Hypercalcemia Flashcards
How do you correct calcium levels when patients have hypoalbuminemia?
Corrected Ca = Measured Ca + 0.02 x (40 - albumin)
What are normal calcium and albumin levels in a patient?
Normal range: 2.15 (KTPH: 2.2) to 2.58
Normal albumin = 40
What are the symptoms of hypercalcemia? (Bones, stones, groans, moans, thrones)
Bone: Bone pain
Stones
- Renal Stones
- NOT Gallstones
Groans: Abdominal pain, due to
- Urinary Colic (stones)
- Constipation
- Peptic Ulcer
- Pancreatitis
Moans: i.e. psychiatric overtones
- Altered Mental State
- Confusion
- Psychosis
- Seizures
Thrones i.e. toilet seat:
- Nephrogenic DI: Ca induced urinary salt wasting (polyuria, polydipsia)
- Nausea & Vomiting –> risk of severe dehydration
Others
- Vomiting
- Anorexia, LOW
- Tiredness
- Weakness
- Hypertension
What are the ECG features of hypercalcemia?
The main ECG abnormality seen with hypercalcaemia is shortening of the QT interval
In severe hypercalcaemia, Osborn waves (J waves) may be seen
Ventricular irritability and VF arrest has been reported with extreme hypercalcaemia
What are the CVS symptoms of hypercalcemia?
- hypertension
- arrhythmia
- short QTC
- deposition of Ca on valves, coronary arteries, myocardial fibres
What are the GI symptoms of hypercalcemia?
- constipation
- anorexia
- nausea
- vomiting (groats)
- PUD
- pancreatitis
What are the renal symptoms of hypercalcemia?
- polyuria (nephrogenic DI)
- polydipsia
- nephrolithiasis (stones)
- renal failure (irreversible)
What are the msk symptoms of hypercalcemia?
- weakness
- bone pain
What are the psychiatric symptoms of hypercalcemia?
> 3 mmol/L
- increased alertness
- anxiety
- depression
- cognitive dysfunction
- organic brain syndromes
> 4 mml/L
- psychosis (moans)
What are the neurologic symptoms of hypercalcemia?
- hypotonia
- hyporeflexia
- myopathy
- paresis
A patient has hypercalcemia. PTH >2.2. Phosphate is low. High Urine Ca >200mg/24hrs What are the differentials?
Primary hyperparathyroidism caused by MEN 1 or 2A
- MEN 1: parathyroid, pancreatic, pituitary
- Men 2a: phaeo, medullary thyroid Ca, parathyroid
A patient has hypercalcemia. PTH >2.2. Phosphate is high. ↑Cr. What are the differentials?
Tertiary PTH (CKD related)
Primary PTH with renal failure
What are cancers that mets to the bone?
- thyroid
- lung
- breast
- kidneys
- ovaries
- prostate
What are the investigations to be performed for hyperca?
Initial: Ca / Pi / Mg, PTH
Subsequently (for specific etiology)
- FBC, Renal panel, Albumin, Alkaline phosphatase (osteolytic lesion)
- Parathyroid USS 🡪 for enlarged parathyroids
- Chest XR: Sarcoidosis, lymphoma (causes mediastinal invasion and enlargement)
- Bone scan: Metastasis to bone
- 24h urine Ca excretion, or check urine Ca/Cr ratio: FHH
- Urine protein electrophoresis: for MM
- TFT: hyperthyroidism
What is the mechanism of CKD causing 2’ hyperPTH?
CKD causing retention of Po4.
CKD reducing kidney’s ability to convert 25hydroxy Vit D to 1,25hydroxy, causing decreased calcium levels.
Increased Po4 and decreased calcium levels, causing increase iPTH levels.
What is the mechanism of CKD causing 3’ hyperPTH?
State of excessive secretion of parathyroid hormone (PTH) after a long period of secondary hyperparathyroidism resulting in a high blood calcium level.
It reflects development of autonomous (unregulated) parathyroid function following a period of persistent parathyroid stimulation
A patient has hypercalcemia. PTH >2.2. Phosphate is normal. Low Urine Ca <200mg/24hrs. What are the differentials?
Familial Hypocalciuric HyperCa.
A patient has hypercalcemia. PTH <2.2. Phosphate is low. What are the differentials?
Malignancy (Paraneoplastic syndrome (PTHrp is produced instead, often seen in SCC of lung and RCC)
Osteolytic lesions- anything with mets to bones (lung, breast Ca etc)/ multiple myeloma
A patient has hypercalcemia. PTH <2.2. Phosphate is high. ↑1,25 Vit D. What are the differentials?
Sarcoidosis, lymphoma (cause increae in 1 alpha hydroxylase –> produce 1,25 vitamin D)
A patient has hypercalcemia. PTH <2.2. Phosphate is high. ↑25 Vit D. What are the differentials?
Vitamin D toxicity
Medications (thiazide, lithium)
Bone lysis
- hyperthyroid: increased bone turn over
- pheochromocytoma: increased bone turnover
- hypercortisolism- inhibits osteoclasts
What are the imaging options to confirm primary hyperthyroid?
