Autoimmune Polyglandular Syndromes 

What Are Autoimmune Polyglandular Syndromes?

[dropcap]A[/dropcap]utoimmune polyglandular syndromes (APS) are rare clusterings of two or more endocrine and non-endocrine autoimmune disorders in the same affected person.

Polyglandular is somewhat of a misnomer since many of the manifestations of the diseases do not concern endocrine glands.¹

Endocrine autoimmune disorders involve the abnormal production of autoantibodies that target and destroy the body’s own endocrine tissues, causing loss of essential hormone production by the targeted glands. Endocrine glands include the pituitary, thyroid, adrenal, parathyroid, islets of Langerhans (pancreas), testes in males, and ovaries in females.

First degree relatives (siblings of same parents, parents, children) have an increased incidence of latent, meaning not apparent, autoimmune pathology.²

Q: How many autoimmune polyglandular syndromes are described?

A: Three syndromes have been identified and they are all inherited: APS type-1, APS type-2, and APS type-3.

• APS type-1 is a genetic mutation inherited in an autosomal recessive manner. A child with APS type-1 has inherited two mutated copies of a gene called the AIRE (autoimmune regulator) gene, which is on the long arm of 21st chromosome present in each cell.³ The parents, called carriers, are unaffected since they each have only a single copy of the AIRE mutated gene. Humans have a total of 23 pairs of chromosomes that contain genes inherited from each parent. Mutations in the genes cause disease.

Diagnosis criteria for autoimmune polyglandular syndrome type-1 includes these three disorders:

1. Chronic candida infection (CMC), which usually develops first, typically attacks skin, but very commonly also nails, mouth, vagina, esophagus and intestine. CMC in APS type-1 patients is usually mild, and in most cases, it is chronic. It is found in 73–100 % of APS type-1 patients. 
2. Hypoparathyroidism, causing loss of parathyroid function (hypoparathyreosis) is found in 76–93 % of APS type-1 patients.
3. Autommune Addison’s disease, also called autoimmune adrenalitis, is found in 72-100 % of APS type-1 patients. Still many of them die for unrecognized or late diagnosed autoimmune Addison’s disease, so regular follow-up for children in suspicion of APS type-1 (with CMC or/and hypoparathyroidism) is necessary.⁴

Other assocated disorders that may develop, but are not required for diagnosis, include: vitiligo, premature menopause, pernicious anemia, parathyroid gland failure, alopecia, and celiac disease. Thyroid disease rarely occurs.⁵

• APS type-2 is linked to the inheritance of HLA antigens on chromosome 6 and appears to be autosomal dominant with incomplete penetrance. This suggests the contribution of environmental factors, such as bacterial and viral infections, medications, psychological factors, etc.⁶ It does not have an identified mutation of the AIRE gene.

Diagnosis criteria for  autoimmune polyglandular syndrome type-2 includes these two disorders:

1. Autommune Addison’s disease combined with
2. Autoimmune thyroid disease (thyroid atrophy, hypertrophic goiter related to Hashimoto’s thyroiditis, Graves’ disease, asymptomatic autoimmune thyroiditis)⁶ and/or type I diabetes mellitus.  The conditions may occur in any order.

Polyglandular autoimmune syndrome type-2  is also known as Schmidt’s syndrome when adrenalitis (adrenal insufficiency) is associated with thyroiditis and Carpenter’s syndrome for adrenal insufficiency with hypoparathyreosis (impaired function of parathyroid glands).

Other disorders that may develop, but are not required for diagnosis, include:  type 1 diabetes (50%), frequently gonadal failure or vitiligos, also celiac disease, autoimmune hepatitis, alopecia, pernicious anemia, and myasthenia gravis.⁷ Decades may arise between the onset of one disease and the onset of the second in the same patient.⁸

Therapy of APS type-2 consists of hormone replacement therapy for each separate condition, except that treatment for adrenal insufficiency must be given before thyroid therapy is started when the conditions occur together.⁹ Thyroxin replacement may induce life-threatening adrenal failure in a patient with untreated Addison’s disease. Thus, in case of doubt hydrocortisone should be given before the thyroxine administration is started.¹⁰

• APS type-3  has a strong genetic background. Diagnosis criteria for autoimmune polyglandular syndrome type-3 involves these conditions:

1.  Autoimmune thyroiditis that occurs with another organ-specific autoimmune disease, but not with autoimmune Addison’s disease, and
2. Other autoimmune diseases can include diabetes mellitus, pernicious anemia, vitiligo, alopecia, myasthenia gravis, celiac disease, and Sjögren’s syndrome. The most common APS type-3 combination is autoimmune disease of thyroid gland and pernicious anemia.¹¹

Who is Affected in the General Population?

