Endocrine Disorders PDF

Endocrine Disorders 15 CHA P TE R Patricia A. Schenck...

Endocrine Disorders 15 CHA P TE R Patricia A. Schenck F. Thyroglobulin autoantibodies (TgAA) (dogs only) DISORDERS OF THYROID METABOLISM 1. Marker for lymphocytic thyroiditis I. Normal thyroid function 2. Can be detected before the development of A. Hypothalamus secretes thyroid-releasing hormone hypothyroidism (TRH), which stimulates the release of thyroid- 3. Detects active inflammation stimulating hormone (TSH) from the pituitary 4. Provides no information concerning thyroid gland. TSH stimulates the release of thyroid function hormones from the thyroid glands. Released G. T3AA, T4AA (dogs only) thyroid hormones exert negative feedback on the 1. Present in some (but not all) dogs that have hypothalamus and pituitary glands to decrease lymphocytic thyroiditis the production of TSH 2. T3AA interfere with measurement of T3 and FT3 B. Hormones produced by the thyroid 3. T4AA interfere with measurement of T4 and 1. Total T4 (thyroxine, tetra-iodothyronine) FT4 (some methods) but do not interfere includes free and protein-bound with FT4d 2. Total T3 (tri-iodothyronine) includes free and H. T3 suppression test protein-bound 1. Used in the diagnosis of hyperthyroid cats 3. Free T4 (FT4) 2. A “pre” sample is taken for measurement of 4. Free T3 (FT3) (the active thyroid hormone) T4, T3, FT4, and FT3. T3 supplement is given II. Tests for thyroid function (25 ug) every 8 hours for six or seven treat- A. Total T4 ments. A “post” sample is collected 2 to 4 1. Measurement readily available hours after the last treatment 2. May be falsely normal in hypothyroid dogs 3. In a normal animal, the administration of T3 that have T4 autoantibodies (T4AA) supplement should result in increases in T3 3. 5% to 10% of hyperthyroid cats have normal and FT3 concentrations in the “post” sample T4 concentrations compared with the “pre” sample. This eleva- B. Total T3. False results occur in 20% of hypothyroid tion of T3 and FT3 should cause suppression dogs because of the presence of T3 autoantibodies of T4 and FT4 production (T3AA). 4. In hyperthyroid cats, T3 and FT3 concentra- C. Free T4 tions increase in the post sample, but there is 1. Different methods available for measurement either no or poor suppression of T4 and FT4, 2. Free T4 by equilibrium dialysis (FT4d) is the indicating a loss of negative feedback “gold standard” measurement III. Hypothyroidism in dogs a. Less affected by illness or medication than A. Hypothyroidism is the most common endocrine are T4 or other methods of FT4 measurement disease in dogs, with an estimated prevalence of b. Free from T4AA interference approximately 0.5%. Most common in middle- c. More consistently increased in hyperthy- aged purebred dogs. Can occur in any breed, but roid cats with other concurrent illnesses golden retrievers and Doberman pinschers have d. Delayed or inappropriate shipping can the highest incidence cause increased values B. Pathogenesis D. Free T3. Not much diagnostic utility as a single 1. Primary hypothyroidism (thyroid defect). In test. False results occur in 20% of hypothyroid primary hypothyroidism, thyroid hormone dogs because of the presence of T3AA synthesis is impaired, and concentrations of E. TSH thyroid hormones decrease in serum. TSH in- 1. Poor accuracy on its own but good accuracy creases in an attempt to stimulate thyroid hor- in combination with thyroid hormone mone production measurement a. Acquired (most common) 2. Elevated in most cases of hypothyroidism but (1) Lymphocytic thyroiditis (about 50% of may also be elevated during recovery from cases) illness or with administration of sulfa-containing (2) Idiopathic thyroid follicular atrophy antibiotics b. Congenital (dyshormonogenesis) 208  CHAPTER 15 Endocrine Disorders 209 2. Secondary hypothyroidism (nonthyroid gland hypertriglyceridemia, nonregenerative anemia defect) in about 35%, nonspecific findings a. Acquired (pituitary masses) 2. Diagnosis should not be based on clinical signs b. Congenital (dwarfism, receptor defects, alone dyshormonogenesis) 3. Primary hypothyroidism is diagnosed based C. Lymphocytic thyroiditis on finding low concentrations of thyroid hor- 1. Thyroglobulin autoantibody is a marker for mones with an elevation of TSH lymphocytic thyroiditis. Some dogs also have 4. Hypothyroidism should not be diagnosed autoantibodies to T3 or T4 based on a single low T4 concentration 2. Present in about 4% of healthy dogs F. Other causes of low thyroid hormone 3. Hereditary concentrations 4. Breed predilection: English setter, dalmatian, 1. Metabolic response to nonthyroidal illness basenji, Rhodesian ridgeback, Old English a. Often termed “sick euthyroid” sheepdog, boxer, others b. FT4 by equilibrium dialysis is often normal 5. Stages of lymphocytic thyroiditis but may be low a. Subclinical thyroiditis 2. Medications such as phenobarbital, glucocorti- (1) TgAA present coids, sulfonamides (2) Thyroid hormone and TSH concent- 3. Sighthound breeds (such as greyhounds, rations normal salukis, others) may normally have lower (3) Focal inflammatory infiltrates of concentrations of thyroid hormones than lymphocytes other breeds (4) No clinical signs relating to hypothy- G. Treatment roidism 1. Supplemental T4: 0.01 mg/lb once to twice daily (5) Treatment with T4 not warranted 2. Fatty foods improve absorption of T4 b. Subclinical hypothyroidism (partial thyroid 3. Peak absorption of supplement typically occurs failure) about 3 to 4 hours after ingestion of supplement (1) TgAA present 4. Monitor thyroid hormone levels 3 to 4 weeks (2) Elevated TSH concentration after starting supplement (3) Thyroid hormone concentrations normal 5. Signs of hyperthyroidism such as anxiousness, or borderline low panting, and hyperactivity may occur if the T4 (4) Extensive lymphocytic inflammatory in- supplement dose is excessive filtrates with follicular cell hypertrophy 6. If thyroid supplement has been started before c. Clinical hypothyroidism a definitive diagnosis of hypothyroidism, all (1) TgAA present supplements must be stopped for 4 to 6 weeks (2) Low thyroid hormone concentrations, before testing thyroid function to determine elevated TSH concentration whether hypothyroidism is actually present (3) Extensive diffuse lymphocytic inflam- IV. Hypothyroidism in cats matory infiltrates A. Naturally occurring is rare (4) Functional thyroid follicles rare B. Clinical signs include dwarfism, stunted growth, D. Clinical signs apathy, lethargy, constipation, thickened skin, 1. Weight gain or obesity seborrhea 2. Lethargy, weakness C. Thyroid hormone concentrations are low, and 3. Cold intolerance, heat seeking TSH is elevated 4. Skin disorders occur in 85% of patients with D. Treatment with T4: 0.01 to 0.02 mg/kg/day hypothyroidism. Skin disorders include poor V. Hyperthyroidism in cats coat quality, alopecia, hypopigmentation, A. The average age for hyperthyroid cats is 12 to secondary pyoderma and pruritus, otitis 13 years. Less than 5% of cases are in cats 5. “Tragic” facial expression younger than 10 years 6. Myxedema B. Hyperthyroidism is usually due to benign