Parathyroid Flashcards
Calcium
Transported in blood bound to proteins including albumin Needed for synapses, muscle contraction and coag function.
Regulated by PTH, Vit D and calcitonin
Parathyroid - has Calcium sensor CaSR
- Decrease in calcium - increase in PTH
- Loss of function - familial hypocalciuric hypercalcaemia
PTH
Parathyroid hormone - Half life 4.5 min, Binds to PTH1R and PTH2R receptors
Acts to increase Ca
- Kidneys - increases resportion Ca, excretion phosphate, renal synthesis of calcitriol
- Bone - mobilizes Ca stores
- Gut 0 - with calcitriol, increased gut resorption
Vit D
Vit D
- Fat soluble vitamin, mostly from UV but also from diet
- Inactive form cholecalciferol D3
- Changed to calcidiol D2 in liver and to active calcitriol (1, 25 hydroxyvitamin D) in kidney
- Promotes gut resorption, bone resorption, decreased renal excretion
Calcitonin
Polypeptide from parafollicular C cells, stimulated by high Ca and tones down the calcium
- Acting on bones and renal
Hypercalcaemia
Aetio - high PTH, FHH, MEN
- Malig - breast, lung, myeloma - PTHrP 80% binds to PTH1R activating, the rest due to osteolytic mets or tumour secreting Vit D calcitriol
- (Other - meds, TPN, osteolytic bone mets, adrenal insuf, hyperthyroid)
N - 2.10-2.55 (corrected)
- Mild - 2.55-3 - fatigue, constipation
- Mod - 3-3.5 nausea, weakness, polyuria
- Sev - >3.5
Work up - malig, endo, FHH, meds,
- Check PTH - if low check PTHrP, Vit D, look for tumours
Hypercalcaemia Tx
Mild - Decrease intake, correct other electrolytes, stop meds, tx cause
- Oral rehydration
Mod - IV rehydration, bisphosphonates, tx cause
Sev - IVF resuscitation aim 200mL per hour out to help excretion
- Bisphosphonates, calcitonin, tx cause
- decrease resorption - loop diuretic once rehydrated
- Calcimimetic - cinacalcet
HyperPTH / HyperCa Effects
Stones, bones, groans, moans
Renal - Nephrolithiasis, nephrocalcinosis, renal impairment
Bone - Osteoporosis, pathological fractures
GI - Constipation, anorexia, nausea, panc
Neuro - anxiety, depression, lethargy, confusion
CVS - arrythmia - short QT
Calciphylaxis
HypoCa
Aetio
- HOPTH - dialysis, post parathyroid, neck radx, sarcoid, familial DiGeorge
- CRF - decreased Vit D conversion, low calcitriol, decr Ca absorption
- Vit D def (or liver problems)
- Meds - cinacalcet, phenytoin, chemo, bisphosphonates, bowel prep
- Hungry bone syn - sudden bone remodelling severe drop
- Other - binding/chelation - citrate, bicarb, lactate,
- low Mg, high phos
- panc - ppt of ca in abdomen
- post op malabsorption, critical illness
Clin - Perioral numbness, peripheral cramps and paraesthesias
- Severe - neuromuscular instability - tetany, seizures, laryngospasm
- Cardiac - prolonged QT, torsades de points
- Chvostek sign - contraction facial muscles tapping over facial N
- Trousseau’s sign - carpopedal spasm, BP cuff occluding art
HypoCa Tx
Bloods - Ca and PTH, Mg and Phos and Vit D
Mild - oral - calcium carbonate 1.2g PO tds
Severe - syx, ECG change, Ca <1.9
- Resus - IVF, oxygen, telemetry
- IV Calcium gluconate - 10mL of 10% (1g) - over 5 min as a bolus
- Can give repeated if needed or an infusion of 20-30mL in 500mL over 4-6 hours
Other - tx low Mg
- Oral Vit D - calcitriol 250 micrograms OD
- then cholecalciferol 1.25g OD 10 days
Familial Hyper PTH
MEN1 - Germline mutation MEN1 menin - rare, with PNET and Pit
- 90 % have 4 gland hyperplasia, extra glands in 20%
- Tx - subtotal / total parathyroidectomy - risk of recurrence, look for supernumerary
MEN2A - Germline mutation RET - Medullary thy ca, phaeo
- Hyper PTH in 20-30% - usually single gland but all at risk - tx as adenoma
- But main focus in medullary thyroid cancer management
FHH - Familial hypocalciuric hypercalcaemia - AD high penetrance, mutation in CaSR
- parathyroid not responsive to Ca - high Ca and low PTH, low urine Ca excretion
- causes mild Hyper Ca, low PTH and low urinary Ca <5mmol/24hour
- rare syx, no tx usually
Secondary Hyper PTH
Low calcium - not enough absorbed from bones, gut and kidneys
- Due to low Vit D or CRF
- Stimulates a high PTH - with gland hyperplasia
Clin - generally asyx, consider in CRF
- pruritus, osseus lesions, calcium deposits including calciphylaxis.
