Hypoparathyroidism

Hypoparathyroidism: Excerpt from The 5-Minute Pediatric Consult

Adda Grimberg, MD

Hypoparathyroidism - BASICS

Hypoparathyroidism - description

Hypoparathyroidism is decreased parathyroid hormone (PTH) effect.

Hypoparathyroidism - epidemiology

Many normal neonates can have hypocalcemia (serum calcium >8 mg/dL) during the 1st 3 weeks of life owing to physiologic transient hypoparathyroidism.

• Parathyroid gland immaturity can lead to deficient PTH release and exaggerated normal fall in serum calcium concentration during the 1st 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).

Hypoparathyroidism - etiology

Hypoparathyroidism - other

• X-linked recessive: Neonatal onset
• Autosomal-dominant and autosomal-recessive forms:
  • Chromosome 3q13: Activating mutations in the calcium-sensing receptor (CaSR) gene
  • Chromosome 6p23-24: Homozygous loss of function of GCMB gene (transcription factor required for parathyroid gland embryology)
  • Chromosome 10p15: GATA3 gene mutations cause dominantly inherited familial hypoparathyroidism, sensorineural deafness and renal anomaly ([HDR] syndrome).
  • Chromosome 11p: Mutations in the PTH gene
  • Chromosome 22q11: DiGeorge syndrome
  • Chromosome 21q22 (AIRE gene): Type 1 polyglandular autoimmune disease
  • Chromosome 20q13: Albright hereditary osteodystrophy
• Mitochondria diseases: Kearns-Sayre syndrome (progressive external ophthalmoplegia before age 20 years and pigmentary retinal degeneration, frequently with other organ system involvement including cardiac, neurologic, and hypoparathyroidism)

Hypoparathyroidism - genetics_classification

• 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
  • Following severe burns
  • 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

Hypoparathyroidism - pathophysiology

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 - DIAGNOSIS

Hypoparathyroidism - signs & symptoms

Hypoparathyroidism - history

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

Hypoparathyroidism - physical exam

• Chvostek sign: Facial nerve stimulation (tapping anterior of external auditory meatus) causes contraction of orbicularis oris, producing upper lip or mouth twitch.
• Trousseau sign: Inflation of BP 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)

Hypoparathyroidism - tests

Hypoparathyroidism - lab

• Total and ionized serum calcium concentrations: Low
  • False positives: Hypomagnesemia
• 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 calcium/creatinine ratio: Low in idiopathic hypoparathyroidism, higher (almost equal to normocalcemic controls) in calcium ion-sensing receptor gain-of-function mutations
• Urinary cyclic AMP response to PTH: Diagnostic test if concerned about pseudohypoparathyroidism; otherwise, not routinely done

Hypoparathyroidism - imaging

• Chest radiograph: Rachitic rosary (rickets), absence of thymus (DiGeorge syndrome)
• Head CT: Intracranial calcifications are associated with chronic hypoparathyroidism and pseudohypoparathyroidism.

Hypoparathyroidism - differencial diagnosis

Hypocalcemia:

• Vitamin D deficiency
• Vitamin D–dependent rickets type I and II
• Hyperphosphatemia
• Prematurity
• Acute pancreatitis
• Malignancy: Osteoblastic metastases, tumor lysis syndrome
• Medication: Citrated blood products, phenobarbital, dilantin, phosphate

Hypoparathyroidism - TREATMENT

Hypoparathyroidism - general measures

Hypoparathyroidism - diet

Unrestricted

Hypoparathyroidism - medication

• Titer therapy to maintain serum calcium concentrations >8.0 mg/dL. In cases requiring lifelong therapy, compromise for serum calciums in the 8–9-mg/dL range to decrease the long-term risk for developing nephrocalcinosis.
  • 1,25(OH)2-vitamin D: <1 year: 0.04–0.08 mcg/kg/d; 1–5 years: 0.25–0.75 mcg/d; >6 years and adults: 0.5–2 mcg/d
  • Calcium: Dose depends on preparation and on patient needs.
  • A recent 3-year trial of synthetic human PTH-(1–34) in patients aged 18–70 years was promising, but it is dosed as b.i.d. daily subcutaneous injections.
  • Duration: For life
• Activating mutations in the calcium sensor are treated with thiazide diuretics and hydration.