• APS type-1 is usually apparent in childhood with the incidence of 1 in100,000 persons. It is more common among Finns (1 in 25,000), Sardinians (1 in 14,000), and Iranian Jews (1 in 6,500 to 1 in 9,000). The age of onset is usually early childhood, but new symptoms can develop throughout life. It affects both sexes equally.
• APS type-2 has a peak onset in middle age, although the first signs usually develop between 20–30 years of age. Its prevalence is 1 in 20,000 persons. It is three times more frequent among women than men.¹²
• APS type-3 is most frequent among middle-aged women.⁷[/box]

What Is Autoimmune Polyglandular Syndrome In Celiac Disease and/or Gluten Sensitivity?

• Relationship between autoimmune polyglandular syndrome and celiac disease. Autoimmune polyglandular syndrome is an associated disorder in celiac disease.
• Relationship between autoimmune polyglandular syndrome and gluten. Autoimmune polyglandular syndromes seem to be related to gluten exposure. Gluten could represent a starting or a maintenance factor of autoimmune processes and the risk is proportional to the duration of exposure to gluten. The association between celiac disease and other immune disorders may be due to the sharing of a common genetic background, such as HLA antigens. However, in a very large study, involving 909 patients with celiac disease, Ventura and his associates found that the development of immune disorders in celiac disease was clearly related to the duration of exposure to gluten.¹³,¹⁴
• Relationship between autoimmune polyglandular syndrome and diabetes mellitus. Screening for a quick singling out of autoimmune pathologies is suggested for type 1 diabetes mellitus patients, their first relatives and for subjects affected by other autoimmune diseases or celiac disease.¹⁵
• Relationship between autoimmune polyglandular syndrome and screening. In patients and their relatives, who have autoimmune disorders, a search for autoimmune polyglandular syndrome is crucial. Consequently, it would be appropriate that the patient and all family members are asked for clinical signs and symptoms of autoimmune disorders.¹⁶

How Prevalent Are Autoimmune Polyglandular Syndromes In Celiac Disease and/or Gluten Sensitivity?

Patients with celiac disease are at great risk for developing autoimmune polyglandular syndromes.¹⁷

In a study of 109 patients with autoimmune Addison’s disease, celiac disease was present in 12.5% of the autoimmune polyglandular syndrome (APS) type-1 cases and in four out of 60 (6.7%) of the APS type-2 cases.¹⁸

What Are The Symptoms Of Autoimmune Polyglandular Syndromes?

Symptoms of autoimmune polyglandular syndromes depend on the individual disorders present in the individual.

How Do Autoimmune Polyglandular Syndromes Develop In Celiac Disease and/or Gluten Sensitivity?

• Autoimmune polyglandular syndromes type-2 and type-3 result from these three features shared by the associated diseases:

• Common autoimmune mechanisms,

• Genetic susceptibility, and

• Favorable environmental factors.¹⁹

Do Celiac Disease-Related Autoimmune Polyglandular Syndromes Respond To Gluten-Free Diet?

Studies are inadequate to determine how a gluten free diet could delay or mitigate the course of autoimmune polyglandular syndromes in genetically predisposed subjects.²⁰

Treatment involves life-long follow up and screening for another glandular failure in patients already diagnosed with APS.

6 Steps To Improve Autoimmune Polyglandular Syndromes In Celiac Disease and/or Gluten Sensitivity:

• [dropcap]1[/dropcap]Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

[box type=”shadow” ]Treatment. This condition responds to the complete elimination of gluten, which is the required treatment that improves both  autoimmune disease and gut health.

• Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
• A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
• Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

• Eat foods that can replenish missing nutrients. Find them under NUTRIENT DEFICIENCIES.
• Take nutritional supplements as needed. Find them under NUTRIENT DEFICIENCIES.

Recovery. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

• Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
• Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.²¹
• The intestinal lining may take up to a year to heal.[/box]

• [dropcap]2[/dropcap] Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

[box type=”shadow” ]Here Are Major Inflammatory Food Types That Reduce Healing:

• Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.²²
• Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
• Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.²²
• Fats. Limit deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.²².
• Excessive Refined White Flours (bran layer removed). Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.²²
• Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
• Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.²²
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.²²
• Cocoa and Black Tea increase blood sugar.
• Rosemary. Increases blood sugar levels and should not be used by persons with insulin resistance or diabetes. [/box]

[box type=”shadow” ]Here Are Important Anti-Inflammatory Food Types to Promote Health:

• Fruits. Contain ample amounts of vitamins, minerals and phytochemicals which are naturally occuring components in plants that detoxify toxins, carcinogens (reducing the risk by 50%) and mutagens.
• Non-Starchy Vegetables. Support intestinal integrity and provide ample amounts of vitamins, minerals and phytochemicals. Includes green leafy vegetables such as lettuce and kale, also onion, broccoli, garlic, and others.
• High Quality Complex Carbohydrates. Provide vitamins, minerals, and fiber while boosting serotonin levels to help you relax and feel calm. Includes whole grains, legumes, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets, and others.
• Antioxidants. Protect the body from inflammatory oxidant molecules that continually occur and help us handle stress and reduce irritability. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries, and others. Also, includes vitamin E-containing foods such as nuts, seeds, avocado, olive oil, and others. Cocoa is good, too.
• Omega-3 Fatty Acids. Balance opposing omega-6 fatty acids and bad fats. Fish sources includes tuna, salmon, cod, and others. Plants sources include flax, chia seeds, canola oil, and others.
• Probiotics. Supply normal microbes needed for colon health and health of the body such as these fermented foods: yogurt, kefir, and unpasteurized apple cider vinegar.
• Prebiotics/ High Fiber Foods.  Food with fiber keeps our population of colonic microbes healthy.
• Protective Herbs and Spices.  See below #6 below for examples.[/box]

• [dropcap]3[/dropcap] Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• [dropcap]4[/dropcap] Manage Your Medications Safely:

[box type=”shadow” ]

Certain medications promote inflammation and predispose to activation of autoimmune disease. Ask your doctor or pharmacist about this possible adverse effect if you are taking medications.

Also, some medication used to treat autoimmune diseases deplete nutrients. See below. Do not stop prescribed medications without supervision.

This is not a complete listing.

ANTI-INFLAMMATORIES disrupt intestinal permeability which complicates celiac disease.

• Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron) deplete Calcium, Vitamin D, Magnesium, Zinc, Vitamin C, Vitamin B6, Vitamin B12, Folic Acid, Selenium, Chromium, Phosphorus.
• NSAIDS (Motrin®, Aleve®, Advil®, Anaprox®, Dolobid®, Feldene®, Naprosyn® and others) deplete Folic acid.
• Aspirin and Salicylates deplete Calcium, Folic acid, Vitamin C, Iron, Pantothenate (vitamin B5).

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• [dropcap]5[/dropcap]Nutritional Supplements To Help Correct Deficiencies:

[box type=”shadow” ]

The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.

• Multivitamin/mineral combination that provides 100% once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications.

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.[/box]

• [dropcap]6[/dropcap]Manage Natural Remedies: 

[box type=”shadow” ]Hydration:

• Eight glasses of water are recommended per day unless there is a contraindication such as kidney or heart disease. The Institute of Medicine recommends approximately 2.7 liters (91 ounces) of total water, from all beverages and foods, each day for women and 3.7 liters (125 ounces) daily of total water for men.
• If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C.
• Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
• What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.[/box]

[box type=”shadow” ]Carminatives. The following  anti-inflammatory plant sources called carminitives help heal the digestive tract. They also tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort.

