Predisposing factors for adrenal crisis in chronic adrenal insufficiency: a case-control study.

OBJECTIVE: This study aims to identify susceptibility markers for adrenal crises (AC) in educated patients with chronic adrenal insufficiency (AI). DESIGN: A case-control study involving 66 patients with AI analyzing the impact of glucocorticoid and mineralocorticoid exposure, adrenomedullary function, inflammatory parameters, and educational status on AC frequency. Patients were categorized into low (n = 32) and high (n = 34) AC frequency groups based on AC occurrence (below or 2 times above the average of the reported AC frequency of 8.3 AC/100 patient-years in a previous prospective study). METHODS: Parameters, including cortisol plasma profile and urinary steroid excretion after administration of the morning glucocorticoid dose, 24-h urinary steroid profiling, salivary cortisol profiling, and hair cortisol, estimated cortisol exposure. Polymorphisms (single nucleotide polymorphism [SNP]) of the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) associated with individual steroid sensitivity were assessed together with SNPs for 11ß-hydroxysteroid dehydrogenase 1 (HSD11B1) and 11ß-hydroxysteroid dehydrogenase 2 (HSD11B2). Mineralocorticoid replacement was evaluated by serum and urinary electrolytes and osmolality, plasma-renin concentration, and ambulatory blood pressure levels. We additionally measured plasma and urinary catecholamines, serum levels of IL6 and hsCRP, and SNPs of IL6 and TNF-alpha. Patient knowledge of AC prevention was assessed by questionnaires. RESULTS: Frequent AC patients had higher daily glucocorticoid doses and hair cortisol levels, with no significant differences in other parameters investigated. AC frequency is inversely correlated with the frequency of self-reported adjustments of the glucocorticoid replacement. CONCLUSION: Higher glucocorticoid dosages in high-risk patients, despite unaffected cortisol metabolism, may be linked to decreased cortisol sensitivity or impaired glucocorticoid absorption. Proactive dose adjustments show a protective effect against AC, regardless of biological vulnerability.

Severe weight loss in a hypothyroid patient as an acute presentation of autoimmune polyglandular syndrome type II.

BACKGROUND: Autoimmune disease, including autoimmune thyroid disease, with uncharacteristic symptoms can be due to additional severe disease. We report a life-threatening debut of autoimmune polyglandular syndrome type II (APS II) defined as Addison's disease combined with autoimmune diabetes and/or thyroid disease. PATIENT FINDINGS: A 33-year-old male with newly diagnosed hypothyroidism was referred to a tertiary center due to fatigue and 20-kg rapid weight loss. Malignancy was excluded. After a gastroscopy, he developed Addison's crisis; he was admitted to our hospital and stabilized. Final diagnoses included Hashimoto's thyroiditis, Addison's disease, vitiligo, and pernicious anemia. Whole genome sequencing found no genetic variants associated with component diseases. Human leukocyte antigen typing revealed DR3/DR4 and DQ8/DQ2 heterozygosity associated with APS II. A patient with Hashimoto's thyroiditis and weight loss presented with Addison's crisis and was diagnosed with APS II. CONCLUSIONS: Awareness of potential polyautoimmunity in clinical evaluation of patients with thyroid disease improves diagnosis and can be lifesaving.

GWAS for autoimmune Addison's disease identifies multiple risk loci and highlights AIRE in disease susceptibility.

Autoimmune Addison's disease (AAD) is characterized by the autoimmune destruction of the adrenal cortex. Low prevalence and complex inheritance have long hindered successful genetic studies. We here report the first genome-wide association study on AAD, which identifies nine independent risk loci (P < 5 × 10-8). In addition to loci implicated in lymphocyte function and development shared with other autoimmune diseases such as HLA, BACH2, PTPN22 and CTLA4, we associate two protein-coding alterations in Autoimmune Regulator (AIRE) with AAD. The strongest, p.R471C (rs74203920, OR = 3.4 (2.7-4.3), P = 9.0 × 10-25) introduces an additional cysteine residue in the zinc-finger motif of the second PHD domain of the AIRE protein. This unbiased elucidation of the genetic contribution to development of AAD points to the importance of central immunological tolerance, and explains 35-41% of heritability (h2).

