Adrenal Autoantibodies Research Articles

Late-onset Schmidt's Syndrome Presenting with Severe Hyponatremia: A Case Report.

Schmidt's syndrome (SS) is a subtype of polyglandular autoimmune syndrome type-2 combining autoimmune thyroiditis (AIT) and autoimmune Addison's disease (aAD). It occurs most frequently in young adult females, and aAD is the most common initial manifestation [1]. We present a rare case of SS with late-onset aAD and severe hyponatremia as the first sign. A 73-year-old woman presented to the emergency department (ED) with a 10-day history of vomiting, diarrhea, and altered mental status. Her past medical history was remarkable for AIT and hypokinetic cardiomyopathy. Moreover, she had recently undergone a 2-week course of corticosteroid therapy for vertiginous symptoms, reporting subjective well-being. In ED, she appeared confused and hypotensive. Blood tests revealed a sodium level of 99 mEq/l with normal potassium. Initial treatment with saline infusions were started, followed by ex juvantibus intravenous hydrocortisone awaiting hormone results, which proved consistent with primary adrenal insufficiency (ACTH 1314 pg/ml, cortisol 4.72 ug/dL). Replacement therapy with both hydrocortisone and fludrocortisone was then implemented, with substantial clinical improvement and normalization of sodium levels. However, the patient later developed right heart failure and hypokalemia, which were likely caused by overreplacement and resolved after adjusting the treatment regimen. The final diagnosis of aAD was confirmed by positive adrenal autoantibodies. aAD should be suspected in each case of severe hyponatremia [2], especially in patients with AIT independent of age. Furthermore, caution is needed in managing high-dose glucocorticoids along with fludrocortisone in elderly patients with cardiac disease to limit the risk of excessive mineralocorticoid activity and heart failure [3].

SARS-COV-2-INDUCED SECONDARY ADRENAL INSUFFICIENCY

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: SARS-CoV-2 has been known to be primarily linked to pulmonic pathology. Endocrine complications of COVID-19 continue to remain elusive. Specifically, adrenal insufficiency in COVID-19 has been thought to be acquired through steroid use. This case describes a 46-year-old woman who suffered from mild COVID-19 illness without hypoxia or prolonged steroid therapy who developed secondary adrenal insufficiency. CASE PRESENTATION: This 46-year-old female presented to the emergency department with hypoglycemia of 40mg/dL. She had associated symptoms of nausea, fatigue, poor oral intake for 2 days. Her past medical history is significant for scleroderma with pulmonary hypertension, Raynaud's phenomenon, and mild COVID-19 infection four weeks prior to current admission. She was treated with Remdesivir and one dose of dexamethasone. She was discharged home without supplemental oxygen. Vital signs were significant for a low blood pressure at 90/50 and the patient was admitted to the ICU. Physical exam was unremarkable. Her initial labs were significant for hyponatremia (131 mmol/L), and hypoglycemia (40 mg/dL). Further lab work showed a low morning cortisol level of 2.1ug/dL (6-18) and ACTH of 4.2pg/mL (10-50). Her subsequent cosyntropin stimulation test showed low cortisol levels at 1.3 (6-18), 5.4 (8), and 7.9 (16) respectively, indicating adrenal insufficiency. Her other labs were normal including TSH, aldosterone, and renin level. Adrenal autoantibodies to 21-hydroxylase and 17-alpha hydroxylase were negative. She had a CT scan of the abdomen which showed no adrenal lesions. She was started on hydrocortisone 10mg twice daily with rapid resolution of all her symptoms. DISCUSSION: Adrenal insufficiency in COVID-19 typically occurs in the setting of hypothalamic-pituitary-adrenal (HPA) axis suppression due to steroid use. True secondary adrenal insufficiency is rare. SARS-CoV-2 infection has not been known to directly attack the adrenal glands. However, SARS-CoV-2 could induce an autoimmune response against ACTH via molecular mimicry. Another prevailing theory is that thromboembolic events at the adrenal level result in impaired hormone production. Initial assessment starts with AM cortisol and ACTH. If low, patients should undergo corticotropin stimulation testing as the gold standard of diagnosis. A complete work up should include an assay of autoantibodies. Lastly, investigation of potential adrenal lesions should be explored with contrast-enhanced CT scan or MRI. Treatment is straightforward: supplementation of glucocorticoids, 2-3 times daily. CONCLUSIONS: No algorithm currently exists to detect adrenal insufficiency;clinical suspicion should guide further work-up. As COVID-19 adrenal insufficiency has an unclear prognosis, the treatment course is also uncertain. As a patient's symptoms and labs normalize, there is a possibility to discontinue treatment altogether. REFERENCE #1: Heidarpour M, Vakhshoori M, Abbasi S, Shafie D, Rezaei N. Adrenal insufficiency in coronavirus disease 2019: A case report. J Med Case Rep. 2020;14(1):10-13. REFERENCE #2: Scaroni C, Armigliato M, Cannavo S. COVID-19 outbreak and steroids administration: are patients treated for Sars-Cov-2 at risk of adrenal insufficiency? J Endocrinol Invest. 2020;43(7):1035-1036. REFERENCE #3: Bellastella G, Maiorino MI, Esposito K. Endocrine complications of COVID-19: what happens to the thyroid and adrenal glands? J Endocrinol Invest. 2020;43(8):1169-1170. DISCLOSURES: no disclosure on file for Justin Dolan;No relevant relationships by Andrew Kim, source=Web Response No relevant relationships by Amy Van, source=Web Response

