Transcript Hyperparathyroidism and Hypoparathyroidism

Dr. Zahoor
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HYPERPARATHYROIDISM AND
HYPERCALCAEMIA
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Parathyroid Hormone
 Parathyroid hormone regulates the calcium
metabolism.
 Serum calcium levels are mainly controlled by
parathyroid hormone (PTH) and vitamin D.
 Hypercalcemia is much more common than
hypocalcaemia.
 It occurs mainly in elderly female and is usually due to
primary hyperparathyroidism.
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Parathyroid Hormone
 There are four parathyroid glands, situated posterior to
the thyroid gland
 PTH is 84 amino acid hormone, is secreted from chief
cells of parathyroid glands
 PTH level rise when serum ionized calcium falls
 There are calcium sensing receptors on the plasma
membrane of parathyroid cells.
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Parathyroid Hormone
PTH increases calcium level by following actions:
 Increase osteoclastic resorption of bone
 Increases intestinal absorption of calcium
 Increases synthesis of 1,25 (OH)2D3
 Increases renal tubular reabsorption of calcium
 Increases excretion of phosphate
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Hypercalcemia
Pathophysiology and causes
Main causes of hypercalcemia
 Primary hyperparathyroidism
 Tertiary hyperparathyroidism
 Malignant disease e.g. myeloma
 Secondary deposits in bone
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Hypercalcemia
Pathophysiology and causes (cont)
 Excess vitamin D intake e.g. milk-alkali syndrome
 Sarcoidosis, TB, lymphoma
 Endocrine causes – thyrotoxicosis, Addison’s disease
 Drugs – lithium, vitamin D analogue, vitamin A,
Thiazide
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Causes of
Hypercalcemia
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Hyperparathyroidism
 Hyperparathyroidism may be
1. Primary
2. Secondary
3. Tertiary
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Primary Hyperthyroidism
It is caused by single parathyroid edenoma > 80%
By diffuse hyperplasia of all glands (15-20%)
Note – parathyroid carcinoma is rare < 1%
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Hyperparathyroidism
1. Primary Hyperparathyroidism (cont)
 Primary hyperthyroidism is of unknown cause though
adenomas and hyperplasia occur
2. Secondary hyperparathyroidism
 It is physiological compensatory hypertrophy of all
parathyroids because of hypocalcemia, such as occurs
in chronic kidney disease or Vitamin D deficiency
 PTH levels are raised but calcium levels are low or
normal
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Hyperparathyroidism
3. Tertiary Hyperparathyroidism
 It is development of autonomous parathyroid
hyperplasia after long standing secondary
hyperparathyroidism most often in renal failure
 Plasma calcium and phosphate are both raised
 Parathyroidectomy is necessary
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Hyperparathyroidism
Symptoms and Signs
 Mild hypercalcemia – calcium < 3mmol/l is asymptomatic
but severe hypercalcemia > 3mmol/l can produce many
symptoms
(Normal calcium level is 2.2 – 2.67mmol/l)
Symptoms of severe hypercalcemia
 General – tiredness, malaise, dehydration and depression
 Renal – renal colic from stones, polyurea, hematuria and
hypertension
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Hyperparathyroidism
Symptoms of severe hypercalcemia (cont)
 Bones – bone pain, bone cyst, brown tumors due to
local destruction (osteoclastic activity)
 Abdomen – abdominal pain
 Chondrocalcinosis and atopic calcification
 Corneal calcification – occurs in long standing
hypercalcemia but causes no symptoms
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HYPERPARATHYROIDISIM
Hypercalcaemia in malignant disease with bony
metastasis.
- The common primary tumors are bronchus, breast,
myeloma, thyroid, prostate, oesophagus, lymphoma
and renal cell carcinoma.
- Most cases are associated with raised levels of PTH –
related protein and local bone resorbing cytokines
may be involved leading to local mobilization of
calcium by osteolysis.
