Disseminated cytomegalovirus infection with bilateral adrenal pseudotumors masquerading as recurrent hematologic malignancy.

BACKGROUND: Mass-like lesions are an uncommon presentation of cytomegalovirus (CMV) disease. CASE: We report on a case of disseminated CMV disease with bilateral adrenal pseudotumors in a patient with a history of acute leukemia in remission. CONCLUSION: In the settings of advanced cancer therapy and organ transplantation, a high index of suspicion for CMV should be maintained for mass-like disease.

l-Lysine Acts as a Serotonin Type 4 Receptor Antagonist to Counteract In Vitro and In Vivo the Stimulatory Effect of Serotonergic Agents on Aldosterone Secretion in Man.

In the normal human adrenal gland, serotonin (5-HT) stimulates aldosterone secretion through the 5-HT4 receptor (5-HT4R). However, the physiological role of the serotonergic control of adrenocortical function is not known. In the present study, we have investigated the ability of l-Lysine, which has been shown to act as a 5-HT4 receptor antagonist, to counteract in vitro and in vivo the stimulatory effect of 5-HT4R agonists on aldosterone production. l-Lysine was found to inhibit aldosterone production induced by 5-HT and the 5-HT4R agonists BIMU8 from cultured human adrenocortical cells. The action of l-Lysine (4.95 g/day orally) on the adrenal cortex was also evaluated in 20 healthy volunteers in a double blind, cross-over, placebo controlled study. l-Lysine had no significant influence on basal plasma aldosterone levels and the aldosterone responses to upright posture, tetracosactide, and low sodium diet (10 mmol/day for 3 days). Conversely, l-Lysine significantly reduced the surge of plasma aldosterone induced by metoclopramide indicating that l-Lysine is able to efficiently antagonize the adrenal 5-HT4 receptors in vivo. These results suggest that l-Lysine supplementation may represent a new treatment of primary adrenal diseases in which corticosteroid hypersecretion is driven by overexpressed 5-HT4 receptors.

The challenge of bleeding in antiphospholipid antibody-positive patients.

Antiphospholipid antibody-positive patients can develop bleeding due to capillaritis, microthrombosis, antiprothrombin antibodies, thrombocytopenia, and/or excessive antithrombotic therapy. Clinical characteristics of patients, e.g., renal impairment, elderly, or concomitant medications, are closely related to the risk of bleeding. The management of bleeding in antiphospholipid antibody (aPL)-positive patients is challenging due to the baseline increased risk of thrombosis. If anticoagulation is stopped, it should be restarted as soon as possible once the acute bleeding is controlled; the continuation of anticoagulation despite active bleeding may be required in selected cases. High-dose corticosteroid is the mainstay treatment for diffuse alveolar hemorrhage, lupus anticoagulant-hypoprothrombinemia syndrome, and severe thrombocytopenia; immunosuppressive drugs are also required to improve the long-term outcomes. Hydrocortisone is critical in adrenal hemorrhage patients due to concomitant adrenal insufficiency; despite bleeding, anticoagulation should be maintained as much as possible. Plasma exchange should be considered in catastrophic antiphospholipid syndrome patients with concurrent bleeding. This article will review the causes of bleeding in aPL-positive patients as well as the management strategies.

Post-transplant lymphoproliferative disorder of the adrenal gland after allogeneic hematopoietic stem cell transplantation: report of two cases and literature review.

Post-transplant lymphoproliferative disorder (PTLD) is one of the life-threatening complications after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), and it is associated almost exclusively with Epstein-Barr virus (EBV). We herein report 2 cases of EBV-associated PTLD after allogeneic HSCT localized in the adrenal gland. Both patients developed adrenal tumor within 3 months after HSCT and were successfully treated with rituximab or tapering immunosuppressive agents. Both remained alive without recurrence. A literature review revealed 12 reported cases of PTLD involving the adrenal gland, but the adrenal gland was involved as one of the lesions of advanced-stage PTLD after SOT. To the best of our knowledge, this is the first report to show cases of isolated EBV-associated adrenal PTLD after HSCT. PTLD should be recognized as one of the causes of isolated adrenal tumor after HSCT.

