Rhabdomyolysis, renal failure, pericardial effusion, and acquired von Willebrand disease resulting from hypothyroidism in a 10-year-old girl.

A 10-year-old girl manifested unexplained muscle aches and high creatine phosphokinase (CPK) concentrations attributed to rhabdomyolysis in association with severe hypothyroidism due to autoimmune thyroiditis. The response to therapy strongly suggested that hypothyroidism was the cause of rhabdomyolysis. Hypothyroidism is a rare cause of rhabdomyolysis. It should always be considered in a patient with muscular symptoms and elevated CPK concentrations. In addition, the patient developed other uncommon manifestations of hypothyroidism such as pericardial effusion, acute renal failure, and acquired von Willebrand disease. After thyroxine replacement, the symptoms and abnormal findings disappeared. The patient was also diagnosed as having celiac disease, which is often associated with autoimmune thyroiditis. Conditions accompanying autoimmune thyroid disease may result from altered thyroid function and from the presence of other autoimmune diseases. The butterfly-shaped thyroid gland has a tremendous impact on metabolism, which may be compared to a phenomenon termed the "Butterfly Effect".     

Autoimmune hypothyroidism nonresponsive to high doses of levothyroxine and severe hypocalcemia

The factors that make difficult the normalization of TSH in hypothyroidism need special attention because some patients on thyroxine replacement do not maintain a normal TSH. We report a 50 year-old woman with autoimmune hypothyroidism of difficult compensation, associated with anemia, hypocalcemia with a previous episode of tetany, hypomagnesemia, psychologic alterations and important weight loss. After compensation of the hypothyroidism with doses of L-thyroxine as high as 325 microg/day, the hypothesis of a malabsorptive syndrome was raised. Celiac disease was confirmed by elevated serum antigliadin antibody. A gluten-free diet was instituted which improved the symptoms associated with malabsorption and reduced the L-thyroxine requirement to 125 microg/day. Because several studies have shown an association of both diseases, a routine screening for celiac disease has been widely proposed in patients with autoimmune thyroid disease.     

Basedow's disease and celiac disease in an adolescent with Down syndrome

INTRODUCTION: Down syndrome is a favourable land to the emergence of auto-immune disease. CASE RECORD: Graves' disease and celiac disease were diagnosed in a 16 years old adolescent with Down syndrome presenting chronic diarrhoea, important delayed development and signs of hyperthyroidism. DISCUSSION: Celiac disease and thyroid dysfunction would be screening in patient with Down syndrome.     

Thyroid disorders in Brazilian patients with celiac disease

INTRODUCTION/AIM: Patients with celiac disease (CD) can develop a gluten related autoimmune disorder that affects not only the small intestine but other tissues as well. An increased prevalence of autoimmune diseases has been reported, particularly autoimmune thyroiditis. The aim of this study was to characterize thyroid disorders in patients with CD. PATIENTS/METHODS: Fifty-two patients with CD (43 female, 9 male; mean age, 41.1 years) were studied. Nine were on a gluten-free diet (GFD). They were divided into four groups: Group 1, without thyroid involvement (n=30); Groups 2A-C, with thyroid involvement (n=22); Group 2A, subclinical hypothyroidism (n=11); Group 2B, clinical hypothyroidism (n=10); and Group 2C, other thyroid disorders (n=1). CD was confirmed by serologic and histologic criteria. Thyroid involvement was detected by measurement of thyroid stimulating hormone (TSH) and anti-thyroperoxidase antibodies (anti-TPO). RESULTS: Increased levels of TSH and/or anti-TPO levels were detected in Groups 2A (21.1%) and 2B (19.2%). The patients of Group 2B presented clinical symptoms of hypothyroidism before the diagnosis of CD, and 5 of these patients were receiving levothyroxine. One woman (Group 2C; 1.92%) had a medullary carcinoma. There was statistical significance between the age when thyroid disease was diagnosed (current age) and the age of CD diagnosis between Groups 1 and 2B. Patients with thyroid involvement presented associated diseases such as diabetes mellitus (2), Down's syndrome (2), ulcerative colitis (1), and dermatitis herpetiformis (2). CONCLUSIONS: Our findings demonstrated an increased prevalence of thyroid disorders (hypothyroidism, 19.2%; and subclinical hypothyroidism, 21.2%), and other associated diseases in celiac patients, even on a GFD, increasing with the age of the patients. Screening for associated diseases is recommended for patients with CD, independent of age at diagnosis or treatment duration.     

Celiac disease presenting as resistant hypothyroidism.

