Exam III Flashcards
Endocrinology
Hypoadrenocorticism
What is it?
Addison’s Disease!
Hypoadrenocorticism
Pattern Recognition
“Great pretender” – looks like many other diseases
Following signs may wax and wane
GI signs Lethargy Weight loss Sick dog with no stress leukogram Lyphocytosis Eosinophilia Hypocholesterolemia Prerenal Azotemia Electrolytes: Hypercalcemia Hyperphophatemia Hyponatremia Hyperkalemia Hypochloridemia
Atypical Addison’s
No electrolyte abnormalities
Layers of the Adrenal Gland
Zona Glomerulosa:
Aldosterone
Salt
Zona Fasiculata:
Glucocorticoids
Sugar
Zona Reticularis:
Androgens
Sex
Medulla:
Catecholamines: Epi and Norepinephrine
Hypoadrenocorticism
Causes
Primary
Adrenal Gland Lesion
Immune mediated destruction of the adrenal cortex (85-90% must be destroyed)
Other: iatrogenic via drugs (mitotane, trilostane), suppression by exogenous steroids, neoplasia, granulomatous disease
Secondary
Pituitary Gland Lesion
Rare, decrease ACTH
Hypoadrenalcorticism
Types
Typical:
Destruction of ZG and ZF => NO aldosterone or glucocorticoids
Deficiency of cortisol (glucocorticoids) and aldosterone (mineralocorticoids)
Atypical: Destruction of ZF Signs of cortisol deficiency only! NO electrolyte changes Some patients do have adlosterone deficiency (which causes electrolyte deficiency in Typical however Atypical will not have electrolyte abnormalities)
Hypoadrenalcorticism
Predisposing Factors
Young to middle age
Females
Breeds: Standard Poodles Portuguese water dog Nova Scotia Duck Tolling Retrievers Bearded Collie
Addisonin Crisis
Presentation
Caused by?
Treatment
Emergency!
Presents: recumbent, shocky
Caused by: iatrogenic administration of steroids
Treatment:
IV fluids (electrolyte balance; correct slowly)
Supportive and symptomatic care
Get blood work including running an ACTH Stim
If suspicious of Addison’s can start dexamethasone therapy (will NOT interfere with cortisol assay) - will help with vascular tone
Sodium must be at homeostatic level before treating with mineralocorticoids
Hypoadrenalcorticism
CBC
Chem
UA
CBC: No stress leukogram! Eosinophilia Lymphocytosis Non-regenerative anemia (masked by dehydration, chronic disease, erythropoiesis)
Chem: Hyponatremia Hyperkalemia (DANGER) Azotemia Hyperphosphatemia Sometimes: Hypercalcemia Hypoalbuminemia Hypoglycemia Hypocholesterolemia Elevated liver enzymes
UA:
Isosthenuria even with dehydration
Medullary washout due to hyponatremia
Cortisol Deficit vs. Aldosterone Deficit
Cortisol:
Vomiting
Diarrhea
Maintains vascular tone
Aldosterone:
PU/PD
Electrolyte control
Both:
Lethargy/weakness
Collapse
Hypovolemic shock
Na:K Ratio
What does this test for?
What is this?
Dx: Hypoadrenocorticism
Typical Addisons:
K is high and Na is low during
Na:K <27
Atypical Addisons:
Electrolytes normal
(can progress to Typical form)
Baseline Cortisol
What does this test for?
Screening test or Diagnostic?
Hypoadrenalcorticism
Screening Test
Rule out test
Cortisol <2 ug/dL = NOT diagnostic must do ACTH stim for confirmation – but is suspicious for it
Cortisol >2 ug/dL = NOT ADDISON’S
ACTH Stim
What does this test for?
Screening test or Diagnostic?
Dx: Hypoadrenalcorticism and Hyperadrenalcorticism
Diagnostic = Addison's Screening = Cushing's
Give cosyntropin IV and measure cortisol 1 hour post administration
Evaluates maximal stimulation of adrenocortical reserve of cortisol
Addisonian patients have pre and post cortisol values <1 ug/dL
<2 ug/dL indicates Addison’s
> 21 ug/dL considered diagnostic in animals with clinical signs and no concurrent illness for Cushing’s
Hypoadrenalcorticism Treatment (Rx) for chronic case
Lifelong!
Glucocorticoids: Pred Daily Physiologic dose: 0.1-0.25 mg/kg May need to increase dose during stressful or exciting events GI signs: too low dose PU/PD, polyphagia: too high of a dose
Mineralocorticoid: DOCP
Percortin - IM injection
Administered 25-30 days
Monitor electrolytes (at first every 2 weeks then once normalized every 6 months)
Glucocorticoid and Mineralocorticoid:
Florinef (oral)
Daily
May need additional Pred
Hypoadrenalcorticism
Prognosis
Good!
