calcium_disorders-p.ppt...................

Mohsen Eledrisi, MD, FACP, FACE
Department of Internal Medicine
Hamad Medical Corporation
Doha, Qatar
Calcium disorders

Case 1
 A 55-year-old man follows for hypertension
 No complaints
 Valsartan/Amlodipine, Atorvastatin
 BP is controlled. Normal examination
 Serum cr, K normal, ALT normal
 Serum calcium 2.82 mmol (11.3 mg) [2.12-2.62 (8.5-10.5)]
 How to approach serum calcium?

Evaluation of high
serum calcium
 Repeat serum calcium
 Check PTH
 Adjust for low albumin per formula (some labs do)
Or do ionized calcium
 Biotin can falsely  PTH. So, stop for 2 days & retest
 Common causes:
– Primary hyperparathyroidism (commonest)
– Medications: vitamin D, calcium, HCTZ
– Malignancy, multiple myeloma

Evaluation of serum calcium
 Serum calcium binds to albumin
 Low albumin results in less bound calcium & falsely
low total serum calcium
 Adjustment should be done for low albumin
 Corrected calcium = (0.8 (Normal albumin - patient’s
☓
albumin) + patient’s serum Ca
 Some labs do the correction. There are calculators
 Or can measure ionized calcium (more expensive)

Causes of hypercalcemia
V
I
T
A
M
I
N
T
R
A
P
FHH:
Familial hypocalciuric
hypercalcemia
itamin intoxication (D, A)
mmobilization
hiazide, Teriparatide, Theophylline,
Tamoxifen, Lithium
ddison’s disease, Acromegaly
ilk-alkali syndrome ( supplemental Ca++)
nflammation/infection
(TB, sarcoidosis, fungal)
eoplasia (kidney, lung, breast, MM,
bone mets, lymphoma, leukemia..)
hyrotoxicosis
habdomyolsis (recovery stage)
IDS
arathyroidism (1ry
,3ry
)
Pheochromocytoma
Parenteral nutrition

Determining the cause of
high serum calcium
  (or high NL) PTH= 1ry
hyperparathyroidism
 No symptoms: usually 1ry
hyperparathyroidism
 Medications history
– Thiazides (HCTZ, chlorthalidone) & Lithium can  Ca++
, PTH
– Stop for 3 months then repeat labs
 If PTH is low normal or low, evaluate for non-PTH causes
 Severe high calcium with symptoms: think malignancy

Defining the severity
of hypercalcemia
 Mild:
 Serum calcium < 3 mmol (12 mg)
 Usually no symptoms
 Moderate:
 Serum calcium 3-3.49 mmol (12-14 mg)
 May have symptoms depending on level and rate of rise
 Severe:
 Serum calcium > 3.49 mmol (14 mg)
 Usually have severe symptoms

Manifestations of
hypercalcemia
 Depend on level of serum calcium & its progression
 Can be asymptomatic (usually with calcium <12 mg)
 Polyuria, polydipsia, anorexia, nausea, constipation
 Weakness, confusion, coma (with severe hypercalcemia)
Kidney involvement (causing AKI or/and CKD):
 Nephrolithiasis (kidney stones)
 Nephrocalcinosis (calcium deposition in kidneys)

high serum calcium
• PTHrp is high in hypercalcemia of malignancy (order if
the diagnosis is not clear)
• If no malignancy, look for other causes
• 1,25-(OH)2 vitamin D is high in granulomas (TB,
sarcoidosis), lymphoma
• 25-(OH) vitamin D is high with vitamin D intoxication
• If suspecting multiple myeloma, do SPEP & UPEP

Back to case 1
 A 55-year-old man follows for hypertension
 No complaints
 Valsartan/Amlodipine, Atorvastatin
 Serum cr, K normal, calcium 11.3 mg (normal: 8.5-10.5)
How to approach serum calcium?
Repeat calcium = 11.2 mg
PTH 75 (15-65 pg/mL)
What is your assessment?

Primary hyperparathyroidism
 High serum calcium with high (or normal) PTH level
 Most often caused by a single parathyroid adenoma
 Evaluation:
 Serum creatinine, eGFR, phosphorus
 25-hydroxyvitamin D
 24-hour urine calcium & creatinine excretion
 DXA scan (lumbar spine, hip, distal 1/3 radius)
 Renal imaging (X-ray, ultrasound or CT scan) to
detect stones
5th
International workshop. J Bone Miner Res 2022;37(11):2293

Indication for surgery in
primary hyperparathyroidism
 Option for all patients (symptomatic & asymptomatic)
 Surgery is recommended if any of the following:
– Serum calcium >1.0 mg (0.25 mmol) above upper limit of normal
– Osteoporosis (T score ≤ -2.5 on DXA) at any site
– Vertebral fracture (by radiograph, CT, MRI, or vertebral fracture assessment)
– eGFR <60 mL/min
– 24-hour urinary calcium [>250 mg/day (6.25 mmol/d) in women;
>300 mg/d (7.5 mmol/d) in men]
– Nephrolithiasis or nephrocalcinosis (by radiograph, ultrasound, or CT)
– Age < 50 years
5th