P027 A case of Henoch-Schonlein purpura complicated by adrenal haemorrhage

Background/Aims Henoch-Schonlein purpura (HSP) is a small vessel vasculitis characterised by IgA deposition. Adrenal haemorrhage has been reported previously in HSP, but is rare. Methods A 33-year-old lady was admitted with myalgia, pyrexia, a faint petechial rash on her legs, a CRP of 92mg/L (<5). No signs of meningism were found. A throat swab for viral pathogens (taken prior to the Covid-19 pandemic) returned negative, and blood culture showed no growth. Within a few days she returned to the Accident & Emergency Department with worsening of the rash but was again discharged. The following week she was admitted with abdominal pain and a prominent purpuric rash on her legs. Results Full blood count, Rheumatoid Factor, Anti-Nuclear Antibodies, ANCA and Anti-Glomerular Basement Membrane Antibodies, serum Tryptase & C1 esterase inhibitor were all within normal limits. Urine culture grew E.coli. Complement C3 was raised at 2.24 g/L (0.75-1.65) and C4 was within normal range. Her blood pressure was raised at 173/104 mmHg. Antistreptolysin O serology was also normal. Urine analysis revealed haematuria and mild proteinuria. Urine Protein:Creatinine ratio of 22mg/mmol (normal <50). Her purpuric rash had progressed, and she had further abdominal pain. She had taken co-codamol which led to nausea & constipation. She had avoided NSAIDs. Her CRP by this stage was 131mg/L. Clinically the rash on the legs, abdominal pain and haematuria was consistent with HSP. She was started on Prednisolone 10mg od, tapering in 2.5mg per week decrements. The patient was discharged home but returned the following weekend with cramping abdominal pain radiating to the back. Abdominal Xray showed dilated colon at the splenic flexure. After review by the Surgical on call team, a CT Abdomen & Pelvis showed a right adrenal haemorrhage, and inflammatory change in both adrenals. Although she did not display clinical signs of Addisonian crisis or sepsis, she was transferred to HDU for monitoring. Her blood pressure was 151/86 mmHg and her serum urea & electrolytes were normal. The Prednisolone dose was changed to Hydrocortisone, and the dose increased to cover stress of acute illness. MRI of the adrenal glands confirmed right adrenal haemorrhage but showed no evidence of aneurysms or tumours. Antiphospholipid & Cryoglobulins screens were negative. Further blood cultures, pneumococcal and legionella antigens returned negative. Viral Hepatitis screen (A, B & E) was negative. Synacthen test revealed a suboptimal response (Cortisol t0=181nmol/L, t30=260nmol/L, normal response >420nmol/L). Adrenal Autoantibodies returned negative. She was discharged home on oral hydrocortisone and fludrocortisone and remained well at Rheumatology and Endocrine follow up. Conclusion Adrenal haemorrhage is a rare complication of HSP and should be considered as part of the differential diagnosis in such patients presenting with acute abdominal pain and vasculitic rash. Disclosure J.G.C. Shek: None. M. Curuvija: None. S. Al-Mudhaffer: None. G. Das: None. E.P.M. Humphreys: Honoraria; E.H. has participated in advisory board meetings for Pfizer. Other; E.H. has received sponsorship to attend conferences from Abbvie, UCB and Celgene.

