Hypercalcemia, Hyperparathyroidism and other Imbalances Flashcards
90% of cases of hypercalcemia are caused by what? 2
Hyperparathyroidism and malignancy
Etiologies of Hypercalcemia:
- Primary HPT causes what?
- Malignancy causes what?
Primary HPT*
1. Increase bone resorption
Usually small elevations in calcium
Malignancy*
2. Occurs w/ solid tumors and leukemia’s
Calcium values are high
In nonmetastatic solid tumors secretion of PTHrP
Milk-Alkali syndrome?
What does it cause?
High intake of milk or calcium carbonate
Metabolic alkalosis stimulates Ca2+ reabsorption
Medications that cause hypercalcemia?
6
- Lithium (increased secretion PTH)
- Thiazide diuretics (lower urinary Ca2+ excretion)
- Thyroid hormone
- Estrogens and progesterones
- Hypervitaminosis A
- Hypervitaminosis D (increase calcitriol)
Pseudohypercalcemia is what?
What causes this? 5
Elevation in total Ca2+, but not ionized, more bound calcium
- Thyrotoxicosis
- Pheochromocytoma
- Adrenal insufficiency
4, Islet cell tumors of the pancreas - Elevated platelet count
Manifestations of Hypercalcemia?
4
“bones, stones, abdominal pain and psychic overtones”
Bones: c/o bone pain and muscle weakness
Stones: nephrolithiasis
Abdominal pain: constipation, nausea, anorexia
Psychic: anxiety, depression and cognitive dysfunction
Clinical Presentation of Hypercalcemia:
Renal? 2
CV? 3
Musculoseletal? 1
CNS? 1
Renal:
Polydipsia
Polyuria
CV:
Bradycardia
Shortening of the QT interval
Varying arrhythmias
Muscle weakness
CNS depression
Work -Up for hypercalcemia:
First thing to do?
(what can make this a false elevation? 3)
Normal calcium level?
What do we get after the serum calcium level?
(normal?)
Elevated Ca2+ found on a asymptomatic patient what do we need to know?
How do we do the calcium correction for abnormal albumen levels?
What is usually slightly decreased in hypercalcemia?
What is increased?
(why?)
WHat do we have to rule out?
What is the last thing we check?
2
Serum Calcium level:
1. Artificially elevated if tourniquet left on too long or if
2. patient dehydrated
Can be artificially increased by
3. elevated albumin or decreased if albumin is decreased
Normal: 8.2-10.2 mg/dL
Ionized calcium:
50% of calcium in this form
Changed by blood pH**
Normal: 1.15-1.35 mg/dL
Need to know albumin!
Correction for abnormal albumen level: Corrected Ca = 7.6 + (0.8 x ( 4.5- alb))
For example measured values:
7.6mg/dL (Ca2+)
2.5g/dL (albumen)
Corrected Ca2+ = 7.6 + (0.8 x (4.5 -2.5)) = 9.2
Phosphate usually slightly decreased
ALP may be slightly increased (liver and bone are getting turned over)
R/O thyroid dysfunction
Check PTH level and if normal check PTHrP
How do we confirm elevated Ca2 levels?
Confirm elevated Ca2+ with two readings with albumin
When will a calcium be be low in a 24 hr urine sample?
- Milk -alkali syndrome
- Thiazide diuretic use
- Familial hypocalciuric hypercalcemia
Treatment of hypercalcemia?
Depends on etiology
Treating the underlying etiology will correct the hypercalcemia
How do we treat a hypercalcemic crisis?
3
1. Saline diuresis: Ca2+ > 14mg/dL Pt usually dehydrated Infuse 250-500 mL/hr of saline to rehydrate 2. Give IV synthetic calcitonin 3. Give IV bisphosphonates: Maximum effect 2-4 days Zoledronic acid or pamidronate
Etiologies of Primary Hyperparathyroidism (HPT)?
3
Parathyroid adenoma: 80%
Hyperplasia: 15%
Parathyroid carcinoma: less than 5%
s
s
Parathyroid Carcinoma
is rare. How does it present?
