Schilling Test Research Articles

The patient that changed my practice: A rare case of organic psychosis

Correspondence Address Jaime Moya, Psychiatry Resident, University Clinic, University of Navarra, Avda. Pio XII N8 36 CP: 31080 Pamplona, Navarra, Spain E-mail: jmoya@unav.es This article presents a patient with a history of depression, progressive impairment of brain functions, diarrhoea and faecal incontinence. A cobalamin deficiency, without megaloblastic anaemia was detected, and an abnormal Schilling test not due to intrinsic factor deficiency was obtained. Once other causes of cobalamin deficiency were ruled out, it was considered caused by blind-loop syndrome. Treatment with vitamin B complex and long-term oral antibiotic therapy led to a complete resolution of neurological and digestive symptoms. This case illustrates B12 deficiency as a possible cause of reversible dementia, as well as the importance of considering B12 screening in a patient with a history of gastric surgery. Given the depressive history of the patient, the case also emphasizes the relevance of distinguishing a dementia from the cognitive symptoms of depression. (Int J Psych Clin Pract 2003; 7: 147 /150)

Vitamin B12 malabsorption following bladder reconstruction or diversion with bowel segments.

Vitamin B12 is absorbed exclusively in the terminal ileum the resection of which may produce malabsorption of B12. The present study aimed to determine whether the length or specific segment of the intestine used in bladder reconstruction affects the overall incidence of B12 malabsorption. It was also aimed at the reasonable way of following these patients. Seventy patients who underwent urinary reconstruction between 1988 and 1997 were studied: 28 had undergone orthotopic reconstruction, 14 had ileal conduit diversion, 8 had continent diversion and 20 had undergone enterocystoplasty. The median follow up was 65 months (10-137 months). Indications for operation included carcinoma of the bladder, neurogenic bladder dysfunction, idiopathic detrusor instability and interstitial cystitis. Schilling tests were performed, and serum B12 level and haematological indices were measured. Patients were classified depending on whether the ileocaecal junction was used. Group 1 included ileal conduit and entero-cystoplasty where 15-20 cm of ileum, 15-20 cm from ileocaecal junction was used. Group 2 consisted of orthotopic reconstruction and continent diversions where the ileocaecal segment was used. Group 3 comprised patients in whom long ileal segments (50-60 cm) had been used for reconstruction. Five patients in group 1 and one in group 2 had low B12 levels, but none had developed neuropathy or megaloblastic anaemia. One patient in group 1, and six patients in group 2 had low Schilling tests indicating intestinal malabsorption of B12. No patient in group 3 had a low B12 or an abnormal Schilling test. This study showed that use of ileocaecal segments results in intestinal malabsorption of B12. The length of ileum alone does not seem to be the determinant factor in causing B12 deficiency or B12 malabsorption.

Vitamin B 12 deficiency in untreated celiac disease

OBJECTIVES: Iron and folate malabsorption are common in untreated celiac disease as the proximal small intestine is predominantly affected. Vitamin B 12 deficiency is thought to be uncommon, as the terminal ileum is relatively spared. This study aims to investigate the prevalence of vitamin B 12 deficiency in patients with untreated celiac disease. METHODS: Prospective study of 39 consecutive biopsy-proven celiac disease patients (32 women, seven men; median age 48 yr, range 22–77 yr) between September 1997 and February 1999. The full blood count, serum vitamin B 12, red blood cell folate, and celiac autoantibodies (IgA antigliadin and IgA antiendomysium antibodies) were measured before and after a median of 4 months (range 2–13 months) of treatment with a gluten-free diet. In vitamin B 12-deficient patients, intrinsic factor antibodies and a Schilling test, part 1, were performed. RESULTS: A total of 16 (41%) patients were vitamin B 12 deficient (<220 ng/L) and 16 (41%) patients (11 women and five men) were anemic. Concomitant folate deficiency was present in only 5/16 (31%) of the vitamin B 12 patients. The Schilling test, performed in 10 of the vitamin B 12-deficient patients, showed five low and five normal results. Although only five patients received parenteral vitamin B 12, at follow-up the vitamin B 12 results had normalized in all patients. Acral paraesthesia at presentation in three vitamin B 12-deficient patients resolved after vitamin B 12 replacement. CONCLUSIONS: Vitamin B 12 deficiency is common in untreated celiac disease, and concentrations should be measured routinely before hematinic replacement. Vitamin B 12 concentrations normalize on a gluten-free diet alone, but symptomatic patients may require supplementation.

