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Objective To report the first case, to our knowledge, of intermittent pancytopenia and cardiac tamponade occurring together in association with Autoimmune Addison's Disease (AAD). Methods A 21 year-old woman presented on three different occasions with multiple complaints. Her evaluation was significant for intermittent pancytopenia (white blood cell, 1.3-3.0 × 103/μL [normal 4.5-11 × 103]; hemoglobin, 8.8-9.6 g/dL [11-16]; and platelets, 102-117 × 103/μL [150-400 × 103/μL]) and pericardial effusion with cardiac tamponade. Further investigation including a morning serum cortisol level of 0.6 μg/dL (5.27-22.45 μg/dL), adrenocorticotropic hormone level of 1027 pg/mL (normal 6-50 pg/mL), and positive 21-hydroxylase antibodies confirmed the diagnosis of primary adrenal insufficiency due to AAD. Treatment with steroids resulted in prompt hemodynamic recovery with normalization of all blood cell lines. Results The diagnosis of AAD is often delayed or overlooked. Pancytopenia occurring in AAD is most likely due to either marrow suppression in the setting of acute illness and exacerbated by hypoadrenalism or possibly an autoimmune-mediated marrow reaction. Pericarditis with cardiac tamponade has been described in AAD occurring in the setting of polyglandular autoimmune syndrome type II. The pathogenesis involves autoimmune inflammation of the pericardium, which precipitates an acute inflammatory reaction and rapid fluid accumulation. Conclusion Pericarditis with cardiac tamponade and intermittent neutropenia may be rare manifestations of an Addisonian crisis.

The aim of our study was to examine whether slow or rapid cryopreservation of adrenal xenografts affected xenotransplant outcome. Adrenal xenografts were got from newborn piglets (24 h after birth). Receptor rats were randomly divided into four groups: a bilateral adrenalectomy group, fresh xenotransplantation group, rapid cryopreservation xenotransplantation group, and a slow cryopreservation xenotransplantation group. 30 days after xenotransplantation, the survival rates of rats in the fresh xenotransplantation group, rapid cryopreservation xenotransplantation group and slow cryopreservation xenotransplantation group were 80 %, 60 % and 60 %, respectively, which were significantly higher than 40 % of the bilateral adrenalectomy group. In addition, the survival rate of rats in the slow cryopreservation group was consistently significantly higher than that in the rapid cryopreservation group at 29 days after xenotransplantation. Morphological observation showed that there were a few medulla cells existed in the adrenal glands in the slow cryopreservation group after 30 days of xenotransplantation, but no medulla cells were found in the rapid cryopreservation group. The plasma cortisol level of rats in the fresh xenotransplantation group and the slow xenotransplantation group 30 days after xenotransplantation was significantly higher than that of the rapid cryopreservation group and bilateral adrenalectomy group (P 0.05). The levels of liver glycogen and cholesterol in the xenotransplantation rats were increased relative to those of the bilateral adrenalectomy rats, and close to normal level. In conclusion, compared with rapidly frozen preserved grafts, slowly frozen preserved grafts not only ensure the structural integrity of adrenal tissues, but also have corresponding physiological functions, which provid a basic research opportunities for the preservation of xenografts and the treatment of adrenal corticosteroid deficiency. Moreover, these findings can provide evidence for xenotransplantation in the treatment of Addison's disease (adrenal cortex hormone deficiency).

Background/Objective: The multisystemic effects of COVID-19 are clearly becoming evident. In the adrenal gland, adrenal hemorrhage and infarction after COVID-19 infection have been reported. Our objective is to present a case of autoimmune adrenal insufficiency diagnosed post-COVID-19 infection, without evidence of hemorrhage or infarction. Case Report: 64-year-old woman with hypothyroidism and type 2 diabetes presented with a 1-week history of abdominal pain, nausea, and vomiting. She experienced an asymptomatic COVID-19 infection five months prior and reported an unintentional 30-pound weight loss. Home medications were enalapril, atorvastatin and levothyroxine. Physical exam was notable for hypotension, epigastric tenderness, and mucocutaneous hyperpigmentation. Labs revealed serum sodium 117 mmol/L (135-145), TSH 0.33 µIU/mL (0.35-4.00), free T4 1.4 ng/dL (0.6-1.7), serum osmoles 253 mOsm/kg (279-300), urine osmoles 324 mOsm/kg (300-900) and urine sodium 104 mmol/L. Morning cortisol was 2.6 µg/dL (ref: >18). A high-dose 250 mcg ACTH stimulation test followed; cortisol levels returned 2.3, 2.9, and 2.6 µg/dl (ref: >18) at baseline, 30, and 60 minutes. ACTH level was 1944 pg/ml (7.2-63.3), aldosterone was