[Unilateral adrenal tuberculosis: a case report].

Computed tomography (CT) performed for a 75-year-old man as a follow-up examination for deep vein thrombosis in October 2010 revealed a left adrenal mass (diameter, 8 mm). In December 2012, the adrenal mass increased to 28 mm in diameter, and he was referred to our department. Several blood examinations revealed that the adrenal mass was non-functioning, and only peripheral lesions were observed to be enhanced by using CT in the arterial phase. Malignancy was suspected due to the irregular shape and growth of the mass, and left adrenalectomy was performed in February 2013. The histopathological diagnosis was adrenal mycobacteriosis, and clinical diagnosis was adrenal tuberculosis. No other tuberculosis infection-related lesion was detected, and the patient was treated with multidrug antituberculous chemotherapy.

Addison's disease presenting with muscle spasm.

Primary hypoadrenalism has various causes and protean manifestation. We report a young female patient who presented with severe muscle spasm as her primary complaint. On evaluation she was found to be a case of Addison's disease secondary to adrenal tuberculosis. Her muscle spasm disappeared rapidly with replacement dose of glucocorticoid.

Adrenal histoplasmosis: unusual presentations.

BACKGROUND: Histoplasmosis has been sporadically reported from India. Though asymptomatic adrenal involvement has been described in patients with disseminated histoplasmosis; isolated adrenal involvement with adrenal insufficiency (AI) as the presenting manifestation of the disease is rare. PATIENTS AND METHODS: We describe 5 immunocompetent men (mean age 55.6 yrs) from a nonendemic area with adrenal histoplasmosis presenting with constitutional symptoms. Three patients had AI at presentation with bilateral adrenal involvement and the other two developed AI during the course of the illness and had unilateral adrenal mass . All the patients had histopathological/cytologically proven adrenal histoplasmosis. 18FDG-PET done in 3 patients helped in delineating the extent of the disease. Adrenalectomy was done in 2 patients who presented with unilateral adrenal mass. All these patients received Amphotericin B and/or itraconazole treatment which led to symptomatic improvement but AI persisted in all at the end of the follow up of 6 to 18 months. CONCLUSION: The diagnosis of adrenal histoplasmosis should be considered in patients presenting with constitutional symptoms and unilateral or bilateral adrenal mass/es with or without AI.

Waterhouse-Friderichsen Syndrome with Bilateral Adrenal Hemorrhage Associated with Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia in an Adult Patient with History of Intravenous Drug Use.

BACKGROUND Waterhouse-Friderichsen syndrome, also known as acute adrenal insufficiency due to adrenal gland hemorrhage, is an uncommon and frequently fatal condition classically presenting with fever, shock, rash, and coagulopathy. Although most often associated with Meningococcemia, many other etiologies have been implicated, including reports of Staphylococcus aureus infection on autopsy examinations. This report details an adult intravenous drug user with adrenal hemorrhage associated with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. CASE REPORT A 58-year-old man with a history of intravenous drug use presented to the hospital with weakness. Vitals were initially normal and exam findings were notable for decreased right-sided motor strength. Magnetic resonance imaging (MRI) revealed a cervical epidural abscess with spinal cord compression. Despite initiation of broad-spectrum antibiotics and intravenous fluids, the patient progressed to shock, requiring vasopressor administration, and his blood cultures later grew MRSA. Further imaging of the abdomen/pelvis was completed, revealing bilateral adrenal hemorrhage. Random cortisol at that time was 5.6 µg/dL, confirming a diagnosis of critical illness-related corticosteroid insufficiency in addition to likely septic and spinal shock. The patient was initiated on hydrocortisone with improvement in his hypotension. He was transitioned to prednisone and fludrocortisone in addition to 8 weeks of antibiotics after achieving clinical stability. CONCLUSIONS This report brings to attention the risk of adrenal hemorrhage and acute adrenal insufficiency as a sequela of the relatively common illness of Staphylococcus aureus bacteremia. As symptoms of adrenal insufficiency can overlap with septic shock related to the primary condition, this diagnosis requires a high index of suspicion in the critically ill patient.

Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis/Renal Failure, and Organomegaly (TAFRO) Syndrome with Bilateral Adrenal Hemorrhage in Two Caucasian Patients.

BACKGROUND Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome is a variant of idiopathic multicentric Castleman disease. Adrenal hemorrhage has rarely been reported in TAFRO syndrome, and previous cases have mainly been Asian patients. This report is of two Caucasian patients with TAFRO syndrome presenting with acute adrenal insufficiency due to bilateral adrenal hemorrhage. CASE REPORT Case 1 was a 19-year-old Caucasian man with no significant past medical history who was admitted with acute abdominal pain, vomiting, anorexia, and moderate weight loss. Case 2 was a 31-year-old Caucasian woman with no past medical history who was admitted to hospital with fever, dyspnea, thoracic and abdominal pain, polyarthralgia, and hypotension. Both patients had splenomegaly, mild lymphadenopathy, thrombocytopenia, acute kidney injury, and myelofibrosis. In both cases, lymph node biopsy histology showed mixed-type idiopathic multicentric Castleman disease. In both patients, a diagnosis of TAFRO was made, and they developed bilateral adrenal hemorrhage with adrenal insufficiency. Case 1 was treated with high-dose steroids, followed by tocilizumab infusion. Due to persistent thrombocytopenia, second-line treatment commenced with rituximab, but the patient relapsed two months later. Tocilizumab treatment was recommenced, which was followed by an immuno-allergic adverse event. He then had a good response to sirolimus. Case 2 died nine months after diagnosis due to acute respiratory distress. CONCLUSIONS Two cases of TAFRO syndrome presented with acute adrenal insufficiency due to bilateral adrenal hemorrhage. The symptoms were only partially controlled with tocilizumab, rituximab, and tacrolimus. Adrenal hemorrhage may be a specific manifestation of TAFRO syndrome.

What is the role of medical therapy in adrenal-dependent Cushing's syndrome?

Medical therapy to control hypercortisolism in adrenal Cushing's syndrome is currently not the first-line therapy. However, in many clinical scenarios like pre-surgical treatment, in patients who are not suitable candidates for surgery or in patients with bilateral hyperplasia, medical therapy can be important representing the only viable treatment option. Adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers have been used for many years: metyrapone, ketoconazole and mifepristone are in current use and effective. Mitotane can be used as well but is considered second-line therapy because of its high toxicity. Etomidate has a special position as emergency medication in severe hypercortisolism. New drugs are tested in prospective trials (levoketoconazole, osilidrostat and relacorilant) and might become effective alternatives to common drugs. Oher drugs - adrenal steroidogenesis inhibitors as well as glucocorticoid receptor antagonists - are currently tested in vitro.

Adrenal paracoccidioidomycosis / [Paracoccidiodomicosis suprarrenal].

Primary adrenal insufficiency is a defect in glucocorticoid, mineralocorticoid and sexual androgens production. Patients with this disorder have low cortisol levels and aldosterone deficiency with concomitant hyponatremia and hyperkalemia. The most common etiology of this disease is the production of antibodies against the enzyme 21 hydroxylase. Another common cause, particularly in low income countries, are infectious diseases. Several micro-organisms have been reported as a causal agent in adrenal insufficiency including Mycobacterium tuberculosis, Mycobacterium avium complex, Neisseria meningitidis, Pseudomonas aeruginosa, Haemophilus influenzae, cytomegalovirus, Pneumocystis jirovecii, Histoplasma capsulatum, Blastomyces dermatiditis, Cryptococcus neoformans, Cocciodiodes immitis, Nocardia spp. and Paracoccidioides brasiliensis. In this article, we present the computerized tomography and the adrenal biopsy of a patient with adrenal insufficiency. The final diagnosis was paracoccidioidomycosis.

