Coeliac disease and autoimmune Addison's disease: a clinical pitfall.

BACKGROUND: Coeliac disease has an increased prevalence in a number of autoimmune endocrine conditions. An association between coeliac disease and Addison's disease has been proposed in isolated case reports, but has not been formally studied. AIM: To investigate the extent of this association. DESIGN: Prospective screening of patients with confirmed Addison's disease. METHODS: From central computerized records, we identified all living patients with a diagnosis of autoimmune Addison's disease in the past 30 years and presently attending our affiliated hospitals. After exclusions, 44 were invited to attend for screening. RESULTS: Of 41 patients screened, five (12.2%) had coeliac disease: Three were previously diagnosed coeliacs and this was confirmed on review, including examination of biopsy material. A further two had positive IgA-endomysial antibodies. Histological confirmation was obtained in both cases. Neither had laboratory or clinical evidence of malabsorption. DISCUSSION: In this series of patients with Addison's disease, a higher co-morbidity with coeliac disease was observed than in any previously studied endocrine condition. We recommend that coeliac serology (anti-endomysial and tissue transglutaminase antibody) testing be incorporated routinely into the autoimmune screen for other conditions in patients with Addison's disease.

The prevalence of coeliac disease among female subjects having bone densitometry.

BACKGROUND: Osteoporosis frequently complicates coeliac disease but most studies focus on symptomatic patients at the time of diagnosis. Screening tests have revealed that many individuals with coeliac disease have mild, atypical, or absent symptoms. AIM: To evaluate the relationship between coeliac disease and osteopenia or osteoporosis in female subjects attending for bone densitometry. METHODS: We studied 371 female subjects attending for bone densitometry, without secondary causes of osteoporosis and included those with normal and with reduced bone mineral density. Mineral density was measured by dual energy X-ray absorptiometry. Screening for coeliac disease was by measurement of anti-endomysial antibody by indirect immunofluorescence. RESULTS: Two of 115 (1.7%) female subjects with normal bone density and five of 256 (1.9%) female subjects with sub-normal bone density were positive for endomysial antibody. Five subjects who underwent small bowel biopsy had histological changes suggestive of coeliac disease. CONCLUSIONS: In females referred for bone densitometry, endomysial antibody positivity was not more prevalent among those with reduced bone mineral density. Examining only patients with clinically detected coeliac disease may overestimate the frequency of complications. This study does not support population screening for coeliac disease in an area with a high frequency of the condition.

Why is celiac disease so common in Ireland?

Celiac disease (gluten sensitive enteropathy) is a condition affecting the small bowel, characterized by permanent intolerance to dietary gluten, and giving rise to varying degrees of malabsorption and diarrhea. With the advent of sensitive screening tests, the condition is being increasingly diagnosed. Celiac disease is more common in the Irish and in those of Irish descent. Simoons (1978, 1981) hypothesized that the present-day prevalence of celiac disease across Europe is related to the interaction between genetic gradients, largely determined by the advance of agriculture, and historical patterns of cereal ingestion. This essay examines Simoons' hypothesis as it relates to Ireland, reviews the ethnic and genetic mix of those living on the island of Ireland and aspects of Irish dietary history, and considers how these factors may have combined to result in a high frequency of celiac disease.

Prevention of postsplenectomy sepsis: how much do patients know?

INTRODUCTION: Asplenia causes a deficiency in immunity with a long-term risk of fulminant infection, associated with significant mortality. Patient compliance requires an understanding of risks of infection and its prevention. The impact of patient education has been little studied. MATERIALS AND METHODS: To ascertain the degree of knowledge held by patients who have undergone splenectomy, a comprehensive survey was designed. This also aimed to determine which group of health professionals was most successful in conveying information to patients. Patients who had undergone total splenectomy were interviewed by telephone, using a standardised list of questions to assess their understanding of the post-operation risks. RESULTS: Of 40 consecutive patients, 32.5% had a good knowledge of the risks of asplenia and their prevention, 52.5% had a fair knowledge and 15% a poor knowledge. Haematologists were most successful in initially conveying information to patients, and general practitioners also played a critical role in patient education. In this survey, it appears that surgeons were not effective at educating patients. CONCLUSION: Patient education postsplenectomy is poor. Measures to prevent infection in the asplenic patient are not being adequately implemented.

