Disorders of Calcium & Parathyroid Glands Flashcards
What makes up total calcium?
free calcium (biologically active) + protein bound (albumin) + complexed to citrate, phosphate, etc.
What are the 3 main calcium hormones?
- calcitonin - produced by thyroid C cells, lowers calcium
- PTH - produced by parathyroid chief cells, increases calcium and decreases phosphorus
- vitamin D3 (calcitriol) - increases GI absorption of calcium and phosphorus
What 4 systems are affected by hypercalcemia? What happens when levels get especially high?
- heart - decreases cell membrane permeability, arrhythmia, mineralization
- CNS - depression, muscle weakness, twitching
- GI - anorexia, vomiting, constipation
- kidneys - PU/PD (blocks ADH receptors), renail failure, decreased GFR, mineralization, calculi
Ca x P > 70 = dystrophic mineralization
What is the most common clinical sign associated with hypercalcemia in dogs? What else is seen?
PU/PD (>15 mg/dL)
- LUT signs, calcium oxalate uroliths
- weakness, exercise intolerance
- listlessness
- inappetence, weight loss, muscle wasting
- vomiting
What is the most common clinical sign associated with hypercalcemia in cats? What else is seen?
vomiting
- weight loss, anorexia
- urinary signs
What is the most common non-pathological cause of hypercalcemia? What are 4 other causes?
lab error —> repeat it!
- post-prandial, lipemia (minimal)
- pediatric in growing puppies (mild)
- hemoconcentration
- hemolysis
What are the rule outs for hypercalcemia?
GOSH DARNIT
- Granulomatous disease: blastomycosis, histoplasmosis, schistomiasis
- Osteolytic disease: osteomyelitis, osteosarcoma, growing puppy
- Spurious: supplementation
- Hyperparathyroidism
- vitamin D
- Addison’s disease: reduced renal calcium removal, increased reabsorption and GI absorption
- Renal failure: iCa usually normal, doesn’t usually need treatment
- Neoplasia: hypercalcemia of malignancy commonly in lymphoma, anal sac carcinoma, multiple myeloma, mammary gland adenocarcinoma, etc.
- Idiopathic: cats, inflammatory
- Toxicity
What are the 5 most common causes of vitamin D toxicity that can cause hypercalcemia?
- psoriasis/eczema cream
- cholecalciferol rodenticides
- over supplementation
- lactulose in cats
- plants
Causes of hypercalcemia
How are differentials for hypercalcemia organized?
check ionized calcium levels and phosphorus!
- high iCa + high P = vitamin D
- high iCa + low/normal P = hyperparathyroidism, neoplasia (PTHrP), etc.
What are the top causes of hypercalcemia in dogs and cats?
DOGS: neoplasia (lymphosarcoma, AGASACA, multiple myeloma, mammary carcinoma, sarcomas, malignant melanoma)
CATS: idiopathic, neoplasia (LSA, SCC)
Why is a good history especially helpful for diagnosing cause of hypercalcemia?
- travel history: granulomatous disease associated with fungal disease and Leishmaniasis)
- plants
- skin creams on owners
What should be included in the PE to diagnose the cause of hypercalcemia?
- palpate lymph nodes - LSA
- rectal exam - anal sac
- cervical palpation - hyperparathyroidism
- oral cavity, ear canal - SCC in cats
- fundic exam
- recheck blood work
What should be the first diagnostic for ruling out causes of hypercalcemia?
cancer screening
- thoracic radiographs
- abdominal ultrasounds
- bone radiographs (if painful)
- cervical ultrasound
What is parathyroid hormone-related protein? What do high levels in blood work indicate? Negative results?
protein similar to PTH isolated from specific tumors as the primary cause of hypercalcemia of malignancy (decreased P, acts like PTH!)
- POSITIVE: strongly supports diagnosis of neoplasias, like LSA< apocrine gland carcinomas, and SCC
- NEGATIVE: does not rule out neoplasia
What is hyperparathyroidism?
sustained increase in PTH secretion, resulting in increased iCa and decreased phosphorus
What is the most common cause of primary hyperparathyroidism? What are some other causes?
excess production of PTH (in face of hypercalcemia) due to a chief cell adenoma
- adenocarcinoma
- hyperplasia
What are 2 secondary causes of hyperparathyroidism?
