Autoimmune polyglandular syndrome]

Among many etiologies for hypoparathyroidism, one of the inheritable forms of hypoparathyroidism, called as autoimmune polyglandular syndrome (APS), appears as a complex of hypofunction of several endocrine glands, candidiasis, pernicious anemia and vitiligo. Idiopathic hypoparathyroidism in APS typically presents by 20 years of age. Among the three most components of APS I, candidiasis is usually the first manifestation. Hypoparathyroidism almost invariably precedes the onset of Addison's disease. One should remember that Addison's disease can mask the presence of hypoparathyroidism and that glucocorticoid replacement therapy alone can cause hypocalcemic crisis.     

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

Introduction: 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. Aims: To evaluate the HPA axis in patients with APS. Methods: 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. Results: 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. Conclusions: 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.     

Epigastric pain as presentation of an addisonian crisis in a patient with Schmidt syndrome

A 39-year-old woman presented with a 10-day history of epigastric pain accompanied by persistent fatigue and loss of appetite for 3 months. She had presented several weeks earlier with adhesive capsulitis, treated by local infiltration of corticosteroids. She was not taking any other medications. Results of heart, lung, and abdominal examinations were unremarkable, except for mild epigastric tenderness. Purple stretch marks were observed on examination of the skin. The only blood chemistry abnormalities were hyponatremia (125 mEq/L) and hyperkalemia (6.8 mEq/L). Based on the clinical and biologic picture, adrenal insufficiency was suspected. The patient was transferred to the intensive care unit and received hydrocortisone intravenously for 3 days. She was then given oral hydrocortisone and fludrocortisone. Biologic abnormalities reversed entirely; the final diagnosis was primary autoimmune adrenal insufficiency (Addison's disease) associated with autoimmune hypothyroidism (Schmidt syndrome). Adrenal insufficiency should be considered in patients with abdominal pain, especially when associated with electrolyte abnormalities.     

Infectious causes of adrenal insufficiency

More than 150 years ago, Thomas Addison first described the clinical features and pathogenesis of adrenal insufficiency. At that time, tuberculosis was the most common cause of this disease. The pathway to diagnosis and treatment of Addison's disease has been well described. However, determining the cause of the disorder remains a challenge. It is important to consider recently described infectious agents in the pathogenesis of Addison's disease. Mycobacterial, bacterial, viral, and fungal infections may lead to the development of adrenal insufficiency. Skin, pulmonary, and imaging findings can aid the clinician in making a prompt diagnosis of specific infections, which is crucial because early identification of infectious causes of Addison's disease may enable recovery of adrenal function. This review describes the clinical presentations of the multiple infectious causes of adrenal insufficiency.     

Polyglandular autoimmune syndrome, type 2

We have described two patients with Addison's disease and associated endocrinopathies, a condition termed polyglandular autoimmune (PGA) syndrome, type 2. One of our patients also had autoimmune hypothyroid disease, and the other had premature gonadal failure and Hashimoto's thyroiditis. This syndrome shows that glandular disorders tend to occur together. It has been suggested that an HLA-associated genetic predisposition coupled with environmental factors triggers an autoimmune process resulting in glandular hypofunction or hyperfunction. We stress the necessity for evaluation of every individual with idiopathic Addison's disease for associated endocrinopathies.     

Addisonian crisis due to adrenal gland metastasis in Hodgkin's disease

Adrenal insufficiency or Addison's disease is a rare illness associated with multiple pathology. We describe the case of a 61-year-old male with Hodgkin's disease and metastases in both adrenal glands who was diagnosed with adrenal insufficiency as a result of an acute addisonian crisis.     

Studies on Auditory Thresholds in Normal Man and in Patients with Adrenal Cortical Insufficiency: The Role of Adrenal Cortical Steroids

Auditory thresholds for sinusoidal tones were determined in eight patients with adrenal cortical insufficiency (four with Addison's disease and four with panhypopituitarism) and compared to those in normal volunteers. In adrenal cortical insufficiency (ACI) the auditory detection sensitivity is significantly more acute than that of normal subjects over most of the frequency range, but especially in the region of greatest hearing sensitivity of normal subjects, 1,000 to 2,000 cycles per second (cps).     

Tuberculous Addison's disease

Addison's disease is a possible diagnosis in any patient who presents with weakness, weight loss, hyperpigmentation, hyponatremia, and hypotension. Laboratory findings, including depressed levels of cortisol and aldosterone, help to confirm the diagnosis. Computed tomography may reveal adrenal calcification and abnormal-sized adrenal glands. In most cases, autoimmune destruction of the adrenal cortex is the cause of Addison's disease; however, as in the patient described here, tuberculosis is a possible cause.     