Type 1 diabetes, thyroid, gastric and adrenal humoral autoantibodies are present altogether in almost one third of adult celiac patients at diagnosis, with a higher frequency than children and adolescent celiac patients

Background: No data are available on the frequency of organ-specific humoral autoimmunity at diagnosis of adult celiac disease (CD).Aim: To evaluate the humoral immunoreactivities specific of type 1 diabetes (T1D), thyroid (THD), atrophic-gastritis (AG) and Addison’s (AD) diseases in 92 adult CD patients at diagnosis and 237 adult healthy subjects (CTRL).Methods: T1D, THD and AD specific autoantibodies were analyzed by radioimmunoprecipitation assays. AG autoantibodies were detected by enzyme-linked immunosorbent assay.Results: Of 92 CD patients, 31.5% were positive for at least one of the organ-specific autoantibodies investigated (p < .0001 vs CTRL). Thyroid, diabetes, gastric and adrenal-autoantibodies, that increase with age at diagnosis, were detected in 12.0%, 10.9%, 10.9%, 2.2% of CD patients, respectively. Gastric- and diabetes- rather than thyroid- and adrenal-autoimmunity seem to be specifically related to presence of CD.Conclusions: One third of adult CD patients at diagnosis is target of at least one organ-specific autoantibody. A systematic organ-specific autoantibody screening in these patients might be of value to promptly identify, prevent or treat the relative diseases.

Evaluation of CD4+CD25+FOXP3+ regulatory T cells and FOXP3 mRNA in premature ovarian insufficiency

Objective: T cell-mediated injury plays an important role in the pathogenesis of autoimmune premature ovarian insufficiency (POI). The purpose of this study was to assess the percentage of CD4+CD25+FOXP3+ regulatory T (Treg) cells and the level of forkhead box protein 3 (FOXP3) mRNA expression in POI patients.Methods: The case–control study compared 30 POI patients with 30 healthy subjects. Peripheral blood mononuclear cells were collected. The percentage of CD4+CD25+FOXP3+ Treg cells was measured by flow cytometry using specific monoclonal antibodies recognizing the CD4+, CD25+, and FOXP3+ markers. FOXP3 gene expression was evaluated by real-time polymerase chain reaction. In addition, the levels of transforming growth factor-β1 (TGF-β1), interferon-γ (IFN-γ), and adrenal cortex autoantibody (AAA) were determined by enzyme-linked immunosorbent assay.Results: The percentage of CD4+CD25+FOXP3+ Treg cells and the level of FOXP3 mRNA expression were significantly decreased in the POI patients compared with the control subjects. Moreover, the women with POI showed significantly increased levels of IFN-γ and AAA but reduced levels of TGF-β1.Conclusions: Our study suggested that POI may be associated with an abrogated function of circulating CD4+CD25+FOXP3+ Treg cells and a decreased level of FOXP3 gene expression. However, these results require further investigation.

First proof of association between autoimmune polyglandular syndrome and multiple endocrine neoplasia in humans.

Autoimmune Addison's disease (AAD) is a rare condition occurring either in isolation or associated with other autoimmune diseases as part of an autoimmune polyglandular syndrome (APS) type 1, 2 or 4. Multiple endocrine neoplasia (MEN) type 1, 2 or 4 is a hereditary autosomal dominant cancer syndrome. Medullary thyroid carcinoma and pheochromocytoma are neoplasms common to MEN-2a and MEN-2b. We describe a unique, complex case of a man resulted affected by both APS-2 and MEN-2a. The patient developed Hashimoto's thyroiditis, diabetes mellitus type 1 and AAD, despite testing negative for adrenal cortex autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21-OHAb). Moreover, he had also a family history for MEN-2a and he first developed medullay thyroid cancer, then bilateral pheochromocytoma on the adrenal substrate of an AAD. On adrenal histology we found complete bilateral cortical atrophy in the presence of a lymphocytic infiltration and fibrosis, confirming an ACA and 21-OHAb-negative AAD. This datum is the first documented in a living individual and confirms that the absence of autoantibodies is not incompatible with an autoimmune disease and confirms that AAD is a cell-mediated autoimmune disease limited to the adrenal cortex and sparing medullary. In the light of a literature review concerning the association between APS and MEN, this is the first proven case to be reported in humans. Finally, our findings suggest that adrenal medullary tumor can develop even on an adrenal gland with cortical atrophy due to autoimmune adrenalitis.

