How to treat HYPOparathyroidism

Maha Khalifa, BS Pharm, PharmD, BCPS, MSc March 22, 2022

Introduction ― Hypoparathyroidism is a deficient secretion of parathyroid hormone (PTH). In primary hypoparathyroidism, absence or dysfunction of the parathyroid gland results in inadequate PTH secretion and subsequent hypocalcemia and hyperphosphatemia. Surgical hypoparathyroidism is the most common etiology, followed by autoimmune disorders. Secondary hypoparathyroidism, a condition in which PTH levels are low in response to hypercalcemia. Hypoparathyroidism is usually asymptomatic. Because parathyroid glands primarily regulate calcium balance, neuromuscular symptoms range from paresthesia to tetany. Hypoparathyroidism may be acute or chronic.

  • Acute: Tetany that is mild (muscle cramps, peri-oral numbness, paresthesias of hands and feet) or severe (carpopedal spasm, laryngospasm, heart failure, seizures, stridor).

    Chronic: Lethargy, anxiety/depression, urolithiasis and renal impairment, dementia, blurry vision from cataracts or keratoconjunctivitis, parkinsonism or other movement disorders, mental retardation, dental abnormalities, and dry, puffy, coarse skin.

DIAGNOSIS

Serum parathyroid hormone (PTH) is Low in hypoparathyroidism (< 20 pg/mL). Hypoparathyroidism is characterized by hypocalcemia (corrected total calcium < 8.4 mg/dL [2.1 mmol/L] OR ionized calcium < 4.4 mg/dL [1.1 mmol/L]) and hyperphosphatemia as a result of inadequate PTH secretion. Two measurements of serum calcium are required for the confirmation of hypocalcemia. Total calcium should be corrected for low albumin (If albumin < 4 g/dL [40 g/L]) utilizing the formula (available at MD+Calc, https://www.mdcalc.com/calcium-correction-hypoalbuminemia)...

Corrected calcium (mg/dL) =
[(4 - serum albumin {in g/dL}) × 0.8] + Total calcium (in mg/dL)
In critically ill patients or those who have acid-base and electrolyte imbalance ionized calcium level is more accurate as it’s not affected by albumin levels.

Both hypomagnesemia and hypermagnesemia can cause hypoparathyroidism. SO, serum magnesium should be measured before final diagnosis of hypoparathyroidism, as hypomagnesemia (Mg < 1.2 mg/dL [0.5 mmol/L]) can cause functional hypoparathyroidism by causing hypocalcemia due to inhibition of PTH secretion and hypermagnesemia may also lead to hypocalcemia due to functional hypoparathyroidism. 24-hr urine calcium and creatinine should be done to evaluate the risk for renal stones. Also, ECG should be considered as hypocalcemia is associated with prolonged QT interval, rarely ST-segment elevations.

NOTE...
  • History and physical examination helping to specify the type of hypoparathyroidism such as patients who with parathyroid, thyroid, laryngeal, or other neck surgeries.
  • Don’t neglect other causes of hypocalcaemia such as: chronic kidney disease, severe vitamin D deficiency, hypomagnesemia, hypermagnesemia, hungry bone syndrome, pseudo-hypoparathyroidism.

MANAGEMENT

DIET — Using calcium-enriched food (i.e., dairy) to meet a need of calcium 1,000-1,500 mg/day and restricting phosphate intake. SEE OUR NOTE, "Using calcium supplements safely" for more information.

ACUTE HYPOPARATHYROIDISM — Patients with severe and/or symptomatic hypocalcaemia, persistent hypocalcaemia who needs hospitalization as such as patient with cardiac arrhythmias due to prolonged QT intervals or laryngospasm, or postsurgical hypoparathyroidism are initially treated with intravenous calcium plus oral calcitriol supplementation.