However, life long treatment required
Monitor for rest of life (once on schedule every 6 months should be fine)
Hypercalcemia
How do you know if it is a true hypercalcemia?
What is your list of DfDx?
True hypercalcemia: ionized calcium
DfDx: G: Granulomatous O: Osteolytic S: Spurious H: Hyperparathyroidism D: Vitamin D A: Addison's R: Renal N: Neoplasia I: Idiopathic, Iatrogenic
Hyperadrenocorticism
What is it?
Cushing’s
Hyperadrenocorticism
Caused by (2 kinds)
Age?
Sex?
Pituitary gland (PDH) 80-85% Benign adenomas Most are microadenomas More common in small breeds Tumors produce ACTH
Adrenal gland(s) (ADH)
50/50 benign adenomas vs carcinomas
Affects large breed dogs more frequently
Tumors produce cortisol
Usually middle to older age dogs
Females
Hyperadrenocorticism
Clinical Signs
PU/PD (ADH no longer functioning properly)
Polyphagia
Panting:
Weakening of diaphragm muscles
Dermatologic problems (truncal alopecia): usually symmetrical, non-pruritic Thin skin Calcinosis cutis (deposition of calcium in skin; telling sign!)
Secondary infections (UTI): culture urine
Abdominal distension: Fat retention Hepatomegaly Weakness of abdominal muscles Muscle wasting (protein catabolism)
Usually a disease of dogs
Hyperadrenocorticism
Macroadenoma
Clinical signs
Neurologic Signs: Inappetance/anorexia Dullness Disorientation Circling Ataxia Behavioral Changes (wandering)
Hyperadrenocorticism
CBC
Chem
UA
CBC:
Stress leukogram
Thrombocytosis
Chemistry:
Increased ALP
Hypercholesterolemia
Increased ALT (hepatomegaly) Hyperglycemia (even when fasted; can enter diabetic state)
UA:
Isosthenuria
Proteinuria
UTI
Hyperadrenocorticism
Screening tests
Urine Cortisol/Creatinine Ratio (Rules out)
ACTH Stimulation Test
Low Dose Dexamethasone Suppression Test
ACTH Stim
Pituitary Tumor response
Tumor is producing high amounts of ACTH
Consistently high ACTH => adrenal glands constantly stimulated to produce cortisol
Give ACTH: adrenal glands respond by releasing all cortisol they have saved
ACTH Stim
Adrenal Tumor Response
Adrenal tumor cells produce cortisol erratically and are not necessarily responsive to exogenous ACTH
Endogenous ACTH will be low
Cortisol may be elevated with an adrenal tumor but a normal result does not rule out ADH
Iatrogenic Cushings
What is it
Diagnosis
Cushing’s like signs due to administration of exogenous steroids
Atophy of adrenal glands causing lack of endogenous steroid production – now us giving them steroids is giving them the cortisol they utilize
Inability of adrenal glands to respond to ACTH and therefore do not produce cortisol
If steroid is discontinued will cause Addisonian Crisis – must taper off
Diagnosis:
Only way to diagnose this is via ACTH Stim
Cortisol will be low b/c body no longer producing cortisol
Low Dose Dexamethasone Suppression Test
What does this test for
Diagnose PDH? ADH?
Dexamethasone suppresses ACTH and decreases cortisol release from adrenals
High sensitivity
Differentiates between PDH and ADH
Protocol:
Check baseline cortisol
Administer dexamethasone
Check cortisol at 4 hours and 8 hours post dex
Interpretation: Note: can diagnose PDH Look at 8 hour: Diagnoses Cushing's >1.4 ug/dL = Cushing's Negative feedback not working 4 hour time point: PDH: tumor cells briefly suppress in response to dexamethasone. At hour 8 will go back to regular high value (escape)
ADH: cortisol will stay high the entire time even with dex on board. Because adrenal tumor producing cortisol erratically – however still cannot diagnose ADH via this method
Hyperadrenalcorticism
Discriminatory Test
LDDS Test HDDS Test Endogenous ACTH Concentration Abdominal U/S CT/MRI
High dose dexamethasone suppression test
Protocol:
Check baseline cortisol
Administer dexamethasone
Check cortisol at 4 hours and 8 hours post dex
Same as LDDS however uses 10x as much dexamethasone
Differentiation based on pattern of suppression and escape
PDH: escape (10% greater chance in identifying compared to LDDS) – differentiation from ADH
OR suppression at both 4 and 8 hours = PDH
ADH: never suppress
But lack of suppression does not definitively differentiate
Endogenous ACTH
What does it test for?
