Emergence of De Novo Conditions Following Remission of Cushing Syndrome: A Case Report and Scoping Review.

OBJECTIVE: Onset and exacerbation of autoimmune, inflammatory or steroid-responsive conditions have been reported following the remission of Cushing syndrome, leading to challenges in distinguishing a new condition versus expected symptomatology following remission. We describe a case of a 42-year-old man presenting with new-onset sarcoidosis diagnosed 12 months following the surgical cure of Cushing syndrome and synthesise existing literature reporting on de novo conditions presenting after Cushing syndrome remission. METHODS: A scoping review was conducted in Medline, Epub, Ovid and PubMed. Case reports and case series detailing adult patients presenting with new-onset conditions following Cushing syndrome remission were included. RESULTS: In total, 1641 articles were screened, 138 full-text studies were assessed for eligibility, and 43 studies were included, of which 84 cases (including our case) were identified. Most patients were female (85.7%), and the median reported age was 39.5 years old (IQR = 13). Thyroid diseases were the most commonly reported conditions (48.8%), followed by sarcoidosis (15.5%). Psoriasis, lymphocytic hypophysitis, idiopathic intracranial hypertension, multiple sclerosis, rheumatoid arthritis, lupus and seronegative arthritis were reported in more than one case. The median duration between Cushing remission and de novo condition diagnosis was 4.1 months (IQR = 3.75). Of those patients, 59.5% were receiving corticosteroid therapy at the time of onset. CONCLUSION: Our scoping review identified several cases of de novo conditions emerging following the remission of Cushing syndrome. They occurred mostly in women and within the year following remission. Clinicians should remain aware that new symptoms, particularly in the first year following the treatment of Cushing syndrome, may be manifestations of a wide range of conditions aside from adrenal insufficiency or glucocorticoid withdrawal syndrome.

Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study.

BACKGROUND: Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described. OBJECTIVE: To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission. DESIGN: Retrospective matched cohort analysis. SETTING: Academic medical center/pituitary center. PATIENTS: Patients with CD with surgical remission and surgically treated NFPA. MEASUREMENTS: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. RESULTS: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%). LIMITATION: The small sample of patients with autoimmune disease limited identification of independent risk factors. CONCLUSION: Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger. PRIMARY FUNDING SOURCE: Recordati Rare Diseases Inc.

New onset of isolated adrenocorticotropin deficiency associated with encephalopathy following coronavirus disease 2019 in a healthy elderly man.

Coronavirus disease 2019 (COVID-19) due to a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can include various systemic organ disorders including endocrinopathies and neurological manifestations. We report the case of a 65-year-old Japanese man who developed isolated adrenocorticotropic hormone (ACTH) deficiency and encephalopathy following SARS-CoV-2 infection. Two weeks after his COVID-19 diagnosis, he was emergently admitted to our hospital because of subacute-onset delirium. On admission, he presented hyponatremia (128 mEq/L) and secondary adrenal insufficiency (ACTH <1.5 pg/mL, cortisol 0.53 µg/dL). Brain imaging and laboratory examinations including SARS-CoV-2 polymerase chain reaction testing in the cerebrospinal fluid revealed no abnormalities. His consciousness level worsened despite the amelioration of hyponatremia by intravenous hydrocortisone (100 mg/day), but his neurological presentations completely resolved after three consecutive days of high-dose (400 mg/day) hydrocortisone. His encephalopathy did not deteriorate during hydrocortisone tapering. He continued 15 mg/day hydrocortisone after discharge. His encephalopathy might have developed via a disturbance of the autoimmune system, or a metabolic effect associated with adrenal insufficiency, although the time lag between the hyponatremia's improvement and the patient's neurological response to the steroid was incompatible with common cases of delirium concurrent with adrenal insufficiency. At 13 months after his hospitalization, the patient's neurological symptoms have not recurred and he has no endocrinological dysfunctions other than the remaining ACTH deficiency. A thorough consideration of the immunological and metabolic characteristics of SARS-CoV-2 is advisable when clinicians treat patients during and even after their COVID-19 disease period.