Type 1 diabetes mellitus, coeliac disease, and lymphoma: a report of four cases.

INTRODUCTION: Patients with Type 1 diabetes mellitus have a high prevalence of coeliac disease, symptoms of which are often mild, atypical, or absent. Untreated coeliac disease is associated with an increased risk of malignancy, particularly of lymphoma. We describe four patients with Type 1 diabetes mellitus and coeliac disease who developed lymphoma. CASE REPORTS: Two patients were male and two female. In three patients, coeliac disease and lymphoma were diagnosed simultaneously. Enteropathy-associated T cell lymphoma occurred in two patients, Hodgkin's disease in one, and B cell lymphoma in one. Response to treatment was in general poor, and three patients died soon after the diagnosis of lymphoma was made. CONCLUSION: As the relative risk of lymphoma is reduced by a gluten-free diet, a high index of suspicion for coeliac disease should exist in all Type 1 diabetic patients with unexplained constitutional or gastrointestinal symptoms.

Plasma homocysteine concentrations in patients with type 1 diabetes.

OBJECTIVE: To determine the plasma concentration of total homocysteine (tHcy), a recognized risk factor for vascular disease, in patients with type 1 diabetes and to examine the relationships with age, sex, duration of diabetes, microvascular complications and neuropathy, and folic acid concentration. RESEARCH DESIGN AND METHODS: Plasma tHcy and folic acid concentrations were measured in a randomly selected cohort of type 1 diabetic patients (n = 119), well characterized as regards microvascular complications, and in a matched control group (n = 51). RESULTS: Plasma tHcy was higher in male than in female control subjects (geometric mean [95% CI]: 9.3 [8.0-10.9] vs. 6.1 [5.2-7.2] micromol/l, P < 0.001), as previously described, but there was no sex difference in diabetic patients. Plasma tHcy significantly correlated with age in patients (r = 0.348, P < 0.01) but not in control subjects (r = 0.007, P = 0.96). Male patients without microvascular complications had lower plasma tHcy concentrations than did male control subjects (6.2 [5.1-7.5] vs. 9.3 [8.0-10.9] micromol/l, P < 0.001), but values in female patients without complications were similar to those of female control subjects. Plasma folic acid concentration was higher in diabetic patients than in control subjects. The expected negative association between plasma tHcy and folic acid was stronger in control subjects than in patients. CONCLUSIONS: Subnormal tHcy concentrations in male patients, the absence of a sex difference, and the positive association with age indicate that homocysteine metabolism differs between type 1 diabetic patients and control subjects. Homocysteine is unlikely to be of pathogenic significance in patients, particularly male subjects, with early microvascular disease and/or neuropathy.

Coeliac disease and epilepsy.

Whether there is an association between coeliac disease and epilepsy is uncertain. Recently, a syndrome of coeliac disease, occipital lobe epilepsy and cerebral calcification has been described, mostly in Italy. We measured the prevalence of coeliac disease in patients attending a seizure clinic, and investigated whether cerebral calcification occurred in patients with both coeliac disease and epilepsy. Screening for coeliac disease was by IgA endomysial antibody, measured by indirect immunofluorescence using sections of human umbilical cord. Of 177 patients screened, four patients were positive. All had small-bowel histology typical of coeliac disease. The overall frequency of coeliac disease in this mixed patient sample was 1 in 44. In a control group of 488 pregnant patients, two serum samples were positive (1 in 244). Sixteen patients with both coeliac disease and epilepsy, who had previously attended this hospital, were identified. No patient had cerebral calcification on CT scanning. Coeliac disease appears to occur with increased frequency in patients with epilepsy, and a high index of suspicion should be maintained. Cerebral calcification is not a feature of our patients with epilepsy and coeliac disease, and may be an ethnically-or geographically-restricted finding.

