Celiac Abstracts 1

© 2010

Risk of thyroid disease in individuals with celiac disease

            (Elfstrom, Montgomery et al. 2008) Download

BACKGROUND: It has been suggested that celiac disease is associated with thyroid disease. Earlier studies, however, have been predominately cross-sectional and have often lacked controls. There is hence a need for further research. In this study, we estimated the risk of thyroid disease in individuals with celiac disease from a general population cohort. METHODS: A total of 14,021 individuals with celiac disease (1964-2003) and a matched reference population of 68,068 individuals were identified through the Swedish national registers. Cox regression estimated the risk of thyroid disease in subjects with celiac disease. Analyses were restricted to individuals with a follow-up of more than 1 yr and with no thyroid disease before study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for subsequent celiac disease in individuals with thyroid disease. RESULTS: Celiac disease was positively associated with hypothyroidism [hazard ratio (HR) = 4.4; 95% confidence interval (CI) = 3.4-5.6; P < 0.001], thyroiditis (HR = 3.6; 95% CI =1.9-6.7; P < 0.001) and hyperthyroidism (HR = 2.9; 95% CI = 2.0-4.2; P < 0.001). The highest risk estimates were found in children (hypothyroidism, HR = 6.0 and 95% CI = 3.4-10.6; thyroiditis, HR = 4.7 and 95% CI = 2.1-10.5; hyperthyroidism, HR = 4.8 and 95% CI = 2.5-9.4). In post hoc analyses, where the reference population was restricted to inpatients, the adjusted HR was 3.4 for hypothyroidism (95% CI = 2.7-4.4; P < 0.001), 3.3 for thyroiditis (95% CI = 1.5-7.7; P < 0.001), and 3.1 for hyperthyroidism (95% CI = 2.0-4.8; P < 0.001). CONCLUSION: Celiac disease is associated with thyroid disease, and these associations were seen regardless of temporal sequence. This indicates shared etiology and that these individuals are more susceptible to autoimmune disease.

Infertility in coeliac disease

            (1983) Download

The changing face of celiac disease: a girl with obesity and celiac disease

            (Arslan, Esen et al. 2009) Download

In this paper, we present an obese patient with Hashimoto’s thyroiditis who was investigated for hypochromic microcytic anaemia that is unresponsive to iron replacement therapy and finally had the diagnosis of celiac disease.

Body mass index in celiac disease: beneficial effect of a gluten-free diet

            (Cheng, Brar et al. 2009) Download

BACKGROUND: There is concern about celiac disease patients being overweight and gaining more weight while on a gluten-free diet (GFD). AIM: To investigate body mass index (BMI) and effect of GFD on BMI of celiac disease patients in the United States where obesity is a systematic problem. METHODS: BMI at diagnosis and after 2.8 years (mean) on a GFD were compared with national data. RESULTS: Among our patients (n=369, 67.2% female), 17.3% were underweight, 60.7% normal, 15.2% overweight, and 6.8% obese. All patients were followed by a dietitian. Compared with national data, females had lower BMI (21.9 vs. 24.2, P<0.0001) and fewer were overweight (11% vs. 21%, P<0.0001); more males had a normal BMI (59.5% vs. 34%, P<0.0001) and fewer were underweight (9.1% vs. 26.7%, P<0.0001). Factors associated with low BMI were female sex, Marsh IIIb/c histology, and presentation with diarrhea. On GFD, 66% of those who were underweight gained weight, whereas 54% of overweight and 47% of obese patients lost weight. CONCLUSIONS: A GFD had a beneficial impact on BMI, underweight patients gained weight and overweight/obese patients lost weight. The improvement in BMI adds to the impetus to diagnose celiac disease. Expert dietary counseling may be a major factor in the beneficial effects we noted.