4
Presentation:
- Mean Ca2+ concentration: 14.6-15.9. Elevated
- Neck mass: 34-52%
- Bone disease: 34-73%
- Renal disease: 32-70 %
Two criteria diagnosing PT cancer
- Local invasion of contiguous structures
2. Lymph node or metastatic spread
What is the primary method of treatment for parathyroid cancer?
There is three outcome with this treatment. What are they?
- Surgery primary method of treatment
Chemo and radiation not very helpful
Three outcomes:
1/3 patients cured at surgery
1/3 recur and may be cured w/ reoperation
1/3 short, aggressive course
If not surgically treatable manage hypercalcemia
Presentation of Primary HPT
3
- Hypercalcemia (asymptomatic)
- PTH-mediated bone resorption:
- CV affects
HPT PTH-mediated bone resorption causes what?
2
- Decreased bone mineral density (BMD)
2. Increased risk of vertebral fractures (fractures you dont see on other ppl)
CV affects of HPT?
2
- HTN
2. Left ventricular hypertrophy/diastolic dysfunction
Secondary HPT
due to malignancy etiologies? 7
Workup?
Etiologies:
- multiple myeloma,
- lung,
- kidney,
- esophagus,
- head and neck,
- breast and skin
- bladder cancers
are some of the more common
Work-up: PTHrH
Chronic to advanced renal disease of HPT findings in the lab?
3
- hypocalcemia/hyperphosphatemia
- Cr/BUN elevated
- PTH increased
Workup for HPT
(whats the most important one?)
5
- Intact PTH: normal 10-50 pg/mL*****
- Serum Creatinine: assess renal function
- Bone-specific alkaline phosphate: assess bone turn-over
- calcitriol: vitamin D metabolites—suppressed in hypercalcemia: normal 1.5 pmol/L
- Bone density measurement (DEXA-scan)
Where is a DEXA-scan usually used to find fractures in HPT?
3
Used to measure bone density of the
- femoral neck,
- lumbar spine and
- wrist
Management of Primary HPT
1
Patients w/ sx or progressive disease: surgical treatment
General surgeons usually, although ENT also can do the surgery
Dont treat if they dont have symptoms
Surgery for PHPT:
What is really important before we do the surgery?
Three imaging studies we do?
Preoperative localization: (not to dx)
Use technetium-99m-sestamibi schintigraphy w/ SPECT imaging
Ultrasonography
CT scan or MRI
Used prior to minimally invasive parathyroidectomy (MIP)
Used if 1st surgery unsuccessful and need to do more extensive procedure or locate ectopic tissue
PHPT:
Before a MIP (minimally invasive parathyroidectom) what do we need to do?
What does this limit?
What do we check right after the surgery?
What are the postsurgical complications?
2
Must do preop imaging
Limits the operative field to localized 2-4 cm incision (drops super fast)
Intraoperative PTH assay (check the PTH 10 min later. goes down then successful)
Post-surgical complication: 1. hypocalcemia,
2. vocal cord paralysis**
PHPT Reoperation:
What do we determine first?
What do we do next before the surgery?
What is the reoperation surgery need to involve?
First determine correct diagnosis of PHPT
Then may need to use localizing modalities again—aberrant location
Need to do bilateral neck exploration to fine causative gland(s)
PHPT Surgery Indications in Asx Pts?
4
- Serum Ca2+: 1.0 mg/dl greater then normal
- Creatinine clearance less than 60
- Bone density that is 2.5 standard deviations from the peak bone mass or w/ a fragility fracture
- Age less than 50 YO
Who would we not treat with surgery for PHPT?
4
How could we manage them?
5
1, Patients with a mild increase in Ca2+
- Patients who are unfit for surgery
- Patients who refuse surgery
- Patients who are asymptomatic
- Avoid meds that can make hypercalcemia worse
- Low calcium diet less than 800-100mg/day
- exercise
- adequate hydration
- adequate vit D
PHPT Management of Asx Pts medications?
3
- Bisphosphonates
- Calcimimetic: (cinacalcet)
- Dialysis a last resort
Bisphosphonates are given in what dosage form?