There is a number of systemic diseases affecting the cornea. These include endocrine disorders (diabetes, Graves' disease, Addison's disease, hyperparathyroidism), infections with viruses (SARS-CoV-2, herpes simplex, varicella zoster, HTLV-1, Epstein-Barr virus) and bacteria (tuberculosis, syphilis and Pseudomonas aeruginosa), autoimmune and inflammatory diseases (rheumatoid arthritis, Sjogren's syndrome, lupus erythematosus, gout, atopic and vernal keratoconjunctivitis, multiple sclerosis, granulomatosis with polyangiitis, sarcoidosis, Cogan's syndrome, immunobullous diseases), corneal deposit disorders (Wilson's disease, cystinosis, Fabry disease, Meretoja's syndrome, mucopolysaccharidosis, hyperlipoproteinemia), and genetic disorders (aniridia, Ehlers-Danlos syndromes, Marfan syndrome). Corneal manifestations often provide an insight to underlying systemic diseases and can act as the first indicator of an undiagnosed systemic condition. Routine eye exams can bring attention to potentially life-threatening illnesses. In this review, we provide a fairly detailed overview of the pathologic changes in the cornea described in various systemic diseases and also discuss underlying molecular mechanisms, as well as current and emerging treatments.

Autoimmunity against the adrenal cortex is the leading cause of Addison's disease in industrialized countries, with prevalence estimates ranging from 93-220 per million in Europe. The immune-mediated attack on adrenocortical cells cripples their ability to synthesize vital steroid hormones and necessitates life-long hormone replacement therapy. The autoimmune disease etiology is multifactorial involving variants in immune genes and environmental factors. Recently, we have come to appreciate that the adrenocortical cell itself is an active player in the autoimmune process. Here we summarize the complex interplay between the immune system and the adrenal cortex and highlight unanswered questions and gaps in our current understanding of the disease.

Patients with adrenal insufficiency require regular, specialised monitoring in order to optimise their replacement therapy, to detect signs of under- and over-dosage, and to examine for possible associated disorders (auto-immune disorders in the case of auto-immune primary adrenal insufficiency either isolated or as part of auto-immune polyendocrinopathy syndrome type 1; illnesses with underlying monogenic causes). The transition period between adolescence and adulthood represents an added risk of a breakdown in monitoring which requires particular attention from medical teams and coordination between adult and pediatric medical teams. It is essential to encourage patient autonomy in the management of their illness, notably their participation in treatment education programs, in particular programs that target avoidance of, or early treatment of acute adrenal insufficiency. The principal educational objectives for patients in such programs are: to be in possession of, and carry the necessary tools for their treatment in an emergency; to be able to identify situations of increased risk and the early signs of adrenal crisis; to know how to adjust their oral glucocorticoid treatment; to be capable of administering hydrocortisone by subcutaneous injection; to be able to predict and therefore adjust treatment to different situations (heat, physical exercise, travel) and to be able to correctly use the appropriate resources of the healthcare services. Other programs could also be developed to respond to needs and expectations of patients, notably concerning the adjustment of hydrocortisone dosage to avoid overdose in the context of chronic fatigue syndrome.

The prevalence of primary adrenal insufficiency is estimated at between 82–144/million, with auto-immunity being the most common cause in adults and genetic causes, especially enzyme defects, being the most common cause in children. The prevalence of secondary adrenal deficiency is estimated to be between 150–280/million. The most frequent occurrence is believed to be corticosteroid-induced insufficiency, despite the incidence of clinically relevant deficiency after cessation of glucocorticoid treatment being widely debated. Data on mortality in adrenal insufficiency are contradictory, with studies from Sweden suggesting a two-fold increase in comparison to the general population, but this is not consistently reported in all studies. However, increased mortality has been consistently reported in young patients, associated with infection and/or acute adrenal insufficiency. Acute adrenal deficiency (adrenal crisis) occurs in primary as well as secondary adrenal insufficiency. Its incidence, mostly determined in retrospective studies, is estimated in Europe at 6–8/100 patients/year. A prospective study reported 0.5 deaths/100 patient-years from adrenal crisis. Long-term morbidity of adrenal insufficiency is not well-established, the increased cardiovascular risk or bone demineralization which are not consistently reported may also be due to a supraphysiological glucocorticoid replacement therapy. However, alteration in quality of life, both in physical and mental health components, has been demonstrated by several studies in both primary and secondary adrenal insufficiency.

Background X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder associated with leukodystrophy, myeloneuropathy and adrenocortical insufficiency. We performed a retrospective cohort study to evaluate long-term outcome of patients with X-ALD. Method All patients with X-ALD diagnosed between 1989 and 2012 were included. Electronic patient charts were reviewed for clinical features, biochemical investigations, molecular genetic testing, neuroimaging, long-term outcome and treatment. Results Forty-eight patients from 18 unrelated families were included (15 females; 33 males). Seventeen patients were symptomatic at the time of the biochemical diagnosis including 14 with neurocognitive dysfunction and 3 with Addison disease only. Thirty-one asymptomatic individuals were identified by positive family history of X-ALD. During follow-up, eight individuals developed childhood cerebral X-ALD (CCALD), one individual developed adrenomyeloneuropathy (AMN), six individuals developed Addison disease only, and five individuals remained asymptomatic. Direct sequencing of ABCD1 confirmed the genetic diagnosis in 29 individuals. Seven patients with CCALD underwent hematopoietic stem cell transplantation (HSCT). Nine patients lost the follow-up. There was no correlation between clinical severity score, Loes score and elevated degree of elevated very long chain fatty acid (VLCFA) levels in CCALD. Conclusion Our study reports forty-eight new patients with X-ALD and their long-term outcome. Only 35% of the patients presented with neurological features or Addison disease. The remaining individuals were identified due to positive family history. Close monitoring of asymptomatic males resulted in early HSCT to prevent progressive lethal neurodegenerative disease. Identification of patients with X-ALD is important to improve neurodevelopmental outcome of asymptomatic males.

