Hyperadrenocorticism associated with sex steroid excess

Diagnosis of sex steroid excess or hyperadrenocorticism in dogs may be challenging. Unlike Cushing's disease, sex steroid excess may have a multitude of manifestations that differ from standard hyperadrenocorticism. In particular, the clinical scenario of a dog with sex steroid imbalance involves one of three systems: dermatologic, reproductive, or hepatic. The history of a dog with hyperadrenocorticism manifesting as sex steroid imbalance often lacks the classical clinical signs of polydipsia and polyuria. Dogs with sex steroid imbalance will often be of specific breeds such as miniature poodles and exhibit trunkal hair loss as the only sign. There is often involvement of the reproductive system, manifested as the growth of perianal adenomas in neutered male or female dogs. The most common laboratory findings consist of elevations in serum alkaline phosphatase and serum alanine transferase. The following article reviews the etiology, common signalment, clinical signs, and laboratory findings associated with atypical hyperadrenocorticism caused by sex steroid imbalance and then explores the medical, surgical, and radiation treatment options.     

Cyclic estrous-like behavior in a spayed cat associated with excessive sex-hormone production by an adrenocortical carcinoma

A 15-year-old, spayed female domestic shorthair cat was evaluated for 1-year duration of cyclic intermittent estrous behavior. Diagnostic testing performed before referral, including baseline progesterone concentration, human chorionic gonadotropin (hCG) hormone stimulation test and surgical exploratory laparotomy, had remained inconclusive for a remnant ovary. Evaluation of sex hormones before and after adrenocorticotropic hormone (ACTH) administration revealed increased basal concentrations of androstenedione, estradiol, progesterone, and 17α-hydroxyprogesterone and normal ACTH-stimulated hormone concentrations. Enlargement of the right adrenal gland was identified by abdominal ultrasound. The cat underwent an adrenalectomy and histopathology of the excised adrenal gland was consistent with an adrenocortical carcinoma. Clinical signs resolved immediately following surgery, and most hormone concentrations declined to within or below the reference interval (RI) by 2 months after surgery.     

Hyperadrenocorticism and hyperprogesteronemia in a cat with an adrenocortical adenocarcinoma

A seven-year-old, neutered male domestic shorthair cat was evaluated for poorly regulated diabetes mellitus and increased skin fragility. Imaging studies revealed a right adrenal gland tumor, but cortisol testing did not support a diagnosis of hyperadrenocorticism. Serum concentrations of progesterone and testosterone were increased compared with a group of normal cats, and the clinical signs were attributed to hyperprogesteronemia. At necropsy, a diagnosis of adrenocortical adenocarcinoma was confirmed, and immunohistochemical staining confirmed the presence of progesterone within the tumor. Clinical signs of hyperadrenocorticism in cats may occur due to increased serum concentrations of hormones other than cortisol.     

Trilostane treatment of bilateral adrenal enlargement and excessive sex steroid hormone production in a cat

A 14-year-old neutered female cat was presented for the investigation of aggression and male-type behaviour. Bilateral adrenal enlargement together with elevated plasma concentrations of oestradiol and testosterone were identified, with no evidence of hypercortisolaemia. These findings are similar to the syndrome of hyperadrenocorticism recognised most commonly in ferrets. The cat was treated for six months with the enzyme inhibitor drug, trilostane, and showed a moderate improvement in clinical signs.     

Dynamic adrenal function testing in eight dogs with hyperadrenocorticism associated with adrenocortical neoplasia.

The results of adrenocorticotropin (ACTH) stimulation and low-dose dexamethasone suppression tests (LDDST) were evaluated retrospectively in eight dogs with clinical signs of hyperadrenocorticism arising from functional adrenocortical tumours, and compared with the results from 12 dogs with confirmed pituitary-dependent hyperadrenocorticism (PDH). The post-ACTH cortisol concentration in the dogs with adrenocortical tumours ranged from 61 to 345-6 nmol/litre (median 251.5 nmol/litre) and they were within the reference range (150 to 450 nmol/litre) in five and unexpectedly low (< 150 nmol/litre) in three dogs. Both the basal and post-ACTH cortisol concentrations were significantly lower in the dogs with adrenocortical neoplasia than in the dogs with PDH. Eight hours after the LDDST, only two of six dogs with adrenocortical tumours had a cortisol concentration above 30 nmol/litre, and the median resting, three, and eight-hour cortisol concentrations were 31.5, 23.0, and 22.7 nmol/litre respectively. There was no significant cortisol suppression during the LDDST, although interpretation was complicated by the low cortisol concentrations, but two dogs showed a pattern of apparent suppression. Two dogs with adrenal tumours showed a diagnostically significant increase in 17-OH-progesterone concentration in response to ACTH although their cortisol concentrations did not increase greatly. These results differ from previous reports of the response of functional adrenal tumours to dynamic endocrine tests.     

