Paracoccidioidomycosis is caused by a fungus (Paracoccidioides brasiliensis), which is endemic to Brazil. It is most frequently found in the lungs, with haematogenous and lymphatic spread. The condition is more prevalent in men, between 30 and 60 years old, commonly rural workers. It is the third leading cause of death among chronic infectious diseases today. The systemic disease has an insidious and nonspecific course, with adrenal involvement being observed in 5% of cases and requiring the destruction of 80% of the glands for symptoms of adrenal insufficiency to appear. Isolated involvement of this gland is quite rare. In this case report, however, our patient presented wasting and adrenal insufficiency with isolated adrenal involvement by the fungus.

At the beginning of each flu season, the Italian Ministry of Health defines the categories at higher risk of influenza complications, for which vaccination is actively and freely offered. The vaccine coverage (VC) of the influenza vaccine in subjects from 6 months to 64 years of age suffering from diseases that increase the risk of complications from influenza during the 2020-2021 season was evaluated. Our study wants to evaluate the VCs of the influenza vaccine in these subjects during the 2020/2021 season in Apulia. The digital archives relative to the Apulian population were used. A retrospective cohort study design was performed. 484,636 Apulian residents aged between 6 months and 64 years suffered from at least one chronic disease; 139,222 of 484,636 subjects received the influenza vaccine (VC: 28.7%) from October 2020 to January 2021. Considering the single comorbidities, the greatest values are found for pathologies for which major surgical interventions are planned and chronic renal failure/adrenal insufficiency patients, while the worst for chronic liver diseases and pathologies for which major surgical interventions are planned. In any case, it would seem that better VC is achieved in subjects with more than one chronic condition. Influenza vaccination must be promoted as a central public health measure, also because by reducing the burden on hospitals, it can greatly benefit the management of COVID-19 patients. Greater efforts by public health institutions must be implemented in order to achieve better VC in the target categories, including chronic patients.

Paracoccidioidomycosis (PCM) is a systemic mycosis endemic in Latin America, mostly in Brazil. The involvement of the gastrointestinal tract is uncommon and usually associated with the acute form. Recently, a cluster of acute PCM cases has been described in Rio de Janeiro, Brazil. We report a 42-year-old male, resident of Rio de Janeiro, presenting chronic diarrhea and abdominal pain in the past 3 years, previously diagnosed as Chron´s disease. When immunosuppressive therapy was prescribed, the patient evolved with worsening of the previous symptoms in addition to odynophagia, 20 kg-weight loss, disseminated skin lesions, diffuse lymphadenopathy and adrenal insufficiency. Histopathological and mycological examination of a skin lesion were compatible with PCM. Itraconazole was prescribed in high doses (400 mg/day). After seven months of treatment, the patient presented with acute abdominal pain which led to an emergent appendectomy, revealing the presence of the fungus. After 24 months, the patient reached clinical cure and recovered from adrenal insufficiency. We emphasize the importance of PCM as a differential diagnosis in patients with chronic diarrhea. The risk of fungal infections should be considered prior to initiating immunosupressive therapies, particularly in endemic areas.

Adrenal insufficiency (AI) is a relatively rare disease. While the adrenocorticotropic hormone (ACTH) stimulation test remains as one of the commonly used diagnostic test for AI, to date there is no consensus on the cortisol cutoff value post-ACTH stimulation test. This study aimed to investigate and characterize the cortisol response after the standard ACTH stimulation test in a group of Saudi Arabian patients. A single center retrospective study was conducted on Saudi Arabian adult patients who underwent ACTH stimulation test at the endocrinology clinics of King Abdulaziz Medical City in Riyadh, Saudi Arabia between 2015 and 2018. Demographic, clinical and biochemical variables were collected and analyzed. A total of 154 medical records of patients (44 males, 110 females, mean age 44.4 ± 17.0 years) were included in the study. All patients underwent ACTH stimulation test. Fatigue was the most common symptom of participants. Type 1 diabetes was the most frequent comorbidity. Cortisol levels were significantly lower in patients who received corticosteroid replacement therapy, and, within the context of ACTH stimulation tests, were useful in diagnosing AI in patients with vague symptoms and signs. For basal cortisol, the cutoff of ≤258.5 has a sensitivity and specificity of 69.2% and 58.6%, respectively. For 30-minute, the cutoff of ≤386 sensitivity and specificity are 61.5% and 69.0%. For 60-minute, the cutoff of ≤491.5 has a sensitivity and specificity of 61.5% and 65.5%, respectively. Higher cortisol cutoff values have better sensitivity. Patients with AI present with mostly nonspecific symptoms, with type 1 diabetes as the most common comorbidity. The cortisol level cutoffs obtained from Arab patients who underwent ACTH stimulation tests showed wide variability for its utility in AI diagnosis. Further studies to evaluate the optimal cortisol cutoff values for AI diagnosis in this population are needed.

