By means of the scientific description of two uncommon cases who underwent. surgical resection of multinodous goiter and following histopathological investigation revealing isolated extrapulmonary manifestation of sarcoidosis, this uncommon diagnosis including symptomatology, clinical findings, diagnostic and therapeutic management is to be illustrated.

Diagnostics: Scintigraphy of the thyroid gland with a left-thyroid cold node; ultrasound-guided puncture (cytological investigation, non-suspicious).

Elective thyroidectomy with no macroscopic anomalies und no abnormal aspects with regard to surgical tactic and technique. Histopathological investigation: Complete resection specimen of the thyroid gland with granulomatous inflammation consistent with sarcoidosis.

Uneventful with no further manifestations of sarcoidosis in the following diagnostics.

Ultrasound, inhomogeneous node (37×30×35 mm) of the right thyroideal gland with echo-poor parts and peripheral vascularization; scintigraphy showing marginally compensated unifocal autonomy of the thyroid gland (laboratory parameters, increased serum level of thyroglobulin [632 ng/mL]).

Planned right hemithyroidectomy with confirmed nodous structure of thyroid parenchyma, without suspicious lymph nodes. Histopathological investigation: 33-mm follicular, nodular, encapsulated structure of thyroid parenchyma (diagnosed as follicular adenoma); 2nd opinion: low-grade differentiated carcinoma of thyroid gland with angioinfiltrating growth and granulomatous inflammation of sarcoidosis type. Procedural intent: After tumor-board consultation, completing thyroidectomy was performed within a 5-weeks interval (pT2 pN0[0/1] V1 L0 G3 R0) with subsequent ablating radio'active iodine therapy; 18 F-FDG-PET-CT (several atypical infiltrates within the right upper lobe of the lung) and bronchoscopy with no detection of further manifestation of sarcoidosis.

Sarcoidosis is considered a rare granulomatous multi-locular, systemic disease of not completely known etiopathogenesis with substantial heterogeneity. In most cases, it is associated with the lung, but which can become manifest in various organs. Frequently, extrapulmonary manifestations are usually detected as histological findings by coincidence, which require further investigation to find out additional manifestations as well as to exclude florid infection or other granulomatous processes (clarifying competently differential diagnosis). Therapy is only indicated in symptomatic organ manifestations, taking into account the high rate of spontaneous healing and possible side effects.

Sarcoidosis, a multisystemic immune disease, significantly impacts patients' quality of life. The complexity and diversity of its pathogenesis, coupled with limited comprehensive research, had hampered both diagnosis and treatment, resulting in an unsatisfactory prognosis for many patients. In recent years, the research had made surprising progress in the triggers of sarcoidosis (genetic inheritance, infection and environmental factors) and the abnormal regulations on immunity during the formation of granuloma. This review consolidated the latest findings on sarcoidosis research, providing a systematic exploration of advanced studies on triggers, immune-related regulatory mechanisms, and clinical applications. By synthesizing previous discoveries, we aimed to offer valuable insights for future research directions and the development of clinical diagnosis and treatment strategies.

Sarcoidosis is a mysterious condition with an etiology that has to date eluded explanation. Innumerable clinical and serological organ- and non-organ-specific autoimmune associations have been reported. Many of the associated conditions are life-threatening but easily manageable if diagnosed early. Due to the long latency that precedes the clinical onset of autoimmune diseases, it is prudent to ensure a long follow-up and a broad viewing perspective while maintaining a high index of suspicion when viewing the autoimmunity iceberg in sarcoidosis.

The degree to which sarcoidosis patients are affected by autoimmune diseases is poorly understood. Prior studies of autoimmune co-morbidities in sarcoidosis have focused on populations outside the USA or have been impeded by small sample sizes and limited scope. This case-control study evaluated the association between sarcoidosis and autoimmune diseases in a large, diverse cohort based in the USA.

We used data from the All of Us research programme to conduct a case-control study involving patients ≥18 years old, from 2018 to the present, diagnosed with sarcoidosis. Sarcoidosis cases and age-, sex- and race-matched controls were identified in a 1:4 ratio. Autoimmune co-morbidities were compared between sarcoidosis patients and controls in univariable and multivariable analyses using logistic regression. The degree of association was measured using the odds ratio (OR).