          IV Calcium. Treatment in adults is initiated with the IV administration of one 10 mL ampule of 10 % calcium gluconate (93 mg of elemental calcium per 10 mL) in 50 mL of 5% dextrose infused over 10 to 20 minutes, followed by an IV infusion of calcium gluconate. The calcium should not be given more rapidly, because of the risk of serious cardiac dysfunction, including systolic arrest. This dose of calcium gluconate will raise the serum calcium concentration for only 2 or 3 hours; as a result, it should be followed by a slow infusion of calcium (0.5 to 2 mg/kg/hr) until calcium levels are in the low-normal range. An IV solution containing 1 mg/mL of elemental calcium is prepared by adding 5 to 6 ampule (10 mL) of calcium gluconate (~ 500 mg elemental calcium) to normal saline or 5% dextrose to provide a final volume of 500 mL. This solution is administered at an initial infusion rate of 50 mL/hour (~ 50 mg elemental/hour). The dose can be adjusted to maintain the serum calcium concentration at the lower end of the normal range (with the serum calcium corrected for any abnormalities in serum albumin ― see Diagnosis).

CHRONIC HYPOPARATHYROIDISM — For the initial management of patients with chronic hypoparathyroidism, oral calcium and vitamin D supplementation are usually suggested. The dose of oral calcium is typically 1 to 2 g of elemental calcium daily, in divided doses, (see Table 1).

          Oral Calcium. Calcium is available in pharmacies as calcium carbonate (Cal-Preg) or calcium citrate (Cal-Mag). Calcium carbonate contains 40% elemental calcium, and calcium citrate contains 21% elemental calcium. Calcium carbonate requires an acidic environment for effective absorption, and as a result, it must be taken with food. Its effectiveness is decreased with concomitant use of H2 blockers or proton pump inhibitors. In such cases, use Calcium citrate, because it does not require an acidic environment for effective absorption (calcium citrate can be taken with or without meals). SEE OUR NOTE, "Using calcium supplements safely" for more information.

Vitamin D. There are several vitamin D preparations available on the pharmacies, but the treatment of choice for patients with hypoparathyroidism is the active form like calcitriol or Alfacalcidol (One-Alpha). A typical starting dose is 0.25 mcg twice daily, with weekly dose increments to achieve a low-normal serum calcium. Many adults require up to 2 mcg daily. Patients on vitamin D analogue calcitriol or alphacalcidol should add vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol) 400-800 units/day to maintain 25-hydroxyvitamin D normal levels.

PTH Replacement. If treatment failed to control the case, start parathyroid hormone replacement therapy with recombinant PTH 1-84 with starting dose equal to dose is 50 mcg subcutaneously once daily, but don’t forget to halve the dose of vitamin D or oral calcium till reaching target levels.

Thiazide diuretics (Hydrozide) may be used at dose of (25 to 100 mg daily) to decrease urine calcium excretion and decrease kidney stones. Potassium supplementation may be necessary to offset thiazide-induced hypokalemia. Additional medications for treatment of hypomagnesemia, hypercalcinuria, or hyperphosphatemia should be tailored according to case presentation.

Table (1). Oral treatment of chronic hypocalcemia in hypoparathyroidism
Treatment Dose - Adults Dose - Children
Calcium 1000 to 2000 mg elemental calcium daily (total diet + supplement) in divided doses (calcium carbonate or calcium citrate) 25 to 50 mg/kg (up to 1000 to 2000 mg) elemental calcium daily (total diet + supplement) in divided doses (calcium carbonate, or calcium citrate)
For adults and children, adjust dose as needed to control symptoms and maintain low-normal serum calcium concentration
Vitamin D
Calcitriol Initial: 0.25 to 0.5 mcg daily
Maintenance: 0.5 to 2 mcg daily		 Infants: 0.04 to 0.08 mcg/kg daily
Children >1 year:
  • Initial: 0.25 mcg once daily
  • Maintenance:
      • Children 1 to 5 years: 0.25 to 0.75 mcg daily
      • Children ≥6 years: 0.5 to 2 mcg daily
Alfacalcidol Initial: 0.25 mcg daily
Maintenance: 0.5 to 1 mcg daily		 Insufficient data
Hydrochlorothiazide
(if required to control hypercalciuria)		 12.5 to 50 mg daily 0.5 to 1.5 mg/kg per day (maximum 50 mg daily)
  • Calcium carbonate absorption is better when taken with meals and has the added benefit of binding phosphate intake. Calcium citrate is absorbed when taken with or without meals, and in achlorhydria and patients taking proton pump inhibitors (PPIs) or H2 agonists. However, calcium citrate does not bind phosphate intake.
  • Calcitriol should be administered in divided doses due to its short half-life.
  • Potassium supplementation may be necessary to offset thiazide-induced hypokalemia.

REFERENCES

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