Hemifacial spasm associated with an intracranial mass in two dogs

Two dogs were presented with hemifacial spasm. Computed tomography images of both the dogs revealed an intracranial mass. In the first dog, a lesion at the level of the medulla oblongata was thought to cause primary irritation of the facial nucleus, with consequently permanent contraction of the ipsilateral facial muscles. In the second dog, a mass seemingly arising from the middle cranial fossa presumably isolated the facial motor neurons from upper motor neuron control, which resulted in hemifacial spasm as a result of loss of inhibitory interneuronal activity.     

Hypercalcaemia in two dogs caused by excessive dietary supplementation of vitamin D

A three-year-old Border collie was presented with a two-week history of lethargy, stiff gait, polydipsia and polyuria. Biochemical analysis revealed hypercalcaemia. Serum concentrations of 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) were markedly elevated and parathyroid hormone was undetectable. Subsequent analysis of the dog's diet revealed that the food contained excessive amounts of vitamin D. The hypercalcaemia resolved following treatment with bisphosphonates and dietary change. Hypervitaminosis D was diagnosed in a second unrelated dog, which had been fed the same brand of dog food as case 1. The dog was also hypercalcaemic and had markedly elevated serum concentrations of 25(OH)D and 1,25(OH)2D. Hypervitaminosis D in dogs has been reported to occur secondarily to ingestion of either rodenticides containing cholecalciferol or antipsoriatic ointments that contain vitamin D analogues. Hypervitaminosis D has also been reported following the treatment of hypoparathyroidism. To the authors' knowledge, this is the first report of hypervitaminosis D in dogs following the accidental over supplementation of a commercial diet with vitamin D. While the benefits of adequate dietary vitamin D are well established in dogs, the potential deleterious effects of over supplementation of vitamin D should also be acknowledged.     

Myotonia associated with hyper-adrenocorticism in two dogs

Two dogs developed a disabling gait abnormality characterised by stiffness. The abnormality was consistent with a diagnosis of myotonia secondary to hyper-adrenocorticism. The first dog had iatrogenic hyperadrenocorticism, and its signs improved substantially after corticosteroid administration was gradually withdrawn. The second had pituitary-dependent hyperadrenocorticism, but myotonic signs progressed despite effective mitotane therapy. Procainamide administration reduced the myotonic stiffness in the second case.     

Electrocardiographic abnormalities associated with tetanus in two dogs

Bradycardia, sinus arrest, and second-degree atrioventricular block developed in 2 dogs with tetanus. Clinical signs attributable to bradycardia were not apparent. Administration of atropine resulted in resolution of the arrhythmias. Both dogs responded well to supportive treatment; the bradycardia resolved within 4 days of onset without specific treatment. Tetanus should be included in the differential diagnosis when increased neuromuscular excitability and bradycardia are evident, as is found in toxicity with acetylcholinesterase inhibitors, increased intracranial pressure, and other neurologic disorders.     

Retinopathy associated with ivermectin toxicosis in two dogs

CASE DESCRIPTION: 2 dogs (dogs 1 and 2) were examined for sudden onset of blindness. Both dogs had mild obtundation and mydriasis in both eyes. It was thought that dog 1 may have ingested ivermectin; dog 2 had been treated with ivermectin for demodectic mange. CLINICAL FINDINGS: On initial examination, both dogs had mydriasis and decreased pupillary light reflexes in both eyes. Dog 1 had an absent menace response bilaterally. Fundic examination of both eyes in both dogs revealed regions of multifocal retinal edema and folds with low-lying retinal separation. The electroretinogram was extinguished in dog 1 and attenuated in dog 2. Ivermectin was detected in serum samples from both dogs. TREATMENT AND OUTCOME: Both dogs made a complete clinical recovery following cessation of exposure to ivermectin; electroretinographic findings improved, and retinal edema resolved with some residual chorioretinal scarring. CLINICAL RELEVANCE: To our knowledge, this is the first report of resolution of retinal edema and electroretinographic changes associated with ivermectin toxicosis in dogs. In dogs that develop blindness suddenly, fundic examination, electroretinography, and assessment of serum ivermectin concentration are diagnostically useful, even if exposure to ivermectin is unknown.     