Background Increased frequency of glucose intolerance, dyslipidaemia, and obesity has been reported in subjects treated for adrenocortical failure (Addison's disease, AD). Glucocorticoid substitution is difficult to adjust and patients display variable responses to steroid dosage. Since local regeneration markedly contributes to the available cortisol pool, the activity of 11β-hydroxysteroid dehydrogenase type 1 ( HSD11B1 gene) may be involved in adverse metabolic profile. Our aim was to explore if HSD11B1 polymorphisms might impact on individual requirements for glucocorticoid replacement and its metabolic effects. Methods This cross-sectional analysis comprised 152 AD patients (aged 47.1±15.1years) receiving regular glucocorticoid substitution. Their daily hydrocortisone dosage (mean 25.5±5.5mg) had been based upon clinical features. Stratification by the HSD11B1 genotypes (rs846910, rs3753519 and rs12086634) enabled comparisons with regard to patients' anthropometric, hormonal, and metabolic characteristics. Results In rs3753519-stratified analysis, carriers of the minor allele presented significantly increased BMI ( p p p =0.021) compared to the wild-type homozygotes, although the HOMA-IR association disappeared when adjusted for age, gender, BMI, and hydrocortisone dose. In contrast, homozygous carriers of two common rs12086634 alleles displayed elevated serum triglycerides ( p =0.035), total, and LDL cholesterol ( p =0.001 and 0.003, respectively) but only total cholesterol association survived after correction for multiple comparisons. Finally, no association of rs846910 with any clinical or laboratory parameter was found. Conclusion Our study provides support for plausible implication of the HSD11B1 polymorphisms in susceptibility to develop undesirable effects of glucocorticoid replacement. Further analyses are warranted to validate the role of HSD11B1 variants in clinical practice.

The number of women with endocrine conditions embarking on pregnancy is growing as more choose to delay conception or require assisted reproduction techniques. It is therefore increasingly important for clinicians to have an understanding of common endocrine disorders and how these may impact on pregnancy and fetal development. Over-investigation and subsequent medicalization and treatment of sub-clinical endocrine conditions, which have uncertain clinical impact for the fetus or mother, is a cause for concern and debate surrounding this practice is ongoing. Vitamin D deficiency is increasing in prominence due to the rise in childhood rickets; this startling re-emergence has led to more work on the prevalence of vitamin D deficiency and identified a higher than expected percentage of women affected. For this reason, national advice has called for routine vitamin D supplementation in pregnancy, and diagnosis and treatment of those most at risk. This review also briefly discusses the management of other rarer endocrine conditions, which can lead to significant maternal and fetal morbidity if the diagnosis is delayed or overlooked.

Anaemia related to the digestive system is mostly secondary to dietary deficiency, malabsorption, or chronic bleeding. We review the World Health Organization definition of anaemia and its morphological classification (microcytic, macrocytic and normocytic). We detail the importance of iron, vitamin B12 and folate deficiency anaemia; the interpretation of laboratory tests to differentiate between the causes of anaemia, especially anaemia of chronic disease; and the management options for patients with anaemia caused by gastrointestinal disease.

Adrenal insufficiency (glucocorticoid deficiency) comprises a group of rare diseases, including primary adrenal insufficiency, secondary adrenal insufficiency and congenital adrenal hyperplasia. Lifesaving glucocorticoid therapy was introduced over 60 years ago, but since then a number of advances in treatment have taken place. Specifically, little is known about short- and long-term treatment effects, and morbidity and mortality. Over the past decade, systematic cohort and registry studies have described reduced health-related quality of life, an unfavourable metabolic profile and increased mortality in patients with adrenal insufficiency, which may relate to unphysiological glucocorticoid replacement. This has led to the development of new modes of replacement that aim to mimic normal glucocorticoid physiology. Here, evidence for the inadequacy of conventional glucocorticoid therapy and recent developments in treatment are reviewed, with an emphasis on primary adrenal insufficiency.

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.

Autoimmune adrenalitis, or autoimmune Addison disease (AAD), is the most prevalent cause of primary adrenal insufficiency in the developed world. AAD is rare and can easily be misdiagnosed as other conditions. The diagnosis depends on demonstrating inappropriately low cortisol production and the presence of high titers of adrenal cortex autoantibodies (ACAs), along with excluding other causes of adrenal failure using other tests as necessary. The treatment corticosteroid replacement, and the prognosis following the treatment is the same as the normal population. Spontaneous recovery of adrenal function has been described but is rare.