Carminative Food Remedies:

• Raspberry.
• Carrot is also a cleansing digestive tonic.
• Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
• Redbeets also stimulate and improve digestion and are easily digested.
• Cabbage also stimulates and improves digestion and is also a liver decongestant.
• Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
• Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

• Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
• Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
• Parsley also relieves indigestion.
• Rosemary as a tea and in cooking also is a nervous system tonic for stress and fatigue, bile stimulant, and can relieve headaches and indigestion. However, because it increases blood sugar levels, it should not be used by persons with insulin resistance or diabete.
• Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

• Cloves are also antispasmodic.
• Nutmeg is also useful for indigestion.
• Ginger.[/box]

[box type=”shadow” ]Exercise Helps:

Exercise improves circulation and rids the body of toxins.

• Walking is aerobic exercise that reconditions the whole body to improve stamina. Read more about Exercise and Fitness.
• Weight training builds muscle. Read more about Exercise and Fitness.
• Stretching improves flexibilty. Read more about Exercise and Fitness.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal. [/box]

What Do Medical Research Studies Tell About Autoimmune Polyglandular Syndromes with Celiac Disease?

RESEARCH STUDY SUMMARIES

“Screening for autoimmune polyglandular syndrome in a cohort of patients with type 1 diabetes mellitus.” This study aimed to characterize a cohort of 151 patients with type 1 diabetes mellitus (T1DM) on the presence of other autoimmune disorders that could establish the diagnosis of autoimmune polyglandular syndrome (APS). The following clinical parameters were analyzed: gender, current age, disease duration, previous history of autoimmune disorders, and familial history for diabetes mellitus. Each patient was analyzed to detect autoimmune markers of thyroiditis, adrenocortical insufficiency, gastritis, and celiac disease, as well as possible associated dysfunctions.

A cohort with 51.7% males, average current age of 33.4 ± 13 years and disease duration of 14.4 ± 9.6 years was analyzed. Previous history of autoimmunity was found in 2%, and familial history for diabetes mellitus in 31.1% of the cohort. Frequency of autoimmune markers was 24% for thyroiditis, 9.4% for adrenocortical insufficiency, 17.2% for gastritis, and 2% for celiac disease. APS was diagnosed on 25.2% of the patients. APS and autoimmune thyroiditis risk was higher in females. Disease duration correlated directly with gastric autoantibodies, and inversely with positive islet cell, glutamic acid decarboxylase, and tyrosine phosphatase antibodies. There was a correlation between autoimmune markers for thyroiditis and gastritis, as well as between celiac disease and adrenocortical insufficiency. Considering APS prevalence and prognosis, the need for APS screening in patients with T1DM is emphasized.²³

“Clinical profile of coexisting conditions in type 1 diabetes mellitus patients.” This study investigating Type 1 diabetes mellitus (T1DM) for various genetic and autoimmune diseases implicated in its etiopathogenesis found that various 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.

Consecutive patients of T1DM presenting to department of Endocrinology from May 1997 to December 2011 were retrospectively analyzed in context of associated clinical profile. Among 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 patient 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). Routine screening is required for early diagnosis and treatment of associated co morbidities.²⁴

“Celiac disease in North Italian patients with autoimmune Addison’s disease.” This study aiming to define the prevalence of celiac disease and of IgA deficiency in a group of Italian patients with autoimmune Addison’s disease (AAD) found that in patients with AAD there is a high prevalence of both celiac disease and IgA deficiency.

One hundred and nine patients with AAD were enrolled and examined for tissue transglutaminase autoantibodies of the IgA class, circulating levels of IgA and adrenal cortex antibodies. Two (1.8%) of the patients were affected by already diagnosed celiac disease and were already on a gluten-free diet. Out of the remaining 107 patients, four (3.7%) were found to be positive for IgA antibodies to human tissue transglutaminase. Three of the four patients who were positive for tissue transglutaminase autoantibodies agreed to undergo endoscopy and duodenal biopsies and, in one, a latent form of celiac disease was identified. The clinical, silent or latent form of celiac disease was present in six out of 109 (5.4%). This prevalence was significantly higher than that reported for the Northern Italian population which was equal to 0.063%.

