parathyroid hormone secretes PTH that regulates calcium level

1. FRONT E
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Lecture 6. Parathyroid
Disease:

3. Hyperparathyroidism:
• Hyperparathyroidism occurs in two major forms:
1. Primary hyperparathyroidism.
2. Secondary hyperparathyroidism.
3. tertiary hyperparathyroidism (less).

4. 1. Primary Hyperparathyroidism:
• Is a common endocrine disorder and an important
cause of hypercalcemia.
• 90% of patients are over 50 years of age.
• Causes:
a) Adenoma—85% to 95%.
b) Primary hyperplasia (diffuse or nodular)—5% to 10%.
c) Parathyroid carcinoma—1%.
• Pathogenesis:
• Abnormalities in two genes are commonly associated
with parathyroid tumors:
1. Cyclin D1 gene rearrangements = cell proliferation.
2. MEN1 mutations.

5. • Morphology:
• Solitary adenoma.
• The typical parathyroid adenoma is a well-
circumscribed, soft, tan nodule, invested by a
delicate capsule.
• Normal or shrunken other gland.
• The chief cells of the adenoma are larger and show
greater nuclear size variability “endocrine atypia”.
• Adipose tissue is inconspicuous within adenomas.
• Parathyroid hyperplasia is typically a
multiglandular process.
• Parathyroid carcinomas may be circumscribed
lesions that are difficult to distinguish from
adenomas.

8. • Morphologic changes in other organs:
• Skeletal changes include increased osteoclastic
activity.
• Thin bone cortex and fibrous tissue contain bone
marrow (osteitis fibrosa cystica).
• Renal changes formation of urinary tract stones
(nephrolithiasis) + calcification of the renal
interstitium and tubules (nephrocalcinosis).
• Metastatic calcification secondary to
hypercalcemia also may be seen in other sites,
including the stomach, lungs, myocardium, and
blood vessels.

9. osteitis fibrosa cystica

10. • Clinical feature:
• More common in women than in men (gender ratio of
nearly 4: 1).
1. Increase in serum ionized calcium.
2. Clinically silent hypercalcemia.
3. Painful bones.
4. Renal stones.
5. Abdominal groans ‘gastrointestinal symptoms of
constipation, indigestion, nausea and vomiting’.
6. Psychic moans.
7. Constipation, nausea, peptic ulcers, pancreatitis, and
gallstones.
8. Weakness and hypotonia.
9. Polyuria and secondary polydipsia.
10. Exacerbation of hypertension.

13. • Diagnosis:
• Elevated serum PTH in individuals with parathyroid
hyperfunction.
• Decreased serum PTH in those with nonparathyroid
diseases, including malignancy.
• Hypophosphatemia.
• ECG - shortening of the QT interval.
• Radiological—90% normal; 10% show evidence of
bone resorption, particularly phalangeal erosions.
• Treatment:
Rehydration.
Bisphosphonates for plasma calcium reduction.
Surgical removal of abnormal parathyroid glands.
• Prognosis:
• Is poor, because it often occurs in those with advanced
cancers.

14. 2. Secondary Hyperparathyroidism:
• Is caused by chronic depression of serum calcium levels,
most often as a result of renal failure, leading to
compensatory overactivity of the parathyroids.
• Pathogenesis:
1. Hyperphosphotemia depress serum calcium levels.
2. Loss of renal α1-hydroxylase activity ‘vitamin D’.
3. Steatorrhoea and other malabsorption syndromes.
• Morphology:
• Hyperplastic; the degree of glandular enlargement is not
necessarily symmetric.
• Hyperplastic glands contain an increased number of chief
cells, or cells with more abundant, clear cytoplasm (water-
clear cells).

15. • Bone changes similar to those seen in primary
hyperparathyroidism also may be present.
• Metastatic calcification may be seen in many tissues.
• Clinical feature:
• Less than primary hyperparathyroidism.
• Bone abnormalities (renal osteodystrophy).
• Calciphylaxis - The metastatic calcification of blood vessels
(secondary to hyperphosphatemia) occasionally may result
in significant ischemic damage to skin and other organs.
• Diagnosis:
• Normal serum calcium level due to the compensatory
increase in PTH levels.
• Treatment:
a) Low phosphorus diet or phosphate binders.
b) Vitamin D derivatives and calcimimetics.
c) Parathyroidectomy.

