Endocrine System Flashcards
Hypothyroidism
OVERVIEW
- results from inadequate production of T4 and T3
- primary hypothyroidism account for ~95% of cases; progressive destruction of thyroid gland; either immune-mediated (lymphocytic thyroiditits - thyroid tissue destroyed and replaced with fibrous connective tissue) or idiopathic atrophy (replaced by adipose tissue)
- less common causes of primary hypothyroidism: follicular cell hyperplasia, infiltrative neoplasia
- secondary hypothyroidism is rare; caused by pituitary malformation or neoplasia
- spayed females and neutered males at greater risk than sexually intact
CLINICAL SIGNS
- nonspecific and gradual onset - lethargy, weight gain, poor hair coat, alopecia; often attributed to aging or over feeding
DIAGNOSIS
- glucocorticoids, phenobarbital, sulfa abx, furosemide, some NSAIDs, clomipramine, and radiocontrast agents have been reported to alter thyroid concentrations
- concurrent illness can cause reduction in thyroid hormone levels (euthyroid sick syndrome/nonthyroidal illness); HAC, renal dz, hepatic dz, heart failure, severe infections, DKA; thought to be physiological adaptation to decrease cellular metabolism and conserve energy; in general the relative reduction of basal T4 correlates with severity of illness
- CBC: mild normocytic normochromic nonregenerative anemia, leukocytosis
- chem: hyperchloesterolemia and/or hypertriglyceridemia despite fasting sample,
- UA: typically normal; in lymphocytic thyroiditis immune complex glomerulonephritis may cause proteinuria
- total T4 (sensitive, not specific): below normal reference range
- FT4ED: decreased
- TSH: increased
- greyhounds, whippets, basenjis, conditioned sled dogs may be euthyroid with decreased T4 levels making dx difficult
- T3 widely variable - not helpful in diagnosis
TREATMENT
- levothyroxine starting at 0.02 mg/kg BID, maximum 0.8 mg PO BID
- post pill T4 4-8 wks after initiating therapy
Hyperthyroidism
OVERVIEW
- aka thyrotoxicosis
- multisystemic disorder; results from excessive production and secretion of T4 and T3
- most common endocrine disorder in cats
- middle-aged to older cats
- 97-99% of cases histologically characterized as benign adenomatous hyperplasia, adenomas, or multinodular adenomas
- remaining 1-3% are malignant thyroid carcinomas
- >70% found to have bilateral involvement with majority having asymmetrical disease
CLINICAL SIGNS
- weight loss despite good appetite (unable to eat enough calories to maintain weight), PU/PD (due to increased renal perfusion), polyphagia, vomiting (chemoreceptor trigger zone CRTZ stimulation and rapid ingestion of food), diarrhea (decreased GI transit time and subsequent malabsorption), increased vocalization/irritability/increased socialization (increased stimulation of sympathetic nervous system), tachycardia, heart murmur, palpable thyroid, unkempt hair coat, cachexia
- thyrotoxicosis causes cardia hypertrophy related to hyper metabolic state, peripheral vasodilation, increased demand for cardiac output; thyroid levels may stimulate myocardial hypertrophy; chronic cases may have left ventricular thickening; concurrent systemic hypertension likely contributes
- high incidence of concurrent systemic hypertension; BP measurement and ophthalmic exam; possibly secondary to concurrent renal dz
DIAGNOSIS
- may be incidental finding on routine lab work
- PE = tachycardia (>220 bpm), systolic heart murmur, cardiac arrhythmias, weight loss, muscle wasting, poor haircoat, thyroid slip
- CBC: erythrocytosis, neutrophilia, lymphocytosis