A total of 1408 sarcoidosis cases and 5632 controls were included in this study. Seven of 24 examined autoimmune diseases were significantly associated with sarcoidosis in our multivariable analysis (P < 0.05). The composite variable of any autoimmune disease was also significantly associated with sarcoidosis (OR = 2.29, P < 0.001).

We demonstrate an association between sarcoidosis and multiple autoimmune diseases in a large and diverse cohort based in the USA. These results underscore the need for careful screening of sarcoidosis patients for concomitant autoimmune disease.

Several pulmonary disorders can cause ocular involvement. Understanding these manifestations is critical for early diagnosis and treatment. Hence, we set out to examine the most common ocular manifestations of asthma, chronic obstructive pulmonary disease (COPD), sarcoidosis, obstructive sleep apnea (OSA), and lung cancer. Allergic keratoconjunctivitis and dry eye are two ocular manifestations of bronchial asthma. The inhaled corticosteroids used to treat asthma can cause cataract formation. COPD is associated with ocular microvascular changes as a result of chronic hypoxia and systemic inflammation spillover into the eyes. Its clinical significance, however, is unknown. Ocular involvement is common in sarcoidosis, occurring in 20% of cases of pulmonary sarcoidosis. It can affect nearly any anatomical structure of the eye. Obstructive sleep apnea has been linked to floppy eye syndrome, glaucoma, non-arteritic anterior ischemic optic neuropathy, keratoconus, retinal vein occlusion, and central serous retinopathy, according to research. However, while an association has been established, causality has yet to be established. The effect of positive airway pressure (PAP) therapy used to treat OSA on the aforementioned ocular conditions is unknown. PAP therapy can cause eye irritation and dryness. Lung cancer can affect the eyes through direct nerve invasion, ocular metastasis, or as part of a paraneoplastic syndrome. The goal of this narrative review is to raise awareness about the link between ocular and pulmonary disorders in order to aid in the early detection and treatment of these conditions.

The association between sarcoidosis and autoimmunity has been reported for years. However, the significance of autoantibodies in the pathophysiology and clinical management of sarcoidosis is not well understood. No autoantibodies that can be used as serologic biomarkers to diagnose the disease, monitor the state of the disease, and predict the prognosis of patients are established.

We performed a comprehensive analysis of serum autoantibodies and analyzed their associations with clinical features of sarcoidosis.

Patients with systemic autoimmune rheumatic diseases-associated autoantibodies had a higher prevalence of advanced radiographic stage and consolidations in high-resolution computed tomography than patients without autoantibodies (p < .05). Age, sex, clinical history, pulmonary function tests, serum angiotensin-converting enzyme levels, rheumatoid factor, and the number of involved organs were not significantly different between the two groups.

There may be an association between autoantibodies and more advanced pulmonary lesions in patients with sarcoidosis. Further investigations are needed to establish the significance of autoantibodies.

Erythropoietin (EPO) is the main mediator of erythropoiesis and an important tissue protective hormone that appears to mediate an ancestral neuroprotective innate immune response mechanism at an early age. When the young brain is threatened-prematurity, neonatal hyperbilirubinemia, malaria- EPO is hyper-secreted disproportionately to any concurrent anemic stimuli. Under eons of severe malarial selection pressure, neuroprotective EPO augmenting genetic determinants such as the various hemoglobinopathies, and the angiotensin converting enzyme (ACE) I/D polymorphism, have been positively selected. When malarial and other cerebral threats abate and the young child survives to adulthood, EPO subsides. Sustained high ACE and angiotensin II (Ang II) levels through the ACE D allele in adulthood may then become detrimental as witnessed by epidemiological studies. The ubiquitous renin angiotensin system (RAS) influences the α-klotho/fibroblast growth factor 23 (FGF23) circuitry, and both are interconnected with EPO. Here we propose that at a young age, EPO augmenting genetic determinants through ACE D allele elevated Ang II levels in some or HbE/beta thalassemia in others would increase EPO levels and shield against coronavirus disease 2019, akin to protection from malaria and dengue fever. Human evolution may use ACE2 as a "bait" for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to gain cellular entry in order to trigger an ACE/ACE2 imbalance and stimulate EPO hypersecretion using tissue RAS, uncoupled from hemoglobin levels. In subjects without EPO augmenting genetic determinants at any age, ACE2 binding and internalization upon SARS-CoV-2 entry would trigger an ACE/ACE2 imbalance, and Ang II oversecretion leading to protective EPO stimulation. In children, low nasal ACE2 Levels would beneficially augment this imbalance, especially for those without protective genetic determinants. On the other hand, in predisposed adults with the ACE D allele, ACE/ACE2 imbalance, may lead to uncontrolled RAS overactivity and an Ang II induced proinflammatory state and immune dysregulation, with interleukin 6 (IL-6), plasminogen activator inhibitor, and FGF23 elevations. IL-6 induced EPO suppression, aggravated through co-morbidities such as hypertension, diabetes, obesity, and RAS pharmacological interventions may potentially lead to acute respiratory distress syndrome, cytokine storm and/or autoimmunity. HbE/beta thalassemia carriers would enjoy protection at any age as their EPO stimulation is uncoupled from the RAS system. The timely use of rhEPO, EPO analogs, acetylsalicylic acid, bioactive lipids, or FGF23 antagonists in genetically predisposed individuals may counteract those detrimental effects.