- calciphylaxis - calcific uraemic arteriopathy - progressive cutaneous ischaemia
Tx underlying cause
Tertiary Hyper PTH
Long term secondary hyperparathyroidism - usually in CRF
- Leads to hyperplasia of the parathyroid glands and high baseline PTH secretion
- Then when the secondary hyperparathyroidism is treated
- Persistent autonomous secretion of PTH after treatment (renal transplant)
- Due to loss of response to Ca
Leads to high Ca absorption
Tx
- Calcimimetics - cincalcet
- If non responding - resection of excess parathyroids - leaving just enough to have normal level.
- Needed in under 5%
- if lasting longer than 12 months - failure of medical management - pruritus, bone pain, muscle pain, bone turnover and path fractures
- intra op frozen section - subtotal or total with auto transplantation.
- complications - missed glands, hypoparathyroidism lifelong replacement
Parathyroid Ca
Rare, presents as uncontrolled primary HPTH - hyperCa severe
- RF, arrhythmias, palpable neck mass, raised Ca, RLN invasion
OT - dense scarred, difficult
- consider oncological resection - ispilateral thyroid lobe, both glands and adjacent nodes, take RLN if invaded. Explore contralateral parathyroids.
Post op - reoperate - remove thyroid and parathyroid ipsilateral, LN
Local recurrence 50%, distant mets 30%
- aggressive OT - threat is from high Ca
- 5y OS 85% but 50% at 10y
Primary Hyper PTH
High PTH secretion relative to calcium
- Common, 85% single adenoma, 5% multiple, 5% 4 gland, 1% Ca
- Adenoma - tan beefy kidney appearance, micro oxyphil cells and fibrous capsule
- Hyperplasia - clonal expansion, uniform cells, chief cells - needs 4 gland exploration
- Ca - rare, difficult - suspect if palpable, RLN involved, adherent
- risk factors - radx, MEN1/2A
- histo bizarre atypia - dx is based on local invasion, mets
- not for mips needs exploration
Clin - most asyx on blood tests
- Syx - Stones, moans, bones, groans
- General - weakness, fatigue, thinning hair
- GI - PUD, constipation, pancreatitis, anorexia, N and V
- CVS - brady, arrhythmias, heart block
- Renal - nephrolithiasis/ nephrocalcinosis, polyuria and polydipsia, renal failure, volume depletion
- MSK - osteopenia, osteoporosis, osteitis fibrosa cystica, fractures, muscle weakness, ataxia
- Neuropsych - anxiety, headaches, confusion, depression and coma
Dx - raised Ca, raised PTH, low phos
- 24 hour urine calcium or urine calcium / creat ratio - high Ca rules out FHH
- BMD for osteopenia
Primary Hyper PTH Tx
Localization for MIPS - not for dx
- USS fast, rule out thyroid and nodes, hypoechoic lesion posterior to the thyroid gland with single feeding vessel
- 4D CT - fine slice CT with dedicated radiologist and 4th D is time - perfusion characteristic of parathyroid
- Sestamibi scan - lipophilic cation with 6 MIBI molecules around a Tc 99, accumulates in mitochondria - good for side but not sup/inf. To diff from thyroid - subtraction imaging (I-123) or dual phase delayed imaging slow washout from parathyroid. Normal uptake thyroid, parathyroid, heart, salivary glands.
- SPECT - sestamibi CT scan
- Angio venous sampling - sens - reoperation - compare CFV to neck vein PTH levels - if double is positive. Rare to need this.
- MRI - rare
Management - parathyroidectomy or monitor
Monitor - patient choice - over age 50, no symptoms or organ dysfunction, calcium level less than 1mg/dL above normal
- annual biochem, periodic DEXA scan
Syx
- Renal - any impairment, stones/calcinosis
- Bones - BMD T score under - 2.5, fractures
- Neurocogn syx
- Abdo syx,
