Clinical Endocrinology of Companion Animals

Jacquie Rand, Ellen Behrend, Danielle Gunn-Moore, Michelle Campbell-Ward, Jacquie Rand, Ellen Behrend, Danielle Gunn-Moore, Michelle Campbell-Ward

• Publisher: Wiley-Blackwell
• Year: 2012
• Print ISBN: 9780813805832
• eBook ISBN: 9781118444979
• Edition: 1
• Topic: Medicina
• Subtopic: Medicina veterinaria

Clinical Endocrinology of Companion Animals offers fast access to clinically relevant information on managing the patient with endocrine disease. Written by leading experts in veterinary endocrinology, each chapter takes the same structure to aid in the rapid retrieval of information, offering information on pathogenesis, signalment, clinical signs, diagnosis, differential diagnosis, treatment, prognosis, and prevention for a broad list of endocrine disorders.  Chapters begin with brief summaries for quick reference, then delve into greater detail.

With complete coverage of the most common endocrine diseases, the book includes chapters on conditions in dogs, cats, horses, ferrets, reptiles, and other species.  Clinical Endocrinology of Companion Animals is a highly practical resource for any veterinarian treating these common diseases.

CHAPTER 1

Hypoadrenocorticism in Dogs

Patty Lathan

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Pathogenesis

• Primary hypoadrenocorticism results from the destruction of >90% of the adrenal cortex.
• Most cases are presumed to be due to an immune-mediated process.
• Combined glucocorticoid and mineralocorticoid deficiency occur most frequently, but isolated glucocorticoid deficiency (“atypical hypoadrenocorticism”) is probably underdiagnosed.

Classical Signs

• Young to middle-age dogs are predisposed, as are poodles, West Highland White Terriers, and Great Danes.
• Addison’s disease is known as the “Great Pretender” because nonspecific signs such as lethargy, decreased appetite, and weight loss predominate.
• Gastrointestinal signs such as vomiting and diarrhea are also common.
• Patients may present in hypovolemic shock or following collapse.

Diagnosis

• ACTH stimulation test demonstrates minimal cortisol response.

Treatment

• Glucocorticoid and mineralocorticoid supplementation, ± intravenous fluids and supportive therapy.

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I. Pathogenesis

A. Pathophysiology:

1. Most patients with naturally occurring hypoadrenocorticism (“Addison’s disease”) suffer from ­combined glucocorticoid and mineralocorticoid deficiency:

Figure 1.1 The adrenal cortex is made up of three layers—the zona glomerulosa, zona fasciculata, and zona reticularis. The zone glomerulosa is responsible for mineralocorticoid synthesis, whereas the inner two layers are responsible for glucocorticoid and sex hormone synthesis. (Image provided by Dr. Jim Cooley.)

a. Aldosterone is a mineralocorticoid secreted in the outermost layer of the adrenal cortex, the zona glomerulosa (Figure 1.1). The major action of aldosterone is the conservation of sodium and water, and excretion of potassium and hydrogen ions (acid), from the distal renal tubule. In ^­normal dogs, secretion of aldosterone is stimulated by hypovolemia and hyperkalemia and is primarily regulated by the renin-angiotensin-aldosterone system (RAAS). In patients with ­hypoadrenocorticism and subsequent aldosterone deficiency, hyponatremia, hyperkalemia, and hypovolemia are common.

b. Cortisol is a glucocorticoid produced in the inner-most layers of the adrenal cortex, the zonae fasciculata and reticularis. Cortisol has activity in almost every cell in the body. Functions include stimulation of gluconeogenesis and erythropoiesis, maintenance of gastrointestinal mucosal integrity, and suppression of the inflammatory response. Additionally, cortisol has important roles in the maintenance of blood pressure and contractility of the heart. Cortisol requirements increase during times of stress. Cortisol release from the adrenal cortex is controlled by adrenocorticotropic hormone (ACTH) (Figure 1.2). Cortisol deficiency in dogs with hypoadrenocorticism may result in gastrointestinal signs, lethargy, hypoglycemia, hypotension, and anemia.

2. Some patients with hypoadrenocorticism suffer from isolated glucocorticoid deficiency. In these cases, aldosterone secretion is preserved, and electrolyte abnormalities are not present. Patients with isolated glucocorticoid deficiency are often said to have “atypical hypoadrenocorticism” or “atypical Addison’s disease.”