Child Neurology: Allgrove Syndrome: An Intriguing Etiology of Motor Neuron Disease in Children

Motor neuron diseases are a rare group of neurodegenerative disorders with considerable phenotypic heterogeneity and a multitude of etiologies in the pediatric population. In this study, we report 2 unrelated adolescents (a boy and a girl) who presented with 4-6 years of progressive difficulty in walking, thinning of limbs, and gradually progressive darkening of the skin. Examination revealed generalized hyperpigmentation of skin and features suggestive of motor neuron involvement such as tongue atrophy, wasting of distal extremities, and brisk deep tendon reflexes. On detailed exploration for systemic involvement, history of dysphagia, inability to produce tears, and Addisonian crises were evident. An etiologic diagnosis of Allgrove syndrome, which is characterized by a triad of achalasia, alacrimia, and adrenal insufficiency was considered. Next-generation sequencing revealed pathogenic variants in the AAAS gene, confirming the diagnosis. Steroid replacement therapy was initiated along with relevant multidisciplinary referrals. The disease stabilized in the boy and a significant improvement was noted in the girl. These cases highlight the value of non-neurologic cues in navigating the etiologic complexities of motor neuron diseases in children and adolescents. It is imperative for neurologists to develop awareness of the diverse neurologic manifestations associated with Allgrove syndrome because they are often the first to be approached. A multidisciplinary team of experts including neurologists, endocrinologists, gastroenterologists, ophthalmologists, and dermatologists is essential for planning comprehensive care for these patients.

Adrenomyeloneuropathy manifesting as adrenal insufficiency and bilateral lower extremity spastic paraplegia: A case report and literature review.

RATIONALE: Adrenomyeloneuropathy (AMN) is a variant type of X-linked adrenoleukodystrophy, and it is a genetic metabolic disease with strong clinical heterogeneity so that it is easily misdiagnosed and underdiagnosed. Moreover, most patients with AMN have an insidious clinical onset and slow progression. Familiarity with the pathogenesis, clinical features, diagnosis, and treatment of AMN can help identify the disease at an early stage. PATIENT CONCERNS: We present a case of 35-year-old male, who was admitted to our hospital due to "immobility of the lower limbs for 2 years and worsening for half a year," accompanied by skin darkening and hyperpigmentation of lips, oral mucosa, and areola since puberty. DIAGNOSIS: The level of very long-chain fatty acids was high and genetic testing depicted that exon 1 of the ABCD1 gene had a missense mutation of C.761c>T, which was diagnosed as AMN. INTERVENTIONS: Baclofen was administered to improve muscle tension combined with glucocorticoid replacement therapy. OUTCOMES: The condition was relieved after half a year. LESSONS: The clinical manifestations of AMN are diverse. When patients with adrenocortical dysfunction complicated with progressive spastic paraplegia of lower limbs are involved, AMN should be highly suspected, and the determination of very long-chain fatty acids and genetic testing should be performed as soon as possible to confirm the diagnosis because early treatment can help prevent or delay the progression of the disease.

Postpartum acute adrenal insufficiency of early-onset Sheehan syndrome: A case series study in a single center.

AIM: To identify the symptoms and relevant factors associated with acute adrenal insufficiency of early-onset Sheehan syndrome. METHODS: We retrospectively reviewed the charts of 125 women admitted to our intensive care unit because of postpartum hemorrhage between January 2011 and December 2021. Three women developed acute adrenal insufficiency. We investigated the total blood loss, shock status, consciousness level upon arrival, and intensive care provided to the women. We also analyzed the symptoms and laboratory data that led to the diagnosis of acute adrenal insufficiency. Continuous variables were presented by median (minimum-maximum). RESULTS: The medians and ranges of age, total blood loss, and shock index [heart rate/systolic blood pressure] on admission were 33.1 (17.2-45.3) years, 3351 (595-20 260) g, and 0.94 (0.55-2.94), respectively. Seven women were older than 40 years, 28 experienced >5000 g blood loss, 17 had shock index >1.5, 27 had impaired consciousness upon arrival, and 15 underwent hysterectomy. Women who developed acute adrenal insufficiency were <40 years old and had a bleeding volume of over 5000 g, impaired consciousness upon arrival, and had undergone hysterectomy. They had experienced lactation failure, presented with hyponatremia-related symptoms on postpartum days 8-9, experienced general malaise, headache, and impaired consciousness, and showed severe hyponatremia. CONCLUSIONS: Massive postpartum hemorrhage over 5000 g, impaired consciousness upon arrival, and hysterectomy as a hemostatic measure were relevant factors associated with acute adrenal insufficiency of early-onset Sheehan syndrome. Hyponatremia-related symptoms occurring after lactation failure are indicative of the onset of acute adrenal insufficiency.