Hyperadrenalcorticism
ADH: ACTH suppressed due to negative feedback therefore levels are low (<5)
Good test for ADH
PDH: Secretion of ACTH is variable; levels are usually normal or high (>30)
Not a good test for PDH
Hyperadrenalcorticism
Abdominal ultrasound
Findings
Evaluate adrenal glands
PDH:
Bilateral enlargement
ADH:
Unilateral enlargement
Hyperadrenalcorticism
CT/MRI
Findings
Recommended test for PDH
Pituitary tumor evaluation:
Macroadenoma?
Differentials for adrenal tumors
Functional adenoma: producing cortisol
Nonfunctional adenoma (incidentaloma): Begin tumor
Cortical Adenocarcinoma: functional or not
Pheochromocytoma: medullary tumor producing catecholamines
Other – Metastasis:
Pulmonary, mammary, prostatic, gastric, pancreatitic carcinoma, melanoma, lymphoma, etc
Hyperadrenocorticism
Complications
Hypertension
Pyelonephritis/Urinary Tract infections
Pancreatitis Diabetes Mellitus (push pre-diabetics into full diabetics also makes control difficult)
Hypercoaguable
uncommon
Hyperadrenocorticism
ADH vs PDH Treatment
ADH: surgery
Adrenalectomy
PDH: medical
Surgery offered at WSU (hypophysectomy – removal of pituitary gland): will have to supplement the other hormones you will be taking away (TSH, ADH)
Mitotane (Lysodren, o,p’-DDD)
What does it treat?
MOA
High dose vs Low dose
Tx: Cushing’s PDH and ADH
This is a chemotherapeutic drug
MOA
Adrenolytic/adrenal cytotoxic
Mainly attacks ZF and ZR with small amount of ZG destruction
High dose: Will create an Addisonian patient; may be easier to treat than Cushing’s
Low dose: slower progression of destruction of the adrenals. Must monitor super closely if any adverse effects occur (GI, lethargy) stop treatment and check ACTH stim test
Trilostane (Vetoryl)
What does it treat?
MOA
Monitor
Tx: Cushing’s PDH and ADH
MOA
A synthetic steroid analog
Competitive enzyme inhibitor that blocks formation of cortisol
More user friendly than Mitotane
Give in the morning; important for re-checks
Monitor:
ACTH stim test in 2 weeks and 4 weeks; do not adjust dose until 4 week check has been done
Also monitor electrolytes
PTH
Where does it work and what does it do there?
Bone:
Increase Ca2+ release
Increase Phosphorous release
Kidney:
Activation of Vitamin D3 –> Calcitriol
Increase Ca2+ reabsorption
Decrease Phosphorous (excrete it!)
Small Intestines:
Calcitriol activity (transport Ca2+ from lumen of the SI)
Increase Ca2+ absorption
Increase Phos absorption
Overall: Increase Ca2+ and decrease Phosphorous
Primary Hyperparathyroidism
What is it?
Causes?
Signalment?
Excessive production of PTH by the parathyroid glands (releases Ca2+)
High Calcium and low phosphorous
Causes:
Adenoma
Carcinoma
Hyperplasia
Signalment?
Middle to older age
Keeshonds
Labs, Goldens, German Shepherds
Primary Hyperparathyroidism
Clinical signs
Not usually clinical b/c a gradual increase in Ca2+
But could possibly see: PU/PD Lethargy/Weakness Urinary signs: infections, calculi Renal failure
Note: most other causes of hypercalcemia will present very ill
Primary Hyperparathyroidism or Hypercalcemia of Malignancy?
