An unusual cause of adrenal insufficiency with elevation of 17-hydroxyprogesterone: case report.

BACKGROUND: We present an intriguing case of primary adrenal lymphoma, with associated primary adrenal insufficiency (PAI), in a patient presenting a transitory partial 21-hydroxylase deficiency during the active phase of the adrenal disease. CASE PRESENTATION: An 85-years old woman was referred because of worsening asthenia, lumbar pain, generalized myalgia and arthralgia. During investigations a computed tomography (CT) scan evidenced two large bilateral adrenal masses, highly suspicious for primary adrenal tumor. The hormonal assessment revealed very low levels of morning plasma cortisol and 24-h urinary cortisol, elevated ACTH levels with low plasma concentration of aldosterone, pointing to the diagnosis of PAI. After diagnosis of PAI our patient started glucocorticoid and mineralcorticoid replacement therapy with clinical benefit. In order to further characterize the adrenal lesions, adrenal biopsy, was performed. The histology revealed a high grade non-Hodgkin lymphoma with an immunophenotype consistent with intermediate aspects between diffuse large B-cell and Burkitt lymphoma, with a high proliferation index (KI-67 > 90%). The patient received chemotherapy with epirubicin, vincristine, cyclophosphamide, and rituximab, associated with methylprednisolone that resulted in a complete clinical and radiological remission within one year. After 2 years from the diagnosis and a total of 6 cycles of rituximab, the patient was in good clinical condition and was taking only the replacement therapy for PAI. The patient initially presented also a slight increase of 17-hydroxyprogesterone (17-OHP) for age that normalize after resolution of lymphoproliferative disease. CONCLUSIONS: In the presence of bilateral adrenal disease and/or in the presence of signs and symptoms of PAI clinicians must exclude the presence of PAL. The evidence of elevated ACTH-stimulated 17-OHP levels also in patients with other adrenal masses, together with the detection of elevated basal 17-OHP levels in our patient make it more plausible, in our view, an effect of the lesion on the "healthy" adrenal tissue residue than a direct secretory activity by the adrenal tumor.

Acute adrenal insufficiency: an aide-memoire of the critical importance of its recognition and prevention.

Adrenal crisis is a life-threatening emergency that causes significant excess mortality in patients with adrenal insufficiency. Delayed recognition by medical staff of an impending adrenal crisis and failure to give timely hydrocortisone therapy within the emergency department continue to be commonly encountered, even in metropolitan teaching hospitals. Within the authors' institutions, several cases of poorly handled adrenal crises have occurred over the last 2 years. Anecdotal accounts from members of the Addison's support group suggest that these issues are common in Australia. This manuscript is a timely reminder for clinical staff on the critical importance of the recognition, treatment and prevention of adrenal crisis. The manuscript: (i) outlines a case and the clinical outcome of sub-optimally managed adrenal crisis, (ii) summarises the clinical features and acute management of adrenal crisis, (iii) provides recommendations on the prevention of adrenal crisis and (iv) provides guidance on the management of 'sick days' in patients with adrenal insufficiency.

The contribution of online peer-to-peer communication among patients with adrenal disease to patient-centered care.

BACKGROUND: Addison's disease and Cushing's syndrome are rare. The Dutch Adrenal Society offers an online forum for Dutch adrenal patients to meet and communicate. However, little is known about the added value such a forum has for the delivery of patient-centered care. OBJECTIVE: Our aim was to analyze the purposes of online patient-to-patient forum conversations, within the context of patient-centered care. METHODS: For this study a consecutive sample of 300 questions ("threads") from the past 3.5 years was selected from the forum. The content of these patient-driven questions was analyzed based on the dimensions of patient-centeredness of the Picker Institute. This analysis was performed using ATLAS.ti. RESULTS: From the 390 questions analyzed, 80.8% (N=315) were intended to gain more information about the disease, the treatment, and to verify if other patients had similar complaints. To a much lesser extent (38/390, 9.7%), questions expressed a call for emotional support. Patients answered primarily by giving practical tips to fellow patients and to share their own experiences. CONCLUSIONS: On an online patient forum for Cushing's syndrome and Addison's disease, patients appear to primarily gain knowledge and, to a lesser extent, emotional support from their peers. This experience-based knowledge has become a very important information source. As such, patients can make a substantial contribution to the creation of patient-centered care if this knowledge is integrated into the care provided by health care professionals.

Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency.

Primary adrenal insufficiency (PAI), or Addison's disease, is a rare, potentially deadly, but treatable disease. Most cases of PAI are caused by autoimmune destruction of the adrenal cortex. Consequently, patients with PAI are at higher risk of developing other autoimmune diseases. The diagnosis of PAI is often delayed by many months, and most patients present with symptoms of acute adrenal insufficiency. Because PAI is rare, even medical specialists in this therapeutic area rarely manage more than a few patients. Currently, the procedures for diagnosis, treatment and follow-up of this rare disease vary greatly within Europe. The common autoimmune form of PAI is characterized by the presence of 21-hydroxylase autoantibodies; other causes should be sought if no autoantibodies are detected. Acute adrenal crisis is a life-threatening condition that requires immediate treatment. Standard replacement therapy consists of multiple daily doses of hydrocortisone or cortisone acetate combined with fludrocortisone. Annual follow-up by an endocrinologist is recommended with the focus on optimization of replacement therapy and detection of new autoimmune diseases. Patient education to enable self-adjustment of dosages of replacement therapy and crisis prevention is particularly important in this disease. The authors of this document have collaborated within an EU project (Euadrenal) to study the pathogenesis, describe the natural course and improve the treatment for Addison's disease. Based on a synthesis of this research, the available literature, and the views and experiences of the consortium's investigators and key experts, we now attempt to provide a European Expert Consensus Statement for diagnosis, treatment and follow-up.

Impact of coronavirus disease 2019 on patients with primary adrenal insufficiency: a cross-sectional study.

Objective: Patients with primary adrenal insufficiency (PAI) are thought to be particularly vulnerable to coronavirus disease 2019 (COVID-19); however, little is known about its true impact on this group. We assessed morbidity and health promotion attitudes during the pandemic amongst a large cohort of patients with PAI. Design: Cross-sectional, single-centre study. Methods: In May 2020, COVID-19 advice on social distancing and sick-day rules was distributed to all patients with PAI registered with a large secondary/tertiary care centre. A semi-structured questionnaire was used to survey patients in early 2021. Results: Of 207 contacted patients, 162 responded (82/111 with Addison's disease, AD; 80/96 with congenital adrenal hyperplasia, CAH). Patients with AD were older than those with CAH (median age 51 vs 39 years; P < 0.001) and had more comorbidities (Charlson comorbidity index ≥2 47.6% vs 10.0%; P< 0.001). By the time of the survey, 47 patients (29.0%) had been diagnosed with COVID-19, the second commonest cause of sick-day dosing during the study and the leading trigger of adrenal crises (4/18 cases). Patients with CAH had a higher risk of COVID-19 compared to AD (adjusted odds ratio 2.53 (95% CI 1.07-6.16), P= 0.036), were less inclined to have the COVID-19 vaccine (80.0% vs 96.3%; P = 0.001), and were less likely to have undergone hydrocortisone self-injection training (80.0% vs 91.5%; P = 0.044) or wear medical alert jewellery (36.3% vs 64.6%; P = 0.001). Conclusions: COVID-19 was a principal trigger for adrenal crises and sick-day dosing in patients with PAI. Despite a higher risk of COVID-19, patients with CAH showed less engagement with self-protective attitudes. Significance statement: We conducted a cross-sectional study on a large and well-characterised group of patients with PAI and demonstrated that COVID-19 was a leading cause of morbidity during the early phases of the pandemic. Patients with AD were older and had a greater burden of comorbidity than those with CAH, including non-adrenal autoimmune disorders. However, patients with CAH were more likely to develop COVID-19 and demonstrated reduced engagement with healthcare services and health promotion strategies.

