Hypoparathyroidism– Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

  • Hypoparathyroidism is a relative or absolute deficiency of parathyroid hormone due to disease, surgical injury, congenital absence or malfunction of parathyroid glands. Manifested as hypocalcemia, producing symptoms ranging from paresthesias to tetany.
  • Parathyroid hormone (PTH) mobilizes calcium from bone, stimulates reabsorption of calcium in distal nephron, and enhances formation of the active vitamin D metabolite, 1,25-dihydroxy-vitamin D.
  • Classifications:
    • Acquired hypoparathyroidism
      • Accidental removal or damage to parathyroid glands or their blood supply during neck surgery. Decreased parathyroid levels may be transient or permanent.
      • Autoimmune: May develop as isolated destruction of parathyroid or part of autoimmune polyendocrine syndrome 1 (APS-1).
      • Deposition of heavy metals in gland (copper or iron), radiation-induced destruction, and metastatic infiltration are less common acquired forms of hypoparathyroidism.
    • Genetic hypoparathyroidism: May be a manifestation of multiple genetic aberrancies. Most commonly involves calcium-sensing receptor.
    • Functional hypoparathyroidism: May be secondary to either hyper- or hypomagnesemia (seen in alcoholics). Parathyroid adenoma may suppress normal parathyroid gland.
  • System(s) affected: Endocrine/Metabolic; Musculoskeletal; Nervous

Pediatric Considerations

  • May occur in premature infants
  • Neonates born to hypercalcemic mothers may experience suppression of developing parathyroid glands.
  • Congenital absence of parathyroids
  • May appear later in childhood as autoimmune or APS-1

Geriatric Considerations

Hypocalcemia is fairly common in the elderly; however, it is rarely secondary to hypoparathyroidism.

Pregnancy Considerations

Use of magnesium as a tocolytic may induce functional hypoparathyroidism.

Epidemiology

Thyroid and parathyroid disease conditions resulting in surgical intervention are more common in women. More than 250,000 individuals undergo thyroid or parathyroid procedures. Affects individuals of all ages.

Incidence

Estimated to occur after 0.5–6.6% of total thyroidectomies; varies depending on skill and experience of surgeon and extent of surgical procedure

Prevalence

Varies widely depending upon etiology

Risk Factors

  • Neck surgery, especially thyroid
  • Neck trauma
  • Head and neck malignancies
  • Family history of hypocalcemia
  • Autoimmune endocrinopathy

Genetics

  • Mutations in transcription factors or regulators of parathyroid gland development:
    • Hypoparathyroidism may present as a component of a larger genetic syndrome (APS-1 or DiGeorge Syndrome) or in isolation (x-linked hypoparathyroidism)
    • May be autosomal dominant (DiGeorge), autosomal recessive (APS-1), or x-linked recessive (x-linked hypoparathyroidism)
  • PTH gene mutations:
    • Hypoparathyroidism presents in isolation
    • May be autosomal dominant or autosomal recessive
  • Mitochondrial disorders with hypoparathyroidism:
    • Typically hypoparathyroidism exists in conjunction with other congenital anomalies or metabolic derangements
    • Maternal transmission

General Prevention

Intraoperative identification and preservation of parathyroid tissue

Pathophysiology

  • PTH is involved in the control of serum ionized calcium levels. PTH:
    • Mobilizes calcium and phosphorus from bone stores
    • Stimulates formation of 1,25-dihydroxy-vitamin D
    • Stimulates reabsorption of calcium in the distal nephron and phosphate excretion
  • Loss of PTH action results in hypocalcemia, hyperphosphatemia, and hypercalciuria
  • Magnesium is crucial for PTH secretion and activation of the PTH receptor; hypo- or hypermagnesemia may result in functional hypoparathyroidism.