A 28-year-old man diagnosed with primary adrenal insufficiency (Addison's disease) in 2002. Following diagnosis, replacement therapy with hydrocortisone and fludrocortisone was indicated. Hydrocortisone replacement therapy was unsuccessful, and increased ACTH levels as high as 996 pg/dl were observed on outpatient follow-up. A pituitary MRI revealed a pituitary microadenoma. These findings raised three possibilities: (1) treatment is insufficient; (2) there is no relationship between Addison's disease and pituitary microadenoma; and (3) the microadenoma is similar to Nelson's syndrome. This latter is the most satisfactory explanation of this patient's clinical picture.

Hypoadrenocorticism or Addison's disease (AD) is a functional disorder in which insufficient mineralocorticoid and glucocorticoid hormones are produced by the adrenal cortex. Human AD is usually attributed to lymphoplasmacytic adrenalitis with autoimmune destruction of the adrenal cortex. Lymphoplasmacytic adrenalitis is also reported in some descriptions of canine AD; however, the histological aspects of adrenalitis or adrenocortical atrophy have not been well characterized because microscopical examination is not required for diagnosis of AD. In this study, sections of adrenal glands from 33 dogs with adrenalitis were compared with those of 37 dogs without adrenal lesions. The affected dogs were classified clinically as having AD (n = 3), being suspected of having AD (n = 17), not having AD (n = 11) or were unclassified (n = 2). The adrenal inflammation was lymphoplasmacytic in 17 dogs, lymphocytic in four, lymphohistiocytic in one, granulomatous in three and neutrophilic in eight cases. Adrenal glands from control dogs lacked leucocyte infiltration and had a cortical to medullary area ratio of 1.1-7.2. All three dogs with AD, 8/17 dogs with suspected AD and 1/11 dogs without AD had a cortical to medullary area ratio1.1. Because the area ratio was correlated (r = 0.94) with a linear cortical to medullary thickness ratio, a thickness ratio1.1 could also indicate severe adrenocortical atrophy. Severe adrenocortical atrophy was associated typically with lymphoplasmacytic infiltration and nearly complete loss of cortical cells; however, the zona glomerulosa was partially spared in three dogs with lymphoplasmacytic adrenalitis and severe cortical atrophy. In contrast, non-lymphoid inflammation was generally part of systemic disease, multifocal and was unaccompanied by severe adrenocortical atrophy.

Endocrine disorders are commonly encountered in pregnancy. To optimize pregnancy outcome, it is essential to understand the physiology underlying these conditions. Clinicians should be aware of which investigations are required for diagnosis and monitoring during pregnancy as well as current guidance on which treatments are safe to use. The most common endocrine disorder encountered in pregnancy is diabetes, followed by hypo and hyperthyroidism. Rarer endocrine disorders including pituitary dysfunction, adrenal and parathyroid disease are as important to be aware of due to the potential for significant maternal and fetal morbidity or mortality if not diagnosed or managed appropriately. Over recent years awareness of the potential adverse effects of vitamin D deficiency has driven the guidance for vitamin D supplementation for pregnant and lactating women. This review focuses on the physiology and current management of thyroid dysfunction and the rarer endocrine disorders in pregnancy, and includes current guidance on vitamin D supplementation.

The silent pheochromocytoma, a hidden form of pheochromocytoma, exposes the patient to an increased risk of mortality if the diagnosis is not established on time. Biological diagnosis of pheochromocytoma can be difficult. Catecholamine secretion is dependent on tumor size and a large number of physiological, pharmacological, lifestyle modifications and sampling conditions influence the measurement of urinary and plasma metanephrines. The prevalence of pheochromocytoma is 2% among adrenal incidentaloma smaller than 3 cm (2/3 of tumors). Recent studies suggest the almost zero risk of pheochromocytoma among these tumors if they are hypodense (

RESUMOA síndrome poliglandular autoimune (SPGA) tipo II define-se pela presença de doença de Addison (DA) autoimune associada a Diabetes Mellitus tipo 1 (DM1) e/ou doença tiroideia autoimune. Habitualmente associa-se a outras doenças autoimunes «minor». Os autores apresentam o caso clínico de um adolescente com SPGA tipo II, manifestada aos doze anos de idade por DM1, hepatite autoimune tipo 1 com cirrose hepática e pancitopenia. No seguimento da investigação confirmou-se DA autoimune, presença de Ac antitiroideus, gastrite autoimune, doença celíaca, trombocitopenia imune e défice seletivo de IgA. No estudo da genotipagem do HLA-DQ foram identificados os haplótipos HLA-DQB1*03,*02. Inicialmente foi medicado com insulina, prednisolona e micofenolato de mofetil com resposta clínica parcial. Atualmente, quatro anos após o diagnóstico, encontra-se com dieta isenta de glúten, medicado com suplementos vitamínicos e minerais, insulina por bomba perfusora continua, prednisolona e azatioprina com controlo da função hepática e resolução da anemia, no entanto com difícil controlo glicémico. Os autores descrevem este caso clínico pela sua complexidade clínica e idade de apresentação, uma vez que esta síndrome é extremamente rara em idade pediátrica.ABSTRACTThe autoimmune polyglandular syndrome (APS) type II is defined by the presence of autoimmune Addison's disease (AD) associated with type 1 diabetes mellitus (T1DM) and/or autoimmune thyroid disease. It is usually associated with other «minor» autoimmune manifestations. The authors report the case of an adolescent with APS type II, presented at the age of twelve by T1DM, autoimmune hepatitis type 1 with cirrhosis and pancytopenia. The clinical and analytical investigation confirmed autoimmune AD, presence of anti-thyroid antibodies, autoimmune gastritis, celiac disease, immune thrombocytopenia and selective IgA deficiency. During the study of genotyping of HLA-DQ the haplotypes HLA-DQB1*03,*02 were identified. Initially the patient was treated with insulin, prednisolone and mycophenolate mofetil with partial clinical response. Currently, four years after the diagnosis, the patient is on a gluten-free diet, vitamins and mineral supplements, insulin pump therapy, prednisolone and azathioprine with control of liver function and anemia resolution, but with difficult glycemic control. The authors describe this case for its clinical complexity and age of presentation, since this syndrome is extremely rare in paediatric age.