The high prevalence of celiac disease in patients with autoimmune hypothyroidism, compared to the general population, has been well documented but screening for celiac disease is not recommended as yet in otherwise asymptomatic hypothyroid patients. In recent years the high prevalence of undiagnosed celiac disease in the general population, largely as a result of the many atypical manifestations of the disease, has become apparent. We report the case of a 58-year-old woman with autoimmune hypothyroidism who was initially suspected of having celiac disease on the basis of apparent resistance to levothyroxine therapy, and who had no other clinical or laboratory clues to suggest the diagnosis. Cases of undiagnosed celiac disease causing levothyroxine malabsorbtion have previously been described, but all previous cases had other obvious manifestations of the disease. We believe that this atypical presentation of celiac disease warrants further attention, and that the diagnosis of celiac disease should always be considered in patients requiring higher than expected doses of thyroid hormone replacement, even in patients with normal bowel habit, and no other apparent manifestations of the disease.     

Unusual association between pure red cell aplasia and primary Sjögren's syndrome: a case report

Pure red cell aplasia (PRCA) is an acute anemia due to selective suppression of erythropoiesis. We report a case of PRCA diagnosed before the onset of primary Sj?gren's syndrome (SS). A young woman, with autoimmune thyroiditis, developed polyarthritis with ANA and Rheumatoid factor positivity, diagnosed as Rheumatoid arthritis. During the time she developed anti-Ro and anti-La antibodies and deformities at proximal interphalangeal joints. After 4 years, she developed severe acute anemia, without reticolocytes: a bone marrow biopsy indicated a PRCA and she started transfusions, steroids, cyclosporin. A steroid-dependent anemia persisted. After 2 years she developed sicca, parotid swelling, fatigue, mild leukopenia, elevated serum creatinine, hypokalemia, hyposthenuria and tubular proteinuria. Lip biopsy and dacriologic tests confirmed a diagnosis of SS, while X-ray revealed a deforming non-erosive arthropathy (Jaccoud type). In present case, PRCA could be considered an autoimmune bone marrow disease within SS, whose extra-glandular manifestations onset before the sicca symptoms.     

Thyroid dysfunction in individuals with Down syndrome

A group of 138 community-based patients with Down syndrome were examined for evidence of autoimmune thyroid dysfunction at the time of their referral for routine health care services provided as part of a model program. Twenty-eight patients (20.3%) were found to have previously unrecognized hypothyroidism, and 2 patients (1.4%) had previously unrecognized hyperthyroidism. In addition, 66 patients were tested for thyroid autoantibodies, and 26 were found to have positive antimicrosomal and/or antithyroglobulin antibody test results. There was no statistically significant association between age or sex and the mean thyrotropin value or the presence of thyroid autoantibodies. The relationship between the mean thyroxine level and sex was mildly significant. Of the patients with hypothyroidism, 78.5% were female, and most were between the ages of 30 and 50 years. However, a higher-than-expected number of patients with autoimmune hypothyroidism were under age 30 years. These findings highlight the lack of adequate health care services available to persons with Down syndrome who live in the community. All persons with Down syndrome must undergo regular clinical and laboratory screening for the presence of thyroid disease.     

Undiagnosed celiac disease in childhood

AIMS: This study was designed to assess the proportion of adult patients with celiac disease who had had undiagnosed symptoms during childhood and to determine the consequences of such diagnostic delay. PATIENTS AND METHODS: One hundred eighty-four patients with celiac disease (56 males, 128 females, age range 17-88 years) were classified according to diagnosis and symptoms of celiac disease during childhood. Prevalence of short stature, low fertility, clinical osteoporosis, cancer, and autoimmune disease were assessed in each celiac group and compared with a control group matched for gender and age. RESULTS: Compared with the control group, patients with celiac disease were shorter (men 171.4 +/- 9.0 cm vs 176.4 +/- 6.9 cm, P<0.01; women 159.7 + 7.3 cm vs 162.7 +/- 6.2 cm, P<0.01) and had a higher prevalence of symptomatic osteoporosis (5%) cancer (10%), and autoimmune disease (25%). Compared with matched controls and with patients whose celiac disease had been diagnosed during childhood (n=36), or who had remained symptom-free (n=95), patients who had undiagnosed symptomatic celiac disease during childhood exhibited higher prevalence of short stature (26%), low female fertility or low birth weight (36%). Multivariate analysis showed that short stature and low fertility correlated with duration of symptoms before diagnosis; osteoporosis and cancer correlated with age. The prevalence of autoimmune disease was unrelated to early onset of symptoms or delay to diagnosis. CONCLUSIONS: Missing the diagnosis of celiac disease in a symptomatic child may lead to short stature and low female fertility.     

