Iatrogenic symptomatic hypoadrenocorticism after treatment with trilostane for hyperadrenocorticism in dogs: eight cases (2008-2019).

OBJECTIVES: Trilostane is the medical treatment of choice for hyperadrenocorticism. Iatrogenic hypoadrenocorticism is thought to be rare, with most cases being transient and only a few cases of permanent hypoadrenocorticism have been reported. This study reports findings from eight cases of iatrogenic hypoadrenocorticism and examines the presence of concurrent diseases at the time of diagnosis. MATERIALS AND METHODS: Medical records of dogs treated for hyperadrenocorticism with trilostane since 2008 were reviewed, and cases of clinical iatrogenic hypoadrenocorticism were extracted. Cases were considered permanent if long-term replacement therapy was required. RESULTS: Eight dogs met the inclusion criteria. The time between the beginning of trilostane treatment and the diagnosis of hypoadrenocorticism ranged from 4 days to 13 months, and the dosage of trilostane ranged between 1 and 8 mg/kg/day. Six dogs had a suspicion of concurrent disease at the time of hypoadrenocorticism diagnosis. The trilostane dose was decreased in two dogs; trilostane was withdrawn in one case without further relapse of hyperadrenocorticism; and glucocorticoids with or without mineralocorticoid supplementation were prescribed in five dogs. Two of these five dogs were lost to follow-up, and the other three had a diagnosis of permanent hypoadrenocorticism. Adrenal gland ultrasonography in these three dogs showed a progressive reduction in gland sizes with heterogeneous echogenicity. CLINICAL SIGNIFICANCE: Iatrogenic hypoadrenocorticism is a rare but potentially life-threatening complication of trilostane treatment in dogs with hyperadrenocorticism. The occurrence of a concurrent disease might trigger the development of clinical signs of hypoadrenocorticism in previously subclinical dogs.

Clinical features and long-term management of cats with primary hypoadrenocorticism using desoxycorticosterone pivalate and prednisolone.

BACKGROUND: Primary hypoadrenocorticism (PH) is rare in cats and knowledge about treatment is sparse. OBJECTIVE: To describe cats with PH with a focus on long-term treatment. ANIMALS: Eleven cats with naturally occurring PH. METHODS: Descriptive case series with data on signalment, clinicopathological findings, adrenal width, and doses of desoxycorticosterone pivalate (DOCP) and prednisolone during a follow-up period of >12 months. RESULTS: Cats ranged from 2 to 10 years (median 6.5); 6 cats were British Shorthair. Most common signs were reduced general condition and lethargy, anorexia, dehydration, obstipation, weakness, weight loss, and hypothermia. Adrenal glands on ultrasonography were judged small in 6. Eight cats could be followed for 14 to 70 months (median: 28). Two were started on DOCP doses ≥2.2 mg/kg (2.2; 2.5) and 6 < 2.2 mg/kg (1.5-2.0 mg/kg, median 1.8) q28 days. Both high-dose cats and 4 low-dose cats needed a dose increase. Desoxycorticosterone pivalate and prednisolone doses at the end of the follow-up period were 1.3 to 3.0 mg/kg (median: 2.3) and 0.08 to 0.5 mg/kg/day (median: 0.3), respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Desoxycorticosterone pivalate and prednisolone requirements in cats were higher than what is currently used in dogs; thus, a DOCP starting dose of 2.2 mg/kg q28 days and a prednisolone maintenance dose of 0.3 mg/kg/day titrated to the individual need seems warranted. Small adrenal glands (width < 2.7 mm) on ultrasonography in a cat suspected of hypoadrenocorticism can be suggestive of the disease. The apparent predilection of British Shorthaired cats for PH should be further evaluated.

Prevalence and clinical relevance of hypercobalaminaemia in dogs and cats.

Hypocobalaminaemia is common in dogs and cats with exocrine pancreatic insufficiency and/or chronic enteropathy. While hypocobalaminaemia has been extensively studied, naturally-occurring serum hypercobalaminaemia (i.e. without supplementation) might be an underestimated finding in small animal medicine. Studies in human medicine have associated hypercobalaminaemia with neoplastic, hepatic and renal disease. Medical records of all dogs and cats with serum cobalamin concentration measurements (2007-2019) were retrospectively analysed; any that had received supplemental cobalamin were excluded from the analysis. Of 654 dogs, 3% (n = 21) were hypercobalaminaemic (median serum cobalamin concentration, 1307 ng/L [965 pmol/L]; range, 914-3561 ng/L [675-2628 pmol/L]). Chronic gastrointestinal signs were common in hypercobalaminaemic dogs (48%). Two of the 21 hypercobalaminaemic dogs were diagnosed with hypoadrenocorticism. Of 323 cats, 11% (n = 34) were hypercobalaminaemic (median serum cobalamin concentration, 1713 ng/L [1264 pmol/L]; range, 1370-3107 ng/L [1011-2293 pmol/L]). The following comorbidities were diagnosed in hypercobalaminaemic cats: chronic enteropathy, 65% (n = 22); acute or chronic pancreatitis, 24% (n = 8); cholangiohepatopathy, 18% (n = 6); gastric lymphoma, 6% (n = 2); and 3% hyperthyroidism (n = 1). Naturally-occurring increased serum cobalamin concentrations occurred infrequently in cats and even less often in dogs. Since hypercobalaminaemia can occur in dogs and cats with severe inflammatory, immune-mediated, and neoplastic conditions, it should not be ignored.

