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Flashcards

Hypercalcaemia

Ellie Britt Endocrinology English 31 cards

hypercalcaemia investigations

Cards in this deck (31)

  1. 1Functions of calcium (6)- muscle contraction
    - stabilisation of membranes
    - bone growth and remodelling
    - second messenger signalling
    - secretion of hormones eg. insulin
    - enzyme co-factor eg. in blood coagulation
  2. 2distribution of calcium in the adult human bodyskeleton 99%
    intracellular 0.01%
    (endoplasmic reticulum, mitochondria)
    extracellular 0.99%
    - 45% ionised, 55% bound (albumin, lactate, phosphate)
  3. 3What is ionised calcium regulated by?PTH and vitamin D
  4. 4Parathyroid glands - how many - where - arteryUsually 4 glands (2-6)
    Posterior aspect of thyroid gland
    10% are ectopic!!
    Weigh 30-50mg
    Supplied by inferior thyroid artery (caution during thyroid surgery)
  5. 5Parathyroid hormone actionINCREASES BLOOD CALCIUM
    Kidney
    - Reabsorption of calcium at distal tubule
    - Internalises sodium-phosphate co-transporters at proximal tubule
    - Inhibits Na+/H+ leading to bicarbonate wasting
    Bone
    - Increased number and activity of osteoclasts in continuous PTH exposure
    - Intermittent exposure increases anabolic activity of osteoblasts
    Gut
    - Stimulates synthesis of active form of Vit D in kidney (1,25 dihydroxy cholecalciferol)
    - Thereby increases calcium absorption from the gut.
  6. 6Parathyroid hormone storage and secretionStored in chief cells of parathyroid glands
    Secretion controlled by the calcium sensing receptor (CaSR)
    -->
    inhibits transcription of PTH gene, PTH secretion inhibited
    (Calcimimetic drugs target the CaSR and inhibit PTH secretion)
    calcium sensing proteases activated --> PTH brokwn down/inactivated
  7. 7PTH loss of function mutationsfamilial hypocalciuric hypercalcaemia
  8. 8calcium sensing receptor actionNot unique to parathyroid gland. Also expressed in brain, intestine and bone where role less well understood.
    Kidney
    - Increases urinary calcium and magnesium excretion
    - Increases sodium, potassium and chloride excretion
    Thyroid
    - Expressed in C-cells
    - Stimulates calcitonin secretion
  9. 9Vitamin D - receptor - action - precursor - active formSteroid hormone i.e. needs to bind to a nuclear receptor (vitamin D receptor)
    Acts to increase serum calcium levels
    Precursors synthesised in the skin (cholecalciferol D3, from 7-dehydrocholesterol)
    storage form 25.HCC in liver
    Active form is 1,25 dihydroxycholecalciferol) - made in kidney
  10. 10actions of vitamin D- increases calcium and phosphate absorption
    - bone mineralisation and mobilises calcium stores
    - immunomodulation (B and T cells)
    - increases muscle strength
    - reduces insulin resistance
    - interacts with RAAS (role in prevention of CVD?)
  11. 11Clinical Vitamin D Assays25-OHD3 is generally accepted for functional measurement of Vit D status as it is the most abundant and stable metabolite.
    cana lso measure 1.25OHD3
    Beware 25-OHD3 measurement in renal disease!
  12. 12symptoms of hypercalcaemiaIf mild, often asymptomatic
    Once calcium >3mmol/L symptoms are common.
    - confusion, depression, fatigue, coma
    - muscle weakness, bone pain, osteoporosis
    - shortening of QTc, bradycardia, hypertension
    - anorexia, nausea, constipation, pancreatitis
    - polyuria, nephrogenic DI, stones, nephrocalcinosis
  13. 13PTH-mediated hypercalcaemia aetiology- Primary hyperparathyroidism
    - Familial syndromes e.g. MEN-1 and MEN-2
    - Familial hypocalciuric hypercalcaemia
  14. 14PTH-independent hypercalcaemia aetiology- Malignancy
    - Granulomatous disorders
    - Vitamin D toxicity
    - Drugs: Thiazides, Lithium, Calcium supplements!
    - Adrenal insufficiency
    - Milk-alkali syndrome
    - Immobilisation
  15. 15hypercalcaemia investigationshypercalcaemia investigations
  16. 16Malignancy and hypercalcaemiaCommonest cause of hypercalcaemia in hospitalised patients
    1) Osteolytic metastases and myeloma
    2) Tumour secretion of PTHrP
    - Binds PTH receptor and stimulates bone resorption and renal Ca2+ reabsorption
    Can be measured directly
    e.g. squamous cell lung cancer; oesophageal cancer; renal cell carcinoma; breast cancer
    3) Tumour production of 1,25 dihydroxycholecalciferol
    - By activated macrophages
    - Occurs in lymphoma
  17. 17vitamin D toxicity - what - why - outcome- Increased bone resorption and gut absorption
    - Ingestion of high doses of calcitriol (e.g. hypoparathyroid or renal disease)
    - Resolves within 48 hrs of stopping offending agent
  18. 18Endogenous production of 1,25 dihydroxycholecalciferolE.g. lymphoma; sarcoid, Wegeners granulomatosis
    Extra-renal activation of cholecalciferol
