DiGeorge Syndrome and Parathyroid Dysfunction
DiGeorge syndrome is classically associated with HYPOparathyroidism, not hyperparathyroidism—hypocalcemia due to parathyroid hypoplasia is one of the defining features of the syndrome. 1
The Classic Triad
DiGeorge syndrome is clinically defined by three cardinal features 1:
- Thymic hypoplasia/aplasia leading to T-cell immunodeficiency
- Hypoparathyroidism causing hypocalcemia
- Congenital heart disease, particularly conotruncal defects
Why Hypoparathyroidism Occurs
The pathophysiology stems from aberrant embryonic development of the third pharyngeal pouch, which gives rise to both the thymus and parathyroid glands 1. This developmental field defect results in hypoplasia or aplasia of the parathyroid glands, leading to insufficient parathyroid hormone (PTH) production and subsequent hypocalcemia 1, 2.
Clinical Presentation of Parathyroid Dysfunction
Hypocalcemia is present in approximately 50-60% of patients with DiGeorge syndrome 2, 3:
- May present with tetany within 24-48 hours after birth in severe cases 4
- Can be transient or persistent throughout life 3
- May manifest later in childhood or remain subclinical 3
- Requires regular calcium monitoring, especially during periods of stress, illness, or surgery 5
Important Clinical Caveat
While hypoparathyroidism is the expected parathyroid abnormality, paradoxical autoimmune thyroid disease (including Graves' disease) has been reported in DiGeorge syndrome patients 6, 4. This represents immune dysregulation rather than hyperparathyroidism, but highlights that the immune dysfunction in partial DiGeorge syndrome can manifest as autoimmune endocrinopathies 6, 4, 7.
Management Implications
Monitor and treat hypocalcemia aggressively 5:
- Regular serum calcium and PTH level monitoring
- Calcium and vitamin D supplementation as needed
- Be vigilant during physiologic stress when calcium demands increase
Screen for other endocrine autoimmunity 5, 6:
- Thyroid function tests (both hypothyroidism and hyperthyroidism can occur)
- Growth hormone deficiency screening if growth concerns arise
The key takeaway: DiGeorge syndrome causes HYPOparathyroidism (low PTH, low calcium), not hyperparathyroidism (high PTH, high calcium) 1.