1. Hyperparathyroidism and Hypoparathyroidism
Dr. Zahoor

2. HYPERPARATHYROIDISM AND HYPERCALCAEMIA

3. 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.

4. 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.

5. 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

6. Hypercalcemia Pathophysiology and causes Main causes of hypercalcemia
Primary hyperparathyroidism
Tertiary hyperparathyroidism
Malignant disease e.g. myeloma
Secondary deposits in bone

7. 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

8. Causes of Hypercalcemia

9. Hyperparathyroidism Hyperparathyroidism may be 1. Primary 2. Secondary
3. Tertiary
Primary Hyperthyroidism
It is caused by single parathyroid edenoma > 80%
By diffuse hyperplasia of all glands (15-20%)
Note – parathyroid carcinoma is rare < 1%

10. 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

11. 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

12. 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

13. 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

14. HYPERPARATHYROIDISIM
Hypercalcaemia occurs 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.

15. HYPERPARATHYOIDISIM
NOTE – Severe Hypercalcaemia , calcium more than 3 mmol/L is usually associated with malignant disease, hyperparathyroidism or vitamin D therapy.

16. 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

17. 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)

18. Subperiosteal bone resorption in hyperparathyroidism

19. Pepper pot skull in hyperparathyroidism

20. 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

21. 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

22. 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

23. FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA
Autosomal Dominant , uncommon condition.
Usually asymptomatic
There is increased renal absorption of calcium despite Hypercalcemia
PTH is normal or slightly increased
Urinary calcium is low
Course is benign
Parathyroid surgery is not indicated

24. TREATMENT OF ACUTE SEVERE HYPERCALCAEMIA
Acute severe hypercalcaemia presents with dehydration, 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 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

25. Hypocalcemia and Hypoparathyroidism

26. HYPOCALCAEMIA AND HYPOPARATHYROIDISM
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

28. Pseudohypoparathyroidism
Pseudohypoparathyroidisim is syndrome of end organ 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

29. short fourth metacarpal in pseudohypoparathyroidism

30. 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

31. HYPOPARATHYROIDISM Clinical features Hypoparathyroidism presents as
Neuromuscular irritability
Neuro psychiatric manifestations
Parasthesiae, circumoral numbness, cramps, anxiety , tetany, convulsions .
Laryngeal stridor , dystonia, psychosis.

32. 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 .

33. CHVOSTE’S SIGN
TROSSEAU’S SIGN

34. IMPORTANT
Severe Hypocalcaemia may cause
Papilloedema
Increased QT interval on ECG

35. 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

36. HYPOPARATHYROIDISM TREATMENT VIT D – Alfacalcidol ( 1alpha-OH- D3 )
When severe Hypocalcaemia- I/v calcium gluconate.

37. 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:
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
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

38. 3. Which is most likely diagnosis in the clinical case described above
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

39. 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

40. Thank you