Identification of patients with primary ovarian insufficiency caused by autoimmunity

Autoimmune pathogenesis is responsible for a subset of primary ovarian insufficiency (POI) cases. The significance of autoantibodies for POI, however, remains unclear. A total of 250 women with idiopathic POI and 256 age-matched healthy women were enrolled. The presence in serum of adrenal cortex autoantibody (AAA), detected by indirect immunofluorescence and non-organ-specific antibodies, including antinuclear antibody, anti-cardiolipin antibody, and anti-double stranded DNA antibody, detected by enzyme-linked immunosorbent assay, was compared. Ovarian biopsy was carried out for histology assessment. Adrenal function was followed-up in 15 women with POI who were positive for AAA. Higher frequency of positive AAA was observed in women with POI (19.2%) compared with controls (5.9%, P < 0.01). No difference in anti-cardiolipin antibody, antinuclear antibody and anti-double stranded DNA antibody was found between the two groups. Ovarian biopsies in 13 women with POI (six AAA positive and seven negative) showed atrophic ovaries devoid of follicles. One out of fifteen women positive for AAA had symptoms of adrenal insufficiency 3 years after POI diagnosis. Significantly higher positive frequency of AAA in POI patients suggests the role of autoimmune disturbance in pathogenesis. Therefore, AAA may serve as a biomarker for ovarian autoimmunity.

Premature Ovarian Failure: An Association with Autoimmune Diseases.

Premature Ovarian Failure (POF) is the cessation of ovarian function before the age of 40 years. POF is reported to be associated with autoimmune diseases in 20-30% of cases. Patients presenting with idiopathic POF were screened for the presence of autoimmune disorders. Twenty patients with idiopathic POF were included in the study. Baseline investigation in all subjects included fasting serum FSH, LH, E2, progesterone, free T3, free T4, Thyroid-Stimulating Hormone (TSH) and Anti-Thyroperoxidase (anti-TPO) antibodies, testosterone and Dehydroepiandrosterone (DHEAS) levels. Fasting and post-glucose (2 hours after 75g of oral glucose) serum calcium and phosphate were estimated using appropriate assays in biochemistry laboratory. Seven patients (35%), who presented with secondary amenorrhea, had thyroid disorders and were already on thyroxine replacement therapy. One patient also had vitiligo. There was no history of adrenal disorder. Anti-TPO levels were elevated in two (10%) patients of secondary amenorrhea group. The levels of serum testosterone were low in three patients. Serum DHEAS levels were low in 13 patients. Blood sugar levels (fasting and 2 hour post 75g glucose load) and fasting insulin levels were normal. Serum calcium and phosphate levels were normal in all the patients. Thyroid autoimmunity is the most common autoimmune disease associated with POF. The finding of low DHEAS in a large percentage of patients (65%), suggests possibility of adrenal dysfunction. This requires further testing for adrenal reserve and adrenal autoantibodies.

From Appearance of Adrenal Autoantibodies to Clinical Symptoms of Addison's Disease: Natural History.

