Presented BY Mr. Pradeepsingh B Asst. Professor & HOD of Medical Surgical Nursing

1. 1

2. • Commonly encountered in Practice
• Diagnosis often is made incidentally
• The most common causes are primary
hyperparathyroidism and malignancy
• Diagnostic work-up includes measurement
of serum calcium, intact parathyroid
hormone (I-PTH), h/o any medications
• Hypercalcemic crisis is a life-threatening
emergency
2

3. • Most often asymptomatic – Incidental Dx
• Mild Hypercalcemia is asymptomatic
• Most important cause is hyper parathyroid
• DD is needed to decide the treatment
• Optimal step by step evaluation is a must.
3

4. • 98% of the body calcium is in the skeleton
• Only 2% is circulation and only half of this
is free calcium (ionized Ca++)
• This only is physiologically active
• The reminder 1% is bound to proteins
• Direct measurement of free Calcium ??
4

5. 5
Parathyroid Hormone
1,25 DHC or Vitamin D3
Calcitonin

6. 6
 Bone Resorption
 Intestinal Absorption
 Renal Excretion

7. (1,000 mg/day)
7

8. Hormone Effect Bone Gut Kidney
PTH  Ca  Po4
Increases
Osteoclasts
Indirect
via Vit. D
Ca reab
Po4 exr.
Vitamin D3  Ca  Po4
No direct
action
 Ca  Po4
absorption
No direct
effect
Calcitonin  Ca  Po4
Inhibits
Osteoclasts
No direct
effect
Ca & Po4
excretion
8

9. Corrected total calcium (mg%) =
[(Measured total calcium mg%) +
{(4.4 - measured albumin g%) x 0.8}]
Example:
[12.0 + {(4.4 – 2.4) x 0.8}] =
[ 12.0 + (2 x 0.8)] = 12.0 + 1.6 = 13.6
mg%
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10. Calcitriol (Active)
Supplements
Vitamin D 2
10

11. Second hydroxylation in the Kidney at first position
1,25 dihydroxy Cholecalciferol Active Vitamin D (Calcitriol)
Successive hydroxylations of Cholecalciferol
25 hydroxylation in the Liver 25 hydroxy Cholecalciferol
Vitamin D is a steroid hormone
From dietary sources Action of Sunlight on skin
11

12. PTH
• 4 PT glands
• 84 AA
hormone
• Low Ca
stimulates it
Calcitriol (D)
• Active bone
formation
• Main effect is
on the Gut
• PTH  Vit. D
Calcitonin
• Para follicular
C of Thyroid
• 34 AA hormone
• On Kidney
12

13. 13
Critical - > 14 mg %
Moderate - 12 to 14 mg %
Mild – 10.4 to 11.9 mg %
Normal – 8.5 to 10.3 mg %

14. 14
Ca++
PTH
PTHrP Calcitriol
 Ca
at GIT

15.  Ca++
PTH
Vitamin D
Malignancy
Medicines
Endocrine
Genetic
15

16. • More than 90 percent of hypercalcemia cases are
Primary hyperparathyroidism and malignancy
• These conditions must be differentiated early
to provide optimal treatment & accurate prognosis
• Humoral hypercalcemia of malignancy implies a
very limited life expectancy — only a matter of
weeks
• Primary hyperparathyroidism has a benign course.
16

17. • Primary hyperparathyroidism
• Sporadic, familial, associated with
Multiple Endocrine Neoplasia (MEN I or II)
• Tertiary hyperparathyroidism
• Associated with chronic renal failure
• PTH  due to Vitamin D deficiency
17

18. • Vitamin D intoxication
• Iatrogenic Vitamin D injections
• Usually 25-hydroxyvitamin D2 in
over-the-counter supplements
• Granulomatous disease –
Sarcoidosis, Berylliosis, Tuberculosis
• Hodgkin’s lymphoma
18