Celiac sprue and insulin-dependent diabetes mellitus

            (De Vitis, D'Addesa et al. 1993) Download

Management of osteoporosis due to ovarian failure

            (Eastell 2003) Download

The management of oestrogen deficiency bone loss needs to include general measures to protect against osteoporosis, the identification and treatment of other reversible causes of bone loss, and the use of proven agents for the treatment of osteoporosis. The general measures include improved physical activity, adequate diet (paying particular attention to calcium and vitamin D), and avoidance of behaviours that promote bone loss, such as smoking and alcohol abuse. The diseases that should be identified, other than estrogen-deficiency, include primary hyperparathyroidism, thyrotoxicosis and celiac disease. The treatments that are proven to prevent fractures in women with estrogen deficiency, include hormone replacement therapy, raloxifene, nasal calcitonin, bisphosphonates, (alendronate and risedronate) and parathyroid hormone. The most appropriate therapy in the younger woman is HRT, although the trial-based evidence that HRT prevents fractures is not strong. There is a wide choice of preparations and the use of continuous combined preparations avoids regular menstrual periods, one of the limitations to the use of HRT. Raloxifene has less effect on bone mineral density than HRT, but a similar effect on vertebral fractures and does not result in menstrual bleeding or increased risk of breast cancer. There is recent evidence suggesting that the beneficial effects on lipids translate into reduced risk of cardiovascular disease. Bisphosphonates are the standard treatment for the older woman with osteoporosis. Alendronate has been found to reduce the risk of spine, hip, and wrist fractures and has approval for a once weekly regimen, an approach that appears to prevent GI side effects. Risedronate reduces the risk of spine and non-vertebral fractures within the first year of treatment and has been shown to reduce the risk of hip fracture. It has not been associated with an excess of GI side effects. Parathyroid hormone therapy results in increases in BMD that are even greater than estrogen and the bisphosphonates and to an even greater reduction in the risk of fractures, particularly non-vertebral fractures. It works by stimulation of bone formation rather than by inhibition of bone resorption. However, it has to be given by daily injection. Thus, we have a wide choice of therapies for the woman with osteoporosis due to ovarian failure.

Male gonadal function in coeliac disease: 2. Sex hormones

            (Farthing, Rees et al. 1983) Download

Hypogonadism, infertility, and sexual dysfunction occur in some men with coeliac disease. We have measured plasma testosterone, dihydrotestosterone, sex-hormone binding globulin, oestradiol, and serum luteinising hormone in 41 men with coeliac disease and have related these findings to jejunal morphology, fertility, semen quality, and sexual function. To determine the specificity of these observations in coeliacs we also studied 19 nutritionally-matched men with Crohn's disease, and men with chronic ill-health due to rheumatoid arthritis and Hodgkin's disease. The most striking endocrine findings in untreated coeliacs were increased plasma testosterone and free testosterone index, reduced dihydrotestosterone (testosterone's potent peripheral metabolite), and raised serum luteinising hormone, a pattern of abnormalities indicative of androgen resistance. As jejunal morphology improved hormone levels appeared to return to normal. This specific combination of abnormalities was not present in any of the disease control groups and, to our knowledge, androgen resistance has not been described previously in any other non-endocrine disorder. Plasma oestradiol concentration was modestly raised in 10% of coeliacs and 11% of patients with Crohn's disease. Unlike plasma androgens and serum luteinising hormone in coeliacs, plasma oestradiol was not clearly related to jejunal morphology. Androgen resistance and associated hypothalamic-pituitary dysfunction appear to be relatively specific to coeliac disease and cannot be explained merely in terms of malnutrition or chronic ill-health. In addition, our findings suggest that this endocrine disturbance may be related to sexual dysfunction in coeliac disease but its relationship to disordered spermatogenesis in this condition has not been clearly established.