Vitamin B12 deficiency in untreated celiac disease.

Iron and folate malabsorption are common in untreated celiac disease as the proximal small intestine is predominantly affected. Vitamin B12 deficiency is thought to be uncommon, as the terminal ileum is relatively spared. This study aims to investigate the prevalence of vitamin B12, deficiency in patients with untreated celiac disease. Prospective study of 39 consecutive biopsy-proven celiac disease patients (32 women, seven men; median age 48 yr, range 22-77 yr) between September 1997 and February 1999. The full blood count, serum vitamin B12, red blood cell folate, and celiac autoantibodies (IgA antigliadin and IgA antiendomysium antibodies) were measured before and after a median of 4 months (range 2-13 months) of treatment with a gluten-free diet. In vitamin B12-deficient patients, intrinsic factor antibodies and a Schilling test, part 1, were performed. A total of 16 (41%) patients were vitamin B12 deficient (<220 ng/L) and 16 (41%) patients (11 women and live men) were anemic. Concomitant folate deficiency was present in only 5/16 (31%) of the vitamin B12 patients. The Schilling test, performed in 10 of the vitamin B12-deficient patients, showed five low and five normal results. Although only five patients received parenteral vitamin B12, at follow-up the vitamin B12 results had normalized in all patients. Acral paraesthesia at presentation in three vitamin B12-deficient patients resolved after vitamin B12 replacement. Vitamin B12 deficiency is common in untreated celiac disease, and concentrations should be measured routinely before hematinic replacement. Vitamin B12 concentrations normalize on a gluten-free diet alone, but symptomatic patients may require supplementation.

A treatable cause of ataxia in children

An 11-year-old black male presenting with severe subacute sensory ataxia, unusual skin hyperpigmentation, megaloblastic anemia, low serum B12 levels, and an abnormal part I Schilling test was diagnosed with pernicious anemia in the context of a polyglandular syndrome. Intrinsic factor and thyroid microsomal antibodies were positive, and thyroid-stimulating hormone levels were undetectable. There was a strong familial aggregation because the mother, a maternal aunt, the maternal grandfather, and the maternal great-grandmother had been diagnosed with pernicious anemia, albeit of unspecified etiology. Spinal magnetic resonance imaging (MRI) demonstrated extensive demyelination of the posterior columns along the entire length of the cord, as well as areas of contrast enhancement. Treatment with cobalamin produced complete remission of the neurologic deficits and normalization of the MRI findings in the short space of 2 months. Although rare, childhood pernicious anemia is a treatable disease that should be included in the differential diagnosis of the sensory ataxias in children. In this article, we review the causes of pernicious anemia in children and discuss the MRI findings.

Vitamin B12 metabolism after urinary diversion with a Kock ileal reservoir.

To elucidate the influence of construction of a Kock reservoir for urinary diversion using 70 cm of the distal ileum on vitamin B12 metabolism. Blood samples for determination of cobalamin concentrations were drawn up to 18 years after construction of a Kock reservoir in 97 patients. Preoperative values were obtained in 20 of these patients. Pre- and postoperative Schilling tests and analyses of methylmalonic acid and homocysteine concentrations were performed in subgroups. The operation did not induce a significant decrease in cobalamin uptake as reflected in the pre- and postoperatively performed Schilling tests. No significant decline in cobalamin concentration postoperatively was noted. The value of analysis of methylmalonic acid and homocysteine concentrations in finding patients with cobalamin deficiency is limited by the fact that kidney function influences the results. Ten per cent of the patients did develop true cobalamin deficiency. A postoperative vitamin B12 value below 200 pmol/l indicates a 50% risk of later cobalamin deficiency. The construction of a Kock reservoir does not per se cause cobalamin deficiency. Substitution should be instituted at a postoperative concentration below 200 pmol/l.