In autoimmune adrenal deficiency, autoantibodies target the 21-hydroxylase (21OH) protein. However, it is presumed that autoreactive T cells, rather than antibodies, are the main effectors of adrenal gland destruction, but their identification is still lacking. We performed a T-cell epitope mapping study using 49 overlapping 20mer peptides covering the 21OH sequence in patients with isolated Addison's disease, Autoimmune Polyendocrine Syndrome 1 and 2. IFNγ ELISPOT responses against these peptides were stronger, broader and more prevalent among patients than in controls, whatever the disease presentation. Five peptides elicited T-cell responses in patients only (68% sensitivity, 100% specificity). Blocking experiments identified IFNγ-producing cells as CD8 T lymphocytes, with two peptides frequently recognized in HLA-B8+ patients and a third one targeted in HLA-B35+ subjects. In particular, the 21OH(431-450) peptide was highly immunodominant, as it was recognized in more than 30% of patients, all carrying the HLA-B8 restriction element. This 21OH(431-450) region contained an EPLARLEL octamer (21OH(431-438)) predicted to bind to HLA-B8 with high affinity. Indeed, circulating EPLARLEL-specific CD8 T cells were detected at significant frequencies in HLA-B8+ patients but not in controls by HLA tetramer staining. This report enlightens disease-specific T-cell biomarkers and epitopes targeted in autoimmune adrenal deficiency.

The association of thymoma with myasthenia gravis has been well documented. However, the relationship between these two syndromes and Addison disease are very rarely encountered in clinical practice. We report on a 32-year-old man who underwent a resection for thymoma 48 months ago. The diagnosis of Addison disease was made followed by a diagnosis of myasthenia gravis on the basis of a high titer of acetylcholine receptor levels. The treatment of oral prednisolone 7.5 mg/day and oral prostigmine 180 mg/day was initiated. His symptoms and physical signs were improved after this treatment. To our knowledge, this is the fourth reported case of thymoma synchronously associated with myasthenia gravis and Addison disease.

Autoimmune Addison's disease and autoimmune ovarian insufficiency are caused by selective targeting by T and B lymphocytes to the steroidogenic apparatus in these organs. Autoantibodies toward 21-hydroxylase are a clinically useful marker for autoimmune Addison's disease. Autoantibodies to 21-hydroxylase are found in premature ovarian insufficiency, but others also can be present, notably antibodies against side-chain cleavage enzyme. The autoimmune response primarily targets the theca cells, yielding elevated concentrations of inhibin, which is emerging as a useful diagnostic marker for autoimmune etiology of ovarian insufficiency. Little is known about its immunogenetics, but in contrast to Addison's disease, several experimental models of autoimmune premature ovarian insufficiency are available for study.

Despite treatment with glucocorticoids and mineralocorticoids, the ability to work and quality of life of patients who have adrenal insufficiency remains low. There are no helpful objective measures of optimal glucocorticoid replacement, so this is best achieved by careful clinical assessment. Adequacy of mineralocorticoid replacement may be judged by assessing postural change in blood pressure, serum electrolytes, and plasma renin activity. Novel delayed-release and sustained-release formulations of hydrocortisone seem to more closely mimic diurnal serum cortisol rhythms than conventional hydrocortisone tablets. Such preparations are currently being evaluated and may play a role in management of patients who have adrenal insufficiency.

Replacement therapy in adrenal insufficiency comprises treatment with glucocorticoids, mineralocorticoids and adrenal androgen precursors. Initiation of hormone replacement therapy in newly diagnosed adrenal insufficiency leads to rapid and impressive improvements. However, despite the use of established replacement concepts, well-being is often not fully restored in patients with adrenal insufficiency, and life expectancy may even be reduced. This has led to a reconsideration of current replacement strategies. Several studies demonstrate that addition of dehydroepiandrosterone (DHEA) to the treatment regimen may lead to further improvement of general well-being and also sexual function. However, long-term trials with DHEA are still lacking, and DHEA alone is not able to restore subjective health status to normal. Further innovations comprise the development of delayed-release glucocorticoid preparations that better allow mimicking of circadian cortisol secretion and may have the potential to significantly improve the treatment of patients with adrenal insufficiency. However, future studies have to prove the clinical importance of physiological cortisol day profiles. To date, no relevant risk factors for susceptibility to adrenal crisis are known, and patient education is key for a successful prevention strategy. In our experience the well-educated patient often guides the physician not familiar with this disease.