Systemic infiltrative diseases are relatively rare conditions consisting of cell infiltration or substance deposition in multiple organs and systems, including endocrine glands. This article reviews endocrine changes in the main four diseases at epidemiological level: sarcoidosis, Langerhans cell histiocytosis, hereditary hemochromatosis, and systemic amyloidosis. Recommendations to endocrinologists for hormone work-up and management of patients with each of these conditions are provided.

Background: Sarcoidosis is multisystem inflammatory granulomatosis that can potentially affect any organ of the human body. We aimed to estimate the prevalence of diabetes mellitus (DM) in sarcoidosis patients and determine the association between sarcoidosis and DM.Method: All relevant articles reporting the prevalence of DM in sarcoidosis published until September 19^th, 2020, were retrieved from ten electronic databases. We used the random effect model to perform the meta-analysis.Results: After screening 2,122 records, we included 19 studies (n = 18,686,162). The prevalence of DM in sarcoidosis patients was 12.7% (95% CI 10-16.1). The prevalence was highest in North America with 21.3% (13.5-31.8), followed by Europe 10.4 (7.9-13.7) and Asia 10% (1.8-39.7). Sarcoidosis patients had higher rates of DM compared to controls (OR 1.75; 95% CI 1.49-2.05). Sensitivity analysis, after removing the largest weighted study, did not reveal any effect on the significance of the results (OR 1.73; 95% CI 1.33-2.25).Conclusion: The prevalence of DM in sarcoidosis is considerably high, with increased odds of DM in sarcoidosis compared to healthy controls. Further research with a wide range of confounders is required to confirm the association of sarcoidosis with DM.

Sarcoidosis is a poorly understood multisystem granulomatous disease that frequently involves the lungs but can affect any organ system. In this review, we summarize recent developments in the understanding of the immune dysregulation seen in sarcoidosis and propose a new expanded definition of human autoimmunity in sarcoidosis, and the implications it would have on treating sarcoidosis with targeted immunotherapy regimens in the future.

Sarcoidosis has been linked to infectious organisms like Mycobacterium and Cutibacterium, and certain manifestations of sarcoidosis have been linked to specific HLA alleles, but the overall pathogenesis remains uncertain. Sarcoidosis patients have similar patterns of cellular immune dysregulation seen in other autoimmune diseases like rheumatoid arthritis, and recent large-scale population studies show that sarcoidosis frequently presents with other autoimmune diseases.

Advancements in the understanding of sarcoidosis support its consideration as an autoimmune disease. Sarcoidosis patients carry a higher risk of comorbid autoimmune conditions which offers an excellent opportunity to further understand autoimmunity and explore biologic therapies in sarcoidosis treatment, and furthermore will better targeted immunotherapy regimens for sarcoidosis patients in the future.

Sarcoidosis is a multisystem disorder of unknown cause, characterised pathologically by granulomas and primarily affecting the lung and lymphatic system of the body. It has been termed the 'great pretender' due to its ability to mimic other diseases. In this article we describe a case of sarcoidosis with simultaneous rare manifestations of extrathoracic disease (thyroid, osseous and renal). It highlights the enigmatic nature of sarcoidosis and the diagnostic challenge it can pose to clinicians. A multidisciplinary approach to both diagnosis and management between endocrinology, nephrology, neurosurgical, rheumatological and respiratory teams was paramount for effective clinical improvement.