B. Etiology:

1. Primary hypoadrenocorticism results from the destruction of greater than 90% of the adrenal cortex. Most cases of naturally occurring hypoadrenocorticism in dogs are idiopathic, most likely due to immune-mediated destruction of the adrenal cortex. Rarely, infiltration of the adrenal cortex by fungal disease, amyloidosis, or neoplasia has been reported. Trauma, hemorrhage, and infarction may also lead to hypoadrenocorticism.

2. Drug-induced adrenocorticolysis can also result in hypoadrenocorticism in dogs being treated for hyperadrenocorticism:

a. Adrenocortical necrosis caused by mitotane is usually selective to the zonae fasciculata and reticularis, resulting in decreased cortisol production. However, inadequate monitoring or use in a ­particularly sensitive patient may lead to destruction of the cells of the zona glomerulosa, resulting in aldosterone deficiency as well.

b. The other commonly used medication to treat hyperadrenocorticism is trilostane. As an inhibitor of at least one enzyme involved in steroid synthesis (3β-hydroxysteroid dehydrogenase), trilostane overdose may lead to cortisol deficiency and, less frequently, aldosterone deficiency. Additionally, idiosyncratic adrenocortical necrosis has been reported to occur in some dogs taking trilostane, resulting in hypoadrenocorticism.

Figure 1.2 (a) The hypothalamic pituitary axis without negative feedback. Corticotropin-releasing hormone (CRH) is released by neurons in the hypothalamus and transported to the anterior pituitary by portal circulation. CRH then stimulates the release of ACTH from the pituitary gland into systemic circulation. ACTH then stimulates the synthesis and secretion of cortisol. (b) Negative feedback is the mechanism by which the endocrine system regulates secretion of its hormones. In the HPA-axis, ACTH feeds back to the hypothalamus to inhibit continued release of CRH, which then leads to decreased release of ACTH. Cortisol feeds back to both the hypothalamus to decrease CRH secretion, and to the pituitary gland to decrease ACTH release. By this mechanism, the HPA-axis is able to maintain the physiologically necessary concentration of cortisol in the bloodstream—not too much, nor too little.

3. Hypoadrenocorticism secondary to decreased ACTH production is characterized by isolated glucocorticoid deficiency since ACTH has little regulatory control of aldosterone production:

a. The most common form of secondary hypoadrenocorticism is iatrogenic, resulting from exogenous glucocorticoid administration (Figure 1.3). Exogenous glucocorticoids inhibit the release of adrenocorticotropic hormone (ACTH) from the pituitary gland. Adrenal gland atrophy then occurs, resulting in decreased secretion of cortisol. Following acute withdrawal of the exogenous glucocorticoid, a stressful event will cause increased release of ACTH, but the atrophied adrenal glands will be unable to respond by secreting an appropriate amount of cortisol, which may result in signs of cortisol deficiency. Chronic administration of glucocorticoids is more likely to result in hypoadrenocorticism than short-term use, and longer-acting repositol steroids (such as methylprednisolone acetate) are more potent suppressors of ACTH than shorter-acting glucocorticoids (such as oral prednisolone). Topical, otic, and ophthalmic preparations containing glucocorticoids may also lead to iatrogenic hypoadrenocorticism, particularly in smaller patients.

b. Naturally occurring causes of secondary hypoadrenocorticism include pituitary masses, trauma, or other lesions that inhibit ACTH release.

Figure 1.3 Diagrammatic representation of the relationship between iatrogenic hyperadrenocorticism and iatrogenic hypoadrenocorticism. Chronic glucocorticoid administration leads to clinical signs of glucocorticoid excess (“iatrogenic hyperadrenocorticism”). At the same time, the exogenous glucocorticoid provides feedback inhibition to the pituitary gland, decreasing the production of ACTH. Without ACTH, the dog’s own adrenal glands atrophy. While the dog is still taking the exogenous glucocorticoids, the dog will appear to have hyperadrenocorticism. Upon abrupt withdrawal of the steroid, the dog’s own atrophied adrenal gland will be unable secrete cortisol, potentially resulting in clinical signs of hypoadrenocorticism. Clinical signs may be seen more often following a stressful event in these patients.

4. At this time, the etiology of atypical hypoadrenocorticism (isolated glucocorticoid deficiency) is un­known. ACTH deficiency has been ruled out in many cases. It may be the result of partial immune-mediated destruction of the adrenal cortex, sparing the zona glomerulosa. Although some have hypothesized that atypical hypoadrenocorticism is simply an early manifestation of “typical” hypoadrenocorticism, many patients never lose their ability to secrete aldosterone.