RECURRENT URINARY TRACT INFECTIONS AND GENITOURINARY TRACT ABNORMALITIES IN THE IMERSLUND-GRASBECK SYNDROME

Two Imerslund-Grasbeck patients who presented with recurrent urinary tract infections and genitourinary abnormalities are described. The patients were evaluated with abdominal ultrasounds, voiding cystourethrograms, and Schilling tests. Each patient had large postvoid residual urine secondary to a motor-neurogenic bladder. One had a duplication of the distal urethra manifesting as two meatal openings. There was lack of urinary excretion of radioactive vitamin B12 on Schilling tests in both patients. Patients with Imerslund-Grasbeck syndrome may be predisposed to urinary tract infections because of incomplete bladder emptying. Complete physical and radiological examinations of the genitourinary tract should be performed.

Cyanocobalamin (vitamin B-12) status in Seventh-day Adventist ministers in Australia

As part of the Adventist Ministers' Health Study, a series of cross-sectional surveys conducted in 1992, 1994, and 1997, the serum vitamin B-12 status of 340 Australian Seventh-day Adventist ministers was assessed in 1997. The ministers in the study participated voluntarily. Of this group, 245 were either lactoovovegetarians or vegans who were not taking vitamin B-12 supplements. Their mean vitamin B-12 concentration was 199 pmol/L (range: 58-538 pmol/L), 53% of whom had values below the reference range for the method used (171-850 pmol/L) and 73% of whom had values <221 pmol/L, the lower limit recommended by Herbert. Dual-isotope Schillings test results in 36 lactoovovegetarians with abnormally low vitamin B-12 concentrations indicated that dietary deficiency was the cause in 70% of cases. Data from the dietary questionnaires supported dietary deficiency as the cause of low serum vitamin B-12 in this population of lactoovovegetarians and vegans, 56 (23%) of whom consumed sufficient servings of vitamin B-12-containing foods to obtain the minimum daily maintenance allowance of the vitamin (1 microg).

Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician.

At one time, the diagnosis of a deficiency of vitamin B12 or folate was considered to be relatively straightforward. As knowledge has accumulated, the limitations of such tests as serum vitamin level measurements and the Schilling test have become apparent. With the development of newer tests, atypical and subclinical deficiency states have been recognized. In this review, available tests used in the diagnosis of vitamin B12 and folate deficiency are discussed, and a rational approach to the diagnosis of these deficiency states is presented.

Assimilation of [57Co]-labeled cobalamin in human fetal gastrointestinal xenografts into nude mice.

Cobalamin (Cbl) and its Cbl-binding proteins are present in amniotic fluid. Because amniotic fluid is swallowed by the embryo-fetus, we studied the ability of Cbl to be transported and metabolized across the embryo-fetal digestive tract. Human embryonic stomachs and intestines were transplanted into nude mice. The basal secretion of Cbl-binding proteins was studied by gel filtration of the graft juices. Intrinsic factor (IF) was looked for in gastric mucosa by immunohistochemistry. The uptake of [57Co]-labeled Cbl by the intestinal graft was studied by Schilling tests and HPLC. IF, haptocorrin, and a transcobalamin-like protein were detected in gastric juice, with concentration ranges of 5.0-26.4, 1.9-27.1, and 5.2-12.6 pmol/mL, respectively. The IF [57Co]Cbl complex had a single isoprotein with a pI at 5.6, which was maintained after incubation with neuraminidase. Urine excretion percentages (Schilling tests) ranged from 5.5 to 21.2% and from 0.3 to 1.6% when cyano-[57Co]Cbl-IF or cyano-[57Co]Cbl, respectively, was instilled in intestinal grafts. Chloroquine reduced significantly the percentage of excreted [57Co]Cbl. The [57Co]Cbl was mainly excreted as cyano-[57Co]Cbl in urines, showing a low coenzyme conversion. In conclusion, IF is secreted by the nonstimulated embryonic stomach and lacks sialic acid. Cbl binds to it and is subsequently transported across the xenografted embryo-fetal intestine. This suggests that amniotic fluid may contribute to Cbl delivery to the embryo-fetus.

Serum antibodies to H+,K+-ATPase, serum pepsinogen A and Helicobacter pylori in relation to gastric mucosa morphology in patients with low or low-normal concentrations of serum cobalamins.

