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Iatrogenic secondary hypoadrenocorticism in a horse with pituitary pars intermedia dysfunction (equine Cushing's disease)
... Die Wirksamkeit von Pergolid wurde in verschiedenen Studien nachgewiesen (Beech 1994, Donaldson et al. 2002, Munoz et al. 1996, Oertel et al. 2006, Perkins et al. 2002, Ranner 2001, Schott 2001, Watson 1998. Mit der empfohlenen initialen Dosierung von 1 µg/kg/Tg (0.5 mg/Tg für 500 kg) werden kaum Nebenwirkungen beobachtet (Beech 1999, Peters 1995, Schott 2001, Watson 1998 (Orsini 2007, Schott 2002, Schott 2003. Cyproheptadin, ein Serotonin-Antagonist und Antihistaminikum, wird ebenfalls zur Behandlung von ECS eingesetzt. ...
This chapter discusses pathogenesis, classical signs, diagnosis and treatment for hypoadrenocorticism in horses, ferrets and pet birds. Hypoadrenocorticism results from an inadequate production of glucocorticoids and/or mineralocorticoids by adrenocortical cells. Primary hypoadrenocorticism occurs in critically ill adult horses due to damage to the adrenal glands. Baseline cortisol and adrenocorticotrophic hormone (ACTH) levels as well as the ACTH stimulation test are critical to achieve a diagnosis. Iatrogenic hypoadrenocorticism is an uncommon complication of subtotal or bilateral adrenalectomy carried out for the treatment of adrenal disease in ferrets. Although there are no appropriately documented cases of hypoadrenocorticism in pet birds, it is likely that adrenal deficiency does occur in this group. Corticosteroid treatment should be slowly tapered off to prevent the development of iatrogenic hypoadrenocorticism.
This is the first fluticasone propianato (FP) long-term study in Recurrent Airways Obstruction (RAO)-aged horses (Equus ferus caballus) that compare Fluticasone Propionate (FP) treat-ment regimens, as well as FP treatment vs. environmental con-trol, over Hypothalamus Pituitary adrenal (HPA) axis, its re-versibility and cortisol suppression clinical consequences. The goal was to follow-up RAO clinical signs and cortisol levels in aged RAO-horses treated with FP. Eleven horses were stabled in moldy-dusty conditions to cause RAO disease. Once they were RAO symptomatic, they were divided in two groups: RAO-FP (treatment group) that were kept over hay/straw and RAO-control (non-treatment) that were kept over pell ets/wood shavings by six months. After that, all the horses were kept on the paddock and pasture. FP (Flovant HFA®) 2000ug B.I.D.(twice-a-day) during six months and 2000ug S.I.D. (once-a-day) during other five months was given using Aero-mask®. Clinical respiratory signs (CRS) were also recorded (nasal flaring and abdominal movement). Cortisol was meas-ured using commercial chemii uminescence (CEIA) kit (Immu-lite 1000®, Siemens)-12,-10 d before and 7, 28, 80,160,200,250,290, 320 d after treatment. Cortisol was used as systemic biomarker in determining any potential suppres-sion and general effect rel ated to FP treatment. FP 2000ug B.I.D. was associated with a decrease in blood cortisol levels on 28, 80 and 160 d in RAO-horses, however cortisol levels re-turns simil ar to basel ine values, as well as simil ar to cortisol values in RAO-control horses whensame FP dose was given just S.I.D. These results suggest that long-term 2000ug/horse B.I.D. inhaled FP treatment suppresses endogenous cortisol through its action over the hypothai amic-pituitary-adrenal (HPA) axis. Cortisol suppression with FP 2000 ug/horse B.I.D., may have deleterious effects if suppression is main-tained for more than six months in those aged horses, proving that FP dose should be adj usted and combined with environ-mental management, according to clinical signs improvement.