- chem: elevated LE (ALT or ALP) possibly due to malnutrition, CHF, infection, hepatic anorexia, or direct toxic effects of thyroid hormones on the liver
- total T4: elevated
- FT4ED: elevated
- TSH: decreased; decreased TSH with normal TT4 and FT4ED may be predictor of future hyperthyroidism dx
- scintigraphy: highly sensitive and specific, allows direct visualization of functional adenomatous tissue, provide definitive diagnosis; especially important prior to thyroidectomy or I-131; uptake 1:1 (thyroid glands:salivary glands) considered normal, more uptake in thyroid glands considered diagnostic for hyperthyroidism
- cardiac screening ideal due to high percentage of hyperthyroid cats with clinical evidence of cardiac disease (TXR, ECG, echo, BNP)
TREATMENT
- medical management: methimazole (US) or carbimazole (other locations than US); inhibit synthesis of thyroid hormones, are not cytotoxic so thyroid nodules will continue to grow; adverse reactions include preauricular pruritis, inappetence, vomiting
- short-term medical management is recommended prior to permanent management to assess for underlying renal and cardiac dz
- I-131: gold standard treatment >95% permanent success rate; scintigraphy provides treatment guidelines prior to radioactive iodine administration (SC or IV) to obliterate hyperfunctional thyroid tissue using gamma rays and beta particles; I-131 is excreted through urine and feces, patients are hospitalized until they are releasing safer levels of radiation; after discharge cats must be kept indoors, close contact should be minimized (or eliminated entirely for pregnant women and children), all waste must be stored according to state and local guidelines
- surgical thyroidectomy: scintigraphy should be performed prior to sx to locate possible ectopic thyroid tissue that can be found in the thoracic inlet or cranial mediastinum; risks include accidental inadvertent removal of adjacent parathyroid gland(s) or their blood supply (resulting in postoperative hypoparathyroidism and subsequent hypocalcemia) - typically not permanent, laryngeal paralysis, Horner’s syndrome, permanent hypothyroidism (requiring supplementation)
- dietary iodine restriction: hyperthyroid cats fed a diet with < or equal to 0.32 PPM of iodine (DMB) can maintain a normal thyroid level; must be fed this diet EXCLUSIVELY only a small amount of regular food will offset the benefits; recheck PE/CBC/chem/UA/T4 q 6mo indefinitely; cats receiving anti thyroid medications should be weaned off while transitioning to iodine-restricted diet
Primary Hyperparathyroidism
OVERVIEW
- an abnormal increase in the amount of functional parathyroid tissue
- primary disease (more common in dogs) or secondary to renal disease (renal secondary hyperparathyroidism)
- naturally occurring primary hyperparathyroidism is most commonly benign and Keeshonds are over represented
- NORMAL: PTH downregulated to respond to hypercalcemia (eg if hypercalcemic, PTH should be decreased)
CLINICAL SIGNS
- all signs are due to hypercalcemia
- PU/PD, if chronic can see weight loss and lethargy
DIAGNOSIS
- CBC: elevated HCT (secondary to PU/PD)
- chem: hypercalcemia (total calcium and ionized calcium), phosphate low to normal (elevated phosphate in renal secondary hyperparathyroidism), elevated BUN (pre-renal/dehydration 2nd to PU/PD), hyperalbuminemia (2nd to PU/PD)
- UA: isosthenuria, even with dehydration
- dx of primary hyperparathyroidism follows r/o of more common causes of hypercalcemia (LSA, AGASACA, renal failure)
- PTH normal to elevated (normal PTH in face of significant hypercalcemia represents inappropriate lack of PTH suppression)
- PTHrP normal (?)