- RENAL: increased phosphorus from renal disease causes increased phosphatonin, which decreases vitamin D and Ca resulting in high PTH
- NUTRITIONAL: diets low in calcium and vitamin D or excessive P elevates PTH
In what animals is primary hyperparathyroidism most common? How does this affect the parathyroid gland?
4-16 y/o dog —> adenoma!
other parathyroid glands will atrophy and are not usually seen —> if they are seen, the cause of hypercalcemia is likely neoplastic and not primary
What breed has an increased predilection for primary hyperparathyroidism? What are the most common clinical signs in dogs and cats?
Keeshounds and Siamese
- DOGS: PU/PD first, hyporexia/anorexia, lethargy, weakness, weight loss, muscle wasting
- CATS: vomiting, lethargy, anorexia, inappetence, pollakiuria, stranguria, hematuria
(increased Ca!)
What is seen in severe cases of primary hyperparathyroidism?
- cardiac arrhythmias (VPCs)
- seizures, muscle twitchin
- soft tissue mineralization when Ca x P > 70
What is the most common diagnostic plan in patients with potential primary hyperparathyroidism?
- CBC/chem: usually normal
- UA: calcium oxalate stones, decreased USG
- iCa + PTH +/- PTHrP: elevated
- look for a reason for elevated iCa - look at the whole animal with rectal palpation, LN palpation, and mammary gland palpation
- chest radiographs: metastasis
- neck U/S: adenoma, hyperplasia
What is most commonly seen on blood work in patients with primary hyperparathyroidism?
- high normal range or above iCa (if persistent, r/o lab error)
- normal to low P
- low urine USG (Ca blocks ADH receptors)
- close to normal tCa due to PD patients “watering down”
What is the expected PTH level when iCa is high?
decreased
- hyperparathyroidism = normal to elevated
How are PTH levels interpreted?
with increased iCa
- PTH upper RI or increased = hyperparathyroidism
- PTH lower RI = maybe hyperparathyroidism
- PTH below RI = not hyperparathyroidism
A 6 y/o Keeshond has:
- elevated tCa
- elevated iCa
- low P
- high RI PTH
Which is correct?
a. The dog is hyperparathyroid.
b. The dog is not hyperparathyroid.
c. You cannot tell.
A
PTH should be below or in the lower RI
A 10 y/o Golden Retriever has:
- increased Ca
- increased iCa
- increased P
- normal creatinine
What is the likely diagnosis?
a. lymphoma
b. renal failure
c. vitamin D toxicosis
d. Addison’s disease
e. hyperparathyroidism
C
increased iCa and P
You are performing a parathyroidectomy for hyperparathyroidism. You see that out of the 4 glands, only one is large, one is normal, and 2 are not visible. You should…..
a. remove the 1 large gland
b. remove the 1 large gland and the normal gland
c. remove the normal gland
d. remove all 4 glands
B
normal seeming gland should be atrophied —> could be neoplastic
What is required for treatment of hypercalcemia?
treating underlying cause
What are 4 indications to directly treat hypercalcemia?
- diagnosis unknown and Ca x P > 70
- hypercalcemia is severe
- clinical signs are present
- idiopathic
What are the 4 major medical treatments of primary hyperparathyroidism when surgery is not possible?
- fluid therapy with 0.9% NaCl
- oral Furosemide when hydrated to increase renal calcium excretion
- oral glucocorticoids decreased absorption of Ca from the intestines and increases urinary loss
- oral bisphosphonate (alendronate) stops removal of calcium from bones and lowers osteoclast poison
What diuretic is avoided when treating primary hyperparathyroidism? When is glucocorticoid usage avoided?
thiazides
only used when diagnosis is definite, since it can mask signs of neoplasia (lymphoma/LSA)
What are 3 other medical managements for primary hyperparathyroidism?
- periodic IV bisphosphonate (pamidronate)
- injectable calcitonin - inhibits osteoclast-mediated bone resorption and increases renal excretion of calcium
- cinacalcet - calcimimetic agent that activates calcium-sensing receptor and lowers PTH secretion
What glands are removed on parathyroidectomies to treat primary hyperparathyroidism? What are some risks?
all enlarged glands
- GA
- close to large vessels and recurrent laryngeal nerve
- can be an ectopic mass (U/S, radiographs)
- possibility of there being no/multiple nodules
- decrease in calcium after removal
- aggressive post-op monitoring required
What are 2 other surgical treatments for primary hyperparathyroidism?