Recent progress in the immunopathology field has greatly improved our understanding of the natural history of autoimmune diseases, particularly of Addison's disease. Addison's disease is known to be a chronic illness characterized by adrenocortical gland insufficiency that develops following a long and mainly asymptomatic period, characterized by the presence of circulating autoantibodies directed to adrenal cortex antigens. In this chapter we describe the groups of subjects at risk of developing Addison's disease, together with the diagnostic tests considered the most appropriate for evaluating adrenal function: determination of basal plasma adrenocorticotropic hormone (ACTH) levels, plasma renin activity, plasma aldosterone and cortisol levels, and cortisol levels after intravenous stimulation with ACTH (ACTH test). The employment of specific clinical, immunological and functional criteria in the subjects with autoantibodies to the adrenal cortex allows identifying those at risk of developing overt disease. The independent risk factors for the progression to adrenal failure have also been identified and they contribute to different risks of developing clinical Addison's disease. Based on the risk level, the subjects should be monitored over time to observe early signs of adrenal dysfunction, and start substitutive treatment as soon as possible. For patients presenting with high risk, prevention strategies and trials might be available.

Conoscerlo per riconoscerlo: morbo di Addison con sindrome poliendocrina autoimmune di Tipo 2

Viene presentato un caso clinico di iposurrenalismo da morbo di Addison primitivo sviluppatosi dopo alcuni anni dalla comparsa di un morbo di Graves. Tale combinazione rappresenta una poliendocrinopatia autoimmune di tipo 2 (SPA-2). La SPA-2 è un processo autoimmune che coinvolge più tessuti endocrini (surrene, tiroide, pancreas) e non endocrini. Si ritiene che la sindrome si sviluppi in pazienti geneticamente predisposti con diversi pattern genetici del complesso maggiore di istocompatibilità MHC II. La SPA-2 è una malattia rara, avendo una frequenza di una persona affetta ogni 7000–8000 abitanti, prevale nel sesso femminile e compare a un'età media di circa 35 anni. L'iposurrena-lismo è caratterizzato da sintomi tipici (astenia, ipotensione ortostatica, calo ponderale, artromialgie, nausea, anoressia, iperpigmentazione cutanea), tuttavia non facili da interpretare, data la scarsa conoscenza della malattia. Nei casi non diagnosticati in tempo utile i sintomi possono peggiorare in rapporto a eventi stressanti che possono far precipitare i pazienti in una crisi addisoniana che può essere potenzialmente fatale. Iposodiemia, iperpotassiemia, iperazotemia, ipercalcemia associati ad aumentati livelli plasmatici di ACTH, renina, e bassi livelli di cortisolo, e alterati indici di epatolisi sono riscontri laboratoristici relativamente tardivi, così come possono esserlo i segni clinici di disidratazione. La storia naturale della malattia si manifesta attraverso varie fasi progressive: a) dapprima con presenza di autoanticorpi anti-surrene presenti anni prima all'esordio clinico, b) poi con un aumento della renina plasmatica e con la diminuzione dell'aldosterone plasmatico, c) poi con la successiva ridotta risposta del cortisolo allo stimolo con ACTH e.v. e d) infine con iperincrezione di ACTH, calo del cortisolo basale e presenza delle manifestazioni cliniche di iposurrenalismo. Il trattamento si basa sulla sostituzione ormonale degli organi endocrini coinvolti.

Knowing it for detecting it: Addison disease with type 2 autoimmune polyendocrine syndrome

Here we describe a patient who developed autoimmune hypoadrenalism many years after developing Graves’ disease. This combination depicts an autoimmune polyendocrine syndrome type-2 (APS-2). APS-2 is an autoimmune syndrome involving endocrine (adrenal glands + thyroid, and/or type 1 diabetes mellitus) and non-endocrine autoimmune disorders. APS-2 has a genetic background showing an association with the class II major histocompatibility complex. APS-2 is an uncommon disease (1:8,000 inhabitants) with higher prevalence in females and mean onset age of 35 years. Despite the fact that hypoadrenalism is characterized by specific symptoms and signs (asthenia, fatigue, orthostatic hypotension, weight loss, nausea, arthralgia, anorexia, skin hyperpigmentation) it is not easy to diagnose at early stages. In late referral patients clinical symptoms can worsen, due to stress events, until a possibly fatal addisonian crisis. Hyponatremia, hyperkalemia, increased levels of ACTH, renin, and low levels of Cortisol, hepatic failure as well as clinical signs and symptoms of dehydration are late laboratory findings. The natural history of the disease develops in different, progressive phases: (i) presence of adrenal cortex autoantibodies many years before the first clinical manifestations, (ii) initial increased levels of plasmatic renin and low levels of aldosterone, (iii) followed by a reduced response of Cortisol to the intravenous ACTH stimulation, (iv) and finally increased levels of plasmatic ACTH and low levels of Cortisol and clinical manifestations of adrenal insufficiency. The therapy of APS-2 is mainly focused on hormone therapy of the affected glands.