- cervical U/S: solitary parathyroid nodule (typically only 1 of the 4 parathyroid glands are affected); diffuse, bilateral enlargement more consistent with renal secondary hyperparathyroidism
TREATMENT
- inpatient treatment: maintenance of ionized calcium levels with IVFT, diuretic therapy (once volume status has normalized), +/- corticosteroids to promote calciuriesis
- medical management ideal prior to surgery to reduce anesthetic risks (calcium and vitamin D3 24-72 hr preoperatively) to help prevent life-threatening hypocalcemia
- parathyroidectomy or percutaneous ablation considered treatment of choice
- outpatient treatment: long term supplementation not typically needed, once PTH and calcium levels have equilibrated; renal secondary hyperparathyroidism requires long-term medical management
- due to dysregulation of PTH response patients often develop severe to life-threatening hypocalcemia post-operatively; frequent monitoring of iCa (and any necessary supplementation) is crucial, especially during postoperative period
Renal Secondary Hyperparathyroidism
OVERVIEW
- hyperphosphatemia from renal disease induces production of PTH —> enhances release of calcium from bone, aids in reabsorption of calcium from renal tubules, and augments the absorption of calcium from intestines
- combination of hyperphosphatemia and hypercalcemia leads to mineralization of soft tissues, joints, and vessels (via calcium phosphorus crystals); kidney, stomach, liver are particularly sensitive to mineralization
- renal secondary hyperparathyroidism often starts BEFORE phosphorus is elevated outside the reference range
- calcitriol (vitamin D) is produced in renal tubule cells; PTH promotes formation of calcitriol —> calcitriol reduces PTH production through negative feedback loop; elevated phosphorus levels reduce formation of calcitriol in renal tubules and without negative feedback of calcitriol, PTH rises —> leading to secondary renal hyperparathyroidism
- as CKD progresses there are fewer tubule cells to produce calcitriol leading to further increases in PTH
- impaired intestinal absorption of calcium due to low levels of calcitriol, and uremic toxins limiting effectiveness of calcitriol to inhibit PTH also important factors
CLINICAL SIGNS
- mental dullness, lethargy, weakness, anorexia, impaired muscle function
DIAGNOSIS
- hypercalcemia (total and ionized)
- phosphorus normal to elevated
- PTH elevated
- PTHrP normal (?)
- changes in bone density (skull and mandible most common - may lead to “rubber jaw” or mandibular fracture)
- other findings consistent with renal dz
TREATMENT
- calcitriol (most active form of vitamin D)
Hypoparathyroidism
OVERVIEW
- characterized by loss of functional parathyroid tissue
- primary hypoparathyroidism is immune mediated and more common in dogs; toy poodles are over represented
- iatrogenic hypoparathyroidism may be seen secondary to inadvertent removal or damage of parathyroid glands (eg during thyroidectomy for treatment of feline hyperthyroidism); or as temporary or permanent result of therapy for primary hyperparathyroidism
CLINICAL SIGNS
- all signs are due to hypocalcemia
- neuromuscular signs are seen with severe hypocalcemia: weakness, lethargy, muscle fasciculations (can be severe enough to resemble tonic clonic seizure activity); hyperthermia may develop 2nd to tremors/seizures; +/- facial pruritis
DIAGNOSIS
- hypocalcemia (ionized calcium preferred, total calcium does not accurately represent)
- PTH decreased
- PTHrP normal (?)
- no specific imaging procedures to aid in diagnosis
TREATMENT
- inpatient treatment: correcting severe hypocalcemia with calcium gluconate (ECG monitoring required during administration) IV, then followed by parenteral or PO calcium supplementation; temp monitoring (for hyperthermia 2nd to tremors); calcitriol PO long term
- outpatient treatment: calcitriol +/- PO calcium (Tums)
Hyperadrenocorticism (HAC)
OVERVIEW
- aka Cushing’s disease (technically reserved for pituitary-dependent HAC)
- NORMAL: pituitary gland secretes ACTH —> stimulates adrenal glands to release cortisol —> presence of cortisol tells pituitary to stop secreting ACTH via negative feedback loop