The clinical features of diabetes with coexisting autoimmune thyroid disease

Summary A study was made of the clinical features of diabetics with coexisting Graves' disease (n=117) or primary hypothyroidism (n=98). Those with Graves' disease developed thyroid dysfunction and diabetes at an earlier age than patients with primary hypothyroidism. There was, however, no difference between the two groups in respect of sex ratio nor proportion of subjects requiring insulin treatment. In contrast to the general diabetic population, 87% of diabetics with thyroid disease were female, 56% required insulin treatment and of patients requiring insulin from diagnosis, the median age at diagnosis of diabetes was 36 years. A strong correlation was observed between age at diagnosis of diabetes and that of hyperthyroidism (r=0.71, p< 0.001) or hypothyroidism (r=0.65, p<0.001). With increasing age at diagnosis of diabetes the interval between diagnosis of diabetes and thyroid disease diminished. The mean ± SEM interval between diagnosis of diabetes and that of thyroid dysfunction was longer in hypothyroid (6.7±1.2 years) than in hyperthyroid diabetics (-2.4 ±1.2 years). Neither insulin-dependent nor non-insulin dependent diabetics with associated thyroid disease exhibited a significant seasonal variation in diagnosis or symptomatic onset of diabetes. It is conceivable that where diabetes accompanies autoimmune thyroid disease in the same patient, both conditions may share a common and coincident pathogenesis which is unrelated to acute environmental influences.     

Autoimmune polyglandular syndrome type 2 and osteoporosis in a 69 years old patient

We present a case of a 69 year old female with autoimmune polyglandular syndrome type 2 or Schmidt's syndrome. The syndrome consists of primary autoimmune adrenocortical insufficiency (Addison's disease), autoimmune hypothyroidism, and type 1 diabetes. In the presented case Addison's disease was diagnosed on the basis of clinical symptoms, low serum cortisol level: at 8 am 129,1 nmol/l (reference range 220,70-689,70), and high ACTH level: 1540,8 pg/ml (reference range 0-50). Hypothyroidism was diagnosed with serum TSH of 4,46 microU/ml (rr 0,20-3,50), aTPO antibodies titer was 117 U/ml (rr 0-60). The patient also presented insulin dependent diabetes treated with insulin and osteoporosis with a compressive vertebral fracture and a hip fracture in the past (hip T-score = -2,62). After substitutional pharmacotherapy was implemented, the patient was discharged in good health. Possible correlation between bone metabolism disorders and autoimmune polyglandular syndrome needs further investigation.     

Celiac sprue (the great modern-day imposter)

PURPOSE OF REVIEW: To review the current epidemiological information on celiac disease and the various presentations and associated. RECENT FINDINGS: Epidemiologic studies reveal celiac disease to be common, occurring in approx. 1% of the population. It is being diagnosed worldwide, even in developing countries. The classic mode of presentation has become less common, with diarrhea or a malabsorption syndrome as the mode of presentation in fewer than 50% of individuals. The other major modes of presentation are iron-deficiency anemia, osteoporosis, screening of family members, or incidentally at endoscopy done for dyspepsia or reflux. Neurological presentations may include peripheral neuropathy or ataxia. Arthritis is commonly found in patients with celiac disease when systematically sought. Patients often have a previous diagnosis of irritable bowel syndrome. Autoimmune diseases occur more frequently (three to ten times more) in those with celiac disease than the general population. However, this increased incidence of autoimmune diseases is not prevented by early diagnosis of celiac disease. SUMMARY: We will review the various associated diseases/presentations of celiac disease. The heterogeneity of the symptoms can make the diagnosis challenging and certainly the great modern-day imposter.     

Holmes-Adie syndrome, autoimmune hepatitis and celiac disease： A case report

A 35-year-old female patient presented with the following symptoms of Holmes-Adie syndrome: photophobia, enlargement of the left pupil unresponsive to light, Achilles areflexia. The pilocarpine test was positive. No tumor or other neurological abnormality was found. She had a 19-year history of autoimmune hepatitis. Flares up were observed following each 3 deliveries. At age of 31 she presented with diarrhea and weight loss. Abdominal tumor was detected by ultrasound. The surgically removed tumor was histologically a benign mesenteric multicystic lymphangioma. Simultaneously, celiac disease was diagnosed. Gluten-free diet resulted in a significant improvement of celiac disease, but not of autoimmune hepatitis. Autonomic neuropathy was proven by standard cardiovascular tests. The patient was a homozygous carrier for HLA DQ2 antigen characteristic for celiac disease and heterozygous for HLA DR3 B8 frequent in autoimmune liver diseases. Our novel observation on association of Holmes-Adie syndrome with autoimmune hepatitis and celiac disease is suggestive for a common immunological background for all three entities present in a patient with mesenteric multicystic lymphangioma.     