Pergolide is the drug of choice for treatment of equine Cushing's syndrome (ECS). There are only few detailed studies describing the longterm effects of pergolide treatment in ECS patients. The goal of this study was to evaluate the long-term effects of a pergolide therapy in ECS patients in Switzerland by means of owners' survey using a questionnaire. Thirty-eight horses diagnosed with ECS between 1999 and 2009 at the Vetsuisse Faculties Zurich and Bern, respectively, and treated for at least 1 month with pergolide (Permax®, Lilly SA, Genf) were included in the study. Diagnosis of ECS was based on history and clinical signs; in 37 horses it was confirmed with a dexamethasone suppression test (DST) and/or measurement of plasma ACTH concentration. The clinical signs before treatment were characterised and the effect of therapy was determined by interrogating the horse owners using a questionnaire. Statistical analysis of the data was performed using a McNemar's test. The examined horses were 22 (13-36) years old (mean (min-max)]. The population contained 22 warmblood horses, 11 cobs und 5 ponies, including 14 mares, 23 geldings und 1 stallion. Clinical signs were hirsutism (33/9) [(number of offected horses before treatment; number after treatment)], hyperhidrosis (24/7), poor performance (21/3), lethargy (22/3), polyuria/polydipsia (15/5), muscle wasting (19/11), weight loss (13/4), laminitis (15/3), ataxia (11/3), skin infections (10/4), bronchitis (4/2) and conjunctivitis (6/2). The dosage of pergolide was 1-2 μg/kg p.o. SID and the duration of treatment was 13.8 (1-38) months. According to the owners, horses responded to treatment within 2 to 4 weeks after initiation of therapy. Thirty-four of the 38 owners (79%) were satisfied with the treatment. Adverse effects were rarely observed (n=11) and if so, they were transient and mild (anorexia, lethargy, diarrhoea). At the time of the study, 10 horses had died or were euthanized (recurrent laminitis, colic, bone fracture, loss of use). The length of survival of these horses after start of treatment was 7.9 (1-22) months. The results indicate an improvement of the clinical signs after pergolide therapy in most of the patients when judged by the owners. At the dosage used here, adverse effects are rare and mostly clinically irrelevant. In conclusion, the administration of pergolide in ECS patients can be supported on the basis of the results in this study.
A 9-year-old male German shepherd dog was evaluated for clinical and clinico-pathological changes that were suggestive of Addison's disease. On further investigation the basal plasma cortisol concentration was high, a normal cortisol response to ACTH stimulation occurred, plasma renin activity was elevated and low serum aldosterone concentration was present. A diagnosis of hyperreninaemic hypoaldosteronism was made. Replacement fludrocortisone resulted in complete normalisation of the electrolyte and fluid imbalances. Hyperreninaemic hypoaldosteronism has never been reported in the dog.
Hypoadrenocorticism secondary to bilateral lymphomatous invasion of adrenocortical tissue was diagnosed in 2 adult castrated domestic shorthair cats. In both cats, findings during initial physical examination (ie, lethargy, anorexia, weight loss, and severe weakness) were consistent with severe hypoadrenocorticism. Hyperkalemia, hyponatremia, and azotemia were also detected, which were consistent with hypoadrenocorticism. Hypoadrenocorticism was documented on the basis of finding low baseline and ACTH-stimulated serum cortisol concentrations. The cats initially responded well to treatment, but both owners chose to have the cat euthanatized. Multicentric lymphoma with infiltration and destruction of the adrenal glands was confirmed during necropsy.
Hypoadrenocorticism (also known as Addison's disease, adrenal insufficiency, or adrenocortical hypofunction) is often called the great pretender because the associated clinical signs can mimic those of other diseases. Primary hypoadrenocorticism is a direct failure of the adrenal glands to produce physiologically adequate amounts of glucocorticoids, mineralocorticoids, or both. In secondary hypoadrenocorticism, decreased secretion of corticotropin in the pituitary or corticotropin-releasing hormone by the hypothalamus can lead to decreased production of glucocorticoids. About 70% of affected dogs are female. The average age at diagnosis is about 5 years. Breeds at risk for developing the disease include the Great Dane, poodle, and West Highland white terrier; the Lhasa Apso and Yorkshire terrier are at lower risk. Clinical signs include vomiting, anorexia, weakness, lethargy, weight loss, diarrhea, and dehydration. Laboratory findings include hyponatremia, hyperkalemia, and a decreased serum:potassium ratio. Affected dogs are more likely than is the general canine population to have anemia or hypothyroidism. Emergency treatment of hypoadrenocorticism deals with patient stabilization; maintenance treatment includes administration of glucocorticoids and mineralocorticoids to reestablish physiologic homeostasis. Dogs with primary disease may require replacement of either or both, whereas dogs with secondary disease usually require glucocorticoids but not replacement of mineralocorticoids.