Brief Report: Adrenal autoimmunity in primary Sjögren's syndrome

To evaluate the prevalence of antibodies to 21-hydroxylase (anti-21[OH]), a marker of autoimmune adrenal disease, in a cohort of patients with primary Sjögren's syndrome (SS) and to investigate whether the presence of anti-21(OH) correlates with clinical, serologic, and salivary gland features of the disease. Sera from 63 consecutive patients with primary SS, 32 patients with autoimmune thyroid disease (AITD), and 20 healthy controls were obtained and anti-21(OH) levels were determined by radioimmunoassay. Clinical, serologic, and histopathologic features were recorded, and a short Synacthen test was used to assess adrenal function reserve. Seven available minor salivary gland (MSG) tissue specimens from patients in the primary SS cohort were also assessed for interferon-α (IFNα), BAFF, and interleukin-21 (IL-21) cytokine transcripts, which are all implicated in B cell activation. Anti-21(OH) positivity was detected in 17.5% and 28.1% of primary SS and AITD patients, respectively, and in none of the healthy controls. While no evidence of adrenal insufficiency was detected in any of the patients studied, a blunted rate of increase in cortisol levels was observed in patients with detectable serum autoantibodies against 21(OH), compared to their anti-21(OH)-negative counterparts. A strong correlation between the serum titer of anti-21(OH) antibodies and expression of IFNα, BAFF, and IL-21 messenger RNA in MSG tissues was also detected. Adrenal autoimmunity occurs in almost 20% of patients with primary SS in association with markers of B cell activation. Although the presence of adrenal autoantibodies was not associated with adrenal insufficiency in the present study, there was a blunted adrenal response, suggesting the need for further followup and monitoring of adrenal function in patients with primary SS who are positive for the autoantibodies.

Measuring adrenal autoantibody response: Interlaboratory concordance in the first international serum exchange for the determination of 21-hydroxylase autoantibodies

21-hydroxylase autoantibodies (21OHAb) are the gold standard immune marker to identify patients with clinical or subclinical autoimmune Addison's disease (AAD). No assessment of interlaboratory concordance has been made for 21OHAb measurement. Serum samples from 267 patients with primary adrenal insufficiency and from 83 healthy control subjects were distributed to four independent laboratories that determined presence and titer of 21OHAb, by using radiobinding assays with either in vitro translated 35S-radiolabelled or 125I-radiolabelled autoantigen. Cohen's κ of inter-rater agreement ranged from 0.857 to 0.983, showing a very good concordance of the positive/negative score among the four laboratories. Passing-Bablok regression showed a good agreement of 21OHAb titers arranged by ranks, but important discrepancies emerged at the Bland-Altman plot, as the repeatability coefficient was much higher than the laboratory cut-offs, which indicates that results from different laboratories cannot be used interchangeably. A standardization international program for 21OHAb measurement is strongly needed.

ORIGINAL ARTICLE: Autoimmunity predominates in a large South African cohort with addison’s disease of mainly European descent despite long‐standing disease and is associated with HLA DQB*0201

We sought to determine whether autoimmunity is the predominant cause of Addison's disease in South Africa and whether human leucocyte antigen (HLA) DQ association exists. We compiled a national registry of patients from primary care, referral centres and private practices. A total of 144 patients, 94 of European descent, 34 Mixed Ancestry, 5 Asian and 11 Black Africans (mean age 45.9 years, range 2.7-88 years; mean duration of disease 13.1 years, range 0-50 years) and controls were matched for gender and ethnicity. All potential causes were investigated. Fifty one per cent of cases (74 patients) were autoimmune in aetiology. Either 21-hydroxylase autoantibodies (72 patients, 50% of entire patient group) or adrenocortical autoantibodies (35 patients, 24%) were present, while 23% of patients had both. None of the Asian (n = 5) or Black (n = 11) patients had evidence of autoimmune disease. Overall 8% of patients had tuberculosis, 4% adrenoleucodystrophy, 1% adrenocorticotrophic hormone resistance syndrome and 6% X-linked adrenal hypoplasia. In those with autoimmune disease primary hypothyroidism (47%), premature ovarian failure (8%) and type 1 diabetes (7%) were the most prevalent accompanying autoimmune conditions. HLA DQB1*0201 alleles predominated in the autoimmune group (DQB1*0201: 65%vs 43% of controls P = 0.017) with the *0201/*0302 heterozygous genotype being the most prevalent (28%vs 8%P = 0.02). While autoimmunity accounts for at least half of patients with Addison's disease in South Africa and is associated with HLA DQB1*0201, none of the Black Africans or Asians in this cohort had adrenal autoantibodies. Moreover, 21-hydroxylase autoantibodies were detectable in a higher proportion than adrenocortical autoantibodies, especially in those patients with a long history after disease onset.

