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Subedited by Dr Phil Tucak
Hyperadrenocorticism is a common endocrinopathy in dogs. In 80-85% of affected dogs the cause is an ACTH-secreting pituitary tumour (adenoma, or less commonly hyperplasia) inciting the excessive adrenal cortisol production, termed pituitary dependant hyperadrenocorticism (PDH or Cushing’s disease)1.
Clinical signs may include polydipsia/polyuria, polyphagia, panting, hepatomegaly, muscle weakness, muscle atrophy, weight gain, development of a pendulous abdomen, dermatological changes (alopecia, comedones, hyperpigmentation and calcinosis cutis), and reproductive abnormalities (anoestrus, testicular atrophy).
Dogs with hyperadrenocorticism may develop urinary tract infections, glucose intolerance—diabetes mellitus and coagulopathies (especially pulmonary and aortic thromboemboli). Compression of the adjacent brain by a growing tumour may cause neurological dysfunction2.
The mainstay of therapy in small animal patients has traditionally been long-term management with medical treatments that aim to suppress adrenocortical production of cortisol (such as mitotane and trilostane). The primary form of treatment offered to humans with Cushing’s disease is transsphenoidal surgery3; this being the only modality with the potential for both a tumour and an endocrine cure.
Transsphenoidal hypophysectomy has rarely been offered for affected dogs and cats, primarily due to a lack of experienced surgical and endocrine teams. This situation is changing however, both internationally and in Australia.
Here we report the case of a five-year-old, female-spayed border collie who was presented to their general practice veterinarian for a six-month history of increasing polyphagia, polydipsia and polyuria, and abnormal hair regrowth after a summer clip, with additional progressive dorsal alopecia.
A complete blood count, analysis of serum biochemistries and thyroid hormone concentration were performed, which were unremarkable. Due to the clinical suspicion of hyperadrenocorticism, an ACTH stimulation test was performed; the post-stimulation serum cortisol concentration was measured at 514 nmol/L, consistent with a diagnosis of hyperadrenocorticism.
The dog was referred to SASH for further investigation of the origin of the hyperadrenocorticism. A computed tomography scan of the head, thorax and abdomen was performed. The left and right adrenal glands measured 7.3mm and 5.2mm respectively. The pituitary gland also appeared unenlarged at 3mm in height. Given the absence of an identifiable adrenal mass, a pituitary origin of the hyperadrenocorticism (microadenoma or nodular hyperplasia) was suspected. An endogenous ACTH concentration was measured. This returned a level of 35pg/mL—consistent with pituitary dependant hyperadrenocorticism.
Treatment options for PDH were discussed with the dog’s owners, which included both medical and surgical therapies. Though outcomes of medical and surgical treatments for PDH in dogs have not been compared directly, results of single treatment studies suggest dogs treated surgically are on average likely to survive longer than those treated medically.
A survival analysis study of 219 dogs diagnosed with spontaneous hyperadrenocorticism (of any cause) managed in primary care practice4 (94.1% of which were treated with trilostane) reported a median survival time from first diagnosis of 510 days (95%CI 412-618 days).
Adverse effects are common5, and care is needed when titrating doses. Drug cost and frequent endocrine testing to monitor therapy add to the long-term financial burden for owners. Adrenal directed medical therapy will also not address potential growth of the pituitary tumour itself.
Surgical removal of the pituitary tumour is the only form of treatment that has the potential to affect both an endocrine and a tumour cure.
A study of 306 dogs with PDH treated by transsphenoidal hypophysectomy6 reported a median survival time after surgery of 781 days (range 0-3808 days) with estimated survival rates of 86% at 1 year, 79% at 2 years, 74% at 3 years, 72% at 4 years and 64% at 5 years. The median disease-free interval after surgery was 951 days (range 31-3808 days) with estimated 1-, 2-, 3-, 4-, and 5-year disease-free fractions of 89%, 79%, 74%, 64% and 57% respectively.
Survival time and disease-free interval were significantly longer in dogs with smaller compared to larger tumours (defined by a pituitary height to brain area ratio of >0.31), a result strongly suggesting the benefit of early surgical intervention.