Malignancy Panel:
iCa
PTH
PTHrp (related peptide)
If tests are negative most likely have hyperparathyroidism
Elevated iCa: inappropriately normal PTH (regular or high) = Hyperparathyroidism
PTHrp = some neoplasia and lack of PTHrp does not rule out neoplasia
Note: rule out malignancy via radiographs, unltrasound, CT
Primary Hyperparathyroidism
Treatment
Severe hypercalcemia Fluid therapy -- diurese to get Calcium out Diuretics Glucocorticoids Bisphosphonates Calcitonin (weak)
PHP: Monitor Surgical removal of affected gland (then monitor for hypocalcemia; start supplementation) Ethanol ablation Radiofrequency heat ablation
Hypoparathyroidism
Kidney function
Parathyroid no longer functioning:
Reduced bone release of Ca2+ and Phosphorous
Hypomagnesiumia
Decrease in Ca (ionized) and increase in phosphorus
Kidneys:
Decrease Ca, Mg, and H reabsorption
Increased P, Na, K, and amino acid reabsorption
Hypoparathyroidism
Causes
Suppressed secretion of PTH without destruction
Atrophy – sudden correction of hypercalcemia (post-op parathyroidectomy for PHP)
Iatrogenic
Idiopathic: destruction of parathyroid gland
Immune mediated
Hypoparathyroidism
DfDx
Phosphate enemas Eclampsia Albumin decrease Chronic renal disease Ethylene glycol toxicity/AKI
PTH deficiency
Acute pancreatitis
Intestinal malabsorption
Nutritional
Hypoparathyroidism
Signalment
Dogs > cats
Middle age
Females > males
Breeds: Poodles Mini Schnauzers German Shepherds Labrador Retrievers Terriers
Hypoparathyroidism
Clinical Signs
Sudden onset
Seizures
Intense facial rubbing/biting or licking paws (tingly feeling)
Tetany/muscle spasms
Cataracts Growling Tense/nervous Stiff gait Anorexia Lethargy/weakness Panting Vomiting/diarrhea Cardiac abnormalities: tachyarrhythmias
Hypoparathyroidism
Treatment
Lifelong usually: Calcitriol Oral Calcium (carbonate)
Monitor Frequent iCa (animals respond different to calcitriol)
Emergency situation:
IV calcium gluconate: administer slowly (otherwise cardiac arrest)
Monitor ECG
Primary Hypothyroidism
Etiology
Most common
Decreases in T3 and T4
Etiology
Thyroiditis:
lymphocytic inflammatory infiltration (immune mediated; antibodies against thyroid)
Replaced with fibrous connective tissue
Idiopathic atrophy (replaced by adipose and connective tissue)
Bilateral neoplasia (uncommon)
Hypothyroidism
Clinical Signs
Metabolic (slow metabolism): lethargy, weight gain, heat-seeking, mental dullness
Dermatologic: symmetric alopecia, hyperpigmentation, dry scaly skin, otitis, rat tail, seborrhea)
“Tragic” expression
Neurologic: less common
Peripheral nervous system (weakness and exercise intolerance to ataxia and quadriparesis)
Central nervous system (seizures, central vestibular disease, mentation)
Cardiovascular:
bradycardia, weak heart
not usually a big problem unless already has DCM!
Hypothyroidism
Diagnosis
History, clinical signs, physical exam
No clinical signs – do NOT PURSUE/TEST
CBC:
Normocytic, normochromic, nonregenerative anemia (chronic disease)
Fasting hypertriglyceridemia
Fasting hypercholesterolemia (high suspicion)
Increased hepatic enzymes
Total T4:
Screening test
Highly sensitive
Can fluctuate during day
Non-thyroidal illness
Lab work
aka: Sick Euthyroid Syndrome
Decrease total T4
Normal to decrease free T4
Normal TSH (decreased during illness b/c do not want to feed potential infectious cause)
Normal physiologic response => do NOT supplement
Treat underlying illness
Interpretation of tT4
Low-normal or Low:
Normal fluctuation of a euthyroid dog (non-thyroidal illness occuring)
Hypothyorid
Cannot differentiate between the two with this test
Screening test
Free T4
What does it test for?
Hypothyroidism
Less affected by non-thyroidal illness
Free T4 = active form of T4
More specific than tT4
Confirmatory test
Note: must be off of medication
TSH
What does it test for?
Can you combine it wit another test?
Hypothyroid
Elevated TSH because it is not getting negative feed back
BUT only elevated in 70% of hypothyroid dogs
Combined with low tT4 than diagnostic for hypothyroidism
Can you look at T3 for diagnosing Hypothyroidism
NO
Fluctuation during the day of both T3 and fT3
Synthetic Levothyroxine (T4) Thyro-Tabs, Synthroid What does it treat? MOA Dose
Treatment of choice for hypothyroidism
MOA: direct hormone replacement
Dose:
Oral
Dogs have higher first past metabolism therefore require higher doses than humans; human pharmacist may deny your request at first
Monitor:
Recheck T4 every 6 months once dose established
Hyperthyroidism
Characteristics
Most common endocrine disorder of older cats
Excessive production and secretion of T4 and/or T3 by thyroid gland
Adenomatous hyperplasia
Adenoma
Benign
95-98% of hyperthyroid
Hyperthyroidism
Clinical Signs
Weight loss
Polyphagia
Vomiting
PU/PD Hyperactivity Palpable thyroid slip Poor hair coat Dehydration Cervical ventroflexion (muscle weakness, cannot hold head up) Tachycardia (potentially gallop rhythm)
Hyperthyroidism
CBC
Chem
UA
CBC: Increased PCV (dehydration)
Chem:
Azotemia (dehydration)
Increased ALT (common!)