Cystic fibrosis (CF) is an inherited syndrome associated with a mutation in a cystic fibrosis transmembrane conductance regulator gene, composed of exocrine gland dysfunction involving multiple systems that may result in chronic respiratory infections, pancreatic enzyme deficiency, and developmental disorders. Our study describes for the first time the urinary profile of glucocorticoid metabolites and the activity of the enzymes involved in the development and metabolism of cortisol in patients with CF, using a gas chromatography/mass spectrometry method. Data were obtained from 25 affected patients and 70 sex- and age- matched healthy volunteers. We have shown a general decrease in the activity of enzymes involved in the peripheral metabolism of cortisol, such as 11β-hydroxysteroid dehydrogenase type 2, 5α- and 5β-reductases. In contrast, the activity of 11β-hydroxysteroid dehydrogenase type 1, the enzyme that converts cortisone to cortisol, increased. Furthermore, our study found a significant decrease in glucocorticoid excretion in patients with CF. This may suggest adrenal insufficiency or dysregulation of the HPA axis and the development of peripheral mechanisms to counteract cortisol degradation in the case of reduced synthesis of glucocorticoids by the adrenal glands. Furthermore, the activity of 5α-reductase seems to be enhanced only through the backdoor pathway, especially when we taking into consideration 11β-hydroxyandrosterone/11β-hydroxyetiocholanolone ratio which has been shown to be the best differential marker for enzyme activity. CF impairs nutritional effects and energetic balance in patients; thus, our findings suggest the existence of adaptive mechanisms due to limited secretion of adrenal steroids and subsequent diminished amounts of their metabolites in urine. On the other hand, local control of cortisol availability is maintained by enhanced 11βHSD1 activity and its recovery from cortisone in organs and tissues which need this. Steroid hormone dysregulation might be another important factor in the course of CF that should be taken into account when planning an effective and comprehensive therapy.

Traumatic brain injury (TBI) is a major health problem affecting millions of people worldwide and leading to death or permanent damage. TBI affects the hypothalamic-pituitary-adrenal (HPA) axis either by primary injury to the hypothalamic-hypophyseal region or by secondary vascular damage, brain, and/or pituitary edema, vasospasm, and inflammation. Neuroendocrine dysfunctions after TBI have been clinically described in all hypothalamic-pituitary axes. We established a mild TBI (mTBI) in rats by using the controlled cortical impact (CCI) model. The hypothalamus, pituitary, and adrenals were collected in the acute (24 h) and chronic (30 days) groups after TBI, and we investigated transcripts and protein-related autophagy (Lc3, Bcln1, P150, Ulk, and Atg5) and apoptosis (pro-caspase-3, cleaved caspase-3). Transcripts related to autophagy were reduced in the hypothalamus, pituitary, and adrenals after TBI, however, this was not reflected in autophagy-related protein levels. In contrast, protein markers related to apoptosis increased in the adrenals during the acute phase and in the pituitary during the chronic phase. TBI stresses induce a variation of autophagy-related transcripts without modifying the levels of their proteins in the HPA axis. In contrast, protein markers related to apoptosis are increased in the acute phase in the adrenals, which could lead to impaired communication via the hypothalamus, pituitary, and adrenals. This may then explain the permanent pituitary damage with increased apoptosis and inflammation in the chronic phase. These results contribute to the elucidation of the mechanisms underlying endocrine dysfunctions such as pituitary and adrenal insufficiency that occur after TBI. Although the adrenals are not directly affected by TBI, we suggest that the role of the adrenals along with the hypothalamus and pituitary should not be ignored in the acute phase after TBI.

