Across-species benefits of adrenalectomy on congenital generalized lipoatrophic diabetes: a review.

Two adrenalectomies py -45erformed fourteen years apart notoriously alleviated insulin resistance in a female teenager with Congenital Generalized Lipoatrophy (CGL, 1988) and in a murine model of CGL (2002). Following a successful therapeutic trial with anti-glucocorticoids, we performed the first surgical procedure on an 18-year-old girl. Before surgery, the anti-glucocorticoid therapy produced a rapid and striking drop in fasting serum insulin levels (from over 400 to 7.0 mU/L) and a slower -but impressive- fall in fasting serum triglycerides from 7,400 to 220-230 mg/dL. In contrast, fasting serum glucose levels dropped more slowly, from 225-290 to 121-138 mg/dL. Two weeks following total adrenalectomy, the fasting serum glucose level was 98 mg/dL, with a corresponding serum insulin level of 10 mU/L. During an Oral Glucose Tolerance Test, the 2-hour serum glucose was 210 mg/dL, and serum insulin values during the test did not exceed 53 mU/L. In 2002, the A-ZIP/F1 hypoleptinemic mouse had its adrenal glands removed. Even though this CGL model does not respond well to leptin replacement, an infusion of recombinant leptin reduced the characteristic hypercorticosteronemia of this murine model of CGL. Adrenalectomy in this transgenic mouse improved insulin sensitivity in the liver and muscle. In summary, adrenalectomy -in both a human and a mouse case of CGL- limited adipose tissue exposure to corticosteroid action and led to a notorious metabolic improvement. On a broader scenario, given that leptin restrains the adrenal axis, the reduced leptin activity of the leptin resistance displayed by obese subjects should lead to adrenal axis overactivity. This overactivity should result in elevated serum levels of free cortisol, free fatty acids, and glycerol. In this manner, leptin resistance should lead to peripheral (adipose tissue, liver, and muscle) insulin resistance and islet beta-cell apoptosis, paving the way to Type 2 diabetes.

Is Methylprednisolone Acetate-Related Insulin Resistance Preventable in Cats?

Methylprednisolone acetate (MPA) is often prescribed to cats despite being recognized eventually as diabetogenic. To assess MPA-related insulin resistance and evaluate the efficacy of metformin or an obesity and diabetes mellitus (O&D) adjuvant diet as protective factors, a randomized clinical trial was conducted with 28 owned cats undergoing glucocorticoid therapy. A single MPA dose of 20 mg intramuscularly was administered to each cat. Controls (n = 10) received only MPA. In the diet group (n = 9), replacement of their habitual diet by ad-libitum feeding of a feline commercial O&D diet (Equilíbrio O&D, Total Alimentos ADM) was made. In the metformin group (n = 9), metformin chlorhydrate 25mg/cat PO/q24h was administered for 30 days. All patients were clinically evaluated at baseline (T0), day 15 (T15), and day 30 (T30) and blood draw for complete blood count, serum biochemistry, and determination of insulin concentrations. Fasting Insulin Sensitivity Index (SI), Amended Insulin to Glucose Ratio (AIGR), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and Homeostatic Model Assessment of beta-cell function (HOMA-B) were calculated based on fasting glycemia and insulinemia. All groups showed significantly higher levels (P < .05) of neutrophils, albumin, glucose, cholesterol, triglycerides, and serum insulin at T15. Patients in the metformin group showed also higher SI, AIGR, and HOMA-IR results at T15. Also, at T15, reduced levels (P < .05) of eosinophils, lymphocytes, and creatinine were documented in all groups. An MPA single dose induced changes in insulin sensitivity in cats; however, neither metformin nor O&D feeding used in this study was effective as protective factors against MPA-related insulin resistance.

Variation in Preventive Care in Children Receiving Chronic Glucocorticoid Therapy.