- ETHANOL ABLATION - percutaneous U/S injection of ethanol into nodule with short GA
- HEAT ABLATION - U/S IV catheter placed into affected gland and an insulated wire is placed, which applies energy to the gland
What considerations need to be taken when using ablation to treat primary hyperparathyroidism?
- cannot be used if nodule is close to carotid artery
- will affect local thyroid tissue
- over effusion of the gland can result in damage to the recurrent laryngeal nerve and laryngeal function (assess for unilateral lar par before!)
What response is commonly seen following surgical removal or ablation of the parathyroid gland? In what 2 ways can this be managed?
calcium levels drop within minutes to 12 hours for 5-7 days —> USUALLY TRANSIENT as long as there is one parathyroid gland left
- pre-treat with calcitriol and oral calcium (Tums) 24 hrs before surgery —> requires iCa test available to know when to wean off ($$$)
- wait to see if treatment is needed, but have IV calcium gluconate and premade calcitriol ready for if hypocalcemia occurs when tCa = 8 mg/dL or iCa = 0.8-0.9 mg/dL —> patient should be in hospital at least 12 hours
(want to use the lowest supplementation available so that the other glands can bounce back)
What is the goal to long-term therapy with hypoparathyroidism status following a parathyroidectomy
- keep iCa on low end or just below normal to stimulate PTH production from remaining glands
- wean off vitamin D over weeks
What emergency treatment is performed in patients with hypocalcemia following parathyroidectomies?
- IV infusion of 10% calcium gluconate - NO EXTRAVASATE OUT OF VEIN
- monitor ECG for bradycardia, shortened QT intervals of VPC
- CRI or oral calcium (Tums)
What are 4 causes of secondary hyperparathyroidism? What does this commonly result in?
prolonged high PTH due to:
- increased serum phosphorus
- normal to low iCa
- decreased calcitriol synthesis in kidney
- parathyroid gland hyperplasia
depletion of skeletal calcium = osteoporosis and pathologic bone fractures (“rubber jaw”)
What is the most common cause of nutritional secondary hyperparathyroidism? What does this result in?
diets with decreased Ca and/or vitamin D or high phosphorus = increased PTH —> all meat, all grain, or homemade diets
osteopenia, pathologic bone fractures, skeletal bone resorption (poor bone density)
What are the 5 multifactoral causes of renal secondary hyperparathyroidism?
- decreased calcitriol (vit D3) production in kidney failure = decreased iCa and increased P
- decreased calcitriol = decreased negative feedback for PTH release
- PTH excretion from renal disease
- decreased GFR = hyperphosphatemia
- fibroblast factor decreases calcitriol synthesis
ALL RESULT IN INCREASED PTH
What are some signs of renal secondary hyperparathyroidism?
PTH is a uremic toxin and causes severe bone demineralization = jaw fractures, teeth loss, facial distortion (rubber jaw)
How is renal secondary hyperparathyroidism treated?
TREAT RENAL DISEASE
- supplement calcitriol early to help reverse or slow progression when P is not elevated
- restrict phosphorus
What is the most common cause of hypercalcemia in cats? What is the most common clinical sign?
idiopathic —> possibly acidifying diets
vomiting
How is idiopathic hypercalcemia diagnosed?
- r/o other causes (neoplasia!)
- elevated iCa
- normal P and PTH
- thoracic radiographs and abdominal U/S
- normal 25-vitamin D levels
What medical treatment is recommended for idiopathic hypercalcemia?
glucocorticoids or bisphosphonates (alendronate)
iCa > 0.25 mmol over RI or with clinical signs
What 4 diets can help manage idiopathic hypercalcemia?
- high fiber canned diets (increased water intake)
- renal diets
- stone diets to decreased calcium oxalate stones (decreased Ca and low acidity)
- low calcium and vitamin D
What medication exacerbates idiopathic hypercalcemia in cats? What order of treatment is recommended?
lactulose
- high fiber diet
- glucocorticoid
- bisphosphonates
When are signs of hypocalcemia observed?