adeno- 7. Cardiac abnormalities including bradycardia, matous hyperplasia. Thyroid carcinoma is rare decreased contractility, and increased risk for C. Clinical signs include weight loss, palpable goiter, atherosclerosis resulting from lipid metabolism polyphagia, polyuria, polydipsia, tachycardia, abnormalities hyperactivity, diarrhea, cardiac abnormalities 8. Neurologic signs including generalized weak- D. Clinical pathology findings ness, forelimb lameness, laryngeal paralysis, 1. Increased alanine aminotransferase (ALT), as- megaesophagus, vestibular disease (circling, partate aminotransferase (AST), alkaline phos- head tilt, incoordination) phatase (ALP), phosphorus 9. Ocular abnormalities including eyelid edema, 2. Azotemia in 25% corneal lipid deposits, keratoconjunctivitis 3. Mild hyperglycemia sicca 4. Stress leukogram, mature neutrophilia E. Diagnosis E. Diagnosis 1. Clinical pathology findings include chronic 1. Significantly elevated thyroid hormones in fasting hyperlipidemia, hypercholesterolemia, many cases of hyperthyroidism 210 SECTION II SMALL ANIMAL 2. Occult hyperthyroidism c. Post-samples taken 3 to 6 hours post and a. Thyroid hormones may be normal or only 8 hours post dexamethasone slightly increased d. Measure cortisol concentration in samples b. May need to perform a T3 suppression test e. Post dexamethasone cortisol concentration to demonstrate loss of negative feedback greater than 30 to 40 nmol/L suggests c. Day-to-day fluctuation in thyroid hormone HAC production may result in normal thyroid f. Suppression of cortisol concentration hormone concentrations greater than 50% of baseline (but still d. Concurrent nonthyroidal illness with hyper- greater than 30 to 40 nmol/L) at 3 to 6 hours thyroidism may suppress hormone concen- post or 8 hours post dexamethasone sug- trations into normal range gests pituitary-dependent hyperadrenocor- F. Treatment ticism (PDH) 1. Surgical thyroidectomy g. Suppression of cortisol concentration less 2. Radioactive iodine therapy than 50% of baseline (but still greater than 3. Chronic methimazole therapy 5 mg twice or 30-40 nmol/L) could indicate either PDH or three times daily an adrenal tumor (not diagnostic for adrenal G. Complications of therapy tumor) 1. Transient or permanent hypoparathyroidism h. If the LDDST is normal, HAC is unlikely post surgery i. False-positive results are seen especially 2. Hyperthyroidism may recur when other illnesses such as diabetes 3. Reduced glomerular filtration rate (GFR) mellitus (DM) are present 4. Renal failure in subclinical or compensated j. Test not appropriate if there is a history renal failure cases of exogenous steroid use VI. Hyperthyroidism in dogs 2. ACTH response test A. Most thyroid tumors are carcinomas and are a. Test of choice if suspect iatrogenic HAC or invasive hypoadrenocorticism, or when monitoring B. Hyperthyroidism occurs in about 10% to 20% of HAC therapy thyroid carcinomas. Most thyroid tumors are b. Measures adrenocortical reserve nonfunctional and do not cause hyperthyroidism c. Baseline blood sample taken before admin- C. Clinical signs include visible neck mass, coughing, istration of ACTH dyspnea, dysphagia, dysphonia, weight loss, d. Depending on the type of ACTH used, the hyperactivity post sample is taken 1 or 2 hours after D. Treatment ACTH 1. Surgery and chemotherapy e. Cortisol is measured in both samples 2. Treatment with oral thyroxine is recommended f. Post ACTH cortisol concentration greater post surgery to suppress TSH and to prevent than 550 to 600 nmol/L suggests HAC stimulation of potentially precancerous cells g. False-positive and false-negative results occur h. Disadvantage is that this test offers no DISORDERS OF ADRENAL FUNCTION insight as to the origin of HAC I. Normal adrenal function 3. Urinary cortisol-to-creatinine ratio (UCCR) A. Adrenal cortex has three zones a. Have owners collect morning urine at home 1. Zona glomerulosa secretes primarily mineralo- (nonstressed environment) corticoids b. If UCCR results are normal, HAC is very 2. Zona fasciculata secretes primarily glucocorti- unlikely costeroids c. Convenient, inexpensive test with little 3. Zona reticularis secretes primarily sex stress on patient hormones d. May be elevated in response to stress or B. Pituitary gland normally secretes endogenous other illness adrenocorticotrophic hormone (eACTH), which e. Elevation of UCCR is not diagnostic acts on the adrenal cortex to cause release of for HAC primarily cortisol. As cortisol increases, negative 4. Corticosteroid-induced ALP (ciALP) feedback mechanisms cause a decrease in a. If not elevated, HAC is very unlikely production of eACTH b. May be elevated in response to stress, II. Tests for adrenal function glucocorticoid administration, or other A. Tests to help support a diagnosis of hyperadreno- illness corticism (HAC) c. Elevation of ciALP is not diagnostic for HAC 1. Low-dose dexamethasone suppression test B. Tests for differentiating the origin of HAC (LDDST) 1. Dexamethasone suppression a. Blood sample collected before administ- a. Low- or high-dose (0.1 mg/kg) dexametha- ration of dexamethasone sone suppression b. Dexamethasone given intramuscularly at b. Greater than 50% suppression of cortisol 0.01 mg/kg from baseline sample suggests PDH  CHAPTER 15 Endocrine Disorders 211 c. Less than 50% suppression of cortisol from 3. Breed predilection baseline sample could indicate either PDH a. Any breed may be affected or adrenal tumor b. PDH: Poodles, dachshunds, and small d. High-dose dexamethasone suppression terriers (Yorkshire terrier, Parson test should not be used for the diagnosis Russell terrier, Staffordshire bull terrier) of HAC as some pituitary tumors will at increased risk remain responsive to a high dose of c. Adrenal tumor is more frequent in large dexamethasone and show normal breeds (weighing more than 20 kg) suppression C. Clinical signs 2. Endogenous ACTH measurement 1. Polyuria or polydipsia a. Concentration is very low with adrenal 2. Polyphagia tumors because of negative feedback of 3. Abdominal distension (pot-bellied excess cortisol on pituitary production of appearance) endogenous ACTH 4. Muscle wasting and weakness b. Concentration of endogenous ACTH may be 5. Lethargy, poor exercise tolerance slightly subnormal, normal, or elevated in 6. Skin thinning, decreased elasticity of skin, cases of PDH calcinosis cutis, hyperpigmentation c. Sample handling is critical since endoge- 7. Symmetrical alopecia nous ACTH is very labile 8. Persistent anestrus or testicular atrophy 3. Abdominal ultrasound D. Clinical pathology findings a. With an adrenal tumor, one adrenal 1. Findings are nonspecific gland may be enlarged and irregular in 2. Stress leukogram: Mature neutrophilia, lympho- contour penia, eosinopenia, monocytosis b. With PDH, both adrenals are enlarged to a 3. Hyperglycemia with or without glucosuria similar degree 4. Hypercholesterolemia, hypertriglyceridemia III. HAC: Canine 5. Increased corticosteroid-induced ALP A. Pathogenesis (ciALP), increased ALT, increased bile acid 1. PDH is caused by a pituitary microadenoma, concentrations macroadenoma, or