Parathyroid Disease Flashcards
Where is 99% of calcium in the body?
- 99% bone/teeth
- Remaining 1% intracellular
- 0.1% extracellular
Forms of calcium
- 50-60% ionized (biologically active form)
- 30-40% protein bound
- 10% chelated/complexed (phosphate, citrate, sulfate, bicarbonate)
Where is parathyroid hormone made?
- parathyroid glands
Where is calcitriol activated?
- Activation occurs in the kidney
Where is calcitonin made?
- Thyroid gland
What three hormones are involved in calcium regulation?
- Calcitriol
- Parathyroid hormone
- Calcitonin
How many parathyroid glands are there?
2 pairs (4 total)
What cells in the parathyroid gland make parathyroid hormone?
- Chief cells
Actions of PTH (broad)
- maintain plasma ionized calcium levels
- Regulate plasma phosphorus levels
What three organs does PTH act on?
- Bone
- Kidney
- Small intestines
PTH effect on bone
- Increase resorption (release) of calcium and phosphorus
- Increases blood levels of both
- Ultimately increases phosphorus and increases calcium
PTH effect on the kidney
- Increase calcium reabsorption (distal tubules and collecting ducts)
- Increase phosphorus excretion (proximal tubules)
- Serum calcium goes up, phosphorus goes down
- Also stimulates synthesis of the active form of Vitamin D (via increased activity of 1-alpha-hydroxylase)
- Ultimately: Increases calcium and decreases phosphorus
PTH effect on small intestines
- Indirectly via increase in calcitriol, leading to an increase in calcium and phosphorus
- Ultimately: Increases calcium and increases phosphorus
What are the there places where calcitriol works in the body?
- Small intestine
- Bone
- Parathyroid glands
Calcitriol effect on the small intestine
- Increases formation of calcium binding protein (CBP) which transports calcium from the lumen into the intestinal epithelial cells
Calcitriol effect on bone
- In large quantities stimulates bone resorption thus increasing calcium and phosphorus
Calcitriol effect on parathyroid glands
- Negative feedback leads to decreased PTH
Where is calcitonin made?
- Parafollicular cells (C cells) of the thyroid
Function of calcitonin
- Decrease serum calcium concentration
Calcitonin effects
- Works on bone
- Decreases osteocytic membrane activity
- Decreases osteoclast formation
Significance of calcitonin compared to PTH
- Much less significant
Look at the chart on Dr. Haines’s slides with the Ca/P summary - seriously do it! It’s helpful
do it
What happens to PTH as calcium goes up?
- PTH will go down
What happens to PTH as calcium goes down?
- PTH will go up
Calcium regulation general
- maintained in a very tight range
What are the three components of total calcium?
- Ionized, protein bound, and chelated forms
How would you confirm hypercalcemia if you have an animal with an elevated total calcium level?
- Need to get an ionized calcium
Differentials for hypercalcemia
HOGS IN YARD
- Hyperparathyroidism (1°)
- Osteolytic
- Granulomatous
- Spurious
- Idiopathic (cats), Iatrogenic (meds, supplements)
- Neoplasia (lymphoma, anal sac adenocarcinoma)
- Young
- Addison’s
- Renal disease
- D toxicosis (vitamin D)
Which differentials for hypercalcemia are driven by PTH?
- Hyperparathyroidism (primar)
- Neoplasia
Which differentials for hypercalcemia are not driven by PTH?
- Granulomatous disease
- Renal disease
- Vitamin D toxicosis
What differentials for hypercalcemia are not driven by PTH and are also calcitriol driven?
- Granulomatous disease
- Vitamin D toxicosis
Hyperparathyroidism mechanism of hypercalcemia
- Increased PTH that does not respond to negative feedback of elevated calcium
Lab findings of hyperparathyroidism (primary)
- Increased iCa
- PTH (high or inappropriately normal)
- Increased Vit D
- Decreased phosphorus
Causes of granulomatous disease
- disseminated fungal disease
Mechanism of hypercalcemia in Granulomatous disease
- Increased Vit D levels via activated macrophages
Lab findings for Granulomatous disease
- Increased Ca
- Normal or increased phosphorus
Which neoplasias can lead to hypercalcemia?
