Use of aminoglutethimide in the treatment of pituitary‐dependent hyperadrenocorticism in the dog

Abstract

The aim of this study was to evaluate the efficacy and safety of aminoglutethimide in the treatment of dogs with pituitary-dependent hyperadrenocorticism (PDH). Ten dogs were diagnosed with PDH based on clinical and laboratory data, adrenal function tests (adrenocorticotropic hormone [ACTH] stimulation test and urinary cortisol/creatinine ratio [UCCR] combined with a high dose oral dexamethasone suppression test) and ultrasonographic evaluation of the adrenal glands. Aminoglutethimide was administered daily at a dose of 15 mg/kg bodyweight for one month. Median basal cortisol concentration and post-ACTH cortisol concentration one month after treatment were significantly lower than pretreatment values. Complete response was achieved in one dog, and partial response was obtained in three dogs. Severe side effects of anorexia, vomiting and weakness occurred in one dog and medication was withdrawn. Two further dogs developed decompensations of concurrent diseases and medication was stopped in these animals as well. Mild toxicity occurred in four dogs. Moderate to severe elevations in liver enzymes occurred in all dogs. The efficacy of this drug is lower than that observed using mitotane and ketoconazole, and adverse effects limit its use. Aminoglutethimide, using the protocol described, cannot be recommended for long-term management of PDH in the dog.

Trismus due to myotonia associated with hyperadrenocorticism in a dog

“…On the other hand, some cases in past studies indicated that remission of myotonia symptoms, especially those of the temporalis muscle, tends to be difficult. In a few past case reports, myotonia of the limbs did not improve despite trilostane treatment [ 9 , 13 , 15 , 19 ]; in this case, as well as in previous cases, no sufficient therapeutic effects were observed on myotonia. The reason for different treatment responses between trismus and myotonia of the extremities is not clear.…”

“…In the young dogs, myotonia can occur as a hereditary condition in Chow Chow, Miniature Schnauzer, Labrador Retriever, Australian Cattle Dog, American Bulldog, and other breeds [ 1 , 5 , 6 , 16 , 17 ]. In an adult dog, acquired myotonia can also develop as an uncommon complication of hyperadrenocorticism [ 13 , 15 , 19 ]. The major clinical presentation of hyperadrenocorticism-associated myotonia is an abnormal gait due to stiff limbs [ 15 ].…”

“…In an adult dog, acquired myotonia can also develop as an uncommon complication of hyperadrenocorticism [ 13 , 15 , 19 ]. The major clinical presentation of hyperadrenocorticism-associated myotonia is an abnormal gait due to stiff limbs [ 15 ]. In some cases, generalized increase in muscle tone with an arched back, drawn-back ears, and tongue hypertrophy are also observed [ 19 ].…”

A Comparison of the Survival Times of Dogs Treated with Mitotane or Trilostane for Pituitary-Dependent Hyperadrenocorticism

“…4,5 In addition, there have been reports of the treatment of HAC using ketoconazole, selegiline hydrochloride, and aminoglutethimide. [6][7][8] Mitotane binds covalently to adrenal proteins before being converted to a reactive metabolite, resulting in the destruction of adrenal tissue. Destruction of the adrenal cortices can be partial or complete, depending on dose and frequency of administration.…”

The Endocrine and Metabolic Systems

“…63 Selegiline (L-Deprenyl; Anipryl) is a monoamine oxidase-B inhibitor approved for the treatment of PDH, but it is not effective by itself. 64 Trilostane (not currently available in the United States) is a safe and effective inhibitor of steroidogenesis.…”