Evaluation of the hypothalamic-pituitary-adrenal axis in patients with antiphospholipid syndrome

Hypothalamic-pituitary-adrenal (HPA) axis insufficiency is the most common endocrine disorder in patients with antiphospholipid syndrome (APS). Primary adrenal failure because of venous thrombosis and/or adrenal haemorrhage is the leading diagnosis, while another possible mechanism is autoimmune adrenal failure. Prospective evaluation of the HPA axis in patients with APS has not been previously performed. To evaluate the HPA axis in patients with APS. Ambulatory patients (age 18 years and older) with APS were given a symptom questionnaire. Baseline aldosterone, corticotropin (ACTH) and adrenal cortex autoantibodies (ACA) were measured. Cortisol was measured at baseline and after 1-mcg ACTH stimulation. In all, 24 patients (18 women/6 men; mean age 44.6 +/- 16.1 years) participated in the study. Of these, 21 had primary APS with disease duration of 5.8 +/- 6.2 years. Baseline cortisol level was 12.6 +/- 4.2 mg/dl (normal 7-25). After ACTH stimulation, it was 24.7 +/- 4.1 mg/dl and 22.8 +/- 7.4 mg/dl at 30 and 60 min respectively. All patients had a stimulated cortisol level of at least 18 mg/dl, although three patients had stimulated cortisol between 18 and 20 mg/dl, one of which reported previous inhaled steroid treatment. Weakness, dizziness and nausea were reported at baseline by 50%, 38% and 25% of the patients respectively. ACA were negative in all patients examined. In our cohort, patients with APS did not have HPA axis insufficiency. Partial adrenal insufficiency could not be excluded in two patients. Further longitudinal studies are needed to determine the significance of periodic evaluation of the HPA axis in patients with APS.

Addison's Disease Revisited in Poland: Year 2008 versus Year 1990.

This study aimed at comparing two groups of patients with Addison's disease: A, including 180 patients described in 1991 and B, consisting of 138 patients registered since 1991. The incidence of coexisting autoimmune disorders was evaluated and etiological factors were analyzed. Immunological and imaging studies (computed tomography in group B) were performed. Adrenal autoantibodies were examined by an indirect immunofluorescence technique in group A, and by the assay measuring autoantibodies against steroid 21-hydroxylase in group B. Adrenal autoantibodies were revealed in 37% of patients examined by the immunofluorescence method and in 63% investigated by the modern technique. Tuberculosis was found in 52 patients in the group A and in two patients in the group B; metastatic infiltrations of the adrenals in CT were detected in 16 patients. Probable autoimmune Addison's disease was diagnosed in 125/180 patients (69%) in the group A and in 116/138 patients (84%) in the group B.

An unusual case of profound hyponatraemia and bilateral adrenal calcifications

We report a case of a 65-year-old lady who presented with acute confusion and profound hyponatraemia (plasma sodium of 97 mmol/L). Five years earlier she had developed sepsis and was found to have hyponatraemia, thought to be due to syndrome of inappropriate antidiuretic hormone secretion. The patient was lost to follow-up. The patient was covered with steroids and investigations confirmed primary adrenal failure with flat response of cortisol to adrenocorticotropic hormone (ACTH) stimulation and very high level of ACTH. Adrenal auto-antibodies were negative and a computed tomography of the adrenals showed bilateral adrenal calcifications, suggestive of previous haemorrhage or infarction. Bilateral adrenal calcification due to haemorrhage/infarction usually does not present with severe hyponatraemia; however, adrenal insufficiency should be excluded in all cases of severe hyponatraemia. In suspected cases, patients should be treated with steroids, even when symptoms or signs are absent, while results of investigations are awaited.

