Match each clinical and laboratory profile describing a disturbance in calcium and phospho… — USMLE Step 2 CK

Match each clinical and laboratory profile describing a disturbance in calcium and phosphorus metabolism to its most likely underlying pathophysiologic mechanism or genetic etiology.

A $14$ -year-old girl with intellectual disability, obesity, shortened fourth and fifth metacarpals, serum calcium $7.2$ mg/dL, phosphorus $6.5$ mg/dL, and intact PTH $150$ pg/mL.Maternal inheritance of a GNAS1 imprinting mutation causing end-organ hormone resistance
A $52$ -year-old man with severe generalized bone pain, serum calcium $9.0$ mg/dL, phosphorus $1.6$ mg/dL, intact PTH $45$ pg/mL, and profoundly elevated plasma fibroblast growth factor 23 (FGF23).Paraneoplastic secretion of a phosphatonin by a benign mesenchymal neoplasm
A $45$ -year-old woman with recurrent mucocutaneous candidiasis, muscle cramps, positive Chvostek sign, serum calcium $6.8$ mg/dL, phosphorus $6.2$ mg/dL, and intact PTH $8$ pg/mL.Autoimmune destruction of glandular tissue mediated by mutations in the AIRE gene
A $65$ -year-old housebound man with proximal muscle weakness, waddling gait, serum calcium $7.8$ mg/dL, phosphorus $2.2$ mg/dL, intact PTH $120$ pg/mL, and alkaline phosphatase $350$ U/L.Nutritional deficiency leading to impaired intestinal absorption and secondary hyperparathyroidism

Answer

The correct pairings identify Pseudohypoparathyroidism type 1a (maternal GNAS1 mutation), Tumor-induced osteomalacia (mesenchymal neoplasm), Autoimmune Polyendocrine Syndrome Type 1 (AIRE gene mutation), and osteomalacia (nutritional vitamin D deficiency).

Each clinical scenario uniquely maps to a distinct pathophysiological disturbance of the bone-mineral axis. Precise interpretation of the PTH response relative to ambient calcium and phosphorus levels dictates the correct etiology.

Step-by-Step Solution

Analyze the first patient's laboratory profile and physical findings.

Hypocalcemia, hyperphosphatemia, and elevated PTH indicate end-organ PTH resistance. The physical features (obesity, shortened metacarpals) represent Albright hereditary osteodystrophy.

Recognizing the combination of PTH resistance and skeletal anomalies isolates the diagnosis to Pseudohypoparathyroidism type 1a (GNAS1 mutation).

Analyze the second patient's isolated laboratory abnormalities.

Profound hypophosphatemia with normal calcium and normal PTH, combined with high FGF23, indicates renal phosphate wasting.

In adults, acquired FGF23 excess is almost exclusively caused by paraneoplastic secretion from a benign phosphaturic mesenchymal tumor (tumor-induced osteomalacia).

Evaluate the third patient's endocrine and infectious manifestations.

Inappropriately low PTH in the setting of hypocalcemia and hyperphosphatemia confirms primary hypoparathyroidism. The concurrent candidiasis points to a polyendocrine syndrome.

The triad of primary hypoparathyroidism, chronic mucocutaneous candidiasis, and primary adrenal insufficiency defines APS-1, which is mediated by AIRE gene mutations.

Assess the fourth patient's presentation of weakness and specific bone markers.

Hypocalcemia combined with hypophosphatemia, elevated PTH, and elevated alkaline phosphatase indicates secondary hyperparathyroidism due to poor substrate availability.

Being housebound restricts sunlight exposure, leading to nutritional vitamin D deficiency. This impairs calcium and phosphorus absorption, triggering a compensatory, but ultimately maladaptive, PTH surge.

Key Concept

The differential diagnosis of complex calcium and phosphorus metabolic disorders relies on interpreting the directional changes of calcium, phosphorus, and PTH, combined with unique clinical phenotypes and genetic mechanisms.

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