- Sestamibi Scan (contrast uptake scan)
- US neck for mass
- MRI neck for mass
- 4D CT scan for mass
GOLD STANDARD = intra-op – based on the surgeon’s clinical judgement (can only be assessed upon examination of the parathyroid size during surgery)
Why is there a need to hydrate patients with hyperCa?
Why the need to hydrate?
- Hypercalcemia cause volume depletion by vomiting and hypercalcemia induced urinary salt wasting
- Hypovolemia exacerbates hypercalcemia by impairing the renal clearance of calcium
MOA of hydration
- Helps dilute serum Ca
- Helps improve renal function – able to give other drugs
Hydration alone is helpful in improving HyperCa 😊 – keep hydrating until HyperCa is corrected!
What is the initial management of HyperCa when renal function is poor?
1) IV hydration aggressively: 0.9% NS >3L a day
- Give at initial rate of 200-300ml/hour then adjust to maintain a urine output at 100-150ml/hr
- Also take into account severity of hypercalcemia, age of patient, co-morbidities like cardiac or renal disease
2) Calcitonin
- Increase renal calcium excretion
- Decrease bone resorption via interference with osteoclast function (1)
- IM or SQ 4 units/kg 12 hourly (max 6-8 units every 6H)
- IV 10 units per kg over 6 hours in 500ml 0.9% NS
What are the disadvantages of calcitonin?
Tachyphylaxis
- Works for 2 days then won’t work anymore (efficacy decreases with use until it drops to 0)
- Aims to improve Ca and renal function by the end of tachyphylaxis 🡪 able to use other drugs
Side effects: Hypersensitivity syndrome, hyperglycemia, neutrophilia, adrenal suppression, psychosis
What is the later treatment of hyperCa when renal function is recovered?
Bisphosphonates
- IV zolendronic acid or pamidronate
- MOA: Inhibit calcium release by inhibiting osteoclasts
- Caution should be exercised in renal impairment, and both pamidronate and zolendronate are relatively contraindicated if the GFR is <30ml/min/1.73m2
Glucocorticoids
- Useful in cases of hypercalcemia resulting from increased exogenous (ie Vit D toxicity) or endogenous 1,25-dihydroxyvitamin D ( ie granulomatous or lymphoproliferative disorders) due to increased metabolism of vitamin D in the context of glucocorticoid therapy.
- Prednisolone 40-60mg once daily
- IV hydrocortisone 100-300mg/day
Other options
- Denosumab: rankL inhibitor
- Furosemide (Ca wasting diuretic) with Fluid infusion
- Calcium free haemodialysis: Only for refractory HyperCa, Indicated for CCF, kidney injury etc.
What are the disadvantages of bisphophonates?
Maximum effect in 2-4 days (drop in Ca is SLOW! Takes ~2days to kick in) – hence start early
Hence the most immediate treatment method is via Calcitonin and Hydration!
Once HyperCa emergency has subsided, we can:
Treat underlying cause
- Lymphoma / Sarcoid: ___________
- Bony Mets: _____________
- MM: __________
- PTHrP: ______________
Consider Parathyroidectomy: watch out for transient HypoPTH due to other PTH glands being “slow to wake” 🡪 need to give __________(since PTH is used to produce Vit D)
If ESRF: Provide ____________
IV Hydrocortisone
IV Steroids + RadioTx +/- Surgical Decompression
ChemoTx +/- ASCT;
Resection of tumor
Ca & Calcitriol ;
Pi Binders to lower Pi levels
What are the differentials of parathyroid hormone dependent hypercalcemia?
- Primary HPT
- Tertiary HPT
- FHH (Familial hypocalciuric hypercalcemia)
- Lithium-associated hypercalcemia
- Antagonistic autoantibodies to the Calcium sensing receptor
What are the differentials for parathyroid hormone independent hypercalcemia?
Neoplasms: PTHrP dept (lung, renal cell, pancreas, esophageus), humoral hypercalcemia of malignancy (HMM) (due to PTHrp oversecretion), ectopic Vit D (lymphoma, leukaemia). Local osteolytic disease (including metastases)
Excess Vit D action: Granulomatous disease (Sarcoidosis, Wegener’s granulomatosis, TB, histoplasmosis, Candidiasis, Leprosy), Ingestion of excess Vit D or Vit D analogues
Endocrine: Thyrotoxicosis,
Adrenal Insufficiency, phaechromcocytoma
Renal Failure: ARF, CRF with aplastic bone disease
Immobilisation
Drugs: Vit A intoxication, Milk-alkali syndrome, Thiazide diuretics, Theophylline, Lithium, Foscarnet
How does malignancy cause hypercalcemia?
1) Local osteolytic hypercalcemia
2) Humoral hypercalcemia of malignancy (due to oversecretion of PTH related protein (90%), TGF alpha, TNF, Various cytokines and interleukins)
3) Increased 1 alpha hydroxylase activity (Some lymphomas express 1 alpha hydroxylase activity that converts 25 hydroxyvitamin D to 1,25-dihydroxyvitamin D, which then stimulates increased intestinal calcium absorption and bone resorption