19. • Humoral hypercalcemia of malignancy
(mediated by PTHrP) – common cause
• Solid tumors, especially lung, head and
neck squamous cancers
• Renal Cell Carcinoma (RCC)
• Local osteolysis (mediated by cytokines)
• Multiple Myeloma
• Breast cancer
19

20. • Thiazide diuretics (usually mild) - common
• Lithium for depressive illnesses
• Milk-alkali syndrome (calcium + antacids)
• Vitamin A intoxication (including
analogs used to treat acne)
20

21. • Hyperthyroidism
• Adrenal insufficiency
• Acromegaly
• Pheochromocytoma
21

22. • Familial hypocalciuric hypercalcemia (FHH)
mutated calcium-sensing receptor gene
• Immobilization, with high bone turnover
(e.g., Paget’s disease, bedridden child)
• Recovery phase of Rhabdomyolysis
22

23. • CNS
• GIT
• SKELETON
• KIDNEY
STONES BONES
GROANS
MOANS
23

24. Renal “stones”
• Nephrolithiasis
• Nephrogenic Diabetes Insipidus
• Dehydration
• Nephrocalcinosis
24

25. Skeleton “bones”
• Bone pains
• Arthritis
• Osteoporosis
• Osteitis fibrosa cystica in HPTH
25

26. Abdominal “Moans”
• Nausea, vomiting
• Severe anorexia, weight loss
• Constipation (not relieved by Rx.)
• Abdominal pain (vague and diffuse)
• Pancreatitis
• Peptic ulcer disease
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27. Psychological “Groans”
• Impaired concentration
• Impaired memory, Depression
• Confusion, stupor, coma
• Lethargy and severe fatigue
• Extreme muscle weakness
• Corneal calcification (band keratopathy)
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28. Cardiovascular
• Hypertension, Increased risk of CHD
• ECG changes of shortened QT interval, PR
prolonged, QRS widened, ST ,
Bradycardia
• Cardiac arrhythmias; Vascular calcification
Others
• Itching (Generalized Pruritus)
• Keratitis, conjunctivitis 28

29. 29
? Suspect
 Calcium
Serum
Calcium
8.5 to 10.3
> 10.3 mg %
< 8.0 mg %
Hypocalcemia
Normal calcium

30. Medications
> 10.3 mg% I-PTH
High/Normal Pri PTH
Suppressed
Vit D Toxicity
Milk Alkali
Cancers/
Lymphoma
Suppressed PTHrP
30

31. PTHrP
Low or
Normal
Low or
Normal
1, 25 Vit. D
If Low
Cancer
If High
Lymphoma
High
24 hr. urine
calcium
Low – FHH
N or 
Sestamibi
31
Endocrine

32. 32

33. 33
• Increased screening for serum Ca++ and
• Wider availability of I-PTH assay
• 80% of cases single parathyroid adenoma
• Usually benign adenoma or hyperplasia
• Rarely parathyroid cancer
• High PTH in the setting of hypercalcemia
• Slowly progressive – Sestamibi N-scan
• 25% require surgery – RLN paralysis

34. 34
64 yrs male - “hyper parathyroid storm”
with a serum calcium level of 16.4 mg%

35. • Serum calcium level > 12 mg % at any time
• Episodes of hyper parathyroid crisis
• Marked hypercalciuria (urinary Ca++ > 400 mg /day)
• Nephrolithiasis; Impaired renal function
• Osteitis fibrosa cystica – Thinning of cortical bone
• Reduced bone density by DEXA scan (Z score < 2)
• Classic neuromuscular symptoms, Proximal muscle
weakness and atrophy, Hyper reflexia and ataxia
• Age younger than 50 years
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36. 36
• 25 OH - Vitamin D2 is the supplemental Vit D
• Level of 25 OH – Vitamin D3 is to be measured
• Macrophages in the granulomas, lymphomas
cause extra renal conversion of 25 OH form to
the1,25 hydroxy derivative –the active Calcitriol
• PTH levels are suppressed; Calcitriol levels 
• Stop the offending use of Vitamin D
• Glucocorticoids – for over one month or more
• Manage hypercalcemia vigorously