Etiology

  • Postsurgical: Transient or permanent
  • Genetic
  • Autoimmune
  • Infiltrative
    • Metastatic carcinoma
    • Hemochromatosis
    • Wilson disease
  • Irradiation
  • Hypo- or hypermagnesemia

Commonly Associated Conditions

  • DiGeorge syndrome
  • Autoimmune polyendocrine syndrome type 1 (APS-1). Features include:
    • Chronic yeast infections
    • Addison disease

Parathyroid hormone, Endocrine Disorders, calcium sensing receptor, hypomagnesemia, neck surgery, blood supply, vitamin d,

Diagnosis

History

  • Chronic hypocalcemia may be asymptomatic.
  • Fatigue
  • Circumoral or distal extremity paresthesias
  • Muscle cramps
  • Neuropsychiatric symptoms
  • Seizures
  • Previous neck trauma or surgery
  • Head and neck irradiation
  • Family history of hypocalcemia
  • Presence of other autoimmune endocrinopathies

Physical Exam

  • Surgical scar on neck
  • Chvostek sign: Positive sign is ipsilateral twitching of the upper lip upon tapping the facial nerve on the cheek.
  • Trousseau sign: Positive sign is painful carpal spasm after 3-minute occlusion of brachial artery with blood pressure cuff.
  • Tetany
  • Laryngo- or bronchospasm
  • Cataracts
  • Cardiac arrhythmias or failure
  • Dry hair, brittle nails

Diagnostic Tests & Interpretation

Lab

Initial lab tests

  • Blood work ()[C]:
    • Calcium: Total and ionized (low)
    • Albumin (correct serum calcium level for albumin)
      • Corrected serum calcium = Total serum calcium + 0.8 (4.0 – serum albumin)
    • Phosphorus (high)
    • Intact PTH (low or inappropriately normal)
    • Magnesium (low or high may cause hypoparathyroidism; may also be normal)
    • BUN, creatinine (normal)
    • 25 OH vitamin D level
  • Urinary calcium (normal or high) (1)[C]

Follow-Up & Special Considerations

  • EKG may show prolonged QT and ST (secondary to hypocalcemia) (1)[C].
  • Gene sequencing may be required to diagnose genetic causes.
  • Evaluation of other hormone levels may be required to diagnose APS-1.

Imaging

Radiographs may show absent tooth roots, calcification of cerebellum, choroid plexus, or cerebral basal ganglia.

Pathological Findings

Parathyroid gland parenchymal tissue completely or almost completely replaced by fat

Differential Diagnosis

  • Vitamin D deficiency/resistance
  • Pseudohypoparathyroidism: Resistance of end organs to PTH resulting in hypocalcemia with high PTH
  • Hypoalbuminemia
  • Renal failure
  • Malabsorption
  • Familial hypocalcemia
  • Hypomagnesemia

Treatment

Medication

First Line

  • No formal guidelines for treatment exist at this time.
  • Severe symptoms (tetany, seizures, cardiac failure, laryngospasm, bronchospasm):
    • Short-term management (1)[C]
      • IV calcium gluconate: 1 or 2 g, each infused over a period of 10 minutes. Central venous catheter preferred because calcium-containing solutions can irritate surrounding tissues.
      • Follow with infusion 10 g calcium gluconate in 1 L 5% dextrose water at a rate of 1–3 mg calcium gluconate/kg of body weight/hour
    • Long-term management
      • Oral calcium carbonate: 500–1000 mg of elemental calcium 3 times a day. Constipation is a common side effect (2)[C]
      • Calcitriol: Start at 0.25 mcg once to twice daily. Max dose 2 mcg daily (1)[C].
  • Asymptomatic, mildly symptomatic, or mild hypocalcemia
    • Oral calcium: as above. Adjust to control symptoms and achieve target serum calcium.
    • Calcitriol: As above

Second Line

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Oral vitamin D: 25,000–100,000 units/day (1)[C]

Additional Treatment

General Measures

  • Monitor EKG during calcium repletion.
  • Maintenance therapy:
    • May require lifelong treatment with calcium and calcitriol
    • Maintain serum calcium in low normal range: 8.0–8.5 mg/dL (2.0–2.12 mmol/L) (1,2)[C]
  • Adequate control requires careful attention to avoid over- or undertreatment.
  • If hypercalcemia occurs, hold therapy until calcium returns to normal.
  • Treat magnesium deficiency if present.
  • Phosphate binders required if high calcium-phosphate product
  • Thiazide diuretics combined with low-salt diet may be used to prevent hypercalciuria, nephrocalcinosis, and nephrolithiasis.
  • Oral calcium administration and vitamin D supplementation post-thyroidectomy may reduce risk for symptomatic hypocalcemia after surgery (3)[C].

