High serum inorganic phosphorus (Pi) (typically >5 mg/dL)
Decreased urinary excretion of both calcium and phosphate
Absence of PTH actions explains these laboratory results.
Underlying Mechanisms
Decreased Bone Resorption: PTH normally stimulates osteoclasts. Without PTH, there is minimal release of calcium into the bloodstream.
Diminished Calcium Absorption: PTH deficiency → decreased renal 1α-hydroxylation of 25-hydroxyvitamin D (25[OH]D) to 1,25-dihydroxyvitamin D (1,25[OH]₂D) → reduced GI calcium absorption.
Excess Phosphate Retention: Without PTH, the renal tubules reabsorb phosphate excessively, elevating serum phosphate. High Pi itself also depresses serum calcium.
Diagnostic Triad
Low serum calcium
High serum phosphate
Normal serum alkaline phosphatase (in the absence of renal failure or malabsorption)
This triad is essentially pathognomonic for hypoparathyroidism.
CAUSES OF PTH DEFICIENCY
Postsurgical Hypoparathyroidism (Most Common)
Neck Surgery: Subtotal or total thyroidectomy, parathyroid surgery, or other neck cancer surgery.
Often transient if some viable parathyroid tissue remains or if the parathyroid glands recover from surgical trauma.
Permanent if all parathyroid tissue was removed or irreversibly damaged.
Hungry Bone Syndrome: Occurs after removal of a hyperfunctioning parathyroid adenoma (bone avidly takes up calcium postoperatively).
Autoimmune Hypoparathyroidism
Autoimmune Destruction of parathyroid glands, often associated with polyglandular autoimmune syndrome type 1 (with adrenal insufficiency + chronic mucocutaneous candidiasis).
Rarely, activating autoantibodies to the Ca²⁺-sensing receptor (CaSR) can cause hypoparathyroidism.
Developmental or Regulatory Defects
Abnormal parathyroid gland embryologic development or PTH synthesis.
Mutations affecting regulation of PTH production, secretion, or action.
GENETIC CAUSES OF HYPOPARATHYROIDISM
Abnormal Parathyroid Development
X-linked or autosomal recessive mutations (e.g., GCM2 gene, encoding a key transcription factor).
PreproPTH Gene Mutations
Defects in the PTH precursor protein → no biologically active PTH.
Autosomal Dominant Activating Mutations of the CaSR
Lower calcium set point for PTH release → PTH not secreted until hypocalcemia is severe.
High urinary calcium excretion (unlike other forms of hypoparathyroidism, which generally show low urinary calcium).
PSEUDOHYPOPARATHYROIDISM (HYPOCALCEMIA DESPITE HIGH PTH)
Definition: Serum PTH is high, but hypocalcemia persists because of end-organ (bone, kidney) resistance or other defects in vitamin D metabolism.
Key Features:
Inadequate PTH-induced bone resorption
Decreased renal 1,25(OH)₂D production
Hypocalcemia remains despite elevated PTH.
CLINICAL MANIFESTATIONS OF ACUTE HYPOCALCEMIA
Range of Symptoms
Minor: Anxiety, mild muscle spasms or cramps, perioral and acral paresthesias
Neuromuscular Irritability: Early signs include perioral numbness, tingling (hands/feet), muscle cramps, hyperreflexia, photophobia, diplopia.
Advanced symptoms:
Carpopedal Spasm (adduction of thumb, finger extension, wrist flexion)
Laryngospasm (stridor due to glottic spasm)
Seizures (grand mal, petit mal, focal)
Clinical Tests
Trousseau Sign: Carpopedal spasm induced by inflating a blood pressure cuff above systolic BP for ~3 minutes.
Chvostek Sign: Ipsilateral facial muscle contraction when tapping the facial nerve below the zygoma. (Not fully specific for hypocalcemia; can also be positive in alkalosis.)