A case of Kearns-Sayre sindrome with autoimmune thyroiditis and complete atrio-ventricular block

The Kearns-Sayre syndrome, (characterized by its onset before the age of 20 years, chronic ophthalmoplegia, pigmentary retinal degeneration and at least one of the following symptoms: ataxia, heart block and high protein content in the cerebrospinal fluid) is a severe variant of chronic progressive external ophthalmoplegia with frequent rearrangements of the mitochondrial DNA (mtDNA). The aim of this paper is to report a sporadic paediatric case of Kearns-Sayre syndrome with mtDNA heteroplasmic deletion, absence of cytochrome c-oxidase in many muscle fibers, autoimmune thyroiditis, complete atrio-ventricular heart block in which the diagnosis of subclinical hypothyroiditis associated with autoimmune thyroid disease was made. The subclinical hypothyroidism, more severe in the presence of thyroid antibodies, may have contributed to the pathogenesis of cardiovascular disease. We hypothesized that in this patient, predisposed by mitochondrial deletion, anti-thyroid antibodies may have interfered with the mitochondrial function of conduction heart system, causing atrio-ventricular heart block. It seems important to study anti-thyroid antibodies in every case of Kearn-Sayre syndrome, specially if cardiac rhythm disturbances are present.     

Type 1 diabetes and autoimmune polyendocrine syndromes

Type 1 diabetes (T1D) is associated with autoimmune thyroid disease (AIT), celiac disease (CD), Addison's disease (AD), and other autoimmune diseases. These diseases can occur simultaneously in defined syndromes with distinct pathophysiology and characteristics: autoimmune polyendocrine syndromes (APSs) and the immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX). APSs were initially defined as a multiple endocrine gland insufficiency associated to an autoimmune disease in a patient. APS-1 is characterized by the evidence of chronic candidiasis, chronic hypoparathyroidism, AD and T1D could be present as part of this syndrome. The combination of autoimmune adrenal insufficiency with AIT and/or type 1 autoimmune diabetes mellitus defines APS-2. AIT associated to other autoimmune diseases (excluding AD and/or hypoparathyroidism) are the main characteristics of APS-3. Different clinical combinations of autoimmune diseases which were not included in the previous groups are the characteristics of APS-4. IPEX is a recessive disorder characterized by the neonatal onset of T1D, infections, enteropathy, thrombocytopenia and anemia, as well as endocrinopathy, eczema and cachexia. These disorders are not common, but their consequences can be life threatening when the diagnosis is overlooked, and the treatment is the same prescribed for isolated disease presentation.     

Unusual association of thyroiditis, Addison's disease, ovarian failure and celiac disease in a young woman.

The coexistence of autoimmune endocrine diseases, particularly autoimmune thyroid disease and celiac disease (CD), has recently been reported. We here present a 23-year-old woman with a diagnosis of hypothyroidism due to Hashimoto's thyroiditis, autoimmune Addison's disease, and kariotypically normal spontaneous premature ovarian failure. Considering the close association between autoimmune diseases and CD, we decided to search for IgA anti-endomysium antibodies (EmA) in the serum. The positivity of EmA and the presence of total villous atrophy at jejunal biopsy allowed the diagnosis of CD. On a gluten-free diet the patient showed a marked clinical improvement accompanied, over a 3-month period, by a progressive decrease in the need for thyroid and adrenal replacement therapies. After 6 months, serum EmA became negative and after 12 months a new jejunal biopsy showed complete mucosal recovery. After 18 months on gluten-free diet, the anti-thyroid antibodies titre decreased significantly, and we could discontinue thyroid substitutive therapy. This case emphasizes the association between autoimmune polyglandular disease and CD; the precocious identification of these cases is clinically relevant not only for the high risk of complications (e.g. lymphoma) inherent to untreated CD, but also because CD is one of the causes for the failure of substitute hormonal therapy in patients with autoimmune thyroid disease.     

Celiac disease: what's new about it?

