Speaker: Dr. Dibbendhu Khanra
Chairperson: Dr. A.K. Banerjee
Calcium
an unparallel hero
 most abundant mineral of body
 maintenance of strong bones
 neuro-mascular action
 blood c...
Calciuma sinister in disguise

HypercalcaemiaToday’s concern!
..Some cases..
3
Mr. K is a 41 year old patient
– Mild depression
– Behavioral abnormality
– Headache
– Fatigue
– Difficulty concentrating
...


Mrs. C is a 57 year old patient, well



t-score – 1.3 (spine), 2. 8 (femur)



Calcium – 12. 5 (8.4 – 10.4 mg/dl)

...
•
•
•
•
•
•
•
•

A 58-year-woman presented to ER
progressive Multiple sclerosis
Osteoporosis
calcium, 600 mg, 3 times dail...
•
•
•
•
•
•

30-year-old female
Fever, cough
Polyuria, polydypsia, GI upset
constipation, confusion, headache
CECT chest –...
•
•
•
•
•

50-year-old male
Diabetic for 10 years
Poorly controlled with OHA
HTN, anasarca, anaemia
serum calcium 14.8 mg/...







Calcium metabolism
Defining hypercalcaemia
Causes of hypercalcaemia
Cl/f of hypercalceimia
Diagnosis to hyper...
10
11
13
Causes

PTH

Genetic

 Ca++

Vitamin
D

Endocrine
Malignancy
Medicines
Renal
‘stone’

Abdominal
‘moan’

Skeletal
‘bone’

Psychis
‘groan’

Also…

15
Digitalis toxicity
A = high calcium levels means
primary hyperparathyroidism
unless the PTH is near zero

B = normocalcemic" hyperparathyroid...
It is IMPOSSIBLE to tell the difference between
FHH and primary hyperparathyroidism
based upon the results of a 24-hour ur...
Corrected serum calcium=
Ionized calcium + 0.8(4-serum albumin)

calcium is high and PTH
is high, d/g is primary
hyperpara...
Neuropsychiatric complaints
Calcium 12.4 mg/dl
iPTH – 509 (12-72 pg/ml)

Thallium subtraction study:
Left lower lobe parat...
Weight loss and generalised weakness
Calcium – 12. 5 (8.4 – 10.4 mg/dl)
iPTH 21 (10 – 65.0 pg/ml)
PTHrp - elevated

Lung b...
•
•
•
•

calcium, cholecalciferol supplement
serum calcium14.6 mg/dL (15.2 mg/dL)
iPTH - 4 pg/mL (N12-65 pg/mL
25-OH D lev...
•
•
•
•
•

CECT chest – hilar lympahedenopathy
serum calcium, 13.8 mg/d
iPTH - 4 pg/mL (N12-65 pg/mL
1, 25-OH D level elev...
•
•
•
•

T2DM
CKD
serum calcium 14.8 mg/d
iPTH – 209 (12-72 pg/ml)

Hypercalcemia Associated with Renal Failure
Hypercalcemia Associated with Renal Failure
Secondary Hyperparathyroidism
Hypocalcaemia is the common denominator
Reversib...
Observation

Pharmacological
Non
Pharmacological
Surgery

Dialysis
Critical - > 14 mg %

1

Moderate - 12 to 14 mg %

2

Mild – 10.4 to 11.9 mg %

3

• Aggressive therapy
• Start therapy
• ...
- thiazide and lithium
- volume depletion

- prolonged bed rest or inactivity
- high calcium diet (>1000 mg/day)

28
A

B

I.V. Saline
Hydration

Bisphosphonates

Dexa
methasone

Calcitonin

D

C

29
Dr. Harold Copp isolated
calcitonin from salmon sperm
Bisphos
phonate:
MOA

Osteonecrosis
of Jaw (ONJ)
mandible > maxilla
Matrix metalloproteinase 2
Treating hypercalcaemia is multidrug approach