- results of hypersecretion of cortisol by a FAT (15-20%) or secondary increase in ACTH from a pituitary tumor (80-85%)
- iatrogenic HAC can occur with corticosteroid administration
- PDH: feedback loop is disrupted by pituitary tumor and ACTH is release despite high cortisol levels
- FAT: excessive amounts of glucocorticoids are released by FAT —> results in low ACTH —> results in atrophy of the contralateral adrenal gland
- middle-aged to older dogs, doxies, terrier breeds, poodles, boxers overrepresented
- rare in cats
CLINICAL SIGNS
- signs are results of excessive glucocorticoid production
- PU/PD/PP, excessive panting
- PE = pendulous abdomen (2nd to muscle wasting from excessive cortisol), weight gain, weakness, truncal bilaterally symmetrical hair loss; less common: calcinosis cutis, facial paralysis
- in cats: all above signs plus excessively fragile skin
DIAGNOSIS
- CBC: stress leukogram - lymphopenia, eosinopenia, neutrophilia, monocytosis
- chem: elevated LE (ALP predominant)
- UA: USG <1.020, proteinuria; may have concurrent UTI; glucosuria less common
- UCCR: highly sensitive but low specificity, useful to r/o but not to diagnose. Normal UCCR (<10) rules out HAC
- ACTH stim: used to evaluate the adrenal gland’s response to exogenous ACTH; most useful for differentiating spontaneous from iatrogenic HAC; dogs with spontaneous HAC have exaggerated response, dogs with iatrogenic HAC or HoAC have normal to diminished response
- LDDST: evaluates negative feedback loop of HPAA; in normal dogs dexamethasone suppresses secretion of ACTH from pituitary gland, decreasing cortisol to <1.4 ug/dL
- LDDST is preferred over ACTH stim to differentiate PDH from FAT (4hr is <1.4 ug/dL or <50% baseline cortisol)
- AUS can also differentiate FAT by visualizing adrenal tumor +/- atrophy of contralateral adrenal gland
- HDDST is the diagnostic test used in cats
TREATMENT
- trilostane/vetoryl PO SID
- mitotane (Lysodren) previously used, but worked by selective adrenocorticolysis, require daily contact to ensure o’ compliance, and could result in complete adrenocorticolysis
- post-pill ACTH stim should be performed at 10d, 1mo, 3mo, and q 6mo thereafter
- unilateral adrenalectomy is preferred treatment for FAT, trilostane can help improve QOL but does little to affect tumor size
NUTRITION
- up to 50% of dogs with HAC have elevated serum cholesterol and triglycerides
- mild fat restriction is recommended
- diet recommendations are often based on concurrent comorbidities, including DM, that have specific dietary requirements
Hypoadrenocorticism (HoAC)
OVERVIEW
- aka Addison’s disease
- characterized by glucocorticoid or mineralocorticoid deficiency, results from failure of the cortex of adrenal glands
- most common cause is immune mediated adrenalitis (aka primary HoAC)
- less common causes: granulomatous destruction, hemorrhagic infarction of the adrenal gland; amyloidosis; necrosis; metastatic neoplasia of the hypothalamus or pituitary gland
- predisposition for young to middle-aged female dogs; inherited in standard poodles, Portuguese Water Dogs, Nova Scotia duck tolling retrievers but can affect any breed
- vague clinical signs (GI signs, etc.), often called “The Great Pretender”
- typical Addison’s = deficiency of glucocorticoids AND mineralocorticoids
- atypical Addison’s = deficiency of glucocorticoids only
CLINICAL SIGNS
- waxing and waning lethargy, vomiting, diarrhea, dehydration; less common PU/PD, muscle tremors, abdominal pain, shock, collapse
- Addisonian Crisis: lethargic, dehydrated, hyponatremic, hyperkalemic due to last of aldosterone
DIAGNOSIS
- CBC: nonregenerative anemia, lack of a stress leukogram; neutrophilia, lymphopenia, eosinopenia may be present
- chem: Na:K ratio < 27:1; hyponatremia, hyperkalemia, prerenal azotemia (2nd to hypovolemia), hypoglycemia, elevated LE, hypercalcemia, hyperphosphatemia, hypoalbuminemia
- UA: USG <1.030
- TXR: microcardia, reduced caudal vena cava size (both 2nd to hypovolemia), +/- megaesophagus
- AXR: often obtained to r/o GIFB; NSF
- AUS: small adrenal glands
- baseline cortisol >2 ug/dL has a high negative predictive value
- baseline cortisol <2 ug/dL suspicious for HoAC, ACTH stim with pre- and post- samples <2 ug/dL confirmatory for HoAC