To compare the diagnostic performance of serum antibodies to H+,K+-ATPase (EC 3.6.1.36), serum pepsinogen A (EC 3.4.23.1) and the Schilling test in diagnosing chronic atrophic body gastritis; to study the interrelationships between H+,K+-ATPase antibodies, serology for Helicobacter pylori, and gastric morphology. Patients with suspected cobalamin deficiency and serum cobalamin < 200 micromol/l were investigated using upper gastrointestinal endoscopy, the Schilling test and serum tests for H+,K+-ATPase antibodies, pepsinogen A, and H. pylori. The Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. Ninety seven consecutively referred patients. Sensitivity and specificity of assays for serum H+,K+-ATPase antibodies, serum pepsinogen A, and the Schilling test. Assays of serum antibodies to H+,K+-ATPase and of serum pepsinogen A displayed equal diagnostic sensitivity for atrophic gastritis (around 0.90 for the severe forms) and higher than that for the Schilling test (0.65). The diagnostic specificity for pepsinogen A (1.0) was higher than for H+,K+-ATPase antibodies (about 0.80). The prevalence of antral gastritis and positivity for H. pylori antibodies declined with the transition of body gastritis into severe atrophy, while the prevalence of H+,K+-ATPase antibodies increased. Pepsinogen A is preferable to serum H+,K+-ATPase antibodies in the diagnosis of gastric body mucosal atrophy. The formation of H+,K+-ATPase antibodies does not seem to be a primary event in the development of gastric body muscosal atrophy.

Sjögren's syndrome and pernicious anaemia: Case report

We describe seven patients (five females and two males) with pernicious anaemia and Sjögren's syndrome. The diagnosis of pernicious anaemia was confirmed by bone marrow aspiration and a Schilling's test. Sjögren's syndrome was diagnosed by the Schirmer-I tear test, salivary gland scintigraphy, minor salivary gland biopsy and determination of lacrimal lysozyme. We have reviewed the literature and found few cases reported of the association of these two diseases. A. Rodríguez-Cuartero, Gran Vía, 21, 4°F. SP-18001-Granada, Spain

Age-related changes in cobalamin (vitamin B12) handling. Implications for therapy.

Cobalamin (vitamin B12) deficiency is more common in the elderly than in younger patients. This is because of the increased prevalence of cobalamin malabsorption in this age group, which is mainly caused by (autoimmune) atrophic body gastritis. Cobalamin supplementation is affordable and nontoxic, and it may prevent irreversible neurological damage if started early. Elderly individuals with cobalamin deficiency may present with neuropsychiatric or metabolic deficiencies, without frank macrocytic anaemia. An investigation of symptoms and/or signs includes the diagnosis of deficiency as well as any underlying cause. Deficiency states can still exist even when serum cobalamin levels are higher than the traditional lower reference limit. Cobalamin-responsive elevations of serum methylmalonic acid (MMA) and homocysteine are helpful laboratory tools for the diagnosis. The health-related reference ranges for homocysteine and MMA appear to vary with age and gender. Atrophic body gastritis is indirectly diagnosed by measuring serum levels of gastrin and pepsinogens, and it may cause dietary cobalamin malabsorption despite a normal traditional Schilling's test. The use of gastroscopy may also be considered to diagnose dysplasia, bacterial overgrowth and intestinal villous atrophy in healthy patients with atrophic body gastritis or concomitant iron or folic acid deficiency. Elderly patients respond to cobalamin treatment as fully as younger patients, with complete haematological recovery and complete or good partial resolution of neurological deficits. Chronic dementia responds poorly but should, nevertheless, be treated if there is a metabolic deficiency (as indicated by elevated homocysteine and/or MMA levels). Patients who are at risk from cobalamin deficiency include those with a gastrointestinal predisposition (e.g. atrophic body gastritis or previous partial gastrectomy), autoimmune disorders [type 1 (insulin-dependent) diabetes mellitus and thyroid disorders], those receiving long term therapy with gastric acid inhibitors or biguanides, and those undergoing nitrous oxide anaesthesia. To date, inadequate cobalamin intake has not proven to be a major risk factor. Intervention trials of cobalamin, folic acid and pyridoxine (vitamin B6) in unselected elderly populations are currently under way.