Interpret the signs, evaluate the findings, follow the workup, and make your diagnosis. In this care, a senior dog suddenly developed seizures along with polyuria, polydipsia, and vomiting.
Interpret the signs, evaluate the findings, follow the workup, and make your diagnosis. This case of a geriatric dog that presents with multiple signs illustrates the importance of fitting together all the pieces of the diagnostic puzzle before initiating treatment.
Medical records of 27 horses (including 13 ponies) treated with pergolide or cyproheptadine for pituitary pars intermedia dysfunction were reviewed to determine the effect of treatment on plasma ACTH, insulin, and glucose concentrations and clinical signs. Prior to treatment, the most common clinical signs were laminitis, hirsutism, and abnormal body fat distribution. The median pergolide dose was 3.0 μLg/kg PO q24h (range, 1.7–5.5 ±g/kg). All horses treated with cyproheptadine were given 0.25 mg/kg PO q24h. After pergolide treatment, ACTH concentrations (n = 20; median = 30.4 pg/ml; range, 4.2–173) were significantly lower (P < .01) than those in horses treated with cyproheptadine (n = 7; median = 141.0 pg/ml; range, 10–1,230). Among horses treated with pergolide, there was a correlation between ACTH concentration after treatment and the duration of treatment (P < .001) and pergolide dose (P= .04). Significantly (P= .02) more owners of horses treated with pergolide (85%, 17/20) reported an improvement in clinical signs compared to owners of horses treated with cyproheptadine (28%, 2/7).
A four-year-old Labrador retriever was presented with lethargy and exercise intolerance. Clinical examination was unremarkable. A subnormal cortisol response to adrenocorticotrophin hormone (ACTH) was demonstrated (plasma cortisol concentrations before and after administration of ACTH were both below the detection limit of the assay) but plasma aldosterone concentrations were within the normal range. Endogenous plasma ACTH concentrations were high, indicating primary adrenocortical disease. Following glucocorticoid supplementation at a replacement dose (prednisolone 0.1 mg/kg) the dog made a full clinical recovery.
Pituitary pars intermedia dysfunction is a slowly progressive disorder that afflicts most breeds of horses. Because it shares features with human Cushing disease, it has been referred to as equine Cushing disease. A variety of tests of pituitary-adrenocortical function were performed on horses with evidence of pituitary pars intermediate dysfunction, and results were compared with those in healthy control horses. Diurnal variations in plasma cortisol concentration were not statistically different between control horses and those with pituitary pars intermedia dysfunction. An ACTH stimulation (1 U of natural ACTH gel/kg of body weight, IM) test or a combined dexamethasone suppression test (10 mg, IM) and ACTH stimulation (100 mg of synthetic ACTH, IV) test also failed to distinguish horses with pituitary pars intermedia dysfunction from control horses. A significant (P < 0.001) dose-related suppression of cortisol concentration in response to increasing doses (5, 10, 20, and 40 micrograms/kg) of dexamethasone was observed in control horses but not in those with pituitary pars intermedia dysfunction. On the basis of plasma cortisol concentration, the dexamethasone suppression test, using 40 micrograms/kg, whether initiated at 5 PM with sample collection at 15 (8 AM) and 19 (12 PM) hours after dexamethasone administration, or initiated at 12 AM with sample collection at 8 (8 AM), 12 (12 PM), 16 (4 PM), 20 (8 PM), and 24 (12 AM) hours after dexamethasone administration, reliably distinguished between control horses and those with pituitary pars intermedia dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal insufficiency was diagnosed in a 9-year-old American Quarter Horse gelding that had received monthly injections of stanozolol for 8 years. After the injections were abruptly discontinued, the horse developed anorexia, lethargy, weight loss, and bilateral forelimb lameness. Secondary hypoadrenocorticism was diagnosed on the basis of clinical signs, lack of high endogenous plasma ACTH concentration, and lack of cortisol response to administration of ACTH. Because the medical history did not include glucocorticoid administration, the cause was determined to be excessive administration of an anabolic steroid. Treatment consisted of physiologic glucocorticoid replacement for 9 months until adrenal function returned. Findings in this horse indicate that anabolic steroids influence the hypothalamic-pituitary axis in horses.