Receptors, antibodies, and disease

Abnormal antibody production is now recognized as the basis of specific endocrine and neurological diseases and their complications. Among the autoimmune diseases, the best understood from a mechanistic point of view are myasthenia gravis, Graves' disease, several variants of insulin resistance, and a variant of bronchial asthma. In each of these human disorders, the clinical symptoms can be traced to the actions of antireceptor antibodies produced by a deranged immune system. The autoantibodies produced in these diseases are functionally heterogeneous. They may produce the clinical symptoms of hormone or neurotransmitter insufficiency either by blocking the binding of these agents to target cell surface receptors or by accelerating the internalization and degradation of these receptors. In other cases, the autoantibodies may produce the clinical signs of hormone excess by mimicking the actions of the hormone, in an uncontrollable fashion. In some cases, functionally different types of autoantibodies will appear in the same patient at different stages of the disease. For all of these autoantibodies, of whatever function, assays for their presence in serum are available, in forms suitable for clinical chemists, as well as for researchers; these will be described in this review. In addition to the known anti-receptor autoimmune diseases, there are a large number of other autoimmune diseases for which there is fragmentary evidence that their clinical symptoms have an anti-receptor autoantibody etiology. Several examples of this group will be discussed, and assays suitable for establishing the presence of anti-receptor antibodies in the sera of such patients will be provided. The disorders to be considered are: type I diabetes mellitus, chronic atrophic gastritis, autoimmune Addison's disease, autoimmune hypoparathyroidism, type II pseudohypoparathyroidism, resistant ovary syndrome, connective tissue diseases, and the HLA-B8/DR3 antigen haplotype as a potential marker for autoimmune diseases of the anti-receptor type.     

Addisonian crisis precipitated by thyroxine therapy: a complication of type 2 autoimmune polyglandular syndrome

Hypothyroidism is a common condition. Rarely, it may occur in combination with autoimmune failure of other endocrine glands (autoimmune polyendocrinopathy syndrome type 2, previously known as Schmidt's syndrome). In such cases, restoring normal thyroid function may precipitate adrenal failure. Clinicians should have a high index of suspicion for this condition in patients with Addison's disease, those with a family history of autoimmune endocrine gland failure, patients with one autoimmune endocrine disease who develop nonspecific or serious illness, and patients with type 1 diabetes mellitus whose insulin requirements drop without obvious explanation.     

Polyglandular type I autoimmune syndrome]

Two HLA-identical sisters have developed the full picture of type I polyglandular autoimmune syndrome over a period of 12 years. Both girls have hypoparathyroidism and Addison's disease. One of them additionally developed diabetes mellitus, hypergonadotropic hypogonadism and hypothyroidism. Autoantibodies to the adrenal, parathyroid and thyroid glands are present in both patients, as well as antinuclear antibodies. HLA associations have been described recently for the type I polyglandular autoimmune syndrome, but this could not be confirmed in the present two cases. Although we assume that the same genetic defect is present in both girls, additional factors to the genetic disposition are important for the clinical expression of the disease. The linkage of the disease-causing gene with the HLA region is not very close.     

Endocrine disorders: causes of hyponatremia not to neglect

Hyponatremia is a common electrolyte abnormality with the potential for significant morbidity and mortality. Endocrine disorders, including adrenal deficiency and hypothyroidism, are uncommon causes of hyponatremia. Primary adrenal insufficiency (i.e. Addison's disease) may well be recognized by clear hall-marks of the disease, such as pigmentation, salt craving, hypotension, and concomitant hyperkalemia. Addison's disease is an important diagnosis not to be missed since the consequences can be grave. On the other hand, hypothyroidism and secondary adrenocortical insufficiency originating from diseases of the hypothalamus and/or pituitary (hypopituitarism) require a high index of suspicion, because the clinical signs can be quite subtle. This review focuses on clinical and pathophysiological aspects of hyponatremia due to endocrine disorders.     

Reversible cardiomyopathy in a child with Addison's disease

An 11-year-old boy in acute adrenal crisis was subsequently diagnosed with Addison's disease and presumably had an unrecognized preceding chronic adrenal insufficiency. His adrenal insufficiency and hypovolemic shock were promptly diagnosed and treated in the emergency room. However, 24 h later, signs of congestive heart failure developed and an echocardiogram revealed cardiomyopathy. He responded to i.v. dopamine and his cardiomyopathy resolved over some days. Acute adrenal insufficiency and actual ventricular dysfunction had not been described in humans until last year; this is the second reported case of cardiomyopathy in a patient with acute adrenal insufficiency.     

Addison's disease

Addison's disease is an uncommon endocrine condition manifested by a variety of nonspecific symptoms, such as malaise, anorexia and nausea. Symptoms usually do not occur until most of the adrenal gland has been destroyed. Autoimmune disease has surpassed tuberculosis as the primary cause of Addison's disease. Nevertheless, tuberculosis still accounts for a significant proportion of cases. The rapid adrenocorticotropic hormone (ACTH) stimulation test is useful for identifying adrenal insufficiency. Maintenance therapy consists of hydrocortisone and fludrocortisone.     

