Pancreatitis and hyperparathyroidism

Hypercalcaemia is considered to be a rare cause of pancreatitis but the true cause-and-effect relationship between hyperparathyroidism and pancreatic inflammatory disease remains controversial. Over 100 patients have been reported in whom both processes have occurred concurrently, but doubts have been expressed as to whether or not this association is due to chance. We report 10 new cases of hypercalcaemic hyperparathyroidism associated with different types of pancreatitis. Seven patients had primary hyperparathyroidism and three had hyperparathyroidism after renal transplantation. Two experienced acute pancreatitis after parathyroidectomy. Of the remaining eight patients, five had hypercalcaemia equal to or above 120 mg/l. The prevalence of pancreatitis in our series of 86 cases of primary hyperparathyroidism is 8 per cent. Acute and chronic calcifying types of pancreatitis were observed. Three patients died of the disease, two of them after renal transplantation. It is suggested that pancreatitis may complicate the clinical course of hyperparathyroidism, particularly when hypercalcaemia is moderate to severe and/or there are other risk factors such as treatment with steroids and azathioprine after renal transplantation.     

Recurrence of disease in patients retransplanted for focal segmental glomerulosclerosis.

The natural history of focal segmental glomerulosclerosis in patients retransplanted after loss of a primary allograft is not well established. We studied 14 patients with FSGS who were retransplanted between April 1964 and September 1990 to determine if recurrence in a second or subsequent allograft could be predicted. In this group, 8 of the primary allografts were lost to recurrent disease and 6 to rejection. None of the 6 patients who lost their primary allograft to rejection without evidence of recurrent FSGS suffered recurrent disease after retransplantation. In contrast, 3 of the 8 patients who lost their primary allograft rapidly to FSGS suffered recurrent disease and loss of function in all subsequent allografts. The remaining 5 patients had prolonged function of the primary allograft ranging between 4 and 10.5 years, despite recurrence of FSGS. Of these 5 patients, 2 have excellent renal function after retransplantation without recurrence of FSGS in the secondary allograft at 9 and 10.5 years posttransplant; 2 have lost their secondary allograft to recurrent FSGS, but are free of recurrence in the third allograft at 0.5 and 5.8 years postoperatively; 1 maintains a serum creatinine level of 1.9 mg% despite recurrence of FSGS in the secondary allograft at 1 year postoperatively. Our data show that, without recurrence of FSGS in the primary allograft, further renal transplants will be free of recurrent disease. Based on this finding, we advocate use of living-related donors for second transplants in these patients. With rapid recurrence of FSGS and subsequent accelerated loss of the primary allograft, further renal transplants carry a high likelihood of recurrent FSGS and graft loss. A substantial proportion of patients with recurrent FSGS in the primary allograft will have prolonged renal function, and are likely to have excellent results with subsequent allografts.     

The Scimitar syndrome: CT findings in partial anomalous pulmonary venous return

An anomalous pulmonary vein draining into the subdiaphragmatic inferior vena cava was initially demonstrated on computed tomographic (CT) scans. The diagnosis of scimitar syndrome was confirmed with digital subtraction angiography. In retrospect, the anomalous vein and dextroposition of the heart were shown on chest radiographs.     

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean ± SD of total stool output (g kg⁻¹) was 532 ± 476 vs 479 ± 354 and the duration (h) of diarrhoea was 108 ± 68 vs 103 ± 53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.     

Donor hyperglycemia as a minor risk factor and immunologic variables as major risk factors for pancreas allograft loss in a multivariate analysis of a single institution''s experience.