New era of therapy for endocrine autoimmune disorders.

The new era of immune and reconstitution therapy of autoimmune disorders is ongoing. However, endocrine autoimmune diseases comprise a group of elaborating pathologies where the development of new treatment strategies remains slow. Substitution of the missing hormones is still standard practice, taking care of the devastating symptoms but not the cause of disease. As our knowledge of the genetic contribution to the aetiology of endocrine disorders increases and early diagnostic tools are available, it is now possible to identify persons at risk before they acquire full-blown disease. This review summarizes current knowledge and treatment of endocrine autoimmune disorders, focusing on type 1 diabetes, Addison's disease, autoimmune thyroid diseases and primary ovarian insufficiency. We explore which new therapies might be used in the different stages of the disease, focus on legalized therapy and elaborate on the ongoing clinical studies for these diseases and the research front, before hypothesizing on the way ahead.

Beyond the adrenals: Organ manifestations in inherited primary adrenal insufficiency in children.

Primary adrenal insufficiency (PAI) in children is mostly due to genetic defects. The understanding of the molecular genetics of the causes of adrenal insufficiency in the pediatric population has made significant progress during the last years. It has been shown that inherited PAI can lead to certain clinical manifestations and health problems in children beyond the adrenals. Organ dysfunctions associated with different forms of PAI in children include a wide range of organs such as gonads, brain, heart, bone, growth, bone marrow, kidney, skin, parathyroid, and thyroid. Diagnosing the correct genetic cause of PAI in children is therefore crucial to adequately control long-term treatment and follow-up in such patients.

Doença de Addison e esclerose múltipla: relato de caso / Addison's disease and multiple sclerosis: case report

A doença de Addison é uma endocrinopatia rara, de etiologia autoimune. É caracterizada por défice na secreção de glicocorticoides e mineralocorticoides. A esclerose múltipla consiste em patologia neurológica, de origem autoimune, que resulta na desmielinização da bainha de mielina. O objetivo deste relato foi demonstrar a associação rara entre essas duas patologias e suas possíveis relações imunológicas. A paciente analisada é do sexo feminino, 41 anos, portadora de esclerose múltipla, que posteriormente foi diagnosticada com insuficiência adrenal primária. (AU)

Addison's disease is a rare endocrinopathy of autoimmune etiology. It is characterized by a secretion's deficit of glucocorticoids and mineralocorticoids. Multiple sclerosis is a neurological pathology of autoimmune origin, which results in demyelination of the myelin sheath. The purpose of this report is to demonstrate the uncommon association between these two pathologies and their possible immunological relationships. The analyzed patient is a woman, 41 years old, with multiple sclerosis, who was later diagnosed with primary adrenal insufficiency. (AU)

HLA-DQB1 Position 57 Defines Susceptibility to Isolated and Polyglandular Autoimmunity in Adults: Interaction With Gender.