Specifically, celiac disease was present in 12.5% of the autoimmune polyglandular syndrome (APS) type 1 cases, in four out of 60 (6.7%) of the APS type 2 cases and in one out of 40 (2.5%) of the isolated AAD cases. IgA deficiency was present in two out of 109 patients (1.8%), all of whom had normal IgG anti-gliadin. Autoantibodies to the adrenal cortex were detected in 81 out of 109 patients (74.3%).Consequently, it is important to screen for celiac disease with tissue transglutaminase autoantibodies of the IgA class and for IgA levels.²⁵ 

CASE REPORT SUMMARIES

“Multiple Disease Associations in Autoimmune Polyglandular Syndrome Type II. “ This case report describes the course of a patient with autoimmune polyglandular syndrome type II (APS II)  with a dramatic development of eight autoimmune diseases over the course of ten years. She developed Addison’s disease, hypothyroidism, type 1 diabetes, Hashimoto’s encephalopathy, vitiligo, celiac disease, sero-negative arthritis, and ulcerative colitis. This represents a particularly aggressive course of APS II and this combination of autoimmune diseases has not been previously reported. It highlights the potential complexity and severity of the clinical course of APS II.

A 25 year old female with a history of ulcerative colitis, celiac disease and type 1 diabetes presented with mental status changes. She was diagnosed with Hashimoto’s encephalopathy and treated with high dose steroids and intravenous immunoglobulin. She recovered well from her encephalopathy but her post-hospitalization course was complicated due to the development of Addison’s disease, vitiligo, sero-negative arthritis, and hypothyroidism.²⁶

“Dermatitis herpetiformis co-localised with vitiligo in a patient with autoimmune polyglandular syndrome.” This case report describes the unusual presentation of dermatitis herpetiformis co-localised with segmental vitiligo in a 37-year-old woman with a background history of autoimmune polyglandular syndrome type 2.

The patient presented with a 3-day history of a severe, itchy, bullous eruption on the trunk and limbs associated with malaise. Her past medical history included Addison’s disease, autoimmune hypothyroidism, type 1 diabetes mellitus, coeliac disease and vitiligo. Coeliac disease was diagnosed following distal duodenal biopsy which demonstrated subtotal villous atrophy. The patient reported strict adherence to a gluten-free diet. Vitiligo on the limbs, trunk, and neck was treated with moderate potency topical corticosteroids fourteen years prior to this acute presentation.

On examination, multiple, well-demarcated, segmental areas of depigmentation were present on the forearms, neck, groin, and upper thighs. There were vesicles and bullae of up to 20 mm in diameter with adjacent crusted, erythematous papules exclusively within the depigmented areas but not within the pigmented patches. She was managed with a gluten-free diet and hydroxyzine 25 mg when required. We propose genetic mosaicism as a possible mechanism. There has only been one previous case report in which dermatitis hepetiformis co-localised in close proximity but not exclusively within vilitigo in a patient with autoimmune thyroiditis.²⁷

“Treatment-refractory hypothyroidism.” This case report describes diagnosing celiac disease and subsequent autoimmune polyglandular syndrome type-2 in a 49-year-old man who was referred to an endocrine clinic because of rising thyroid-stimulating hormone (TSH) levels despite increasing doses of levothyroxine. The patient had a history of Grave’s disease, which had been successfully treated with radioiodine ablation 15 years earlier. Over the past several years, his serum TSH levels had risen to 31.5 (normal 0.4–4.5) mU/L, and the dose of levothyroxine he was prescribed had been increased to 225 μg per day, or 2.7 (usual recommended dose 1.6) μg/kg daily.

The patient’s adherence to the drugs he had been prescribed was confirmed, and to exclude impaired bioavailability of the medication,a medically supervised test for the absorption of levothyroxine was performed. The results of the test showed that only 30% of the medication administered was absorbed.

In the investigation of intestinal malabsorption, the screening serum test for gluten enteropathy was abnormal; the level of immunoglobulin A antibodies against transglutaminase was 75.4 (negative < 9.0, borderline 9–16, positive > 16.0) units/mL. A subsequent endoscopic biopsy of the patient’s bowel was consistent with a diagnosis of celiac disease. The patient was directed to follow a low-gluten diet. The patient’s histological abnormalities resolved, and his serum level of TSH normalized with his usual dose of thyroxine (225 μg daily).

