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