OBJECTIVE: To assess preventive care measure prescribing in children exposed to glucocorticoids and identify prescribing variation according to subspecialty and patient characteristics. STUDY DESIGN: Retrospective cohort study of children initiating chronic glucocorticoids in the gastroenterology, nephrology, and rheumatology divisions at a pediatric tertiary care center. Outcomes included 25-hydroxyvitamin D (25OHD) and lipid testing, pneumococcal polysaccharide (PPV) and influenza vaccination, and stress dose hydrocortisone prescriptions. RESULTS: A total of 701 children were followed for a median of 589 days. 25OHD testing was performed in 73%, lipid screening in 29%, and PPV and influenza vaccination in 16% and 78%, respectively. Hydrocortisone was prescribed in 2%. Across specialties, 25OHD, lipid screening, and PPV prescribing varied significantly (all P < .001). Using logistic regression adjusting for specialty, 25OHD testing was associated with older age, female sex, non-Hispanic ethnicity, and lower baseline height and body mass index z-scores (all P < .03). Lipid screening was associated with older age, higher baseline body mass index z-score, and lower baseline height z-score (all P < .01). Vaccinations were associated with lower age (P < .02), and PPV completion was associated with non-White race (P = .04). CONCLUSIONS: Among children chronically exposed to glucocorticoids, 25OHD testing and influenza vaccination were common, but lipid screening, pneumococcal vaccination, and stress dose hydrocortisone prescribing were infrequent. Except for influenza vaccination, preventive care measure use varied significantly across specialties. Quality improvement efforts are needed to optimize preventive care in this high-risk population.

Canine eosinophilic furunculosis / Furunculose eosinofílica canina

Background: The eosinophilic furunculosis is an uncommon skin disease that affects young dogs aged between two and five years. Sex predilections are not noted. Most reported cases have been in large breeds with abundant access to the outdoors like public gardens and parks. The exact pathogenesis remains unknown but the pattern of lesions development suggests involvement reaction to insect bites and arthropods. The time between contact with the agent and the appearance of lesions is short, often less than 24 h. The skin lesions appear suddenly in the face, usually on the dorsal muzzle and/ or periocular region, pinnae and lips. More rarely on the trunk, chest and legs and it is characterized by predominantly hemorrhagic ulcers with edema. Pustules, nodules and plaques rapidly fistulate and drain serosanguinous exudates. Pruritus is variable, but may be severe. Severely affected dogs may be febrile, lethargic and anoretic. Peripheral blood eosinophilia is seen in the majority of cases. Clinical differential diagnosis include demodicosis, dermatophytosis, nasal deep bacterial folliculitis and furunculosis, pemphigus foliaceus, pemphigus erythematosus and drug reactions. None of these diseases share the fulminant rapid onset of eosinophilic furunculosis. The diagnosis is based on history, clinical signs, cytology and skin biopsies. The treatment involves oral steroids until complet

Background: The eosinophilic furunculosis is an uncommon skin disease that affects young dogs aged between two and five years. Sex predilections are not noted. Most reported cases have been in large breeds with abundant access to the outdoors like public gardens and parks. The exact pathogenesis remains unknown but the pattern of lesions development suggests involvement reaction to insect bites and arthropods. The time between contact with the agent and the appearance of lesions is short, often less than 24 h. The skin lesions appear suddenly in the face, usually on the dorsal muzzle and/ or periocular region, pinnae and lips. More rarely on the trunk, chest and legs and it is characterized by predominantly hemorrhagic ulcers with edema. Pustules, nodules and plaques rapidly fistulate and drain serosanguinous exudates. Pruritus is variable, but may be severe. Severely affected dogs may be febrile, lethargic and anoretic. Peripheral blood eosinophilia is seen in the majority of cases. Clinical differential diagnosis include demodicosis, dermatophytosis, nasal deep bacterial folliculitis and furunculosis, pemphigus foliaceus, pemphigus erythematosus and drug reactions. None of these diseases share the fulminant rapid onset of eosinophilic furunculosis. The diagnosis is based on history, clinical signs, cytology and skin biopsies. The treatment involves oral steroids until complet

