Parathyroid/ Calcium

Question 1

What is PTH

Answer 1

polypeptide hormone secreted from the parathyroid gland.

It has an important role in calcium homeostasis.

It acts on cell-surface receptors to generate a coordinated response throughout the body and maintain blood calcium within a narrow range.

Question 2

Calcium enters the body through the

Answer 2

intestines

Question 3

The main reservoir of calcium in the body is the bone, containing

Answer 3

1 kg of complexed calcium and phosphate

Question 4

In the blood, calcium exists in three main forms:

Answer 4

free calcium
bound to albumin
complexed with anions

Question 5

It is free calcium which is physiologically active and can travel into cells to exert a function.

Answer 5

true

Question 6

PTH is secreted from

Answer 6

Chief cells of the parathyroid glands, located on the posterior aspect of the thyroid.

Question 7

Effector organs associated with PTH include the bone and kidney:
At the bone

Answer 7

PTH acts to increase the activity of osteoclastic cells, which are responsible for bone resorption. In this way, the bone releases some of its calcium, and phosphate, stores into the bloodstream.

Question 8

Effector organs associated with PTH include the bone and kidney:
At the kidney

Answer 8

PTH as two actions. One is to increase the hydroxylation and activation of vitamin D in the proximal convoluted tubules. Another in to increase calcium reabsorption from the distal convoluted tubules and increase phosphate excretion.

Question 9

How does active vitamin D work

Answer 9

Active vitamin D has a similar action to PTH
One of its unique actions is to increase dietary calcium absorption from the intestine by increasing expression of calcium-binding hormone.

Question 10

What type of hormone is active vitamin d

Answer 10

it is a steroid hormone.

Question 11

How is PTh regulated?

Answer 11

calcium levels in the blood fall, which is detected by the parathyroid gland
chief cells secrete PTH into the blood
calcium is released from bone and reabsorbed from the renal tubules, causing its level to rise
increased calcium levels are detected by the parathyroid gland, which decreases PTH secretion

Question 12

What is PTHrp

Answer 12

polypeptide which has a similar structure to PTH, hence its name ‘related peptide’. It can be secreted from cancer cells, notably squamous cell bronchial carcinoma, to cause hypercalcaemia. PTHrp has all the same effects as PTH, however it cannot activate vitamin D.

Question 13

Describe the hormone profile in Primary hyperparathyroidism

Answer 13

PTH (Elevated)
Ca2+ (Elevated)
Phosphate (Low)

Urine calcium : creatinine clearance ratio > 0.01

Question 14

Describe the hormone profile in Secondary hyperparathyroidism

Answer 14

PTH (Elevated)
Ca2+ (Low or normal)
Phosphate (Elevated)
Vitamin D levels (Low)

Question 15

Describe the hormone profile in Tertiary hyperparathyroidism

Answer 15

Ca2+ (Normal or high)
PTH (Elevated)
Phosphate levels (Decreased or Normal)

Vitamin D (Normal or decreased)
Alkaline phosphatase (Elevated)

Question 16

Causes of Primary hyperparathyroidism

Answer 16

80%: solitary adenoma
15%: hyperplasia
4%: multiple adenoma
1%: carcinoma

Question 17

Causes of Secondary hyperparathyroidism

Answer 17

Parathyroid gland hyperplasia occurs as a result of low calcium, almost always in a setting of chronic renal failure

Question 18

Causes of Tertiary hyperparathyroidism

Answer 18

Occurs as a result of ongoing hyperplasia of the parathyroid glands after correction of underlying renal disorder, hyperplasia of all 4 glands is usually the cause

Question 19

How is familial hypocalciuric hypercalcaemia inherited?

Answer 19

autosomal dominant genetic disorder

Question 20

familial hypocalciuric hypercalcaemia diagnosis

Answer 20

genetic testing and concordant biochemistry (urine calcium : creatinine clearance ratio <0.01-distinguished from primary hyperparathyroidism).

Question 21

In exams, primary hyperparathyroidism is stereotypically seen in

Answer 21

elderly females with an unquenchable thirst and an inappropriately normal or raised parathyroid hormone level.

Question 22

sx primary hyperparathyroidism?

Answer 22

Features - ‘bones, stones, abdominal groans and psychic moans’
polydipsia, polyuria
peptic ulceration/constipation/pancreatitis
bone pain/fracture
renal stones
depression
hypertension

Question 23

associations of primary hyperparathyroidism?

Answer 23

hypertension

multiple endocrine neoplasia: MEN I and II

Question 24

Ix primary hyperparathyroidism?