Fourteen dogs diagnosed with Addison's disease and having atypical serum electrolyte levels are described. Seventy-eight percent were female, and most showed signs of inappetence, weakness, or vomiting. Ninety-three percent of the cases had either hyponatremia without hyperkalemia or normal serum electrolyte concentrations. Hemogram features were variable and were not useful in suggesting a diagnosis of hypoadrenocorticism. The results of this study show that normal or mild serum electrolyte changes in a dog with clinical signs compatible with Addison's disease should not exclude this diagnosis from consideration. Definitive diagnosis depends on the demonstration of inadequate adrenocortical response to adrenocorticotropic hormone (ACTH) stimulation.
The reader should have a better working knowledge of several rare adrenal diseases after reading this article. Although they are rare, these adrenal diseases may be seen in many nursing settings. Astute nursing assessment and monitoring of signs and symptoms of these diseases are essential during diagnosis and treatment. A detailed case study illustrates Cushing's syndrome and pheochromocytoma as well as adrenal insufficiency.
A 3-day-old female Pinto was admitted with profuse watery diarrhea and severe hypovolemic shock. After 1 week of intensive care, the foal developed seizures associated with profound serum electrolyte abnormalities suggestive of hypoadrenocorticism. Treatment with prednisone and isotonic saline (0.9% NaCl) solution led to prompt clinical response. Premature withdrawal of prednisone resulted in relapse of clinical signs. A diagnosis of adrenal insufficiency was made on the basis of clinical signs, electrolyte abnormalities, low baseline cortisol concentration, and lack of response to administration of exogenous adrenocorticotropin. Two months later, adrenocortical function was normal and the foal was doing well clinically. Clinical signs of acute adrenal insufficiency in neonatal foals can be confused with other conditions, such as septicemia, enteritis, and ruptured urinary bladder. A persistently low serum sodium-to-potassium ratio associated with CNS malfunction should warrant investigation of adrenal gland function. Acute hypoadrenocorticism in foals may be reversible.
Plasma ACTH levels have been variable in horses with a positive clinical response for therapy for equine Cushing's Disease (ECD). Therefore, our purpose was to determine the value of monitoring plasma adrenocorticotropin (ACTH) levels during treatment of equine Cushing's disease (ECD) with either cyproheptadine (n = 32) or pergolide (n = 10). First, we validated the chemiluminescent ACTH assay (specificity, precision, accuracy, intra‐assay and interassay variations) and tested methods of handling the whole blood from the time of collection to when the ACTH was assayed. The sensitivity and specificity of high plasma ACTH levels for detecting ECD was determined in a retrospective study on hospitalised horses (n = 68). Surveys were sent to veterinarians who submitted equine ACTH levels that were high initially and had at least 2 ACTH samples to determine the value of monitoring ACTH levels during therapy of ECD.
The ACTH chemiluminescent assay was valid. The ACTH was stable when whole blood was collected and held in plastic tubes for 8h before separating the plasma. The sensitivity and specificity of plasma ACTH levels for detecting ECD were 84% (n = 19, 95% CI 60, 97) and 78% (n = 49, 95% CI 63, 88), respectively. Treated horses generally showed a decrease in plasma ACTH. Plasma ACTH levels may be helpful when monitoring therapy of ECD, although improvement in clinical signs should be considered most important. There were no differences between cyproheptadine and pergolide in terms of improvements in any of the clinical signs.
Medical records of 27 horses (including 13 ponies) treated with pergolide or cyproheptadine for pituitary pars intermedia dysfunction were reviewed to determine the effect of treatment on plasma ACTH, insulin, and glucose concentrations and clinical signs. Prior to treatment, the most common clinical signs were laminitis, hirsutism, and abnormal body fat distribution. The median pergolide dose was 3.0 microg/kg p.o. q24h (range, 1.7-5.5 microg/kg). All horses treated with cyproheptadine were given 0.25 mg/kg p.o. q24h. After pergolide treatment, ACTH concentrations (n = 20; median = 30.4 pg/ml; range, 4.2-173) were significantly lower (P < .01) than those in horses treated with cyproheptadine (n = 7; median = 141.0 pg/ml: range, 10-1,230). Among horses treated with pergolide, there was a correlation between ACTH concentration after treatment and the duration of treatment (P < .001) and pergolide dose (P = .04). Significantly (P = .02) more owners of horses treated with pergolide (85%, 17/20) reported an improvement in clinical signs compared to owners of horses treated with cyproheptadine (28%, 2/7).
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