UA:
Isothenuria (common)
Dehydration
Renal disease and Hyperthyroidism goes hand in hand
Hyperthyroidism
Definitive diagnosis
Screening Test: Total T4
Increased total T4 has high sensitivity and specificity
Not much else it can be but hyperthyroidism!
Some may have clinical signs but have a normal T4!
Daily fluctuation or non-thyroidal illness
Free T4 Equilibrium Dialysis
What is this?
What does it diagnose?
Hyperthyroidism
More sensitive than total T4 but less specific (more false positives)
Use in combination with total T4
T3 Suppression Test
What does it test for?
How does it work?
Hyperthyroidism (last resort test)
T3 should inhibit TSH production
Decrease TSH => Decrease T4 (<50% baseline)
Hyperthyroid: minimal suppression
Takes 3 days
Hyperthyroidism
Nuclear Scintigraphy
Radioactive isotope administration:
Hyperthyroid cats have increased uptake of isotope; will radiate upon evaluation
Confirms Hyperthyroidism
Unilateral, bilateral, ectopic tissue
Hyperthyroidism
Physical exam diagnostics
Blood pressure:
Hypertensive
End organ damage: ocular, neurologic, cardiac, kidney
Fundic exam
Due to hypertension: tortuous retinal arterioles and venules, may also see small intraretinal hemorrhages
Methimazole (Felimazole, Tapazole)
What does it treat?
MOA
Administration
Tx: Hyperthyroidism
MOA: Inhibits thyroid peroxidase Inhibits iodine binding tyrosine Decrease thyroid hormone production ONLY direct hormone replacement
Administration:
Daily PO: good bioavailability
Transdermal: Must be put in pluronic lecthin organogel
Fewer GI side effects
Monitor:
CBC/Chem/UA/total T4
Note:
Can cause facial excoration!
Renal decompensation
Hyperthyroidism
Treatment for hypertension and sympathetic overdrive
Amlodipine (peripheral Ca2+ channel blocker)
Beta blockers (decrease sympathetic tone): Atenolol
I-131 (radioactive iodine)
What does it treat?
MOA
Tx: Hyperthyroidism
MOA:
I-131 cocentrated in hyperfunctional thyroid cells as they take up iodine to make thyroid hormone
Normal tissue will be fine!
Function of normal thyroid tissue is suppressed and not producing hormone
I-131 (radioactive iodine)
Considerations
First treat with Methimazole to identify any underlying renal disease. Do NOT want to treat with I-131 if there is renal disease
Insulin
Characteristics
Anabolic
Facilitates tissue uptake of: Glucose! Amino acids Fatty acids K, Phos, Mg
Stimulates:
Glycogen synthesis
Decreases BG
Inhibits: Gluconeogenesis Glycogenolysis Protein catabolism Lipolysis Ketogenesis
Diabetes Mellitus
What is it?
Dog vs Cat
Insufficient production of insulin by beta cells of the pancreas
PU/PD
Hyperglycemia
Glucosuria
Dog:
Insulin-dependent
Absolute insulin deficiency
Beta cells are NOT functional
Cat: Relative insulin deficiency Non-insulin dependent in 80% Dysfunctional beta cells: impaired insulin secretion; makes some insulin but not enough to keep up with demand Peripheral insulin resistance May enter remission BUT can also relapse
Diabetes Mellitus
Pathogenesis of Dogs
Genetic predisposition + Autoimmune or Environmental factors or Predisposing conditions = Beta-cell degeneration and destruction => Insulin-dependent DM (NO beta cells)
Non-reversible; diabetic for life
Diabetes Mellitus
Pathogenesis of Cats
Complicated
Genetic predisposition
Predisposing factors
Amyloid deposition (beta cell degeneration)
Hyperglycemia (due to downregulation of transporter)
Reversible! – may go into hypoglycemic event so be careful!
Insulin Resistance
Predisposing Factors
Obesity
Pancreatitis
Glucocorticoids (cause insulin resistance; make cells less sensitive to insulin)
Progesterone (pregnancy; saving glucose for milk and babies)
Infection
Concurrent disease
Stress
Getting down regulation of receptors
Diabetes Mellitus
Dog Signalment
Female
Middle aged
Terriers
Schnauzers
Miniature poodles
Diabetes Mellitus
Cat Signalment
Males
Older
Burmese
Abyssinians
Siamese
Three presentations of Diabetes Mellitus
“Well” diabetic
Ketoacidotic (DKA) - VERY sick animals (emergency treatement often needed)
Hyperglycemic/Hyperosmolar Syndrome
Diabetes Mellitus
Concurrent endocrinopathies
Hyperadrenocorticism
Hyperthyroidism, acromegaly
Diabetes Mellitus
Physical Exam
Hepatomegaly Dehydration Cataracts (dogs) Poor coat Peripheral neuropathy (cats)
Stress hyperglycemia
What does this entail?