Hypoparathyroidism - FOLLOW UP

Hypoparathyroidism - prognosis

Fair; long-term outcome: Development of nephrocalcinosis resulting in renal insufficiency

Hypoparathyroidism - complications

• Hypocalcemia can cause tetany, arrhythmias, seizures, and respiratory arrest.
• Long-standing untreated hypoparathyroidism and pseudohypoparathyroidism can lead to intracranial calcifications, especially in the basal ganglia. These may cause extrapyramidal signs (e.g., choreoathetosis, dystonic spasms, parkinsonism). Cognitive impairment and psychiatric disturbances can also be seen.
• Untreated hypoparathyroidism can also lead to dilated cardiomyopathy, which improves with restoration of normocalcemia.

Hypoparathyroidism - patient monitoring

• Regularly with the endocrinologist
• When to expect improvement: Immediately
• Signs to watch for:
  • Patients with acute, severe hypocalcemia should be placed on telemetry to monitor for cardiac arrhythmias (especially prolonged QTc)
  • Muscle cramps
  • Carpopedal spasms
  • Seizures

Hypoparathyroidism - bibliography

1. Cuneo BF, Driscoll DA, Gidding SS, et al. Evolution of latent hypoparathyroidism in familial 22q11 deletion syndrome. Am J Med Genet. 1997;69:50–55.
2. De Sanctis V, Eleftheriou A, Malaventura C; Thalassaemia International Federation Study Group on Growth and Endocrine Complications in Thalassaemia. Prevalence of endocrine complications and short stature in patients with thalassaemia major: A multicenter study by the Thalassaemia International Federation (TIF). Pediatr Endocrinol Rev. 2004;2(Suppl 2):249–255.
3. Gelfand IM, Eugster EA, DiMeglio LA. Presentation and clinical progression of pseudohypoparathyroidism with multi-hormone resistance and Albright hereditary osteodystrophy: A case series. J Pediatr. 2006;149:877–880.
4. Guise TA, Mundy GR. Evaluation of hypocalcemia in children and adults. J Clin Endocrinol Metab. 1995;5:1473–1478.
5. Hieronimus S, Bec-Roche M, Pedeutour F, et al. The spectrum of parathyroid gland dysfunction associated with the microdeletion 22q11. Eur J Endocrinol. 2006;155:47–52.
6. Klein GL, Langman CB, Herndon DN. Persistent hypoparathyroidism following magnesium repletion in burn-injured children. Pediatr Nephrol. 2000;14:301–304.
7. Kowdley KV, Coull BM, Orwoll ES. Cognitive impairment and intracranial calcification in chronic hypoparathyroidism. Am J Med Sci. 1999;317:273–277.
8. Levine MA. Pseudohypoparathyroidism: from bedside to bench and back. J Bone Miner Res. 1999;14:1255–1260.
9. Marx SJ. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med. 2000;343:1863–1875.
10. Nesbit MA, Bowl MR, Harding B, et al. Characterization of GATA3 mutations in the hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome. J Biol Chem. 2004;279:22624–22634.
11. Perheentupa J. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab. 2006;91:2843–2850.
12. Suzuki M, Aso T, Sato T, et al. A case of gain-of- function mutation in calcium-sensing receptor: Supplemental hydration is required for renal protection. Clin Nephrol. 2005;63:481–486.
13. Thakker RV. Genetic developments in hypopara- thyroidism. Lancet. 2001;357:974–976.
14. Thomusch O, Machens A, Sekulla C, et al. The impact of surgical technique on postoperative hypopara-thyroidism in bilateral thyroid surgery: A multivariate analysis of 5846 consecutive patients. Surgery. 2003;133:180–185.
15. Winer KK, Ko CW, Reynolds JC, et al. Long-term treatment of hypoparathyroidism: A randomized controlled study comparing parathyroid hormone-(1–34) versus calcitriol and calcium. J Clin Endocrinol Metab. 2003;88:4214–4220.
16. Yamamoto M, Akatsu T, Nagase T, et al. Comparison of hypocalcemic hypercalciuria between patients with idiopathic hypoparathyroidism and those with gain-of-function mutations in the calcium-sensing receptor: Is it possible to differentiate the two disorders? J Clin Endocrinol Metab. 2000;85: 4583–4591.

Hypoparathyroidism - CODES

Hypoparathyroidism - icd9

252.1 Hypoparathyroidism

Hypoparathyroidism - FAQ

• 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.

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

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