Saturated very long-chain fatty acids (VLCFA, ≥ C22), enriched in brain myelin and innate immune cells, accumulate in X-linked adrenoleukodystrophy (X-ALD) due to inherited dysfunction of the peroxisomal VLCFA transporter ABCD1. In its severest form, X-ALD causes cerebral myelin destruction with infiltration of pro-inflammatory skewed monocytes/macrophages. How VLCFA levels relate to macrophage activation is unclear. Here, whole transcriptome sequencing of X-ALD macrophages indicated that VLCFAs prime human macrophage membranes for inflammation and increased expression of factors involved in chemotaxis and invasion. When added externally to mimic lipid release in demyelinating X-ALD lesions, VLCFAs did not activate toll-like receptors in primary macrophages. In contrast, VLCFAs provoked pro-inflammatory responses through scavenger receptor CD36-mediated uptake, cumulating in JNK signalling and expression of matrix-degrading enzymes and chemokine release. Following pro-inflammatory LPS activation, VLCFA levels increased also in healthy macrophages. With the onset of the resolution, VLCFAs were rapidly cleared in control macrophages by increased peroxisomal VLCFA degradation through liver-X-receptor mediated upregulation of ABCD1. ABCD1 deficiency impaired VLCFA homeostasis and prolonged pro-inflammatory gene expression upon LPS treatment. Our study uncovers a pivotal role for ABCD1, a protein linked to neuroinflammation, and associated peroxisomal VLCFA degradation in regulating macrophage plasticity.

We report a case of a 58-year-old woman with secondary adrenocortical insufficiency due to adrenocorticotropic hormone (ACTH) deficiency after pembrolizumab treatment that required differentiation from low cardiac output syndrome. The patient had chronic heart failure due to radiation cardiomyopathy and underwent implantation of cardiac resynchronization therapy defibrillator (CRT-D). One year ago, she was diagnosed with squamous cell lung cancer and started combination therapy with carboplatin, paclitaxel, and pembrolizumab. She was hospitalized for anorexia, nausea, and hypotension. A diagnosis of secondary hypoadrenocorticism due to isolated ACTH deficiency was made, and from the course of the disease, it was diagnosed as a side effect of immune checkpoint inhibitors (ICIs). As the indications for ICIs continue to expand, it is necessary to understand the screening and management of their side effects.

Histoplasmosis is a chronic, infectious disease caused by the environmental fungus H. capsulatum, primarily affecting the respiratory system. In immunocompromised patients, histoplasmosis can become severely complicated due to dissemination into various other organ systems. Adrenal insufficiency is an uncommon complication of disseminated histoplasmosis, as its manifestation requires necrotizing granulomatous inflammation of both adrenal glands. We describe a rare case of delayed histoplasmosis in the bilateral adrenal glands and liver of an immunocompromised patient with development of symptoms at 21 years after liver transplant and nine years after renal transplant. In addition, this patient presented with secondary adrenal insufficiency due to long-term use of corticosteroids rather than the typical primary adrenal insufficiency seen in histoplasmosis with adrenal involvement.

Adrenal insufficiency is a life-threatening condition requiring chronic glucocorticoid replacement therapy, as well as stress adaptation to prevent adrenal crises. To increase patients' self-sustainability, education on how to tackle an adrenal crisis is crucial. All patients should carry the European Emergency Card.

Adrenal insufficiency ranges from mild nonspecific symptoms to life-threatening shock condition. Adrenal insufficiency is a diagnosis that will not be made unless the clinician maintains a level of suspicion. The decreasing or suppressed adrenal function may be masked until stress or illness triggers an adrenal crisis.[1][2][3] An important distinction in these patients is the presence of mineralocorticoid deficiency. Those with secondary or tertiary adrenal insufficiency will typically have preserved mineralocorticoid function due to the separate feedback systems. Mineralocorticoid levels are regulated by the renin-angiotensin system, independent of hypothalamic or pituitary signals. Another important distinction is the acute versus chronic nature of the disease. Acute adrenal insufficiency patients often present in a critically ill state while chronic presentations can be insidious.

