parathyroid glands Flashcards
what are the parathyroid glands composed of
chief cells
what do the parathyroid gland chief cells secrete
PTH
what does PTH act on
CASR (calcium sensing receptor)
what kind of receptor is the CASR
GPCR that regulates extracellular calcium homeostasis
what do chief cells look like
round cells with moderate cytoplasm and bland round central nuclei
what cells support the chief cells
oxyphil cells (slightly larger with acidophilic cytoplasm)
what does PTH do to osteoclast activity
increases osteoclast activity releasing Ca and phosphate
what does PTH do to small bowel absorption of calcium and phosphate
indirectly increases small bowel absorption of Ca and phosphate by activating vitamin D
what does PTH do to kidney reabsorption of calcium
increased calcium reabsorption in distal tubule
what does PTH do to phosphate excretion in kidney
decreased phosphate excretion in proximal tubule
what effect does increased serum calcium have on PTH secretion
negative feedback
what are the 4 main symptoms of hypercalcaemia
BONES
MOANS
STONES
GROANS
BONES
pain
fracture
osteoporosis
osteitis fibrosa cystica
what is osteitis fibrosa cystica
resorption of bone leading to fibrosis and cystic spaces
what ix should be done in ‘bones’ symptoms of hypercalcaemia
DEXA
STONES
nephrolithiasis and complications
GROANS
GI complications - nausea, constipation, peptic and duodenal ulcers, acute pancreatitis, gall stones, abdominal pain
MOANS
depression, lethargy, seizures, weakness and fatigue
what are some other symptoms of hypercalcaemia
nephrocalcinosis - calcification of renal tubules - can lead to renal insufficiency and polyuria
calcification of the aortic and mitral valves
hypertension
what are s/s of acute hypercalcaemia
thirst
dehydration
confusion
polyuria
what is the treatment of acute hypercalcaemia
fluids (0.9% saline, 4-6L in 2 hours) loop diuretics (avoid thiazide)
what is the treatment of acute hypocalcaemia
IV calcium gluconate (10ml in 50ml saline or dextrose)
what are some s/s of hypocalcaemia
muscle weakness muscle spasm (tetany) muscle cramps fits fatigue paraesthesia of fingers, toes and perioral area bronchospasm or laryngospasm
what is an ECG change of hypocalcaemia
QT prolongation
what 2 signs are positive in hypocalcaemia that show muscle spasm/tetany
Chovslek’s sign - tapping over facial nerve
Trosseau sign - carpopedal spasm - filling of a BP cuff
how is vitamin D3 formed
by the skin on exposure to the sun
where can you get Vitamin D3 and D2
from diet
the liver metabolises vitamin D3 to
25-OH-vitamin D
the kidney metabolises 25-OH-vitamin D to
1,25-hydroxy vitamin D
in what condition will almost always develop a parathyroid adenoma and hypercalcaemia at a young age
MEN 1/2
what are some causes of hypocalcaemia
hypoparathyroidism vit D deficiency chronic renal failure pancreatitis hyperventilation osteoblastic bone mets rhabdomyolysis high turnover - bed ridden, thyrotoxic, Pagets granulomatous disease e.g. sarcoid/TB drugs - Vit D, thiazides, lithium
primary hyperparathyroidism biochemistry: Ca PTH Phosphate urinary cAMP ALP
HIGH Ca HIGH PTH low phosphate HIGH urinary cAMP HIGH ALP
what is primary hyperparathyroidism
primary overactivity of the parathyroid galnds
what are the 4 main causes of primary hyperparathyroidism
adenoma
hyperplasia
carcinoma
malignancy
what is the most common cause of primary hyperparathyroidism
adenoma
how many glands are affected in parathyroid adenoma
just one - other glands are atrophic
how does an parathyroid adenoma usually present
usually asymptomatic hypercalcaemia but may get BSMG
what is the treatment of a parathyroid adenoma
removal of affected gland
although an adenoma may resemble a normal parathyroid gland microscopically, what might you see
fibrous connective tissue capsule with adjacent rim of compressed parathyroid tissue
what syndromes is parathyroid hyperplasia associated with
MEN 1 / MEN2b
parathyroid hyperplasia usually involves what glands
all glands
what is the treatment of parathyroid hyperplasia
removal of all affected glands
what % of primary hyperparathyroidism is due to hyperplasia
5-10%
what % of primary hyperparathyroidism is due to carcinoma
1%
what are some complications of parathyroid excision
recurrent laryngeal nerve palsy
hypoparathyroidism
low Ca - hungry bone sydrome
what cancer causes a paraneoplastic syndrome there there is release of PTHrp from solid tumours
squamous cell lung cancer
breast/renal cell carcinomas
how is hyperparathyroidism caused by malignancy diagnosed