- Lymphosarcoma (esp T cell)
- Multiple myeloma
- Adenocarcinoma of anal sac and mammary glands, etc.
What is the mechanism of hypercalcemia in neoplasia?
- PTH-rp (related peptide)
Lab findings for Neoplasia hypercalcemia
- Increased iCa (and usually total)
- Regular PTH will be inappropriately normal or decreased
- Phosphorus decreased to normal
What is the mechanism of hypercalcemia in renal disease?
- Decreased excretion of Phos, Ca, and PTH by poorly functional kidneys OR
- Renal secondary hyperparathyroidism
Lab findings for renal disease (relevant to hypercalcemia)
- Possibly high total Ca, usually normal iCa, PTH normal, Phosphorus high
What is the mechanism of hypercalcemia in Vitamin D toxicosis?
- Increased Ca and Phos bone release and intestinal absorption
What can cause vitamin D toxicosis?
- Cholecalciferol rodenticide, dietary supplements, Psoriasis cream, some plants
Lab findings for Vitamin D toxicosis
- High calcium and phosphorus
Primary hyperparathyroidism definition
- Excessive production of PTH by the parathyroid glands
Primary hyperparathyroidism Causes (3, and which is most likely?)
- Parathyroid Adenoma (most common)
- Parathyroid Carcinoma
- Parathyroid Hyperplasia
- Can affect 1+ gland
Typical age of Primary hyperparathyroidism
- Middle aged to older
Typical sex of PHP
- No sex predilection
Typical Breeds of PHP
- Keeshonds
- Labs, Goldens, German Shepherds
Will most dogs with PHP be clinical or not?
- Most dogs with PHP are usually NOT CLINICAL
Clinical signs of PHP if present
- PU/PD
- Lethargy/Weakness
- Urinary signs: infections, calculi
- Long standing hypercalcemia can lead to renal failure
Typical physical exam findings for a dog with PHP
- Most of the time normal
- Any signs present are often subtle or non-specific, related to urinary issues, or due to unrelated causes
What cause of hypercalcemia would you expect in an older, apparently healthy dog with hypercalcemia?
- More than likely going to have PHP
What tends to be a unifying feature of dogs with hypercalcemia not due to PHP? (IMPORTANT)
- Many other causes generally result in a sick to very sick dog
CBC findings in PHP
- Usually normal
- Small % may have mild anemia
Chem panel findings in PHP
- Hypercalcemia (All)
- Low or low normal phosphorus (most)
UA findings in PHP
- Isosthenuria or hyposthenuria
- UTI
- Evidence of calculi
Typical Malignancy Panel with Primary HyperPTH
- iCa
- PTH
- PTHrp (PTH related peptide)
- iCa: high
- PTH: normal
- PTHrp: normal (AKA low)
- Elevated iCa and inappropriately normal PTH is consistent with HyperPTH
- Lack of PTHrp does not completely rule out neoplasia
PHP further diagnostics
- Abdominal radiographs, ultrasound, or CT
- Thoracic radiographs or CT
- Cervical ultrasound or CT
Abdominal radiographs, ultrasound, or CT of an animal with PHP findings (possibly)
- Nephroliths, cystic calculi
- stones are fairly common
Thoracic radiographs or CT of an animal with PHP
- Look for evidence of metastasis
Cervical ultrasound or CT of an animal with PHP
- A mass in the area of the thyroid glands supports PHP
- Parathyroids should be <3 mm but can be difficult to visualize
Treatment for PHP if severely hypercalcemic (e.g. iCa >2)
- Fluid therapy
- Diuretics
- Glucocorticoids
- Bisphosphonates
- Calcitonin
- Can do surgery of affected glands (would likely want to stabilize first)
- Radiofrequency heat ablation
- Ethanol ablation
Treatment for PHP if mild and not clinical
- Monitor
+/- Can do surgery of affected glands (would likely want to stabilize first)
+/- Radiofrequency heat ablation
+/- Ethanol ablation
Surgical management of PHP
- Normal parathyroid glands may be atrophied due to constant negative feedback from overactive parathyroid gland PTH production
- After surgery, hypocalcemia can occur until the glands recover
What should you start before and after surgery to remove a PTH producing tumor
- Start prophylactic calcitriol (vitamin D) therapy
- Start 1-2 days prior to surgery
- Slowly taper over 2-4 months by gradually increasing the time between doses
- Short term Ca2+ supplementation (Ca carbonate AKA tums) and taper slowly over 2-4 months
- Goal is to keep Ca2+ high enough tp prevent clinical signs (normal set point is also higher, so they can start showing clinical signs at a higher than normal set point)
What would you worry about if you did not treat primary hyperparathyroidism?