Because of the patient’s previous Grave’s disease, an autoimmune polyglandular syndrome was investigated. Subsequent tests showed elevated antiadrenal and 21-hydroxylase antibodies, suggesting autoimmune adrenalitis. A short intravenous adrenocorticotropic hormone (ACTH) stimulation test was consistent with diminished adrenal cortisol reserve.²⁸

“Multiple immune disorders in unrecognized celiac disease: a case report.” This case report describes the course of a 34 year old female patient with unrecognized celiac disease and multiple extra intestinal manifestations, mainly related to a deranged immune function, including macroamilasemia, macrolipasemia, IgA nephropathy, thyroiditis, and anti-b2-glicoprotein-1 antibodies, that disappeared or improved after the implementation of a gluten-free diet.

After six months of controlled gluten free diet, the patient’s body weight increased 12 kg; laboratory investigations demonstrated normalization of serum amylase, serum lipase and immunoglobulin levels; antigliadin, anti-2-glicoprotein-1 and anti-thyreoglobulin antibodies were no longer detectable, but antiendomysial antibodies were still present. Endoscopy showed a normal appearance of duodenal mucosa, and duodenal biopsy revealed a partial recovery of duodenal morphology. Due to the persistence of proteinuria (2.3 g/day), microscopic hematuria and hyaline and granular casts, a kidney biopsy showed that it was IgA nephropathy. After 18 months of gluten-free diet, antiendomysial antibodies disappeared; creatinine clearance increased, but proteinuria further worsened (2.9 g/day, Table 1), and albumin levels were still low. After 24 months of gluten-free diet, a new duodenal biopsy showed complete recovery of villous architecture. Renal function further improved and proteinuria markedly decreased (Table 1). Amylase, lipase, and immunoglobulin levels were within the normal range. Anti-2-glicoprotein-1, anti-thyreoglobulin, antigliadin, antiendomysial and anti-TTG antibodies were undetectable. A coagulation study was normal.

“Although both celiac disease and the other manifestations of a deranged immunity might be explained on the basis of a common genetic predisposition to this kind of disorders, some findings suggest that celiac disease itself is responsible for the initiation of the immunological response. Indeed, persistent stimulation by some proinflammatory cytokines, such as interferon  and tumor necrosis factor , could induce further processing of autoantigens and their presentation to T lymphocytes by macrophage-type immunocompetent cells. As a matter of fact, the prevalence of immune diseases among patients with celiac disease seems proportional to the time of exposure to gluten, and many immune alterations disappear following the recognition of celiac disease and appropriate treatment, just as it occurred in this patient.”²⁹

“We report on a 19-year-old woman with polyglandular autoimmune syndrome type II (APS II).” This case report describes diagnosing autoimmune polyglandular syndrome type-2 in a patient who was diagnosed with Addison’s disease and hypothyroidism due to chronic autoimmune thyroiditis. Her mother had celiac disease and her brother had diabetes mellitus type 1. Chronic autoimmune thyroiditis was diagnosed in her mother, subsequently. In patients and their relatives, who have autoimmune disorders, a search for autoimmune polyglandular syndrome is crucial. Consequently, it would be appropriate that the patient and all family members are asked for clinical signs and symptoms of autoimmune disorders.

Annual measurement of morning cortisol, TSH and fasting plasma glucose may useful. Screening of affected individuals as well as their first-degree relatives for celiac disease is recommended. Therapy of APS II consists of hormone replacement therapy, but thyroxin replacement may induce life-threatening adrenal failure in a patient with untreated Addison’s disease. Thus, in case of doubt hydrocortisone should be given before the thyroxine administration is started.¹⁰

“Coeliac disease associated with Sjogren’s syndrome, renal tubular acidosis, primary biliary cirrhosis and autoimmune hyperthyroidism.” This case report of a patient diagnosed with biliary cirrhosis, Sjogren’s syndrome, and renal tubular acidosis who developed diarrhea and weight loss, describes subsequent diagnosis of celiac disease. She went on to develop autoimmune hyperthyroidism despite a gluten free diet.³⁰

Sources:

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