Endocrinology Flashcards
What is the stimulus for insulin release
rising blood glucose levels (after eating a carbohydrate-rich meal)
What are the 2 effects of insulin
1) Body cells take up more glucose
2) Liver takes up glucose and stores it as glycogen \
*Blood glucose levels declines to a setpoint, stimulus for insulin release diminishes
Is insulin anabolic or catabolic
anabolic- increases storage of glucose, FA, and amino acids
suppresses all forms of energy production (fat lipolysis, FA oxidation, gluconeogenesis, glycogenolysis)
Is glucagon anabolic or catabolic
catabolic- increases mobilization of glucose, FA, amino acids
How do cataracts develop in dogs with diabetes mellitus
glucose converted to lactic acid (anaerobic glycolyic pathway
glucose converted to sorbitol and fructose where it cant diffuse out of the eye
What three ways do recurrent infections occur in patients with diabetes mellitus
1) Decreased blood flow due to microangiopathies and atherosclerosis
2) Abnormal neutrohpil chemotaxis
3) Impaired cell-mediated response
T/F hepatomegaly is a symptom of diabetes mellitus
T - without insulin you get hyperglycemia, hyperlipidemia, ketones, increased gluconeogenesis, increased glycogenolysis
What is the renal threshold of glucose to get glucouria in dogs
180 mg/dl
What is the renal threshold of glucose to get glucouria in cats
250 mg/dl
What are the 5 clinicopathologic changes in patients with Diabetes mellitus
1) Hyperglycemia
2) Glucosuria
3) Elevated cholesterol
4) Elevated liver enzymes
5) minimally concentrated urine (osmotic diuresis)
What three ways are responsible for elevated blood cholesterol in patients with diabetes mellitus
1) Lack of Insulin- fat metabolism derangement
2) Impaired Lipoprotein lipase (clears VLDLs and chylomicrons)
3) Impaired LDL receptor- clears LDLs (cholesterol)
What portion of the adrenal gland cortex produces mineralocorticoids (aldosterone and RAAS) ?
Glomerulosa (outermost layer of adrenal cortex)
What portion of the adrenal gland cortex produces glucocorticoids (cortisol)
Fasciculata (middle layer of adrenal cortex)
What portion of the adrenal gland cortex produces androgens
Reticularis (innermost layer of adrenal cortex)
What portion of the adrenal gland produces Epinephrine, Norepineohrine, and Dopamine
the medulla
Adrenal glomerulosa produces ______
Mineralocorticoids (aldosterone and RAAS)
Adrenal fasciculata produces _______
Glucocorticoids (cortisol)
Adrenal reticularis produces _______
Androgens
What enzymes do Zona Glomerulosa and Fasciculata have
Glomerulosa: Aldosterone Synthase for Aldosterone production
Fasciculata: 17-a hydroxylase for cortisol, DHEA, and Androstenedione production
What initiates the first step of steroid synthesis
Endogenous ACTH
What does the hypothalmus release in the hypothalamic-pituitary-adrenal axis
CRH (corticotropin releasing hormone)
What does the pituitary release in the hypothalamic-pituitary-adrenal axis
ACTH (Adrenocorticotropic hormone)
What does the adrenal gland release in the hypothalamic-pituitary-adrenal axis
cortisol
What is a result of an adrenal gland tumor
1) high amounts of cortisol
2) one adrenal gland enlarged, one is atrophied
3) Low ACTH
What is the result of a pituitary tumor releasing excess ACTH
1) high amounts of cortisol
2) Both adrenal glands become hyperplastic
3) excessive ACTH
What is a result of iatrogenic Cushing’s
1) Suppression of pituitary ACTH by exogenous steroid (Low ACTH)
2) only atrophy to zona fasciculata atrophy
3) Low cortisol (but not glucocorticoid)
Two Results of Typical Addisons
1) Low Cortisol (immune destruction of zona fasciculata)
2) Low Mineralocorticoids (immune destruction of zona glomerulosa)
3) High ACTH
What is the Result of atypical Addison’s
1) Low Cortisol only (immune destruction of zona fasciculata)
2) High ACTH
Is cortisol anabolic or catabolic
catabolic
-increases glucose for energy
-Breaks down protein
-Liberates lipids for b oxidation
What vascular effect does cortisol deficiency have
hypotension
What vascular effect does cortisol excess have
hypertension
What effect does cortisol have on the immune system?
excess leads to immunosuppression
-Inhibits phospholipase A2, which prevents the formation of important inflammatory products as this enzyme forms Arachidonic acid which later forms leukotrienes, prostaglandins, thromboxane, and prostacyclins through COX
What areas does cortisol excess cause alopecia in?
Perineum
Caudal thighs
Lateral thorax and abdomen
What is the cause of calcinosis cutis
Cushings Disease (excess cortisol)
Does cortisol excess of deficiency result in PU/PD?
They both do! through different mechanisms
What are the GI symptoms of addisons (cortisol deficiency)
vomiting and bloody diarrhea through the lack of GI mucosa maintenance
What CBC results are seen in Cushings
Stress Leukogram
-Neutrophilia- prevents migration out of circulation
-Lymphopenia- immune suppression
-Eosinopenia - immune suppression
What CBC results are seen in in Addisons
Lack of Stress Leukogram
Anemia
What biochem results are seen in Cushings
1) increased in ALP/GGT that are larger than ALT and AST
2) Increased cholesterol (increased lipolysis)
3) Increased glucose (mild) - increased gluconeogenesis and glycogenolysis
What biochem results are seen in Addisons
1) Increased ALT
2) Decreased Cholesterol (less GI uptake)
3) Decreased glucose mild(decreased gluconeogenesis/glycogenolysis)
4) Increase K* (less mineralocorticoids)-not atyical Addisons
5) Decrease Na+ (less mineralocorticoids) - not atypical Addisons
What urinalysis results are seen in Cushings
Decreased USG (ADH inhibition)
Proteinuria (multifactorial)
Bacteriruia without pyuria (immunosuppression)
What urinalysis result is seen in Addisons
Decreased USG due to decreased mineralocorticoids (not in atypical addisons disease)
Does thyroid hormone bind to receptors on membrane or in the nucleus
receptors in nucleus, forms a hormone-receptor complex to initiate gene transcription or inhibition
What hormone is released from the hypothalamus in the thyroid axis?