- endogenous ACTH and aldosterone concentrations are available but of limited value
TREATMENT
- Addisonian crisis: true medical emergency; correction of hypovolemia, electrolyte abnormalities, and metabolic acidosis; bolus of IVF, ACTH to confirm/dx, dexamethasone IV ok to give prior to ACTH (will not interfere)
- long-term txt: supplementation of glucocorticoids (physiologic dosing: 0.1-0.22 mg/kg/day, doubled at times of stress), +/- mineralocorticoids (if typical Addison’s); fludrocortisone (Florinef) provides both glucocorticoid and minderalocorticoid
Pheochromocytoma
OVERVIEW
- neuroendocrine tumor of the sympathetic nervous system capable of secreting catecholamines; typically arises from chroma fin cells of adrenal medulla, but can also arise form extramedullary chroma fin cells in sympathetic ganglia in other parts of the body (rare)
- tumor is typically solitary and slow-growing
- in rare cases bilateral pheo or pheo with FAT on contralateral adrenal gland have been reported
- catecholamine release may be stimulated by blood flow, direct pressure, various chemicals or drugs
- positive correlation may exist between size of tumor and presence and severity of clinical signs
CLINICAL SIGNS
- vague and intermittent
- signs are associated with either the sporadic and unpredictable release of catecholamines (epi, norepi, dopamine), or relate to the space occupying nature and locally invasive and metastatic behavior of the tumor
- arteriolar vasoconstriction and hypertension, mydriasis, increased smooth muscle sphincter tone, stimulation of hepatic gluconeogenesis and glycogenolysis
- patient may present in hypertensive crisis: intermittent collapse and generalized weakness
- intermittent excessive panting, agitation, “pounding” heart, syncope, PU/PD, lethargy, vomiting, inappetence, anxiety
- less common: flushing, sudden blindness (2nd to systemic hypertension), signs associated w/ spontaneous hemorrhage (weakness, epistaxis, neuro signs)
- rarely: sudden death from sustained release of catecholamines by tumor
- PE = variable; may be unremarkable but may see signs of catecholamine release can involve the respiratory (increased bronchovesicular or alveolar sounds, crackles), cardiovascular (tachycardia, arrhythmias, weak femoral pulses, pale MM), and musculoskeletal systems (weakness, muscle atrophy)
- mydriasis, retinal hemorrhage, retinal detachment, blindness, epistaxis (2nd to hypertension)
- neuro signs: systemic hypertension and CNS hemorrhage or metastasis —> seizures, head tilt, nystagmus, strabismus
- palpable abdominal mass rare but ascites, peripheral edema of hind limbs, and abd pain may be appreciated if caval invasion or obstruction
DIAGNOSIS
- requires a high index of suspicion, as signs are vague and episodic
- labs rarely helpful: anemia, erythrocytosis, thrombocytopenia, elevated LE, hypercholesterolemia, azotemia, isosthenuria, proteinuria are all possible
- LDDST to r/o FAT as cause of signs
- BP to assess for systemic hypertension (though normotension does not r/o pheo)
- AXR = perirenal mass, not specific enough for diagnosis of pheo
- TXR = assess for pulmonary mets (~10% of cases); evidence of pulmonary congestion of edema 2nd to hypertension may be seen
- AUS = most reliable screening test, adrenal tumor +/- abdominal metastasis
- CTA (or MR) = diagnostic and assesses for local invasion of vasculature, kidney, and epaxial muscles
- measurement of serum and urine catecholamines of limited value due to inconvenience of 24hr urine collection and sample storage requirements
TREATMENT
- medical management prior to surgical resection: alpha-antagonist (phenoxybenzamine) PO for 1-3 wk prior to adrenalectomy; beta-blockers (propranolol) to treat arrhythmias AFTER alpha-antagonists
- adrenalectomy postoperative complications: hypertension, hemorrhage, arrhythmias, respiratory distress; should only be performed by a skilled surgeon at a 24hr facility
- RT for inoperable tumors, palliative care with phenoxybenzamine indicated for widespread metastatic dz
ANESTHESIA/ANALGESIA
- anesthetic induction and intraoperative tumor manipulation associated with life-threatening complications