Celiac Disease: The Great Masquerader

            (Gaby 2010) Download

Reversible insensitivity to androgens in men with untreated gluten enteropathy

            (Green, Goble et al. 1977) Download

Plasma androgen and gonadotrophin concentrations have been measured before and during treatment of 23 men with gluten enteropathy. Before treatment, there was marked rise in total plasma-testosterone, free testosterone concentration (as assessed by the free testosterone index), and plasma-luteinising-hormone concentration. In contrast, 5 alpha-dihydrotestosterone concentrations were lower than normal. All these abnormalities reverted towards normal with successful treatment of the jejunal mucosal lesion. These data are consistent with a reversible tissue resistance to circulating plasma-testosterone in men with gluten enteropathy and subtotal villous atrophy.

Hypoglycemia and reduction of the insulin requirement as a sign of celiac disease in children with IDDM

            (Iafusco, Rea et al. 1998) Download

Obstetric and gynecological problems in women with untreated celiac sprue

            (Molteni, Bardella et al. 1990) Download

We investigated the obstetric and gynecological history of 54 consecutive women (aged 16-62 years, median of 35 years) with newly diagnosed celiac sprue and 54 healthy controls matched for age, origin, and sexual behavior. The mean age of menarche was significantly delayed in these untreated patients with respect to controls (13.5 vs. 12.1 years; p less than 0.0001). Of the patients, 38.8% complained of amenorrhea, compared with 9.2% of the controls (p less than 0.001). Thirty-eight patients and 38 controls were in reproductive age; they had a normal sexual life and did not use contraceptive measures. Five celiacs, but no controls, had repeated abortions (p less than 0.03). Eight celiacs and six controls were in menopause, the mean age at onset being 45.5 and 49.5 years respectively (not significant).

A boy with coeliac disease and obesity

            (Oso and Fraser 2006) Download

AIM: To report the case of a 14-y-old boy with coeliac disease and obesity. METHODS AND RESULTS: A 14-y-old boy presented with episodic diarrhoea associated with eating spaghetti. His body mass index (BMI) at presentation was 37.2 kg/m2 (>99.9th centile). Both antigliadin and anti-endomysial antibodies were positive, and coeliac disease was diagnosed by jejunal biopsy. His diarrhoea ceased and the gliadin and endomysial antibodies disappeared after starting gluten-free diet. At 17 y, his BMI increased to 42.7 kg/m2 despite dietary support. CONCLUSION: Obesity in a child does not exclude the diagnosis of coeliac disease, especially if presenting with suggestive symptoms.

Obesity in celiac sprue

            (Semeraro, Barwick et al. 1986) Download

Celiac sprue usually results in biochemical and clinical signs of malabsorption, nutrient loss, and resulting growth failure. We report a child with celiac sprue diagnosed at 1 year of age who was initially cachectic but who eventually developed obesity while taking a gluten-containing diet.

Gynaecological and obstetric disorders in coeliac disease: frequent clinical onset during pregnancy or the puerperium

            (Smecuol, Maurino et al. 1996) Download

BACKGROUND AND AIM: While gynaecological and obstetric disorders have been reported among women with coeliac sprue, their true prevalence and relationship to the coeliac disease process has not been completely elucidated. Our aims were to determine: (1) the prevalence of gynaecological and obstetric problems in patients with coeliac disease and the influence of strict gluten restriction on their occurrence, (2) the effect of pregnancy on the clinical course of coeliac disease and (3) the clinical features of those patients with onset of coeliac disease during pregnancy and the puerperium. PATIENTS AND METHODS: The gynaecological and obstetric history of 130 coeliac patients and 130 age-matched healthy female controls were compared in a case-control study. RESULTS: In comparison to the controls, untreated coeliac disease patients exhibited significantly later menarche, an earlier menopause, an increased prevalence of secondary amenorrhoea and a greater incidence of spontaneous abortions. Patients who had adhered, in the long term, to a gluten-free diet had gynaecological and obstetric history indistinguishable from controls. Clinical deterioration of coeliac disease was observed in untreated patients during 17% of their pregnancies. In 14% of those untreated patients who were pregnant symptoms related to coeliac disease were manifested for the first time during either pregnancy (n = 7) or the puerperium (n = 4). Nine of these patients had underestimated features suggestive of coeliac disease. CONCLUSION: The early diagnosis and treatment of coeliac disease may avoid significant gynaecological and obstetric complications in affected women. Celiac sprue must always be borne in mind among patients who develop diarrhoea and weight loss during pregnancy and/or the puerperium.