adenocarcinoma 6. Decreased thyroid hormone concentrations 2. Adrenal-dependent HAC is caused by an (with no elevation of TSH) adrenal adenoma or adenocarcinoma 7. Decreased urine specific gravity (USG), 3. Iatrogenic HAC is due to chronic exogenous increased incidence of urinary tract steroid administration infections a. Chronic steroid use causes clinical signs E. Radiography findings of HAC with suppression of cortisol pro- 1. Nonspecific findings duction by the adrenal glands 2. Hepatomegaly, increased abdominal fat b. Ear and eye medications containing steroids 3. Distended urinary bladder, cystic calculi are readily absorbed and can cause iatro- 4. Soft tissue calcification genic HAC F. Diagnosis c. The ACTH response test is the test of 1. Diagnosis is based on a combination of clini- choice if iatrogenic HAC is suspected. cal signs and appropriate adrenal function Resting cortisol concentration is test findings. The test of choice for diagnosis typically low with subnormal stimulation of naturally occurring HAC is the low-dose of cortisol with the administration of dexamethasone suppression test ACTH 2. False-positive and false-negative results occur d. Treatment is to remove the source of the with any adrenal function test exogenous steroids 3. Stress of other concurrent illness often causes e. Suppression of adrenal cortisol production false-positive results (especially DM) from exogenous steroid administration 4. Borderline or positive test results in the may last 4 weeks or longer, depending absence of clinical signs is probably not HAC on type of steroid used, the route of 5. An elevated resting cortisol concentration or administration, and the duration of elevated ALP concentration is not specific for therapy HAC B. Signalment 6. Once a diagnosis of HAC has been made, fur- 1. Middle-aged to older dogs ther testing should be performed to determine a. PDH, approximately 7 to 9 years old the cause of the HAC (range, 2 to 16 years) G. Treatment b. Adrenal tumor, approximately 11 to 12 years 1. Iatrogenic HAC: remove source of exogenous old (range, 6 to 16 years) steroids 2. Sex predilection 2. Adrenal tumor a. No difference in PDH a. Surgery is the treatment of choice, but it b. More females than males are affected with may be difficult because adrenal tumors are adrenal tumors very vascular 212 SECTION II SMALL ANIMAL b. Medical therapy B. Clinical signs (1) Mitotane is used at higher doses 1. Polyuria or polydipsia (usually secondary to than in PDH, with longer periods of DM) induction 2. Pot-bellied appearance (2) Frequent monitoring (with ACTH 3. Polyphagia response test) necessary 4. Muscle wasting (3) Median survival time is 11 months 5. Hair loss, thin skin, fragile skin 3. PDH 6. Lethargy, obesity, weight gain a. Surgery to remove the pituitary mass has C. Diagnosis very limited availability 1. Clinical pathology b. Medical therapy a. Hyperglycemia, glycosuria (1) Mitotane b. Lymphopenia, eosinopenia, monocytosis (a) Causes destruction of the adrenal c. Hypercholesterolemia, increased ALT, cortex increased ALP (b) Induction phase (25 to 50 mg/kg 2. Adrenal function tests daily) followed by the maintenance a. ACTH response test phase (25 to 50 mg/kg once to twice b. Dexamethasone suppression test weekly) D. Treatment (c) Monitor with ACTH response test 1. Adrenalectomy is the most successful method (d) Oversuppression of cortisol produc- of treatment tion can occur, resulting in hypoad- a. Unilateral if adrenal tumor renocorticism b. Bilateral if PDH. Will require mineralocorti- (2) Trilostane coid and glucocorticoid supplementation (a) Inhibits glucocorticoid, mineralo- c. May have increased risk of infection and corticoid, and adrenal androgen delayed wound healing production 2. Hypophysectomy for PDH (not readily available) (b) Daily medication 3. Medical therapy has been disappointing (c) Monitor with ACTH response test V. Hypoadrenocorticism (3) L-Deprenyl (selegiline hydrochloride) A. Pathogenesis (a) Long-term results are disappointing 1. Primary hypoadrenocorticism with deficiency (b) No severe adverse side effects of both glucocorticoid and mineralocorticoid (c) Use clinical signs to monitor production effectiveness a. Deficiency of glucocorticoid and mineralo- (4) Ketoconazole corticoid (a) Suppresses steroidogenesis b. Idiopathic adrenocortical atrophy is (b) Monitor using ACTH response test most common due to immune-mediated H. Atypical HAC (dogs) destruction 1. Clinical signs of HAC are present, but dogs c. Mitotane-induced adrenocortical necrosis have normal cortisol values after adrenal d. Bilateral adrenalectomy function testing e. Other causes such as hemorrhage, infarc- 2. Perform an ACTH response test, and measure tion, neoplasia, granulomas of adrenal intermediates in the cortisol pathway and sex glands steroids (progesterone, 11-deoxycorticosterone, 2. Secondary hypoadrenocorticism 17-hydroxyprogesterone, androstenedione, a. Deficiency of eACTH production or release dehydroepiandrosterone, testosterone, b. Mineralocorticoid production is normal estradiol) c. Caused by tumors of pituitary or hypotha- 3. Abnormal elevations of intermediates or sex lamus or prolonged suppression of ACTH steroids in response to ACTH administration by drug therapy may suggest an adrenal tumor B. Signalment a. Elevated 17-hydroxyprogesterone can 1. Very rare in cats occur with either pituitary or adrenal 2. Age: Young to middle-aged dogs (median, tumors 4 years old; range, 3 months to 14 years) b. Elevated 17-hydroxyprogesterone can also 3. Gender: Approximately 70% of cases are female occur with nonadrenal illness 4. Breed: Any breed can be affected; however, 4. If an adrenal tumor is present, adrenalectomy incidence is greater in the Great Dane, is the treatment of choice. Patients may also Portuguese water dog, rottweiler, standard be treated with mitotane or trilostane poodle, West Highland white terrier, soft- IV. HAC: Feline coated wheaten terrier, Great Pyrenees, A. Signalment bearded collie, Chinese crested 1. Uncommon in the cat; disease of middle-aged C. Clinical signs to older cats 1. Acute (life-threatening) 2. Most cases are PDH a. Hypovolemic shock 3. Most cats have concurrent DM b. Collapse  CHAPTER 15 Endocrine Disorders 213 c. Weak pulse, bradycardia (Figure 15-1) concentration will be normal in secondary d. Hypothermia hypoadrenocorticism (or iatrogenic HAC) e. Abdominal pain, vomiting, diarrhea E. Treatment 2. Chronic 1. Acute a. Vague, nonspecific signs exacerbated by a. Try to obtain diagnostic samples before stress treatment b. Waxing and waning course b. Resuscitate intravascular volume c. Episodic weakness and collapse c. Provide glucocorticoids. Use dexame- d. Anorexia, weight loss, failure to gain weight thasone if diagnostic samples cannot be e. Lethargy, depression obtained before treatment f. Vomiting, diarrhea, melena, abdominal pain d. Correct hyperkalemia g. Polyuria, polydipsia e. Treat life-threatening cardiac arrhythmias D. Diagnosis 2. Chronic 1. Clinical pathology a. Mineralocorticoids a. Lymphocytosis, eosinophilia, neutropenia (1) Fludrocortisone once daily