Hypercalcemia

Question 1

How do you correct calcium levels when patients have hypoalbuminemia?

Answer 1

Corrected Ca = Measured Ca + 0.02 x (40 - albumin)

Question 2

What are normal calcium and albumin levels in a patient?

Answer 2

Normal range: 2.15 (KTPH: 2.2) to 2.58

Normal albumin = 40

Question 3

What are the symptoms of hypercalcemia? (Bones, stones, groans, moans, thrones)

Answer 3

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

Question 4

What are the ECG features of hypercalcemia?

Answer 4

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

Question 5

What are the CVS symptoms of hypercalcemia?

Answer 5

• hypertension
• arrhythmia
• short QTC
• deposition of Ca on valves, coronary arteries, myocardial fibres

Question 6

What are the GI symptoms of hypercalcemia?

Answer 6

• constipation
• anorexia
• nausea
• vomiting (groats)
• PUD
• pancreatitis

Question 7

What are the renal symptoms of hypercalcemia?

Answer 7

• polyuria (nephrogenic DI)
• polydipsia
• nephrolithiasis (stones)
• renal failure (irreversible)

Question 8

What are the msk symptoms of hypercalcemia?

Answer 8

• weakness

- bone pain

Question 9

What are the psychiatric symptoms of hypercalcemia?

Answer 9

> 3 mmol/L

• increased alertness
• anxiety
• depression
• cognitive dysfunction
• organic brain syndromes

> 4 mml/L
- psychosis (moans)

Question 10

What are the neurologic symptoms of hypercalcemia?

Answer 10

• hypotonia
• hyporeflexia
• myopathy
• paresis

Question 11

A patient has hypercalcemia. PTH >2.2. Phosphate is low. High Urine Ca >200mg/24hrs What are the differentials?

Answer 11

Primary hyperparathyroidism caused by MEN 1 or 2A

• MEN 1: parathyroid, pancreatic, pituitary
• Men 2a: phaeo, medullary thyroid Ca, parathyroid

Question 12

A patient has hypercalcemia. PTH >2.2. Phosphate is high. ↑Cr. What are the differentials?

Answer 12

Tertiary PTH (CKD related)

Primary PTH with renal failure

Question 13

What are cancers that mets to the bone?

Answer 13

• thyroid
• lung
• breast
• kidneys
• ovaries
• prostate

Question 14

What are the investigations to be performed for hyperca?

Answer 14

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

Question 15

What is the mechanism of CKD causing 2’ hyperPTH?

Answer 15

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.

Question 16

What is the mechanism of CKD causing 3’ hyperPTH?

Answer 16

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

Question 17

A patient has hypercalcemia. PTH >2.2. Phosphate is normal. Low Urine Ca <200mg/24hrs. What are the differentials?

Answer 17

Familial Hypocalciuric HyperCa.

Question 18

A patient has hypercalcemia. PTH <2.2. Phosphate is low. What are the differentials?

Answer 18

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

Question 19

A patient has hypercalcemia. PTH <2.2. Phosphate is high. ↑1,25 Vit D. What are the differentials?

Answer 19

Sarcoidosis, lymphoma (cause increae in 1 alpha hydroxylase –> produce 1,25 vitamin D)

Question 20

A patient has hypercalcemia. PTH <2.2. Phosphate is high. ↑25 Vit D. What are the differentials?

Answer 20

Vitamin D toxicity

Medications (thiazide, lithium)

Bone lysis

• hyperthyroid: increased bone turn over
• pheochromocytoma: increased bone turnover
• hypercortisolism- inhibits osteoclasts

Question 21

What are the imaging options to confirm primary hyperthyroid?

Answer 21

• 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)

Question 22

Why is there a need to hydrate patients with hyperCa?

Answer 22

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!

Question 23

What is the initial management of HyperCa when renal function is poor?

Answer 23

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

Question 24

What are the disadvantages of calcitonin?

Answer 24

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

Question 25

What is the later treatment of hyperCa when renal function is recovered?

Answer 25

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.

Question 26

What are the disadvantages of bisphophonates?

Answer 26

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!

Question 27

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 ____________

Answer 27

IV Hydrocortisone IV Steroids + RadioTx +/- Surgical Decompression ChemoTx +/- ASCT; Resection of tumor Ca & Calcitriol ; Pi Binders to lower Pi levels

Question 28

What are the differentials of parathyroid hormone dependent hypercalcemia?

Answer 28

- Primary HPT - Tertiary HPT - FHH (Familial hypocalciuric hypercalcemia) - Lithium-associated hypercalcemia - Antagonistic autoantibodies to the Calcium sensing receptor

Question 29

What are the differentials for parathyroid hormone independent hypercalcemia?

Answer 29

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

Question 30

How does malignancy cause hypercalcemia?

Answer 30

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