A 67-year-old woman with bilateral hand numbness

Carpal tunnel syndrome due to hypothyroidism

Our patient also could have primary hypothyroidism as a result of thyroidectomy. Hypothyroidism can cause bilateral hand numbness due to carpal tunnel syndrome, which is mediated by mucopolysaccharide deposition and synovial membrane swelling.¹¹ One study reported that 29% of patients with hypothyroidism had carpal tunnel syndrome.¹² Symptoms of carpal tunnel syndrome in hypothyroid patients may occur despite thyroid replacement therapy.¹³

Carpal tunnel syndrome is a clinical diagnosis. Patients usually experience hand paresthesia in the distribution of the median nerve. Provocative physical tests for carpal tunnel syndrome include the Tinel test, the Phalen test, and the Katz hand diagram, which is considered the best of the 3 tests.^14,15 Based on how the patient marks the location and type of symptoms on the diagram, carpal tunnel syndrome is rated as classic, probable, possible, or unlikely (Table 1).^14,16,17 The sensitivity of a classic or probable diagram ranges from 64% to 80%, while the specificity ranges from 73% to 90%.^14,15

Carpal tunnel syndrome is less likely to be the cause of our patient’s symptoms, as her Katz hand diagram indicates only “possible” carpal tunnel syndrome. Her perioral numbness and positive Trousseau sign make hypocalcemia a more likely cause.

Diabetic peripheral neuropathy

Sensory peripheral neuropathy is a recognized complication of diabetes mellitus. However, neuropathy in diabetic patients most commonly manifests initially as distal symmetrical ascending neuropathy starting in the lower extremities.¹⁸ Therefore, diabetic peripheral neuropathy is less likely in this patient since her symptoms are limited to her hands.

Vitamin B₁₂ deficiency

Metformin-induced vitamin B₁₂ deficiency is another possible cause of peripheral neuropathy. It might be secondary to metformin-induced changes in intrinsic factor levels and small-intestine motility with resultant bacterial overgrowth, as well as inhibition of vitamin B₁₂ absorption in the terminal ileum.¹⁹

However, metformin-induced vitamin B₁₂ deficiency is not the most likely cause of our patient’s neuropathy, since she has been taking this drug for only 1 year. Vitamin B₁₂ deficiency with consequent peripheral neuropathy is more likely in patients taking metformin in high doses for 10 or more years.²⁰

Laboratory results and electrocardiography

Table 2 shows the patient’s initial laboratory results. Of note, her serum calcium level is 5.7 mg/dL (reference range 8.9–10.1). Electrocardiography in the emergency department shows:

• Prolonged PR interval (23 msec)
• Wide QRS complexes (13 msec)
• Flat T waves
• Prolonged corrected QT interval (475 msec)
• Occasional premature ventricular complexes.

CLINICAL MANIFESTATIONS OF HYPOCALCEMIA

2. Which of the following is not a manifestation of hypocalcemia?

• Tonic-clonic seizures
• Cyanosis
• Cardiac ventricular arrhythmias
• Acute pancreatitis
• Depression

Hypocalcemia can cause a wide range of clinical manifestations (Table 3), the extent and severity of which depend on the severity of hypocalcemia and how quickly it develops. The more acute the hypocalcemia, the more severe the manifestations.²¹

Tetany can cause seizures

Hypocalcemia is characterized by neuromuscular hyperexcitability, manifested clinically by tetany.²² Manifestations of tetany are numerous and include acral paresthesia, perioral numbness, muscle cramps, carpopedal spasm, and seizures. Tetany is the hallmark of hypocalcemia regardless of etiology. However, certain causes are associated with peculiar clinical manifestations. For example, chronic primary hypoparathyroidism may be associated with basal ganglia calcifications that can result in parkinsonism, other extrapyramidal disorders, and dementia (Table 4).⁶

Airway spasm can be fatal

A serious manifestation of acute severe hypocalcemia is spasm of the glottis muscles, which may cause cyanosis and, if untreated, death.²¹

Ventricular arrhythmias

Another potential fatal complication of acute severe hypocalcemia is polymorphic ventricular tachycardia due to prolongation of the QT interval, which is readily identified with electrocardiography.²³

Hypocalcemia does not cause pancreatitis

Hypercalcemia, rather than hypocalcemia, may cause acute pancreatitis.²⁴ Conversely, acute pancreatitis may cause hypocalcemia due to precipitation of calcium in the abdominal cavity.²⁵

Psychiatric manifestations

In addition to depression, hypocalcemia is associated with psychiatric manifestations including anxiety, confusion, and emotional instability.