Purpose: To report three cases of eyelid involvement by sarcoidosis. In one of them, it mimicked a malignant lesion.Methods: Retrospective case reports.Results: A 73-year-old man presented with destruction of the left lower eyelid for 2 years. He had granulomatous uveitis in the left eye. Chest CT scan showed parenchymal abnormalities that could correspond to sarcoidosis. Skin biopsy revealed noncaseating granuloma. Oral and topical corticosteroids resulted in improvement of the condition. A 72-year-old female patient presented with cutaneous infiltration of the left upper eyelid for 1 month. Biopsy was consistent with sarcoidosis. Endobronchial biopsies showed interstitial fibrosis. Oral prednisone improved the condition. A 65-year-old female patient presented with edema of the right upper eyelid for 2 months. Full-thickness biopsy showed granuloma without necrosis. There was an improvement with oral steroid.Conclusion: Although eyelid involvement in sarcoidosis is uncommon, different forms of presentation, including destructive lesions, can be observed.

Little is known about the prevalence, clinical characteristics and impact of hypothyroidism in patients with sarcoidosis. We aimed to determine the prevalence and clinical features of hypothyroidism and its relation to organ involvement and other clinical manifestations in patients with sarcoidosis. We conducted a national registry-based study investigating 3835 respondents to the Sarcoidosis Advanced Registry for Cures Questionnaire between June 2014 and August 2019. This registry is based on a self-reported, web-based questionnaire that provides data related to demographics, diagnostics, sarcoidosis manifestations and treatment. We compared sarcoidosis patients with and without self-reported hypothyroidism. We used multivariable logistic regression and adjusted for potential confounders to determine the association of hypothyroidism with nonorgan-specific manifestations. 14% of the sarcoidosis patients self-reported hypothyroidism and were generally middle-aged white women. Hypothyroid patients had more comorbid conditions and were more likely to have multiorgan sarcoidosis involvement, especially with cutaneous, ocular, joints, liver and lacrimal gland involvement. Self-reported hypothyroidism was associated with depression (adjusted odds ratio (aOR) 1.3, 95% CI 1.01-1.6), antidepressant use (aOR 1.3, 95% CI 1.1-1.7), obesity (aOR 1.7, 95% CI 1.4-2.1), sleep apnoea (aOR 1.7, 95% CI 1.3-2.2), chronic fatigue syndrome (aOR 1.5, 95% CI 1.2-2) and was borderline associated with fibromyalgia (aOR 1.3, 95% CI 1-1.8). Physical impairment was more common in patients with hypothyroidism. Hypothyroidism is a frequent comorbidity in sarcoidosis patients that might be a potentially reversible contributor to fatigue, depression and physical impairment in this population. We recommend considering routine screening for hypothyroidism in sarcoidosis patients especially in those with multiorgan sarcoidosis, fatigue and depression.

Systemic infiltrative diseases are relatively rare conditions consisting of cell infiltration or substance deposition in multiple organs and systems, including endocrine glands. This article reviews endocrine changes in the main four diseases at epidemiological level: sarcoidosis, Langerhans cell histiocytosis, hereditary hemochromatosis, and systemic amyloidosis. Recommendations to endocrinologists for hormone work-up and management of patients with each of these conditions are provided.

Addison's disease (AD) is a rare disorder and among adult population in developed countries is most commonly caused by autoimmunity. In contrast, in children genetic causes are responsible for AD in the majority of patients.

This review describes epidemiology, pathogenesis, genetics, natural history, clinical manifestations, immunological markers and diagnostic strategies in patients with AD. Standard care treatments including the management of patients during pregnancy and adrenal crises consistent with the recent consensus statement of the European Consortium and the Endocrine Society Clinical Practice Guideline are described. In addition, emerging therapies designed to improve the quality of life and new strategies to modify the natural history of autoimmune AD are discussed.

Progress in optimizing replacement therapy for patients with AD has allowed the patients to lead a normal life. However, continuous education of patients and health care professionals of ever-present danger of adrenal crisis is essential to save lives of patients with AD.

