r2 = 0.001). Normal human parathyroid glands gave values of 8.0 and 16.6 fg/ng, whereas normal bovine parathyroid glands had a mean of 20 +/- 0.6 fg/ng (n = 4). CONCLUSIONS: There is no apparent relationship between CaR mRNA levels in adenomas and preoperative Ca and PTH levels. Our findings suggest that defective Ca sensing in adenomas may involve post-translational modification or signal transduction distal to the receptor. Our highly sensitive assay for CaR mRNA should prove useful in examining further the role of CaR in Ca sensing in parathyroid tissue.

Parathyroid hormone secretion and target organ response in experimental acute pancreatitis.

To determine changes in parathyroid hormone secretion and target organ response caused by acute pancreatitis before the development of systemic toxic conditions, experimental acute pancreatitis was induced in rats with a choline-deficient, ethionine-supplemented diet. After 7 days, the rats were weighed and bled, and one kidney was assayed for 25-hydroxyvitamin D1 hydroxylase activity. Several manifestations of pancreatitis were observed in rats given the diet: weight loss (from 29.6 to 26.3 g vs that for control rats, from 29 to 52.8 g) and lower dietary intake (15.5 vs 47 g per rat per 7 days). Serum amylase levels fell from 1794 to 350 U/L in rats given the choline-deficient, ethionine-supplemented diet compared with levels of 1800 to 2100 U/L in control rats. The pancreases of rats given the choline-deficient, ethionine-supplemented diet showed degeneration, necrosis, and hemorrhaging. Serum levels of calcium, phosphorus, chloride, and parathyroid hormone did not change significantly throughout the experiment. Renal 25-hydroxyvitamin D1 hydroxylase activity was higher than in control rats (8.9 +/- 0.8 vs 7.6 +/- 0.6 fmol/mg of kidney per minute). Acute pancreatitis in this experimental animal model does not alter serum levels of calcium and parathyroid hormone or reduce target organ responsiveness to the hormone.