What is the workup for hypoparathyroidism?

Diagnostic Workup for Hypoparathyroidism

The diagnostic workup for hypoparathyroidism should include measurement of serum calcium, phosphate, PTH, magnesium, alkaline phosphatase (ALP), and vitamin D levels, with confirmation of low or inappropriately normal PTH in the setting of hypocalcemia and hyperphosphatemia. 1

Initial Laboratory Evaluation

• Serum calcium: Typically low (hypocalcemia)
• Serum phosphate: Typically elevated (hyperphosphatemia)
• Parathyroid hormone (PTH): Low or inappropriately normal relative to calcium levels
• Magnesium: To exclude hypomagnesemia as a cause of functional hypoparathyroidism
• 25-hydroxyvitamin D: To exclude vitamin D deficiency
• 1,25-dihydroxyvitamin D: Typically low due to lack of PTH-stimulated 1-alpha-hydroxylase activity
• Alkaline phosphatase (ALP): To assess bone turnover
• Serum creatinine: To assess kidney function

Additional Testing

• Urinary calcium excretion: 24-hour urine collection to assess for hypercalciuria
• Urinary phosphate: To calculate maximum tubular reabsorption of phosphate (TmP/GFR)
• Urinary markers: Measure urinary excretion of amino acids, glucose, and low-molecular-weight proteins to exclude renal Fanconi syndrome 2
• Serum bicarbonate: To exclude metabolic acidosis 2

Differential Diagnosis Considerations

It's essential to differentiate between various causes of hypocalcemia:

1. Primary hypoparathyroidism: Low PTH with hypocalcemia
2. Pseudohypoparathyroidism: Elevated PTH with hypocalcemia due to PTH resistance
3. Secondary causes: Hypomagnesemia, vitamin D deficiency
4. Other causes of renal phosphate wasting: Various genetic disorders affecting phosphate handling 2

Genetic Testing

• Genetic analysis should be considered to confirm clinical diagnosis, especially in cases of suspected congenital hypoparathyroidism 2
• If molecular genetic analysis is not available, family history and biochemical profile can support diagnosis 2

Imaging Studies

• Renal ultrasonography: To detect nephrocalcinosis or kidney stones, especially in chronic cases
• Brain imaging (MRI): If neurological symptoms are present, to evaluate for basal ganglia calcifications
• Dental orthopantomogram: To evaluate for dental abnormalities in chronic cases 2

Monitoring Parameters

Once diagnosed, regular monitoring should include:

• Serum calcium: Initially weekly during dose titration, then monthly when stable
• Serum phosphate: Same schedule as calcium
• PTH levels: Every 3-6 months
• Urinary calcium excretion: Periodically to assess for hypercalciuria
• Renal function tests: To monitor for potential complications of treatment 3

Treatment Initiation

After diagnosis, treatment typically begins with:

• Oral calcium supplements: Usually calcium carbonate (40% elemental calcium) or calcium citrate (21% elemental calcium) for those with achlorhydria or on proton pump inhibitors 4
• Activated vitamin D (calcitriol): Starting dose of 0.25 mcg/day, titrated based on serum calcium levels 5
• Dietary calcium intake: Ensure adequate intake of 600-1200 mg daily 5

Pitfalls to Avoid

• Don't miss hypomagnesemia: Both hypomagnesemia and hypermagnesemia can cause functional hypoparathyroidism 1
• Don't overlook pseudohypoparathyroidism: Check PTH levels to differentiate from true hypoparathyroidism
• Don't delay treatment of severe hypocalcemia: Corrected calcium <1.9 mmol/L requires immediate IV calcium administration 1
• Don't forget to exclude other causes: Autoimmune disorders, genetic abnormalities, and infiltrative disorders can all cause hypoparathyroidism 1

The workup for hypoparathyroidism requires a systematic approach to confirm the diagnosis, identify the underlying cause, and guide appropriate treatment to prevent complications and improve quality of life.