    Usually responsive to steroid treatment
  19. 19Adrenal insufficiency and hypercalcaemiaIncreased proximal tubule calcium reabsorption; increased bone resorption
  20. 20Milk-Alkali syndromeHypercalcaemia, metabolic alkalosis, renal insufficiency
    Due to ingestion of calcium and antacids
  21. 21management of hypercalcaemia1. Stop offending / contributing medications
    2. Rehydration!
    - Normal saline
    - 3-4 litres in first 24 hours unless contraindicated
    3. + / - loop diuretic
    - Promote calciuria
    4. Bisphosphonates
    - Inhibit bone resorption
    - E.g. zoledronic acid 4mg IV
    - Takes effect within 24-48 hrs
    - Last several weeks
    5. Steroids
    Effective in haematological malignancy; vitamin D intoxication; granulomatous disease
  22. 22Primary hyperparathyroidism - who - whyAffects up to 1 in 500 general population
    Female preponderance (postmenopausal)
    85% isolated parathyroid adenoma
    14% parathyroid hyperplasia-often assoc with familial conditions e.g. MEN etc
    <1% parathyroid carcinoma
  23. 23end-rgan damage in primary hyperparathyroidismBone
    - Osteoporosis (peripheral cortical bone)
    - Other radiological changes e.g. bone cysts; subperiosteal resorption
    Kidneys
    - Renal calculi
    - Nephrocalcinosis
    - Renal impairment
    Other, e.g. pancreatitis
  24. 24investigations in primary hyperparathyroidism1. Confirm diagnosis
    Drugs
    UEs
    PTH
    Urine calcium: creatinine ratio (differentiate from FHH where usually <0.01)
    Vit D (deficiency can cause elevated PTH)
    2. End organ damage?
    DEXA
    KUB/renal US
    3. Other conditions?
    Consider MEN-1 or MEN-2 if <40 years old or history of hyperparathyroidism in 1st degree relative
    4. If surgery indicated
    Localise abnormal gland
    - 2 separate techniques – Sestamibi and ultrasound neck
    - Minimally invasive neck exploration
  25. 25—Brown Tumours
    Result of excess osteoclast activity
    Collection of osteoclasts, poorly mineralised bone and fibrous tissue
    “Brown” because of appearance – haemosiderin deposition    Brown Tumours Result of excess osteoclast activity Collection of osteoclasts, poorly mineralised bone and fibrous tissue “Brown” because ...
  26. 26management of primary hyperparathyroidismParathyroidectomy?
    Calcium > 3.0 mmol/L; hypercalciuria; osteoporosis; age under 50 years; intractable symptoms; renal stones.
    Observation
    If no end-organ damage or unfit for surgery
    - Annual bone profile; renal function; urinary calcium
    - DEXA and renal US every 3 years
    Medical treatment
    Only indicated if not fit for surgery!
    - Bisphosphonates preserve bone mass but little effect on calcium
    - Calcium sensing receptor antagonists (Cinacalcet)
    (Reduces serum (not urine!) calcium
    Doesn’t prevent end-organ damage)
  27. 27complications of parathyroidectomy (3)Mechanical
    - Vocal cord paresis
    - Haematoma causing tracheal compression
    Metabolic
    - Transient hypocalcaemia (suppression of remaining glands)
    - May require oral calcium / vit D supplementation
    “hungry bones”
    Uncommon
    - Occurs in patients who have significant bone disease pre-op or v elevated PTH.
    - Sudden withdrawal of PTH leads to IMBALANCE BETWEEN BONE RESORPTION AND FORMATION – marked net increase in uptake of calcium, phosphate and magnesium by bone
    - Requires calcium and vitamin D supplementation
  28. 28vitamin D deficiency causes- Poor sunlight exposure (i.e. elderly or housebound)
    - Malabsorption
    - Gastrectomy
    - Enzyme inducing drugs e.g. anticonvulsants
    - Renal disease (impaired hydroxylation of 250H Calcitriol)
  29. 29Osteomalacia - why - what - presentation - bloodsClassically associated with very low levels of vitamin D
    Failure to ossify bones in adulthood as a result of Vit D deficiency
    Hypo-mineralisation of trabecular and cortical bone
    Presents insidiously with: BONE PAIN, PROXIMAL MYOPATHY, HYPOCALCAEMIA
    Low calcium; low phosphate; high alk phos; Low Vit D; elevated PTH.
  30. 30radiological signs of osteomalaciaosteopenia and Looser zones
  31. 31Vitamin D Deficiency - treatmentCHOLECALCIFEROL (D3)
    - Restore body stores
    - Correct metabolic disturbance
    - Heal bony abnormalities
    - Or, large dose of Ergocalciferol / D2
    - Biochemistry may not settle for several months
    ALFACALCIDOL (i.e. active Vit D)
    - In renal impairment!!!
    - In hypoparathyroidism!!! (cannot activate Vit D in gut)
    - Not measured by traditional lab Vit D assay (25-OHD3)
    - Higher risk of hypercalcaemia

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Endocrinology Flashcards on Hypercalcaemia, created by Ellie Britt on 22/01/2018.
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Ellie Britt
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