[Canine hypoadrenocorticism - an update on pathogenesis, diagnosis and treatment]. / Hypoadrenokortizismus beim Hund ­ ein Update zu Pathogenese, Diagnose und Therapie.

Canine hypoadrenocorticism (HoAC) results from a loss of functional adrenal cortex, the most common etiology of which is an immune-mediated destruction leading to an inadequate production of glucocorticoids and mineralocorticoids. The term "atypical" HoAC is used for a subgroup of dogs with either an isolated glucocorticoid deficiency or a combined glucocorticoid and mineralocorticoid deficiency but normal electrolytes. Dogs with HoAC can present with a large variety of clinical signs, ranging from shaking, weakness, and mild gastrointestinal signs to seizures, hypovolemic shock, and collapse. Routine clinicopathologic and diagnostic imaging findings are usually nonspecific and frequently mimic those of other common diseases. However, the absence of a stress leukogram, eosinophilia, hyponatremia, hyperkalemia, and azotemia and small adrenal glands on abdominal ultrasound are characteristic findings in dogs with HoAC. The ACTH stimulation test is currently the gold standard method for diagnosing HoAC. Other endocrine laboratory diagnostics, including the quantification of endogenous ACTH, basal and ACTH-stimulated aldosterone levels, cortisol:ACTH ratio, and aldosterone:renin ratio, may further aid in differentiating between primary, secondary, and "atypical" HoAC. Aggressive intravenous fluid therapy is the cornerstone of treatment in paients with an acute Addisonian crisis because it restores normovolemia and normal blood electrolytes. Maintenance therapy consists of glucocorticoid (e.g., prednisolone) and mineralocorticoid (e.g., des- oxycortone pivalate) supplementation and aims for stable electrolyte concentrations and a clinically well dog. The optimal dose of desoxy- cortone pivalate for a specific dog is determined based on blood so- dium and potassium concentrations by using a standardized protocol. Regular reevaluation of blood electrolytes is required for early identifi- cation of a mineralocorticoid deficiency in dogs with "atypical" HoAC. The long-term prognosis for dogs with HoAC is excellent provided that patients receive adequate treatment and there is good owner com- pliance.

Glucocorticoid-deficient hypoadrenocorticism secondary to intravascular lymphoma in the adrenal glands of a dog.

CASE REPORT: A 2-year-old neutered male German Shepherd dog was presented with weakness, poor appetite and weight loss. Glucocorticoid-deficient hypoadrenocorticism was diagnosed with undetectable pre- and post-ACTH cortisol concentrations but normal sodium and potassium concentrations. Despite appropriate supplementation with glucocorticoids, the patient's weakness progressed and neurological deficits developed. The patient was euthanased. Histopathological analysis of multiple organs, including the adrenal glands, showed an accumulation of neoplastic lymphocytes within blood vessels, consistent with a diagnosis of intravascular lymphoma. Histologically, in both adrenal glands, the architecture of the zona fasciculata and reticularis was disrupted by blood vessels congested with a neoplastic population of T-lymphocytes; the zona glomerulosa remained intact. CONCLUSION: This is the first report of intravascular lymphoma causing glucocorticoid-deficient hypoadrenocorticism in a dog.

Successful treatment of a cat with primary hypoadrenocorticism and severe hyponatremia with desoxycorticosterone pivalate (DOCP).

A 6-year-old, castrated male Siamese cat was diagnosed with primary hypoadrenocorticism, confirmed by an adrenocorticotopic hormone (ACTH) stimulation test documenting both hypocortisolism and hypoaldosteronism. The cat was successfully treated using a combination of prednisolone and desoxycorticosterone pivalate (DOCP). This case demonstrates that DOCP can be used successfully as mineralocorticoid supplementation in cats with hypoadrenocorticism and may have a longer therapeutic duration than that in dogs.