[X-Linked Adrenoleukodystrophy or the Management of Rare Diseases in the General Practice]. / Die X-chromosomale Adrenoleukodystrophie oder vom Umgang mit seltenen Erkrankungen in der hausärztlichen Praxis.

X-Linked Adrenoleukodystrophy or the Management of Rare Diseases in the General Practice Abstract. We report on a 48-year-old patient with X-linked adrenoleukodystrophy with slowly progressive leg-accentuated spastic paraparesis, vegetative dysfunction with bladder and sexual dysfunction, and primary adrenal insufficiency. The diagnosis of adrenomyeloneuropathy, the adult form of adrenoleukodystrophy, and Addison's disease was made at the age of 20 by evidence of an increased concentration of long-chain fatty acids in the plasma. The therapy is symptom-oriented.

Addison's disease in antiphospholipid syndrome: a rare complication.

Addison's disease (AD) is the most common endocrine manifestation of antiphospholipid syndrome (APS), but it remains a very rare complication of the syndrome. It is caused by adrenal venous thrombosis and consequent hemorrhagic infarction or by spontaneous (without thrombosis) adrenal hemorrhage, usually occurring after surgery or anticoagulant therapy. We present a clinical case of a 36-year-old female patient with a previous diagnosis of APS. She presented with multiple thrombotic events, including spontaneous abortions. During evaluation by the third episode of abortion, a CT imaging revealed an adrenal hematoma, but the patient was discharged without further investigation. A few weeks later, she presented in the emergency department with manifestations suggestive of adrenal insufficiency. Based on that assumption, she started therapy with glucocorticoids, with significant clinical improvement. After stabilization, additional investigation confirmed AD and excluded other etiologies; she also started mineralocorticoid replacement. This case illustrates a rare complication of APS that, if misdiagnosed, may be life threatening. A high index of suspicion is necessary for its diagnosis, and prompt treatment is crucial to reduce the morbidity and mortality potentially associated. Learning points: AD is a rare but life-threatening complication of APS. It is important to look for AD in patients with APS and a suggestive clinical scenario. APS must be excluded in patients with primary adrenal insufficiency and adrenal imaging revealing thrombosis/hemorrhage. Glucocorticoid therapy should be promptly initiated when AD is suspected. Mineralocorticoid replacement must be started when there is confirmed aldosterone deficiency. Hypertension is a common feature of APS; in patients with APS and AD, replacement therapy with glucocorticoids and mineralocorticoids may jeopardize hypertension management.

Autoimmune Polyglandular Syndrome type 2

SUMMARY Autoimmune polyglandular syndrome type 2 (APS 2) is defined by the presence of Addison's disease (AD) associated with autoimmune thyroid disease and/or Type 1 diabetes mellitus (T1DM). It is a rare disease, affecting about 1.4-2 cases/100,000 inhabitants. Its less frequent clinical presentation is the combination of AD, Graves' disease, and T1DM. We present the case of a 42-year-old woman with a history of total thyroidectomy due to Graves' disease, type 2 diabetes mellitus, and hypertension, who sought the ED due to asthenia, dizziness, nausea, and vomiting. She reported having stopped antihypertensive therapy due to hypotension and presented a glycemic record with frequent hypoglycemia. On physical examination, she had cutaneous hyperpigmentation. She had no leukocytosis, anemia, hypoglycemia, hyponatremia or hyperkalemia, and a negative PCR. Serum cortisol <0.5 ug/dl (4,3-22,4), urine free cortisol 9 ug/24h (28-214), ACTH 1384 pg/mL (4,7-48,8), aldosterone and renin in erect position of 0 pg/ml (41-323) and 430.7 uUI/ml (4.4-46.1) respectively. Quantiferon TB was negative; computerized axial tomography of the adrenals showed no infiltrations, hemorrhage, or masses. The 21-hydroxylase antibody assay was positive. B12 vitamin was normal, anti-GAD antibodies were positive, anti-insulin, anti-IA2, and anti-transglutaminase antibodies were all negative. The patient started insulin therapy and treatment for AD with prednisolone and fludrocortisone with good clinical response. This case aims to alert to the need for high clinical suspicion in the diagnosis of AD. Since this is a rare autoimmune disease, it is important to screen for other autoimmune diseases in order to exclude APS.