Autoimmune polyendocrine syndrome type II (APS-II) is the most common immunoendocrinopathy syndrome. APS-II is defined by the development of two or more of the following entities: primary adrenal insufficiency (Addison's disease), Graves' disease, type 1A diabetes mellitus, autoimmune thyroiditis, primary hypogonadism, celiac disease, and myasthenia gravis. Other frequent clinical findings are vitiligo, alopecia, pernicious anemia and/or serositis. Primary adrenal insufficiency in these patients affects the adrenal cortex, which is destroyed by autoantibodies against 21-hydroxylase. Unlike other causes of adrenal insufficiency (infectious diseases, infiltrative diseases, bleeding, tumors), the adrenal medulla is not involved. Pheochromocytomas are tumors arising from the chromaffin cells of the sympathetic nervous system in the adrenal medulla. The clinical symptoms of these tumors vary from isolated hypertension or hypertension accompanied by paroxysmal episodes -including the classical triad of headache, palpitations and diaphoresis-to potentially serious manifestations such as acute pulmonary edema, arrhythmias and sudden death. Nevertheless, up to 40% of affected patients are asymptomatic. We present the case of a patient diagnosed with APS-II who developed a pheochromocytoma. In this patient, the adrenal gland cortex was atrophied and the tumor was attached to the adrenal medulla. This coexistence of endocrinopathies, with no etiologic connection, is a surprising finding, which has not previously been described in the current literature.

The foundation doctor may need to deal with pituitary or adrenal pathology in the acute setting as part of a medical emergency or because an incidental lesion within the gland has been found on imaging. Pituitary apoplexy refers to a vascular event within a pituitary tumour, and the clinical features include acute onset headache, reduced consciousness, visual disturbance and diplopia. A high index of suspicion is required to make the diagnosis and appropriate imaging is needed. Acute adrenal insufficiency presents with hypoglycaemia, hypotension, hyponatraemia, hyperkalaemia and dehydration. Intravenous hydrocortisone should be given empirically if the clinical features are suggestive, as the condition may be fatal if untreated. A systematic approach is required to determine the clinical significance of incidentally found pituitary and adrenal lesions, which includes determining the size of the lesion and biochemical assessment to exclude endocrine hypersecretion.

Endocrine disorders are increasingly encountered in pregnancy. To optimize pregnancy outcome, it is essential to understand the physiology underlying these conditions, as well as which investigations and treatments are safe to use. Thyroid disease is the second most common endocrine condition encountered in women of childbearing age after diabetes. Other endocrine disorders, such as pituitary dysfunction and adrenal and parathyroid disease, are less frequently encountered in pregnancy due to lower population prevalence in combination in some cases with associated subfertility. Women whose pregnancies are complicated by endocrine disease are at risk of maternal and foetal complications, but these can be minimized with appropriate multidisciplinary management.

Objective To determine the characteristics of tuberculous Addison's disease on the axial and multiplanar reformatted (MPR) images of the multidetector-row computed tomography (MDCT). Materials and methods The unenhanced and contrast-enhanced MDCT features in 19 patients with tuberculous Addison's disease were retrospectively assessed for the location, contour, size, calcification, attenuation, and enhancement patterns. The correlation between the duration of Addison's disease and the percentage of calcification presence was evaluated. Results The adrenal glands were infected bilaterally in all of the 19 cases (100%, 38 glands). Enlargement of the glands appeared in 18 cases (94.7%, 36 glands) and the remaining one case (5.3%, two glands) showed atrophy bilaterally. Of the 36 enlarged adrenals, 13 (36.1%) had preserved contours, and the other 23 (63.9%) were mass-like. The size of the adrenals ranged from 0.6 to 4.8 cm (mean 1.92 ± 0.96 cm). Calcification was revealed in 16 adrenals (16/38, 42.1%), increasing in incidence with disease progression. Fourteen of the 36 (38.9%) enlarged adrenals showed peripheral enhancement while the remaining 22 (61.1%) demonstrated heterogeneous enhancement. The ΔCT value, the attenuation measurement of mass-like lesions, was less in the central area (7 ± 4 HU) than that in the peripheral area (32 ± 14 HU) ( P 0.01) between the unenhanced and contrast-enhanced scan. Conclusion MDCT can reveal the characteristic morphology and CT attenuation in the tuberculous Addison's disease. Combined with its clinical presentations and biochemical findings, we can diagnose and stage adrenal tuberculosis with high specificity and accuracy on MDCT.