- anesthetic drugs should be selected to limit potentiation of catecholamine-induced hypertension and arrhythmias
- monitoring of invasive/direct arterial BP and ECG perioperatively and for 24hr post op
- phentolamine +/- esmolol to treat hypertension intra-op
- intraoperative hypotension after tumor resection common; treat by reducing or discontinuing phentolamine; short-acting alpha-adrenergic (phenylephrine); colloid administration; crystalluria administration to expand ECF volume
Insulinoma
OVERVIEW
- insulin-secreting tumor(s) arising from beta cells in the pancreatic islets
- beyond ingestion of macronutrients body is dependent on glucose production by the liver for energy for cell metabolism
- NORMAL: glucose provided by hepatic breakdown of stored glycogen (glycogenolysis) —> once depleted main source of glucose arises from production of glucose from fatty acids, amino acids (supplied by muscles), lactate (supplied by blood via glycolysis), and glycerol (supplied by fat); pancreatic beta cells responsible for regulating BG, when BG exceeds normal insulin is secreted and BG reduced to normal range via cell utilization and suppression of hepatic glucose production; when BG low insulin synthesis and secretion is inhibited
CLINICAL SIGNS
- typical in older dogs
- all signs 2nd to hypoglycemia
- seizures, weakness/ataxia, tremors, behavioral changes
DIAGNOSIS
- mild to marked hypoglycemia
- AXR = NSF, insulinomas are usually small (<3 cm) pancreatic nodules, not typically visible on radiographs
- TXR = to assess for pulmonary mets
- AUS = pancreatic nodule supportive of diagnosis
- CT = may be more sensitive for detecting primary and metastatic tumors
- insulin:glucose ratio = collected when BG <50-60 mg/dL
TREATMENT
- acute/hospitalized patient: priority is NOT to establish euglycemia ASAP; instead, diagnostic testing should be prioritized (I:G ratio prior to dextrose, etc), establish whether surgery is to be pursued, and minimize C/S 2nd to hypoglycemia (through IV dextrose); frequent or rapid IV dextrose boluses may lead to rebound hypoglycemia by stimulating tumor to secrete insulin
- pancreatectomy to debulk or remove tumor seldom curative, but can improve response to chronic medical management and prolong survival times; in rare cases may be curative
- postoperative complications are common and include: pancreatitis, DM (rare complication of aggressive resection, atrophy of remaining islet cells results in insufficient insulin production), hypoglycemia (due to incomplete tumor resection or persistence of functional mestastases)
- chronic medical management: in lieu of surgery or postoperative - frequent feedings, minimizing exercise and excitement, glucocorticoids, diazoxide (diuretic that inhibits insulin secretion and tissue utilization of glucose, and stimulates hepatic gluconeogenesis) euglycemia may never be achieved
Pancreatitis
OVERVIEW
- ACUTE (AP): fully reversible inflammation with histologic presence of edema, neutrophilic infiltrate, and necrosis
- CHRONIC (CP): continuing inflammation (lymphocytic/lymphoplasmacytic) with irreversible changes such as fibrosis; can be subclinical or recurrent with episodes of more or less severe illness, as in AoCP
- in some cases loss of pancreatic tissue leads to decreased exocrine and/or endocrine function
- etiology remains idiopathic
- miniature schnauzers, yorkies and other terriers appear to be predisposed
- majority of cats with acute necrotic and suppurative pancreatitis are DSH
- CP more common in CKCS, English cocker spaniels, boxers, and collies
- hypertriglyceridemia and obesity important risk factors for canine pancreatitis; dietary indiscretion considered risk factor for AP
- bile duct obstruction may exacerbate pancreatitis and impair ability to clear bacteria in cats with pancreatic fibrosis and disorders of the major papilla due to joint termination of the CBD and pancreatic duct in this species
- endocrine disorders linked to canine AP include HAC, hypothyroidism, and DM (including DKA)
- CP considered cause of DM, not a consequence of DM in both cats and dogs