Prospective evaluation of protein bound vitamin B12(cobalamin) malabsorption in the elderly using trout flesh labelled in vivo with 57Co-cobalamin

Background—The frequency of dietary protein bound vitamin B12 malabsorption in elderly patients remains controversial.Aims—To evaluate this malabsorption in elderly hospitalised patients using a modified Schilling test.Patients—Fourteen elderly patients with low...

Maladie d'Imerslund. Aspects cliniques et biologiques. À propos de six cas

Imerslund syndrome, a recessive autosomal disease, initially described by Imerslund and Grasbeck in 1960, associates megaloblastic anemia and proteinuria. We report on six cases, studied in five different families. All patients (mean age: 3.5 years) had clinical symptoms of anemia, three had malabsorption, proteinuria was present in five, at the time of diagnosis. Hemogram and decreased serum vitamin B12 levels were consistent with the diagnosis in all cases. Intra-muscular injections of cyanocobalamine was instituted on a life-time basis and the long term prognosis is good. The diagnosis should be evoked when the three typical features are present: macrocytic anemia, decreased serum B12 level and proteinuria. It will be confirmed by the bone marrow megaloblastic aspects and the Schilling test findings.

Schilling and protein-bound cobalamin absorption tests are poor instruments for diagnosing cobalamin malabsorption.

To assess the advantage of a protein-bound cobalamin absorption test (PBAT) over the Schilling test in patients with suspected cobalamin (vitamin B12) malabsorption. Clinical study of consecutive patients referred from primary care units, medical and neurological clinics. The catchment area of Sahlgrenska University Hospital, Göteborg. Referred patients (n = 155) with suspected cobalamin deficiency and at least one serum cobalamin value < 200 pmol L-1. All patients were investigated with upper gastrointestinal endoscopy with biopsies taken from the gastric body and duodenal mucosa. Serum methylmalonic acid (MMA) and homocysteine (Hcy) were determined in all 109 patients not on cobalamin substitution. A dual isotope cobalamin absorption test was then performed with the concomitant administration of crystalline (Schilling) and protein-bound cobalamin (PBAT). Number of patients with gastric body atrophy diagnosed with each absorption test and the relation between these results and functional cobalamin deficiency defined as elevated MMA and Hcy, that normalized after cobalamin substitution treatment. The majority of patients with abnormal absorption tests had already developed elevated MMA and/or Hcy. PBAT was more sensitive than the Schilling test in identifying patients with gastric body atrophy but the sensitivity was too low for clinical use. About 1/3 of the patients with gastric body atrophy and normal absorption tests had elevated MMA and/or Hcy, indicating cobalamin deficiency. PBAT may be somewhat more sensitive than the Schilling test but neither test is sensitive enough for diagnosing cobalamin malabsorption at an early stage.

Vitamin B12 deficiency in patients with urinary intestinal diversion.

Because vitamin B12 is absorbed exclusively by the terminal ileum, we investigated vitamin B12 deficiency as a potential metabolic complication after urinary intestinal diversion. We measured serum levels in patients with Kock pouches (n = 35); Indiana pouches (n = 27); and ileal conduits (n = 25). Serial determinations of serum B12 levels were obtained in 19 patients with kock pouches and 14 patients with Indiana pouches. The dual-isotope Schilling test was performed in 9 patients with Kock pouches and 6 patients with Indiana pouches. No patient had an abnormally low serum B12 level (< 200 pg/mL). Mean (+/-SD) serum B12 levels in patients with the Kock pouch (506 +/- 202 pg/mL) and the Indiana pouch (536 +/- 249 pg/mL) were lower than that in patients with the ileal conduit (727 +/- 391 pg/mL). The mean serum B12 level was not significantly different between patients with and without preoperative irradiation. Serial determinations showed that serum B12 levels in some patients with continent urinary reservoirs were persistently near the lower normal limit, or became progressively lower. Three of the 9 patients (33%) with Kock pouches and 4 of the 6 patients (67%) with Indiana pouches were B12 malabsorbers, although no patients had megaloblastic anemia or neurologic symptoms. Some patients with continent urinary reservoirs are at risk for vitamin B12 deficiency due to malabsorption. Routine evaluation of serum B12 levels is recommended for all patients with continent urinary reservoirs, and a Schilling test for those with subnormal serum B12 levels.