b. Normocytic, normochromic, nonregenera- (2) Desoxycorticosterone every 25 days tive anemia b. Glucocorticoids c. Azotemia c. Monitor effectiveness of therapy by evalua- d. Hyponatremia, hyperkalemia (Na:K less tion of clinical signs and electrolytes than 23:1) VI. Hyperaldosteronism e. Hypochloremia, hypoglycemia, A. Pathogenesis hypercalcemia 1. Aldosterone is produced by the zona 2. Adrenal function tests glomerulosa a. ACTH response test is the test of choice 2. Influenced by renin-angiotensin system (RAS) b. Can measure both cortisol and aldosterone and plasma potassium concentration in pre- and post-samples 3. Primary hyperaldosteronism (adrenal tumor) c. Both cortisol and aldosterone concentra- a. Increased production of aldosterone in the tions will be low in the baseline sample with presence of low plasma renin concentration little or no response to ACTH stimulation in b. Leads to hypernatremia, water retention, primary hypoadrenocorticism hypokalemia, and suppression of RAS d. Cortisol concentration will be low in 4. Secondary hyperaldosteronism baseline with little or no response to a. Hyperaldosteronism caused by continued ACTH stimulation, but aldosterone stimulation of RAS A B Figure 15-1 Electrocardiograms from a 4-year-old bearded collie dog with primary hypoadrenocorticism taken (A) before and (B) after supplementation with glucocorticoids and mineralocorticoids. Paper speed is 25 mm/sec and sensitivity is 1 cm  1 mV. A, The P waves are absent, the T waves are peaked, and there is profound bradycardia. The serum sodium concentration was 138 mEq/L and the serum potassium 9.5 mEq/L. B, Electrocardiogram after treat- ment showing sinus arrhythmia. The serum sodium concentration was 142 mEq/L and the serum potassium 5.4 mEq/L. (From Ettinger SJ, Feldman EC. Textbook of Veterinary Internal Medicine, 6th ed. St. Louis, 2005, WB Saunders.) 214 SECTION II SMALL ANIMAL b. Considered in any patient with cardiac failure, G. As iCa levels increase, PTH production renal disease, or hepatocellular disease decreases B. Signalment H. Elevated phosphorus levels exert a negative feed- 1. Primary hyperaldosteronism is rare, but it is back on the production of calcitriol more common in cats II. Measurement of calcium 2. Typically occurs in older animals A. Serum total calcium (tCa) is the sum of serum C. Clinical signs ionized calcium (iCa), complexed calcium (cCa), 1. Related to decreased potassium and protein-bound calcium (pCa). Ionized calcium 2. Weakness, lethargy, depression, polyuria or is the most important biologically active polydipsia, ventroflexion of the neck fraction 3. Reluctance to move, poor muscle tone, B. tCa does not accurately predict iCa. Concentra- apparent muscle pain tion of iCa should be measured, especially if a 4. Systemic hypertension resulting from sodium calcium metabolic disorder is suspected and fluid retention C. Formulas to adjust tCa to protein or albumin D. Diagnosis should not be used as this adjustment does not 1. Clinical pathology improve the prediction of iCa status a. Hypokalemia; serum potassium often below III. Hypercalcemia (Table 15-1) 3.0 mmol/L A. Mechanism of hypercalcemia b. Elevation of creatine kinase usually 1. Parathyroid-dependent (primary hyperpara- c. Blood urea nitrogen (BUN) typically normal thyroidism) 2. Adrenal function testing a. Parathyroid tumor secretes excess PTH a. Perform ACTH response test (same proce- causing hypercalcemia dure as for HAC or hypoadrenocorticism b. The increase in ionized calcium does not testing) turn off PTH production by the tumor b. Aldosterone is typically markedly elevated 2. Parathyroid-independent in both the pre- and post-ACTH samples a. Ionized calcium concentration increases in c. If hypokalemia is present, aldosterone serum concentration should be normal to low. b. Negative feedback causes suppression of Markedly elevated aldosterone concent- PTH production ration with concurrent hypokalemia sug- 3. Hypercalcemia can be nephrotoxic as a result gests primary hyperaldosteronism of vasoconstriction of renal vasculature (1) Primary hyperaldosteronism: Increased 4. Nephrocalcinosis can occur, especially if phos- aldosterone concentration with normal phorus concentration increases or decreased renin concentration 5. Hypercalcemia causes antagonism of (2) Secondary hyperaldosteronism: Increased vasopressin (Box 15-1) aldosterone concentration with increased B. Clinical signs of hypercalcemia renin concentration 1. Polyuria and polydipsia are the most common E. Treatment clinical signs in dogs, but hypercalcemia is un- 1. Correct hypokalemia common in cats 2. Potassium gluconate orally 2. Anorexia is the most common clinical 3. Spironolactone sign in cats a. Potassium-sparing diuretic 3. Depression, weakness b. Aldosterone receptor antagonist 4. Vomiting, diarrhea 4. Surgical adrenalectomy for adrenocortical 5. Cardiac arrhythmias tumors 6. Seizures C. General treatment of hypercalcemia 1. Remove underlying cause DISORDERS OF CALCIUM METABOLISM 2. Volume expansion (correct dehydration) I. Normal calcium metabolism 3. Furosemide A. Parathyroid gland secretes parathyroid hormone 4. Glucocorticoids (PTH) when ionized calcium (iCa) falls a. Decreased bone resorption B. PTH acts on the kidney to cause retention of b. Decreased intestinal calcium absorption calcium c. Increased renal calcium excretion C. Ingested vitamin D is converted to 5. Bisphosphonates, which act to decrease bone 25-hydroxyvitamin D in the liver turnover (osteoclast poisons) D. PTH increases conversion of 25-hydroxyvitamin 6. Calcitonin, which inhibits bone resorption D to 1,25-dihydroxyvitamin D (calcitriol) in the D. Primary hyperparathyroidism kidney 1. Mechanism: Parathyroid tumor secretes PTH, E. PTH acts on bone to cause bone resorption which causes ionized calcium to elevate F. Synthesized calcitriol causes bone resorption 2. Signalment and increases calcium absorption in the a. More common in dogs than in cats intestine b. Middle-aged to elderly animals  CHAPTER 15 Endocrine Disorders 215 Table 15-1 Anticipated Changes in Calcemic Hormones and Serum Biochemistry Associated with Disorders of Hypercalcemia Corr I,25 PTG ULS, tCA iCa alb tCa Pi PTH PTHrP 25(OH)-D (OH)2 –D Surgery Primary hyperparathyroidism ↑ ↑ N N ↓N ↑N N N N↑ Single↑ Nutritional secondary N↓ N↓ N N↓ N↑ ↑ N ↓N N↓ Multiple↑ hyperparathyroidism Renal secondary N↑↓ N↓ N N ↑N ↑ N N↓ N↓ Multiple↑ hyperparathyroidism Tertiary hyperparathyroidism ↑ ↑ N ↑ ↑ ↑ N N↓ ↓N Multiple↑ Malignancy associated Humoral hypercalcemia ↑ ↑ N↓ ↑N ↑N ↓N ↑N N ↓N↑ ↓ Local osteolytic ↑ ↑ N↓ ↑N N↑ ↓N N↑ N N ↓ Hypervitaminosis D Cholecalciferol ↑ ↑ N ↑ ↑N ↓ N ↑ N↑ N↓ Calcitriol ↑ ↑ N ↑ N↑ ↓ N N ↑ ↓N Calcipotriene ↑ ↑ N ↑ ↑N ↓ N N ↓N ↓N Hypoadrenocorticism ↑ ↑ N↓ ↑ ↑N ↓N N N ↓N N Hypercitaminosis A ↑ ↑ N ↑ N ↓ N N N↓ ↓N Idiopathic (cat) ↑ ↑ N ↑ N↑ ↓N N N N↓↑ ↓N Dehydration ↑ N↑ ↑N ↑N N↑ N↓ N N N N Aluminum exposure (renal failure) ↑ ↑ N ↑ ↑N ↓N N N N↓ N ↑↓ Hyperthyroidism (cat) ↑ ↑ N ↑ N↑ N↑↓ N N N↓ N↑ Raisin/grape toxicity (dog) ↑ — N ↑ N↑ — — — — — ↓, Decreased concentration; ↑, increased concentration; N, normal; tCa, serum total calcium; iCa, serum ionized