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
What investigations are necessary after diagnosis of primary hyperPTH?
Assess symptoms + comorbiditities
Measure eGFR or serum creatinine
DEXA scan of lumbar spine, distal radius and hip
USS renal tract
How do you manage primary hyperparathyroidism?
Surgery:
- Symptomatic patients (thirst, frequent excessive urination, constipation) -OR
- End organ damage (renal stones, fragility fractures or osteoporosis)
- Asymptomatic patients with an adjusted calcium of >2.85mmol/L
Calcimimetics:
- e.g. Cinacalcet
- If unsuitable for surgery, or it was unsuccessful
- Unsuitable in pregnancy
Bisphosphonates:
- To reduce fractures in those deemed to be at risk ONLY
Monitoring:
- Adjusted Ca once a year
- eGFR once a year
- ?DEXA scan 2-3yrs
What are the causes of hypoparathyroidism?
Iatrogenic:
- Following anterior neck surgery
- The most common cause
Radiation/drugs/surgery to PTH glands:
- For cancer, hyperparathyroidism etc
- Alcohol
Infiltration of glands:
- Fe - in haemochromatosis
- Cu - in Wilson’s
- Cancer/mets
Magnesium imbalances:
- Deficiency (chronic alcoholism, burns)
- Excess (when used in preterm labour or preeclampsia)
Transient neonatal hypoparathyroidism:
- Healthy term neonates drop their Ca between 24-48hrs of age
- Some are at greater risk (mothers with DM, prems, perinatal asphyxia)
- Requires supplementation for at least 72hrs
DiGeorge syndrome:
- Ch22 disorder affecting 3rd/4th pharaneal pouch development
- The PTH glands, thymus gland, aortic arch and parts of the lips and ears develop from these pouches
- Hypoparathyroidism, T-cell immune deficiency, abnormal facies such as cleft palate, and cardiac anomalies
Pseudohypoparathyroidism:
- rare inherited disorder where there is failure of target cells to respond to PTH/PTH resistance
How does hypoparathyroidism present?
Asymptomatic, lab finding
Muscle pain
Bone pain - due to decreased turnover and high bone mineral density
Abdo pain
Paraesthesiae of face, fingers and toes
Facial twitching - Chvostek’s sign = tapping of facial nerve in front of the ear with the patient’s mouth slightly open causes twitching of facial muscles
Trousseaus sign
Inflation of sphyg. cuff above systolic pressure for 3 mins causes titanic spasm of fingers and wrist
Headaches
Memory impairment
Emotional lability, anxiety depression, confusion
Lethargy
Hyperreflexia
Convulsions
Dry skin Brittle nails Painful menstruation Stridor Raised ICP Cataracts
What blood tests are important in hypoparathyroidism?
Corrected calcium - low
Serum phosphate - high
Alk phos - normal
PTH - low (will be high/normal in pseudohypoparathyroidism)
Magnesium - may be low if its a cause
U+E - to exclude CKD
25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3:
- To exclude vitamin D deficiency as a cause of hypocalcaemia
- 25-hydroxyvitamin D3 is normal in hypoparathyroidism and pseudohypoparathyroidism but 1,25-dihydroxyvitamin D3 is low because PTH is not available for its activation
24hr urinary Ca - usually low
Other: ECG - prolonged QT? Echo - cardiac abnormalities in DiGeorge's? Renal USS - calculi? Genetic studies as appropriate
If autoimmune process suspected:
- Blood TSH, thyroxine + thyroid autoantibodies - to exclude co-occurring thyroid insufficency
- Blood adrenocorticotrophic hormone (ACTH) and adrenal antibodies - to exclude co-occurring adrenal insufficiency
How do you treat hypoparathyroidism?
Ca + Vit D3 supplementation:
- Tailored to individual need - sometimes once adequate stores are reached, dietary control is enough, for others lifelong supplementation is required
- Regular monitoring needed
How do you quickly remember the difference between the hyperparathyroidisms?
Primary = tumour (kidney function normal), raised Ca
Secondary = Vit D low/CKD, normal/low Ca
Tertiary = hyperplasia (i.e. secondary gone wild i.e. kidney function off), high Ca
