MANAGING HYPERCALCEMIA

Speaker: Dr. Dibbendhu Khanra

Chairperson: Dr. A.K. Banerjee

- most over-the-counter sold drug

- 43% Indian women on

supplement

- prescribed by doctors commonly

most abundant mineral of body

maintenance of strong bones

neuro-mascular action

blood clotting, blood pressure

hormone regulation

Calcium an unparallel hero

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Calcium- a sinister in disguise

Hypercalcaemia- Today’s concern!

..Some cases..

CASE 1

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)

CASE 2

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

CASE 3

• 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

• 30-year-old female• Fever, cough• Polyuria, polydypsia, GI upset• constipation, confusion, headache• CECT chest – hilar lympahedenopathy• serum calcium, 13.8 mg/d

CASE 4

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

CASE 5

We will come back to the cases..

Learning Objectives

Calcium metabolism Defining hypercalcaemia Causes of hypercalcaemia Cl/f of hypercalceimia Diagnosis to hypercalcaemia Management

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Calcium Metabolism

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Defining Hypercalcemia

Defining Hypercalcemia

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Ca+

+

PTH

Vitamin D

MalignancyMedicines

Endocrine

Genetic

Causes

Clinical features

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Renal ‘stone

’

Abdominal

‘moan’

Skeletal

‘bone’

Psychis

‘groan’

Also…

Clinical features (Cont.)

Digitalis toxicity

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

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

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Diagnostic Approach

Sestamibi N-scan

Familial Hypocalciuric Hypercalcemi

a

calcium is high and PTH is high, d/g is primary hyperparathyroidism.

IF calcium is mildly raised in background of highly elevated PTH, then urinary ca can be ordered to rule out FHH

Corrected serum calcium=Ionized calcium + 0.8(4-serum albumin)

CASE 1

Neuropsychiatric complaints

Calcium 12.4 mg/dl

iPTH – 509 (12-72 pg/ml)

Thallium subtraction study: Left lower lobe parathyroid adenoma

CASE 2

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

• 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)

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CASE 3

Vit D overdose

• 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

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CASE 4

Hilar LN Bx – non caseating granulomasSarcoidosis

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

CASE 5

Hypercalcemia Associated with Renal Failure

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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

Hypercalcemia Associated with Renal Failure

Secondary Hyperparathyroidism

Tertiary Hyperparathyroidism

• Long-standing, inadequately treated chronic renal failure• True clonal outgrowth (irreversible)

TREATMENT

Observation

Pharmacological

NonPharmacological

Surgery

Dialysis

Hypercalcemia: to treat or not to

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Critical - > 14 mg %

Moderate - 12 to 14 mg %

Mild – 10.4 to 11.9 mg %

Normal – 8.5 to 10.3 mg %

1 • Aggressive therapy

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• Start therapy• When

symptomatic• When

PrHyperPTHism

3• No therapy• Except

PrHyperPTHism

Hypercalcaemia should always be treated

Avoid factors that can aggravate hypercalcemia

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- thiazide and lithium- volume depletion- prolonged bed rest or inactivity- high calcium diet (>1000 mg/day)

The Four Rx Modalities

I.V. Saline Hydration

Dexamethason

e

Bisphos- phonate

s

Calcitonin

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A

B C

D

Dr. Harold Copp isolated calcitonin from salmon sperm

Bisphosphonate:

MOA

Osteonecrosis of Jaw (ONJ)

 mandible > maxilla  Matrix metalloproteinase 2

In HF, CKD; lowers ca by 1-3 mg/dl

Routine use not recommended

Calcitonin and hydration provide a rapid reduction, while a bisphosphonate provides a sustained effect

Do not give bisphosphonates until patient is fully rehydratedcontraindicated in patients with cr cl <10 mL/min

Caution with NSAIDS, ACE inhibitors, aminoglycosides

Treating hypercalcaemia is multidrug approach

Monitoring

Mildly elevated calcium

No previous episodes of life threatening hypercalcemia

Normal renal function Normal bone status

Surgery• Serum calcium level

> 1 mg % above normal• Creatinine clearance

< 60 ml/minute• Bone density: T score <–

2.5

at Any of 3 sites• Age younger than 50

years33

Asymptomatic patient ofParathyroid adenoma

Serum caserum creatinine

Bone density

Significant symptoms – Rx surgery

Surgical TherapyMinimally 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

• If an enlarged gland is found, a normal gland should be sought.

• if an intra-operative frozen section biopsy of a normal-sized second gland confirms its histologic normality, no further exploration, biopsy, or excision is needed.

• recurrence rate of hyper-parathyroidism may be high if a second abnormal gland is missed.

• all four glands be sought

• most of the total parathyroid tissue mass be removed.

• unnecessary surgery & un-acceptable rate of hypoparathyroidism and hypocalcamia.

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SURGICAL THERAPY (cont.)

Conventional

Surgery for MEN syndrome Conventional

• 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

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CASE 1

calcium 12.4 mg/dl

(8.4 – 10.4 mg/dl)

parathyroid adenoma

M/N= Surgery (MIP)

CASE 2

Malignancy related hypercalcaemia

(Breast, Lung, Lymphoma, Thyroid, Kidney, Prostate, Multiple Myeloma)

N Saline calcitonin Zoledronic acid

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CASE 3

• 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

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CASE 4

• Hypercalcemia Associated with Renal Failure• Secondary hyperparathyroidism• calcitriol

CASE 5

Hypercalcemia Associated with Renal Failure

• 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

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In CKD

Dialysis Controversial

Malignancy or Vit D associated cases

Avoid factors that can

aggravate hypercalcemia

SUMMARY

Take home messages

• 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

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THANK YOU

ddk3987@gmail.com