What are the different Bisphosphonates drugs? 2
Side effects? 2
IV—effects last for a week
Meds: Pamidronate (Aredia) and Zoledronate (Zometa)
Renal problems and jaw necrosis
Calcimimetic: (cinacalcet) MOA?
What pts is it used in? 2
Activates the calcium-sensing receptor in the PT gland inhibiting PTH secretion
Used in pts w/ parathyroid carcinoma or those w/ secondary hyperparathyroidism
Bisphosphonates SE
7
- Flu-like symptoms
- Ocular inflammation (uveitis)
- Hypocalcemia
- Hypophosphatemia
- Impaired renal function (nephrotic syndrome)
- Osteonecrosis of the jaw (more common in pts w/ cancer)
- Nephrotoxic
Hypercalcemia of Malignancy
how do we treat?
3
What about pts in renal failure?
Treat underlying malignancy
- Use bisphosphonates
- Calcitonin:
SQ or IM - Rapid antiresorptive agent
Dialysis in Ca2+ free bath for patients in renal failure (secondary HPT)
Etiologies of Hypocalcemia
3
- Hypoparathyroidism
- Hypovitaminosis D
- Hyperphosphatemia
What is hypocalcemia caused by HPT usually from?
2
- Usually from surgery for thyroid disease or for surgery for hyperparathyroidism
- Autoimmune
Hypocalcemia caused bby Hyperphosphatemia is usually from what?
usually secondary to renal failure
Hypocalcemia symptoms:
Mild? 4
Severe? 6
Mild:
- Circumoral parethesias/hyperventilation
- Myalgias, muscle cramps
- Fatigue
- hyperirritability, anxiety
Severe:
- Tetany/laryngospasm
- Seizures 3. Papilledema
- Myopathy 5. Hypotension
- Prolonged QT interval on EKG
Trousseau’s Sign
indicates what?
hypocalcemia
weird spasm with BP cuff on
Work up for hypocalcemia?
4
- Decreased serum Ca2+ (what do you need to know with this?) Albumin!
- Increased serum phosphate
- 1,25(OH)2D (vit 2D) levels can be low
- Usually high PTH levels (no neg feedback with calcium)
- Treatment for hypocalcemia?
- What kind of Calcium?
- What can we add and why would we add it?
(2) - What do we want to watch for?
- Vitamin D supplement + Calcium
- (600-1200 mg elemental calcium a day—divided doses)
- -Can add thiazide diuretic (Why- hangs on to Ca in kidneys)
- -Calcitriol can be given as increases levels more rapidly
Watch Ca2+ levels carefully as can get hypercalcemia
Hyperphosphatemia
Etiologies:
6
- Marked tissue breakdown
- Can induce hypocalcemia because of calcium-phosphate precipitation in tissue
- Lactic acidosis/DKA
- Renal failure (biggy!)
- Hypoparathyroidism (what else do these patients have?) (hypocalcemia)
- Vitamin D toxicity
Work-up for Hyperphosphatemia?
(most important?)
6
- Serum posphate:
Measured on whole blood
Level usually the inverse of calcium when abnormal values
Normal: 2.5-4.5 mg/dL - CMP
- Check renal function
- Glucose
- ABG for pH
- Urinalysis
Hyperphosphatemia treatment:
Acute? 2
Chronic? 2
Acute:
- Saline infusion to increase phosphate excretion, but can lower Ca2+ more
- Hemodialysis
Chronic:
- Low phosphate diet—900mg a day
- Phosphate binders
Hypophosphatemia
etiologies?
Etiologies:
Redistribution of phosphate from extracellular fluid into cells
Administration of insulin in treating DKA
Refeeding malnourished patients such as alcoholics and those with anorexia nervosa
Acute respiratory alkalosis
Decreased intestinal absorption
Increased urinary excretion
Hypophosphatemia is caused by what two processes?