The impact of multiple donor and recipient variables on functional survival of 307 cadaveric pancreas allografts transplanted in 253 recipients at the authors' institution between July 25, 1978 and September 4, 1990 was determined using the Cox proportional hazards regression model. Relative risk of graft loss was calculated for all cases as well as for technically successful (TS) ones. Factors with an impact in descending order of significance for TS cases were immunosuppression (RR = 3.9 for double-drug versus triple-drug maintenance, p less than 0.0001); recipient category (RR = 2.4 for pancreas alone versus simultaneous pancreas/kidney, p = 0.009); retransplantation (RR = 1.8 for retransplants versus primary grafts, p = 0.007); donor hyperglycemia (RR = 1.7 for blood glucose greater than or equal to 200 versus less than 200 mg/dL, p = 0.02); human leukocyte antigen (HLA) matching (RR = 2.1 for poor versus a good match, p = 0.04). A logistic regression analysis also was performed to determine which factors predisposed to technical failure; none were identified. To make the model as relevant as possible to their current program, the authors analyzed only the bladder-drained cases (n = 221; 1984 to 1990). All patients received triple therapy. Recipient category, retransplantation, donor hyperglycemia, and degree of HLA matching remained as significant risk factors. Construction of estimated survival curves showed that the results of retransplantation were significantly improved, and the penalty incurred by using hyperglycemic donors was partially ameliorated by using well-matched donors. Because preservation times up to 30 hours did not exert an adverse effect on outcome, an argument is made to share pancreata between centers to achieve good matches.     

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.      

Apoptotic body engulfment by a human stellate cell line is profibrogenic

Hepatocyte apoptosis and stellate cell activation are both features of chronic liver diseases, but a relationship between these events has not been explored. In macrophages, engulfment of apoptotic bodies induces expression of transforming growth factor-beta (TGF-beta), a profibrogenic cytokine. We examined whether a similar response occurs in stellate cells. Fluorescently labeled hepatocyte apoptotic bodies were added to cultures of primary and immortalized human stellate cells. Stellate cells, but not hepatocytes, readily engulfed apoptotic bodies in a time-dependent manner as assessed by confocal microscopy. The activation of primary and immortalized human stellate cells after incubation with apoptotic bodies, as well as their fibrogenic activity, was indicated by an increase in alpha-smooth muscle actin (primary cells), TGF-beta1, and collagen alpha1(I) mRNA (primary and immortalized cells). The profibrogenic response was dependent upon apoptotic body engulfment, because nocodazole, a microtubule-inhibiting agent, blocked both the engulfment and the increase of TGF-beta1 and collagen alpha1(I) mRNA. As described in primary rodent stellate cells, up-regulation of collagen alpha1(I) mRNA was inhibited by a PI-3K inhibitor (LY294002) and a p38 mitogen-activated protein kinase inhibitor (SB203580) in LX-1 cells. In conclusion, these data support a model in which engulfment of hepatocyte apoptotic bodies by stellate cells leads to a fibrogenic response by eliciting a kinase-signaling pathway.     

Serum calcium as an early indicator for surgical treatment of hyperparathyroidism after renal transplantation

In an attempt to find out if a particular group of patients with hyperparathyroidism after renal transplantation (HRT) are at risk of developing complications, 14 patients with overt untreated HRT who had at least 1 serum calcium determination 12 mg/100 ml were evaluated and compared retrospectively with 11 normocalcemic transplant recipients at 6 and 30± 8 months after successful renal allografting. Serum calcium was 12 mg/100 ml within 6 months of transplantation in 13 of the 14 HRT patients. At 6 months significant differences were found between HRT and controls in mean serum calcium (11.6 versus 9.2 mg/100 ml) and alkaline phosphatase (228 versus 120 U/l). At 30±8 months differences were found in serum calcium (10.2 versus 9.4 mg/100 ml), phosphate (2.8 versus 4.8 mg/100 ml), and alkaline phosphatase (180 versus 88 U/l). Serum creatinine levels were similar in the 2 groups. A significant correlation was found between early and late determinations of alkaline phosphatase when all 25 patients were studied as a single group (r=0.72, p<0.001). Bone pain and/or radiological evidence of hyperparathyroid bone disease were significantly associated with HRT (8 versus 1 and 7 versus 0, respectively). A higher but not significant incidence of vascular calcifications (5 versus 1) and acute pancreatitis (2 versus 0) was found in HRT. Patients who develop moderate to severe HRT as defined by at least 1 serum calcium determination 12 mg/100 ml do so within 6 months of renal transplantation, have increased morbidity, particularly involving the skeleton, and might benefit from early subtotal parathyroidectomy.

