Endocrine Flashcards
What cells are pheochromocytoma derived from?
Chromaffin cells of the adrenal medulla.
Chromaffin cells also called APUD cells → responsible for amine precursor uptake and decarboxylation
What are the clinical signs of pheochromocytoma?
- Systemic hypertension
- Tachyarrhythmias/ bradyarrhythmias
- syncope
- v/d
- PUPD
- tachypnea
- abdominal distention/pain
True or False: High concentration of urinary normetanephrine was highly suggestive of pheochromocytoma.
True
* Urinary normetanephrine-to- creatinine ratio proved to be superior to epinephrine-, norepinephrine-, or metanephrine-to-creatinine ratios
In human, what drug can be given to reverse the catecholamine-induced vasoconstriction from pheochromocytoma?
Phentolamine, an reversible non-selective α-adrenergic antagonist
What drugs should be avoided in pheochromocytoma patients due to possible acute hypertensive crisis?
- Metoclopramide: In patients with pheochromocytoma, metoclopramide can cause a surge in catecholamine release from the tumor by antagonizing presynaptic dopaminergic inhibition. Normally, dopamine acts to inhibit norepinephrine release, so blocking this effect leads to increased norepinephrine release.
- Histamine: can case vasodilation with reflex tachycardia and further vasoconstriction
- Glucagon: activates adenylate cyclase, leading to an increase in intracellular cyclic AMP (cAMP), which can promote catecholamine secretion from the tumor
What are the pre-, peri-, and post- anesthetic management for pheochromocytoma?
Pre:
1) start non-competitive α-adrenergic blockade with phenoxybenzamine (0.5 to 2.5 mg/kg PO q12h) 1 week before sx
2) blood type
Peri:
1) opioid + bzd + propofol for premed and induction
2) avoid halothane → sensitizes the myocardium to catecholamine- induced arrhythmias
3) monitor ECG and blood pressure
4) prepare esmolol (0.05 to 0.5 mg/kg IV followed by 10 to 200 mcg/kg/min IV), vasodilators such as nitroprusside (0.5 to 5 mcg/kg/min IV) or magnesium sulfate
5) prepare phenylephrine (0.5 to 5 mcg/kg/min IV) or norepinephrine (0.1 to 2 mcg/kg/ min IV) because patient may become hypotensive after tumor removal
What is the medical management for pheochromocytoma?
Phenoxybenzamine, β-blockers, and/or other anti-arrhythmic agents
* β-Blockers should not be given without concurrent α-blockade → loss of β2 receptor–mediated vasodilation may exacerbate hypertension
What is Budd-Chiari-like syndrome?
Mechanical obstruction of the hepatic venous outflow → liver congestion, right upper quadrant pain, ascites
For pheochromocytoma, what are the negative prognostic indicators for surgical outcome?
- Vena cava invasion
- older age
- intra-op arrhythmias
- prolonged surgical time
How are NE and Epi synthesized?
Tyrosine enters the nerve → DOPA → Dopamine → enters the vesicles → NE → exits the vesicle and receives a methyl group → Epi → re-enters the vesicles
Resources: https://cvpharmacology.com/norepinephrine
How are NE and Epi metabolized?
1) Neuronal re-uptake
2) Catechol-o-methyltransferase (COMT) and monoamine oxidase(MAO)
How is the ketone body synthesized?
Fatty acids went through 𝜷-oxidation and form Acetyl-CoA.
Normal situation: Glucose degraded into pyruvate → both Acetyl-CoA and pyruvate enter TCA cycles
Diabetic: No pyruvate; two Acetyl-CoA → form ketone bodies
What are three types of ketone bodies?
Acetoacetate (strong acid)
𝜷-hydroxybutyrate (strong acid)
acetone
Which ketone body cannot be detected by the urine strip test (nitroprusside reaction)?
𝜷-hydroxybutyrate
Why occasionally there will be negative urine ketone on day 1 but became positive on day 2 or 3 after the treatment is started?
After starting the insulin treatment, the urine 𝜷-hydroxybutyrate : Acetoacetate ratio may decrease because more 𝜷-hydroxybutyrate is metabolized back to acetoacetate and therefore can be detected with nitroprusside test
What are the most common concurrent diseases in dogs with DKA?
Acute pancreatitis
Bacterial UTI
Hyperadrenocorticism
What are the most common concurrent diseases in cats with DKA?
Hepatic lipidosis
CKD
Acute pancreatitis
Bacterial/viral infection
Neoplasia
What is the concentrations of K and Phos in Kphos?
K: 4.4 mEq/ml
Phos: 3 mM/ml
What is the rate to supply phos in patient with DKA and hypophoshpatemia?
0.03 - 0.12 mM/kg/hr
Describe the CRI regular insulin protocol for DKA.
What is the recommendation from The American Diabetes Association for bicarb supplementation for pediatric DKA patients?