CONTEXT: Autoimmune endocrinopathies result from environmental triggers on the genetic background of risk alleles, especially HLA-DR and HLA-DQ with alanine (Ala) in HLA-DQB1 position 57 (Ala57), whereas amino acid Asp57 is protective. OBJECTIVES: Differentiate the effects of HLA-DQB1 amino acid variants at position 57 in adult patients with isolated endocrinopathies and autoimmune polyglandular syndrome type 2 (APS-2) compared with healthy controls in relation to gender. SETTING: University Hospital Frankfurt, Frankfurt, Germany. PARTICIPANTS: Two hundred seventy-eight patients with APS-2 and 1373 patients with isolated endocrinopathies: [type 1 diabetes (T1D), n = 867], Addison disease (AD, n = 185), autoimmune thyroiditis (AIT, n = 321) and 526 healthy controls. RESULTS: Homozygous HLA-DQB1 Ala57 was more frequent in polyglandular T1D/AIT (OR 11.7, Pc = 3 × 10-7) and AD/AIT (OR 4.0, Pc = 3 × 10-7), as well as in isolated T1D (OR 9.7, Pc = 3 × 10-7) and AD (OR 3.1, Pc = 3 × 10-7). Heterozygous HLA-DQB1 57 Ala/non-Ala was increased in women with isolated AD and polyglandular AD/AIT (both OR 1.7, Pc= 0.02) whereas the same amino acid variant was overrepresented in men with T1D compared with women (OR 1.6, Pc = 0.004). The amino acid Ala57 was more frequent (OR 2.0, Pc = 0.02) and the amino acid Asp57 was much more rare (OR 0.4, Pc = 0.007) in the APS-2 cohort T1D/AIT than in AD/AIT. CONCLUSION: HLA-DQB1 confers strong susceptibility by Ala57 homozygosity and protection by non-Ala57, both in adult isolated and polyglandular diseases. Frequencies of HLA-DQB1 amino acids differentiate between APS-2 T1D/AIT and AD/AIT. HLA-DQB1 Ala57 heterozygous women are at increased risk for AD or AIT, whereas men were found to have an increased susceptibility for T1D.

Vitamin D effects on monocytes' CCL-2, IL6 and CD14 transcription in Addison's disease and HLA susceptibility.

Addison's disease is a rare autoimmune disorder leading to adrenal insufficiency and life-long glucocorticoid dependency. Vitamin D receptor (VDR) polymorphisms and vitamin D deficiency predispose to Addison's disease. Aim of the current study was, to investigate potential anti-inflammatory vitamin D effects on monocytes in Addison's disease, focusing on inflammatory CCL-2 and IL6, as well on monocyte CD14 markers. Addison's disease is genetically linked to distinct HLA susceptibility alleles. Therefore we analyzed, whether HLA genotypes differed for vitamin D effects on monocyte markers. CD14+ monocytes were isolated from Addison's disease patients (AD, n=13) and healthy controls (HC, n=15) and stimulated with 1,25-dihydroxyvitamin D3 and IL1ß as an inflammatory stimulant. Cells were processed for mRNA expression of CCL-2, IL6 and CD14 and DNA samples were genotyped for major histocompatibility class (MHC) class II-encoded HLA- DQA1-DQB1 haplotypes. We found a downregulation of CCL-2 after vitamin D treatment in IL1ß-stimulated monocytes both from AD patients and HC (AD p<0.001; HC p<0.0001). CD14 expression however, was upregulated in both HC and AD patients after vitamin D treatment (p<0.001, respectively). HC showed higher CD14 transcription level than AD patients after vitamin D treatment (p=0.04). Compared to IL1ß-induced inflammation, HC have increased CD14 levels after vitamin D treatment (p<0.001), whereas the IL1ß-induced CD14 expression of AD patients' monocytes did not change after vitamin D treatment (p=0.8). AD patients carrying HLA high-risk haplotypes showed an increased CCL-2 expression after IL1ß-induced inflammation compared to intermediate-risk HLA carriers (p=0.05). Also HC monocytes' CD14 transcription after IL1ß and vitamin D co-stimulation differed according to HLA risk profile. We show that vitamin D can exert anti-inflammatory effects on AD patients' monocytes which may be modulated by HLA risk genotypes.

Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept.

In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

Focus on vitamin D and the adrenal gland.

The main role of vitamin D is to maintain calcium and phosphorus homeostasis, thus preserving bone health. However, recent evidences have demonstrated that vitamin D may also play a role in a variety of nonskeletal disorders such as endocrine diseases and in particular type 1 diabetes, type 2 diabetes, adrenal diseases, and the polycystic ovary syndrome. Despite controversial results on an association of low vitamin D levels with cortisol and aldosterone overproduction, encouraging in vitro findings have been reported on vitamin D effects in adrenocortical cancer cells. The focus of this review is the role of vitamin D in adrenal diseases and the results of vitamin D supplementation studies in patients. Although many studies support a beneficial role of vitamin D in adrenal disease, randomized controlled trials and mechanistic studies are required to provide more insight into the efficacy and safety of vitamin D as a therapeutic tool.