In HF, CKD; lowers ca by 1-3 mg/dl
Routine use not recommended

Do not give...
Monitoring

Surgery
• Serum calcium level

 Mildly elevated calcium
> 1 mg % above normal
 No previous episodes of
• Cre...
Minimally Invasive Parathyroidectomy (MIP)

 an outpatient procedure
 Pre-op localization with Sestamibi Tc scan
 cervi...
• If an enlarged gland is found, a
• all four glands be
normal gland should be sought.
sought
• if an intra-operative froz...
• totally remove three
glands with partial
excision of the fourth
gland
• care is taken to leave
a good blood supply
for t...
 calcium 12.4 mg/dl
(8.4 – 10.4 mg/dl)
 parathyroid adenoma
 M/N= Surgery (MIP)
 Malignancy related
hypercalcaemia
(Breast, Lung, Lymphoma,
Thyroid, Kidney, Prostate,
Multiple Myeloma)
 N Saline

 ca...
• Vit D overdose
• Half life of Vit D is very short
no further treatment required
• Withhold Vit D
• Steroid can be used

...
•
•
•
•

Acute symptomatic hypercalcaemia
Sarcoidosis (granulomatous disease; DHCC related)
NS
Steroid

40
• Hypercalcemia Associated with Renal Failure
• Secondary hyperparathyroidism
• calcitriol
• Dialysis if life threatening
Secondary hyperparatyroidism
• restriction of dietary phosphate,
• the use of non-absorbabl...
S
U
M
M
A
R
Y

Dialysis

Controversial

Malignancy or Vit D
associated cases
Avoid factors
that can
aggravate
hypercalcemi...
• Most common cause of hypercalcaemia is primary
hyperparathyroidism
• Any hypercalcaemia should be worked up and treated....
THANK YOU

ddk3987@gmail.com

45
Managing hypercalcaemia presented on CMC, Kol, 1.10.2013
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Managing hypercalcaemia presented on CMC, Kol, 1.10.2013