1) Who should be treated?
who maintain a pH < 7.0 after 1 hour of fluid therapy
2) How to treat it?
Sodium bicarb 2 mEq/kg added to 0.9% NaCl, in a solution that does not exceed 155 mEq/L of sodium over 1 hour.
3) How to monitor?
The pH is monitored q1h and treatment is repeated until pH ≥ 7.0
What is the hallmarks for HHS?
- BG > 34mmol/L (600 mg/dL)
- Minimal or negative urine ketone
- Serum osmolarity > 350 mOsm/kg (cat) or 325 mOsm/kg (dog)
- Ketotic vs non-ketotic
Describe the pathogenesis of HHS.
1) Hormone alteration
Insulin deficiency + increased countercurrent hormone (e.g. epinephrine, glucagon, cortisol, growth hormone)
- Epinephrine & glucagon inhibit insulin-mediated glucose uptake in muscle and stimulate hepatic glycogenolysis and gluconeogenesis
- Cortisol & growth hormone inhibit insulin activity and potentiate the effects of glucagon and epinephrine
2) severe osmotic diuresis due to hyperglycaemia (usually extreme)
3) dehydration and decrease GFR
4) worsening of hyperglycaemia
such extreme hyperglycaemia can only occur with decreased GFR as once reached threshold the rest of glucose should be excreted with urine
What is the main difference between HHS and DKA?
HHS usually has higher BG level and higher osmolarity. Patients with HHS also have higher circulating insulin level and lower glucagon level → this inhibits the liver to perform lipolysis due to presence of insulin.
What is the equation of serum osmolality?
Serum osmolality (mOsm) = 2 x Na + BUN/2.8 + BG/18
- Unit for Na = mEq/L
- Unit for BUN & BG = mg/dL
What is the equation of effective osmolality
Effective osmolality (mOsm) = 2 x Na + BG/18
What are the main contributors for metabolic acidosis in DKA and HHS, respectively?
DKA: ketones
HHS: uremic acids, lactic acids
What is the equation to correct Na in HHS patient?
Corrected Na = Patient’s Na + 1.6 x [(Measured BG - Normal BG)/100]
- Unit for Na = mEq/L
- Unit for BG = mg/dL
True of False: For HHS management, using IM or IV protocols of regular insulin at dosages 50% of those used for DKA should reduce the risk of a too rapid decline of serum glucose.
True
What is the target rate to reduce BG in HHS patients?
No more than 2-4 mmol/L/hr
True or False: Many dogs with HHS has recent steroid administration
True (18%)
- In the same study, poor outcome was associated with abnormal mentation and low venous pH
Reference: Trotman TK, Drobatz KJ, Hess RS. Retrospective evaluation of hyperosmolar hyperglycemia in 66 dogs (1993-2008). J Vet Emerg Crit Care (San Antonio). 2013;23(5):557-564.
How is potassium affected in patients with DKA/HHS?
1) Acidosis → K+ is shifted out of the cell in exchange with H+
2) Decreased dietary intake → K ↓
3) Hypovolemia induced hyperaldosteronism → increased renal loss
4) Insulin deficiency → decreases the amount of K co-transported into cells
5) Decreased GFR → K accumulates in the blood
True or False: The BG level in the brain is the same as plasma.
False
Glucose concentrations in the brain are up to 30% lower compared to plasma
The brain relies on facilitated diffusion via GLUT-1 and GLUT-3 (insulin independent)
What is the cutoff to diagnose insulinoma with insulin:glucose ratio?
Amended Insulin-Glucose Ratio (AIGR) > 30 is supportive of insulinoma
- Equation: AIGR = (insulin × 100) ÷ (plasma glucose − 30)
- Need to collect the blood when BG < 60
Where is the glucagon from? Where does it work?
1) 𝜶 cells in the pancreas
2) liver, promote glycogenolysis and gluconeogenesis
When should you raise a concern for insulin resistance?
when insulin dose > 1.5U/kg q12h
What are the four factors contributing to thyroid storm in cats?
1) Higher concentration of circulating thyroid hormone
2) Acute, rapid increase of circulating thyroid hormone
3) Hyperactivity of the sympathetic nerve system
4) Increased cellular response to thyroid hormone
What is the axis stimulating thyroid synthesis?
TRH from hypothalamus → TSH from Anterior pituitary gland → thyroid gland
What are the differences between T3 and T4?
T4 (thyroxine)
- 93% of the thyroid hormone released from the gland
- When enters the cells, one iodide is removed and most of T4 are converted to T3
T3 (triiodothyronine)
- 7% of the thyroid hormone released from the gland
- biologically active form
- Has much higher affinity to the intracellular receptors for nucleus transcription
List 5 precipitating events for feline thyroid storm.