16. Renal osteodystrophy:
• Skeletal abnormalities, arising as a result of raised PTH
secondary to chronic renal disease.
• Abnormalities vary widely according to the:
1. Nature of the renal lesion.
2. Its duration.
3. Age of the patient.
• Renal osteodystrophy include:
• Osteitis fibrosa cystica.
• Rickets or osteomalacia due to reduced activation of
vitamin D.
• Osteosclerosis—increased radiodensity of certain
bones, particularly the parts of vertebrae adjacent to
the intervertebral discs.

17. Osteosclerosis

18. 3. Tertiary Hyperparathyroidism:
• This condition, resulting from chronic overstimulation
of the parathyroid glands in renal failure,
causes one or more of the glands to become an
autonomous hypersecreting adenoma with resultant
hypercalcaemia.
• 1/3 transplant renal pateints.
• 1-3% may require:
• Subtotal or total parathyroidectomy.

20. Hypoparathyroidism:
• Less common than hyperparathyroidism.
• Hypoparathyroidism is of 3 types:
1. Primary hypoparathyroidism.
2. Pseudo hypoparathyroidism.
3. Pseudopseudo-hypoparathyroidism.

21. 1= Primary hypoparathyroidism:
• Most common hypoparathyroidism.
• Causes:
1. Surgical ablation: during thyroidectomy or other
surgical neck dissections.
2. Congenital absence: This occurs in conjunction with
thymic aplasia (Di George syndrome) and cardiac
defects, secondary to deletions on chromosome
22q11.2.
3. Autoimmune hypoparathyroidism: mutations in the
autoimmune regulator (AIRE) gene.
4. Hypomagnesemia: leads inactivation of adenylate
cyclase, so there is no PTH activation and secretion.

22. • Clinical feature:
• Neuromuscular _ tingling, muscle spasms, facial grimacing,
and sustained carpopedal spasm or tetany.
• Cardiac _ arrhythmias.
• CNS _ increased intracranial pressure, seizures and
calcification of cerebral basal ganglia.
• Eye _ cataract.
• Mouth _ dental abnormalities.
• Diagnosis:
• Measures levels of calcium, phosphorus, magnesium and
PTH.
• A urine test may also be ordered if it is suspected that the
kidneys are excreting too much calcium.
• Treatment:
Administer activated vitamin D (calcitriol) and calcium
supplements.
Some people may also need magnesium supplementation.

23. Trousseau sign
Chvostek's Sign

25. 2= Pseudo hypoparathyroidism:
• The tissues fail to respond to parathyroid hormone
though parathyroid glands are usually normal.
• Rare inherited autosomal dominant character.
• Mostly occurs in females.
• Clinical feature:
1. Short stature.
2. Short metacarpals and metatarsals.
3. Flat nose.
4. Round face.
5. Multiple exostoses.
6. Hypercalciuria, hypocalcaemia and
hyperphosphataemia due to renal tubules does not
response to PTH.

27. Multiple exostoses.

28. Multiple exostoses.

29. • Treatment:
• Calcium.
• 1alpha-hydroxylated vitamin D metabolites, such as
calcitriol.

30. 3= Pseudopseudo-
hypoparathyroidism:
• Is another rare familial disorder.
• Have all the clinical features of
pseudohypoparathyroidism except that these patients
have no hypocalcaemia or hyperphosphataemia.
• These people their tissues respond normally to
parathyroid hormone.
• Pseudopseudo-hypoparathyroidism has been
considered an incomplete form of pseudo-
hypoparathyroidism.

32. 1. Parathyroid adenoma ‘most common’.
2. Parathyroid carcinoma

33. Parathyroid Adenoma:
• Most common.
• Occur at any age and in either sex.
• More frequently in adult life.
• Features of hyperparathyroidism.

34. Parathyroid Carcinoma:
• Rare.
• Produces manifestations of hyperparathyroidism.
• Carcinoma tends to be irregular in shape and
is adherent to the adjacent tissues.
• Most parathyroid carcinomas are well-differentiated.
• It may be difficult to distinguish carcinoma of
parathyroid gland from an adenoma but local invasion
of adjacent tissues and distant metastases are helpful
criteria of malignancy in such cases.