Thyrotropin-releasing hormone (TRH)
What hormone is released from the anterior pituitary in the thyroid axis?
Thyroid stimulating hormone (TSH)
What hormone is released from the thyroid in the thyroid axis?
T4 and T3
What are the 2 stimuli for the hypothalmus to release Thyrotropin-releasing hormone (TRH)
Stress and Cold
A disproportionate dwarf is a result of ______
lack of thyroid hormone
A proportionate dwarf is a result of ______
lack of growth hormone
Why do you see tachycardia and hypertension +/- arrhythmias and murmurs in cats with hyperthyroidism
Beta-adrenergic receptor numbers and affinity are unregulated to increase cardiac output
What are the cardiovascular effects of hyperthyroidism in cats
tachycardia and hypertension
+/- arrhythmias and murmurs
What are the CNS effects of cats with hyperthyroidism
nervousness, hyperactivity, aggression
What are the CNS effects of dogs with hypothyroidism
*Demyelination and decreased action potential
-mental dullness
-Decreased reflexes
-Forelimb and/or limb paresis
-Cranial nerve deficits
-Tragic face
What might be noticable about a hyperthyroid cat’s haircoat
It will be unkept
T3/T4 moves hair from the telogen to anagen phase
CNS effects and less grooming might also be a factor
What might be seen in a hypothyroid dog’s haircoat
hair gets stuck in telogen (resting) stage
alopecia in areas of wear
lack of regrowth after clipping
hyperpigmentatio
Hyperthyroid cats have extra oxygen consumption and increased cariac output leading to increased renal blood flow and what symptoms
1) Muscle wasting
2) Fat loss
3) Tachypnea
4) PU/PD
Hypothyroid dogs have what changes in their weight?
They gain weight
What biochem abnormalities is seen in hypothyroid dogs
increased cholesterol due to disrupted cholesterol synthesis and degradation
What biochem abnormalities is seen in hyperthyroid cats
Increased BUN
Increased glucose (mild)
Increased liver enzymes (ALT>ALP)
due to liver hypoxia from increased O2 consumption
What urinalysis abnormalities will be seen in cats with hyperthyroidism
Decreased USG (Increased cardiac output leads to increased renal blood flow and medullary washout)
Where is calcitonin produced and what does it result in?
C cells of the thyroid (parafollicular cells)
tones down calcium when it is high
what kind of cells produce parathyroid hormone
chief cells of the parathyroid gland
function to increase calcium levels
Vitamin D results in increases of ________
Ca2+ and PO4
What are the 10 differentials for hypercalcemia
GOSH DARNIT
1) Granulomatous (fungal)
2) Osteolytic
3) Spurious
4) Hyperparathyroidism (adenomas or hyperplasia)
5) Vitamin D Toxicosis
6) Addisons Disease
7) Renal secondary hyperparathyroidism (decreased Vit D production and Phosphorus retention)
8) Neoplasia
9) Idiopathic
10) Toxin
What factors cause spurious hypercalcemia
-Lipemia
-Hemolysis (sample handling)
-Hemoconcentration
-Hyperalbuminemia
-Acidosis
-Young animals
How does renal disease lead to hypercalcemia
Renal secondary hyperparathyroidism
-Decreased Vit D production leading to increased PTH
-Phosphorus retention (kidney dysfunction)
Total calcium is often elevated in renal disease but ionized calcium is often _________
normal or decreased
What are the two most common tumors causing hypercalcemia
Lymphoma
Apocrine gland adenocarcinomas of the anal sac
What common toxins can cause hypercalcemia?
Day-blooming jessamine (Cestrum diurnum)
Vitamin D
Excessive volume excretion of urine
Polyuria
Pollakiuria
excessive frequency/urgency of urination
Dysuria
difficult or painful urination
excessive frequency/urgency of urination
Pollakiuria
slow, painful urination, caused by muscular spasms of the urethra and bladder
Stranguria
excessive volume of drinking
polydipsia
What volume determines an animal is polyuric?
if they produce more than 50ml/kg/day of urine
*not feasible to determine
What volume determines an animal is polydipsia?
if they drink more than 60-80 ml/kg/day of water
Secondary (compensatory) polydipsia
excessive drinking that occurs as a result of primary polyuria
majority of case
peeing too much, compensate by drinking more water
What are your 4 differentials for osmotic diuresis for PU/PD patients
1) Diabetes mellitus- excess glucose overwhelms renal reabsorption
2) Post-obstructive diuresis- blocked tom, urea cant get out and accumulates until the obstruction is relieved, also some damaged tubular cell
3) Chronic kidney disease- less urea and sodium reabsorbed. also lost of medullary gradient
4) Fanconi Syndrome- tubular defects prevent various solute reabsorption including glucose and sodium
What are your 5 main categories of differentials for PU/PD animals
1) Central diabetes insipidus
2) Primary polydipsia
3) Primary nephrogenic diabetes insipidus
4) Secondary nephrogenic diabetes insipidus
5) Osmotic diuresis
What are your major rule out for Secondary nephrogenic diabetes insipidus
1) Addisons
2) Cushings
3) Hyperthyroidism
4) Pyometra
5) Hypercalcemia
6) Drugs
7) Medullary washout
8) Hepatic insuffiency
9) Pyelonephritis
10) Hypokalemia
How does Cushings result in PU/PD
excess glucocorticoids interferes with ADH rceptors and ADH release
What three ways does Addisons cause PU/PD?
1) lack of mineralocorticoids (no aldosterone leading to Na+ wasting)
2) Osmotic agent
3) Medullary washout
How does hyperthyroidism result in PU/PD cats?
being in a hypermetabolic state leads to increased blood flow to the kidney and decreased time for sodium reabsorption, creating a decreased osmotic gradient leading to increased PU/PD
What is often the chief complaint in pyometra cases
PU/PD.