High prevalence of celiac disease among patients with insulin-dependent (type I) diabetes mellitus.

OBJECTIVES: Diagnosis of unrecognized celiac disease is potentially important. The prevalence of celiac disease in patients with insulin-dependent diabetes mellitus is uncertain. We report the prevalence of celiac disease in a stratified random sample (n = 101) of adult insulin-dependent diabetic patients (age, 18-59 yr) attending our clinic, and in an age- and sex-matched control group (n = 51). METHODS: Screening was by anti-endomysial antibody, measured by indirect immunofluorescence using sections of human umbilical cord. RESULTS: Celiac disease had not been suspected in any patient at the time of screening. Eight patients tested positive for anti-endomysial antibody, all of whom had a distal duodenal biopsy performed. Five patients had histologic evidence of celiac disease. One patient with negative histology was receiving immunosuppressive therapy for a renal-pancreas transplant. Of the five patients with abnormal histology, two improved on gluten restriction, one was unable to comply, one refused treatment, and one was lost to follow-up. No control subject tested positive for endomysial antibody. CONCLUSIONS: Patients with insulin-dependent diabetes have an increased prevalence of celiac disease. Because most cases are clinically unrecognized, consideration should be given to screening all insulin-dependent diabetes mellitus patients with endomysial antibodies.

Supervised drug administration in patients with refractory hypertension unmasking noncompliance.

Noncompliance with medication is common, particularly in asymptomatic conditions such as hypertension that require long-term treatment, and is often unsuspected. We describe two patients with refractory hypertension in whom noncompliance was confirmed by a precipitous fall in blood pressure when antihypertensive medications were given under direct supervision.

Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden.

Patients with inflammatory bowel disease have an increased frequency of thromboembolism, and microvascular thrombosis has been proposed as a contributory pathogenic factor. The mechanism of enhanced procoagulant activity is not understood. We examined the clinical setting of thromboembolic events in 52 patients with Crohn's disease or ulcerative colitis, and assessed the procoagulant laboratory profile, including Factor V Leiden, in a subset of 20 patients to identify procoagulant risk factors. Patients who developed thrombosis tended to be young; 60% of thrombotic events occurred in patients under 50 years. Multiple thromboembolic episodes occurred in 13% and unusual sites of thrombosis (e.g. intracardiac, cerebral, inominate veins) in 11%. No risk factor was identifiable in 52% of cases and two-thirds of thromboses occurred in an out-patient setting. The mortality rate was 8%. Evidence for inflammatory disease activity was found in only 45% of patients with ulcerative colitis at the time of the thromboembolic event, in contrast to 89% of those with Crohn's disease. Assays for specific coagulation defects were negative in all cases tested (protein S, C were normal in 17/17; anti-thrombin III, anti-phospholipid antibodies and activated protein C resistance were negative in 20/20, and only 1/20 patients was found to be heterozygous for Factor V leiden. Thrombosis in inflammatory bowel disease is important because it occurs in a young population, often in unusual sites, and has a high mortality. The development of thrombosis is related to active inflammatory disease in most patients with Crohn's disease but apparently not in those with ulcerative colitis. Since approximately half of the patients had no other identifiable risk factor, there remains a substantial group of patients with IBD who develop thrombosis for unknown reasons.

Addison disease in patients treated with glucocorticoid therapy.

Acute adrenal crisis in patients with unrecognized chronic adrenocortical failure is difficult to diagnose and potentially fatal. We describe 2 patients with acute adrenal crisis whose diagnoses were hindered because of concomitant glucocorticoid treatment. Acute adrenal insufficiency is primarily a state of mineralocorticoid deficiency. Prednisolone and prednisone, the most frequently prescribed anti-inflammatory corticosteroid agents, have minimal mineralocorticoid activity. Several conditions that may be treated with pharmacological glucocorticoids are associated with an increased risk of Addison disease. An acute adrenal crisis, against which concurrent glucocorticoid therapy does not confer adequate protection, may develop in such patients.

