• Diminished or absent PTH activity results in:
  • Hypocalcemia and hyperphosphatemia
  • Reduced vitamin D activation to 1,25(OH)₂ Vitamin D
  • Hypocalcemia leads to increased neural excitability.
• Hypoparathyroidism
  • Transient
    • Fetal parathyroid suppression: maternal hypercalcemia, diabetic mother
    • Hypomagnesemia: direct effects (suppressed PTH secretion, increased PTH resistance)
    • Alcohol intoxication
  • Congenital
    • Familial: X-linked recessive, autosomal dominant, autosomal recessive
    • Sporadic and isolated
    • DiGeorge syndrome: parathyroid gland hypoplasia, thymic hypoplasia/aplasia, facial abnormalities, aortic arch and cardiac defects
  • Acquired
    • Postsurgical
    • Postirradiation
    • Type 1 polyglandular autoimmune disease (Blizzard syndrome): hypoparathyroidism associated with chronic mucocutaneous candidiasis and autoimmune adrenal insufficiency; can also have diabetes mellitus, lymphocytic thyroiditis, hypogonadism, pernicious anemia, chronic hepatitis
    • Iron deposition: thalassemia, hemochromatosis
    • Copper deposition: Wilson disease
    • Metastatic carcinoma
    • Miliary tuberculosis
• Pseudohypoparathyroidism: resistance to PTH
  • Albright Hereditary Osteodystrophy: G protein mutation

• X-linked recessive: neonatal onset
• Autosomal dominant and autosomal recessive forms
  • Chromosome 3q13: mutations in the calcium-sensing receptor gene
  • Chromosome 11p: mutations in the PTH gene
  • Chromosome 22q11: DiGeorge syndrome
  • Chromosome 21q22: Type 1 polyglandular autoimmune disease
  • Chromosome 20q13: Albright hereditary osteodystrophy
• Mitochondria diseases: Kearns-Sayre syndrome (hypoparathyroidism and deafness)

• Parathyroid gland immaturity can lead to deficient PTH release and exaggerated normal fall in serum calcium concentration during the first 3 days of life.
• Relative immaturity of renal phosphorus handling and response to PTH can lead to late neonatal hypocalcemia precipitated by a high phosphate diet (cow’s milk-based formulas).

• Vitamin D deficiency
• Vitamin D–dependent rickets type I and II
• Hyperphosphatemia
• Prematurity
• Acute pancreatitis
• Malignancy: osteoblastic metastases, tumorlysis syndrome
• Medication: citrated blood products, phenobarbital, dilantin, phosphate

• In neonates: maternal calcium and magnesium abnormalities, maternal diabetes
• Family history of calcium disorders
• Medications
• Recurrent infections
• Recurrent muscle cramps
• Paresthesias

• Chvostek sign: Facial nerve stimulation (tapping anterior of external auditory meatus) causes contraction of orbicularis oris, producing upper lip or mouth twitch.
• Trousseau sign: Insufflation of blood pressure cuff reduces the blood flow to peripheral motor nerves and thereby can elicit carpopedal spasm in latent tetany.
• Carpopedal spasm
• Laryngeal stridor
• Mental status changes
• Irritability
• Papilledema
• Cataracts
• Bradycardia, hypotension
• Dry skin, coarse hair, brittle nails
• Albright hereditary osteodystrophy (pseudohypoparathyroidism type Ia): short stature, round face, thick neck, barrel chest, obesity, subcutaneous calcifications, brachydactyly (short 4th metacarpal bones)

• Total and ionized serum calcium concentrations: low
• Serum phosphorus concentration: elevated in hypoparathyroidism; low in rickets
• Serum magnesium concentration: rule out hypomagnesemia
• Albumin: assess calcium binding (if cannot get ionized calcium)
• Intact PTH levels
• 25-OH- and 1,25(OH)₂-Vitamin D levels: distinguish hypoparathyroidism from rickets
• Urinary cyclic AMP response to PTH: diagnostic test if concerned about pseudohypoparathyroidism; otherwise, not routinely done

• Chest x-ray: rachitic rosary (rickets), absence of thymus (DiGeorge syndrome)

• Hypomagnesemia

• 1,25(OH)₂ Vitamin D: less than 1 year: 0.04 to 0.08 µg/kg/d; 1 to 5 years: 0.25 to 0.75 µg/d; greater than 6 years and adults: 0.5 to 2.0 µg/d.
• Calcium: Dose depends on preparation and on patient needs.

• For life

• Unrestricted

• Immediately

• Patients with acute, severe hypercalcemia should be placed on telemetry to monitor for cardiac arrhythmias (especially prolonged QTc).
• Muscle cramps
• Carpopedal spasms
• Seizures

Q: Is the thyroid also involved?
A: No.

Q: Are seizures common?
A: Yes, seizures are a common presentation of hypoparathyroidism in childhood, and physiologic transient hypoparathyroidism is the most common cause of neonatal seizures.

Q: Can hypoparathyroidism be associated with other abnormalities?
A: Yes. Investigate neonates at the time of diagnosis for cardiac defects and thymic aplasia (DiGeorge syndrome), and monitor patients with hypoparathyroidism for development of other autoimmune endocrinopathies and chronic mucocutaneous candidiasis (type 1 polyglandular autoimmune disease).

Q: When should IV versus oral calcium supplementation be used?
A: IV calcium supplementation provides the quickest correction of hypocalcemia and is therefore useful in severe cases (seizures, stridor, tetany, cardiac arrhythmias) or in the initiation of therapy (as you await establishment of adequate vitamin D levels, which are necessary for enteral calcium absorption). Switch to oral calcium supplementation as soon as possible to reduce the risk of potential IV calcium-mediated venous sclerosis and tissue extravasation.

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