Imaging in primary
hyperparathyroidism
 Preoperative imaging is not recommended for
diagnostic purposes
 Preoperative imaging is recommended for those who
are going to have parathyroid surgery to locate the
abnormal parathyroid gland(s)
 Preoperative imaging modalities include high resolution
neck ultrasound, technetium-99 sestamibi scintigraphy,
and contrast-enhanced four-dimensional (4D)
computed tomography
5th

Follow up if no surgery
 Monitor the following:
• Serum calcium, 25-OH vitamin D every year
• Serum creatinine, eGFR every year
• DXA (3-site) every 1-2 years (as clinically indicated)
• Spine imaging if indicated (height loss or symptoms of
vertebral facture)
• Renal imaging (X-ray, U/S or CT), 24-hour urine calcium:
if clinically indicated (suspected kidney stones)
5th

When to recommend surgery in
patients who are monitored?
 Serum calcium consistently >1.0 mg (0.25 mmol) above
the upper limit of normal
 A low trauma fracture
 A kidney stone
 A significant reduction in BMD to a T-score ≤ -2.5 at
any site
 A significant reduction in eGFR:
(>3 mL/min per year over 1-2 years)
5th

Medical management of
primary hyperparathyroidism:
general measures
 This can be offered for patients who refuse surgery or
when there is a contraindication for surgery
 Deficiencies in vitamin D and dietary calcium worsen
hyperparathyroidism
 Adequate calcium diet:
• 800 mg/ day for women <50 years and men <70 years
• 1000 mg/ day for women >50 years and men >70 years
 Adequate vitamin D intake:
• Serum 25-hydroxyvitamin D >30 ng (75 nmol)
5th

Medical management of
primary hyperparathyroidism:
drug therapy
1) Cinacalcet:
- Used if serum calcium > 1 mg (0.25 mmol) above the
upper limit of normal
- Decreases serum calcium
- Decreases PTH
2) Bisphosphonate (e.g. alendronate) or Denosumab:
- If low BMD
5th

Normocalcemic
primary hyperparathyroidism
 Normal total adjusted serum calcium, normal
ionized calcium and high PTH on at least 2 tests
over 3-6 months
 Rule out causes of secondary hyperparathyroidism
(vitamin D deficiency, CKD, celiac disease, bariatric surgery,
 calcium intake, malabsorption by pancreatic insufficiency )
 No adequate studies to guide management
 Some physicians use the same indications for surgery
in hypercalcemic primary hyperparathyroidism
 Many will obtain localization study before surgery
5th

Familial hypocalciuric
hypercalcemia (FHH)
 A genetic condition due to mutations in the calcium-
sensing receptor gene leading to ↓ receptor activity
 Mildly high calcium with normal or mildly high PTH
 No symptoms, young (<30 y), family history of  Ca++
 Low urine Calcium:
- Calculate calcium-creatinine clearance (Ca/Cr Cl) ratio
[24-hour urine Ca x serum Cr] ÷ [serum Ca x 24-hour urine Cr]
♦ <0.01 with 24-hour urine <100 mg = highly likely FHH

Case 2
 A 65-year-old woman presents with nausea, vomiting
and confusion for 3 days
 Past history: DM, HTN
 Metformin, Lisinopril, Statin
 BP 110/66, pulse 112/min, normal temperature,
confused, systematic examination is normal
 Hb 9.2, creatinine 186 umol (2.1 mg), sodium 134,
potassium 4 mEq, calcium 3.24 mmol (13.0 mg)
 How would you approach?

Approach to severe
hypercalcemia
• Severe hypercalcemia:
– Severe symptoms
– Very high serum calcium [usually > 3.26 mmol (14 mg)]
– Commonly due to non-parathyroid cause
– Malignancy is the commonest
• Check PTH:
– High normal or high = primary hyperparathyroidism
– Low normal or low = Non-PTH causes

severe hypercalcemia
• Malignancy can be clear clinically
– Lung, breast, kidney, head & neck cancers, bone metastasis
– Multiple myeloma
• PTHrp is high in malignancy (order if diagnosis is not clear)
• If no malignancy, look for other causes
• 1,25-(OH)2 vitamin D is high in granulomas (TB, sarcoidosis), lympho
• 25-(OH) vitamin D is high with vitamin D intoxication
• If suspecting multiple myeloma, do SPEP & UPEP

Management of
1) IV Hydration:
 Patients are dehydrated
 IV normal saline
 Rate of IVF depends on patient’s age, presence of
cardiac or kidney disease
 If no evidence of edema, start 200 to 300 mL/hour
 Adjust rate to maintain urine output at 100-150 mL/hour
 Diuretics are not recommended