calcium; alb, albumin; Corr tCa, corrected total calcium; Pi, inorganic phosphorus; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related protein; 25 (OH)-D, 25-hydroxyvitamin D; 1,25-dihydroxyvitamin D; PTG, parathyroid gland; ULS, ultrasound. c. Usually due to a solitary parathyroid b. Polyuria, polydipsia, weakness, lethargy, adenoma inappetance, calcium-containing urinary d. Often palpable in cats, but not palpable calculi in dogs 4. Diagnosis e. Breeds predisposed to primary hyperpara- a. Visualization of parathyroid tumor with thyroidism include the keeshond, ultrasound dachshund, golden retriever, poodle, b. Increased ionized calcium concentration Labrador retriever with an inappropriately high PTH 3. Clinical signs concentration a. Clinical signs may occur over a long period before diagnosis Box 15-1 Causes of Hypercalcemia G Granulomatous disease O Osteolytic disease S Spurious H Hypercalcemia of malignancy, hypoadrenocorticism, hypervitaminosis D D Vitamin D toxicity A Addison disease, aluminum toxicity, vitamin A toxicity R Renal disease N Neoplasia I Idiopathic (cats) T Temperature (hypothermia) 216 SECTION II SMALL ANIMAL 5. Treatment 2. Clinical signs a. Removal of parathyroid tumor is treatment a. May have sudden onset of choice b. May be seen in young animals b. Expect transient hypoparathyroidism and c. Increased phosphorus concentration is seen hypocalcemia post-surgery until remaining d. Acute renal failure may result from nephro- parathyroid glands can recover calcinosis E. Humoral hypercalcemia of malignancy 3. Diagnosis 1. Mechanism a. Parathyroid-independent hypercalcemia a. Tumor secretes factors that result in with increased iCa concentration and sup- hypercalcemia pressed PTH production b. Factors that cause hypercalcemia include b. 25-hydroxyvitamin D concentration interleukins, tumor necrosis factor, tumor (1) Increased with oversupplementation or growth factor, parathyroid hormone related rodenticide ingestion protein (PTHrP) (2) Will be normal with plant or anti- c. Increased iCa causes suppression of PTH psoriasis cream ingestion production (parathyroid-independent 4. Treatment hypercalcemia) a. Control hypercalcemia and 2. Signalment hyperphosphatemia a. Dogs b. May need to treat for a long period because (1) Lymphosarcoma is most common of the long half-life of ingested vitamin D (2) Anal sac apocrine gland adenocarcinoma compounds (3) Thymoma H. Idiopathic hypercalcemia in cats (4) Carcinomas 1. Mechanism unknown (5) Hematologic malignancies 2. Signalment b. Cats a. Young to old cats (1) Lymphosarcoma and squamous cell b. Higher incidence in long-haired cats carcinoma are most common 3. Clinical signs (2) Multiple myeloma, osteosarcoma, fibro- a. Many have no clinical signs sarcoma, bronchogenic carcinoma, he- b. May have history of weight loss, anorexia, matologic malignancies chronic constipation, calcium oxalate- 3. Diagnosis containing uroliths a. Increased iCa concentration with sup- c. May develop chronic renal failure pressed PTH production 4. Diagnosis b. If PTHrP is secreted by tumor, PTHrP will be a. Parathyroid-independent hypercalcemia elevated in plasma with elevated iCa concentration and sup- (1) PTHrP is similar to PTH in structure pressed PTH production (2) Causes bone resorption and renal cal- b. Diagnosis by exclusion (no evidence of malig- cium conservation nancy, parathyroid tumor, vitamin D toxicity) (3) PTHrP is not normally excreted in an 5. Treatment adult animal in any appreciable a. No treatment works consistently amount b. Switch to a high fiber diet first. If that is not (4) If PTHrP is present in any significant effective, try glucocorticoid therapy. If that amount, malignancy is suspected is not effective, then try bisphosphonates (5) The absence of detectable PTHrP does IV. Hypocalcemia (Table 15-2) not rule out malignancy A. Mechanism of hypocalcemia F. Hypoadrenocorticism 1. Parathyroid-dependent hypocalcemia (primary 1. Increase in iCa concentration is usually mild hypoparathyroidism) 2. Parathyroid-independent hypercalcemia is a. Destruction of parathyroid glands seen with increased iCa concentration and sup- b. iCa concentration falls, but parathyroid pressed PTH production glands are unable to secrete PTH 3. Magnitude of hypercalcemia parallels severity 2. Parathyroid-independent hypocalcemia where of hyperkalemia and hypovolemia the demand for iCa exceeds the supply or mo- 4. Hypercalcemia resolves with treatment of hy- bilization (Box 15-2) poadrenocorticism B. Clinical signs of hypocalcemia G. Vitamin D toxicosis 1. Stiff gait, muscle tremors, spasms, seizures 1. Mechanism 2. Increased anxiety, aggression a. Oversupplementation of vitamin D 3. Intense pruritus, facial rubbing, self-mutilation b. Cholecalciferol rodenticide ingestion C. Primary hypoparathyroidism c. Ingestion of plants containing vitamin D me- 1. Mechanism tabolites (Cestrum diurnum) a. Lymphoplasmacytic destruction of parathy- d. Ingestion of anti-psoriasis creams contain- roid glands so that parathyroid glands are un- ing vitamin D metabolites able to secrete an appropriate level of PTH  CHAPTER 15 Endocrine Disorders 217 Table 15-2 Anticipated Changes in Calcemic Hormones and Serum Biochemistry Associated with Disorders of Hypocalcemia Corr PTG ULS, tCa iCa alb tCa Pi PTH PTHrP 25(OH)-D 1,25(OH)2 - D Surgery Primary hypoparathyroidism ↓ ↓ N ↓ ↑N ↓N N N N↓ Multiple↓ Pseudohypoparathyroidism ↓ N↓ N ↓ ↑N ↑ N N N↑ N↑ Sepsis/critical care ↓N ↓ N ↓N N↑ ↑N N N N N Ethylene glycol toxicity ↓ ↓ N ↑ ↑N ↑ N N ↓N N Paraneoplastic ↓ ↓ N ↓ ↓ ↑N N N N N↑ Phosphate enema ↓ ↓ N ↓ ↑ ↑ N N N↓↑ N Eclampsia ↓ ↓ N ↓ ↓ Mild↑, N N N N↓ N Hypoalbuminemia ↓ ↓N ↓ N N N↑ N N N↑ N↑ ↓, Decreased concentration; ↑, increased concentration; N, normal; tCa, serum total calcium; iCa, serum ionized calcium; alb, albumin; Corr tCa, corrected total calcium; Pi, inorganic phosphorus; PTH, parathyroid hormone; PTHrP, parathyroid hormone related protein; 25(OH)-D, 25-hydroxyvitamin D; 1,25(OH)2-D, 1,25-dihydroxyvitamin D; PTG, parathyroid gland; ULS, ultrasound. b. Iatrogenic hypoparathyroidism 3. Diagnosis is based on finding decreased iCa (1) Parathyroid glands damaged or re- concentration with an inappropriately low PTH moved during surgery of the neck concentration (2) Common in hyperthyroid surgery or 4. Treatment post-parathyroid adenoma removal a. Acute (3) May be transient, or require treatment (1) 10% calcium gluconate administered in- for life travenously (IV) 2. Signalment (2) Avoid fluids containing lactate, bicar- a. Uncommon in dogs and rare in cats bonate, or acetate b. More common in young adults (3) Do not give calcium-containing fluids c. Breeds predisposed include miniature subcutaneously schnauzer, miniature poodle, terriers, b. Maintenance Siamese cats (1) Treat with both calcium and vitamin D supplementation (2) Oral calcium 50 to 100 mg elemental calcium/kg/day (3) Vitamin D preparations Box 15-2 Causes of Hypocalcemia (a) Ergocalciferol is the poorest choice, longest-acting M Magnesium depletion, malabsorption (b) Dihyrotachysterol (off the market) A Albumin ↓, atrophy of parathyroid gland (c) Calcitriol is the