How to tell if truly hyperglycemic?
Cats
Normal: 80-120
Usually: <250 with stress but can go over 400
Stress: will have normal fructosamine so could test this
Stress hyperglycemia would not have diabetic clinical signs
Could re-check in a few hours or have owner check at home (send home with some urine strips and can test the urine X times through the day)
Diabetes Mellitus CBC Chem UA Urine Culture
CBC:
Normal unless infection occuring (neutrophilia, toxic change, left-shift)
Elevated PCV if dehydrated
Chem: Hyperglycemia Hypercholesterolemia Increase ALT and ALP (dogs not so much cats) \+/- azotemia if dehydrated
UA:
Dilute
Glucosuria
+/-: ketonuria, proteinuria, bacteriuria, pyuria
Urine culture:
MUST do
Common to have UTI in diabetic animals
Perform one EVERY 6 months
Diabetes Mellitus
Ultrasound?
Looking for underlying/complicating disease
Must address these or will be difficult to treat Diabetes
Example: Cushing’s and Diabetes Mellitus - diagnose diabetes and treat (regulate) it then start addressing Cushings; most likely will have to adjust diabetes treatment again
Diabetes > Cushings
Hyperthyroid cat? Treat at same time as Diabetes b/c if you treat Hyperthyroid might help with the diabetes
Diabetes Mellitus
Treatment caution
Hypoglycemic state!
Signs: Muscle tremors Seizures Lethargy Dull Disorientation Ataxia Coma
Diabetes Mellitus
Treatment considerations
Address any predisposing conditions: maintain ideal body condition Exercise Diet: increase fiber and decrease sugar and decrease fat. High protein diets are good. Insulin
CONSISTENCY is key; same thing every day at the same time
Diabetes Mellitus
Insulin Treatment - Dog
Vetsulin: Porcine Lente Insulin
Insulin of choice for dogs! (have similar structure to procine => controls diabetes better)
Administer after meal
Considerations:
Refrigerate
shake thoroughly before drawing up
U-40 syringes
Diabetes Mellitus
Insulin Treatment - Cat
Glargine: Human recombinant, insulin analog
Commonly used insulin for cats
Long acting (12-24 hours)
Promotes remission
Administer after meal
Considerations
Vials good for up to 6 months in refrigerator
Pens good for 1 month unrefrigerated (must)
Do NOT shake bottle - roll gently
U-100 syringes
U-40 vs U-100
2.5 overdose if you use a U-40 to give the same number of unites as a U-100
Underdose if you use U-100 to give same number of unites as a U-40
How to monitor Insulin Therapy
Improvement/Resolution of clinical signs
Blood glucose curves
Glycosylated Proteins
Fructosamine
Glycosylated Hemoglobin
Urine glucose strips
Blood glucose curves
Performed 7 days post-initiation of treatment, after changing insulin dose, after changing insulin type
Once regulated:
1 time/month
3-6/month
Feed and give insulin at normal time in morning (at home or hospital)
Check BG every 2 hours for a total of 12 hours (if gets close to 100 then check every hour) –need to determine Nadir
Duration:
Amount of time following insulin therapy in which the BG is <250
Target range: 100-250
NEVER change insulin dose without doing an insulin curve
Blood glucose curves
Dose vs. Insulin change
Nadir occurring at right time but value too low or too high?
Change dose
Nadir occurring at wrong time (too late or too early)? 6 hours is the ideal nadir time.
Change insulin type
Duration is inappropriate you will have to change dose or type depends on nadir
Somogyi effect
What is it
Too much insulin => hypoglycemia <65
Diabetogenic hormones take over! – rebound hyperglycemia
Diabetic hormones: cortisol, growth hormone, catecholamines, glucagon
SAVES animal’s life
May take two readings but if far enough apart you will miss the extreme hypoglycemic event
May even see significant hyperglycemia which may promt an increase in dose but this WILL kill the animal.
First:
Glucose curve
Change dose and see what happens
Then change type and see if that helps
Diabetes Mellitus
Complications
Hypoglycemia Insulin Resistance DKA Diabetic Neuropathy Diabetic Nephropathy Cataracts
Hypoglyemia
Prevention:
If pet does not eat or vomits do NOT administer insulin
Event occuring:
Owner administers Karo syrup
Hospitalization (receive Dextrose IV)
Insulin Resistance
What does this mean? Why?