- trauma and surgical or minimally-invasive interventions are also possible risk factors: traumatic pancreatitis from high-rise syndrome in cats, previous abdominal surgery has been associated with increased odds ratio in dogs, endoscopic retrograde cholangiopancreatography (ERCP) has potential to induce AP
- CP thought to be either late complication of AP or a consequence of chronic immune-mediated inflammation
- CP more common than AP in cats
- pancreatic tissue loss due to fibrosis in CP can lead to EPI and/or DM in end-stage disease
- EPI in dogs more often caused acinar atrophy following another pathophysiologic mechanism
PATHOPHYSIOLOGY
- AP and acute pancreatic necrosis are suggested to be responses to same stimuli with different progression and outcome; mild AP is localized process with uncomplicated full recovery, while severe AP with necrosis can be localized but also cause SIRS, resulting in multi organ dysfunction syndrome (MODS) and death
- activation of trypsin within acinar cells, caused by three basic scenarios: 1) blockage of the acinar cell apex in the pancreatic duct, leading to co-localization and fusion of zymogen and lysosomal granules, 2) oxidative stress, 3) hypertension
Exocrine Pancreatic Insufficiency (EPI)
OVERVIEW
- condition associated with digestive enzyme deficiencies which may result in malassimilation (intestinal malabsorption), voluminous stools, steatorrhea, borborygmus, flatulence, and weight loss
- caused by progressive immune-mediated acinar and ductal atrophy; chronic pancreatitis may also be a cause
- more common in dogs, but being diagnosed in cats more frequently
- in cats: CP thought to be most common cause of EPI
- GSD overrepresented
CLINICAL SIGNS
- diarrhea, steatorrhea, voluminous stools, borborygmus, flatulence, weight loss
DIAGNOSIS
- trypsin-like immunoreactivity (TLI): decreased
TREATMENT
- pancreatic enzyme supplementation
- +/- cobalamin supplementation (if deficient)
Hypersomatotropism and Hyposomatotropism
OVERVIEW
- Acromegaly is the syndrome developed as a result of hypersomatotropism
- benign functional tumor of the feline pituitary gland, autonomously secretes excess growth hormone (GH)
- typically older cats (8-14yr), M>F
- GH is a natural diabetic Enid hormone and antagonizes the effects of insulin
- most common presentation is insulin-resistant feline DM
- DOGS: functional pituitary tumors less common; acromegaly often associated with natural estrous cyst less or exogenous progesterone therapy; has also been associated with various neoplasticism processes (mammary carcinoma); GH deficiency (hyposomatotropism) most commonly a congenital lesion, patients classified as pituitary “dwarfs”, GSD overrepresented
CLINICAL SIGNS
- C/S most often associated with poorly regulated DM in cats: PU/PD/PP, weight loss, diabetic neuropathy
- GH has effect of promoting linear growth (with insulin-like growth-factor 1 [IGF-1]) —> associated with abnormal growth in adult animals - increasing body weight, widening interdental spaces, organomegaly, enlarging skull size; late-stage may see cardiomegaly which progresses to CHF and azotemia
- hyposomatotropism manifests as poor weight gain, unthrifty body condition, and juvenile hair coat
DIAGNOSIS
- hypersomatotropism: IGF-1 levels (serum, frozen and sent on ice to MSU); IGF-1 is an indirect measurement of GH excess, levels will be elevated in patients with acromegaly
- hyposomatotropism: IGF-1 can be measured, but xylazine response test is preferred; SST baseline, xylazine 100pg/kg IV, then SST at 15min, 30min, 45min, and 60min
- CT can detect pituitary tumors in suspected acromegaly cases
- CTA can rule out differential dx for microstature (PSS, etc) in suspected hyposomatotropism
TREATMENT
- acromegaly: radiation therapy (RT) can be considered to reduce size of pituitary tumor; higher doses on insulin typically required, aggressive glycemic control required; RT has helped reduce insulin requirements post-RT txt
- hyposomatotropism: hormone supplementation (porcine GH +/- thyroxine or other hormone deficiencies)
Central Diabetes Insipidus (DI)
OVERVIEW
- abnormality in the formation of ADH
CLINICAL SIGNS
- ADH responsible for concentration of urine, in absence of normal ADH urine remains dilute
- severe PU/PD
DIAGNOSIS
- diagnosis of exclusion (work-up for PU/PD)
- UA: hyposthenuria (<1.008)