  1. 1. Speaker: Dr. Dibbendhu Khanra Chairperson: Dr. A.K. Banerjee
  2. 2. Calcium an unparallel hero  most abundant mineral of body  maintenance of strong bones  neuro-mascular action  blood clotting, blood pressure  hormone regulation -most over-the-counter sold drug - 43% Indian women on supplement - prescribed by doctors commonly
  3. 3. Calciuma sinister in disguise HypercalcaemiaToday’s concern! ..Some cases.. 3
  4. 4. Mr. K is a 41 year old patient – Mild depression – Behavioral abnormality – Headache – Fatigue – Difficulty concentrating – TSH - 2.06 (0.5 – 4.00) – calcium 12.4 mg/dl (8.4 – 10.4 mg/dl)
  5. 5.  Mrs. C is a 57 year old patient, well  t-score – 1.3 (spine), 2. 8 (femur)  Calcium – 12. 5 (8.4 – 10.4 mg/dl)  weight loss and generalised weakness  Cough and hemoptysis
  6. 6. • • • • • • • • A 58-year-woman presented to ER progressive Multiple sclerosis Osteoporosis calcium, 600 mg, 3 times daily 5000-IU cholecalciferol supplement OD tremors Altered sensorium serum calcium 15.2 mg/dL
  7. 7. • • • • • • 30-year-old female Fever, cough Polyuria, polydypsia, GI upset constipation, confusion, headache CECT chest – hilar lympahedenopathy serum calcium, 13.8 mg/d
  8. 8. • • • • • 50-year-old male Diabetic for 10 years Poorly controlled with OHA HTN, anasarca, anaemia serum calcium 14.8 mg/d
  9. 9.       Calcium metabolism Defining hypercalcaemia Causes of hypercalcaemia Cl/f of hypercalceimia Diagnosis to hypercalcaemia Management
  10. 10. 10
  11. 11. 11
  12. 12. 13
  13. 13. Causes PTH Genetic  Ca++ Vitamin D Endocrine Malignancy Medicines
  14. 14. Renal ‘stone’ Abdominal ‘moan’ Skeletal ‘bone’ Psychis ‘groan’ Also… 15
  15. 15. Digitalis toxicity
  16. 16. A = high calcium levels means primary hyperparathyroidism unless the PTH is near zero B = normocalcemic" hyperparathyroidism. this is the only group that we believe should have a urinary calcium level performed
  17. 17. It is IMPOSSIBLE to tell the difference between FHH and primary hyperparathyroidism based upon the results of a 24-hour urine test 1. Urinary calcium can be anything (very low to very high) in Pr HyperPTHism. 2. The arbitrary cut off of urinary ca excretion/ 24 hr 100 lacks any rationality. 3. Nor elevated serum ca neither elevated urinary ca has any association with renal stones. 4. Low urinary ca does not always mean FHH. FHH is so rare, that few doctors will ever see it. FHH is diagnosed incorrectly about 95-99% of the time
  18. 18. Corrected serum calcium= Ionized calcium + 0.8(4-serum albumin) calcium is high and PTH is high, d/g is primary hyperparathyroidism. IF calcium Familial is mildly Hypocalciuric raised in background of Hypercalcemia Sestamibi highly elevated N-scan PTH, then urinary ca can be ordered to rule out FHH 19
  19. 19. Neuropsychiatric complaints Calcium 12.4 mg/dl iPTH – 509 (12-72 pg/ml) Thallium subtraction study: Left lower lobe parathyroid adenoma
  20. 20. Weight loss and generalised weakness Calcium – 12. 5 (8.4 – 10.4 mg/dl) iPTH 21 (10 – 65.0 pg/ml) PTHrp - elevated Lung biopsy with IHC: Well differentiated, low grade squamous cell lung carcinoma
  21. 21. • • • • calcium, cholecalciferol supplement serum calcium14.6 mg/dL (15.2 mg/dL) iPTH - 4 pg/mL (N12-65 pg/mL 25-OH D level 103 ng/mL (N>30 ng/ml) Vit D overdose 22
  22. 22. • • • • • CECT chest – hilar lympahedenopathy serum calcium, 13.8 mg/d iPTH - 4 pg/mL (N12-65 pg/mL 1, 25-OH D level elevated Serum ACEase – highly raised Hilar LN Bx – non caseating granulomas Sarcoidosis 23
  23. 23. • • • • T2DM CKD serum calcium 14.8 mg/d iPTH – 209 (12-72 pg/ml) Hypercalcemia Associated with Renal Failure
  24. 24. Hypercalcemia Associated with Renal Failure Secondary Hyperparathyroidism Hypocalcaemia is the common denominator Reversible (adaptive) growth of parathyroid gland • Resistance to the normal level of PTH • Increased level of FGF23 • Reduction in 1,25(OH)2 vitamin D Tertiary Hyperparathyroidism • Long-standing, inadequately treated chronic renal failure • True clonal outgrowth (irreversible) 25
  25. 25. Observation Pharmacological Non Pharmacological Surgery Dialysis