Medial arterial calcification, calcific aortic stenosis and mitral annular calcification in a diabetic patient with severe autonomic neuropathy.

Medial arterial calcification (Mönckeberg's arteriosclerosis) is well described in diabetic patients with autonomic neuropathy. There is also a high prevalence of diabetes mellitus among subjects with calcific aortic stenosis and mitral annular calcification. We describe a diabetic patient with autonomic neuropathy and extensive medial arterial calcification who also had calcification of the aortic valve and of the mitral valve annulus. We propose that autonomic neuropathy may play a role in calcification of these structures at the base of the heart.

Concomitant Graves' disease and Hashimoto's thyroiditis, presenting as primary hypothyroidism.

Hypothyroidism in patients with Graves' disease is usually the result of ablative treatment. We describe a 58 year old man with Graves' ophthalmopathy and pre-tibial myxoedema, who presented with spontaneous primary hypothyroidism. Circulating TSH receptor antibody activity was increased, while thyroid microsomal antibody was detectable in titres greater than one in one hundred thousand. It is likely that the TSH receptor antibody of Graves' disease was ineffective in stimulating hyperthyroidism because of concomitant thyroid destruction due to Hashimoto's disease. Alternatively, primary hypothyroidism could have resulted from the effects of a circulating TSH receptor blocking antibody.

Appropriateness of laboratory tests: requests for atypical pneumonia serology in a teaching hospital.

The cost of providing medical care is ever-increasing but the resources available are at best static. Major savings can be made by reducing inappropriate investigations. Using serological testing for organisms causing atypical pneumonia as an example, we examined the appropriateness of requests and also physicians' understanding of the test. Of 119 patients tested, only 3 had titres indicative of acute infection. Most patients were tested within 2 days of hospital admission, before receipt of results excluding more likely diagnoses. Forty-five patients had no current or recent respiratory symptoms, in whom infection was highly unlikely. Titres were most often requested by the least experienced members of the clinical team. Of 70 patients with an acute illness in whom a definitive diagnosis, bacteriological or otherwise, was not made, in only 9 was a convalescent specimen sent for follow-up titres. Most requests for serology for organisms causing atypical pneumonia were inappropriate. Furthermore, in the majority of cases the test was incorrectly used.

Reduced plasma aldosterone concentrations in randomly selected patients with insulin-dependent diabetes mellitus.

Abnormalities of the renin-angiotensin system have been reported in patients with diabetes mellitus and with diabetic complications. In this study, plasma concentrations of prorenin, renin, and aldosterone were measured in a stratified random sample of 110 insulin-dependent (Type 1) diabetic patients attending our outpatient clinic. Fifty-four age- and sex-matched control subjects were also examined. Plasma prorenin concentration was higher in patients without complications than in control subjects when upright (geometric mean (95% confidence intervals (CI): 75.9 (55.0-105.6) vs 45.1 (31.6-64.3) mU I-1, p < 0.05). There was no difference in plasma prorenin concentration between patients without and with microalbuminuria and between patients without and with background retinopathy. Plasma renin concentration, both when supine and upright, was similar in control subjects, in patients without complications, and in patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was suppressed in patients without complications in comparison to control subjects (74 (58-95) vs 167 (140-199) ng I-1, p < 0.001) and was also suppressed in patients with microvascular disease. Plasma potassium was significantly higher in patients than in control subjects (mean +/- standard deviation: 4.10 +/- 0.36 vs 3.89 +/- 0.26 mmol I-1; p < 0.001) and plasma sodium was significantly lower (138 +/- 4 vs 140 +/- 2 mmol I-1; p < 0.001). We conclude that plasma prorenin is not a useful early marker for diabetic microvascular disease. Despite apparently normal plasma renin concentrations, plasma aldosterone is suppressed in insulin-dependent diabetic patients.