The adrenal gland is made up of two parts, the cortex and the medulla. The adrenal cortex produces hormones necessary for normal body functioning; deficiency of these hormones results in adrenal insufficiency. The cortex is responsible for producing glucocorticoids, mineralocorticoids, and androgens. Destruction or dysfunction of the adrenal cortex mainly causes glucocorticoid and mineralocorticoid deficiency. Primary adrenal insufficiency is also known as autoimmune adrenalitis or Addison disease. Adrenal insufficiency ranges from mild nonspecific symptoms to life-threatening shock conditions. Due to its vague symptoms and varying degree of clinical presentation, a clinician must maintain a high level of suspicion for this disease. The decreasing or suppressed adrenal function may be masked until stress or illness triggers an adrenal crisis. Adrenal insufficiency can be classified into primary, secondary, and tertiary causes. Primary adrenal insufficiency occurs when there is a pathology affecting the adrenal gland itself. Secondary adrenal insufficiency results from a decreased level of adrenocorticotrophin hormone (ACTH) released from the pituitary gland, and tertiary adrenal insufficiency results from a decreased level of corticotrophin-releasing hormone (CRH) released from the hypothalamus.   An important distinction in these patients is the presence of mineralocorticoid deficiency. Those with secondary or tertiary adrenal insufficiency will typically have preserved mineralocorticoid function due to the separate feedback systems. Mineralocorticoid levels are regulated by the renin-angiotensin system that is independent of hypothalamic or pituitary signals. Another important distinction is the acute versus chronic nature of the disease. Acute adrenal insufficiency patients often present in a critically ill state, while chronic presentation can be insidious.[1][2][3][4][5]

ICI therapy has greatly improved patient outcomes in melanoma, but at the cost of immune-related adverse events (irAEs). Data on the chronicity of irAEs, especially in real-world settings, are currently limited. We performed a retrospective chart review of 161 adult patients with melanoma treated with at least one cycle of ICI regimen in the adjuvant or metastatic setting: 129 patients received PD-1 inhibitor monotherapy and 32 received dual immunotherapy. Patients were grouped by duration of irAE: permanent (no complete resolution), long-term (resolution over a period ≥ 6 months), transient (resolution over a period < 6 months), or no irAEs. A total of 283 irAEs were reported in the whole patient population. Sixty-six (41.0%) patients developed permanent irAEs, fifteen (9.3%) experienced long-term irAEs as their longest-lasting toxicity, thirty-four (21.1%) developed transient irAEs only, and forty-six (28.6%) experienced no irAEs. Permanent irAEs occurred in 21 (65.6%) patients treated with dual immunotherapy and in 45 (34.9%) patients treated with monotherapy. The majority of permanent irAEs were endocrine-related (36.0%) or skin-related (32.4%). Grade 3-4 permanent irAEs occurred in 20 (12.4%) patients and included toxicities such as adrenal insufficiency, myocarditis, and myelitis. Fifty-three (32.9%) patients were still requiring treatment for long-term or permanent irAEs 6 months or more following the completion of ICI therapy, including twenty-four patients on thyroid hormone replacement and twenty-two on oral steroids. ICI treatment was temporarily interrupted for 64 (22.6%) irAEs and permanently discontinued due to irAEs in 38 patients (13.6% of irAEs, 23.6% of patients); additionally, 4 (2.5%) patients died of irAEs. Our findings show that ICI treatment in melanoma is associated with a wide range of toxicities that can be permanent and may have long-lasting impacts on patients, which should therefore be discussed when obtaining consent for treatment.