Resistance: >2 U/kg per dose
User/Owner-error:
Insulin storage
Improper administration
Shaking vial (not rolling)
Other:
Somogyi effect
Steroid medication administration
Concurrent disease (hypothyroidism, hyperthyroidism, hyperadrenocorticism, infections, renal failure, hepatic disease) – treat underlying disease
DKA
Life threatening, acute complications of untreated diabetes mellitus
Even if being treated this can occur if there is an underlying disease occuring (infection, pancreatitis, cancer, etc.)
PU/PD amount definitions
PU: > 50 mls/kg/day urine
PD: > 100 mls/kg/day
Pathophysiology PD
Due to ADH
Water balance due to osmolarity of plasma
Increase in osmolarity then increased thirst via ADH production (at level of kidney will stimualte water resorption)
Kidney should make isosthenuric urine
Disease that can effect ADH
Cushing's: glucocorticoids inhibiting ADH release Pheochromocytoma Hypercalcemia Neoplasia Hypokalemia Endotoxemia Diabetes Mellitus
Diabetes Insipidus
Secondary condition and primary disease
Revolves around ADH production and function
Cannot concentrate urine!
Diabetes Insipidus
2 kinds
Central DI:
ADH is not being made
Decreased ability or inability of the kidneys to conserve water and concentrate urine in response to increases in plasma osmolality
Congenital or acquired
Nephrogenic DI
Kidneys are not responding to ADH
Receptors not present or not responsive
Diabetes Insipidus
Nephrogenic DI
Secondary (acquired)
Conditions affecting ADH binding and function of the renal tubules resulting in loss of medullary gradient, or causing osmotic diuresis
Examples: Chronic kidney disease Diabetes Mellitus Hyperadrenocorticism Hyperthyroidism
Confirming PU/PD
Monitor: water intake, USG (first urine of the day)
Lab work: elevated PCV, protein levels, electrolytes, iCa, renal values, liver values, glucosuria, pyuria, bacteruria
Rads/Ultrasound: pyelonephritis, pyometra, hepatic, renal, endocrine, neoplasia
Endocrine tests Kidney tests
Not getting up to drink at night? Suggests psychogenic PU/PD
Serum Osmolality
What does it diagnose?
Dx: Diabetes Insipidus
Must rule everything that causes PU/PD out first
Serum Osmolality Testing:
CDI: high-normal range or above normal
Psychogenic polydipsia: low-normal to below-normal serum osmolality
Note: Dehydration causes increased osmolality.
Exogenous DDAVP
What does it diagnose?
Dx: Diabetes Insipidus
DDAVP acts like ADH
Will increase USG at least 50% compared with pretreatment USG by day 5 to 7 OR USG > 1.030 will support CDI
Result in concentrated urine also in:
Psychogenic polydipsia
Hyperadrenocorticism
Water Deprivation Test
What does it test for?Precautions?
Procedure
Dx: Diabetes Insipidus
Precautions:
Useless information if not done correctly
Can kill patient if not monitored (causing severe dehydration, hypernatremia, hyperosmolar, azotemia, etc.)
Procedure:
Recommended for in-hospital monitoring /testing
GRADUALLY limit water intake over a 3-5 day period
Monitor: weight, PCV, TP, BUN, Na (every 1-2 hours)
Endpoint: 5% dehydration or USG reaching >1.025 (displays that ADH is working)
No concentration reached? Give DDAVP and monitor USG and urine osmolality: CDI diagnosed when USG or urine osmolality increases by 50% or more
Diabetes Insipidus (NDI, CDI) Treatment
Secondary Nephrogenic DI
Address underlying cause!
Central DI:
Lifelong therapy needed
DDAVP (Desmopressin) – ocular administration
Free choice water (always)
Ensure access to outside always available
Thiazide diruetics
What do they treat?
MOA
Interactions
Tx: Diabetes Insipidus NDI
MOA Reduces clinical PU/PD K+ wasting Must have good RBF
Mechanism not well understood: Inhibit distal sodium resorption Causes volume contraction Increased proximal tubular sodium and water resorption
Interactions: MANY! Check with plumb’s
What Endocrine diseases:
Cause PU/PD
Do NOT cause PU/PD
Cause: Diabetes Mellitus Hyperthyroidism Hyperadrenocorticism Hypoadrenocorticism Primary hyperaldosteronism Acromegaly Diabetes Insipidus Primary Hyperparathyroidism (if hypercalcemic)
Do NOT cause:
Hypothyroidism
Hypoparathyroidism
Acromegaly
What is it?
What causes it?
Dogs? Cats?