E coli endotoxins interfere with ADH receptor (secondary NDI)
T/F hypercalcemia causes PU/PD
interference with function of ADH receptors and tubular cells
What are the causes of primary polydipsia (brain causes)?
-Hyperthyroidism
-Hyperadrenocorticism
-Hepatic Disease
-Learned behavior- psychogenic polydipsia
Primary polydipsia leads to __________ which leads to eventual _______ _________
Primary polydipsia leads to overhydration which leads to eventual medullary washout
What is the result of no ADH
Water channels do not get inserted into the distal tubules leading to no water absorption and diuresis
If urine is hypersthenuric (Dog > 1.030/35 & Cat > 1.040/45) then are they PU/PD?
No they are not. they can concentrate their urine
At what USG, should you do a workup for PU/PD?
urine that is minimally concentrated, isosthenuric, or hyposthenuric
Dog: < 1.030
Cats: < 1.040
Dog with history of PU/PD. Urinalysis, CBC, Biochem, and imaging is normal. ACTH stim rules out hyperadrencorticism. nx bile acids What are the next steps
Use the dreaded modified water deprivation test to diagnose psychogenic polydipsia, medullary washout, or central diabetes insipidus
How does the modified water deprivation test work
*rule out absolutely everything before performing
1) Hospitalize and withhold water until 5% dehydrated
-if USG > 1.030- psychogenic polydipsia
2) If USG <1.030- Give ADH
-if USG > 1.030 - Central Diabetes Insipidus
-If USG < 1.030- medullary washout or NDI
How does hepatic insufficiency lead to PUPD
direct brain effects on the thirst center
impaired urea production
impaired cortisol metabolism
Where and how does Furosemide act
it acts to inhibit NaCl reabsorption in the thick ascending limb of the loop of Henle
A patient presents with weight loss. What should you first ask about?
If they have polyphagia or anorexia
Polyphagia: Inadequate Intake, Hypermetabolism, Nutrient loss
Anorexia: Primary, pseudoanorexia, primary gi, non GI
Patient with Weight Loss and Polyphagia
You determine the patient is not being fed enough
What do you consider as diagnosing?
-Insufficient quantity of food
-Poor food quality
-Increased exercise and demand
-Growing animal
-Pregnancy
Patient with Weight Loss and Polyphagia
You determine the patient is being fed enough
What could be occurring
1) Hypermetabolism (Hyperthyroidism, Fever, Neoplasia, Pregnancy, Lactation)
2) Nutrient loss
a) Glucose- Spill-over from DM, cant absorb in Fanconi
b) Protein- GI (PLE, parasite maldigestion, mabsorption), kidney (protein losing nephropathy), skin (severe burns, open abdomen), third space (osmotic pressure- cardiac disease, portal hypertension)
c) Fats- GI
Pseudoanorexia
Weight loss with anorexia that is due to issues with:
-teeth (dental dz)
-Mucosa (abscess, neoplasia, ulcerations)
-Bone (fracture, neoplasia)
-Joint (osteoarthritis, polyarthritis)
-Muscle (myopathy)
-Nerves (trigeminal nerve)
What are broad reasons that a patient might be anorexic
1) Hunger center- CNS disorders
2) Pseudoanorexia- due to teeth, mucosa, bone, joint, muscle, nerves
3) Primary GI- Intolerance (allergy), inflammation (IBD), infection, obstruction (Mechanical or functional) , GI neoplasia (lymphoma, adenocarcinoma, leiomyosarcoma, mast cell tumor)
4) Secondary GI - organ system disease, metabolic (diabetes, hyperthyroidism, Addisons) systemic neoplasia
What are the different waves of diagnostics for a complaint of weight loss
1) History of appetite, Physical exam, intake relation to weight, minimum database, fecal
2) Based on the first wave: Total T4 and FeLV/FIV in cat, Texas GI panel, chest and abdominal films
3) Barium series (rarely done), ultrasound, endoscopy, abdominal exploratory
4) Last resort- CT or MRI scan to rule out central disease
How do you calculate RER
RER= 70 * BW(kg)^0.75
What are your differentials for weight gain with increased food intake and polyphagia
Hyperadrenocorticism
Insulinoma
Growth Hormone
Pregnancy
Drugs
What are your differentials for weight gain with normal or decreased appetite/intake
Hypothyroidism (Dogs)
Central Disease
Characteristics: Female, Neutering, Breed, owner related
Edema, Ascites, intra-abdominal masses, organomegaly
What are your waves of diagnostics for a complaint of weight gain in an animals
1) History of appetite, Physical exam, Calculate intake, Minimum database
2) Thyroid panel (dog), Adrenal testing for Cushings
3) CT or MRI scan
Are males or female dogs more prone to diabetes mellitus?
Females are twice as affected as males
When do most dogs present for diabetes mellitus
Between 7-9 years (middle aged)
What breeds of dogs are predisposed to diabetes mellitus
Keeshond *
Beagles
Miniature Schnauzers
Miniature Pinschers
Cairn Terriers
Are males or female cats more prone to diabetes mellitus?
Males are twice as likely as females
T/F Diabetes mellitus has a breed predilection in cats
False
What are the similarities between dogs and cats with diabetes mellitus
Both are
1) PU/PD
2) Polyphagia with weight loss
3) Fasting hyperglycemia
4) Glucosuria
5) Prone to infections
Is dog diabetes mellitus due to a lack of insulin or insulin resistance
Type I: lack of insulin from immune-mediated beta cell destruction
Is cat diabetes mellitus due to a lack of insulin or insulin resistance
Type 2: Insulin resistance (relative lack of insulin)
What is significant about the clinical signs of dogs with diabetes mellitus
they can develop cataracts due to the lack of insulin
What is significant about the clinical signs of cats with diabetes mellitus
They might have Frosty paws or develop neuropathies (plantigrade stance)
Profound stress (epi induced) hyperglycemia
How do the dietary requirements of dogs with diabetes mellitus differ from cats with diabetes mellitus
Dogs: Need complex carbs
Cats: Need high protein diet, carbs need to be avoided
Why is hyperglycemia and glucosuria not significant for a diabetes mellitus diagnosis in cats?