Background Neurosarcoidosis is not a common entity from an endocrinology standpoint. Prompt diagnosis is essential in order to determine appropriate treatment and to establish prognosis. Case presentation Our case illustrates the difficulties encountered in making a diagnosis of sarcoidosis in an adolescent who presented with polyuria, polydipsia and hypernatremia. She developed panhypopituitarism and her deficits did not improve after treatment. Conclusion Pediatric endocrinologists diagnose and treat panhypopituitarism associated with many conditions. Neurosarcoidosis should be considered as part of the diagnosis in patients with panhypopituitarism, especially if there is evidence of multi organ disease. Case reports can effectively address the gap in knowledge due to the limited exposure of physicians to this field, especially in children.

A 53-year old female was referred to our hospital with bilateral abnormal shadow in the chest X-ray. Computed tomography revealed multifocal ill-defined densities and thickening of bronchial wall and pulmonary vessels by fine nodules combined with massive enlargement of bilateral mediastinal and hilar lymph nodes. Analyses of bronchoalveolar lavage fluid and transbronchial lung biopsy specimen showed the increase in CD4/CD8 ratio and the presence of non-caseating granulomas, respectively. In addition, serum angiotensin-converting enzyme was extremely high, leading to the diagnosis of sarcoidosis. Simultaneously, she complained of palpitation and sweating. Endocrinological examination showed comorbid hyperthyroidism without anti-TSH receptor antibody (TRAb). In the first 2-3 months, pulmonary shadow gradually disappeared without steroid administration. In parallel, serum thyroid hormone levels were gradually normalized in the beginning, but increased after 3 months with an appearance of TRAb. After initiation of treatment with antithyroid agent, hyperthyroidism was improved within 9 months, and changed into hypothyroidism thereafter. The clinical course of this rare case suggest that immunological storm by exacerbation of sarcoidosis may trigger the onset of autoimmune thyroid disease, in which hyperthyroidism with stimulating type of TRAb subsequently changed into hypothyroidism with blocking-type TRAb.

Sarcoidosis is a multisystemic granulomatous disease with diverse and often non-specific symptoms during childhood. The clinical manifestations sometimes include endocrinopathies related to sarcoid infiltration of various endocrine organs, but more commonly due to the associated autoimmune endocrine disorders. There are only a few reports of multiple autoimmune and non-autoimmune endocrine problems occurring simultaneously in patients with sarcoidosis. We report a girl with probable sarcoidosis who also had Hashimoto's thyroiditis, Type 1 diabetes (T1D) and secondary adrenal insufficiency.

A 9-year-old girl previously diagnosed with autoimmune hypothyroidism and vitamin D deficiency, presented with hypercalcemic pancreatitis after initiating vitamin D supplementation that lead to a diagnosis of probable sarcoidosis. Secondary adrenal insufficiency and T1D were subsequently diagnosed. Her angiotensin converting enzyme levels on 2 occasions were 106 and 135 nmol/mL/min (normal range 10 - 43). All investigations conducted to exclude several infectious and malignant conditions that may mimic sarcoidosis were negative. The patient showed a good response to treatment with hydrocortisone, levothyroxine, insulin and methotrexate.

To our knowledge, ours is the youngest ever patient reported in the literature with sarcoidosis to develop multiple autoimmune and non-autoimmune endocrinopathies.

A 66-year-old woman, who was diagnosed with iritis, visited our hospital due to general malaise. A blood analysis revealed hypercalcemia. Computed tomography revealed mediastinal and hilar lymph node hyperplasia. Moreover, ⁶⁷Gallium scintigraphy demonstrated strong accumulation in the lesions, suggesting sarcoidosis. A core needle biopsy (CNB) of the hypoechoic areas of the thyroid was performed because the patient refused to undergo a bronchoscopic examination. The scattering of slightly acidophilic epithelioid cell granulomas was observed in the pathological examination of the biopsy specimen. Based on this finding, the patient was diagnosed with sarcoidosis. Although sarcoidosis rarely involves the thyroid gland, in the present case, thyroid CNB was an alternative diagnostic method that allowed a pathological diagnosis to be obtained.