Issues for Referral

May require referral to endocrinologist

Additional Therapies

Parathyroid hormone 1–34 (subcutaneous) (4)[C]

  • May be as effective as calcitriol for maintaining growth and serum calcium levels in children with chronic hypoparathyroidism
  • Unproven method of treatment at this juncture; further study required

In-Patient Considerations

Initial Stabilization

See Treatment, Medications

Admission Criteria

  • Laryngospasm
  • Seizures
  • Tetany
  • QT prolongation

Nursing

Monitor for hypocalcemic symptoms.

Discharge Criteria

  • Resolution of hypocalcemic symptoms
  • Patient educated on hypoparathyroidism and treatment protocol
  • Outpatient follow-up scheduled

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

  • Goal of treatment is to reach a total corrected serum calcium level in low normal range (8.0–8.5 mg/dL or 2.0–2.12 mmol/L), 24-hour urine calcium below 300 mg and calcium-phosphate product below 55.
  • Outpatient measurement of serum calcium, phosphorus, and creatinine weekly to monthly during initial management
  • Once regimen stable, measure serum calcium, phosphate, and creatinine twice yearly.
  • Measurement of urine calcium and creatinine twice yearly
  • Annual slit lamp and ophthalmologic evaluation are recommended.

Diet

Low phosphate diet in patients with hyperphosphatemia

Patient Education

  • Provide careful and detailed instructions about maintenance therapy.
  • Explain importance of periodic blood chemistry evaluations.
  • Instruct patient to watch for signs and symptoms of over- and undertreatment.

Prognosis

  • Hypoparathyroidism following neck surgery is often transient.
  • Length of required treatment may vary depending on origin.
  • Symptoms and serum calcium can be well controlled with treatment.

Complications

  • Neuromuscular symptoms (resolve with treatment)
  • Hypercalciuria, nephrocalcinosis, nephrolithiasis
  • Hypercalcemia with excessive treatment
  • Calciphylaxis with high calcium-phosphate product
  • Cataracts
  • Basal ganglia calcifications with Parkinsonian symptoms
  • If condition starts early in childhood: Stunting of growth, malformation of teeth, mental retardation

References

1. Shoback D. Clinical practice. Hypoparathyroidism. N Engl J Med. 2008;359:391–403.

2. Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. 2008;336:1298–302.

3. Roh JL, Park CI et al. Routine oral calcium and vitamin D supplements for prevention of hypocalcemia after total thyroidectomy. Am J Surg. 2006;192:675–8.

4. Winer KK, Sinaii N, Reynolds J, Peterson D, Dowdy K, Cutler GB et al. Long-Term Treatment of 12 Children with Chronic Hypoparathyroidism: A Randomized Trial Comparing Synthetic Human Parathyroid Hormone 1–34 versus Calcitriol and Calcium. The Journal of clinical endocrinology and metabolism. 2010

Additional Reading

Betterle C, Zanchetta R. Update on autoimmune polyendocrine syndromes (APS). Acta Biomed Ateneo Parmense. 2003;74:9–33.

Gunn IR, Gaffney D. Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review. Ann Clin Biochem. 2004;41:441–58.

Thakker RV. Genetics of endocrine and metabolic disorders: parathyroid. Rev Endocr Metab Disord. 2004;5:37–51.

Codes

ICD9

252.1 Hypoparathyroidism

Snomed

36976004 Hypoparathyroidism (disorder)

Clinical Pearls

  • The most common etiology of hypoparathyroidism is damage to the parathyroid glands or blood supply during neck surgery; other causes include congenital and infiltrative disease.
  • Patients with hypoparathyroidism may be asymptomatic or present with symptoms of hypocalcemia, including paresthesias, tetany, or laryngospasm.
  • In the presence of severe neuromuscular or cardiac symptoms, emergent treatment should begin with parenteral calcium.
  • Treatment with calcium and calcitriol may be required transiently or permanently depending on origin of hypoparathyroidism.
  • Treatment goal is total serum calcium in low-normal range: 8.0–8.5 mg/dL (2.0–2.12 mmol/L).

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