Because they can have a profound stress hyperglycemia that can be up to 350 mg/dL and the spill over is 250mg/dL
How can you differentiate chronic hyperglycemia from acute hyperglycemia in cats for diabetes mellitus diagnosis?
Fructosamine test
What three ways can insulin resistance develop in cats?
1) Glucose toxicity (chronic hyperglycemia impairs function of beta (less release) and peripheral cells (glucose transport down-regulation) leading to more hyperglycemia)
2) Beta cell destruction (chronic hyperinsulinemia destroys the beta cell thus reducing insulin production)
3) obesity induced insulin resistance (both dog and cat) circulating fatty acids induces insulin resistance in the peripheral tissues
What hormones interfere with the normal amount of insulin (resulting in insulin resistance)
1) Epinephrine (infections/inflammation)
2) Cortisol (infections/inflammation, Cushings, Steroids)
3) Progesterone (pregnancy)
4) Growth hormone (acromegaly)
5) Glucagon (glucagon-secreting tumors)
6) Thyroid hormone (hyper AND hypothyroidism)
7) Obesity induced- multifactorial
How might a patient present if they have undiagnosed Diabetes mellitus
-PU/PD
-Polyphagia with weight loss
-Fasting hyperglycemia with glucosuria
-Infections
-Cataracts (dog)
-Neuropathies/plantigrade stance (cat)
-Frosty paws (cat)
What is special about the insulin you give for Diabetic ketoacidosis patients
GIVE IM (q2-4 hours) or IV as a CRI
-regular insulin (Humulin- R or Novalin-R)
What insulin do you give dogs with DM and at what dosing frequency
-Intermediate action insulin - lente (Vetsulin)
Given SQ twice a day
Lente / Vetsulin
Insulin used for Dogs
Intermediate Duration
Crystalline
Given SQ twice daily
Regular insulin / Humulin-R / Novalin-R
Insulin used for DKA patients
Short Duration
Crystalline
Given IM (q2-4hrs) or IV as CRI
What is the go to insulin for cats in the management of DM
Glargine (Given SQ twice daily)
Glargine or Detemir
Insulin for Cats
Long duration
Analog
Given SQ twice daily
Why are oral hypoglycemics that reduce peripheral insulin resistance and increase insulin secretion not useful in dogs?
The dogs have no b cells to produce the insulin
Why are oral hypoglycemics that reduce peripheral insulin resistance and increase insulin secretion not useful in cats?
fill in later
What diet considerations should you take when managing a dog with DM
Complex carbs and fiber
regular or moderate exercise
What diet considerations should you take when managing a cat with DM
Protein, low carbs
What should you do at recheck appointments of patients with DM
Urine dipstick, spot glucose, or fructosamine (cats)
Minimum database for concurrent disease
Glucose curve (to assess insulin duration, effectiveness and glucose nadir)
When should the appropriate blood glucose nadir be in a glucose curve?
At 6 hours post-injection
What should the appropriate time duration of insulin be?
About 12 hours (to decrease and return back to appropriate blood glucose levels
What should the appropriate effectiveness of insulin be (glucose range)
Dogs: 80 - 200 mg/dl
Cats: 80 - 300 mg/dl
What should the appropriate glucose nadir be at?
80-100 mg/dl
What are the features of an appropriate glucose curve?
1) Appropiate time of nadir (at 6 hours)
2) Appropriate duration of curve (12 hours)
3) Glucose range of 80 to 200 (dogs) or 300 (Cats)
4) Nadir Range at 80 - 100mg/dl
At what insulin dose might dogs and cats develop insulin resistance?
Dogs: > or equal to 1.5 units/kg/dose
Cats: > 5 units/dose
What are the two likely patients presenting with Diabetic Ketoacidosis (DKA)
Previously undiagnosed diabetics
Unregulated diabetics
Describe the pathogenesis of DKA
the body perceives starvation
lipolysis to liberate free fatty acids leading to increased uptake of circulating fatty acids into the liver where beta oxidation occurs
acetone, b-hydroxybutyrate, and acetoacetate leads to acidosis (Lethargy, anorexia, vomiting)
A patient presents with hx of PU/PD, polyphagia with weight loss, lethargy, anorexia, vomiting, dehydration, and hypovolemia
Clinpath abnormalities: Acidosis, hyperglycemia, Azotemia, increased liver enzymes, Hyponatremia, Hypochloremia, hyperkalemia, glucosuria, and ketonuria
What is the diagnosis
Diabetic ketoacidosis
What additional tests might you perform to diagnose DKA
1) Venous blood gas: for electrolytes (Na, K, Cl), Acid-base status (pH), Perfusion (lactate), degree of hyperglycemia (glucose), degree of dehydration (cretinine)
2) Urine dipstick: confirms glucosuria and ketonuria
What are the treatment goals of DKA
Steps
1) Restore fluid and electrolytes
2) Correct acidosis
3) Provide regular insulin (IM or CRI)
4) Provide glucose
5) Identify trigger
How does giving fluids help initially with DkA
- Corrects dehydration and Improves perfusion, decreasing acidosis
-Corrects electrolyte abnormalities as it replaces Na+ and Cl-, also decreases potassium, phosphorus, and magnesium
Why shouldnt you give regular insulin in a DKA patient
because it will not be well absorbed in a dehydrated patient
What is the most common trigger for DKA
urinary tract infection
also dental abscess, pancreatitis, pneumonia
What a potential triggers for DKA
anything that results in insulin resistence
-Epinephrine (infections/inflammation)
-Cortisol (infections/inflammation or steroids or Cushings)
-Progesterone (pregnancy)
-Growth hormone (acromegaly- cats)
-Glucagon (glucagon-secreting tumors- v rare)
-Thyroid hormone (hyper and hypo)
-Obesity
What are you next steps for determining the trigger for DKA
- Acquire a Minimum Database
- Urine culture for UTI
- Abdominal ultrasound
-Abdominal or Thoracic radiographs
Cervical ventroflexion in a DKA patient is a result of
Muscle weakness from being hypokalemic
Hemolysis in a DKA patient is a result of
Hypophosphatemia
What 5 things should you monitor in a patient with DKA
1) Cervical ventroflexion or muscle weakness (potassium decrease)
2) Hemolysis (phosphorus)
3) Mentation change (cerebral edema)
4) pH change- worsening acidosis
What are the typical presenting problems in patients with Addison’s Disease
1) PU/PD
2) collapse
What age is Addisons typically diagnosed in dogs?