We report a 62-year-old woman with a history of Basedow's disease and Sjogren's syndrome who presented with slowly progressive limb muscle weakness over the course of ten years. On physical examination, she had dry eye and mouth, but was otherwise normal. Neurological examination revealed symmetrical proximal dominant muscle weakness. Polymyositis was suspected at initial diagnosis due to her clinical course, physical examination, and autoimmune disease. However, the final diagnosis based on a muscle biopsy was the chronic myopathic type of sarcoid myopathy. Among 25 definite sarcoid myopathy cases in the National Center of Neurology and Psychiatry muscle repository from 2010 to 2015, 6/25 had autoimmune diseases. All 6 patients were female and had the chronic myopathic type of sarcoid myopathy. The number of patients with Sjogren's syndrome, thyroid disease, autoimmune hepatitis, and idiopathic thrombocytopenia were 4, 1, 1, and 1, respectively. Only the present case had both thyroid disease and Sjogren's syndrome. In conclusion, the chronic myopathic type of sarcoid myopathy is one possibility to consider in patients who present with progressive myopathy together with autoimmune diseases.

Most of the studies have shown a higher risk for subclinical and clinical hypothyroidism, antithyroid autoantibodies [overall antithyroid peroxidase antibodies (TPOAb)], and in general, thyroid autoimmunity, overall in the female gender in patients with sarcoidosis (S). A significantly higher prevalence of clinical hypothyroidism and Graves' disease was also described in female S patients with respect to controls. Gallium-67 (Ga-67) scyntigraphy in S patients, in the case of thyroid uptake, suggests the presence of aggressive autoimmune thyroiditis and hypothyroidism. For this reason, ultrasonography and thyroid function should be done in the case of Ga-67 thyroid uptake. In conclusion, thyroid function, TPOAb measurement, and ultrasonography should be done to assess the clinical profile in female S patients, and the ones at high risk (female individuals, with TPOAb positivity, and hypoechoic and small thyroid) should have periodically thyroid function evaluations and suitable treatments.

The aim of this study was to identify the frequency and prevalence of comorbidities in sarcoid patients and to assess their influence on overall mortality in the cohort of patients with sarcoidosis.

A cohort of 557 patients with histologically confirmed sarcoidosis diagnosed between 2007 and 2011 and a group of non-sarcoid controls were observed. All patients were carefully observed for comorbidities and mortality.

291 males (52.2%) and 266 females (47.8%) with mean age 48.4 ± 12.0 years in sarcoidosis group and a group of 100 controls with mean age (49.25 ± 10.3) were observed. The mean number of comorbidities in both groups was similar (0.9 ± 0.99 vs 0.81 ± 0.84 NS). The frequency of thyroid disease was significantly higher in sarcoidosis group comparing to controls at the time of diagnosis (OR = 3.62 P = 0.0144). During the observation period (median 58.0 months), 16 patients died (2.9%). The mean number of comorbidities was significantly higher in the groups of non-survivors as compared to survivors (2.8 ± 1.0, vs 0.8 ± 0.9), P < 0.0001.

The comorbidity burden has strong impact on mortality in sarcoidosis. Thyroid diseases are more frequent in sarcoidosis than in non-sarcoid controls.

Minimal-change glomerular disease, sarcoidosis and autoimmune thyroid disease rarely occur in the same patient. We herein report a patient in which minimal-change glomerular disease and Hashimoto's thyroiditis developed during the treatment of sarcoidosis with steroids. A 66-year-old female was admitted to our hospital with symptoms of nephrotic syndrome. Nine months before admission, she was diagnosed as having ocular and pulmonary sarcoidosis, for which prednisolone at an initial dose of 40 mg/day was started. When the dose of prednisolone was tapered to 20 mg/day, she noticed swelling of the lower extremities. Examination confirmed the simultaneous occurrence of minimal-change glomerular disease and Hashimoto's thyroiditis, which were diagnosed based on kidney histology, ultrasonography of the thyroid gland and positive antithyroglobulin antibodies. We used intravenous methylprednisolone pulse therapy followed by 40 mg/day oral prednisolone. The patient achieved complete remission of nephrotic syndrome and steroids were tapered without relapse.