- If hypercalcemia is present long enough it can lead to renal failure
Hypoparathyroidism definition
- Cessation of parathyroid function
Classic lab characteristics of hypoparathyroidism
- Decrease in serum calcium and an increase in phosphorus
Decreased secretion of PTH effect on bone
- Reduced bone resorption of calcium and phosphorus
Decreased secretion of PTH effect on kidneys
- Decreased calcium, magnesium, and hydrogen ion reabsorption
- Increased phosphorus, sodium, potassium, and amino acid reabsorption by the kidneys
What are 4 potentials causes of HypoPTH?
- Suppressed secretion of PTH without destruction (e.g. trauma from surgery or other)
- Atrophy - sudden correction of chronic hypercalcemia (post-op parathyroidectomy for PHP)
- Iatrogenic - removal of parathyroid glands during removal of thyroid glands
- Idiopathic - destruction of parathyroid gland (Primary; suspected immune mediated destruction)
Differentials for hypocalcemia
- P = phosphate enemas
- E = eclampsia
- A = albumin decrease
- C = chronic renal disease
- E = ethylene glycol toxicity/acute kidney injury
- P = PTH deficiency
- A = Acute pancreatitis
- I = intestinal malabsorption
- N = nutritional (vit D deficiency)
and many more!!!
HypoPTH more common in cats or dogs?
- Dogs
Average age of HypoPTH
4.8 years
Sex predisposition in HypoPTH
- Females more common than males
HypoPTH Breeds
- Poodles
- Mini Schnauzers
- German Shepherds
- Labrador Retrievers
- Terriers
Timing of clinical disease in HypoPTH
- Signs often present suddenly
- True course of disease is gradual in onset
Two most common clinical signs of HypoPTH
- Seizures prior to diagnosis (Common
- 80%)
- Intense facial rubbing/biting or licking paws (Common - 60%)
Other clinical signs of HypoPTH
- Tetany/muscles spasms
- Tense/nervous
- Stiff/stilted gait
- Anorexia
- Lethargy/weakness
- Panting
- Vomiting/Diarrhea
- Cataracts
- Fever
- Growling
- Cardiac abnormalities
Changes on physical exam with HypoPTH
- Muscle fasiculations
- Seizures during exam
- Cardiac abnormalities in up to 40% (Tachyarrhythmias, muffled heart sounds, weak pulses)
- May not be contracting as well
Diagnosis of HypoPTH based on labwork
- Clinical signs = decreased serum Calcium
- Rule out other dfdx
- Increased serum Phosphorus
- Ionized calcium decreased
- PTH and calcitriol levels
PTH and Calcitriol levels in HypoPTH
- Parathyroid hormone low to low normal
- Decreased calcitriol
Duration of treatment for HypoPTH
- LIFELONG
Emergency therapy for hypocalcemia (HypoPTH)
- IV calcium gluconate
- Give SLOWLY (10-30 minutes)
- If given too quickly you can stop the heart
- Subcutaneous administration an option after tetany is controlled
- Use diluted 10% Ca Gluconate only
- Potential risk of inflammation or skin sloughing
Treatment for HypoPTH
- Calcitriol (oral or injectable)
- Generally lifelong
- Oral calcium
- Calcium carbonate - Tums
- Can usually be tapered down or stopped after stabilization of disease
Monitoring of HypoPTH
- Frequent rechecks of iCa if necessary
- Every animal responds differently to calcitriol and dose and frequency adjustments are often needed
Goal of HypoPTH therapy
- Low normal or slightly low calcium levels
- Avoid hypercalcemia due to risk of renal failure and other complications