often young to middle aged dogs (around 2 years)
Are patients with Addisons typically male or female
Female
What breeds are predisposed to Addison’s disease
-Standard Poodle
-Portugese Water dog
-Labrador Retriever
-Bearded Collie
What are the diagnostic findings of a patient with Addisons
USG: low (PU/PD)
CBC: lack of a stress leukogram, anemic once rehydrated
Pre-Renal Azotemia
Decreased glucose
Decreased cholesterol
Decreased Na and Cl - lack of aldosterone
What are the clinical signs associated with Addisons Disease
Cortisol: Waxing/waning illness, lethargy, anorexia, weight loss, vomiting, diarrhea, regurgitation?, slightly thin, abdominal pain, blood/melena on rectal, bradycardia despite hypotension, shock from hypotension
Aldosterone: PU/PD, shock due to hypovolemia
What you expect to see in the UA of a patient with Addisons
Only abnormality is a low urine specific gravity due to aldosterone deficiency
What would you expect to see in the CBC of a patient with Addisons
-Lack of Stress Leukogram
-anemia (decreased erythropoiesis and/or GI blood bloss and/or anemia of chronic disease)
What would you expect to see in the biochem of a patient with Addisons
Increased: Azotemia (BUN, Creatinine, P), Potassium, Calcium, +/- elevated liver enzymes
Decreased: Glucose, Cholesterol, Sodium/chloride, Bicarbonate, +/-
What three characteristics are unique about the EKG findings of a patient with Addisons
-No P-wave
-Wide QRS complex
-Spiked T wave (can be inverted)
from hyperkalemia
Why do patients with Addisons have an EKG with No P wave, Wide QRS complex, and a spiked T wave
hyperkalemia (although not all patients with hyperkalemia have this)
What layers of the adrenal glands are impacted in a patient with typical Addisons
both the zona glomerulosa and fasiculata
What else might be on your differentials for a patient with atypical Addisons (vomiting, diarrhea, painful abdomen, normal Na+ and K+)
-GI foreign body
-Pancreatitis
-Acute hemorrhagic diarrhea syndrome (AHDS)
What ratio of sodium to potassium should you consider for typical Addisons?
Na:K < 28:1 - Consider typical Addisons
Na:K < 25:1- Highly suspicious for typical Addisons
Na:K < 21:1 - Slam dunk for typical Addisons
*Does not rule out atypical Addisons because you dont get the electrolyte abnormalities
How do you get a definite diagnosis of Addisons Disease?
ACTH Stimulation Test
Pre: Low cortisol
Give eACTH: High Cortisol
Post: Low cortisol
What is a good screening test for Addisons Disease
Baseline Cortisol
-If <2: Do ACTH Stim for definite diagnosis
-If >2: Not Addisons, sufficient cortisol test
good for ruling out Addisons but not good the definite diagnosis
What is the importance of giving fluids in an Addisonian emergency
Its important for hypovolemic shock
-Restores NaCl levels
-Helps dilute K+
-Helps correct acidosis
What should you give in an Addisonian emergency to replace glucocorticoids
Dexamethasone only
only one type of glucocorticoid prior to ACTH Stimulation test
All other glucocorticoids cross-react with the cortisol assay (leading to false negative)
Calcium gluconate
given to Addisonian patients in an emergency
doesnt change the hyperkalemia levels but it prevents the entry into the heart
Bicarbonate use in Addison emergency
allows the entry of potassium into the cell to correct hyperkalemia
Do patients on DOCP require prednisone?
Yes
Prednisone
exogenous glucocorticoid that can be dosed physiologically for the maintenance of Addison patients
Owners must increase dose before stressful events
Desoxycorticosterone pivalate (DOCP)
an injectable mineralocorticoid that is given once every 25 days
patients receiving it still need to get prednisone
Florinef (Fludrocortisone)
a mineralocorticoid oral medication that is given daily
50% do not need prednisone, start all on prednisone and discontinue if PU/PD/polyphagia is severe
Are the majority of Cushing cases PDH or Adrenal Tumors
Pituitary Dependent (PDH)
Name the disease: high ACTH and high cortisol
Pituitary Dependent Cushings
Name the disease: low ACTH and high cortisol
Adrenal Dependent Cushings
Name the disease: low ACTH and low cortisol
Iatrogenic Cushings
atrophy of the adrenal gland, if stopped giving, go into Addisonian Crisis
Do small dogs typically get pituitary dependent or Adrenal dependent Cushings?
Pituitary dependent
Do large dogs typically get pituitary dependent or Adrenal dependent Cushings?
Adrenal tumors
What are the clinical signs of Cushings
PU/PD
Polyphagia
Panting
Weight gain
Alopecia
Potbelly
Hepatomegaly
Muscle wasting (apaxial)
lameness and weakness
What should you do as your initial diagnostics if you suspect Cushings?
Minimum database (CBC, biochem, urinalysis)
Urine culture (more prone to UTI)
Check systemic blood pressure for hypertension as excess cortisol can create hypertension
What urinalysis findings might you find in a patient with Cushings
Minimally concentration (>1.012 - 1.025)
Isosthenuric (1.008 - 1.012)
Hyposthenuric (<1.008)
Proteinuria
Urinary Tract Infection (Bacteriuria without pyuria- cortisol prevents neutrophil egress from vessels to the site of infection
What CBC findings will you see in a patient with Cushings
A Stress Leukogram
What biochem findings will you see in a patient with Cushings
Hyperglycemia (mild)
Hypercholesterolemia
Elevated liver enzymes (ALP>ALT)
What liver enzyme will be raised the most in Cushings?
ALP
Name the 3 diagnostic screening tests for Cushings
Used to screen the patient. Is this Cushing’s disease or not?