Associations between Klinefelter's syndrome and autoimmune diseases: English national record linkage studies.

There are reports suggesting that people with Klinefelter's syndrome (KS) may be at increased risk of some autoimmune diseases, but the evidence is not substantial. We wanted to add to the evidence by systematically assessing the risk of autoimmune diseases in a national cohort of people with KS. We selected records of all people with KS in a record-linked dataset of all hospital day cases and inpatient admissions in England, 1999-2011; and we followed them up by electronic record linkage to identify the occurrence of autoimmune diseases. We compared their occurrence in the KS cohort with a control cohort, studied in the same way, and expressed the results as rate ratios (RR). Of 30 autoimmune diseases studied in people with KS, there were significantly increased risks of seven-Addison's disease (RR 11.7, 95% confidence interval 2.4-34.4), diabetes mellitus type 1 (6.1, 4.4-8.3), multiple sclerosis (4.3, 1.2-11.0), acquired hypothyroidism (2.7, 1.8-4.0), rheumatoid arthritis (3.3, 2.0-5.2), Sjogren's syndrome (19.3, 4.0-57.0) and systemic lupus erythematosus (18.1, 2.2-65.6). We concluded that people with KS have increased risk of some autoimmune diseases, particularly those that are female-predominant. The increased risk of autoimmune diseases associated with the XXY karyotype may hold clues to the pathogenesis of some aspects of autoimmunity.

Embryological and molecular development of the adrenal glands.

In this mini review, the embryological and functional development of the adrenal glands is presented from a molecular perspective. While acknowledging that this is a highly complex series of events, the processes are described in simple and broad strokes in a single text for the reader who is interested in this field but is not an active researcher. The origin of the adrenal glands is in the mesodermal ridge as early as the fourth week of gestation. Between the eighth and ninth weeks of gestation, the adrenal glands are encapsulated and this results in the presence of a distinct organ. There have been great strides in deciphering the very complicated molecular aspects of adrenal gland development in which multiple transcription factors have been identified, directing the adrenogonadal primordium into the adrenal cortex, kidney, or bipotential gonad. Adrenocorticotrophic hormone is critical for early development of the hypothalamic-pituitary adrenal axis. Several mutations in transcription factors, responsible for normal adrenal gland development have been found to induce the familial syndrome of congenital adrenal hypoplasia or neoplasia.

Adult cerebral adrenoleukodystrophy and Addison's disease in a female carrier.

We described a 38-year-old woman of rapidly progressive dementia with white matter encephalopathy and death. She had Addison's disease but the adrenal glands were hyperplastic. Brain magnetic resonance imaging revealed diffuse white matter lesion predominantly in the frontal lobe with band-like contrast enhancement. l-Methyl-11C-methionine positron emission tomography revealed accumulation of tracer in bilateral frontal lobes. Stereotactic biopsy demonstrated demyelination changes. A number of urinary organic acids were elevated. Adrenoleukodystrophy was diagnosed by elevated plasma very long chain fatty acid and ABCD1 gene mutation (C1544C/T). Adrenoleukodystrophy should be considered as a differential diagnosis in women with rapidly progressive white matter encephalopathy.

The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.

Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD.

Addison's disease: a survey on 633 patients in Padova.