Partial recovery of adrenal function in a patient with autoimmune Addison’s disease

To our knowledge, no case of remission in autoimmune Addison's disease has previously been reported. We describe a patient with primary adrenal insufficiency caused by autoimmune adrenalitis in whom partial remission was observed after 7 yr. A 39-yr-old male was referred because of extreme fatigue, weight loss, anorexia, nausea, and bouts of fever. During physical examination hyperpigmentation was seen. Laboratory tests showed a plasma cortisol of 0.02 micromol/l (08:30 h). Cortisol failed to increase during the ACTH stimulation test (0.02 to 0.03 micromol/l) and ACTH was markedly elevated (920 pmol/l). Adrenal auto-antibodies were weakly positive. A CT-scan showed no evidence of calcifications or other abnormalities of the adrenal glands. The diagnosis of autoimmune Addison's disease was made and replacement therapy with hydrocortisone and fludrocortisone was started. During the following years the dose of hydrocortisone was gradually decreased. Eventually, the patient decided to stop his medication completely. A repeated ACTH-stimulation test revealed a basal cortisol of 0.25 micromol/l and a peak cortisol of 0.30 micromol/l with a basal ACTH of 178 pmol/l. The patient did not have any complaints. Recovery of adrenal insufficiency, due to causes other than autoimmune adrenalitis, has been reported in the past. If our case of partial recovery of autoimmune adrenalitis is not unique this could have profound effects on treatment and follow-up of Addison's disease.

Estimated Risk for Developing Autoimmune Addison's Disease in Patients with Adrenal Cortex Autoantibodies

Estimated Risk for Developing Autoimmune Addison's Disease in Patients with Adrenal Cortex Autoantibodies

Islet cell, thyroid, adrenal and celiac disease related autoantibodies in patients with Type 1 diabetes from Sri Lanka

The prevalence of islet cell, thyroid, adrenal and celiac disease related autoantibodies in patients with Type 1 diabetes mellitus (Type 1 DM) from Sri Lanka is described. Autoantibodies to glutamic acid decarboxylase 65 (GAD65Ab), protein tyrosine phosphatase IA-2 (IA-2Ab), insulin (IAAb), thyroglobulin (TgAb), thyroid peroxidase (TPOAb), TSH receptor (TRAb), 21-hydroxylase (21-OHAb) and tissue transglutaminase (tTGAb) were measured in 122 Type 1 DM patients who had low C-peptide activity or were >20 yr old at the time of diagnosis and in 100 non-diabetic blood donors. GAD65Ab and/or IA-2Ab were present in 74/122 (60.7%) Type 1 DM subjects with a significantly higher prevalence compared to non-diabetic controls (no. 100) (GAD65Ab-59 vs 4%; IA-2Ab-14 vs 0%; respectively) (p<0.001). The median (inter-quartile range) Type 1 DM duration in antibody positive subjects was 3.3 (0.99-6.9) vs 4.9 (1.7-7.5) yr in antibody negative subjects (p=0.23). IA-2Ab prevalence decreased with disease duration > or =5 yr (19 vs 4%) (p<0.001). There was no difference in the prevalence of TgAb (25 vs 33%)(p=0.21) and TPOAb (22 vs 18%) (p=0.48) in Type 1 DM and non-diabetic subjects. Also, there was no difference in TgAb and TPOAb prevalence in antibody positive Type 1 DM (34.7%) compared to antibody negative Type 1 DM (24.4%) subjects (p=0.24). tTGAb (3/119) and TRAb (1/119) were found in low prevalence and 21-OHAb were not detected. Diabetes associated autoantibodies were detected in the majority of Type 1 DM subjects, suggesting a major role for autoimmunity in the pathogenesis of Type 1 DM in Sri Lankans. The prevalence of TgAb and TPOAb in Type 1 DM subjects and non-diabetic controls was relatively high and similar in both groups.