Pseudohypoparathyroidism
Pseudohypoparathyroidism is a rare genetic cause of hypocalcemia from end-organ (kidney and bone) resistance to parathyroid hormone, most often from a maternally inherited inactivating GNAS mutation that produces the Albright hereditary osteodystrophy phenotype alongside hypocalcemia, hyperphosphatemia, and an elevated, not low, PTH level. Acute symptomatic hypocalcemia is treated with intravenous calcium, and chronic disease is managed with oral calcium and calcitriol.
- Topic reviewThe full article, organized the way the exam asks it.
- ABIM-format MCQsVignettes with an explanation for every wrong answer.
- Key factsThe numbers and thresholds worth memorizing, up front.
- AI tutorMedBrain answers the question you're stuck on.
What this article covers
- Overview
Definition: pseudohypoparathyroidism is a rare genetic cause of hypocalcemia in which the kidney and bone are resistant to the actions of parathyroid hormone (PTH) because of a receptor or…
- Epidemiology
A rare cause of hypocalcemia: PTH resistance (pseudohypoparathyroidism) is a rare genetic cause of hypocalcemia, distinct from the far more common postsurgical or autoimmune hypoparathyroidism.
- Risk factors
Maternal inheritance of an inactivating GNAS mutation: because the GNAS gene is imprinted, inheriting the mutated allele from the mother produces the full syndrome of end-organ PTH resistance with…
- Pathophysiology
Normal PTH signaling requires an intact Gs alpha-adenylate cyclase pathway: PTH binds its receptor on kidney and bone, activating a Gs protein alpha subunit that stimulates adenylate cyclase to…
- Clinical features
Albright hereditary osteodystrophy phenotype: short stature, round face, obesity, shortened fourth and fifth metacarpal (or metatarsal) bones, subcutaneous calcifications, and developmental delay (mild intellectual disability).
- Differential diagnosis
Hypoparathyroidism (postsurgical, autoimmune, or DiGeorge syndrome): a low PTH level in a hypocalcemic patient, unlike the elevated PTH of pseudohypoparathyroidism.
- Diagnosis
The diagnostic basis is the biochemical triad of hypocalcemia, hyperphosphatemia, and an elevated PTH level, in a patient who often also has the Albright hereditary osteodystrophy phenotype.
- Management
First, for acute severe or symptomatic hypocalcemia (tetany, laryngeal stridor, convulsions, QT prolongation), give intravenous calcium, administered through central intravenous access, not…
- Complications
Laryngeal stridor and convulsions: life-threatening manifestations of severe, uncorrected hypocalcemia.
- Prognosis
Chronic, lifelong biochemical disease requiring indefinite therapy: because the underlying end-organ resistance to PTH is genetic, oral calcium and calcitriol therapy continues long-term with close monitoring.
- Prevention
Monitor therapy closely to keep serum calcium just below the lower limit of the reference range and urinary calcium under 300 mg in 24 hours, preventing hypercalciuria, nephrolithiasis, and nephrocalcinosis from overcorrection.
Read the whole article
Subscribing to Internal Medicine opens every article, the full question bank and MedBrain, on the web, iPhone and Android.
Related articles
- Hypocalcemia
Hypocalcemia is a low serum calcium concentration, most often from insufficient parathyroid hormone action (postsurgical or autoimmune hypoparathyroidism, hypomagnesemia, or PTH resistance) or from vitamin D deficiency and chronic kidney disease. Severe or symptomatic disease requires urgent intravenous calcium, while chronic disease is managed with oral calcium, vitamin D repletion, and calcitriol when PTH is absent or the kidney cannot activate vitamin D.
- Hypoparathyroidism
Hypoparathyroidism is PTH deficiency causing hypocalcemia and hyperphosphatemia, most often from inadvertent parathyroid injury during anterior neck surgery. First-line treatment is oral calcium plus calcitriol titrated to a low-normal serum calcium, with recombinant PTH reserved for inadequate control.
- Familial hypocalciuric hypercalcemia
Familial hypocalciuric hypercalcemia is an autosomal dominant, lifelong, asymptomatic hypercalcemia caused by an inactivating mutation of the calcium-sensing receptor, which raises the parathyroid hormone and renal calcium reabsorption set point. The clinching test is a 24-hour urine calcium-creatinine clearance ratio below 0.01, and management is reassurance and family screening, since parathyroidectomy does not correct the calcium and is not indicated.