best choice for T Trauma treatment at 30 to 60 ng/kg/day. C Chelation, critical care, calcitonin Calcitriol has the shortest onset of H Hypoparathyroidism, hypoproteinemia action and is the shortest acting hypomagnesmia c. Hypercalcemia can occur with treatment I Infarct of parathyroid gland D. Puerperal tetany (eclampsia) N Nutritional (Ca ↓, P ↑, Vit D ↓) 1. Seen in the lactating bitch or queen during the G Gastrointestinal disease (malabsorption, first 3 weeks postpartum pancreatitis) 2. Most common in small dogs D Drugs, diet 3. Rapidity of calcium utilization overwhelms the R Rhabdomyolysis, renal failure ability to maintain normal iCa concentration A (see A above) 4. Supplementation of pregnant bitch with cal- P Parathyroid atrophy, destruction; pancreatitis; cium may predispose the lactating bitch to phosphate enemas, periparturient hypocalcemia (as a result of atrophy of the E Eclampsia, ethylene glycol, enema parathyroid glands) S Sepsis E. Acute pancreatitis 1. Hypocalcemia is typically mild 2. Clinical signs of hypocalcemia are unlikely 218 SECTION II SMALL ANIMAL 3. Hypocalcemia is caused by the saponification b. Breeds of peripancreatic fat following leakage of lipase (1) Genetic basis in keeshond V. Secondary hyperparathyroidism (2) Other predisposed breeds include A. Mechanism of secondary hyperparathyroidism miniature and toy poodle, dachshund, 1. Secondary hyperparathyroidism is miniature schnauzer, beagle, puli, Cairn characterized by excessive bone resorption terrier, miniature pinscher and osteopenia c. Gender: More common in females 2. It is typically due to either nutritional 2. Cats deficiencies or chronic renal failure a. Incidence is approximately 0.5% B. Diagnosis b. More than 50% are older than 10 years 1. An elevated serum PTH concentration is c. Obesity increases the risk threefold to observed, with a normal or decreased iCa fivefold concentration d. Gender 2. Concentration of 25-hydroxyvitamin D may be (1) Neutered cats are at twice the risk for low in cases of nutritional secondary hyper- developing DM parathyroidism (2) Male cats have an increased risk C. Nutritional secondary hyperparathyroidism C. Clinical signs 1. Due to diets with excessive phosphate or inade- 1. Usually do not develop until blood glucose quate calcium and vitamin D content. Deficient concentration is greater than 180 to 200 mg/dL diets are typically homemade diets made pri- in dogs and 200 to 280 mg/dL in cats marily with meat 2. Polyuria and polydipsia, polyphagia 2. Clinical signs include bone pain, lameness, 3. Weight loss (usually rapid) is common limb deformities, fractures in dogs 3. More common in young, growing animals 4. Acute blindness due to cataracts 4. Can also occur in cases of gastrointestinal dis- 5. Nonspecific physical examination findings in- ease, causing decreased absorption of calcium clude dehydration, muscle wasting, cataracts or vitamin D in 40% of dogs, hepatomegaly 5. Treat by providing a balanced diet D. Clinical pathology findings D. Renal secondary hyperparathyroidism 1. Fasting hyperglycemia and glycosuria 1. Progressive reduction in renal tubule cells with 2. Hypercholesterolemia, hypertriglyceridemia a decrease in calcitriol production (fasting hyperlipidemia) 2. Decreased ability to retain calcium by the 3. Increased liver enzymes (ALP, ALT) kidneys 4. Neutrophilic leukocytosis 3. Decreased calcitriol causes a decrease in iCa 5. Proteinuria, increase USG 4. PTH secretion increases in response, resulting E. Diagnosis in increased resorption of calcium from bone, 1. Persistent fasting hyperglycemia and glycosuria particularly in the bones of the skull (“rubber 2. Presence of ketonuria confirms diabetic jaw”) ketoacidosis (DKA) 5. Excess PTH is a uremic toxin and contributes 3. Mild hyperglycemia (less than 180 mg/dL) to neurologic signs of CRF associated with polyuria and polydipsia is 6. Calcitriol therapy (2.5-3.0 ng/kg/day) to de- most likely not due to DM crease production of PTH and decrease bone 4. Severe hyperglycemia can occur in acutely resorption. Serum phosphorus must be stressed cats controlled for maximal effectiveness of 5. In IDDM, glucose concentration is increased calcitriol with a decrease in insulin 6. In NIDDM, glucose concentration is increased with a low, normal or increased insulin concen- DISORDERS OF GLUCOSE METABOLISM tration (Box 15-3) I. Diabetes mellitus (DM) F. Therapy A. Pathogenesis 1. Goal of therapy is to eliminate clinical signs 1. Dogs and development of complications and prevent a. Most have insulin-dependent DM (IDDM) hypoglycemia with decreased serum insulin concentration 2. Dietary therapy and no increase in insulin after the adminis- a. Correct obesity if present tration of glucose b. Maintain consistent times and content of b. Non-insulin-dependent DM (NIDDM) is very meals uncommon in dogs c. Feed high-fiber diet (only if not thin) 2. Cats 3. Exercise: Maintain constant daily exercise a. Many have NIDDM 4. Oral hypoglycemic drugs b. May become permanently insulin-dependent a. Only for NIDDM in cats B. Signalment b. Glipizide 2.5 mg twice daily with food 1. Dogs c. If hyperglycemia persists or recurs, switch a. Age: Peak incidence at 7 to 9 years to insulin therapy  CHAPTER 15 Endocrine Disorders 219 (2) Lente or NPH preferred Box 15-3 Causes of Hyperglycemia (3) Use human or porcine origin; beef ori- gin may induce antibody formation S Stress (cat), steroids (4) Initial dose is 0.5 unit/kg twice daily C Cushing disease (hyperadrenocorticism) (5) Measure glucose concentration 4 and 6 R Renal disease to 7 hours after initial insulin A Acromegaly (cat) c. Cats P Postprandial, pancreatitis, pheochromocytoma (1) Insulin best given twice daily (dogs), progesterone, parenteral nutrition (2) Lente or PZI preferred (human or beef E Exocrine pancreatic insufficiency, eating origin) D Diabetes mellitus, diestrus (dog), drugs (3) Glargine lasts 12 to 16 hours in cats (glucocorticosteroids, progesterone, megestrol and takes several days for maximum acetate, thiazide diuretics), dextrose-containing effect fluids (4) 1 to 3 units/cat twice daily initially (5) May need to decrease dose after 2 weeks, especially if using glargine (6) Measure glucose concentration 4 and 6-7 hours after initial insulin 5. Insulin therapy (7) Cats requiring high doses during initial a. Types of insulin treatment usually have poor absorption (1) Short-acting (switch to PZI or Lente) (a) Regular 6. Monitoring treatment (Figure 15-2) (b) Semi-Lente a. Monitor clinical signs such as appetite, wa- (2) Intermediate-acting ter consumption, urination, activity, general (a) Neutral protamine Hagedorn (NPH) well-being or isophane b. Glucose curves (b) Lente (1) Perform during initial regulation, when (3) Long-acting hypoglycemia is suspected, and in (a) Ultralente poorly controlled DM (b) Protamine zinc insulin (PZI) (2) Procedure (c) Glargine (a) Feed before test b. Dogs (b) Obtain blood glucose (1) Insulin is best given twice daily (c) Administer insulin Unregulated diabetic patient (persistent PU/PD, polyphagia, and weight loss) Management errors Yes Correct (improper injection technique, outdated insulin, improper storage of insulin, etc.) No Insulin dose  2.2 U/kg Insulin dose 2.2 U/kg Rapid metabolism Serial blood glucose monitoring Antibody formation Hyperthyroidism Insulin antagonism Hyperadrenocorticism Nadir too high Short duration of action Insulin-induced hyperglycemia Exogenous steroids 500 Progestogen therapy 300 300 Blood glucose Blood glucose Blood glucose 400 Unspayed bitch Bacterial infection 200 200 300 Hypothyroidism 200 Acromegaly 100 100 100 Hyperandrogenemia Pheochromocytoma 0 0 0 0 2 4 6 8 1012141618 2022 0 2 4 6 8 1012141618 2022 0 2 4 6 8 1012141618 2022 Hyperglucagonemia Time (hours) Time (hours) Time (hours) Increase dose Change to twice daily Reduce dose or longer acting insulin Figure 15-2 Algorithm for the unregulated diabetic dog or cat. (From Miller E. Long-term monitoring of the diabetic dog and cat: Clinical signs, serial blood glucose determinations, urine glucose, and glycated blood proteins. Vet Clin North Am Small Anim Pract 25:582, 1995; with permission.) 