A 39-year-old woman comes to the physician with a "pins and needles" sensation around her mouth for the last 2-3 weeks. She occasionally has similar sensations in her feet, along with muscle cramps, especially at the end of the day. Her past medical history is unremarkable, and she does not use tobacco, alcohol, or illicit drugs. Family history is not significant. Vital signs are normal, and examination is unremarkable. Laboratory findings results are as follows:
Complete blood count Hemoglobin 13.2 g/dL Leukocytes 6,300/µL Serum chemistry Sodium 140 mEq/L Potassium 4.0 mEq/L Chloride 100 mEq/L Bicarbonate 24 mEq/L Blood urea nitrogen 10 mg/dL Creatinine 0.8 mg/dL Glucose 100 mg/dL Calcium 6.5 mg/dL Phosphorus 5.8 mg/dL Total protein 7.0 g/dL Albumin 4.0 g/dL
Which of the following is the most likely cause of this patient's condition?
This patient's clinical features and laboratory findings are consistent with hypocalcemia caused by autoimmune primary hypoparathyroidism. Symptoms of hypocalcemia usually stem from neuromuscular irritability and manifest as perioral tingling and numbness, muscle cramps, tetany, carpopedal spasms, and seizures. Prolongation of the QT interval can also occur. If the hypocalcemia develops rapidly, as in surgical patients, the symptoms are typically more severe, even with modestly reduced serum calcium levels. However, chronic hypocalcemia may be asymptomatic even with markedly reduced serum calcium levels.
The causes of primary hypoparathyroidism include:
Post-surgical hypoparathyroidism can occur during thyroidectomy and sub-total parathyroidectomy (ie, removal of 3½ parathyroid glands for parathyroid hyperplasia). Autoimmune hypoparathyroidism is the most common nonsurgical syndrome.
(Choice A) Drugs such as phenytoin, carbamazepine, and rifampin cause vitamin D deficiency by inducing the P450 cytochrome system in the liver, which degrades vitamin D to inactive metabolites. This patient does not take any medications.
(Choice C) The kidneys are responsible for converting 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by the enzyme 1-alpha-hydroxylase. Impaired 1-alpha-hydroxylation occurs with chronic kidney disease, which can lead to hyperphosphatemia, hypocalcemia, and secondary hyperparathyroidism. However, this patient's renal function appears normal.
(Choice D) Serum phosphorus is usually low in vitamin D deficiency.
(Choice E) Insufficient calcium intake induces the secretion of parathyroid hormone, causing secondary hyperparathyroidism. High parathyroid hormone levels have the following major effects on calcium homeostasis: increase in bone resorption with release of calcium into the circulation; increased conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D in the kidneys, which stimulates gut calcium absorption; and increased renal phosphate loss resulting in hypophosphatemia.
(Choice F) Precipitation of calcium with phosphate in the peripheral tissues can cause hypocalcemia, which can occur in renal failure, rhabdomyolysis, and phosphate administration. Hypocalcemia often also occurs in acute pancreatitis (due to precipitation of calcium soaps in the abdominal cavity) or in diffuse osteoblastic metastases (eg, prostate and breast cancer). This patient exhibits no signs or clinical features suggestive of these possible causes of hypocalcemia.
Educational objective:
Hypoparathyroidism (parathyroid hormone deficiency) is characterized by hypocalcemia and hyperphosphatemia in the presence of normal renal function. Causes of hypoparathyroidism include post-surgical, autoimmune and non-autoimmune parathyroid destruction, and defective calcium-sensing receptor.