Immune checkpoint inhibitor (ICI)-induced hypophysitis is an immune-mediated pituitary inflammation that tends to cause long-term pituitary deficiency. Management of ICI-induced hypophysitis includes corticosteroids for acute inflammation and long-term hormone replacement due to irreversible pituitary cell damage. We report a case of recurrent hypophysitis following ICI rechallenge for metastatic melanoma. A 33-year-old woman with recurrent metastatic melanoma with adrenal, pelvic, and inguinal metastases developed recurrent hypophysitis during treatment with ipilimumab and nivolumab which recurred with rechallenge >5 years later. In both cases, headache was the most notable symptom and brain MRI showed pituitary enlargement and edema without evidence of metastases. Central adrenal insufficiency and symptoms caused by mass effect were treated with acute high-dose corticosteroids and long-term replacement corticosteroids. Based on recurrence and failure of symptomatic treatment with continued steroid treatment, ICI was discontinued. This case illustrates that hypophysitis may recur with ICI rechallenge, challenging traditional assumptions that chronic, irreversible irAEs are unlikely to recur or flare. The regenerative potential of pituitary cells after ICI-induced damage or additional damage to previously unaffected cells may be more conceivable than previously realized. Additional research on the potential for recurrent ICI-induced endocrinopathies are needed.

A 6-year-old male neutered domestic longhair cat was referred for investigation of weight loss, hyporexia, vomiting and diarrhoea. The cat was diagnosed with primary hypoadrenocorticism, exocrine pancreatic insufficiency, cobalamin deficiency and a chronic enteropathy, and started on therapeutic treatment. Diabetes mellitus developed 4.5 months later, and the cat was started on insulin therapy. The cat was euthanased 10 months following the diagnosis of hypoadrenocorticism due to the development of status epilepticus, which was not associated with glucose or electrolyte abnormalities. Histopathological assessment of the adrenal glands at post-mortem examination documented lymphoplasmacytic adrenalitis, with the lymphocytic population being predominant. Immunohistochemical staining classified the lymphocytic infiltrate as T-cell rich, supportive of the cat's hypoadrenocorticism being due to autoimmune disease.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

We aim to review data on 3beta-hydroxysteroid dehydrogenase type II (3βHSD2) deficiency. We identified 30 studies within the last decade on PubMed: 1 longitudinal study (N = 14), 2 cross-sectional studies, 1 retrospective study (N = 16), and 26 case reports (total: 98 individuals). Regarding geographic area: Algeria (N = 14), Turkey (N = 31), China (2 case reports), Morocco (2 sisters), Anatolia (6 cases), and Italy (N = 1). Patients' age varied from first days of life to puberty; the oldest was of 34 y. Majority forms displayed were salt-wasting (SW); some associated disorders of sexual development (DSD) were attendant also-mostly 46,XY males and mild virilisation in some 46,XX females. SW pushed forward an early diagnosis due to severity of SW crisis. The clinical spectrum goes to: premature puberty (80%); 9 with testicular adrenal rest tumours (TARTs); one female with ovarian adrenal rest tumours (OARTs), and some cases with adrenal hyperplasia; cardio-metabolic complications, including iatrogenic Cushing' syndrome. More incidental (unusual) associations include: 1 subject with Barter syndrome, 1 Addison's disease, 2 subjects of Klinefelter syndrome (47,XXY/46,XX, respective 47,XXY). Neonatal screening for 21OHD was the scenario of detection in some cases; 17OHP might be elevated due to peripheral production (pitfall for misdiagnosis of 21OHD). An ACTH stimulation test was used in 2 studies. Liquid chromatography tandem-mass spectrometry unequivocally sustains the diagnostic by expressing high baseline 17OH-pregnenolone to cortisol ratio as well as 11-oxyandrogen levels. HSD3B2 gene sequencing was provided in 26 articles; around 20 mutations were described as "novel pathogenic mutation" (frameshift, missense or nonsense); many subjects had a consanguineous background. The current COVID-19 pandemic showed that CAH-associated chronic adrenal insufficiency is at higher risk. Non-adherence to hormonal replacement contributed to TARTs growth, thus making them surgery candidates. To our knowledge, this is the largest study on published cases strictly concerning 3βHSD2 deficiency according to our methodology. Adequate case management underlines the recent shift from evidence-based medicine to individualized (patient-oriented) medicine, this approach being particularly applicable in this exceptional and challenging disorder.