raised Ca and ALP xray CT MRI isotope bone scan
what is PTH like in hyperparathyroidism caused by malignancy
PTH low - PTHrp causes high Ca which negatively feeds back to PTH
what is familial isolated hyperparathyroidism
inherited form of hyperparathyroidism
get an adenoma
what are the indications for a parathyroidectomy
end organ damage (bone disease, gastric ulcers, renal stones)
Ca > 2.85
< 50
eGFR < 60
what is secondary hyperparathyroidism
chronic hypocalcaemia causes compensatory over activity of the parathyroid glands
secondary hyperparathyroidism biochemistry Ca PTH phosphate ALP
LOW calcium
HIGH PTH
HIGH phosphate
raised ALP
what is the most common cause of secondary hyperparathyroidism
chronic renal failure
how does chronic renal failure lead to secondary hyperparathyroidism
renal insufficiency leads to decreased phosphate excretion
increased serum phosphate binds to free Ca
decreased free Ca stimulates all 4 parathyroid glands
increased PTH —> bone resorption
what is the parathyroid tissue like in secondary hyperparathyroidism
hyperplastic
what is the treatment for secondary hyperparathyroidism
phosphate binders
vit D
what else might be raised in secondary hyperparathyroidism
25-OH vit D
metabolised by the kidneys so accumulation
what is tertiary hyperparathyroidism
parathyroid gland becomes autonomous due to many years over over activity e.g. in renal failure
tertiary hyperparathyroidism biochemistry
Ca
PTH
Phosphate
HIGH Ca
HIGH PTH
raised phosphate
what is cinacalcet
calcium mimetic
when is cinacalcet used
tertiary hyperparathyroidism
carcinoma
primary if not fit for surgery
how does cinacalcet decrease PTH
increases sensitivity of parathyroid cells to Ca so decreases PTH secretion
familial hypocalciuric hypercalcaemia biochemistry
Ca
urine Ca
PTH
mild hypercalcaemia
decreased urine calcium excretion
marginally elevated PTH
usually benign/asymptomatic
what is the inheritance of FHH
autosomal dominant
what is the genetic cause of FHH
deactivating mutation in CASR
what does vit D deficiency lead to with regard to calcium levels
low calcium
Low calcium muscle wasting - proximal myopathy dental defects (Caries, enamel) tender bones/fractures/rib deformitity/limb deformity waddling gait loosers zones
osteomalacia
rickets in children
what is Vitamin D resistant rickets
X linked hypophosphataemia
what is the gene mutation in X linked hypophosphataemia
PHEX or FGF23
what does the FGF23 gene usually do
regulates phosphate levels in plasma
what are the levels of phosphate and vitamin D like in vitamin D resistant rickets
high vitamin D
low phosphate
what is the treatment for vitamin D resistant rickets
phosphate and vitamin D supplements
what are some long term consequences of vitamin D deficiency
bone disease
malignancy (esp colon)
heart disease
diabetes
what is the treatment for vitamin D deficiency
Vit D3 tablets
calcitrol
alfacalcidol
combined calcium + vit D e.g. adcal D3
what is the PTH and Ca level in hypoparathyroidism
low PTH
low Ca
what is the treatment of hypoparathyroidism
calcium supplements and vitamin D tablets
calcitrol
synthetic PTH
is hypo or hyper parathyroidism more common
hyper
hypo is very rare
what are some causes of hypoparathyroidism
usually post op - surgery/radiotherapy malignancy congenital absence - Di George Syndrome (22q11.2) familial hypomagnesaemia
how does hypomagnesaemia cause hypoparathyroidism
calcium release from cells + PTH secretion both rely on magnesium
what is the treatment of hypomagnesaemia
calcium and magnesium replacement
what can cause hypomagnesaemia
alcohol, drugs (thiazide, PPI), GI illness, pancreatitis, malabsorption
what is pseudohypoparathyroidism
failure of target cell response to PTH
what is the genetic defect in pseudohypoparathyroidism
dysfunction of G protein (Gs alpha subunit)
GNAS-1 gene
what is the biochemistry of pseudohypoparathyroidism
Ca
phosphate
PTH
Low Ca
High phosphate
High PTH
what are some s/s of pseudohypoparathyroidism
obesity/round face subcutaneous calcification learning disability calcified basal ganglia AD form assoc. short stature and brachydactylyl of 4th and 5th metacarpals bone abnormalities
what is the treatment of pseudohypoparathyroidism
calcium and vit D supplements
what is pseudopseudohypoparathyroidism
normal biochemistry but morphological features of pseudohypoparathyroidism
what is another name for pseudopseudohypoparathyroidism
albright’s hereditary osteodystrophy
what is a sign of mccune albright syndrome in bones
areas of abnormal fibrous scarring in bones
