Hypercalcemia and Hyperparathyroidism

Primer

Hypercalcemia and hyperparathyroidism are frequently under-diagnosed in psychiatric practice and there are recommendations that calcium levels should be monitored in patients on long‐term treatment.[1] Like with other electrolyte and fluid imbalances (see: hyponatremia, hypokalemia, hypomagnesemia, hypocalcemia),[2] hypocalcemia can cause neuropsychiatric symptoms. Long-term lithium can cause hypercalcemia and hyperparathyroidism.

Signs and Symptoms

Sequelae of long-term chronic hypercalcemia includes renal stones, osteoporosis, dyspepsia, hypertension and renal impairment. Symptoms of hypercalcemia (and consequently hyperparathyroidism) can also mimic as psychiatric disorders, with disturbances of mood, energy, and cognition.

Mnemonic

The mnemonic painful bones (abnormal bone remodeling), renal stones (kidney stones from hypercalciuria), abdominal groans (hypercalcemia-induced ileus and abdominal pain), thrones (urinary frequency), and psychic moans (depression) can be used to recall the common symptoms of hypercalcemia.

Causes

Lithium

Lithium increases the risk of hypercalcemia and hyperparathyroidism (prevalence of ~5%).[3] Lithium is thought to cause hyperparathyroidism due to it altering the set point of receptors that sense calcium in parathyroid cells, and thus causing excess parathyroid hormone release.[4] Up to 10% of patients on long-term lithium treatment develop hypercalcaemia and hyperparathyroidism, and this is even higher in the geriatric population.[5]

Other

Hyperparathyroidism can occur due to primary, secondary, or tertiary causes. Primary causes include parathyroid adenomas, and carcinomas. Secondary causes include decreased calcium absorption, vitamin D deficiency, and chronic kidney disease. Tertiary causes include refractory hyperparathyroidism from chronic renal disease.

Comparison

Comparison of Various Electrolyte Disturbances

Hypo (Low Concentration) Hyper (High Concentration)
Sodium Hyponatremia: Nausea, malaise, stupor, coma, seizures Irritability, stupor, coma
Potassium Hypokalemia: Arrhythmias, muscle cramps, spasm, and weakness. ECGs will show U waves and flattened T waves Arrhythmias, muscle weakness. ECGs will show Wide QRS and peaked T waves.
Calcium Hypocalcemia: Tetany, seizures, QT prolongation, twitching (e.g. - Chvostek sign), spasm (e.g. - Trousseau sign) Hypercalcemia: Stones (renal), bones (pain), groans (abdominal pain), thrones (urinary frequency), psychiatric overtones (anxiety, altered mental status)
Magnesium Hypomagnesmia: Tetany, torsades de pointes, hypokalemia, hypocalcemia Decreased deep tendon reflexes, hypotension, lethargy, bradycardia, cardiac arrest, hypocalcemia
Phosphate Bone loss, osteomalacia (adults), rickets (children) Renal stones, metastatic calcifications, hypocalcemia

Hyperparathyroidism Fig. 1

Treatment

If hyperparathyroidism is thought to be due to lithium, then stopping lithium is the definitive treatment for reversing symptoms of hyperparathyoidism. Otherwise, a parathyroidectomy is the only cure for hyperparathyroidism.

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References

1) Shapiro, H. I., & Davis, K. A. (2014). Hypercalcemia and “primary” hyperparathyroidism during lithium therapy. American Journal of Psychiatry, 172(1), 12-15.
2) Webb Jr, W. L., & Gehi, M. (1981). Electrolyte and fluid imbalance: neuropsychiatric manifestations. Psychosomatics, 22(3), 199-203.
3) Lehmann, S. W., & Lee, J. (2013). Lithium-associated hypercalcemia and hyperparathyroidism in the elderly: What do we know?. Journal of affective disorders, 146(2), 151-157.
4) Nair, C. G., Menon, R., Jacob, P., & Babu, M. (2013). Lithium-induced parathyroid dysfunction: A new case. Indian journal of endocrinology and metabolism, 17(5), 930.
5) Lehmann, S. W., & Lee, J. (2013). Lithium-associated hypercalcemia and hyperparathyroidism in the elderly: What do we know?. Journal of affective disorders, 146(2), 151-157.