Hypersomatoropism (HS) = overproduction of growth hormone
Functional adenoma in the pars distalis of the anterior pituitary: excessive GH secretion causes liver to produce somatomedins (insulin like growth factors)
Almost all cats reported with Acromegaly have Diabetes Mellitus (BUT opposed to weight loss there is weight gain) Because: growth hormone is a glucose protective hormone during times of hypoglycemia => results in insulin resistance
More common in males
Acromegaly
Physical Exam findings
Cardiomegaly, systolic murmurs, interventricular septal thickening of LV (congestive heart failure)
Hypertension
CNS signs – large pituitary mass and diabetic neuropathy
Thickening of the skin and excessive skin folds around head and neck (also a big head)
Renomegaly, proteinuria, diabetic nephropathy: Chronic renal failure
Acromegaly
Treatment
Surgery: Transsphenoidal hypophysectomy (remission of DM)
Radiation:
Response variable
Medical Therapy: Somatostatin analogs (more research needed)
Palliative:
Give a lot of insulin (up to 20 U) and diet change
Poor long term prognosis b/c of organ failure
Feline Cushing’s
Kinds
RARE: Noniatrogenic or spontaneous hyperadrenocorticism
PDH most prevalent (adenoma of pars intermedia or pars distalis)
ADH: benign functional adenoma of one adrenal gland
Feline Cushing’s
Clinical signs
Cause
Present with signs of diabetes Weight loss Abdominal distension Panting Muscle atrophy Poor haircoat Predisposed to infections Sloughing of skin Poor QOL
Cause:
Excess of endogenous or exogenous glucocorticoid –> marked insulin resistance
Fragile skin syndrome
What is this?
Due to Feline Cushing’s
Tearing of the skin under normal conditions => handle gently
Felines do not develop Calcinosis cutis
Due to macroadenoma (blindness, abnormal behavior)
Feline Cushing’s
Bloodwork
Stress leukogram (inconsistent)
USG abnormalities if DM present
Proteinuria
Feline Cushing’s
How to test for it
Screening vs Differentiation
Screening: LDDST: test of choice Higher dose than dogs 0.1 mg/kg vs. 0.01 mg/kg ACTH Stim: okay test
Differentiation:
HDDS: 50% of PDH cats show no suppression
Endogenous ACTH
Imaging
Primary Hyperaldosteronism
What is it
Signalment
aka: Conn’s Syndrome
Mainly seen in cats; dogs rarely affected
Adrenocortical carcinoma
Adenoma
Bilateral nodular hyperplasia
Signalment:
Middle to older age
Aldosterone
Function
Produced by the ZG
Regulated by: RAAS
Released due to:
Hypovolemia
Hyponatremia
Hyperkalemia
Function:
Increase Na and Cl reabsorption
Increase K and H secretion
Primary Hyperaldosteronism
Clincial Signs
Pendulous abdomen PU/PD Hypokalemia: Muscle atrophy Arrhythmia Plantigrade stance Cervical ventroflexion
Hypertension (can cause loss of vision due to retinal detachment)
Restlessness
Anorexia
Weight loss
Primary Hyperaldosteronism
Chemistry
Hypokalemia
Metabolic alkalosis
Azotemia Hyperphosphatemia Increase CK Hyperglycemia Hypernatremia
Primary Hyperaldosteronism
Diagnosis
Increased aldosterone (6x) Hypokalemia (aldosterone should be low!) Hypertension Inappropriate kaliuresis (excretion of potassium)
Ultrasound, CT, MRI (adrenal mass, metastasis)
Primary Hyperaldosteronism
Treatment
Surgery:
Adrenalectomy (high rate of complications)
Medical:
Aldosterone blocker (Spironolactone)
Potassium supplementation (K gluconate)
Antihypertensive (Amlodipine)
Insulinoma
What is it?
Species?
Clinical signs?
Pancreatic Beta-Cell tumors:
excess production of insulin by functional tumor
Most are carcinomas and malignant
Species:
Dog, cat, and FERRET
Clinical signs:
Hypoglycemia
Insulinoma
Diagnostics
Chemistry:
Marked hypoglycemia
+/- Mild hypokalemia
+/- Elevated ALP or ALT
Paired Insulin/BG levels:
Blood sample must be obtained when animal is hypoglycemic
Abdominal ultrasound Pancreatic mass Metastatic lesion (liver, lymph nodes)
Insulinoma
Hallmark
Increased blood insulin concentrations despite low blood glucose concentration
Insulinoma
Treatment
Surgery
Treatment of choice but often the cancer has metastasized
High recurrence rate
Chemotherapy:
Streptozotocin (destroys beta cells)
Not the greatest prognosis still
Medical management
Monitor for hypoglycemic events
Frequent small meals
High protein, fat, complex carbs
Anti-insulin drugs
Glucocorticoids
Somatostatin
Glucagon
Median survival time: 12-14 months