In this case, the dog’s owners elected surgical treatment, and a transsphenoidal hypophysectomy was performed. The dog was anesthetised and positioned in sternal recumbency with head elevated and placed in a surgical head frame. The mouth was secured open, and the skull base was accessed via soft palate incision. A section of the pre- and basisphenoid bone immediately ventral to the pituitary fossa was removed using a rotating burr. The pituitary gland was identified and extirpated, carefully avoiding surrounding blood vessels and neural structures.
Recovery from surgery was rapid with the patient able to eat and drink within hours of recovery from anaesthesia. A moderate hypernatraemia developed within six hours of surgery, which resolved over the next six hours with adjustment intravenous fluid therapy and desmopressin dose.
Animals that have undergone hypophysectomy require lifelong hormonal replacement therapy (hydrocortisone, thyroxine, +/- desmopressin). This is relatively inexpensive and usually well tolerated by the patient.
The dog was discharged four days after surgery, with cortisone acetate, levothyroxine, and desmopressin as ongoing therapy, and several more days of analgesia and antibiosis.
Histopathology of the pituitary confirmed a diagnosis of adenohypophyseal nodular hyperplasia. The postoperative endogenous ACTH concentration of <5pg/mL (below the detection limit of the assay) suggested complete removal of the hyperplastic adenohypophysis.
The dog’s clinical signs of hyperadrenocorticism (polydipsia/polyuria and polyphagia) resolved post-operatively. There was a marked improvement in the quality of the dog’s hair coat and resolution of the dorsal alopecia over the months following surgery.
Transsphenoidal surgery is a well-established treatment with good outcomes for dogs with pituitary dependant hyperadrenocorticism, and is increasingly available as more experienced neurosurgical and endocrine teams are able to offer this procedure.
1. Kooistra H & Galac S (2010) Recent Advances in the Diagnosis of Cushing’s Syndrome in Dogs. Vet Clin North Am Small Anim Pract 40:259-267
2. Behrend EN, Kooistra HS, Nelson R, et al (2013) Diagnosis of spontaneous canine hyperadrenocorticism: 2012 ACVIM consensus statement (small animal). J Vet Intern Med 27:1292–1304 3. Nieman LK, Biller BMK, Findling JW, et al (2015) Treatment of Cushing’s syndrome: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 100:2807–2831 4. Schofield I, Brodbelt DC, Wilson ARL, et al (2020) Survival analysis of 219 dogs with hyperadrenocorticism attending primary care practice in England. Vet Rec 186:348 5. Scudder C, Kenny PJ & Niessen SJM (2015) Treatment of canine and feline hyperadrenocorticism: trilostane and the alternatives. Companion Animal 20,230–238 6. van Rijn SJ, Galac S, Tryfonidou MA, et al. (2016) The influence of pituitary size on outcome after transsphenoidal hypophysectomy in a large cohort of dogs with pituitary-dependent hypercortisolism. J Vet Intern Med 30:989–995
Dr. Patrick Kenny, BVSc (Hons) DipACVIM (Neurology) DipECVN FHEA MRCVS
Dr Patrick Kenny graduated from the University of Sydney in 2002. He then completed a rotating internship in small animal medicine and surgery at Queensland Veterinary Specialists in Brisbane, Australia before undertaking a residency in Neurology and Neurosurgery at the University of California, Davis.
Dr Kenny was admitted to the American College of Veterinary Internal Medicine (Neurology) and the European College of Veterinary Neurology in 2007.
He subsequently held positions in England and Norway, and for the past six years at SASH in Sydney, where he is head of the Neurology and Neurosurgery Department.
Dr Amy Lam, BVSc (Hons) GradCertVetStud MANZCVS MRCVS FANZCVS
Dr Amy Lam graduated from the University of Sydney in 2004. After several years in small animal practice, she undertook an internship at the University of Sydney and completed a Graduate Certificate in Veterinary Clinical Sciences with a project on feline hyperthyroidism.
In 2008, Dr Lam joined the team at SASH, as a small animal medicine resident.
She has published papers on pituitary apoplexy, canine systemic mycobacteriosis, and feline laryngeal disease, and won awards from the Australian Small Animal Veterinary Association for Best Research Publication and Case Report.