The diagnosis and treatment of hypoadrenocorticism can be one of the greatest challenges faced by veterinary practitioners, as Addison's disease may have many faces and many presentations. Although the disease is most often diagnosed in dogs, cats may also suffer from Addison's disease. The practitioner must have a high index of suspicion to make a diagnosis of hypoadrenocorticism. This index of suspicion is based on knowledge of the common signalment, history, physical examination, and laboratory findings. Diagnosis of hypoadrenocorticism is supported by appropriate choice of diagnostic endocrine tests that are described in detail in this article. Once a diagnosis of hypoadrenocorticism has been made, expedient treatment is of foremost concern. Timely treatment using fluids, corticosteroids, and supportive care will ensure a successful outcome; the emergency treatment of Addison's is covered briefly in this article and fully in another article in this issue. The purpose of this review was to describe the clinical diagnosis and chronic treatment of hypoadrenocorticism in dogs and cats.

Measurements of the auditory brainstem response (ABR) were obtained in 96 individuals with X-linked adrenoleukodystrophy (X-ALD). The patients were divided into five diagnostic groups on the basis of neurologic diagnosis. The five groups were cerebral childhood and adolescent, pure adrenomyeloneuropathy (pure AMN), adrenomyeloneuropathy cerebral (AMN cerebral), Addison's only and symptomatic female heterozygotes. Results indicated the presence of marked ABR abnormalities for all groups most frequently involving Wave V, followed by Wave III and Wave I. Abnormalities of all interpeak latency intervals (i.e., I-III, III-V and I-V) were observed for all groups. ABR abnormalities were most frequently seen in the AMN-cerebral and pure AMN groups but were also common in the symptomatic female heterozygote group. The ABRs in the cerebral childhood and adolescent group were the least impaired of the five groups examined. Age was found to be a significant independent predictor of bilateral ABR abnormalities but VLCFA levels, MRI Loes score, and duration of symptoms were not found to be independent predictors of bilateral ABR abnormalities after adjusting for ALD phenotype. Patients with AMN were significantly more likely to have bilateral ABR abnormalities than the cerebral childhood and adolescent group after adjusting for age, duration of symptoms, EDSS score, VLCFA levels and MRI Loes scores. The prevalence of peripheral hearing loss was not found to exceed that present in age and sex matched normal control groups derived from the NHANES (1999-2000), indicating a lack of association between peripheral hearing loss and X-linked adrenoleukodystrophy. It was concluded that: (1) auditory sensitivity in X-ALD is not significantly impaired; (2) ABR abnormalities are a frequent finding and may be caused by abnormalities of fiber tracts in the region of the lateral lemniscus and inferior colliculus; and, (3) the abnormalities progress slowly and appear to be associated mainly with the AMN phenotype.

Regulation of the adrenal and thyroid glands by the hypothalamo-pituitary axis depends on feedback loops. A breakdown in this feedback system may lead to chronic stimulation or inhibition and endocrine disorders. The adrenal gland secretes steroids (mineralocorticoids, glucocorticoids and androgens) and catecholamines. Adrenal insufficiency (Addison’s disease) is an autoimmune condition that results in the destruction of the adrenal glands. Treatment is by replacement of glucocorticoids and mineralocorticoids. Primary hyperaldosteronism (Conn’s syndrome) and Cushing’s syndrome arise through mineralocorticoid and glucocorticoid secreting tumours, respectively. Both are treated by surgery where possible. Pharmacological management is by inhibitors of dehydrogenation (trilostane) and hydroxylation (metyrapone) in the steroidogenic pathway. Tumours of the adrenal medulla (phaeochromocytoma) require alpha- and beta-blocker treatment to lower blood pressure (phenoxybenzamine) and reduce tachycardia (propanolol) before surgical removal. The thyroid gland secretes triiodothyronine (T3) and thyroxine (T4). Hypothyroidism arises through iodine deficiency, autoimmunity or surgery: treatment is by replacement of T3 and T4. Hyperthyroidism is also an autoimmune disease, commonly Graves’ disease. Treatment is by selective destruction of thyroid cells by radioiodine. Alternatively thioureylenes (carbimazole) are used to inhibit iodination of thyroglobulin, thereby reducing T3 and T4 synthesis. The parathyroid gland contributes to serum calcium homeostasis by secreting parathyroid hormone. Hyperparathyroidism leads to hypercalcaemia, which is reversed by surgery or calcitonin treatment. Hypercalcaemia of malignancy is managed by bisphosphonates, which reduce bone turnover. Hypoparathyroidism and vitamin D deficiency lead to hypocalcaemia, which is treated by calcium and vitamin D metabolite replacement.