Autoimmune endocrinopathies and, less commonly, thyroid autoimmune disease have been reported in patients with sarcoidosis. Similarities exist in the pathogenesis of these two conditions. Concomitant sarcoidosis in the thyroid gland in patients with Graves' disease may contribute to the resistance to antithyroid drugs and radioiodine therapy. We present the clinical, laboratory, imaging, and pathologic findings of a patient with Graves' disease who was unresponsive to medical management. This 37-year-old man presented with thyrotoxicosis. Thyroid hormone assays and (99m)Technitium findings were consistent with Graves' disease. He was also found to have hilar lymphadenopathy. Patient failed to achieve remission with high doses of antithyroid drugs and 2 sessions of radioiodine ablative therapy. Histopathology of lymph nodesdisclosed noncaseating granulomas, consistent with sarcoidosis. Patient's thyrotoxicosis subsided only following steroid administration. The histopathology of the thyroid gland on aspiration and the subsidence of symptoms with steroids reiterate the possibility of thyroid sarcoidosis. This diagnosis needs biopsy for confirmation, which our patient didn't consent for.

Sarcoidosis rarely involves the thyroid gland. Pain in the thyroid gland area was only sporadically reported in patients suffering from this disease. The aim of this paper is to report and discuss the cases of two female patients with Graves' disease who presented painful, rapidly growing, recurrent goiters (after strumectomy in their early adult lives). Invasive treatment was applied and sarcoidosis was revealed histologically. The first patient suffered from dysphagia and dyspnoea due to large goiter; skin lesions were present as well. Sarcoidosis was diagnosed in histological examination of the thyroid tissue specimens. Steroid treatment was ineffective; thus, the thyroid was removed. Two years later thyroid sarcoidosis recurred as a painful goiter and surgical treatment was applied once again. In the second case, thyroid ultrasound findings suggesting malignancy, and prompted the decision to perform thyroidectomy despite the fact that FNAB (fine needle aspiration biopsy) revealed cells indicative of a "granulomatous disease in the post-resection scar" and results of the thorax high-resolution computed tomography scan suggested pulmonary sarcoidosis. Pathological examination confirmed sarcoidosis. However, a papillary cancer focus was also found.

A growing number of case reports suggest that pulmonary disease occurs in association with inflammatory bowel disease (IBD) more frequently than previously recognized. Screening studies have also identified pulmonary abnormalities in a significant proportion of IBD patients.

A focused literature review of respiratory abnormalities in IBD patients and 55 English-language case series documenting 171 instances of respiratory pathology in 155 patients with known IBD.

Screening studies using respiratory symptoms, high-resolution CT, and pulmonary function testing support a high prevalence of respiratory abnormalities among patients with IBD. Case reports and series document a spectrum of respiratory system involvement that spans from larynx to pleura, with bronchiectasis as the single most common disorder. IBD patients have a threefold risk of venous thromboembolism, and recent investigations have also revealed possible ties between IBD and other diseases involving the respiratory system, including sarcoidosis, asthma, and alpha(1)-antitrypsin deficiency.

Respiratory symptoms and diagnosed respiratory system disorders are more common among patients with IBD than generally appreciated. The spectrum of respiratory disorders occurring among patients with IBD is very broad. Diseases of the large airways are the most common form of involvement, with bronchiectasis being the most frequently reported form of IBD-associated lung disease.

To report a case of Graves' disease with concomitant sarcoidosis involving the thyroid gland.

We present the clinical, laboratory, imaging, and pathologic findings and describe the clinical course of a patient with Graves' disease and sarcoidosis, who was unresponsive to propylthiouracil and radioiodine treatment.

A 23-year-old woman presented with thyrotoxicosis and a large goiter. Laboratory studies and findings on thyroid uptake and scan were consistent with Graves' disease. She was also found to have hilar lymphadenopathy and hepatosplenomegaly. Despite treatment with antithyroid drugs and radioiodine therapy, her hyperthyroidism persisted. Surgical resection of the thyroid gland and 2 lymph nodes disclosed noncaseating granulomas, consistent with sarcoid.

Autoimmune endocrinopathies and, less commonly, thyroid autoimmune disease have been reported in patients with sarcoidosis. Similarities exist in the pathogenesis of these two conditions. Concomitant sarcoidosis in the thyroid gland in patients with Graves' disease may contribute to the resistance to antithyroid drugs and radioiodine therapy.

Sarcoidosis is a systemic disease characterized by non-caseating granulomas that rarely involve the thyroid gland. Thyroid sarcoidosis has seldom been documented, and few cases have so far been described in association with hyperthyroidism. Here, we review the literature on this association, report two patients presenting with hyperthyroidism and histologically-proven sarcoidosis, and discuss related clinical, biochemical, pathological and genetic findings.