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HYPERPARATHYOIDISIM
 NOTE – Severe Hypercalcaemia , calcium more than 3
mmol/L is usually associated with malignant disease,
hyperparathyroidism or vitamin D therapy.
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HYPERPARATHYOIDISIM
Investigation of Primary Hyperparathyroidism
 Serum calcium is raised – hypercalcemia
 Hypophosphatemia
 PTH is raised
 Elevated serum alkaline phosphate is found in severe
parathyroid bone disease
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HYPERPARATHYOIDISIM
Investigation of Primary Hyperparathyroidism (cont)
Imaging
 Abdominal X-ray may show renal calculi or
Nephrocalcinosis
 X-ray hand may show sub periosteal erosions in the middle
or terminal phalanges
 DXA bone density scan
 Parathyroid imaging – ultrasound, CT, MRI, radio isotope
scanning using 99mTc-sestamibi (99% sensitive in detecting
adenoma)
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Subperiosteal bone resorption in hyperparathyroidism
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Pepper pot skull in hyperparathyroidism
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HYPERPARATHYOIDISIM
Treatment of Primary Hyperparathyroidism
 There is no effective medical therapy for primary
hyperparathyroidism at present
 Following things are advised:
- High fluid intake
- Avoid high calcium or vitamin D intake
- Exercise is encouraged
- Calcium sensing receptor blockers e.g. cinacalcet are used
in parathyroid carcinoma, dialysis patients and in primary
hyperthyroidism where surgical intervention is
contraindicated
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HYPERPARATHYOIDISIM
Treatment of Primary Hyperparathyroidism (cont)
 Surgery is indicated in primary hyperparathyroidism for
- people with renal stones or impaired renal function
- bone involvement or marked reduction in cortical bone
density
- marked hypercalcemia – serum calcium > 3mmol/l
- previous episode of severe acute hypercalcaemia
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HYPERPARATHYOIDISIM
Treatment of Primary Hyperparathyroidism (cont)
 Parathyroid surgery when performed by experienced
surgeons has 90% successful results in removing
adenoma or removing 4 hyperplasic parathyroids
Complications
- Post operative hypocalcemia
- Bleeding
- Recurrent laryngeal nerve palsies less than 1%
- Hungry bone syndrome
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FAMILIAL HYPOCALCIURIC
HYPERCALCAEMIA
 Autosomal Dominant , uncommon condition.
 Usually asymptomatic
 There is increased renal absorption of calcium despite
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Hypercalcemia
PTH is normal or slightly increased
Urinary calcium is low
Course is benign
Parathyroid surgery is not indicated
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TREATMENT OF ACUTE SEVERE
HYPERCALCAEMIA
 Acute severe hypercalcaemia presents with dehydration,
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nausea and vomiting, polyuria, drowsiness and altered
consciousness. Serum calcium is over 3mmol/L .
TREATMENT
Rehydration- 4-6 L of 0.9% saline on day 1, and 3-4 L for
several days thereafter.
I/V bisphosphonates e.g. Pamidronate 60- 90 mg I/v
infusion in o.9% saline over 2-4 hours
Prednisolone is effective in Myeloma, sarcoidosis, VitD
excess
Calcitonin – 200 units I/V 6 hourly, short lived action
Oral phosphate
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Hypocalcemia and
Hypoparathyroidism
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HYPOCALCAEMIA AND
HYPOPARATHYROIDISM
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Hypocalcaemia may be due to
Hypoparathyroidism
Increased phosphate level – as in chronic renal failure
Vit D deficiency e.g. Osteomalacia, Rickets
Drugs- Biphosphonates, calcitonin
Other causes- Acute pancreatitis , Malnutrition,
Malabsoption
After Thyroid or Parathyroid surgery
Pseudohypoparathyroidisim- Resistance to PTH
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Pseudohypoparathyroidism
 Pseudohypoparathyroidisim is syndrome of end organ
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resistance to PTH .