TNF mediates a murine model of Addison's crisis

Addison's crisis is the most serious complication of adrenal insufficiency. To elucidate the mechanism of this disorder following infection, the role of TNF in adrenalectomized murine models of Addison's crisis and Addison's disease (chronic hypoglucocorticoidism) were examined. Adrenalectomy conferred a 40-fold increased sensitivity to the lethal effects of lipopolysacharride (LPS) (P < .001). Enhanced sensitivity to LPS was found to increase with duration of adrenal insufficiency (P < .02). Enhanced lethality to heat-killed Streptococcus pneumonia was also demonstrated (P < 0.02). Necropsy of endotoxin-killed adrenalectomized mice demonstrated similar pathologic findings to those found by others when the control mice were administered a lethal dose of either LPS or TNF. Adrenalectomized TNF receptor Ia and Ib double null mice were demonstrated to be resistant to the lethal effects of LPS (P < 0.02). Pretreatment with anti-TNF, but not control antisera, was found to prevent death in LPS-treated wild-type adrenalectomized mice as well (P < 0.02). Studies into the mechanism by which TNF was precipitating Addison's crisis demonstrated enhanced sensitivity to TNF (3-fold; P < 0.02), and a marked increase in serum TNF concentration (approximately 5-fold; P < 0.001) following LPS challenge. The effect of TNF upon long-term survival in adrenalectomized mice was examined in TNF-receptor Ia- and Ib-deficient mice. Deficiencies in either the TNF-receptor Ia or Ib was noted to confer a survival advantage relative to colony controls following adrenalectomy (P < 0.02). In summary, both LPS-induced Addison's crisis and chronic adrenal insufficiency are disorders of TNF disregulation. Based upon these data, therapeutic strategies targeted at controlling TNF in adrenal insufficiency are suggested.     

Epidermolysis bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen.

Epidermolysis bullosa acquisita (EBA) is a severe, chronic blistering disease of the skin. EBA patients have circulating and tissue-bound autoantibodies to a large (Mr = 290,000) macromolecule that is localized within the basement membrane zone between the epidermis and dermis of skin, the site of blister formation. The "EBA antigen" is known to be distinct from laminin, heparan sulfate proteoglycan, fibronectin, the bullous pemphigoid antigen, elastin, and collagen types I, II, III, IV, and V. Sera from patients with EBA, two monoclonal antibodies to the EBA antigen, and a monoclonal antibody to the carboxyl terminus of type VII procollagen identically label human amnion and skin by immunofluorescent and immunoelectron microscopy. Western immunoblots of the EBA antigen extracted from skin and of type VII procollagen labeled with the above sera and antibodies are identical. None of the sera or antibodies labels Western blots of pepsinized type VII collagen which is missing the globular amino and carboxyl terminal domains. These data show that the EBA antigen is the carboxyl terminus of type VII procollagen.     

POLYSEROSITIS AS A RARE COMPONENT OF POLYGLANDULAR AUTOIMMUNE SYNDROME TYPE II

Polyglandular autoimmune (PGA) syndromes (types I and II) may affect various endocrine and non-endocrine organs in the body. In the commoner PGA type II, primary adrenal insufficiency, autoimmune thyroid disease and type I diabetes mellitus are the most frequent manifestations. Serositis with pericardial or pleural involvement is not a well known component of the disease. Here, we report a 21-year-old man who first presented with a pleuropericardial effusion and Graves' disease, and who then developed type I diabetes mellitus.     

Addison's disease with enlarged adrenal glands in sonography and computer tomography. Differential diagnostic considerations based on 2 cases of tuberculous adrenalitis

One of the major causes of chronic adrenal insufficiency (Addison's disease) is tuberculous adrenalopathy. Since sonography and computed tomography have become generally available in recent years and are of potential help in the diagnosis of this disease the merits of these methods are discussed in the light of 2 cases of adrenal tuberculosis, followed by a review of the literature. Adrenal calcification is the most significant, although not specific sign of adrenal insufficiency due to tuberculosis. Computed tomography has proven to be the method of choice in the non-invasive diagnosis of tuberculous adrenalopathy and in the monitoring of tuberculostatic treatment in this disease. Sonography is helpful as a preliminary investigation.     

The antiphospholipid syndrome]

Antiphospholipid antibodies such as anticardiolipin antibodies and lupus anticoagulant are frequently detected in sera from patients with systemic lupus erythmatosus and from those with related autoimmune disorders. Thromboembolic manifestations, fetal losses or thrombocytopenia in association with antiphospholipid antibodies, are hallmarks of the antiphospholipid syndrome (APS). Recent studies indicates that anticardiolipin antibodies bind to beta 2-glycoprotein I and that a part of lupus anticoagulant binds to beta 2-glycoprotein I or to prothrombin. Antiphospholipid antibodies might induce thrombosis by altering the function of vascular endothelial cells or by accelerating the progression of atherosclerosis. Warfarin, heparin or low dose aspirin have been recommended to prevent recurrent episodes of thrombosis in patients with the APS.