Parathyroid Pathologies Flashcards
What causes parathyroid secretion?
- Parathyroid hormone is normally secreted in response to low ionised calcium levels by four parathyroid glands which are situated posterior to the thyroid gland
- The glands are controlled by positive feedback via Ca2+ levels
What is the normal function of parathyroid hormone?
- They increase osteoclast activity releasing calcium and phosphate from bones
- Increased calcium and decreased phosphate reabsorption in the kidney
- Active calcitriol production is increased
- Overall effect is increased calcium and decreased phosphate
What is hyperparathyroidism and what are the two types?
- Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood.
- This occurs either from a disorder within the parathyroid glands (primary hyperparathyroidism) or disorder outside the parathyroid glands (secondary hyperparathyroidism) resulting in them making too much PTH.
What are the causes of primary hyperparathyroidism?
- Solitary adenoma
- Hyperplasia of all glands
- Parathyroid cancer
How does primary hyperparathyroidism presented?
- Often asymptomatic
- Increased calcium on routine tests
- Weak
- Tired
- Depressed
- Thirsty
- Dehydrated but pilyuric
- Renal stones
- Abdominal pains
- Pancreatitis
- Ulcers
- Bone resorption effects of PTH can cause pain, fractures and osteopenia/osteoporosis
- Hypertension
What the tests do you carry out to investigate primary hyperparathyroidism?
- Increased serum or urinary calcium and PTH (or if its inappropriately normal
- Decreased phosphate
- Raised ALP from bone activity
- 24hr urinary calcium
- Imaging to check for osteoporosis or osteopenia signs
- Decreased renal function
- Renal calculi
How is primary hyperparathyroidism treated?
- Increase fluid intake to prevent renal stones
- AVoid thiazides and high calcium and vitamin D intake
- Excision of the adenoma or of all four hyperplastic glands to prevent fractures and peptic ulcers
- A calcimimetic (such as cinacalcet) is a potential therapy for some people with severe hypercalcemia and primary hyperparathyroidism who are unable to undergo parathyroidectomy and for secondary hyperparathyroidism on dialysis.
How does cinacalet work?
- It is a calcimemetic so increases sensitivity of parathyroid cells to calcium therefore decreasing PTH secretion
What are the side effects of cinacalcet?
- Myalgia
- Decreased testosterone
What is secondary hyperparathyroidism?
- In people with secondary hyperparathyroidism, the high PTH levels are an appropriate response to low calcium
What are the causes of secondary hyperparathyroidism?
- Vitamin D deficiency
- Chronic kidney disease
- Other causes of low blood calcium
How is seconday hyperparathyroidism diagnosed?
- Low serumc calcium, high PTH
How is secondary hyperparathyroidism treated?
- Treat underlying cause of this (usually vitamin D deficiency or chronic kidney failure).
- If this is successful PTH levels should naturally return to normal levels unless PTH secretion has become autonomous (tertiary hyperparathyroidism)
- Cinacalcet if PTH and parathyroidectomy is tricky
What is tertiary hyperparathyroidism?
- Tertiary hyperparathyroidism is seen in patients with long-term secondary hyperparathyroidism, which eventually leads to hyperplasia of the parathyroid glands and a loss of response to serum calcium levels
- This disorder is most often seen in patients with end-stage kidney disease and is an autonomous activity.
- Serum calcium and parathyroid levels are raised
- Increased serum calcium from very increased secretion of PTH unlimited by feedback control
What is malignant hyperparathyroidism?
- Parathyroid related protein is produced by some sqaumous cell lung cancers, breast and renal cell carcinomas
- This mimics PTH resulting in increased calcium
- PTH is decreased and calcium is raised
- PTHrP is not detected in the assay
What is hypoparathyroidism?
- Hypoparathyroidism is the state of decreased secretion or activity of parathyroid hormone (PTH).
- This leads to decreased blood levels of calcium (hypocalcemia) and increased levels of blood phosphorus (hyperphosphatemia).
What is primary hyperparathyroidism?
- Decreased PTH secretion due to gland failure
- Low Calcium and raised or normal phosphorus levels
- Patient presents with signs of hypocalcaemia
Patients with primary hyperparathyroidism present with signs of hypocalcaemia. What are the signs of hypocalaemia?
- confusion or memory loss.
- muscle spasms.
- numbness and tingling in the hands, feet, and face.
- depression.
- hallucinations.
- muscle cramps.
- weak and brittle nails.
- easy fracturing of the bones.
What are the causes for primary hypoparathyroidism?
- Autoimmune
- Congenital
How is primary hypoparathyroidism treated?
- Calcium supplements and Calcitriol
What are the causes of secondary hypoparathyroidism?
- Surgery (thyroidectomy/parathyroidectomy)
- Trauma
- Radiation
- Hypomagnasaemia
- Magnesium is required for PTH secretion
What is pseudoparathyroidism?
Failure of target cells to respond to PTH
How does pseudoparathyroidism present?
- Short metacarpals (especially 4th and 5th)
- Round face
- Short stature
- Calcified basal ganglia
- Decreased IQ
- Low calcium
- High PTH
- Normal or high ALP
How is pseudohypoparathyroidism treated?
- Calcium supplements and calcitriol
- Or synthetic PTH as it prevents hypercalciuria
What is pseudopseudohypoparathyroidism?
- The morphological features of pseudohypoparathyroidism but with normal biochemistry
- The cause of both is genetic
What are MEN syndromes?
- The MEN syndromes are conditions which cause overactivity and enlargement in certain endocrine glands.
- MEN syndromes are usually (but not always) inherited conditions and therefore they run in families.
- They are inherited as autosomal dominant
- There are functioning hormone-producing tumours in multiple organs
- They comprise MEN 1 and 2 and endocrine tumours eg:
- Pituitary adenoma
- Adrenal hyperplasia
- Testicular tumour
What are the causes of MEN 1, 2a and 2b syndrome?