1) Urine-cortisol:creatinine ratio
2) ACTH Stimulation
3) Low-dose dexamethasone suppression test
Name the 3 diagnostic discriminatory tests for Cushings, determining what form
1) High-dose dexamethasone suppression test (HDDST)
2) Endogenous ACTH (eACTH)
3) Imaging (ultrasound, CT, MRI)
Is the urine cortisol:creatinine ratio test highly sensitive or specific?
highly sensitive: a negative test is more reliable.
Use it to rule out HAC
ACTH stimulation test
Synthetic ACTH given, and increased cortisol should be released
Only test for iatrogenic Cushings
Only test for monitoring Cushing treatment
Only test for Addisons
1) Collect blood at 0 hrs (measure cortisol)
2) Give synthetic ACTH IV
3) Collect blood at 1 hour (measure cortisol)
*If below normal post-ACTH range (>18) then they are not Cushings
*If it is above, it is Cushings but we cannot determine the etiology
Low dose dexamethasone suppression test
A screening test for Cushings. Dexamethasone suppresses ACTH secretion and therefore cortisol in a normal dog for 8 hours
One test can determine if they are Cushings and if it is PDH
Stressed or patients with co-morbidities can result in false positives
1) Collect blood at 0 hours (measure cortisol)
2) Give dexamethasone IV
3) Collect blood at 4 hr (measure cortisol)
4) Collect blood at 8 hours (cortisol)
*If 8 hour value is less than 1.4 or 50% then it is not Cushings
*If it is, look at 4 hours, if it is suppressed then it is PDH. If it is not suppressed then it is either PDH or AT.
You perform a LDDS. There is suppression (<50%) at both 4hr and 8hr. What is the interpretation?
The patient does not have Cushings
You perform a LDDS. There is no suppression (<50%) at both 4hr and 8hr. What is the interpretation?
The patient has Cushings but you cannot determine if it is Pituitary dependent or an adrenal tumor
You perform a LDDS. There is suppression (<50%) at both 4hr but not at the 8hr point. What is the interpretation?
The patient has pituitary dependent Cushing’s
This outcome is a discriminatory test
You perform a LDDS. There is suppression and then escape. What is the outcome
The patient has pituitary dependent Cushing’s
This outcome is a discriminatory test
Endogenous ACTH assay
Used as a discriminatory test for Cushings.
-Low: AT- suppressed
-High: PDH
single blood draw.
Most reliable if it is high because it is a labile hormone
Endogenous ACTH assay is most reliable when it is___________
high. it is extremely labile
High-dose dex suppression test
a discriminatory test for Cushings
Large amount of dexamethasone will suppress ACTH production by even stubborn pituitary tumors by 8 hours
Adrenal tumors never suppress
PDH tumors suppress (70%)
What will the adrenal glands look like on ultrasound if there is a pituitary tumor
both of the adrenals will be enlarged
What will the adrenal glands look like on ultrasound if the patient has an adrenal tumor
one will be enlarged, and one will be atrophied
Upon ultrasound for suspected Cushings, you notice that both of the adrenals are enlarged. What is the diagnosis
Pituitary tumor
Upon ultrasound for suspected Cushings, you notice that one of the adrenals is enlarged, while the other is atrophied. What is the diagnosis
Adrenal tumor
Upon ultrasound for suspected Cushings, you notice that both of the adrenals are atrophied. What is the diagnosis
Iatrogenic Cushings
Trilostane
a 3-b-hydroxysteroid dehydrogenase inhibitor that interferes with steroid production.
For tx of PDH Cushings
Fewer side effects
Reversible
What medication can you give for Pituitary Dependent Hyperadrenocorticism
Trilostane
What two ways can you treat PDH Cushings
1) Stereotactic Radiosurgery
2) Trilostane
T/F Trilostane can be used to tx adrenal tumor Cushings
it may not control
What two ways can you treat adrenal tumors?
1) Trilostane (may not control)
2) Adrenalectomy
What should you consider when performing a unilateral adrenalectomy
The other adrenal gland is atrophied so there could be an Addisonian Crisis
Are females or male cats more susceptible to feline hyperadrenocorticism
Females
What are the differences between Cushings in dogs and cats
Cats- very uncommon
fragile skin syndrome
Concurrent diabetes mellitus - 85%
PU/PD and ALT from diabetes
ALP often normal because not steroid-induced isoenzyme
tx with bilateral adrenalectomy or trilostane
Is there polyphagia or anorexia with CKD
anorexia
What are the physical exam findings of a feline patient with hyperthyroidism
-Growling and pacing around the room
-Dilated eyes
-Nodules in the cervical area
-High heart rate
-Gallop rhythm
-Left systolic murmur
-Panting
-Thin
-Rough, unkempt haircoat
-Weight loss with polyphagia
-PU/PD
What single test should you perform if PU/PD is on the problem list
a urinalysis
What CBC findings will you see in a cat with hyperthyroidism
-Stress leukogram
-Slightly increased PCV
What biochem findings will you see in a cat with hyperthyroidism
Increased ALT (especially), ALP, and AST
Hyperglycemia
Increased BUN
What is the first test you should do if you suspect hyperthyroidism for cats
Total T4
-Positives are reliable but there are some false negative
99% of the time, is hyperthyroidism a result of thyroid adenomas or adenocarcinomas
thyroid adenomas
bilateral 70& of the cases
What is the summary of all findings with cats with hyperthyroid
-Weight loss
-Polyphagia
-PU/PD
-Hyperactivity
-GI signs
-Skin changes
-Respiratory
-Apathetic
-Thyroid slip
-Gallop rhythm/murmur
-hypertension
-retinal petechiae
-Detached retinas
-Increased ALT
-Increased PCV
-Elevated BUN
-Decreased USG
What disease can mask the signs of CKD
Feline Hyperthyroidism
Is total T4 or free T4 more sensitive
Total T4- it is a good screening test. Good for ruling out- positives are reliable (some false negatives)
Nuclear Scintigraphy
Method for diagnosing hyperthyroidism in cats
uses Technetium and compares radioactivity compared to the salivary glands
compares bilateral vs unilateral
What diet should you have a hyperthyroid cat on?