RESUMO A síndrome poliglandular autoimune tipo 2 (SPGA2) é definida pela presença de doença de Addison (DA) associada à doença tiroideia autoimune e/ou diabetes mellitus tipo 1 (DMT1). Trata-se de uma doença rara, afetando cerca de 1,4-2 casos/100.000 habitantes. A apresentação clínica menos frequente é a combinação de DA, doença de Graves e DMT1. Apresenta-se mulher de 42 anos, com antecedentes de tiroidectomia total por doença de Graves, diabetes mellitus tipo 2 e hipertensão, que recorre ao SU por quadro arrastado de astenia, emagrecimento, tonturas, náuseas e vômitos. Referia ter suspendido terapêutica anti-hipertensora por hipotensão e apresentava registro glicêmico com hipoglicemias frequentes. Ao exame físico, salientava hiperpigmentação cutânea. Analiticamente sem leucocitose, anemia, hipoglicemia, hiponatremia ou hipercaliemia, PCR negativa. Cortisol sérico matinal <0,5 ug/dl (4,3-22,4), cortisol livre na urina 9 ug/24h (28-214), ACTH 1.384 pg/mL (4,7-48,8), aldosterona e renina em posição ereta de 0 pg/mL (41-323) e 430,7 uUI/mL (4,4-46,1), respectivamente. Realizado estudo complementar para averiguar causa de insuficiência suprarrenal primária. Quantiferon TB negativo, tomografia axial computadorizada das suprarrenais sem infiltrações, hemorragia ou massas. Anticorpos anti-21-hidroxilase positivos. Foi aprofundada a investigação com vitamina B12 normal, anti-GAD positivo, anti-insulina, anti-IA2, antitransglutaminase, negativos. Nesse contexto, a doente iniciou insulinoterapia e tratamento dirigido para a DA com prednisolona e fludrocortisona, com boa resposta clínica. Este caso tem como objetivo alertar para a necessidade de elevada suspeição clínica no diagnóstico de DA. Sendo esta uma doença autoimune rara, é importante rastrear outras doenças autoimunes no sentido de excluir SPGA.

Erythema induratum of Bazin associated with Addison's disease: first description / Eritema indurado de Bazin associado à doença de Addison: primeira descrição

CONTEXT: Erythema induratum of Bazin (EIB) is considered to be a tuberculid reaction and consists of recurrent painful nodules. The differential diagnosis includes diseases like nodular vasculitis, perniosis, polyarteritis nodosa and erythema nodosum. CASE REPORT: We report the case of a woman with EIB who developed Addison's disease during treatment with anti-tuberculosis drugs with good response to glucocorticoid replacement. The diagnosis was obtained through the clinical picture, positive tuberculin test and positive BCG (bacillus Calmette-Guérin) test on the histological sample. Anti-tuberculosis drugs and glucocorticoid replacement led to disappearance of the signs and symptoms. CONCLUSIONS: This is the first description of an association between EIB and Addison's disease. It should be borne in mind that tuberculosis is an important etiological factor for Addison's disease.

CONTEXTO: O eritema indurado de Bazin (EIB) é considerado uma reação tuberculoide e consiste de nódulos dolorosos recorrentes. O diagnóstico diferencial inclui doenças como vasculite nodular, perniose, poliarterite nodosa e eritema nodoso. RELATO DE CASO: Nós reportamos o caso de uma mulher com EIB que desenvolveu doença de Addison durante tratamento com drogas tuberculostáticas e com boa resposta com reposição de glicocorticoide. O diagnóstico foi realizado pela apresentação clínica, teste tuberculínico positivo e positividade para BCG (bacilo Calmette-Guérin) no espécime histológico. A reposição de glicocorticoides e drogas tuberculostáticas levou ao desaparecimento dos sinais e sintomas. CONCLUSÕES: Este é o primeiro caso reportando a associação entre EIB e doença de Addison. Tuberculose é um importante agente etiológico da doença de Addison.