- UTIs common
- water deprivation tests have been used but are seldom advised due to possibility of severe dehydration, renal damage, and death
- must rule out other causes of PU/PD, then trial treatment with desmopressin
TREATMENT
- desmopression (synthetic ADH) results in increased urine concentration and reduction of PU/PD
- under no circumstances should water be withheld, o’ may be tempted to limit water intake to reduce urination, but can cause life-threatening dehydration and renal insult with possible permanent renal damage
Hyperaldosteronism
OVERVIEW
- aldosterone secreting adrenal tumor
- aldosterone is principle mineralocorticoid synthesized and secreted by the zona glomerulosa (ZG) of the adrenal cortex; primary function is regulation of Na and K+ and intravascular volume homeostasis; increase in serum K+ directly stimulates aldosterone secretion; decrease in BP (sensed in kidneys) stimulates synthesis and release of renin which, through angiotensin II, stimulates aldosterone secretion (RAAS)
- aldosterone acts on distal nephrons to promote Na reabsorption and K+ and hydrogen excretion, in conserving Na, aldosterone indirectly conserves water, raising blood volume and, in turn, BP; also directly increases BP via enhancement of total peripheral resistance
- aldosterone is also synthesized in heart, brain, and vasculature tissues
- PRIMARY HYPERALDOSTERONISM (PHA): autonomous aldosterone secretion by adrenocortical cells; characterized by circulating aldosterone exces and, through negative feedback, renin suppression
- SECONDARY HYPERALDOSTERONISM : result of a condition (heart failure, CKD), which stimulates RAAS, thus associated with enhanced renin concentration
- CATS: PHA typically from malignant aldosteronoma (unilateral much more common than bilateral); tumors that secrete glucocorticoids and mineralocorticoids uncommon; secondary hyperaldosteronism due to CKD most commonly
- DOGS: PHA typically from unilateral solitary adrenal adenoma or carcinoma, rarely bilateral idiopathic adrenocortical hyperplasia; tumors that secrete glucocorticoids and mineralocorticoids uncommon
CLINICAL SIGNS
- CATS: C/S related to hypokalemia or hypertension (cervial ventroflexion, hindlimb weakness/plantigrade stance, difficulty jumping, listlessness, ataxia); hypertension may rarely cause seizures, ataxia, behavior changes as result of CNS edema, hemorrhage, or ischemia; hypokalemia can cause irreversible nephrogenic diabetes insidpidus and PU/PD
- DOGS: lethargy, anorexia, weakness, PU/PD
DIAGNOSIS
- CATS: PE = findings related to hypokalemia or hypertension; tortuous retinal vessels, retinal detachment, hemorrhage, and/or edema; signs consistent with glucocorticoid/progesterone excess include fragile skin, alopecia, pendulous abdomen; heart murmur/gallop rhythm/arrhythmias secondary to LV hypertrophy (2nd to hypertension)
- CATS LABS: mod-severe hypokalemia despite K+ supplementation, increase urinary fractional K+ excretion, hypernatremia uncommon (“aldosterone escape”), metabolic acidosis; serum aldosterone confirms dx; plasma renin activity (PRA) assess on same sample as aldosterone = below or within ref range (not currently available in USA)
- CATS IMAGING: large tumor possible on AXR (though often not helpful), pulmonary mets uncommon, AUS = adrenal tumor (contralateral adrenal gland atrophy suggests functional adrenal tumor), bilateral masses uncommon; CTA to assess for local invasion
- DOGS: hypertension
- DOGS LABS: hypokalemia, Na high-normal to mildly elevated, metabolic alkalosis; increased baseline PRA and suppressed PRA in conjunction with exclusion of other causes of hypokalemia (PRA not currently available)
- DOGS IMAGING: AUS = adrenal tumor, if no tumor may be idiopathic adrenocortical hyperplasia, CTA to assess for local invasion/mets
TREATMENT
- CATS: adrenalectomy (in theory could cause hypoaldosteronism due to atrophy of contralateral adrenal gland)
- DOGS: unilateral adrenalectomy for solitary adrenal mass
- MEDICAL MANAGEMENT (BOTH): management of hypokalemia and systemic hypertension = oral K+ supplementation, amlodipine (for BP), spironolactone (mineralocorticoid receptor blocker); monitoring of BP and electrolyte levels