La insuficiencia suprarrenal primaria es un defecto en la producción de glucocorticoides, mineralocorticoides y andrógenos sexuales. Los pacientes afectados por esta condición se caracterizan por concentraciones bajas de cortisol y deficiencia de aldosterona con hiponatremia e hiperpotasemia concomitantes. La etiología más común es el desarrollo de anticuerpos contra la enzima 21 hidroxilasa. Otra causa importante de la insuficiencia suprarrenal primaria son las enfermedades infecciosas, en especial en los países de bajos ingresos. Entre las causas infecciosas que se han descrito se encuentran: Mycobacterium tuberculosis, el complejo de Mycobacterium avium, Neisseria meningitidis, Pseudomonas aeruginosa, Haemophilus influenzae, citomegalovirus, Pneumocystis jirovecii, Histoplasma capsulatum, Blastomyces dermatiditis, Cryptococcus neoformans, Cocciodiodes immitis, Nocardia spp. y Paracoccidioides brasiliensis. En este artículo se presenta la imagen de la tomografía de un paciente que presentó falla suprarrenal, con masas en las glándulas suprarrenales, cuya biopsia permitió establecer el diagnóstico final de paracoccidioidomicosis.

Bilateral adrenal haemorrhage secondary to rivaroxaban in a patient with antiphospholipid syndrome.

A 46-year-old man with antiphospholipid syndrome (APS) and previous pulmonary embolism on anticoagulation with rivaroxaban was brought in to the hospital after a syncopal episode. He was found to be hypotensive and tachycardic and later admitted to the intensive care unit. Clinical presentation and laboratory findings were consistent with adrenal insufficiency. MRI revealed bilateral adrenal haemorrhage and he received appropriate steroid replacement therapy. Symptoms slowly subsided and anticoagulation regimen was changed to warfarin. Adrenal haemorrhage was likely caused by APS and rivaroxaban, which brings into question whether novel oral anticoagulants are safe in this patient population.

Comparison of corticoid substitution versus combined oral contraception administration in the treatment of non-classic adrenal hyperplasia: a prospective study.

OBJECTIVE: The clinical symptoms of non-classic adrenal hyperplasia (NCAH) are the same as those in patients with polycystic ovary syndrome (PCOS). The aim of our study was to compare conventional corticoid treatment of NCAH with the effect of combined oral contraception (COC) administration (used in treatment of PCOS) on clinical and laboratory parameters of NCAH. DESIGN: A prospective clinical study, cross-over design. MATERIAL AND METHODS: Since 1999 from 298 hyperandrogenic women, eight patients having 21-hydroxylase deficient NCAH have been identified. They were divided equally into two groups according to the order of application treatment modality (hydrocortison vs. COC). Effect of treatment of both modalities on clinical symptoms (hirsutism - FG score, acne, menstrual cycle) and laboratory parameters (testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulphate, sex hormone binding globulin (SHBG)) were evaluated. RESULTS: We observed the decrease of plasma androgens in both groups, which did not differ significantly. Significant increase of SHBG (i.e. decrease of free androgens) was, however, documented in each period with COC administration. Not surprisingly, improvement of the most frequent clinical symptom of NCAH in our study group, oligomenorrhea, was also more apparent in COC. Hirsutism was only a minor problem in our group that did not allow to evaluate treatment effect of both the modalities CONCLUSION: Our results indicate that ovarian suppression by COC administration can effectively suppress androgen production and improve the most frequent clinical symptom (irregular cycle) in patients with NCAH, so can be successfully used for the treatment at least under basal conditions. Whether corticosteroid substitution can be limited to patients with inadequate response to COC on plasma androgen levels or with signs of adrenal insufficiency requires further data.

Pneumocystis jirovecii infection of bilateral adrenal glands in an immunocompetent adult: a case report.

Pneumocystis jirovecii (PJ) infection is one of the most common opportunistic infections occurring in patients with HIV/AIDS and other immunocompromised states. It is not known to cause clinically significant illness in immunocompetent hosts. We report a 48-year-old HIV-negative, diabetic male who presented with fever and adrenal insufficiency. Abdominal sonography and PET-CT revealed bilateral enlarged adrenal glands with peripheral enhancement and central necrosis. An endoscopic ultrasound-guided fine-needle aspiration cytology of the left adrenal gland demonstrated well-defined, round cysts of PJ. There was no evidence of pulmonary involvement. The response to first-line treatment was poor and the patient responded to second-line treatment for Pneumocystis infection.

Spontaneous heparin-induced thrombocytopenia syndrome presenting as bilateral adrenal infarction after knee arthroplasty.