C. Risk factors for hypoadrenocorticism:

1. Dogs with other immune-mediated endocrinopathies, such as diabetes mellitus and hypothyroidism, may be at increased risk for hypoadrenocorticism.

2. Dogs with the disease are more likely to have clinical signs during or following a stressful event.

II. Signalment

A. Any breed of dog may be afflicted with hypoadrenocorticism, including mixed-breeds. However, an increased prevalence of hypoadrenocorticism has been documented in all sizes of poodles, West Highland white ­terriers, Great Danes, bearded collies, Portuguese water dogs, Leonbergers, Nova Scotia duck-tolling ­retrievers, and possibly Saint Bernards.

B. A genetic basis has been proved in standard poodles, Bearded collies, and Nova Scotia duck-tolling retrievers.

C. Young to middle-aged dogs (2–5 years old) are predisposed. However, dogs of any age can be diagnosed with hypoadrenocort...

Table of contents

• Cover
• Title page
• Copyright page
• Dedication
• Contributors
• Preface
• CHAPTER 1: Hypoadrenocorticism in Dogs
• CHAPTER 2: Hypoadrenocorticism in Cats
• CHAPTER 3: Hypoadrenocorticism in Other Species
• CHAPTER 4: Critical Illness-Related Corticosteroid Insufficiency (Previously Known as Relative Adrenal Insufficiency)
• CHAPTER 5: Hyperadrenocorticism in Dogs
• CHAPTER 6: Primary Functioning Adrenal Tumors Producing Signs Similar to Hyperadrenocorticism Including Atypical Syndromes in Dogs
• CHAPTER 7: Hyperadrenocorticism in Cats
• CHAPTER 8: Primary Functioning Adrenal Tumors Producing Signs Similar to Hyperadrenocorticism Including AtypicalSyndromes in Cats
• CHAPTER 9: Hyperadrenocorticism in Ferrets
• CHAPTER 10: Hyperadrenocorticism and Primary Functioning Adrenal Tumors inOther Species (Excluding Horses and Ferrets)
• CHAPTER 11: Hyperadrenocorticism (Pituitary Pars Intermedia Dysfunction) in Horses
• CHAPTER 12: Primary Hyperaldosteronism
• CHAPTER 13: Pheochromocytoma in Dogs
• CHAPTER 14: Pheochromocytoma in Cats
• CHAPTER 15: Canine Diabetes Mellitus
• CHAPTER 16: Feline Diabetes Mellitus
• CHAPTER 17: Diabetes Mellitus in Other Species
• CHAPTER 18: Canine Diabetic Emergencies
• CHAPTER 19: Feline Diabetic Ketoacidosis
• CHAPTER 20: Equine Metabolic Syndrome/Insulin Resistance Syndrome in Horses
• CHAPTER 21: Insulinoma in Dogs
• CHAPTER 22: Insulinoma in Cats
• CHAPTER 23: Insulinomas in Other Species
• CHAPTER 24: Gastrinoma, Glucagonoma, andOther APUDomas
• CHAPTER 25: Hypothyroidism in Dogs
• CHAPTER 26: Hypothyroidism in Cats
• CHAPTER 27: Hypothyroidism in Other Species
• CHAPTER 28: Hyperthyroidism in Dogs
• CHAPTER 29: Hyperthyroidism in Cats
• CHAPTER 30: Hyperthyroidism/Thyroid Neoplasia in Other Species
• CHAPTER 31: Hypocalcemia in Dogs
• CHAPTER 32: Hypocalcemia in Cats
• CHAPTER 33: Hypocalcemia in Other Species
• CHAPTER 34: Hypercalcemia in Dogs
• CHAPTER 35: Hypercalcemia in Cats
• CHAPTER 36: Hypercalcemia in Other Species
• CHAPTER 37: Nutritional Secondary Hyperparathyroidism in Reptiles
• CHAPTER 38: Hyposomatotropism in Dogs
• CHAPTER 39: Hyposomatotropism in Cats
• CHAPTER 40: Acromegaly in Dogs
• CHAPTER 41: Acromegaly in Cats
• CHAPTER 42: Diabetes Insipidus and Polyuria/Polydipsia in Dogs
• CHAPTER 43: Diabetes Insipidus in Cats
• CHAPTER 44: Hyponatremia, SIADH, andRenal Salt Wasting
• CHAPTER 45: Estrogen- and Androgen-Related Disorders
• CHAPTER 46: Progesterone and Prolactin-Related Disorders; Adrenal Dysfunction and Sex Hormones
• CHAPTER 47: Pathologic Reproductive Endocrinology in Other Species
• Index
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