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Resumen Con el propósito de determinar si el grupo particular de pacientes con hiperparatiroidismo después de transplante renal (HTR) posee riesgo de desarrollar complicaciones, se realizó la evaluación de 14 casos definidos de HTR no tratados y que presentaban por lo menos un valor de calcio sérico 12 mg/100 ml, los cuales fueron comparados con 11 recipientes normocalcémicos de transplante renal a los 6 y 30 ±8 meses después de un aloinjerto renal exitoso. El calcio sérico apareció en 12 mg/100 ml dentro de los primeros 6 meses de efectuado el transplante en 13 de 14 pacientes con HTR. A los 6 meses se hallaron diferencias significativas entre los pacientes con HTR y los controles en el valor promedio del calcio sérico (11.6 vs. 9.2 mg/100 ml) y de la fosfatasa alcalina (228 vs. 120 U/l). A los 30±8 meses se hallaron diferencias en el calcio sérico (10.2 vs. 9.4 mg/100 ml), fosfato (2.8 vs. 4.8 mg/100 ml) y fosfatasa alcalina (180 vs. 88 U/l). Los niveles de creatinina sérica aparecieron similares en los 2 grupos. Se encontró una correlación significativa entre las determinaciones tempranas y las tardías de la fosfatasa alcalina cuando la totalidad de los 25 pacientes fue estudiada como grupo único (r= 0.72, p<0.001). El dolor óseo y/o la evidencia radiológica de enfermedad ósea paratiroidea aparecieron en asociación significativa con el HTR (8 vs. 1 y 7 vs. 0, respectivamente). Una incidencia mayor, aunque no significativa, de calcificaciones vasculares (5 vs. 1) y de pancreatitis aguda (2 vs. 0) fue hallada en el HTR. Los pacientes con HTR severo definido como el hallazgo de por lo menos una determinación de calcio sérico 12 mg/100 ml, lo desarrollan dentro de los 6 meses siguientes al transplante renal, presentan morbilidad aumentada, especialmente con afección esquelética, y es posible que se beneficien de paratiroidectomía subtotal.

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Résumé Dans le but de déterminer les risques de complications chez un groupe de malades ayant présenté un hyperparathyroïdisme après transplantation rénale les auteurs ont comparé une série de 14 cas où le taux de calcium avait été au moins une fois supérieure à 12 mg/100 ml et une série de 11 receveurs où le taux de calcium était normal et ce 6 et 30±8 mois après allogreffe rénale. Au bout de 6 mois le taux de calcium fut supérieur à 12 mg/100 ml chez 13 des 14 malades qui avaient subi une transplantation rénale. Des différences significatives furent constatées entre les transplantés et les sujets appartenant au groupe de contrôle aussi bien en ce qui concerne le calcium sérique (11.6 contre 9.2 mg/100 ml) et la phosphatase alcaline (228 contre 120 U/l). Au terme de 30±8 mois des différences furent également constatées pour le calcium (10.2 contre 9.4 mg/100 ml), pour le phosphore (2.8 contre 4.8 mg/100 ml) et pour la phosphatase alcaline (180 contre 88 U/l). Les taux de créatinine sérique étaient identiques dans les 2 groupes. Une corrélation significative fut constatée entre les déterminations précoces et tardives de la phosphatase alcaline chez les 25 sujets rassemblés en un seul groupe (r=0.72, p<0.001). La douleur osseuse et/ou des signes radiologiques évidents d'atteinte osseuse d'origine hyperparathyroïdienne allaient de pair significativement chez les transplantés (8 contre 1 et 7 contre 0 respectivement). Chez ceux-ci fut constatée une fréquence supérieure mais non significative de calcifications vasculaires (5 contre 1) et de pancréatite aiguë (2 contre 0). Les opérés qui ont développé un hyperparathyroïdisme modéré ou intense (un taux supérieur à 12 mg/100 ml, au moins une fois) au cours des 6 mois qui suivirent la transplantation rénale, en particulier lorsqu'ils présentèrent une atteinte du squelette, devraient bénéficier d'une parathyroïdectomie subtotale.

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Presented at the International Association of Endocrine Surgeons in Paris, September 1985.

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Supported by a grant from the Fondo de Investigaciones Sanitarias de la Seguridad Social. Ministerio de Sanidad, Spain.