Hypoparathyroidism for USMLE Step 1
Hypoparathyroidism for the USMLE Step 1 Exam
- Pathophysiology
- Hypoparathyroidism is characterized by insufficient secretion or action of parathyroid hormone (PTH), resulting in hypocalcemia and hyperphosphatemia.
- Parathyroid Hormone (PTH): Normally increases serum calcium by stimulating bone resorption, increasing renal calcium reabsorption, and enhancing intestinal calcium absorption via activation of vitamin D. It also reduces phosphate levels by promoting renal phosphate excretion.
- Mechanisms:
- Decreased PTH Secretion: Direct damage to or destruction of the parathyroid glands.
- PTH Resistance: Seen in pseudohypoparathyroidism where PTH levels are normal or high, but target tissues are resistant to its effects.
- Etiology
- Post-Surgical Hypoparathyroidism: The most common cause, occurring after thyroidectomy or other neck surgeries that damage or remove the parathyroid glands.
- Autoimmune Hypoparathyroidism: Autoimmune destruction of the parathyroid glands, often seen in autoimmune polyglandular syndrome.
- Genetic Causes:
- DiGeorge Syndrome: Congenital absence or underdevelopment of the parathyroid glands.
- Familial Hypoparathyroidism: Inherited mutations affecting PTH production or function.
- Radiation Therapy: Exposure to radiation during treatment for head and neck cancers may damage the parathyroid glands.
- Hypomagnesemia: Severe magnesium deficiency can impair PTH secretion and action.
- Clinical Features
- Neuromuscular Symptoms:
- Tetany: Involuntary muscle cramps and spasms, often in the hands and face.
- Chvostek’s Sign: Facial muscle twitching upon tapping the facial nerve.
- Trousseau’s Sign: Carpal spasm induced by inflating a blood pressure cuff.
- Paresthesia: Tingling or numbness around the mouth, hands, or feet.
- Seizures: Severe hypocalcemia lowers the seizure threshold.
- Cardiovascular Symptoms:
- Prolonged QT Interval: Hypocalcemia prolongs the QT interval, increasing the risk of arrhythmias.
- Hypotension: Hypocalcemia can cause reduced vascular tone.
- Other Features:
- Laryngospasm or Bronchospasm: Severe hypocalcemia can cause airway muscle spasm, leading to respiratory distress.
- Mental Status Changes: Confusion, anxiety, irritability, and, in severe cases, depression.
- Diagnosis
- Serum Calcium: Low total and ionized calcium.
- Serum Phosphate: Elevated due to decreased renal phosphate excretion in the absence of PTH.
- Serum PTH: Low or inappropriately normal in the presence of hypocalcemia.
- Magnesium Levels: Low magnesium can contribute to hypocalcemia.
- ECG: Prolonged QT interval due to hypocalcemia.
- Vitamin D Levels: Evaluated to rule out vitamin D deficiency as a cause of hypocalcemia.
- Management
- Acute Hypocalcemia:
- Intravenous Calcium: Used for acute, severe hypocalcemia with tetany, seizures, or cardiac complications. Calcium gluconate is preferred.
- Chronic Management:
- Oral Calcium Supplements: Long-term oral calcium (calcium carbonate or calcium citrate) is used to maintain serum calcium in the low-normal range.
- Vitamin D Supplementation:
- Calcitriol (Active Vitamin D): Essential for hypoparathyroidism as the conversion of vitamin D to its active form is impaired.
- Thiazide Diuretics: May be used to reduce urinary calcium excretion and prevent nephrolithiasis.
- Magnesium Supplementation: Important to correct hypomagnesemia, which can exacerbate hypocalcemia.
- Recombinant Human PTH (rhPTH):
- rhPTH (Natpara): Can be used in patients who are refractory to conventional therapy or require high doses of calcium and vitamin D.
- Complications
- Hypocalcemic Crisis: Severe hypocalcemia with life-threatening symptoms, including laryngospasm and arrhythmias, requiring emergency calcium replacement.
- Nephrocalcinosis: Can result from prolonged high-dose calcium and vitamin D supplementation, leading to calcium deposition in the kidneys.
- Ectopic Calcifications: Chronic hypoparathyroidism can lead to calcification in soft tissues, including the basal ganglia, causing movement disorders.
Key Points
- Hypoparathyroidism is primarily caused by post-surgical damage or autoimmune destruction of the parathyroid glands, leading to hypocalcemia and hyperphosphatemia.
- Clinical features include tetany, muscle spasms, prolonged QT interval, and mental status changes. Severe hypocalcemia can lead to life-threatening complications like laryngospasm and cardiac arrhythmias.
- Diagnosis is confirmed with low serum calcium, high phosphate, and low PTH levels. Magnesium levels should also be checked, as hypomagnesemia can impair PTH secretion.
- Treatment involves acute IV calcium replacement for severe symptoms, and long-term management with oral calcium, calcitriol, and magnesium supplementation. Recombinant PTH can be used for refractory cases.