Etomidate is commonly used for the facilitation of endotracheal intubation. While etomidate possesses multiple qualities that are beneficial in hemodynamically unstable patients who require a sedative or amnestic, its potential to negatively impact corticosteroid production is well-documented. Given the frequency of relative adrenal insufficiency observed in the critically ill and the increasing use of corticosteroids in patients with septic shock, an appraisal of the status of etomidate as an induction agent in patients with evolving or established septic shock is indicated. A review of the relevant literature suggests that its use in this setting may be harmful. It is proposed that, pending the performance of a randomized, controlled clinical trial, considerable caution should accompany its administration in patients with evolving or established septic shock. The potential role for concomitant empiric steroid replacement and the comparability of alternative induction regimens are also discussed

Aldosterone's main actions are to regulate intravascular volume and serum electrolytes by controlling sodium absorbtion and potassium excretion in the distal nephron. Inherited defects in aldosterone biosynthesis thus cause hypovolemia, hyponatremia and hyperkalemia. Defective aldosterone biosynthesis may be caused by congenital adrenal hyperplasia due to 21-hydroxylase (CYP21) deficiency, in which case cortisol biosynthesis is also affected, or as an isolated defect termed aldosterone synthase (corticosterone methyloxidase, CYP11B2) deficiency. Many mutations have been documented in each of these genes; in general enzymatic activity must be reduced to

Introduction Addison's disease is a rare chronic illness caused by adrenocortical insufficiency. Understanding the process of family adaptation to this chronic illness in a child will help practitioners enhance the ability of the child and family to cope with this stressful diagnosis. Method A qualitative descriptive case study methodology was used to explore the process of family adaptation to this chronic illness. Eight interviews were conducted with a newly diagnosed 11-year-old White girl with Addison's disease, along with her parents, grandparents, and siblings. Participant observations were made in the family's home. Drawings by the girl with Addison's Disease were included in the data analysis, along with an interview with the child. Results The overall theme of adaptation to this chronic illness is living a normal life. The family noted that after reaching some acceptance, they began learning how to manage the disease. This process was enhanced by seeking information about the disease and receiving the support of others; in addition, the child was affected by the acceptance of her peers. Discussion Recognizing factors that may influence the family's adjustment to the diagnosis of Addison's disease in a child will help to direct educational and support efforts by practitioners.

Stress from many sources, including pain, fever, and hypotension, activates the hypothalamic-pituitary-adrenal (HPA) axis with the sustained secretion of corticotropin and cortisol. Increased glucocorticoid action is an essential component of the stress response, and even minor degrees of adrenal insufficiency can be fatal in the stressed host. HPA dysfunction is a common and underdiagnosed disorder in the critically ill. We review the risk factors, pathophysiology, diagnostic approach, and management of HPA dysfunction in the critically ill.

To examine the incidence and response to treatment of adrenal insufficiency (AI) in high-risk postoperative patients.Prospective observational case series.Large urban tertiary-care surgical ICU (SICU).Adults55 years of age who required vasopressor therapy after adequate volume resuscitation in the immediate postoperative period.Each patient underwent a cosyntropin (ACTH) stimulation test; at the discretion of the clinical team, some patients were empirically given hydrocortisone (100 mg IV q8h for three doses) before serum cortisol values became available.Adrenal dysfunction (AD), defined as serum cortisol20 microg/dL at all time points, with Delta cortisol (60 min post-ACTH minus baseline) ofor = 9 microg/dL; functional hypoadrenalism (FH), defined as serum cortisol30 microg/dL at all time points or Delta cortisol (60 min post-ACTH minus baseline)or = 9 microg/dL; and AI, as the presence of either AD or FH.One hundred four patients were enrolled with a mean age (SD) of 65.2 +/- 16.9 years. AI (AD plus FH) was found in 34 of 104 patients (32.7%): AD was found in 9 patients (8.7%), FH in 25 patients (24%), and normal adrenal function in 70 patients (67.3%). The absolute eosinophil count was significantly higher in the combined AD and FH groups compared with the group with normal adrenal function (p0.05). Forty-six of 104 patients (44.2%) received hydrocortisone; 29 (63%) could be weaned from treatment with vasopressors within 24 h. This beneficial effect of hydrocortisone reached statistical significance in the FH group when compared with untreated patients (p0.031); a similar trend was seen in the AD group (p = 0.083). Mortality was also lower in the hydrocortisone-treated AI patients (5 of 23 [21%] vs 5 of 11 [45%] in those not receiving hydrocortisone; p0.01).There is a high incidence of AI among SICU patients55 years of age with postoperative hypotension requiring vasopressors. There is also a significant association between hydrocortisone replacement therapy, resolution of vasopressor requirements, and improved survival.

Transient left ventricular apical ballooning syndrome, also known as Takotsubo Cardiomyopathy (Broken Heart Syndrome) is increasingly being reported in the medical literature. Its clinical picture resembles of an acute coronary syndrome with transient apical dyskinesia and normal coronary arteries. We report here a case of Takotsubo cardiomyopathy in a patient with Addison disease with reversible cardiomyopathy. To the best of our knowledge there has been only one other reported case of this syndrome with Addison disease but with a different outcome.

Autoimmune Addison's disease (autoimmune adrenalitis) often occurs in autoimmune polyendocrinopathy syndromes APS1 (APECED) and APS2. Although the genetic background and etiology of the two syndromes is remarkably different, they both result in a similar autoimmune destruction of the adrenal cortex. Recently, the defective gene in APS1, AIRE (autoimmune regulator) was identified, whereas in APS2, the major genetic factor remains to be found in the human major histocompatibility complex haplotype (HLA) region. In addition to the genetic factors, the recent findings in genetics and immunity leading to the pathogenesis of adrenal autoimmunity in polyendocrinopathy syndromes are discussed.