Morbidity in Patients with Chronic Adrenal Insufficiency - Cardiovascular Risk Factors and Hospitalization Rate Compared to Population Based Controls.

Patients with adrenal insufficiency (AI) have been found to have increased cardiovascular morbidity, partly associated with nonphysiologic glucocorticoid replacement. We included two separate cohorts (cohort 1 n=384 patients, cohort 2 n=180 patients) of patients with chronic primary and secondary AI under standard replacement therapy and compared them to two age- and sex-matched population-based studies (SHIP-TREND/DEGS). Odds ratios with 95% CI for hypertension, hyperlipidemia/HLP, type 2 diabetes/T2DM, obesity, and hospitalization with adjustment for confounders were evaluated by logistic regression. Patient cohort 1 had significantly lower ORs for obesity [0.4 (0.3-0.6), p<0.001] and hypertension [0.5 (0.3-0.6), p<0.001] compared to SHIP-TREND and for obesity [0.7 (0.5-0.9), p=0.01], hypertension [0.4 (0.3-0.5), p<0.001] and HLP [0.4 (0.3-0.6), p<0.001] compared to DEGS. In cohort 2, ORs were significantly lower for HLP compared to both SHIP-TREND [0.4 (0.2-0.7), p=0.001] and DEGS [0.3 (0.2-0.5), p<0.001] and for hypertension [0.7 (0.4-0.9), p=0.04] compared to SHIP-TREND. In patients with SAI from cohort 2, ORs for DM2 [2.5 (1.3-4.9) p=0.009], hypertension [2.5 (1.4-4.5), p=0.002] and obesity [1.9 (1.1-3.1), p=0.02] were significantly higher compared to DEGS, whereas ORs for HLP were significantly lower compared to both SHIP [0.3 (0.1-0.6), p=0.002] and DEGS [0.3 (0.1-0.6), p<0.001]. In most of our AI patients treated with conventional glucocorticoid doses, the risk for T2DM, obesity, hypertension, and HLP was not increased. The number of hospitalizations was significantly higher in AI patients compared to controls, which might reflect increased susceptibility but also a more proactive management of concomitant diseases by physicians and patients.

Hypoglycaemia in adrenal insufficiency.