In the present review we will try to summarize the clinical and diagnostic features of celiac disease (CD) as well as the new findings on extraintestinal manifestation. CD is an immune-mediated enteropathy caused by a permanent gluten intolerance. In the last years, the diagnosis is becoming more and more frequent because of the recognition of 'new' symptoms and associated extraintestinal manifestations. Classical CD is dominated by symptoms and sequelae of gastrointestinal malabsorption. In the 'atypical forms', the extraintestinal features usually predominate, with few or no gastrointestinal symptoms. Silent CD refers to asymptomatic patients with a positive serologic test and villous atrophy on biopsy. This form is detected by screening of high-risk individuals, or villous atrophy occasionally may be detected by endoscopy and biopsy conducted for another reason. The potential form is diagnosed in groups at risk including relatives of celiac patients, Down syndrome and autoimmune diseases. Latent CD is defined by positive serological tests but not histological changes on biopsy. These individuals are asymptomatic, but later may develop symptoms and/or histological alterations. Recognition of atypical manifestations of CD is very important because many cases can remain undiagnosed with an increased risk of long-term complications.     

Glycogenic hepatopathy associated with type 1 diabetes mellitus as a cause of recurrent liver damage

Aminotransferase elevation is a frequent cause of consultation for the Hepatologist, in both the outpatient and inpatient settings, but identifying the origin of these biochemical alterations may be challenging. Here we report a case where acute elevation of aminotransferases, associated with abdominal symptoms, was the cause of two hospitalizations in a short period of time. As the patient suffered from type 1 diabetes, celiac disease, and autoimmune thyroiditis, several potential causes of damage could be hypothesized, including celiac hepatitis, fatty liver, and autoimmune hepatitis. A liver biopsy performed in the occasion of the second hospitalization allowed to rule out autoimmune hepatitis and celiac hepatitis, showing mild signs of fatty infiltration. Staining with periodic acid-Schiff with or without diastase showed a marked accumulation of glycogen, indicating the presence of a glycogenic hepatopathy associated with poorly controlled type 1 diabetes. This condition may be a cause of liver damage in patients with type 1 and occasionally type 2 diabetes, but its occurrence is often overlooked. This case report illustrates the fact that glycogenic hepatopathy may relapse, and prompts the clinician to take into account this condition in the differential diagnosis of causes of liver injury.     

Celiac disease and autoimmune diseases or systemic disease. Six cases and a review of the literature

BACKGROUND: Celiac disease is an autoimmune disorder which may be associated with another autoimmune or systemic disease. OBJECTIVE: To determine the links between autoimmune diseases and celiac disease. PATIENTS AND METHODS: Among 31 patients with a celiac disease, we selected those who had another autoimmune or systemic disease. RESULTS: We report 6 patients with such disease association: 3 with autoimmune thyroiditis including one also with Grave's disease, 2 with systemic lupus erythematosus including one also with insulin-dependent diabetes mellitus, and 1 with temporal arteritis. CONCLUSION: The link between celiac disease and autoimmune thyroiditis or insulin-dependent diabetes mellitus seems to be real but many discrepancies are observed for the other autoimmune diseases. After a literature review, we suggest a summary of effective associations between celiac disease and autoimmune or systemic diseases.     

Sobreposición entre los trastornos funcionales de dolor abdominal y enfermedades orgánicas en niños

Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults.     

Clinical profile of coexisting conditions in type 1 diabetes mellitus patients

AimsType 1 diabetes mellitus (T1DM) is associated with various genetic and autoimmune diseases implicated in its etiopathogenesis. We hereby profile the clinical association of such diseases among patients from our center.MethodsConsecutive patients of T1DM presenting to department of Endocrinology from May 1997 to December 2011 were retrospectively analyzed in context of associated clinical profile.ResultsAmong 260 patients diagnosed as T1DM, 21 (8%) had hypothyroidism, 4 (1.5%) had hyperthyroidism and 2 (0.7%) had primary adrenal insufficiency. Eighteen patients (7%) had celiac disease, 9 (3.5%) had Turner's syndrome, 5 patients (1.9%) had Klinefelter's syndrome, whereas Down's syndrome and Noonan's syndrome was present in 2 and 1 patients (0.7%) respectively. One patient had Wolframs’ syndrome and 1 patients had myasthenia gravis. Systemic lupus erythematosus and rheumatoid arthritis were present in 3 and 1 patients respectively. Total of 5 patients with cerebral palsy, 4 cases with deaf mutism, 4 cases with acute psychosis and 16 patients with depression were noted. Mean age of study patients was 20.8 ± 9.8 years (range, 3–23 years).ConclusionVarious conditions including genetic (Down, Turner, Noonan, and Klinefelter's), autoimmune (thyroid and adrenal disorders, myasthenia gravis, SLE, rheumatoid arthritis) and central nervous system diseases were the associated diseases encountered in our patients. Routine screening is required for early diagnosis and treatment of associated co morbidities.