A diet that is deficient in iodine
What drug is used to treat hyperthyroidism in cats?
Methimazole: blocks thyroid synthesis
What is methimazole used to treat
hyperthyroidism in cats - blocks thyroid synthesis
Methimazole
tx hyperthyroidism in cats - blocks thyroid synthesis
Pros: Non-invasive, Inexpensive, Reversible
Cons: Pill cat, doesnt cure, Adverse effects (hepatotoxicity, bloo dyscrasias, GI signs, facial excoriation)
What are the adverse signs of Methimazole that you should watch for
GI upset
Facial excoriation
Blood dyscrasias (anemia, thrombocytopenia, neutropenia)
Hepatotoxicity
Monitor T4, Kidney function (BUN, creatinine, USG), Complete blood count, liver enzymes
I-131 treatment
SQ injection for permanent treatment of hyperthyroidism
Selects abnormal cells
Expensive
Do methimazole challenge prior to I-131 to assess renal function
isolation for long time
Describe of I-131 treatment works
Atrophy of healthy cells due to lack of TSH stimulation because of hyperthyroidism
1) SQ injection of I-131
2) Healthy (atrophied) cells do not take up the I-131
3) Adenoma cells take up the I-131
4) Abrupt stop of T4 from the adenoma
5) The healthy cells will return to normal in 1-6 months as they are stimulated by TSH
What are the 3 possible complications with thyroidectomy
1) Transient or permanent hypothyroidism
2) Laryngeal paralysis
3) Hypoparathyroidism leading to hypocalcemia (muscle tremors, facial pruritus, seizures)
How do you treat hypertension and hypertensive retinopathies due to hyperthyroidism
Give Amlodipine (Calcium channel blockers)
Amlodipine
A calcium channel blocker that is used to treat hypertension and hypertensive retinopathies
What two ways does primary hypothyroidism occur in dogs?
1) Lymphocytic thyroiditis (against thyroglobulin)
2) Idiopathic atrophy
How does euthyroid sick syndrome occur
Suppression of T4 by other conditions such as concurrent illness, many medications (steroids), Cushing’s disease
What dog breeds have a predilection for hypothyroidism
Doberman, Golden Retriever, Labrador, Dachshund, Schnauzer, Great Dane, Cocker
How might a hypothyroid dog present?
Lethargy
Mental dullness
Weight gain/obesity
Dermatologic lesion (alopecia, seborrhea, pyoderma)
Hypercholesterolemia
What two clinical signs common to the other endocrinopathies that hypothyroid dogs do not have
PU/PD
Polyphagia
What skin abnormalities is seen in hypothyroid dogs
fluffy, puppy coat
alopecia in areas of wear
shaved area with no growth
hyperkeratosis in inguinal and axillary regions
What disease do you see the tragic face in?
Hypothyroidism from facial nerve paralysis and decreased reflexes
Does megaesophagus go away when completing the treatment of hypothyroidism in dogs?
NO
What diseases might be tied to hypothyroidism but it isnt determined due to breed predispositions?
1) Megaesophagus
2) Laryngeal paralysis
3) Von Willibrand factor deficiency
4) Infertility
What are the only findings from the minimum database that you will see in a hypothyroid dog
CBC: Mild, non-regenerative anemia
Biochem: High amounts of cholesterol
What is the first test you should perform if you suspect hypothyroidism in dogs?
Total T4 and eTSH
TgAA assay
Thyroglobulin autoantibody
present in 50-60% of hypothyroid dogs
Suggest the presence of autoimmune thyroiditis
*Does not predict the current or even future hypothyroidism
Is TT4 or Free T4 more sensitive for the testing of hypothyroidism
fT4
What would you expect tT4, fT4 and TSH to be in a patient with primary hypothyroidism
tT4: Low
fT4 : Low
TSH: High
*but TSH can be normal in 25% of dogs
What would you expect tT4, fT4 and TSH to be in a patient with euthyroid sick syndrome
tT4: Low
fT4 : normal
TSH: Normal to Decreased
What would TSH levels be in a patient that has euthyroid sick syndrome
Normal to Decreased
What is the best test for hypothyroidism in dogs?
Screen with TT4 + TSH (limited thyroid panel)
If suspect still, add fT4 and autoantibodies
What should you not do when interpreting a total T4 for hypothyroid dogs
Do not interpret it alone
You must have both TT4 (+/- fT4) and TSH because otherwise you cant differentiate true primary hypothyroidism from euthyroid sick syndrome
What should you do to treat hypothyroid dogs?
Supplement with L-thyroxine (T4), twice daily dose
What is the response time to L-thyroxine?
Activity level: 2 weeks
Haircoat, body weight, bloodwork abnormalities: 6-8 weeks
Neurologic signs- months
Megaesophagus: may not resolve
How should you monitor a patient after treatment with L-thyroxine
after 6-8 weeks of therapy
take a 4-6 hours post-pill sample
maintain in high normal or slightly increased range
What should you consider if there is a high total calcium but ionized calcium is low to normal (with azotemia present
Chronic kidney disease
What are your 4 differentials for high calcium and phosphorus
1) Renal disease
2) Addisons
3) Vitamin D toxicosis
4) Osteolysis
What do you suspect with calcium is high and phosphorus is low
Primary hyperPTH
Neoplasia
What should you consider if a patient has
-High total calcium and ionized calcium
-Low Phosphorus
-LN aspirate or rectal exam (Lymphoma/AGASACA)
-Cervical ultrasound (Hyperparathyroidism)
-PTH panel (Hyperparathyroidism)
What results would you expect to see in a patient with primary hyperPTH
tCa2+: High
iCa2+: High
PTH: High
PTHrp: 0
P: Low
What results would you expect to see in a patient with lymphoma or AGASACA
tCa2+: High
iCa2+: High
PTH: Low
PTHrp: High
P: Low
Is PTH of a patient with lymphoma or AGASACA low or high
Low
Is PTH of a patient with Vitamin D toxicosis low, high, or normal
Low to normal - there is already high calcium so no stimulus
What are the two most common diseases with increased total calcium
1) Secondary Renal Hyperparathyroidism (has normal to low iCa2+)
2) Neoplasia
What are 5 therapy optins for hypercalcemia
1) Sodium diuresis (competes with Ca2++ reabsorption)
2) Furosemide (Inhibits Ca2+ reabsorption in the thick ascending loop of Henle)
3) Glucocorticoids: inhibits GI absorption, bone reabsorption, increases calciresus (Get aspirates and biopsies first)
4) Bisphosphonate: inhibits osteoclast function
5) Salmon calcitonin
What else can cause the parathyroid to become hyperplastic that is not primary hyperPTH
Secondary to Renal disease
How can you differentiate renal hyperparathyroidism from primary hyperparathyroidism
Calcium (ionized) will be low to normal
What is the therapy for primary hyperparathyroidism
Surgical removal
Try to leave at least one of the 4 parathyroid gland
Recurrence is more likely if there is hyperplasia
How do you manage a patient that just had its parathyroidglands removed
Monitor calcium (Usually declines within 1-7 days)
Supplement with vitamin D and calcium (often for life)
Look out for hypocalcemia signs (Muscle tremors, facial pruritus
Of the two synthetic mineralocorticoids available, which one must always be supplemented with prednisone?