Adrenal insufficiency encompasses a group of congenital and acquired disorders that lead to inadequate steroid production by the adrenal glands, mainly glucocorticoids, mineralocorticoids and androgens. These may be associated with other hormone deficiencies. Adrenal insufficiency may be primary, affecting the adrenal gland's ability to produce cortisol directly; secondary, affecting the pituitary gland's ability to produce adrenocorticotrophic hormone (ACTH); or tertiary, affecting corticotrophin-releasing hormone (CRH) production at the level of the hypothalamus. Congenital causes of adrenal insufficiency include the subtypes of Congenital Adrenal Hyperplasia, Adrenal Hypoplasia, genetic causes of Isolated ACTH deficiency or Combined Pituitary Hormone Deficiencies, usually caused by mutations in essential transcription factors. The most commonly inherited primary cause of adrenal insufficiency is Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency; with the classical form affecting 1 in 10,000 to 15,000 cases per year. Acquired causes of adrenal insufficiency can be subtyped into autoimmune (Addison's Disease), traumatic (including haemorrhage or infarction), infective (e.g. Tuberculosis), infiltrative (e.g. neuroblastoma) and iatrogenic. Iatrogenic acquired causes include the use of prolonged exogenous steroids and post-surgical causes, such as the excision of a hypothalamic-pituitary tumour or adrenalectomy. Clinical features of adrenal insufficiency vary with age and with aetiology. They are often non-specific and may sometimes become apparent only in times of illness. Features range from those related to hypoglycaemia such as drowsiness, collapse, jitteriness, hypothermia and seizures. Features may also include signs of hypotension such as significant electrolyte imbalances and shock. Recognition of hypoglycaemia as a symptom of adrenal insufficiency is important to prevent treatable causes of sudden deaths. Cortisol has a key role in glucose homeostasis, particularly in the counter-regulatory mechanisms to prevent hypoglycaemia in times of biological stress. Affected neonates particularly appear susceptible to the compromise of these counter-regulatory mechanisms but it is recognised that affected older children and adults remain at risk of hypoglycaemia. In this review, we summarise the pathogenesis of hypoglycaemia in the context of adrenal insufficiency. We further explore the clinical features of hypoglycaemia based on different age groups and the burden of the disease, focusing on hypoglycaemic-related events in the various aetiologies of adrenal insufficiency. Finally, we sum up strategies from published literature for improved recognition and early prevention of hypoglycaemia in adrenal insufficiency, such as the use of continuous glucose monitoring or modifying glucocorticoid replacement.

Anterior hypopituitarism due to primary empty sella syndrome in a critically unwell patient.

A previously fit and well male in his early 40s, presented to the emergency department, hypotensive, bradycardic and hypothermic with reduced levels of consciousness after being found diaphoretic and unwell at his home. Despite fluid resuscitation with warmed saline, he remained hypotensive and required vasopressor support leading to intensive care admission. Initially, the patient was managed for suspected meningoencephalitis but was later found to have hypopituitarism leading to secondary hypothyroidism and adrenal insufficiency. Subsequent investigations revealed it is due to empty sella syndrome.

The 1 µg Synacthen stimulation test in the diagnosis of secondary adrenal insufficiency in patients with Rathke's cleft cyst and empty sella syndrome.

INTRODUCTION: Rathke's cleft cyst (RCC) and primary empty sella syndrome (PESS) are usually incidental findings on magnetic resonance imaging (MRI) scans. In most cases, these lesions do not cause mass effect symptoms and do not require surgical intervention. In patients with RCC or PESS, it is important to exclude secondary adrenal insufficiency (SAI), which may be a life-threatening condition. MATERIAL AND METHODS: The incidence of SAI was assessed in patients with RCC or PESS detected by MRI, using the 1 µg Synacthen stimulation test. A total of 38 patients were analysed. Test results were linked to clinical symptoms and the type of cystic lesion. RESULTS: Assuming that cortisol levels < 14.6 µg/dL in Synacthen test are the criterion of SAI diagnosis, SAI was diagnosed only in 2 patients (5%). Adopting the traditional criterion of cortisol levels < 18 µg/dL, SAI would be diagnosed in 7 patients (18.4 %). Dizziness (Chi2 = 3.89; p = 0.049) and apathy (Chi2 = 3.87; p = 0.049) were significantly more frequent in the PESS group than in the RCC group. CONCLUSIONS: The incidence of SAI in the general patient population with empty sella syndrome and Rathke's cleft cysts is low. The 1 µg Synacthen test seems to be a valuable tool in the diagnosis of SAI among patients with RCC and PESS. Further studies are necessary to determine the sensitivity and specificity of the 1 µg Synacthen test with the standardization of test protocol and considering the cortisol level at the 20-minute timepoint. PESS patients report dizziness and apathy more frequently than RCC patients, which does not result from the disturbance of the hypothalamic-pituitary-adrenal axis, but probably from the different pathogenesis of these cystic lesions.

Bilateral adrenal hemorrhage: learning notes from clinical practice and literature review.