2
- Decreased intestinal absorption
2. Increased urinary excretion
Why will there be decreased intestinal absorption in hypophosphatemia? 3
- Poor intake combined w/ chronic diarrhea or steatorrhea
- Vitamin D deficiency
- Antacids w/ aluminum or magnesium
Why will there be increased urinary excretion in hypophosphatemia? 3
- Primary and secondary hyperparathyroidism
- Primary renal phosphate wasting (rare)
- Osmotic diuresis (usually secondary to glucosuria)
Hypophosphatemia signs and symtpoms?
5
CNS CV MS Lungs Metabolic
Hypophosphatemia CNS signs?3
Hypophosphatemia CV signs?1
Hypophosphatemia MS signs? 3
Hypophosphatemia Respiratory signs?
Hypophosphatemia metabolic signs? 1
CNS
- paresthesia’s,
- irritability,
- can progress to seizures and coma
CV: Decreased contractility may lead to CHF
MS:
- proximal myopathy,
- dysphagia,
- may progress to rhabdomyalysis
Lungs:
1. decreased ventilation
Heme:
Releases PH04 from bone and with it Ca2+ resulting in hypercalcemia
Work up for Hypophosphatemia? 3
Whats very important?
Describe when this one specifically is high (2) or low (3).
- Serum phosphate level
- CMP
- Measure 24 urine phosphate excretion*****
Low:
DKA (diabetic ketoacidosis), refeeding
Intestinal malabsorption
High:
Hyperparathyroidism
Renal tubular defect
Treatment
of Hypophosphatemia:
If they have DKA?
If they have a phosphate less than 2?
If they have a phopshate less than 1 and are symptomatic?
With DKA the phosphate will correct on it’s own
If the phosphate is less than 2.0 and the patient is asx use oral phosphate
If the patient is less than 1.0 and symptomatic use IV replacement
Vitamin D Toxicity usually due to those taking what?
Usually due to those taking “megadose’s” of Vitamin D
What kind of vitamin is vitamin D?
Where is excess of it stored? 2
fat soluble vitamin and
excess is stored in the liver and adipose tissue
Main presenting symtpoms?
Mild? 4
Extreme? 3
- Hypercalcemia
- hypophospatemia
- Confusion,
- anorexia and vomiting
Extreme:
- muscle weakness and
- bone demineralization
- Peeing out excess calcium and get dehydrated
Vitamin D Toxicity
Work-up: 2
Treatment:
Not severe? 1
Severe? 2
Vitamin D level
Hypercalcemia work-up
If not severe: IV saline
If more severe:
Glucocorticosteroids
IV Bisphophonates
Vitamin D Deficiency etiologies?
7
- Elderly
- Winter months/housebound
- Northern climate
- Chronic renal disease
- GI disease—malabsorption
- Liver failure
- Drugs
GI disease—malabsorption Vit D deficiencies are caused by what?
3
- Celiac
- Gastric Bypass patients
- Inflammatory Bowel disease
Drugs than cause Vit D deficiency?
6
- phenytoin
- phenobarbitol,
- cararbomazepine,
- isoniazid,
- rifampin, and
- prolonged glucocorticoid
Vitamin D Deficiency presentation:
- Initially what labs are reduced? 2
- What does this lead to?
- With persistent deficiency what can happen?
- What does this lead to?
- And this results in?
- Initially reduced absorption of Ca2+ and PO4-
- Leading to hypophophotemia > hypocalcemia
- Hypocalcemia that results in hyperparathyroidism
- This leads to phosphoturia
- Which results in demineralization of bone
Without treatment how will Vitamin D Deficiency manifest? 2
osteomalacia/osteoporosis (adults) and rickets (children)
Vitamin D Deficiency symtpoms?
3
- Bone pain
- Muscle weakness—difficulty walking
- Fractures
Vitamin D Deficiency work up?
7
- Vitamin D level
- Serum Ca2+
- Phosphorus
- PTH
- Alkaline Phosphatase
- Electrolytes
- BUN and creatinine
Vitamin D Deficiency Tx:
What does the dosing depend on?
What kind of supplement is recommended?
For those will malabsorption issues what should we do?
2
Depending on how low the level of serum vitamin D determines the dosing of supplement
Oral replacement of Vitamin D and not it’s metabolites is recommended
For those w/ malabsorption sometime the metabolites are given or sun is “prescribed”
