Parathyroid/ Calcium Flashcards
What is PTH
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.
Calcium enters the body through the
intestines
The main reservoir of calcium in the body is the bone, containing
1 kg of complexed calcium and phosphate
In the blood, calcium exists in three main forms:
free calcium
bound to albumin
complexed with anions
It is free calcium which is physiologically active and can travel into cells to exert a function.
true
PTH is secreted from
Chief cells of the parathyroid glands, located on the posterior aspect of the thyroid.
Effector organs associated with PTH include the bone and kidney:
At the bone
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.
Effector organs associated with PTH include the bone and kidney:
At the kidney
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.
How does active vitamin D work
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.
What type of hormone is active vitamin d
it is a steroid hormone.
How is PTh regulated?
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
What is PTHrp
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.
Describe the hormone profile in Primary hyperparathyroidism
PTH (Elevated)
Ca2+ (Elevated)
Phosphate (Low)
Urine calcium : creatinine clearance ratio > 0.01
Describe the hormone profile in Secondary hyperparathyroidism
PTH (Elevated)
Ca2+ (Low or normal)
Phosphate (Elevated)
Vitamin D levels (Low)
Describe the hormone profile in Tertiary hyperparathyroidism
Ca2+ (Normal or high)
PTH (Elevated)
Phosphate levels (Decreased or Normal)
Vitamin D (Normal or decreased) Alkaline phosphatase (Elevated)
Causes of Primary hyperparathyroidism
80%: solitary adenoma
15%: hyperplasia
4%: multiple adenoma
1%: carcinoma
Causes of Secondary hyperparathyroidism
Parathyroid gland hyperplasia occurs as a result of low calcium, almost always in a setting of chronic renal failure
Causes of Tertiary hyperparathyroidism
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
How is familial hypocalciuric hypercalcaemia inherited?
autosomal dominant genetic disorder
familial hypocalciuric hypercalcaemia diagnosis
genetic testing and concordant biochemistry (urine calcium : creatinine clearance ratio <0.01-distinguished from primary hyperparathyroidism).
In exams, primary hyperparathyroidism is stereotypically seen in
elderly females with an unquenchable thirst and an inappropriately normal or raised parathyroid hormone level.
sx primary hyperparathyroidism?
Features - ‘bones, stones, abdominal groans and psychic moans’
polydipsia, polyuria
peptic ulceration/constipation/pancreatitis
bone pain/fracture
renal stones
depression
hypertension
associations of primary hyperparathyroidism?
hypertension
multiple endocrine neoplasia: MEN I and II
Ix primary hyperparathyroidism?
raised calcium, low phosphate
PTH may be raised or (inappropriately, given the raised calcium) normal
technetium-MIBI subtraction scan
What is a classic x ray finding for primary hyperparathyroidism
pepperpot skull is a characteristic X-ray finding of hyperparathyroidism
Mx primary hyperparathyroidism
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
Basic problems in chronic kidney disease
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
Primary hyperparathyroidism
Indications for surgery
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)
How is Secondary hyperparathyroidism usually managed?
medical therapy.
Indications for surgery in secondary (renal) hyperparathyroidism:
Bone pain
Persistent pruritus
Soft tissue calcifications
Tertiary hyperparathyroidism mx
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.
The main symptoms of hypoparathyroidism are secondary to
hypocalcaemia
Sx HYPOparathyroidism?
tetany: muscle twitching, cramping and spasm perioral paraesthesia Trousseau's sign Chvostek's sign if chronic: depression, cataracts
What is Trousseau’s sign?
carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systoli
What is Chvostek’s sign?
tapping over parotid causes facial muscles to twitch
What ECg changes would you see in hypocalcaemia?
prolonged QT interval
Hormone profile hypoparathyroidism?
decrease PTH secretion
low calcium, high phosphate
Mx hypoparathyroidism
treated with alfacalcidol
What is Pseudohypoparathyroidism?
target cells being insensitive to PTH
due to abnormality in a G protein
Pseudohypoparathyroidism associations
low IQ, short stature, shortened 4th and 5th metacarpals
Pseudohypoparathyroidism hormone profile
low calcium, high phosphate, high PTH
Pseudohypoparathyroidism diagnosis
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.
Pseudohypoparathyroidism I vs II
pseudohypoparathyroidism type I neither cAMP nor phosphate levels are increased whilst in pseudohypoparathyroidism type II only cAMP rises.
What is Pseudopseudohypoparathyroidism?
similar phenotype to pseudohypoparathyroidism but normal biochemistry
Hypocalcaemia: causes?
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
Contamination of blood samples with EDTA may also give falsely low calcium levels.
True
Management hypocalcaemia?
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
Two conditions account for 90% of cases of hypercalcaemia:
- Primary hyperparathyroidism: commonest cause in non-hospitalised patients
- 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
Other causes of hypercalcaemia include
sarcoidosis vitamin D intoxication acromegaly thyrotoxicosis Milk-alkali syndrome drugs: thiazides, calcium containing antacids dehydration Addison's disease Paget's disease of the bone