Cobalamin deficiency with megaloblastic anaemia in one patient under long‐term omeprazole therapy

The first case of cobalamin deficiency with megaloblastic anaemia in a patient under long-term omeprazole therapy is presented. This patient received omeprazole at a daily dose of 40-60 mg for 4 years as treatment for a gastro-oesophagal reflux complicated by peptic oesophagitis. Seric vitamin B12 was dramatically decreased at 80 pmol L-1. The Schilling test was normal (13%) with crystalline [57Co] cobalamin and it was at 0% with [57Co] cobalamin-labelled trout meat. All other assimilation tests were normal except an expiratory hydrogen breath test performed with lactulose. The haematological status was restored after intramuscular treatment with cobalamin. In conclusion, prolonged omeprazole therapy can be responsible for a cobalamin deficiency due to protein-bound cobalamin malabsorption.

Changes in parietal cell structure and function in HIV disease

The mechanisms underlying acid secretory failure in patients with HIV disease are unknown. We evaluated, in a series of preliminary studies, changes associated with parietal cell structure and function in early and late HIV disease, in an attempt to elucidate possible underlying mechanisms. Gastric acid and intrinsic factor secretion, vitamin B12 absorption, and light and electron microscopic evaluation of gastric mucosa were evaluated in patients with early and late HIV infection (AIDS) and compared to non-HIV-infected controls. Immunolocalization of HIV-related antigens in gastric mucosa was also examined. Fasting gastric juice pH and intrinsic factor (IF) concentration in AIDS and HIV infected subjects were significantly different from controls (P = 0.012 and P = 0.025, respectively for pH, and 0.029 and 0.035 for IF; ANOVA LSD test). By contrast, maximal acid output (MAO) was significantly lower in AIDS, but not HIV-infected subjects (P = 0.043 and P = 0.322, respectively). Similarly, Schilling test phases 1 and 2 results were significantly lower in AIDS, but not HIV-infected subjects. Varying degrees of vacuolar degeneration of parietal cells were seen on light microscopy. On electron microscopy (EM), tubulovesicles were reduced and intracellular canaliculi dilated with striking loss of microvilli. Immunofluorescent staining with antibodies to gp120, gp41, p24, and p17 demonstrated positive punctate signals in the cytoplasm of gastric glands, which includes parietal cells. Immunogold EM with anti-gp120, localized predominantly to the microvilli of intracellular canaliculi in parietal cells. Abnormal secretory function of parietal cells occurs early in HIV disease, affects acid as well as intrinsic factor secretion, and is associated with morphological changes in the acid secretory apparatus.

Prevalence of undiagnosed pernicious anemia in the elderly

Background : Existing information about the prevalence of pernicious anemia is largely based on older surveys that favored florid manifestations, tended to be retrospective analyses of previously diagnosed disease, and usually studied homogeneous European populations. The lack of current data in the United States has, among other things, hampered discussions of the proposal to increase folate intake by the general population. Objective : To estimate the prevalence of undiagnosed and untreated pernicious anemia among the elderly. Methods : A prospective survey of cobalamin levels and anti-intrinsic factor antibody was done in the elderly. Blood testing was done in 729 people aged 60 years or older and follow-up assessment with the Schilling test and other tests was offered when results were abnormal. Resuts : Seventeen subjects were found to have pernicious anemia, usually with only minimal clinical manifestations of cobalamin deficiency. Although cobalamin deficiency had been suspected by the physicians of three subjects, they had been treated inadequately and still had evidence of deficiency. Excluding these three partially treated subjects from the analysis, 1.9% of the survey population had unrecognized and untreated pernicious anemia. The prevalence was 2. 7% in women and 1.4% in men ; 4.3% of the black women and 4.0% of the white women had pernicious anemia. Conclusions : Undiagnosed pernicious anemia is a common finding in the elderly, especially among black and white women. If these findings can be extrapolated, almost 800 000 elderly people in the United States have undiagnosed and untreated pernicious anemia, and, thus, would be at possible risk for masked cobalamin deficiency if exposed to large amounts of folate. This number does not include those elderly with cobalamin deficiency caused by other disorders or the still unknown number of younger people with unrecognized pernicious anemia and other causes of deficiency.