😱Emergencies in Hematolo...

Metadata

• Author: @NicoGagelmann on Twitter
• Full Title: 😱Emergencies in Hematolo...
• Category: #tweets
• URL: https://twitter.com/NicoGagelmann/status/1665397810206744576

Highlights

• 😱Emergencies in hematology😱
  Hypercalcemia of malignancy (HoM)
  A short 🧵 #MedTwitter
  1/17
  (View Tweet)
• What causes hypercalcemia?
  Before you think malignancies, think Chimpanzees:
  Calcium supplementation
  HCT
  Iatrogenic
  Myeloma, milk-alkali syndrome, medics
  Parathyroid hyperplasia/adenoma
  Alcohol
  Neoplasm
  Zollinger Ellison
  Excessive vitamin D
  Excessive vitamin A
  Sarcoidosis
  2/17
  (View Tweet)
• Now to HoM:
  -Ca2+⬆️common in advanced cancer (-30% of patients)
  -most common in myeloma, non-small cell 🫁 cancer, renal cell, breast, non-Hodgkin lymphoma, leukemia
  -adverse prognostic factor
  BUT
  -effective therapy, both for hypercalcemia + cancer, improves outcomes
  3/17
  (View Tweet)
• Pathophysiology:
  -4 subtypes: humoral, osteolytic, excess production of Vit D analogues, ectopic hyperparathyroidism (rare)
  HOWEVER
  -pathophysiology may be more complex than suggested
  -~30% may have humoral + Vit D irritations
  HOWEVER
  -for simplicity, we stick to the 4
  4/17 https://t.co/orHyL1Etrv (View Tweet)
• Humoral:
  -by tumor secretion of PTHrP (locally produced growth factor)
  👉osteoclastic bone resorption⬆️
  👉Ca2+ renal tubular reabsorption⬆️by binding PTH–PTHrP type 1 receptor in 🦴 and kidneys
  -🫁squamous + breast tumors
  -patients often with few or no 🦴 metastases
  5/17
  (View Tweet)
• Osteolytic:
  -through extensive bone metastases
  -often resulting from breast cancer or myeloma
  -tumor cells in bone produce cytokines
  👉osteoclastic bone resorption⬆️
  👉suppress osteoblastic bone formation
  -Ca2+ outflow exceeds renal clearance
  👉hypercalcemia
  6/17
  (View Tweet)
• Vit D analogue excess:
  -tumors upregulate expression of Cyp27B1
  👉encodes 1-alpha-hydroxylase (converts 25-hydroxyvitamin D to active hormone 1,25-dihydroxyvitamin D)
  -excess increases intestinal Ca2+ absorption +🦴 resorption
  -eg in Hodgkin, non-Hodgkin lymphomas
  7/17
  (View Tweet)
• Ectopic hyperparathyroidism:
  -caused by rare tumors that produce PTH instead of PTHrP
  -parathyroid cancers also cause hypercalcemia by secreting PTH
  -RULE OUT primary hyperparathyroidism
  👉more common in women, esp >45 years
  👉history of head and neck irradiation
  👉lithium
  8/17
  (View Tweet)
• Clinic:
  -often overt signs of cancer
  -often nonspecific
  👉lethargy, confusion, anorexia, nausea, constipation, polyuria, polydipsia
  -severity may correlate with hypercalcemia degree
  -rapid severe hypercalcemia
  👉🫀 dysrhythmias (bradycardia, short QT, arrest)
  9/17
  #MedTwitter
  (View Tweet)
• Diagnosis:
  -serum calcium level
  -ionized calcium is preferred method -if you measure total serum calcium
  👉CAVE correct for albumin level: measured total calcium + [0.8 × (4.0 − albumin)]
  -ECG!
  -PTH (usually low in HoM)
  -PTHrP not needed but may elucidate etiology
  10/17
  (View Tweet)
• Treatment of HoM:
  -principles: correct volume depletion, inhibit bone resorption, address underlying cancer
  -asymptomatic/mildly symptomatic (<12 mg/dL) do not require immediate treatment
  BUT
  -avoid factors for hypercalcemia (eg thiazides, lithium, volume depletion)
  11/17
  (View Tweet)
• Volume:
  -most patients with severe hypercalcemia have marked intravascular volume depletion
  -isotonic saline for 24 to 48 hours
  -suggested: 200-300 mL/hour, then adjusted to maintain urine output at 100-150 mL/hour
  -CAREFUL with using loop diuretics
  12/17 https://t.co/TLK8DG7B6O (View Tweet)
• Bisphosphonates:
  -pamidronate, zoledronate interfere with protein prenylation and inhibit osteoclast function by inducing apoptosis
  -among IV probably best zoledronic acid (initial dose 4 mg IV over 15 mins)
  -IV not recommended in severe volume depletion or GFR <35
  13/17
  (View Tweet)
• Denosumab:
  -human monoclonal antibody
  -binds RANKL
  -prevents binding to receptor activator of NFκB on mature/precursor osteoclasts
  👉formation, differentiation, functioning of osteoclasts⬇️
  👉🦴resorption⬇️
  -for refractory patients
  -CAVE HYPOcalcemia in renal insufficiency
  14/17
  (View Tweet)
• Calcitonin:
  -peptide hormone secreted by parafollicular cells of thyroid gland
  -inhibits osteoclast activity
  -promotes renal calcium excretion
  -for immediate, short-term management
  -in combination with saline hydration and bisphosphonates
  -initial dose 4 units/kg SC or IM
  15/17
  (View Tweet)
• Other treatments:
  -steroids, dialysis
  -cinacalcet
  👉calcimimetic by allosteric activation of calcium-sensing receptor expressed in various tissues
  ❗️Successful treatment of cancer-associated hypercalcemia ultimately depends on treatment of the underlying cancer❗️
  16/17
  (View Tweet)
• Summary of HoM:
  ❗️Emergency
  ❗️Often late in disease course
  ❗️Myeloma, breast, (squamous)🫁cancer
  ❗️Humoral, osteolytic causes
  ❗️Differential: Know your CHIMPANZEES🐵
  ❗️Serum & ionized Ca2+, PTH often low, albumin
  ❗️correct volume, inhibit bone resorption, treat underlying cancer https://t.co/Kfa4peo2p7 (View Tweet)
• References & resources:
  https://t.co/FHaYXivslv
  https://t.co/BUtgTVHbfg
  https://t.co/w3n2hxu0tI
  https://t.co/LXPQXGpn8E https://t.co/auzo45qeZg (View Tweet)