The association of sarcoidosis (S) and thyroid autoimmunity has been reported by several studies in a wide range of variability. The aim of our study was to evaluate the prevalence of clinical and subclinical thyroid disorders in patients with S vs gender-matched and age-matched control subjects.

Thyroid hormones and antithyroid antibodies, thyroid ultrasonography and fine-needle aspiration were performed in 111 patients with S who had been consecutively referred to the Respiratory Pathophysiology Section of the University of Pisa, and the results were compared to 333 gender-matched and age-matched control subjects from the same geographic area.

The odds ratio for subclinical hypothyroidism for female patients with S vs control subjects was 2.7 (95% confidence interval [CI], 1.3 to 5.9); for anti-thyroid peroxidase antibody titer (AbTPO) positivity, 2.2 (95% CI, 1.2 to 3.9); and for thyroid autoimmunity, 1.9 (95% CI, 1.1 to 3.2). The mean values of thyroid-stimulating hormone and AbTPO were higher in female S patients than in control subjects (p < 0.01). A significantly higher prevalence of clinical hypothyroidism (four patients) and Graves disease (three patients) was observed in female S patients than in control subjects (none; p = 0.005 and 0.0026, respectively). Two cases of papillary thyroid cancer were detected in S patients. No significant difference between S patients and control subjects was detected for free triiodothyronine and thyroxine, antithyroglobulin autoantibodies, thyroid volume and nodularity, and subclinical hyperthyroidism.

Thyroid function, AbTPO antibodies, and ultrasonography should be tested as part of the clinical profile in female S patients. Subjects who are at high risk (female subjects, those with positive AbTPOs, and those with hypoechoic and small thyroid) should have thyroid function follow-up and appropriate treatment in due course.

Autoimmunity encompasses a wide spectrum of diseases from organ-specific diseases like Hashimoto thyroiditis, to systemic diseases such as systemic lupus erythematosus. These diseases are characterized by inflammation and the production of a wide range of autoantibodies directed against multiple autoantigens. Although their etiology is still poorly understood, genetic, immunological, hormonal, and environmental factors are major predisposing and triggering factors. These multiple factors, like pieces in a mosaic, may interplay in different forms, leading to the expression of various autoimmune manifestations and diseases. This phenomenon, which has been referred by us as the "mosaic of autoimmunity", illuminates the diversity of autoimmune manifestations among susceptible individuals. From this theoretical framework we conducted a wide search of the literature, on the prevalence of thyroid autoimmunity, the commonest of the autoimmune conditions, among other autoimmune diseases, and discuss the possible clinical significance of this association.

Autoimmune polyglandular syndrome Type I (APS I) is a disorder defined by the presence of at least two of the following diseases: Addison's disease, hypoparathyroidism, and chronic mucocutaneous candidiasis. We present the case of a 45-yr-old woman, affected by APS I, in chronic treatment with betamethasone. She was referred to a Division of General Medicine for jaundice, ascites and peripheral edema attributed to worsening of pre-existing autoimmune chronic hepatitis. During hospitalization, the following drugs were given: Amoxicillin/Clavulanic acid and Levofloxacin for bronchopneumonia, Furosemide and Canreonate for renal impairment, Pantoprazole for gastric protection, and Itraconazole for oral candidiasis. After about a month, she developed widespread, sheet-like, epidermal detachment, with painful lesions of the conjunctiva, lips and mouth. Toxic epidermal necrolysis (TEN) was diagnosed, and the patient was transferred to a Burn Center, where she died 10 days after the first onset of cutaneous rash. Autoptic and histopathological findings (epidermal necrosis and detachment, lymphomonocytic infiltration of the dermis) confirmed the clinical diagnosis. TEN is a usually drug-induced cutaneous inflammatory disorder characterized by extensive epidermal detachment and frequent mucosal involvement. It has also been associated with immuno-mediated disorders (HIV infection, graft-vs-host disease, systemic lupus erythematosus, mixed essential cryoglobulinemia), in keeping with immuno-mediated pathogenesis. We present, to our knowledge, the first report of TEN in a patient with APS I, and suggest that some pathogenetic mechanisms of APS I are shared with TEN. We stress how such a disease can occur in an autoimmune syndrome, even during corticosteroid treatment.