220 SECTION II SMALL ANIMAL (d) Measure blood glucose concentra- c. Signs include ataxia, weakness, lethargy, tion every 2 hours until 8 to seizures 12 hours after insulin (if giving d. Treat with glucose administration (food, insulin twice daily) sugar water, or IV dextrose) (3) Interpretation 3. DKA (a) Maintain glucose between 100 and a. Occurs most commonly in dogs and cats 200 mg/dL in dogs and 100 and with previously undiagnosed DM 250 mg/dL in cats b. May occur in patients receiving inadequate (b) Glucose nadir should be between 80 insulin and a concurrent infection, inflam- and 120 mg/dL. The time of nadir mation, or insulin-resistant disorder indicates peak insulin action. The c. Clinical signs may develop over time. The nadir should occur approximately time from onset of signs to development of halfway through the dosing DKA ranges from a few days to more than interval 6 months (c) Glucose differential is the difference (1) Once ketoacidosis develops, severe ill- between the glucose nadir and ness occurs within 7 days blood glucose just before the next (2) Clinical signs include dehydration, de- insulin dose. The differential should pression, weakness, tachypnea, vomit- be less than 100 mg/dL in dogs ing, abdominal pain, odor of acetone on without cataracts, and less than the breath, slow and deep breathing 150 mg/dL in dogs with cataracts d. Diagnosis is based on the presence of fasting (d) If the glucose nadir is too high, hyperglycemia, glucosuria, and ketonuria increase the dose of insulin e. Treatment (e) If the nadir occurs too soon, change (1) If signs are mild, use short-acting regu- to a longer-acting insulin lar insulin three times daily until keto- (f) If the nadir occurs too close to next nuria resolves. Give one third the daily dose of insulin, change to a shorter food ration at the same time as insulin duration of insulin (2) If systemically ill, blood glucose is (4) Somogyi effect greater than 500 mg/dL, or severe meta- (a) Insulin concentration is too low at bolic acidosis is present, treat more ag- the nadir and induces stress hor- gressively. Aggressive therapy involves mone release fluid therapy with potassium and phos- (b) Marked hyperglycemia can occur as phate supplement, bicarbonate therapy, a result insulin therapy with short-acting regular (c) Poor control of DM due to too much insulin, and additional ancillary therapy insulin if concurrent conditions are present (d) Decrease insulin dose by 25% f. Prognosis (e) Repeat glucose curve 1 week after (1) Approximately 30% with severe DKA die altering insulin dose or are euthanized c. Other monitoring methods (2) Death is usually due to severe meta- (1) Urine glucose concentration bolic acidosis (2) Glycosylated hemoglobin II. Insulinoma (3) Fructosamine reflects blood glucose A. Etiology over the previous 5 to 8 days and can- 1. Uncommon in dogs; rare in cats not detect hypoglycemia, so Somogyi ef- 2. Occurs in middle-aged to older dogs. The aver- fect will look like poor control age age is 9 years, with a range of 2.5 to 15 years G. Complications 3. Medium-breed to larger-breed dogs are predis- 1. Insulin resistance posed a. Inadequate control of glucose with insulin 4. Tumor of pancreatic -cells, which secrete in- doses greater than 2 units/kg/day sulin; usually malignant b. Factors contributing to insulin resistance in- B. Clinical signs clude obesity, HAC, hypothyroidism, develop- 1. Clinical signs may be episodic and are more ment of insulin antibodies, and acromegaly in common after eating, excitement, and exercise cats. It can be difficult to diagnose HAC when 2. Clinical signs include lethargy, weakness, DM is present because the stress of diabetes of- ataxia, dementia, seizures, coma, death ten causes false-positive adrenal function test 3. Weight gain may be noted results 4. Subclinical polyneuropathies such as facial pa- 2. Hypoglycemia ralysis or proprioceptive deficits may be present a. Common complication of insulin therapy C. Causes of hypoglycemia b. May occur following an increase in insulin 1. Artifact (serum left on clot) dose, strenuous exercise, or prolonged 2. Congenital enzyme deficiency (glycogen stor- inappetence age disease)  CHAPTER 15 Endocrine Disorders 221 3. Hunting dog hypoglycemia 2. Simple autosomal recessive mode of inheri- 4. Hepatic disease (liver failure, vascular shunts) tance in German shepherd dog and Carnelian 5. Sepsis bear dog 6. Polycythemia C. Clinical signs 7. Nonpancreatic tumors (hepatic carcinoma, 1. Lack of growth (short stature) with normal leiomyosarcoma) body proportions 8. Growth hormone (GH) deficiency 2. Testicular atrophy in males, no estrus activity 9. Hypoadrenocorticism in females 10. Insulinoma 3. Retention of secondary hairs with absence of 11. Administration of insulin or drugs primary hairs 12. Toxins a. Soft and wooly initially (puppy coat), but D. Diagnosis this hair is easily epilated, so alopecia de- 1. Hypoglycemia with an inappropriately high in- velops sulin level b. Skin becomes hyperpigmented, thin, and 2. Animal should be fasted before testing, as the scaly, with secondary pyoderma normal response to feeding is insulin release 4. Mental dullness 3. Blood glucose below 60 mg/dL (3.3 mmol/L) 5. Bone deformities should inhibit insulin release 6. Delayed growth plate closure E. Treatment 7. Delayed eruption of teeth 1. Surgical D. Clinical pathology findings a. Monitor glucose concentrations because 1. Findings are usually normal if the deficiency is handling of tissue can cause insulin release uncomplicated b. Pancreatitis is common post-surgery 2. If there are signs related to deficiencies of c. Up to 50% have metastatic disease at time other pituitary hormones (e.g., hypoadreno- of surgery corticism, hypothyroidism), there may be clini- 2. Dietary cal pathology findings typical of these other a. Diet high in fat, protein, and complex carbo- conditions hydrates E. Diagnosis b. Feed small meals frequently, limit exercise 1. Insulin-like growth factor 1 (IGF-1) concentra- 3. Medical tion is usually low, especially for a young age a. Glucocorticoids 2. Breed differences do exist, so an age-matched (1) Insulin antagonist control for IGF-1 determination is useful (2) Increases gluconeogenesis F. Treatment b. Diazoxide 1. Injections of GH (1) Decreases insulin release from -cells 2. Skin and hair responds within 6 to 8 weeks of (2) Effective in 85% of cases, expensive GH therapy c. Octreotide 3. There is usually no appreciable growth (1) Inhibits insulin synthesis G. Prognosis is poor. Most live only 3 to 8 years (2) Patients become refractory II. Acromegaly F. Prognosis A. Pathogenesis 1. Short-term prognosis is good; long-term prog- 1. Acromegaly is due to an excess of GH nosis is guarded to poor production 2. Mean survival time if treated medically is 2. In cats, this is usually caused by a pituitary 12 months functional neoplasia 3. If metastasis is present at time of surgery, 3. In dogs, acromegaly due to pituitary functional prognosis is poor neoplasia is very rare. Most often, acromegaly is related to an excess of progesterone (either endogenous or exogenous) which induces the DISORDERS OF GROWTH HORMONE systemic release of GH from mammary tissue I. Growth hormone (GH) deficiency B. Signalment A. Pathogenesis 1. Acromegaly is more common in male cats 1. Congenital deficiency of GH 2. Usually older cats (8-14 yrs old) 2. Associated with congenital cystic distention or C. Clinical Signs persistence of craniopharyngeal duct (Rathke’s 1. Acromegaly is usually considered only when in- pouch), especially in brachycephalic breeds sulin is ineffective at controlling hyperglycemia 3. Deficiencies of other pituitary hormones may 2. Polyuria and polydipsia are the earliest clinical also be present (TSH, ACTH, lutenizing hor- signs mone [LH], follicle-stimulating hormone [FSH]) 3. Weight gain is an important sign in poorly con- B. Signalment trolled diabetics 1. Primarily in the German shepherd, 4. Increased size Weimaraner, spitz, Carnelian bear dog; also 5. Enlargement of head, extremities, feet, abdo- seen in cats men, heart, viscera 222 SECTION II SMALL ANIMAL 6. Broad face, widened interdigital spaces C. Clinical signs 7. Inspiratory stridor, panting, apnea 1. Polyuria or polydipsia 8. Neurologic signs as a result of expanding 2. Animals may appear incontinent pituitary tumor 3. Neurologic signs may be seen with CDI as D. Clinical pathology a result of head trauma or tumors or if 1. Poorly controlled DM (hyperglycemia, dehydrated glucosuria) 4. Animals may be thin because they would 2. Persistent hyperproteinemia rather seek water than eat E. Diagnosis D. Diagnosis 1. Elevated concentration of IGF-1 accompanied 1. Rule out other causes of polyuria and polydip- by appropriate clinical signs. IGF-1 production sia and acquired NDI (e.g., HAC, hypercalce- parallels GH production and can be used as a mia, hyperthyroidism, DM, acromegaly) measure of GH concentration 2. Urine is usually hyposthenuric, but isosthenuria 2. Elevated concentrations of IGF-1 also occur in (USG 1.008 to 1.012) does not rule out DI association with DM, so caution should be ex- 3. Hypernatremia with hyposthenuria raises sus- ercised in diagnosing acromegaly in a diabetic picion for DI cat that does not have strong clinical signs 4. Differentiating absolute and partial CDI 3. The presence of acromegaly may result in a. Absolute vasopressin deficiency causes insulin-resistant DM or poor control of existing persistent hyposthenuria and severe diure- diabetes sis even if dehydrated 4. Documentation of pituitary mass in cats by b. In partial CDI, animals can increase USG computed tomography or magnetic resonance into isosthenuric range but typically not imaging above 1.015 F. Treatment 5. Modified water deprivation test 1. Radiation therapy of the pituitary mass has a. Assesses the effects of water deprivation limited availability, and acromegaly often re- and dehydration on USG curs 6 to 18 months later b. Do not perform if animal is dehydrated or 2. Surgery to remove a pituitary mass has very has compromised renal function limited availability c. Normal animals or those with psychogenic 3. In dogs, treatment is to remove the source of water consumption should be able to con- progesterone (ovariohysterectomy) centrate urine to greater than 1.030 4. Manage long-term consequences in the cat, d. Animals with CDI or familial NDI cannot con- such as chronic renal failure, heart failure, in- centrate urine when dehydrated sulin resistance 6. Response to desmopressin (dDAVP, synthetic G. Prognosis: Long-term prognosis is poor, with sur- vasopressin) vival of 4 to 42 months a. Give one to four drops dDAVP into conjunc- tival sac once or twice daily for 5 to 7 days b. See marked increase in USG in animals OTHER ENDOCRINE DISORDERS with CDI I. Diabetes insipidus (DI) c. Minimal improvement in those with NDI A. Pathogenesis E. Treatment 1. Primary DI (central DI [CDI]) 1. For CDI, dDAVP is either administered in the a. Defective synthesis or secretion of vaso- conjunctival sac once or twice daily, or it is pressin by the hypothalamus given parenterally b. May be idiopathic or due to head trauma, 2. No treatment really necessary as long as there neoplasia, hypothalamic or pituitary is a constant water supply malformations II. Gastrinoma 2. Secondary DI (nephrogenic DI [NDI]) A. Etiology a. Renal tubules are unable to respond to 1. Pancreatic tumor secreting primarily gastrin vasopressin 2. Usually malignant b. May be familial or acquired B. Signalment (1) Familial NDI is a rare congenital 1. Age at presentation disorder a. Dogs: Mean age is 7.5 years (range, 3 to (2) Acquired NDI is the most common 12 years) form of DI b. Cats: Mean age is 11 years B. Signalment 2. No breed predisposition 1. No breed, gender, or age predilection in dogs 3. Females may be more commonly affected than 2. In cats, most are domestic short hair (DSH) males or domestic long hair (DLH); documented in C. Clinical signs Persians and Abyssinians 1. Vomiting and weight loss are most common 3. Primary DI is usually diagnosed in puppies, kit- 2. Depression, lethargy, diarrhea, hematemesis, tens, or young adults melena, abdominal pain, collapse  CHAPTER 15 Endocrine Disorders 223 D. Diagnosis D. Differential diagnosis 1. Complete blood cell count (CBC)-biochemistry 1. Nonfunctional adrenal mass profile: Regenerative anemia, leukocytosis, 2. HAC due to an adrenal tumor hypochloremia, hypokalemia, hypoalbumin- 3. HAC can occur simultaneously with pheochro- emia, hypoproteinemia, mild increase in liver mocytoma enzymes E. Diagnosis 2. Elevated gastrin concentration 1. No consistent abnormalities on CBC, chemistry a. Must rule out other causes of elevated gas- profile, or urinalysis trin concentration 2. History of episodic collapse b. Causes of elevated gastrin include gastri- 3. Identification of an adrenal mass noma, renal failure, pyloric stenosis, hypo- 4. Documentation of hypertension in nonazo- chlorhydria, atrophic gastritis, small intesti- temic dogs with adrenal mass and normal ad- nal resection, liver disease, gastric renocortical function. Hypertension may be dilatation and volvulus, administration of life-threatening antacids, histamine type 2 blockers, proton 5. Urinary catecholamine concentrati