Stress
Vigorous palpation of the thyroid
Thyroidal or parathyroidal surgery
Radioactive iodine therapy
Sudden withdrawal of the methimazole
Administration of iodinated contrast dyes
Administration of stable iodine compounds
Nonthyroidal illness (e.g. infection)
Amiodarone therapy
Is T4 and T3 highly protein bound? What are the protein they bind to?
Yes both are highly protein-bound
About 60% is bound to thyroxine binding globulin, 17% to transthyretin, 12% to albumin and 11% to various lipoprotein fractions.
Only about 0.3 - 1% are free form (active form)
What is the MOA for methimazole?
Methimazole inhibits the action of thyroid peroxidase → inhibits the incorporation of iodide into thyroglobulin → decrease T4 & T3 production
Dose: 5mg per cat q12h
What are the medical treatments to decrease thyroid hormone production/secretion for suspect thyroid storm?
1) **methimazole **(cannot stop the release of stored thyroid hormone)
2) potassium iodide (stable iodine compounds)
- Prevent secretion of thyroid hormone
- Need to give 1 hr after methimazole administration
- 25mg PO q8h
3) **iopanoic acid **(lipid-soluble radiographic contrast agent)
- Prevent secretion of thyroid hormone
- block peripheral conversion of T4 to T3
- block T3 from binding to its receptor
- inhibit thyroid hormone synthesis
- 100mg per cat PO q12h
4) Dexamethasone
- inhibit peripheral conversion of T4 into T3
- 0.1-0.2 mg/kg PO/IV
Why illness can cause decreased thyroid hormone production?
Illness can increase plasma glucocorticoid concentration → inhibit TSH secretion from anterior pituitary gland
What are the pros and cons for each beta blockers for treating feline thyroid storm?
Propranolol
- Pros: can inhibit peripheral T4 conversion to T3 (slow)
- Cons: poor oral bioavailability, short half-life (need TID)
- 5mg PO q8h
Atenolol
- Pros: better oral bioavailability and SID administration
- Cons: doesn’t affect the T4 conversion
- 1 mg/kg PO q12h-q24h
Esmolol
- very short acting
- 0.1-0.5 mg/kg IV, followed with CRI 10-200 mcg/kg/min
However remember that propanolol not a selective 𝛽 blocker, so can be detrimental in asthamtic cats and also can cause hyperglycaemia.
What are the clinical signs in cats with feline thyroid storm (organ system)?
Fever
GI system
CNS
Cardiovascular system
Hypercoagulable state
Which breed is predisposed to hypothyroid crisis?
Rottweiler
What are the 6 classic hallmark for hypothyroid crisis?
myxedema (accumulation of glycosaminoglycan hyaluronic acid) in the dermis
coma
hypothermia
bradycardia
hypoventilation
hypotension
What are the risk factors of developing hypothyroid crisis?
Infection (e.g. pneumonia)
NSAIDs or glucocorticoid use
Surgery
Others in humans: burns, hypoglycemia, infection, hypothermia, trauma, and various medications, including anesthetics, barbiturates, narcotics, phenothiazines, and tranquilizers.
What are the six hormones that the anterior pituitary gland produces?
What are the two hormones that the posterior pituitary gland produces?
Anterior glands
ACTH (Adrenocorticotrophic hormone)
TSH (Thyroid-stimulating hormone)
Growth hormone (GH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Prolactin
Posterior glands
Oxytocin
Vasopressin
* These hormones are synthesized in the hypothalamus and stored in the posterior pituitary gland
List the 4 stimulating hormones and 2 inhibitory hormones released by the hypothalamus.
Describe the anatomic compositions of adrenal glands and the hormones each part secretes
From outside to inside:
Cortex
- Glomerulosa: Aldosterone (minerocorticoid)
- Fasciculata: Glucocorticoid
- Reticularis: sex hormones
Medulla: catecholamine
In the synthesis of adrenal hormones, which step is the rate limiting step?
Conversion of cholesterol to pregnenolone
Describe the function of aldosterone
- Mainly works at the collecting duct
- Account for 5-10% Na absorption
- At the principle cells
- Increases number of epithelial Na channels (ENaC) and Na-K ATPase → increase Na and water resorption and K excretion
- At the intercalated cells
- Increases H ion pump → increases H secretion in exchange with Na
- At the colon
- Increases Na resorption (small amount)
Write down the different steroid, their minerocorticoid and glucocorticoid effects, plasma half life, and biological half-life.
Fill out the blank
What are the 4 types of vasopressin receptors and what are their functions?
V1- vascular smooth muscle
V2 - renal collecting duct, platelet, endothelium, vascular endothelium
V3- pituitary gland
Oxytocin - uterus, GI tract, mammary gland
- Platelet also has V1R → facilitates thrombosis by increasing in intracellular Ca
- V3R also is responsible for all the CNS effect (e.g. temperature regulation, sleep)
How does glucocorticoid affect vasopressin?
It inhibits vasopressin release.
Interferes with cAMP formation