Traitement réussi d'un chat atteint d'hypoadrénocorticisme primaire et d'hyponatrémie à l'aide de pivalate de désoxycorticostérone (DOCP). Un diagnostic d'hypoadrénocorticisme primaire a été posé pour un chat Siamois castré âgé de 6 ans et confirmé par un test de stimulation de l'hormone adrénocorticotope (ACTH) qui a documenté l'hypocortisolisme et l'hypoaldostéronisme. Le chat a été traité avec succès à l'aide d'une combinaison de prednisolone et de pivalate de désoxycorticostérone (DOCP). Ce cas démontre que le DOCP peut être utilisé avec succès en tant que supplément de minéralocorticoïdes chez les chats atteints d'hypoadrénocorticisme et peut présenter une durée thérapeutique plus longue que chez les chiens.(Traduit par Isabelle Vallières).

Canine hypoadrenocorticism: pathogenesis, diagnosis, and treatment.

Hypoadrenocorticism (Addison disease) is an uncommon condition in dogs and even more rare in cats. Hypoadrenocorticism is most often caused by immune-mediated destruction of the adrenal glands resulting in decreased mineralocorticoid and glucocorticoid production. Although less common, some dogs with hypoadrenocorticism have normal serum electrolytes. Hypoadrenocorticism causes a wide variety of clinical symptoms including gastrointestinal upset, weakness, weight loss, and hypovolemia. Laboratory and diagnostic findings vary, but classic abnormalities include hyperkalemia, hyponatremia, azotemia, anemia, and lack of a stress leukogram. However, many other diseases present with similar symptoms and diagnostic findings. Definitive diagnosis requires adrenocorticotropic hormone (ACTH) stimulation testing to demonstrate low basal and post-ACTH cortisol levels. In some cases, ACTH level or basal- and ACTH-stimulated aldosterone levels must also be measured. The prognosis for hypoadrenocorticism is good with appropriate mineralocorticoid and glucocorticoid supplementation.

Hypercalcemia due to latrogenic secondary hypoadrenocorticism and diabetes mellitus in a cat.

A 9-year-old, spayed female domestic shorthair cat presented for polyphagia, polydipsia, and polyuria following chronic methylprednisolone acetate therapy for pruritus. Initial diagnostics were consistent with uncomplicated diabetes mellitus. Serum calcium was within reference range. Within 12 hours the cat developed depression, anorexia, vomiting, and severe dehydration. Laboratory analysis indicated marked hypercalcemia as measured by both ionized and total calcium concentration. No underlying neoplastic or inflammatory process was identified. An adrenocorticotropic hormone stimulation test was indicative of adrenocortical insufficiency. The hypercalcemia resolved with glucocorticoid supplementation and correction of the dehydration. The diabetes mellitus and adrenal insufficiency both resolved within 9 weeks.

Primary hypoadrenocorticism in a dog receiving glucocorticoid supplementation.

A 5-year-old, spayed, female husky-Labrador retriever cross was diagnosed with primary hypoadrenocorticism, an uncommon endocrine disorder caused by a deficiency of glucocorticoid and mineralocorticoid hormones. Subtle clinical signs and previous treatment with exogenous glucocorticoid drugs required an adrenocorticotropic hormone stimulation test to confirm the diagnosis.

Glucocorticoid deficient hypoadrenocorticism in dogs: 18 cases (1986-1995).

OBJECTIVE: To characterize naturally developing glucocorticoid deficiency in dogs. DESIGN: Retrospective case series. ANIMALS: 18 dogs with glucocorticoid deficiency defined by an inadequate response to stimulation with adrenocorticotropic hormone (ACTH), a normal Na:K ratio (> 27), and no history of receiving corticosteroids for at least 6 weeks. PROCEDURE: Information including signalment, body weight, clinical signs on admission, historical findings, physical examination findings, results of CBC and serum biochemical analyses, results of ACTH stimulation tests and other ancillary endocrine tests, diagnostic imaging findings, findings from other procedures such as endoscopy and surgery, and information on concurrent diseases, management, and outcome were retrieved from the medical records of dogs with glucocorticoid deficiency treated between 1986 and 1995 at the University of Pennsylvania's School of Veterinary Medicine and 2 dogs from private practices. RESULTS: Most dogs were young (< 7 years) and represented larger breeds (> 20 kg). Clinical signs were nonspecific: lethargy, weight loss, and gastrointestinal disturbances including regurgitation with radiographic evidence of megaesophagus. Hypocholesterolemia, hypoalbuminemia, hypoglycemia, and a mild, nonregenerative anemia were common. Ten of the 18 dogs responded well to glucocorticoid supplementation alone, with only 2 dogs developing electrolyte abnormalities. Four (22%) of the dogs died, with death usually occurring as a result of secondary disease processes rather than hypoadrenocorticism. CLINICAL IMPLICATIONS: An ACTH stimulation test should be considered as part of the diagnostic plan in dogs with signs of weight loss, inappetence, and intermittent vomiting and diarrhea. Glucocorticoid-deficient dogs may not require supplemental mineralocorticoids.