Adrenal hemorrhage is a rare, but important, diagnosis to recognize, in particular when there is involvement of both adrenal glands. Bilateral adrenal hemorrhage can in fact lead to adrenal insufficiency, with dramatic consequences if not promptly recognized and treated. It is normally caused by systemic conditions that lead to the vasoconstriction and thrombosis of the adrenal vein. Oftentimes, the clinical diagnosis of this condition can be very challenging, as its signs and symptoms are generalized and nonspecific (abdominal pain, nausea, and fatigue). Here, we present the cases of two patients admitted to the Emergency Department in 2016 and 2022 with acute abdominal pain, having recently undergone surgery and subsequently prescribed low-molecular-weight heparin. In both cases, laboratory results revealed neutrophilic leukocytosis and an unexplained anemia. Due to the persistence of abdominal pain despite medication, a CT scan was performed, showing an enlargement of both adrenal glands suggestive of bilateral adrenal hemorrhage. Adrenal function was tested that correlated with a diagnosis of adrenal insufficiency, and both patients were promptly treated with parenteral hydrocortisone as a result. On 5 years' follow-up from the acute event, the second patient's adrenal function had returned to normal, and he has not needed further adrenal replacement therapy; the first patient however demonstrated persistence of adrenal failure requiring replacement therapy. In this paper, through our experience and a literature analysis, we will aim to outline some clues to identify patients at potential risk of bilateral adrenal hemorrhage.

Factors underlying a disproportionate increase in hospital admissions for adrenal insufficiency in women aged 20-29 years.

Since the year 2000, admissions for adrenal insufficiency (AI) and adrenal crises (AC) have shown a particular increase in young adult females. We examined data on acute non-surgical hospitalisations for AI/AC from New South Wales, Australia, to determine relevant factors that may have contributed to this increase. Data were analysed to ascertain associations between various comorbid psychosocial issues, identified by relevant ICD-10-AM codes in each record, and ACs. From 2005 to 2021. There were 877 admissions for an acute non-surgical illness in this age group. The average admission rate for females [63.5/million/year] was almost twice that for males [34.0/million/year] (p<0.01), as was the average female AC admission rate [14.7/million/year] relative to that in males [6.75/million/year] (p=NS). Infection was present in 41.6% (n=365) of the admissions and Type 1 diabetes mellitus was present in 12.2% (n=107). Overall, psychosocial factors were considered by the senior clinician to have contributed to the illness episode in 22.1% of all admissions and 29.0% of AC admissions. Having one or more psychosocial problems was associated with an AC in females (37.4%, n=49, in those having an AC, p<0.001) but not males. Females with an AC also had a higher mean composite psychosocial, psychiatric and drug/alcohol score [0.47 (0.67)] than females without an AC [0.32 (0.62) p<0.05]. No comparable associations were found in male patients. An increase in the rates of hospitalisations that included a code for at least one psychosocial problem was highly correlated with increases in admission rates for both ACs (r=0.82, p<0.001) and all AI (r=0.98, p<0.001) in females but there was no such relationship in males. This new evidence suggests that psychosocial factors may play an important role in ongoing rates of ACs in treated AI (incidence approximately 6-8 ACs/100PY) particularly in young adult females. In order to minimize AC episodes, all barriers to self-management need exploration on an individual patient basis and with regard to the patient population as a whole.

Further Characterization of the Neuroendocrine Phenotype Associated With the PPOX-Related Variegate Porphyria.

BACKGROUND: Variegate porphyria is caused by mutations in the PPOX gene; it usually presents in adolescents and adults as an autosomal dominant condition, with cutaneous features or acute peripheral and/or central nervous system crises. A rarer variant, homozygous variegate porphyria, presents in childhood with cutaneous manifestations as well as neurophenotypes. This study sought to further characterize the homozygous PPOX-related neuroendocrine phenotype. METHODS: This study is a retrospective review of the patients' charts, including their clinical evaluation and molecular genetics, neurodiagnostic, and neuroradiological investigations. RESULTS: We describe here three children from a consanguineous family who presented with nystagmus, developmental delay and ataxia, photosensitive skin manifestations, and adrenal insufficiency. Analysis of porphyrins in plasma, urine, and stool together with a genetic study of the PPOX gene confirmed the diagnosis. Interestingly, brain MRI showed severe hypomyelination, a finding rarely reported in variegate porphyria, together with adrenal insufficiency. CONCLUSION: We recommend analysis of porphyrins in unexplained hypomyelination disorders. Patients with variegate porphyria should be tested for adrenal insufficiency.