Adrenal gland infarction resulting from adrenal vein thrombosis is an infrequently recognised entity with a limited differential diagnosis. When bilateral, it can result in acute life-threatening adrenal failure. Heparin-induced thrombocytopenia (HIT) is an antibody-mediated, prothrombotic state that represents an important cause of adrenal vein thrombosis leading to associated infarction. Sometimes, the clinical picture of HIT-including the presence of HIT antibodies-occurs despite absence of proximate heparin exposure ('spontaneous HIT syndrome'). We report a case of nearly missed adrenal failure secondary to bilateral adrenal infarction that evolved during the second week following knee arthroplasty (a known trigger of spontaneous HIT syndrome). The combination of bilateral adrenal infarction, thrombocytopenia and presence of platelet-activating HIT antibodies not explainable by preceding heparin exposure led to a diagnosis of postknee arthroplasty spontaneous HIT syndrome. The case also highlights the clinical and laboratory findings associated with rapidly progressive acute adrenal failure.

Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development.

Corticotropin releasing factor (CRF) is a major integrator of adaptive responses to stress. Two biochemically and pharmacologically distinct CRF receptor subtypes (CRFR1 and CRFR2) have been described. We have generated mice null for the CRFR1 gene to elucidate the specific developmental and physiological roles of CRF receptor mediated pathways. Behavioral analyses revealed that mice lacking CRFR1 displayed markedly reduced anxiety. Mutant mice also failed to exhibit the characteristic hormonal response to stress due to a disruption of the hypothalamic-pituitary-adrenal (HPA) axis. Homozygous mutant mice derived from crossing heterozygotes displayed low plasma corticosterone concentrations resulting from a marked agenesis of the zona fasciculata region of the adrenal gland. The offspring from homozygote crosses died within 48 hr after birth due to a pronounced lung dysplasia. The adrenal agenesis in mutant animals was attributed to insufficient adrenocorticotropic hormone (ACTH) production during the neonatal period and was rescued by ACTH replacement. These results suggest that CRFR1 plays an important role both in the development of a functional HPA axis and in mediating behavioral changes associated with anxiety.

[Current views on the role of dehydroepiandrosterone in physiology, pathology and therapy]. / Wspólczesne poglady na temat roli dehydroepiandrosteronu w fizjologii, patologii i terapii.

Dehydroepiandrosterone (DHEA) and its sulfate metabolite (DHEAS) are the major androgens secreted by the human adrenal gland. The decline in their production is the most characteristic age-related change in the adrenal cortex. This process, known as 'adrenopause' may contribute to the increased incidence of atherosclerosis, cancer, or dementia in older people. The possibility of using DHEA in management has attracted considerable attention over recent years. Whereas DHEA therapy seems to be effective in treating patients with adrenal insufficiency and systemic lupus erythematosus, clinical studies investigating the potential efficacy of DHEA therapy in multiple other disorders (Alzheimer disease, depression, cardiovascular disease, osteoporosis, sexual dysfunctions) have not provided consistent results. Further research is also needed to better assess the efficacy and safety of DHEA supplementation in patients with advanced age. This review evaluates current understanding of physiology and pathology of DHEA production and summarizes the possible therapeutic value of this hormone.

[Bilateral adrenal tuberculosis: about a case]. / Tuberculose surrénalienne bilatérale: à propos d'un cas.

Isolated adrenal tuberculosis accounts for less than 2% of adrenal incidentalomas. This is the most frequent infectious cause of adrenal insufficiencies. We report the case of a 53-year old patient with no previous medical history presenting with adrenal insufficiency with slow progression over six months. Physical examination didn't show any mass or hepatosplenomegaly. Blood pressure was 120/60 mmHg. Laboratory tests didn't show inflammatory syndrome. LDH level was normal. CT scan showed bilateral hypertrophy of the adrenal glands characterized by calcifications. Intradermo tuberculin reaction was positive at 25mm. The analyses to detect Koch's bacillus in the sputum and in the urine were negative. Quantiferon® test was positive. Trial antibacillar treatment was started with clinical improvement and 5kg weight gain in 12 months. Hormonal assays were low.