Importance of gluten in the induction of endocrine autoantibodies and organ dysfunction in adolescent celiac patients

            (Toscano, Conti et al. 2000) Download

OBJECTIVE: It is well known that a high number of celiac patients may develop autoantibodies against endocrine glands, but it has not yet been clarified if this increased autoimmune response and the impaired organ function that can develop may be related to the presence or absence of gluten in the diet. The aim of the present study was to evaluate the effect of gluten on the autoimmunity and function of the endocrine glands in adolescent celiac patients. METHODS: To clarify this aspect we investigated 44 patients (28 females), aged 11-20 yr (15.21+/-2.7 yr): 25 (mean age, 15.1+/-2.2 yr) on a gluten-free diet (treated patients) and 19 (mean age 15.4+/-2.9 yr) with a diet containing gluten (untreated patients). Forty adolescent subjects, aged 14-19 yr (mean age, 14.9+/-2.7 yr), of whom 20 were females, were studied as controls. Antibodies against the thyroid, adrenal, and pancreas were evaluated. Thyroid-stimulating hormone FT3, FT4, T3, T4, dehydroepiandrosterone sulphate, 17-OH progesterone, and cortisol, analyzed basally and 60 min after intravenous ACTH stimulation, were assayed to evaluate thyroid and adrenal function. The fasting glycemia level was used to evaluate the endocrine pancreas function. An ultrasonogram of the thyroid gland was performed on all patients. HLA class II typing for DR3 and DQB1 was performed in 32 of 44 patients. RESULTS: Seven of 44 (15.9%) patients were positive for antibodies against peroxidase. Six of 44 (13.6%) were positive for antibodies against thyreoglobulin and four of them also showed positive antibodies against peroxidase. Therefore, in nine of 44 at least one antibody directed against thyroid tissue was positive. Seven of 44 (15.9%) were positive for antibodies against islet cell, one of 44 (2.3%) positive for antibodies against glutamic acid decarboxilase, one of 44 (2.3%) positive for antibodies against insulin, and none for antibodies against islet cell- 512bdc. In 15 of 44 (34%) at least one antibody against an endocrine tissue was positive. The genotype DR3 was found in 21 of 32 (65.6%) celiac patients (10 in the untreated and 11 in the treated group, respectively) and the genotype DQB1*02 (DQ2) was found in 30 of 32 (93.8%) patients (16 in the treated and 14 in the untreated group, respectively). DHA-S values were significantly lower in the untreated (30.5+/-28.5 microg/dl) than in the treated group (61.3+/-59.4 microg/dl, p < 0.05), and both showing significantly (p < 0.01) lower levels with respect to the controls (161+/-52 microg/dl). One patient showed diabetes, another one clinical hypothyroidism (thyroid-stimulating hormone > 6), and two patients showed preclinical hypothyroidism. Interestingly, at least one antibody was positive in 10 of 19 untreated patients (52.6%) but only in five of 25 treated patients (20%), with a significantly different distribution (p < 0.001) between the two groups and without differences in the HLA genotype. The ultrasonographic evaluation of the thyroid resulted in a pathological score in six patients of the 44 examined (13.6%), suggesting the presence of thyropathy. CONCLUSIONS: The main results of this study are the high incidence of thyroid and pancreatic antibodies, and the possible role of gluten in the induction of the antibodies as well as, in few cases, the consequent organ dysfunction.