Management of
2) Calcitonin:
  Renal calcium excretion and  bone resorption
 IM or subcutaneous
 Nasal administration is not effective for hypercalcemia
 Starting dose: 4 units/kg every 8 hours
 For 24-48 hours
 No response after 48 hours (tachyphylaxis)
 Lowers serum calcium by 1 to 2 mg

Management of
3) Bisphosphonate:
 Usually the preferred agents
 Effect takes 2-4 days
 Given on presentation (with IVF and calcitonin)
 IV Zoledronic acid
 If not available, use Ibandronate or pamidronate (less effective)
4) Denosumab:
Use if severely low cr (eGFR<30) or if hypercalcemia
is not responsive to Bisphosphonate
Some centers use it as 1st
option
5) Dialysis

Management of
 Due to granulomatous disease (sarcoidosis,
TB), lymphoma)
–  1,25-dihydroxycholecalciferol (calcitriol) leads to 
intestinal calcium absorption
– Treatment: treat the underlying disease, glucocorticoids
– Glucocorticoids (as prednisone 20 to 40 mg/day)

Case 3
 A 45-year-old woman presents with muscle pain &
cramps, numbness over the hands for 3 months
 Thyroid surgery for “overactive thyroid” 6 months ago
Thyroxine 100 mcg qd
Normal BP, neck scar, thyroid is not palpable
 TSH 2.3, Serum cr, K normal, ALT normal
 Serum calcium 1.62 mmol (6.5 mg) [2.12-2.62 (8.5-10.5)]
 How would you approach serum calcium?

Approach to hypocalcemia
1) Repeat test
2) Check serum albumin
- Correct calcium if albumin is low
- Some labs do the correction. There are calculators
3) Can check ionized calcium, but expensive
4) Check PTH
5) Creatinine, phosphorus, magnesium, 25-OH vitamin D

Causes of hypocalcemia
 Post-surgical (thyroid, parathyroid surgery)
 Autoimmune hypoparathyroidism
– Can be isolated
– Or with chronic mucocutaneous candidiasis + adrenal
insufficiency (polyglandular syndrome type 1)
 Vitamin D deficiency
 Pseudohypoparathyroidism (PTH resistance)
 Acute or chronic kidney disease
 Acute pancreatitis
 Tumor lysis syndrome
 Hypomagnesemia, hyperphosphatemia
 Acute illness, burns, sepsis

Manifestations of hypocalcemia
 Perioral numbness
 Paresthesia of hands and feet
 Muscle cramps & pains
 Carpopedal spasm
 Laryngospasm
 Seizures (focal or generalized)
 Fatigue, irritability, anxiety, depression
 Some have no symptoms

Physical examination
• Trousseau's sign:
Induction of carpal spasm by inflation
of a sphygmomanometer above
systolic blood pressure for 3 minutes
• Chvostek's sign:
Contraction of the ipsilateral facial
muscles elicited by tapping the facial
nerve just anterior to the ear
(may occur in normal persons)

Evaluation of hypocalcemia
PTH Phosphorus Magnesium 25-OH vit D creatinine
Hypoparathyroidism   Normal Normal Normal
Pseudohypoparathyroidism   Normal Normal Normal
Hypomagnesemia Normal
or 
Normal  Normal Normal
Vitamin D deficiency   or normal Normal  Normal
Chronic kidney disease   Normal or  Normal 

Treatment of hypocalcemia
♦ Emergency management (IV calcium) if:
● Acute symptoms (carpopedal spasm, laryngospasm,
bronchospasm, seizures) or
● Serum calcium <1.75 mmol (7 mg)
 IV 1 gram calcium gluconate (10 ml, 10%) in 50 mL
5% dextrose or normal saline) over 10 minutes
 Can be repeated after 30-60 minutes
 Followed by IV infusion:
- 10 ampules of calcium gluconate in 1 liter D5 or NS
at rate of 50 ml/hour (can  to 100 ml/hour)
 Monitor serum calcium every 6 hours
 Treat underlying cause (hypoMg, vit D deficiency,…)

Treatment of hypocalcemia
♦ Further treatment:
 Start oral calcium
 Oral elemental calcium 1-2 grams/day
– Ca carbonate = 40% elemental calcium (1250 mg = 500 mg)
– Ca citrate = 21% elemental calcium
– Ca lactate = 13%
 If there is hypoparathyroidism:
 Vitamin D forms:
– Calcitriol 0.25 to 2 mcg /day (higher doses can be used)
– Or Alfacalcidiol 0.25 to 2 mcg/day (may need )
 Target calcium (in hypoparathyroidism):
- Low normal [2 to 2.12 mmol (8 to 8.5 mg)]

Easy Medicine ‫الزبدة‬
For talks & educational materials:
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