Question 5

College Answer

(see J Am Soc Nephrol 2001; 12: S3-9) (a) Manifestations include

-kidney: polyuria, polydipsia, muscle weakness, oliguria, renal failure

-GIT   : anorexia, nausea, vomiting, constipation

-CNS   : weakness, lethargy and depression

-CVS   : hypertension, shortened QT

-Musculoskeletal: bone pain

Common causes:

-hyperparathyroidism (primary, secondary, tertiary)

-neoplasia (humeral)

-immobilisation

-sarcoidosis

-Vit D intoxication

-recovery stage of pancreatitis or rhabdomyolysis.

(b) Treatment, if due to metastatic carcinoma of breast:

-     rehydration with saline

-     frusemide if fluid overloaded

-     aggressive diuresis has a limited potential to remove calcium and may lead to renal dysfunction if inappropriate negative fluid balances ensues.

-     Bisphosphonates are first line therapy in malignancy. They prevent osteolysis

-     Calcitonin may be adjuvant

-     Haemodialysis may be necessary if acute oliguric renal failure occurs.

Discussion

This question closely resembles Question 8 from the second paper of 2000 (How  would  you  determine the  aetiology of  severe hypercalcaemia? List  the  treatments appropriate for each aetiology) and Question 9 from the second paper of 2013 (List the clinical features of severe symptomatic hypercalcaemia and outline the treatment of this condition).

Question 18.1 from the the first paper of 2011 also deals with hypercalcaemia of malignancy, but in the context of a clinical scenario.

Causes and consequences of hypercalcemia are treated in slightly greater detail elsewhere.

Causes of Hypercalcemia

Primary endocrine causes Primary hyperparathyroidism Thyrotoxicosis Adrenal insufficiency Paraneoplastic causes PTH-related protein carcinoma of lung oesophageal carcinoma head and neck SCC renal cell carcinoma Breast cancer Ovarian cancer Bladder cancer Ectopic 1,25-dihydroxyvitamin D Lymphoma Lytic bone lesions Multiple myeloma Breast cancer Hematological malignancies Phaeochromocytoma VIP-secreting gastric adenoma

Granulomatous disease Sarcoidosis HIV Tuberculosis Histoplasmosis Coccidioidomycosis Leprosy Drug-induced hypercalcemia Vitamin D oversupplementation Thiazide diuretics Lithium carbonate Oestrogens and HRT Androgens  Theophylline and aminophylline Vitamin A Aluminum toxicity Total parenteral nutrition (TPN) Random miscellaneous causes Immobilization (eg. spinal injury) Chronic renal failure Milk alkali syndrome Rhabdomyolysis

Clinical Manifestations of Hypercalcemia

Early manifestations (levels < 3.5mmol/L) Constipation Peptic ulcer exacerbation Polyuria Nephrogenic diabetes insipidus Nephrolithiasis Type 1 (distal) renal tubular acidosis Shortened QT interval Bone pain

Late manifestations (levels over 3.5mmol/L) Pancreatitis Renal failure (due to vasoconstriction) Hypertension Delirium, progressing to coma Arrhythmia Muscle weakness

Management

• Dilute serum calcium
  • Rehydration with IV fluids
• Decrease calcium resportion from bone
  • Calcitonin
  • Bisphosphonates
  • Gallium nitrate
• Decrease calcium resportion from renal tubule
  • Loop diuretics (this has fallen out of favour)
  • Calcitonin
• Decrease calcium absorption from the gut
  • Corticosteroids (also they decrease the 1,25-dihydroxyvitamin D production by monocytes within granulomae)
• Forcibly remove excess calcium from the circulation
  • Haemodialysis
  • EDTA administration (as chelating agent)

Laupacis, Andreas, and Dean Fergusson. "Drugs to minimize perioperative blood loss in cardiac surgery: meta-analyses using perioperative blood transfusion as the outcome." Anesthesia & Analgesia 85.6 (1997): 1258-1267.

 

Levi, Marcel, et al. "Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints." The Lancet 354.9194 (1999): 1940-1947.