An unusual cause of abdominal pain: spontaneous bilateral adrenal hemorrhage.

Bilateral adrenal hemorrhage (BAH) is a rare condition that can lead to acute adrenal insufficiency and death if not recognized and treated promptly. We report the case of a 30-year-old male who presented to the emergency department with acute abdominal pain, nausea, and vomiting. On emergency room admission, the first abdominal CT revealed normal adrenal glands without enlargement, but with the development of hypotension and hypoglycemia, a second CT performed four days later showed enlargement due to hemorrhage in both adrenals. The diagnosis of BAH associated with acute adrenal insufficiency was retained. Prompt treatment with intravenous and oral corticosteroids resulted in successful conservative management. We describe the clinical, biological, radiological and etiological features of this condition based on a review of the literature.

Case report: a premature infant with severe intrauterine growth restriction, adrenal insufficiency, and inflammatory diarrhea: a genetically confirmed case of MIRAGE syndrome.

Introduction: MIRAGE syndrome is a rare disease characterized by myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital phenotypes, and enteropathy. Herein, we report the case of a girl with MIRAGE syndrome who presented with adrenal insufficiency and chronic diarrhea. Case presentation: The patient was born at 29 + 6 weeks of gestational age with a birth weight of 656 g (<3p). Her height and head circumference were also <3p. At birth, she presented with respiratory distress, meconium staining, and pneumomediastinum, which were managed with high-frequency ventilation and empirical antibiotics. Physical examination showed generalized hyperpigmentation and normal female genitalia. A few days after birth, polyuria and hypotension developed, and laboratory findings revealed hypoglycemia, hyponatremia, and hyperkalemia. Plasma adrenocorticotropic hormone levels were elevated with low serum cortisol levels and high plasma renin activity, which were suggestive of adrenal insufficiency. Hydrocortisone and fludrocortisone were introduced and maintained, and hyperpigmentation attenuated with time. Both kidneys looked dysplastic, and adrenal glands could not be traced on abdominal ultrasound. From the early days of life, thrombocytopenia and anemia were detected, but not to life-threatening level and slowly recovered up to the normal range. Despite aggressive nutritional support, weight gain and growth spurt were severely retarded during the hospital stay. Additionally, after introducing enteral feeding, she experienced severe diarrhea and subsequent perineal skin rashes and ulcerations. Fecal calprotectin level was highly elevated; however, a small bowel biopsy resulted in non-specific submucosal congestion. The patient was diagnosed with MIRAGE syndrome with SAMD9 gene mutation. She was discharged with tube feeding and elemental formula feeding continued, but chronic diarrhea persisted. By the time of the last follow-up at 15 months of corrected age, she was fortunately not subjected to severe invasive infection and myelodysplastic syndrome. However, she was dependent on tube feeding and demonstrated a severe developmental delay equivalent to approximately 5-6 months of age. Conclusion: The early diagnosis of adrenal crisis and hormone replacement therapy can save the life of -patients with MIRAGE syndrome; however, chronic intractable diarrhea and growth and developmental delay continue to impede the patient's well-being.

Risk factors that are associated with adrenal insufficiency among patients with fever of unknown origin.