37. 37
• Most commonly mediated by systemic PTHrP
• Humoral Hypercalcemia of malignancy
• PTHrP mimics the bone & renal effects of PTH
• Normal Calcitriol and suppressed PTH levels
• Excessive bone lysis due to primary or bone
secondaries can cause hypercalcemia
• MM and metastatic Br Ca present in this way.
• In Osteolytic hypercalcemia, SAP is markedly 
• Hodgkin’s lymphoma –  production of Calcitriol

38. • Thiazide diuretics increase renal calcium
resorption and cause mild hypercalcemia
• Resolves after discontinuing the drug
• Thiazide unmasks hyperparathyroidism
• Milk–alkali syndrome – Ca + Antacids
• Lithium –  the set point for PTH 
• Excess Vitamin A -  bone resorption and
causes hypercalcemia.
38

39. • FHH – Familial Hypocalciuric Hypercalcemia
• AD – 100% penetrance – Ca-R gene mutation
• Moderate hypercalcemia with normal/  PTH
• 24 hour urinary calcium is very low
• No benefit from parathyroidectomy
• High bone turnover in Paget’s disease or
prolonged immobilization
• Recovery phase of Rhabdomyolysis
39

40. • Ca <12 but > 10.3 mg% – no appreciable
clinical benefit – they need evaluation
• Any patient with Serum Ca > 12 mg%
should be aggressively treated
• Ca > 14 mg% is Hypercalcemic crisis
• Always correct the Ca value for Sr
Albumin
40

41. I.V. Saline
Hydration
& Diuresis
Gluco-
Corticoids
Bisphos-
phonates
Calcitonin
I.M/S.C.
41

42. • Vigorous I.V. Nacl Diuresis – N Saline
• Adequate hydration – urine out put must be
maintained 200 ml/hour = 5 L /day
• The safest and most effective treatment of
Hypercalcemic crisis is saline rehydration
• Once the urine out put is maintained – give I.V.
Furosemide – a loop diuretic in low doses of 10
to 20 mg
• ERT - might be beneficial in PMW – new RCT
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43. • In severe hypercalcemia refractory to
saline diuresis
• Calcitonin (Zycalcit, Miacalcin) 6 -8 U/kg
IM/SC (400 i.u) given every six hours.
• This treatment has a rapid onset but short
duration of effect
• Patients develop tolerance to the calcium-
lowering effect of Calcitonin.
43

44. • Zoledronic acid (Zometa) - 4 mg IV diluted in
100 ml of N Saline - over at least 15’ once a
M
• Pamindronate (Pamidria) - 60 mg IV infusion
over 4 h initial – repeated after a month
• Etidronate (Didronel) - 7.5 mg/kg IV over 4 h
daily for 3-7 d; dilute in at least 250 ml of
sterile N Saline
• They inhibit bone resorption, inhibit the
Osteoclastic activity. 44

45. • Dialysis for refractory Hypercalcemic crisis
• Parathyroidectomy for adenomas
• Rx. of the underlying cause – Eliminate drugs
• Plicamycin (Mithracin) 25 mcg/kg/d IV for 4 d
• Gallium nitrate (Ganite) 100 mg/m2/d IV for 5
days in 1 L of NS or 5% Dextrose
• Cinacalcet (Sensipar) - 30 mg PO od –
(increases sensitivity of calcium sensing
receptor) 45

46. • Hypercalcemia is often asymptomatic
• Screen all suspected by doing Sr Calcium
• If elevated, do I-PTH and follow algorithm
• 90% Hyperparathyroidism and malignancy
• Vitamin D toxicity is an important cause
• Thiazide diuretics common cause, Vitamin A
• Adequate hydration - N Saline + Furosemide
• Calcitonin + Zoledronic acid main stay of Rx.
46