Furunculose eosinofílica canina / Canine eosinophilic furunculosis

Background: The eosinophilic furunculosis is an uncommon skin disease that affects young dogs aged between two and five years. Sex predilections are not noted. Most reported cases have been in large breeds with abundant access to the outdoors like public gardens and parks. The exact pathogenesis remains unknown but the pattern of lesions development suggests involvement reaction to insect bites and arthropods. The time between contact with the agent and the appearance of lesions is short, often less than 24 h. The skin lesions appear suddenly in the face, usually on the dorsal muzzle and/ or periocular region, pinnae and lips. More rarely on the trunk, chest and legs and it is characterized by predominantly hemorrhagic ulcers with edema. Pustules, nodules and plaques rapidly fistulate and drain serosanguinous exudates. Pruritus is variable, but may be severe. Severely affected dogs may be febrile, lethargic and anoretic. Peripheral blood eosinophilia is seen in the majority of cases. Clinical differential diagnosis include demodicosis, dermatophytosis, nasal deep bacterial folliculitis and furunculosis, pemphigus foliaceus, pemphigus erythematosus and drug reactions. None of these diseases share the fulminant rapid onset of eosinophilic furunculosis. The diagnosis is based on history, clinical signs, cytology and skin biopsies. The treatment involves oral steroids until complete remission of lesions and the antibiotic therapy is indicated in cases of associated bacterial infection. Case: The patient was a 4-year-old, male Pit Bull dog attended in a small animal clinic in Niteroi-Rio de Janeiro, which presented ulcerated, exudative lesions on the dorsal muzzle and right leg. After sedation, clinical examination was performed and an exudate was collected from the ulcerated skin lesion for cytopathological analysis .The slide containing the lesion impression was stained by a quick panoptic method. In order to collect samples, the dog was sedated with a combination of ketamine hydrochloride and acepromazine and a skin fragment was collected from the nasal bridge lesion with a 6 mm punch after local anesthesia with 2% lidocaine hydrochloride. The specimen was fixed in 10% buffered formalin and sent for histopathological analysis. The cytopathological exam revealed a marked eosinophilic inflammation. Histopathological examination revealed ulcerated skin. The epidermis was moderately acanthotic with mild espongiosis and the dermis was characterized by intense eosinophilic folliculocentric inflammations. An extensive folicular rupture, eosinophilic mural foliculitis were presented and PAS staining did not identify fungal structures. Oral prednisone (2 mg/Kg) at 24h intervals was prescribed until complete remission of the lesions. After fifteen days of glucocorticoids therapy, involution of the skin lesions was observed by physical examination and was also reported by the owner. Discussion: The eosinophilic furunculosis is an acute, severe predominantly facial disease of outdoor dogs, which occurrence is rare. The diagnosis and treatment of this disease are frequently neglected because they are not included in the differential diagnosis of diverse cutaneous infections. In view of the scarcity of reports and to alert veterinarians that the disease should be included in the differential diagnosis with other bacterial diseases, this report described a case of canine eosinophilic furunculosis.

Canine eosinophilic furunculosis / Furunculose eosinofílica canina

Background: The eosinophilic furunculosis is an uncommon skin disease that affects young dogs aged between two and five years. Sex predilections are not noted. Most reported cases have been in large breeds with abundant access to the outdoors like public gardens and parks. The exact pathogenesis remains unknown but the pattern of lesions development suggests involvement reaction to insect bites and arthropods. The time between contact with the agent and the appearance of lesions is short, often less than 24 h. The skin lesions appear suddenly in the face, usually on the dorsal muzzle and/ or periocular region, pinnae and lips. More rarely on the trunk, chest and legs and it is characterized by predominantly hemorrhagic ulcers with edema. Pustules, nodules and plaques rapidly fistulate and drain serosanguinous exudates. Pruritus is variable, but may be severe. Severely affected dogs may be febrile, lethargic and anoretic. Peripheral blood eosinophilia is seen in the majority of cases. Clinical differential diagnosis include demodicosis, dermatophytosis, nasal deep bacterial folliculitis and furunculosis, pemphigus foliaceus, pemphigus erythematosus and drug reactions. None of these diseases share the fulminant rapid onset of eosinophilic furunculosis. The diagnosis is based on history, clinical signs, cytology and skin biopsies. The treatment involves oral steroids until complet