BACKGROUND: Adrenal insufficiency is one of the causes of fever of unknown origin (FUO). The purpose of this study is to find out risk factors that are associated with adrenal insufficiency in FUO patients. METHODS: This study was conducted retrospectively in a tertiary hospital with 846 beds in South Korea. All adult inpatients (age ≥19 years) who have requested a consult with the department of infectious disease for FUO between 1 July 20191 July 2019 and 30 June 202030 June 2020 were included in the study. Among them, those who underwent an adrenocorticotropic hormone (ACTH) stimulation test and had a fever of 37.8°C or higher within 48 hours of the ACTH stimulation test were finally included in the study subjects. RESULTS: A total of 202 FUO patients were enrolled and 61 (30.1%) were finally diagnosed with adrenal insufficiency. In a multivariate analysis, use of immunosuppressant within 3 months (OR 6.06, 95% CI 1.82-20.13, P = 0.003), use of corticosteroid within 3 months (OR 8.23, 95% CI 1.35-50.17, P = 0.022), sodium ≥ 136.7 (OR 3.43, 95% CI 1.49-7.88, P = 0.004), and calcium ≥ 8.4 (OR 0.31, 95% CI 0.14-0.71, P = 0.005) were proven to be factors associated with adrenal insufficiency in FUO patients. CONCLUSION: In conclusion, 30.1% of FUO patients were diagnosed with adrenal insufficiency. The risk factors that are associated with adrenal insufficiency in FUO patients were immunosuppressive prescription or systemic steroid prescription within 3 months, or with sodium ≥ 136.7 or calcium < 8.4.

Possible development and resolution of dilated cardiomyopathy phenotype secondary to atypical hypoadrenocorticism in a dog.

OBJECTIVE: To report the possible occurrence of dilated cardiomyopathy phenotype associated with atypical hypoadrenocorticism and subsequent marked improvement with treatment in a mixed breed dog. CASE SUMMARY: A 4.5-year-old, neutered male mixed breed dog was evaluated for a history and clinicopathological changes consistent with atypical hypoadrenocorticism. The dog was being fed a grain-free diet. While hospitalized for supportive care and diagnostics, the patient developed and was diagnosed with biventricular congestive heart failure secondary to dilated cardiomyopathy phenotype and IV fluid administration. The left-sided congestive heart failure resolved with discontinuation of IV fluid therapy and short-term administration of diuretics. After treatment of atypical hypoadrenocorticism with glucocorticoid supplementation, and while continuing to be fed varying grain-free diets, the patient's dilated cardiomyopathy phenotype largely resolved. The patient fully recovered and did not require any long-term cardiac medications. NEW OR UNIQUE INFORMATION PROVIDED: Development of dilated cardiomyopathy phenotype has not been described in dogs as a sequela of untreated hypoadrenocorticism but has been reported in human literature. Given the fact that standard management of hypoadrenocorticism typically involves aggressive fluid resuscitation, awareness of this potential sequela is important for patients that fail to respond or develop signs consistent with volume overload.

Primary adrenal insufficiency due to bilateral adrenal hemorrhage-adrenal infarction in a patient with systemic lupus erythematosus and antiphospholipid syndrome: case presentation and review of the literature.

Primary adrenal insufficiency (PAI) is a rare disease which represents the end stage of a destructive process involving the adrenal cortex. Occasionally it may be caused by bilateral adrenal hemorrhagic infarction in patients with antiphospholipid syndrome (APS). We herein report the challenging case of a 30-year-old female patient with systemic lupus erythematosus (SLE) and secondary APS who was admitted to the emergency department (ED) due to fever, lethargy, and syncopal episodes. Hyponatremia, hyperkalemia, hyperpigmentation, shock, altered mental status, and clinical response to glucocorticoid administration were features highly suggestive of an acute adrenal crisis. The patient's clinical status required admission to the intensive care unit (ICU), where steroid replacement, anticoagulation, and supportive therapy were provided, with a good outcome. Imaging demonstrated bilateral adrenal enlargement attributed to recent adrenal hemorrhage. This case highlights the fact that bilateral adrenal vein thrombosis and subsequent hemorrhage can be part of the thromboembolic complications seen in both primary and secondary APS and which, if misdiagnosed, may lead to a life-threatening adrenal crisis. High clinical suspicion is required for its prompt diagnosis and management. A literature search of past clinical cases with adrenal insufficiency (AI) in the setting of APS and SLE was conducted using major electronic databases. Our aim was to retrieve information about the pathophysiology, diagnosis, and management of similar conditions.