Diagnosis and treatment of naturally occurring hypoadrenocorticism in 42 dogs.

Hypoadrenocorticism was diagnosed in 42 dogs over a two-and-a-half-year period. The disease occurred more commonly in young to middle-aged dogs, with a female:male ratio of 2:1. Most dogs had chronic intermittent signs (eg, poor appetite, lethargy and vomiting), but more than a third were in acute adrenal crisis at the time of diagnosis. Serum biochemical testing revealed azotaemia, hyperphosphataemia, hyperkalaemia and hyponatraemia in almost all the dogs. In all dogs, results of adrenocorticotrophic hormone (ACTH) stimulation testing revealed a low to low-normal serum baseline cortisol concentration that failed to increase after ACTH administration. In two dogs with persistently normal serum electrolytes concentration, one had a markedly high plasma ACTH concentration diagnostic for primary hypoadrenocorticism, whereas the other had a low concentration confirming secondary hypoadrenocorticism. Fludrocortisone acetate was initially used for mineralocorticoid replacement in 33 of the 37 treated dogs with primary hypoadrenocorticism (final median dosage, 27.0 micrograms/kg/day), but supplementation was changed to desoxycorticosterone pivalate (DOCP) in four dogs because of poor response or adverse effects. Seven dogs with primary hypoadrenocorticism were treated with DOCP (final median dosage, 2.02 mg/kg/month). Prednisone, initially administered to 36 dogs, was discontinued in 11 dogs because of side effects. Of the dogs treated with fludrocortisone, the response was considered good to excellent in 26 dogs (78.8 per cent), fair in three, and poor in four. All dogs treated with DOCP responded well.

Effects of desoxycorticosterone pivalate administration on blood pressure in dogs with primary hypoadrenocorticism.

A study was designed to evaluate the effects of desoxycorticosterone pivalate (DOCP) on blood pressure in 8 dogs with primary hypoadrenocorticism, and to attempt to identify other factors that might suggest overdosage of the drug. In 4 dogs, primary hypoadrenocorticism had been diagnosed immediately before entry of the dog into the study, and the dogs had not received any mineralocorticoid supplementation. In the other 4 dogs, primary hypoadrenocorticism had been diagnosed 1 to 6 years previously, and dogs were being treated with DOCP at the time of entry into the study. In all 8 dogs, DOCP (2.2 mg/kg of body weight, IM) was administered on days 0, 30, 60, and 90 of the study; each dog was examined on days 0, 30, 60, 75, 90, and 105. At the time of each visit, a medical history was obtained, a complete physical examination and serum biochemical analyses were performed, and body weight and blood pressure were measured. Doppler-shift ultrasonic sphygmomanometry was used to indirectly record systemic systolic and diastolic pressures. None of the dogs developed hypernatremia or hypokalemia or any clinical signs suggestive of hypoadrenocorticism during the study. However, in 6 dogs (3 that had not been previously treated with mineralocorticoids and 3 that had been), there was a significant increase in body weight over the course of the study. Compared with baseline (day 0) arterial blood pressure, neither systolic nor diastolic blood pressure was significantly increased during the study, and all systolic and diastolic blood pressure measurements were within reference ranges at all evaluation times.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicity of desoxycorticosterone pivalate given at high dosages to clinically normal beagles for six months.

Desoxycorticosterone pivalate was administered IM to juvenile Beagles at 0, 2.2, 6.6, or 11 mg/kg of body weight daily over a consecutive 3-day period every 28 days (equivalent to a cumulative monthly dosage of 0, 6.6, 19.8, or 33 mg/kg) for 6 months. Polyuria, polydipsia, and decreases in serum potassium and BUN concentrations were detected while the dogs were being treated. Transient increases in serum sodium concentrations also were detected. The treated males had significant decreases in body weight gain, resulting in an 18% decrease in body weight in the 11-mg/kg dosage group, compared with the controls. The weights of the adrenal glands, epididymides, and testes also were lower in the treated males. Organ weights for the 2.2, 6.6, and 11-mg/kg dosage groups were: 86, 79, and 69%, respectively, of the controls (adrenal glands); 80, 70, and 68%, respectively, of the controls (epididymides); and, 79, 75, and 67%, respectively, of the controls (testes). When normalized to body weight, these decreases in organ weight were still dosage-dependent, but the differences were less remarkable. In contrast, the relative weight (to body weight) of the kidneys (males and females) and of the thyroid and parathyroid glands (males) were higher dosage-dependently. All of the treatment-related effects, other than organ and body weight changes, appeared to be reversible following the cessation of treatment. On the basis of these results, it was concluded that treatment with desoxycorticosterone pivalate could be tolerated, even when given at dosage 15-fold the therapeutic dosage of 2.2 mg/kg every 25 days.