Low Serum PTH (Hypoparathyroidism)

Classification of Hypocalcemia by PTH Level

Causes of Low PTH (Hypoparathyroidism)

1. Iatrogenic (Most Common in Adults)

• Surgery - inadvertent removal of or damage to the parathyroid glands or their blood supply during thyroidectomy, parathyroidectomy, or radical neck dissection. Most post-surgical cases are transient ("stunning"); persistent hypoparathyroidism >6 months is relatively rare.
• Radiation - external beam radiation for head and neck cancers, or rarely radioactive iodine therapy for hyperthyroidism.
• Medications - cinacalcet (a calcimimetic) activates calcium-sensing receptors (CaSR) on parathyroid cells, suppressing PTH secretion.

2. Autoimmune (Second Most Common in Adults)

• Immune-mediated parathyroid destruction - can be isolated or part of Autoimmune Polyglandular Syndrome type 1 (APS-1), caused by mutations in the AIRE gene. APS-1 features hypoparathyroidism, chronic mucocutaneous candidiasis, and adrenal insufficiency.
• Activating antibodies to CaSR - these mimic high calcium, persistently suppressing PTH secretion.
• Even late-onset idiopathic adult hypoparathyroidism frequently involves anti-CaSR and anti-NALP5 antibodies.

3. Infiltrative Disease

• Sarcoidosis, IgG4-related disease
• Iron overload (hemochromatosis, transfusion-dependent thalassemia)
• Copper overload (Wilson's disease)

4. Other / Genetic

• DiGeorge syndrome (chromosome 22q11.2 deletion) - congenital absence of parathyroids with thymic aplasia and cardiac defects.
• Inactivating mutations in GCM2, GATA3, or the PTH gene itself.
• Activating mutations in CaSR or GNA11 (autosomal dominant hypocalcemia).
• Hypomagnesemia - impairs intracellular PTH synthesis and release. Causes include alcohol abuse, cisplatin, anti-EGFR antibodies, proton pump inhibitors.
• Severe hypermagnesemia (e.g., obstetric Mg infusions) - can suppress PTH via CaSR activation.
• COVID-19 infection caused transient hypoparathyroidism by unknown mechanism.

Lab Pattern

Clinical Manifestations (Due to Hypocalcemia)

• Paresthesias (fingers, toes, perioral)
• Chvostek's sign - facial twitch on tapping facial nerve (also present in ~10% of normals)
• Trousseau's sign - carpal spasm on BP cuff inflation 20 mmHg above systolic for 3 min
• Tetany, carpopedal spasm
• Bronchospasm, laryngospasm
• Seizures
• QTc prolongation → ventricular tachyarrhythmia (Torsade de Pointes), sudden death

• Cataracts
• Calcification of basal ganglia
• Dental abnormalities

Diagnosis

• Serum albumin (to calculate corrected calcium)
• Serum phosphorus, magnesium
• 25(OH)D levels
• 24-hour urinary calcium
• History of neck surgery, radiation, family history

Treatment

• IV calcium gluconate - 10 mL of 10% solution (90 mg elemental Ca) diluted in 50 mL dextrose/saline, given over 5-10 min with telemetry, repeated as needed.
• May require continuous IV calcium infusion (~1 mg/min elemental calcium) titrated to symptoms, ECG, and blood levels.
• Correct hypomagnesemia first if present - PTH cannot be secreted adequately with low Mg.

• Oral calcium supplements + active vitamin D (calcitriol) - since PTH is absent, 1α-hydroxylation of 25(OH)D in the kidney is impaired, so the active form must be supplemented directly.
• Monitor urinary calcium to avoid hypercalciuria (without PTH, kidneys don't retain calcium normally).
• Recombinant PTH 1-84 (natpara) - approved for chronic hypoparathyroidism uncontrolled by supplements.