Hypoglycemia associated with nonislet cell tumor in 13 dogs

Hypoglycemia associated with nonislet cell tumor was found in 13 dogs. In each dog, clinical signs were related directly to adrenergic and neuroglucopenic effects of hypoglycemia and included collapsing episodes, tremors, restlessness, weakness, and grand mal seizures that were responsive to glucose administration. Eight of the dogs had hepatocellular carcinoma; surgical resection of the tumor achieved remission of clinical signs in 3 of these dogs. Other hepatic tumors associated with hypoglycemia included leiomyosarcoma and hemangiosarcoma involving solitary lobes of the liver. Nonhepatic tumors included splenic hemangiosarcoma, diffuse metastatic melanoma, and salivary gland adenocarcinoma.     

Corticoid production by four dogs with hyperfunctioning adrenocortical tumours during treatment with mitotane (o,p'-DDD).

In two dogs with hyperadrenocorticism due to an adrenocortical tumour, treatment with o,p'-DDD was started. Their hormonal response was monitored by measurements of the urinary corticoid/creatinine ratio. In one dog, two courses of 10 days treatment with o,p'-DDD were ineffective, whereas in the other dog the urinary corticoids decreased to very low levels after only six days of treatment, and corticosteroid supplementation had to be started. Two other dogs received o,p'-DDD according to a protocol used for the treatment of pituitary-dependent hyperadrenocorticism which aims at the complete destruction of the adrenal cortices, with substitution for the induced hyperadrenocorticism. Both dogs made a good recovery and their urinary corticoid/creatinine ratio decreased to within the reference range. In one of them the tumour had decreased considerably in size by five weeks after the start of the treatment.     

Potentiation of porcine circovirus 2-induced postweaning multisystemic wasting syndrome by porcine parvovirus is associated with excessive production of tumor necrosis factor-alpha

This study investigated the potentiation of porcine circovirus 2 (PCV2)-induced postweaning multisystemic wasting syndrome by porcine parvovirus (PPV) and found it was associated with excessive production of tumor necrosis factor-alpha (TNF-alpha). Colostrum-deprived conventional pigs were inoculated intranasally with PCV2 or PPV alone or in combination (PCV2 and PPV). In vitro assay of TNF-alpha, obtained from alveolar macrophages coinfected with PCV2 and PPV, showed a significant increase in TNF-alpha compared to single infection of macrophages with either PCV2 or PPV alone (P < 0.05). All pigs inoculated with PCV2 and PPV developed severe postweaning wasting syndrome, whereas clinical signs (e.g., weight loss) were present but perhaps less severe in either PCV2- or PPV-inoculated pigs. Compared to the pigs inoculated with PCV2 or PPV alone, pigs inoculated dually with PCV2 and PPV showed significantly (P < 0.05) increased levels of TNF-alpha. Levels of TNF-alpha in the sera were reversely correlated with the body weight in pigs experimentally infected with dual inoculation of PCV2 and PPV (r(s) = -0.92, P < 0.001). These data suggest that a potentiation of PPV in PCV2-induced PMWS is associated with the excessive production of TNF-alpha.     

Prolonged coagulopathy associated with brodifacoum poisoning in two dogs

Two dogs developed a generalised bleeding disorder after ingestion of brodifacoum, a compound belonging to a new generation of more potent and longer-acting anticoagulant rodenti-cides. Haemorrhage recurred after treatment with conventional dosages of vitamin K₁ Successful therapy required dosages of vitamin K₁ of 5 mg/kg for a period of up to eight weeks.     

Polymyositis associated with Ehrlichia canis infection in two dogs

Clinical, haematological, biochemical, electrophysiological and pathological features of two dogs infected with Ehrlichia canis and with concurrent signs of polymyositis are presented. Both dogs had a history of relatively acute onset, progressive tetraparesis, hyporeflexia and generalised muscle wasting. Skeletal muscles were atrophic and characterised histologically by plasmocytic, lymphocytic and immature lymph-oreticular cellular infiltrates with accompanying areas of necrosis. Histopathological similarities between ehrlichiosis and polymyositis are noted and a probable aetiological relationship is inferred.