Background: The eosinophilic furunculosis is an uncommon skin disease that affects young dogs aged between two and five years. Sex predilections are not noted. Most reported cases have been in large breeds with abundant access to the outdoors like public gardens and parks. The exact pathogenesis remains unknown but the pattern of lesions development suggests involvement reaction to insect bites and arthropods. The time between contact with the agent and the appearance of lesions is short, often less than 24 h. The skin lesions appear suddenly in the face, usually on the dorsal muzzle and/ or periocular region, pinnae and lips. More rarely on the trunk, chest and legs and it is characterized by predominantly hemorrhagic ulcers with edema. Pustules, nodules and plaques rapidly fistulate and drain serosanguinous exudates. Pruritus is variable, but may be severe. Severely affected dogs may be febrile, lethargic and anoretic. Peripheral blood eosinophilia is seen in the majority of cases. Clinical differential diagnosis include demodicosis, dermatophytosis, nasal deep bacterial folliculitis and furunculosis, pemphigus foliaceus, pemphigus erythematosus and drug reactions. None of these diseases share the fulminant rapid onset of eosinophilic furunculosis. The diagnosis is based on history, clinical signs, cytology and skin biopsies. The treatment involves oral steroids until complet

Tratamento com hrGH da baixa estatura induzida pelo uso crônico de glicocorticóide em crianças: [revisão] / hrGH treatment of glucocorticoid-induced short stature in children: [review]

O uso crônico de glicocorticóides no tratamento de doenças sistêmicas causa diminuição da velocidade de crescimento (VC), podendo acarretar perda estatural final. As interações entre o eixo adrenal e o eixo GH-sistema IGF têm sido descritas, podendo ocorrer em nível hipotalâmico-hipofisário e na regulação do sistema IGF, inclusive modulando o sinal do IGF-1R. Pode-se dizer que o quadro clínico deve ser considerado como estado de deficiência de Igf-1, absoluta e/ou funcional. As intervenções que possibilitam a normalização funcional do eixo GH-IGF poderiam reduzir a perda estatural destas crianças. Os estudos realizados em pacientes com artrite reumatóide juvenil em tratamento com corticóides mostraram aceleração da VC e diminuição da perda protéica com o uso de GH recombinante humano (hrGH). A aceleração da VC foi também descrita em pacientes sob corticoterapia crônica por causa da doença intestinal inflamatória ou do transplante renal após o uso de hrGH. A dose de hrGH guarda correlação positiva com a aceleração da VC e os resultados reforçam que esta deficiência funcional do eixo GH-IGF pode ser revertida com a administração de hrGH. O efeito do hrGH é restrito ao período de tratamento e depende do esquema de reposição do hrGH, do estado nutricional e das condições da doença de base.

The treatment of systemic diseases with glucocorticoids is often associated with decreased height velocity (HV), and can result in shorter final height. Interactions between adrenal and GH-IGF axis have been described and can occur at hypothalamic-pituitary level or at the regulation of IGF system, including the IGF1R signaling. The clinical state of these patients may be considered as an absolute and/or functional IGF-1 deficiency. Interventions aiming to restore the normal function of GH-IGF axis might reduce the glucocorticoids-induced growth suppression in these children. It has been shown that recombinant human GH (hrGH) induces an increase in HV and a decrease in protein loss in patients with juvenile idiopathic arthritis treated with glucocorticoids. Significant increment in HV was also described after hrGH treatment in children under glucocorticoid therapy due to inflammatory bowel disease or renal transplantation. There is a positive correlation between HV and the dose of hrGH. The results support that the IGF-1 deficiency in these children may be counteract by hrGH therapy. The effect of hrGH is observed only during the treatment period and depends on the replacement strategy, nutritional status and disease control.