OBJECTIVE: Addison's disease (AD) is a rare endocrine condition. DESIGN: We aimed to evaluate clinical, immunologic, adrenal imaging, and genetic features in 633 Italian patients with AD followed up since 1967. METHODS: Adrenal cortex autoantibodies, presence of other autoimmune and nonautoimmune diseases, nonadrenal autoantibodies, adrenal imaging, and genetic profile for HLA-DRB1 and AIRE were analyzed. RESULTS: A total of 492 (77.7%) patients were found to be affected by autoimmune AD (A-AD), 57 (9%) tuberculous AD, 29 (4.6%) genetic-associated AD, 10 (1.6%) adrenal cancer, six (0.94%) post-surgical AD, four (0.6%) vascular disorder-related AD, three (0.5%) post-infectious AD, and 32 (5.1%) were defined as idiopathic. Adrenal cortex antibodies were detected in the vast majority (88100%) of patients with recent onset A-AD, but in none of those with nonautoimmune AD. Adrenal imaging revealed normal/atrophic glands in all A-AD patients: 88% of patients with A-AD had other clinical or subclinical autoimmune diseases or were positive for nonadrenal autoantibodies. Based on the coexistence of other autoimmune disorders, 65.6% of patients with A-AD were found to have type 2 autoimmune polyendocrine syndrome (APS2), 14.4% have APS1, and 8.5% have APS4. Class II HLA alleles DRB1*03 and DRB1*04 were increased, and DRB1*01, DRB1*07, DRB1*013 were reduced in APS2 patients when compared with controls. Of the patients with APS1, 96% were revealed to have AIRE gene mutations. CONCLUSIONS: A-AD is the most prevalent form of adrenal insufficiency in Italy, and ∼90% of the patients are adrenal autoantibody-positive at the onset. Assessment of patients with A-AD for the presence of other autoimmune diseases should be helpful in monitoring and diagnosing APS types 1, 2, or 4 and improving patients' care.

Polymorphisms in the interferon-induced helicase (IFIH1) locus and susceptibility to Addison's disease.

OBJECTIVE: The interferon-induced helicase C domain-containing protein 1 (IFIH1) gene encodes a sensor for double-stranded RNA that initiates antiviral activity against enteroviruses. Previous investigations have indicated a role for IFIH1 in autoimmunity, as common and rare polymorphisms in this gene have been associated with type 1 diabetes. We hypothesized that polymorphisms in the IFIH1 locus may play a role in the pathogenesis of autoimmune Addison's disease (AAD). DESIGN: We analysed the association of rs3747517, rs1990760, rs2111485 and rs13422767 single-nucleotide polymorphisms (SNPs) in the IFIH1 gene and intergenic region with AAD in a Polish cohort. The study comprised 120 patients with AAD and 689 healthy control individuals. Genotyping was performed using TaqMan genotyping assays. RESULTS: The major AA genotype of the coding SNP rs1990760 appeared significantly more frequently in AAD compared with healthy individuals (AG vs AA OR 0·62, 95%CI 0·40-0·95, P = 0·03). We also observed a significant difference in the distribution of the rs13422767 SNP alleles. The major G allele was more frequent in the AAD group (A vs G OR 0·65, 95%CI 0·43-0·98, P = 0·04). Both statistically significant differences, for rs1990760 and rs13422767 SNPs, did not survive the Bonferroni correction (P = 0·11 and P = 0·15, for AA genotype and G allele, respectively). Subsequently, a meta-analysis of 519 patients with AAD and 1362 controls from three different European populations was performed. Under a fixed-effect model, a pooled OR for A allele and AA genotype of rs1990760 did not display any significant increase among AAD (OR = 1·05, P = 0·56 and OR = 1·08, P = 0·50, respectively). CONCLUSION: The IFIH1 locus polymorphisms are unlikely to be associated with Addison's disease.

BclI polymorphism of the glucocorticoid receptor gene is associated with increased bone resorption in patients on glucocorticoid replacement therapy.