They produce PTH, but their bones and kidneys do
not respond to it, therefore called
pseudohypoparathyroid.
There is short stature, short metacarpals,
subcutaneous calcification and sometimes intellectual
impairment
PTH is high , serum calcium is low, phosphates is high
Gene defect from mother
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short fourth metacarpal in pseudohypoparathyroidism
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PSEUDO- PSEUDOHYPOPARATHYOIDISM
 Phenotype defects present (physical characters') but
without any abnormalities of calcium metabolism.
 PTH is normal , serum calcium and phosphate are
normal
 Gene defect from father
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HYPOPARATHYROIDISM
Clinical features
Hypoparathyroidism presents as
 Neuromuscular irritability
 Neuro psychiatric manifestations
 Parasthesiae, circumoral numbness, cramps, anxiety ,
tetany, convulsions .
 Laryngeal stridor , dystonia, psychosis.
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TWO SIGNS OF HYPOCALCAEMIA
1. CHVOSTE’S SIGN
 Gentle tapping over the Facial nerve causes twitching
of the ipsilateral facial muscles.
2. TROSSEAU’S SIGN
 When inflation of sphygmomanometer cuff above
systolic Blood pressure for 3 minutes induces tetanic
spasm of fingers, wrist .
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CHVOSTE’S SIGN
TROSSEAU’S SIGN
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 IMPORTANT
Severe Hypocalcaemia may cause
 Papilloedema
 Increased QT interval on ECG
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HYPOPARATHYROIDISM
INVESTIGATIONS
 Serum calcium is low
 PTH levels in serum – Absent or Low
 Serum and urine creatinine for Renal disease
 Parathyroid antibodies – present in idiopathic
hypoparathyoidism
 25- hydroxy VitD serum level – low in Vit D deficiency
 Magnesium level – severe Hypomagnesaemia results
in functional hypoparaparathyroidism, which is
reversed by Magnesium replacement
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HYPOPARATHYROIDISM
TREATMENT
 VIT D – Alfacalcidol ( 1alpha-OH- D3 )
 When severe Hypocalcaemia- I/v calcium gluconate.
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CASE HISTORY – A Patient with
hypercalcemia
A 60 year old woman is referred to out patient for investigation. A routine
biochemical profile has shown hypercalcemia.
Questions:
1.
It would be important to take a drug history because which of the following
drugs may commonly cause hypercalcemia?
a. Lithium
b. Loop diuretic
c. Steroid inhaler
d. Biphosphonate
2.
Although hypercalcemia may be detected in asymptomatic person, all of the
following clinical features may be associated except which one?
a. Constipation
b. Poly urea
c. Carpopedal spasm
d. Vomiting
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3. Which is most likely diagnosis in the clinical case described above?
a. Malignancy
b. Laboratory error
c. Hyperparathyroidism
d. Hyperthyroidism
4. If there was a family history of hypercalcemia, which of the
following diagnosis would be likely?
a. Auto immune hyperthyroidism
b. Pseudo hyperparathyroidism
c. Familial hypercalciuric hypercalcemia
d. Pseudo Pseudo hyperthyroidism
5. Which of the following result may indicate an alternate cause for the
hypercalcemia?
a. Elevated Cortisol
b. Increased TSH
c. Reduced magnesium
d. Undetectable Cortisol
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Answers:
Answer to Question 1:
a. Lithium
Lithium, Thiazide diuretic, Vitamin D cause hypercalcemia
Answer to Question 2:
c. Carpopedal spasm
It occurs in hypocalcemia
Answer to Question 3:
c. Hyperparathyroidism
Primary hyperthyroidism is the commonest cause of hypercalcemia in asymptomatic
patient
Answer to Question 4:
c. Familial hypercalciuric hypercalcemia
It is Autosomal dominant
Answer to Question 5:
d. Undetectable Cortisol
Addison’s disease may cause hypercalcemia
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Thank you
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