This review highlights oral anomalies with major clinical impact in Addison disease (AD), including dental health and dermatologic features, through a dual perspective: pigmentation issues and AD comorbidities with oral manifestations. Affecting 92% of AD patients, cutaneomucosal hyperpigmentation is synchronous with or precedes general manifestations by up to a decade, underlying melanocytic infiltration of the basal epidermal layer; melanophages in the superficial dermis; and, rarely, acanthosis, perivascular lymphocytic infiltrate, and hyperkeratosis. Intraoral pigmentation might be the only sign of AD; thus, early recognition is mandatory, and biopsy is helpful in selected cases. The buccal area is the most affected location; other sites are palatine arches, lips, gums, and tongue. Pigmented oral lesions are patchy or diffuse; mostly asymptomatic; and occasionally accompanied by pain, itchiness, and burn-like lesions. Pigmented lingual patches are isolated or multiple, located on dorsal and lateral areas; fungiform pigmented papillae are also reported in AD individuals. Dermoscopy examination is particularly indicated for fungal etiology; yet, it is not routinely performed. AD's comorbidity burden includes the cluster of autoimmune polyglandular syndrome (APS) type 1 underlying AIRE gene malfunction. Chronic cutaneomucosal candidiasis (CMC), including oral CMC, represents the first sign of APS1 in 70-80% of cases, displaying autoantibodies against interleukin (IL)-17A, IL-17F ± IL-22, and probably a high mucosal concentration of interferon (IFN)-γ. CMC is prone to systemic candidiasis, representing a procarcinogenic status due to Th17 cell anomalies. In APS1, the first cause of mortality is infections (24%), followed by oral and esophageal cancers (15%). Autoimmune hypoparathyroidism (HyP) is the earliest endocrine element in APS1; a combination of CMC by the age of 5 years and dental enamel hypoplasia (the most frequent dental complication of pediatric HyP) by the age of 15 is an indication for HyP assessment. Children with HyP might experience short dental roots, enamel opacities, hypodontia, and eruption dysfunctions. Copresence of APS-related type 1 diabetes mellitus (DM) enhances the risk of CMC, as well as periodontal disease (PD). Anemia-related mucosal pallor is related to DM, hypothyroidism, hypogonadism, corresponding gastroenterological diseases (Crohn's disease also presents oral ulceration (OU), mucogingivitis, and a 2-3 times higher risk of PD; Biermer anemia might cause hyperpigmentation by itself), and rheumatologic diseases (lupus induces OU, honeycomb plaques, keratotic plaques, angular cheilitis, buccal petechial lesions, and PD). In more than half of the patients, associated vitiligo involves depigmentation of oral mucosa at different levels (palatal, gingival, alveolar, buccal mucosa, and lips). Celiac disease may manifest xerostomia, dry lips, OU, sialadenitis, recurrent aphthous stomatitis and dental enamel defects in children, a higher prevalence of caries and dentin sensitivity, and gingival bleeding. Oral pigmented lesions might provide a useful index of suspicion for AD in apparently healthy individuals, and thus an adrenocorticotropic hormone (ACTH) stimulation is useful. The spectrum of autoimmune AD comorbidities massively complicates the overall picture of oral manifestations.

A 13-year-old spayed female Schnauzer dog with chronic kidney disease (CKD; International Renal Interest Society stage 2, non-proteinuric, normotensive), diabetes mellitus, hypercortisolism and myxomatous mitral valve degeneration (American College of Veterinary Internal Medicine stage B2) presented with electrolyte imbalance that had progressed to hyperkalaemia and hyponatremia, with a sodium to potassium (Na:K) ratio of 19.6. Cortisol levels after the adrenocorticotropic hormone stimulation test were within the therapeutic range, but aldosterone levels were below the reference range; hence, isolated hypoaldosteronism was diagnosed. After administration of deoxycorticosterone pivalate (DOCP), the electrolyte imbalance improved with a Na:K ratio of 27.7. This is the first report of the management of isolated hypoaldosteronism and hypercortisolism using trilostane and DOCP in a dog. This case highlights the importance of recognizing isolated hypoaldosteronism after long-term treatment with trilostane in a canine patient with CKD.