CONTEXT: Patients with primary adrenal insufficiency (PAI) and patients with congenital adrenal hyperplasia (CAH) receive weight-adapted standard glucocorticoid replacement therapy. Clinically, some patients appear more sensitive to therapeutic administration of glucocorticoids than others. Glucocorticoid sensitivity is at least partially genetically determined by polymorphisms of the glucocorticoid receptor (GR) and might influence bone mineral density (BMD). OBJECTIVES: To determine if bone turnover markers and BMD are associated with the GR gene polymorphism BclI in patients with PAI and CAH. DESIGN AND PATIENTS: A prospective, cross-sectional study including 74 PAI and 38 CAH patients. BMD was evaluated by DXA. Serum levels of bone turnover markers, minerals, vitamins and hormones, and urinary crosslinks were measured. RESULTS: Patients carrying the homozygous BclI polymorphism (GG) had significantly higher serum ß-CrossLaps (0.37 ± 0.34 µg/l; P < 0.05) and urinary collagen crosslinks (NTX, 68.1 ± 32.4 nmol/g; P < 0.005) despite receiving the lowest average daily hydrocortisone dose of 9.9 ± 3.7 mg/m(2) (P < 0.05). The GG genotype occurred significantly more frequently in patients with increased NTX (OR=6.7, 95% CI = 1.78-25.38) than in patients with normal NTX. However, BMD was not significantly different between different allelic variants. No significant differences in associations of the genotypes with outcomes (or in clinical characteristics) were found between the sexes. CONCLUSIONS: Although the sample sizes were relatively small and the results should be interpreted with caution, this study suggests that the homozygous (GG) genotype may be associated with higher bone resorption in adult PAI and CAH patients. GG-carriers needed a lower hydrocortisone dose on average supporting the concept that this GR variant is associated with increased cortisol sensitivity.

Non-HLA autoimmunity genetic factors contributing to Autoimmune Polyglandular Syndrome type II in Tunisian patients.

Autoimmune Polyglandular Syndrome Type II (APSII) is characterized by the co-occurrence of clinical insufficiency of at least two endocrine glands. Although, HLA determinants of APSII predisposition have been identified, little attention has been paid to non-HLA genes. Here, we used SNP genotyping in a Sequenom platform and genetic association tests to study a cohort of 60 APSII Tunisian patients presenting highly frequent co-occurrence of Autoimmune Thyroid Disease (AITD) and Type 1 Diabetes (T1D) and lower frequency of Addison's disease (AD). We tested the high a priori possibility that well-established non-HLA autoimmunity loci were involved in APSII and confirmed five association signals to APSII, namely: (1) two T1D-associated SNPs, in CTLA4 and IL2RA, suggest their involvement in T1D pathogenesis in this cohort; (2) two SNPs in STAT4 and IL15 not previously associated to endocrinopathies, are possibly involved in co-occurrence of organ autoimmunity in APSII, and; (3) one SNP in TNF alpha showed association to APSII irrespective of AD. While this work was performed in a relatively small cohort, these results support the notion that the non-HLA genetic component of APSII include genetic factors specific of particular autoimmune manifestations as well as genetic factors that promote the co-occurrence of multiple autoimmune endocrinopathies.

Autoimmune polyglandular syndrome type II after bone marrow transplant: real transfer or acceleration of a programmed disease?

We report a case of autoimmune polyglandular syndrome type II that developed in an 11-year-old boy with homozygous sickle cell disease after allogeneic bone marrow transplant; the donor was his father, who was human leukocyte antigen identical and had vitiligo. On day 24 after transplant, the patient developed grade 1 acute graft-versus-host disease, which was controlled over a period of 3 months with corticosteroid-induced immunosuppression. Full donor engraftment was documented on day 31 after transplant, and this was further confirmed on days 59, 231, 321, 472, 549, and 720. Three months after transplant, the recipient developed adrenal insufficiency, and at 13 months, he developed vitiligo. Seventeen months after transplant, autoimmune thyroid disease, positive for thyroid peroxidase and thyroglobulin autoantibodies, was diagnosed. At the same time, we identified adrenal insufficiency in the donor. We analyzed a serum sample from the recipient for autoantibody markers for type 1 autoimmune diabetes mellitus. The sample was positive for antiglutamic acid decarboxylase. Antibody against 21-hydroxylase enzyme was also found (261 U/mL; normal value, < 1 U/mL). We conclude that the recipient developed autoimmune polyglandular syndrome type II after bone marrow transplant from his father, who was probably affected by the same syndrome.