Hypo- and Hyperparathyroidism Flashcards
What is the epidemiology of hyperparathyroidism?
Primary hyperparathyroidism:
- F>M
- Most cases occur after 50yrs
- Uncommon
What is some key micro/anatomy of the parathyroid glands?
4x oval shaped glands in the posterior surface of the thyroid; 2x superior (derived from 4th pharyngeal arch) and 2x inferior (derived from 3rd pharyngeal arch)
Supplied by inferior thyroid arteries, drained by thyroid plexus of veins, innervated by thyroid branches of cervical ganglia
Parathyroid chief cells produce + secrete PTH in response to low serum Ca detected by calcium-sensing receptors
What is the clincal relevance of the embryology of the PTH glands?
DiGeorge syndrome:
- Congenital T-cell immunodeficiency from a microdeletion on Ch22 leading to defective development of 3rd + 4th pharyngeal pouches
Gives rise to aplastic parathyroid glands and hypocalcaemia due to PTH deficiency
What is the process of calcium and phosphate homeostasis?
Organs:
- Bone
- Kidneys
- GI tract
Players:
- Ca
- PTH
- 1,25-dihydroxyvitamin D3
Process:
- 1,25-dihydroxyvit D3 facilitates GI Ca absorption
- 1,25D3 + PTH stimulate Ca release from bone
- PTH stimulates 25hydroxyvit D3 to 1,25D3 - enabling distual renal tubular Ca reabsorption
- High serum Ca inhibits PTH and low Ca stimulates PTH
- Low PTH levels mean an increase in serum phosphate (and vice versa)
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What are the classifications of hyperparathyroidism and their causes?
Primary:
- Tumour of the parathyroid gland - most commonly a noncancerous adenoma (or gland hyperplasia)
Secondary (reactive):
- Low level of Ca induces parathyroid gland to produce large amounts of PTH; hypocalcaemia usually caused by:
- CKD/Renal failure (most common)
- Insufficient vit D
- Insufficient dietary Ca/malabsorption
- Excess dietary Mg
Tertiary:
- Occurring after years of secondary hyperparathyroidism but when the secondary cause has resolved - parathyroid gland used to producing excess PTH for a long time; gland hyperplasia and loss of homeostatic response to increasing plasma Ca
Also ectopic secretion of PTHrP from a NSCLC:
- Will have high Ca, Low PTH
What is the pathophysiology of primary hyperparathyroidism?
Overproduction of PTH by parathyroid chief cells
Effects on bone:
- PTH increases bone resorption thus increasing release of calcium phosphate and increasing serum calcium
- Bone resorption by: RANKL expression in osteoblasts - RANKL binds to RANK in osteoclasts and activates them; IL-1 expression in osteoblasts activates osteoclasts
Effects on kidneys:
- Increases phosphate excretion - phosphaturia
What is the pathophysiology of secondary hyperparathyroidism?
Low serum calcium or rising serum phosphate leads to a reactive hyperplasia of PTH glands and subsequent increase in PTH secretion
CKD:
- Impaired renal phosphate excretion leads to increasing blood phosphate levels and increasing PTH secretion
- Also biosynthesis of active vit D in kidneys is poor leading to a drop in intestinal calcium absorption + renal reabsorption - hypocalcaemia and subsequent PTH secretion
How does primary hyperparathyroidism present?
Majority are asymptomatic
(Signs of hypercalcaemia: Bones, stones, abdo groans and psychic moans:)
Renal:
- Nephrolithiasis
- Dehydration, poluria/nocturia - impaired urine concentration that is refractory to exogenous vasopressin = a renal diabetes insipidus
Cardiovascular:
- Calcification of arteries or heart muscle leading to LVH and HTN
MSK:
- Bone, muscle and joint pain
- Pseudogout
- Granular decalcification of the skull = salt+pepper skull
GI:
- Lack of appetite - weight loss
- Nausea, constipation
- Gastric or duodenal ulcers
- Pancreatitis
Psych:
- Depression
- Anxiety
- Sleep disorders
- Fatigue
How does secondary hyperparathyroidism present?
Signs of hypercalcaemia
Symptoms relating to underlying cause - often renal failure
Bone pain + risk of fractures
What are the blood results of the different classes of hyperparathyroidism?
Primary: Ca - high Urine Ca - normal (as PTH acts on DCT, increasing reabsorption) Phosphorus - low Alk phos - high PTH - high
Secondary: Ca - normal/low Phosphorus - normal/high (high in CKD) Alk phos - high PTH - high
Tertiary: Ca - high Phosphorus - variable (depending on kidney function) Alk phos - high PTH - very high
What calcium result do you need to use to interpret your findings and why?
The albumin-adjusted serum calcium/corrected calcium NOT ionised calcium
As most of calcium in serum is bound to albumin
However, in interpreting values adequate consideration must be paid to other factors which may affect albumin binding, for example, other proteins in myeloma, individual variation, cirrhosis etc.
If a one off corrected Ca >2.6mmol/L then repeat
What other tests are used to investigate hyperparathyroidism?
Primary:
- Hypercalciuria + increased cAMP in urine
Secondary:
- Underlying cause? e.g. serum creatinine
Primary + teritary:
- USS - performed before surgery to determine location of glands
- skeletal XR - usually findings are incidental as not used routinely in Dx - decreased bone mineral density, cortical thinning, salt and pepper skull Rugger-jersey spine sign (alternating low and high density in the vertebrae produces a banded pattern, similar to a striped rugby jersey)
What other disorder needs to be excluded and how?
Familial hypocalciuric hypercalcaemia
Needs differentiating from primary hyperparathyroidism
24hr urinary calcium excretion OR random renal Ca:creatinine ratio