Association of insulin-dependent diabetes mellitus and celiac disease: a study based on serologic markers

            (Vitoria, Castano et al. 1998) Download

BACKGROUND: The association of celiac disease and insulin-dependent diabetes mellitus has been known for some time. In an attempt to clarify this association, the prevalence of celiac disease among diabetic children was determined, and the risk of insulin-dependent diabetes mellitus was defined in pediatric patients with celiac disease. METHODS: Ninety-three children with diabetes were analyzed for the presence of celiac disease-related markers (antigliadin and antiendomysial antibodies) and characteristic alterations in the intestinal mucosa. In another group, 93 children with celiac disease were screened for pancreatic autoantibodies and pancreatic beta-cell function. RESULTS: Among children with insulin-dependent diabetes mellitus, a 6.45% prevalence of celiac disease was observed, a value significantly higher than that found among healthy controls. In contrast, only three celiac disease patients showed potential autoimmunity toward the pancreatic beta cell, a proportion not significantly different from that in the general population. Additionally, no alteration of glucose metabolism was observed in the antibody-positive patients. CONCLUSION: The increased risk of celiac disease among patients with diabetes requires a long follow-up to determine the presence of celiac disease markers among patients with diabetes, to avoid potential malignant disease derived from untreated celiac disease. In contrast, there is no evidence to support an increased risk of insulin-dependent diabetes mellitus among children with celiac disease. In accordance with the accepted influence of diet in the development of autoimmune diabetes, a hypothetical mechanism of protection against insulin-dependent diabetes mellitus that is mediated by environmental factors related to restricted diet is suggested in this population.


References

(1983). "Infertility in coeliac disease." Lancet 1(8322): 453-4.

Arslan, N., I. Esen, et al. (2009). "The changing face of celiac disease: a girl with obesity and celiac disease." J Paediatr Child Health 45(5): 317-8.

Cheng, J., P. S. Brar, et al. (2009). "Body mass index in celiac disease: beneficial effect of a gluten-free diet." J Clin Gastroenterol 44(4): 267-71.

De Vitis, I., S. D'Addesa, et al. (1993). "Celiac sprue and insulin-dependent diabetes mellitus." J Clin Gastroenterol 17(4): 354-5.

Eastell, R. (2003). "Management of osteoporosis due to ovarian failure." Med Pediatr Oncol 41(3): 222-7.

Farthing, M. J., L. H. Rees, et al. (1983). "Male gonadal function in coeliac disease: 2. Sex hormones." Gut 24(2): 127-35.

Gaby, A. (2010) "Celiac Disease: The Great Masquerader." Clinical Research Update Volume,  DOI:

Green, J. R., H. L. Goble, et al. (1977). "Reversible insensitivity to androgens in men with untreated gluten enteropathy." Lancet 1(8006): 280-2.

Iafusco, D., F. Rea, et al. (1998). "Hypoglycemia and reduction of the insulin requirement as a sign of celiac disease in children with IDDM." Diabetes Care 21(8): 1379-81.

Molteni, N., M. T. Bardella, et al. (1990). "Obstetric and gynecological problems in women with untreated celiac sprue." J Clin Gastroenterol 12(1): 37-9.

Oso, O. and N. C. Fraser (2006). "A boy with coeliac disease and obesity." Acta Paediatr 95(5): 618-9.

Semeraro, L. A., K. W. Barwick, et al. (1986). "Obesity in celiac sprue." J Clin Gastroenterol 8(2): 177-80.

Smecuol, E., E. Maurino, et al. (1996). "Gynaecological and obstetric disorders in coeliac disease: frequent clinical onset during pregnancy or the puerperium." Eur J Gastroenterol Hepatol 8(1): 63-89.

Toscano, V., F. G. Conti, et al. (2000). "Importance of gluten in the induction of endocrine autoantibodies and organ dysfunction in adolescent celiac patients." Am J Gastroenterol 95(7): 1742-8.

Vitoria, J. C., L. Castano, et al. (1998). "Association of insulin-dependent diabetes mellitus and celiac disease: a study based on serologic markers." J Pediatr Gastroenterol Nutr 27(1): 47-52.