Answer 24

raised calcium, low phosphate
PTH may be raised or (inappropriately, given the raised calcium) normal
technetium-MIBI subtraction scan

Question 25

What is a classic x ray finding for primary hyperparathyroidism

Answer 25

pepperpot skull is a characteristic X-ray finding of hyperparathyroidism

Question 26

Mx primary hyperparathyroidism

Answer 26

the definitive management is total parathyroidectomy conservative management may be offered if the calcium level is less than 0.25 mmol/L above the upper limit of normal AND the patient is > 50 years AND there is no evidence of end-organ damage calcimimetic agents such as cinacalcet are sometimes used in patients who are unsuitable for surgery

Question 27

Basic problems in chronic kidney disease

Answer 27

low vitamin D (1-alpha hydroxylation normally occurs in the kidneys) high phosphate low calcium: due to lack of vitamin D, high phosphate secondary hyperparathyroidism: due to low calcium, high phosphate and low vitamin D

Question 28

Primary hyperparathyroidism | Indications for surgery

Answer 28

Elevated serum Calcium > 1mg/dL above normal Hypercalciuria > 400mg/day Creatinine clearance < 30% compared with normal Episode of life threatening hypercalcaemia Nephrolithiasis Age < 50 years Neuromuscular symptoms Reduction in bone mineral density of the femoral neck, lumbar spine, or distal radius of more than 2.5 standard deviations below peak bone mass (T score lower than -2.5)

Question 29

How is Secondary hyperparathyroidism usually managed?

Answer 29

medical therapy.

Question 30

Indications for surgery in secondary (renal) hyperparathyroidism:

Answer 30

Bone pain Persistent pruritus Soft tissue calcifications

Question 31

Tertiary hyperparathyroidism mx

Answer 31

Allow 12 months to elapse following transplant as many cases will resolve The presence of an autonomously functioning parathyroid gland may require surgery. If the culprit gland can be identified then it should be excised. Otherwise total parathyroidectomy and re-implantation of part of the gland may be required.

Question 32

The main symptoms of hypoparathyroidism are secondary to

Answer 32

hypocalcaemia

Question 33

Sx HYPOparathyroidism?

Answer 33

``` tetany: muscle twitching, cramping and spasm perioral paraesthesia Trousseau's sign Chvostek's sign if chronic: depression, cataracts ```

Question 34

What is Trousseau's sign?

Answer 34

carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systoli

Question 35

What is Chvostek's sign?

Answer 35

tapping over parotid causes facial muscles to twitch

Question 36

What ECg changes would you see in hypocalcaemia?

Answer 36

prolonged QT interval

Question 37

Hormone profile hypoparathyroidism?

Answer 37

decrease PTH secretion | low calcium, high phosphate

Question 38

Mx hypoparathyroidism

Answer 38

treated with alfacalcidol

Question 39

What is Pseudohypoparathyroidism?

Answer 39

target cells being insensitive to PTH | due to abnormality in a G protein

Question 40

Pseudohypoparathyroidism associations

Answer 40

low IQ, short stature, shortened 4th and 5th metacarpals

Question 41

Pseudohypoparathyroidism hormone profile

Answer 41

low calcium, high phosphate, high PTH

Question 42

Pseudohypoparathyroidism diagnosis

Answer 42

diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH. In hypoparathyroidism this will cause an increase in both cAMP and phosphate levels.

Question 43

Pseudohypoparathyroidism I vs II

Answer 43

pseudohypoparathyroidism type I neither cAMP nor phosphate levels are increased whilst in pseudohypoparathyroidism type II only cAMP rises.

Question 44

What is Pseudopseudohypoparathyroidism?

Answer 44

similar phenotype to pseudohypoparathyroidism but normal biochemistry

Question 45

Hypocalcaemia: causes?

Answer 45

vitamin D deficiency (osteomalacia) chronic kidney disease hypoparathyroidism (e.g. post thyroid/parathyroid surgery) pseudohypoparathyroidism (target cells insensitive to PTH) rhabdomyolysis (initial stages) magnesium deficiency (due to end organ PTH resistance) massive blood transfusion acute pancreatitis

Question 46

Contamination of blood samples with EDTA may also give falsely low calcium levels.

Answer 46

True

Question 47

Management hypocalcaemia?

Answer 47

acute management of severe hypocalcaemia is with intravenous replacement. The preferred method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes intravenous calcium chloride is more likely to cause local irritation ECG monitoring is recommended further management depends on the underlying cause

Question 48

Two conditions account for 90% of cases of hypercalcaemia:

Answer 48

1. Primary hyperparathyroidism: commonest cause in non-hospitalised patients 2. Malignancy: the commonest cause in hospitalised patients. This may be due to number of processes, including; bone metastases, myeloma, PTHrP from squamous cell lung cancer

Question 49

Other causes of hypercalcaemia include

Answer 49

``` sarcoidosis vitamin D intoxication acromegaly thyrotoxicosis Milk-alkali syndrome drugs: thiazides, calcium containing antacids dehydration Addison's disease Paget's disease of the bone ```