  26. 26. Critical - > 14 mg % 1 Moderate - 12 to 14 mg % 2 Mild – 10.4 to 11.9 mg % 3 • Aggressive therapy • Start therapy • When symptomatic • When PrHyperPTHism • No therapy • Except PrHyperPTHism Normal – 8.5 to 10.3 mg % Hypercalcaemia should always be treated 27
  27. 27. - thiazide and lithium - volume depletion - prolonged bed rest or inactivity - high calcium diet (>1000 mg/day) 28
  28. 28. A B I.V. Saline Hydration Bisphosphonates Dexa methasone Calcitonin D C 29
  29. 29. Dr. Harold Copp isolated calcitonin from salmon sperm
  30. 30. Bisphos phonate: MOA Osteonecrosis of Jaw (ONJ) mandible > maxilla Matrix metalloproteinase 2
  31. 31. Treating hypercalcaemia is multidrug approach In HF, CKD; lowers ca by 1-3 mg/dl Routine use not recommended Do not give bisphosphonates until patient is fully rehydrated contraindicated in patients with cr cl <10 mL/min Caution with NSAIDS, ACE inhibitors, aminoglycosides Calcitonin and hydration provide a rapid reduction, while a bisphosphonate provides a sustained effect
  32. 32. Monitoring Surgery • Serum calcium level  Mildly elevated calcium > 1 mg % above normal  No previous episodes of • Creatinine clearance life threatening hypercalcemia < 60 ml/minute  Normal renal function • Bone density: T score <–2.5  Normal bone status at Any of 3 sites • Age younger than 50 years Serum ca serum creatinine Bone density Significant symptoms – Rx surgery 33
  33. 33. Minimally Invasive Parathyroidectomy (MIP)  an outpatient procedure  Pre-op localization with Sestamibi Tc scan  cervical block anesthesia  minimal surgical incision  Intra-op PTH level obtained before and 5 mins after removal  If PTH levels fall by greater than 50% operation terminated  IF PTH Levels fall by less than 50%, full neck exploration  clear-cut cost benefit  Accepted in asymptomatic patients  not proper for multiple tumour or large tumours
  34. 34. • If an enlarged gland is found, a • all four glands be normal gland should be sought. sought • if an intra-operative frozen section biopsy of a normal-sized • most of the total parathyroid tissue second gland confirms its mass be removed. histologic normality, no further exploration, biopsy, or excision is • unnecessary surgery & un-acceptable rate needed. of hypoparathyroidism • recurrence rate of hyperand hypocalcamia. parathyroidism may be high if a second abnormal gland is missed. 35
  35. 35. • totally remove three glands with partial excision of the fourth gland • care is taken to leave a good blood supply for the remaining gland • total parathyroidectomy with immediate transplantation of a portion of a removed, minced parathyroid gland into the muscles of the forearm • surgical excision is easier from the ectopic site in the arm if there is recurrent hyperfunction 36
  36. 36.  calcium 12.4 mg/dl (8.4 – 10.4 mg/dl)  parathyroid adenoma  M/N= Surgery (MIP)
  37. 37.  Malignancy related hypercalcaemia (Breast, Lung, Lymphoma, Thyroid, Kidney, Prostate, Multiple Myeloma)  N Saline  calcitonin  Zoledronic acid
  38. 38. • Vit D overdose • Half life of Vit D is very short no further treatment required • Withhold Vit D • Steroid can be used 39
  39. 39. • • • • Acute symptomatic hypercalcaemia Sarcoidosis (granulomatous disease; DHCC related) NS Steroid 40
  40. 40. • Hypercalcemia Associated with Renal Failure • Secondary hyperparathyroidism • calcitriol
  41. 41. • Dialysis if life threatening Secondary hyperparatyroidism • restriction of dietary phosphate, • the use of non-absorbable antacids • careful, selective addition of calcitriol Tertiary Hyperparatyroidism • Partial removal of parathyroid gland 42
  42. 42. S U M M A R Y Dialysis Controversial Malignancy or Vit D associated cases Avoid factors that can aggravate hypercalcemia In CKD 43
  43. 43. • Most common cause of hypercalcaemia is primary hyperparathyroidism • Any hypercalcaemia should be worked up and treated. • First investigation to seek for is an intact PTH • Surgery is often provided to apparently aysmptomtic patients of primary hyperparathyroidism • FHH, practically does NOT occur • Hydration is the mainstay of therapy • Managing hypercalcaemia is a multidrug approach • Calcitriol can be given in CKD associated hypercalaemia
  44. 44. THANK YOU ddk3987@gmail.com 45

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