Hypoparathyroidism

Risk factors

• Anterior neck surgery: total or near-total thyroidectomy, parathyroidectomy (especially for 4-gland hyperplasia), radical neck dissection
• Neck radiation
• Autoimmune (isolated or part of APS-1: hypoparathyroidism + adrenal insufficiency + mucocutaneous candidiasis)
• DiGeorge syndrome (22q11.2 deletion): hypocalcemia, conotruncal heart defects, thymic aplasia, palatal anomalies
• Severe hypomagnesemia (functional hypoparathyroidism — impairs PTH secretion and action)
• Infiltrative: Wilson disease, hemochromatosis, metastatic disease
• Activating CaSR mutations (autosomal dominant hypocalcemia)

Pathophysiology

Inadequate PTH reduces osteoclast-mediated bone resorption, decreases renal calcium reabsorption (urinary calcium increases for a given filtered load), reduces 1-alpha-hydroxylation of vitamin D (less intestinal calcium absorption), and decreases renal phosphate excretion. Net effect: hypocalcemia, hyperphosphatemia, low 1,25-OH vitamin D, and (paradoxically) hypercalciuria during treatment.

Clinical presentation

Differential diagnosis

• Pseudohypoparathyroidism — End-organ PTH resistance (GNAS mutation); high PTH with low calcium and high phosphate; Albright hereditary osteodystrophy phenotype in type 1a (short stature, round face, brachydactyly, obesity)
• Vitamin D deficiency — Low 25-OH vitamin D; secondary hyperparathyroidism (PTH elevated); calcium low-normal, phosphate low
• Hypomagnesemia — Impairs PTH secretion and action — must correct Mg first; common in PPI users, alcohol use, diuretics
• Chronic kidney disease — Hyperphosphatemia, low 1,25-OH vitamin D, elevated PTH (secondary)
• Acute pancreatitis — Calcium saponification in necrotic fat; acute setting
• Massive transfusion / citrate — Acute symptomatic hypocalcemia; correct with IV calcium
• Tumor lysis / rhabdomyolysis — Hyperphosphatemia binds calcium; acute setting with markers of cell turnover

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Hypocalcemia + paresthesias<br/>Chvostek/Trousseau positive] --> B[Check ionized Ca, PTH,<br/>Mg, phosphate, vitamin D]
  B --> C{Magnesium low?}
  C -->|Yes| D[Replete Mg first<br/>recheck PTH and Ca]
  C -->|No| E{PTH level}
  E -->|Low / inappropriately normal| F[Hypoparathyroidism]
  E -->|Elevated| G{Phosphate level}
  G -->|High| H[Pseudohypoparathyroidism<br/>(end-organ PTH resistance)]
  G -->|Low| I[Vitamin D deficiency<br/>or 2° hyperparathyroidism]
  F --> J[Treat: oral Ca + calcitriol<br/>± thiazide; goal Ca 8.0-8.5]
  F --> K[Acute symptomatic: IV Ca gluconate<br/>continuous monitoring]

Complications

• Acute: tetany, seizure, laryngospasm, prolonged QT → arrhythmia
• Chronic: nephrolithiasis and nephrocalcinosis (from over-replacement with hypercalciuria), cataracts, basal ganglia calcification (Fahr syndrome), CKD
• Cardiomyopathy, congestive heart failure
• Hungry bone syndrome (post-parathyroidectomy)
• Calcium-phosphate product >55 → ectopic soft-tissue calcification

PANCE pearls

• ALWAYS check and correct magnesium first — hypomagnesemia produces a functional hypoparathyroidism that does not respond to calcium.
• Chvostek sign has low sensitivity (positive in some normals); Trousseau sign is more specific.
• Treatment target is low-normal calcium (~8.0-8.5) — aggressive correction to mid-normal causes hypercalciuria, stones, and nephrocalcinosis.
• Thiazides reduce urinary calcium; loops increase it — use thiazides as adjuncts in hypoparathyroidism.
• DiGeorge syndrome = 22q11.2 deletion — think hypocalcemia + cardiac anomaly + immunodeficiency in a child.

References

• ESE 2015 — European Society of Endocrinology Clinical Guideline: Treatment of Chronic Hypoparathyroidism in Adults (Bollerslev et al., Eur J Endocrinol 2015)
• Workshop 2016 — Management of Hypoparathyroidism: Summary Statement and Guidelines (Brandi et al., J Clin Endocrinol Metab 2016)
• Endocrine Society 2022 — Hypoparathyroidism in the Adult: ES Updated Practice Guideline (Khan et al., J Bone Miner Res 2022)