- Ca < 6-7 mg/dL
- iCa < 0.7 mmol/L
When total calcium is low, what else should be checked? When is correction recommended? How is this calculated?
albumin
if albumin is < 3.5, need to correct up to normal to better understand the true total calcium
(3.5 - ALB) + total calcium = corrected calcium
What is the most common clinical sign associated with hypocalcemia? What else is seen?
intense facial pruritus, face rubbing, biting at feet
- tenseness, nervousness
- stiff gait
- leg cramping or pain
- focal or general tremors
- tetany or seizures
- weakness, anorexia
- panting, small capsular cataracts
What are 4 effects of hypocalcemia?
- neuromuscular dysfunction
- decreased neurotransmitter release
- destabilized nerve cell membranes
- death from respiratory or cardiac dysfunction or seizures
What are the major rule outs for hypocalcemia?
MATCHING DRAPES
- Magnesium depletion or malabsorption (necessary to produce PTH)
- Albumin deficiency (normal iCa)
- Toxins
- Chelation
- Hypoparathyroidism, hypoproteinemia, hypomagnesemia
- Infarct of parathyroid gland, iatrogenic
- Nutritional secondary hyperparathyroidism
- GI disease
- Drugs, diet
- Rhabdomyolysis, renal failure
- A seen above
- Parathyroid atrophy, pancreatitis, phosphate enema
- Eclampsia
- Sepsis
What toxins cause hypocalcemia? Drugs?
ethylene glycol and phosphate enemas
steroids and citrate
What is the diagnostic plan for patients with hypocalcemia?
- HX: lactating female, (para)thyroidectomy, phosphate enema
- draw blood for calcium
- treat if acute
hypocalcemia noted on chemistry: amylase, lipase, cPLI (r/o pancreatitis), correct formula if decreased ALB
What must be ruled out for hypocalcemia and hyperphosphatemia with/without azotemia?
WITH AZOTEMIA: acute renal failure (ethylene glycol), CKD
WITHOUT AZOTEMIA: hypomagnesemia, primary hypoparathyroidism
In what 4 types of patients is eclampsia (puerperal tetany) seen? How does this affect calcium?
- lactating bitches and queens during first 3 weeks postpartum
- small dogs or cats with first pregnancy
- large dogs in the last trimester
- supplementation of a pregnant bitch with calcium causes atrophy of the parathyroid gland
rapidity of calcium utilization overwhelms ability to maintain normal iCa concentration
What treatment is recommended for patients with puerperal tetany? What are 2 ways of prevention?
- IV calcium gluconate, continuous IV drip, SQ
- wean puppies or kittens
- supplement diet with Ca or vit D
- feed adequate Ca during pregnancy and lactation
- feed diet with Ca:P of 1:1
What are 4 laboratory results indicative of hypoparathyroidism?
- low PTH
- low calcium
- high phosphorus
- low magnesium
What is the most common signalment for hypoparathyroidism? When are signs worse?
young adults - Mini Poodles/Schnauzer, Terriers, Siamese
with exercise or excitement (tend to wax and wane)
What is indicative of primary hypoparathyroidism? What are the 3 most common causes?
hypocalcemia with a low/low-normal PTH (inappropriate rection) and mild to marked hyperphosphatemia +/- hypomagnesemia
- spontaneous parathyroiditis or adenoma infarction
- post-op parathyroidectomy
- neck surgery
What are 7 causes of hyperphosphatemia?
- decreased GFR: azotemia***
- disturbances in calcium metabolism (hypoparathyroidism) or vitamin D toxicity
- bone growth in young animals, osteolysis
- in vitro hemolysis - blood sits before spun, left in heat
- muscle damage
- tumor lysis syndrome
- phosphate supplementation
What is the main treatments of acute hypocalcemia? What 2 treatments are avoided?
10% calcium gluconate IV
- avoid fluids containing lactate, bicarbonate, or acetate
- calcium-containing fluids SQ
What is main maintenance treatments for hypocalcemia? Examples?
calcium and vitamin D supplementation
- CA: oral elemental
- VIT D: ergocalciferol (long-acting, poor choice), dihydrotachysterol, calcitriol (shortest onset and safest for adjusting dose)