DOCP
Desoxycorticosterone (DOCP) only has mineralocorticoid properties. Patient receiving DOCP must receive prednisone. About 50% of patients receiving fludrocortisone require prednisone, but the other 50% of patients can be successfully treated with fludrocortisone alone.
Which insulin is used for diabetic ketoacidosis?
Regular insulin is the insulin of choice for a patient with DKA. It should be given as intermittent intramuscular (IM) injections or IV as a constant rate infusion while the patient is dehydrated and not eating. Sometimes we will use subcutaneous injections before we transition to intermediate acting insulin but only if the the patient is eating and drinking. You can also go directly from IM or IV regular insulin to intermediate-acting insulin once the animal is eating and drinking on its own.
When should you measure insulin?
To diagnose an insulinoma
You should never measure insulin as part of a diabetic or acromegalic workup. The only time we measure insulin is if the glucose is low and we suspect an insulinoma. A diagnosis of insulinoma is made when the fasted glucose is low at the same time that the insulin level is high, since that is inappropriate. When a patient is hypoglycemic, insulin secretion should be shut down.
You should not run a HDDS (a discriminating test) before running a screening test like LDDS.
Explain why the results can make it hard to differentiate between a normal patient and one with PDH.
You have to think about the theory behind the HDDs. The theory is that even though a pituitary dependent tumor might not suppress with a low dose of steroids, it could suppress for 8 hours with even higher doses. It might even suppress at 4 hours and stay suppressed at 8 hours.
But remember that a normal dog will suppress at 8 hours with the low dose of steroids, which means it will ALSO suppress with high dose of steroids.
That means that the results for both a normal dog and a PDH dog that suppresses at both 4 and 8 hours will have the same curve. Therefore, if you do a HDDS test first, you can’t differentiate between a normal dog and one that has PDH.
What species is a thyroid panel for?
Dogs
“Tim”, 12 yr old, MC, DSH
Tim has a recent history of PU/PD. His blood glucose is 310 and he has trace glucose in his urine.
What do you recommend next?
This is the ideal situation to run a fructosamine since it will help you difference chronic hyperglycemia from epinephrine-induced hyperglycemia. It is not safe in this situation, given the barely detectable glucosuria, to start insulin. Better to wait for 24 hours for a test that helps you feel more confident in your diagnosis. Retesting the urine may or may not change the result. We do not measure insulin levels in our diabetic patients, so please don’t select insulin levels for any answers on this exam!
“Michael”, 5 yr old, MC, Keeshond
Michael has been diagnosed with DKA and you are treating him with fluids and insulin. This morning his PCV is 25% (low).
What would you like to measure next?
Phosphorus
“Boggy”, 2 yr old, MC, lab
Boggy presents to your emergency clinic with acute onset of vomiting, diarrhea, and abdominal discomfort. You suspect Addison’s, but on his venous blood gas, his potassium and sodium are normal.
What are the possible differentials diagnoses? Select all that apply.
Atypical Addisons
Pancreatitis
GI foreign body
“Lila”, 12 yr old, FS, mixed breed dog
Lila has hair loss on her sides and thinning skin. She presents with lethargy, anorexia and a single episode of vomiting.
Of the possible diagnoses listed below, which one is the most likely?
The clinical signs of hair loss along her trunk should make you think Cushing’s or hypothyroidism. The thinning skin points to Cushing’s.
But, more important is the patients with pituitary-dependent Cushing’s or adrenal, or hypothyroidism are not sick!
Addisonian patients are sick but they don’t have thinning skin or an endocrine alopecia pattern.
A patient with iatrogenic Cushing’s will have the clinical signs of Cushing’s, but if the exogenous steroid is abruptly stopped, they will develop an Addisonian crisis (which is atypical since electrolytes are normal) and present with GI signs and shock. Remember the cortisol allows us to respond to stress, including raising blood pressure during stressful events, so you don’t need a mineralocorticoid deficiency to present in shock.
“Liddy”, 3 yr old, FS, Westie
Presents in an Addisonian’s crisis with a potassium of 6.8 (high).
Your supervising clinician recommends giving insulin and dextrose. Why?
Insulin will cause glucose uptake into the cells. Glucose uptake is a co-transporter with potassium, which helps move potassium from the bloodstream into the intracellular space where it normally resides. Don’t forget to provide glucose when giving insulin!
Addisonian patients have normal or decreased glucose, not hyperglycemia.
Addisonian patients mild hypercalcemia, not hypocalcemia.
Although shifting K+ into the cells may help somewhat with the acidosis, it is not the primary goal of insulin and glucose as the acidosis is almost always corrected with fluid administration.
Insulin-glucose therapy does not impact the sodium levels.
“Daschell”, 3 yr old, MC, Portuguese water dog
You suspect atypical Addison’s and perform a baseline cortisol (screening test for Addison’s). The value is 1.5 (low).
What is your next best step?
Perform an ACTH stim
Would you use DOCP in atypical Addison
NO
