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 A 17-year-old boy comes to the physician for a follow-up examination. Two months ago,
he suffered a spinal fracture after a fall from the roof. He feels well. His father has multiple
endocrine neoplasia type 1. Vital signs are within normal limits. Examination shows no
abnormalities. Laboratory studies show:

Hemoglobin 13.7 g/dL

Serum
Creatinine 0.7 mg/dL
Proteins
Total 7.0 g/dL
Albumin 4.1 g/dL
Calcium 11.4 mg/dL
Phosphorus 5.3 mg/dL
Alkaline phosphatase 100 U/L

Which of the following is the most likely cause of these findings?

The hypercalcemia in this adolescent is due to excess osteoclastic bone resorption.

 

Sarcoidosis

Granulomatous diseases such as sarcoidosis can result in hypercalcemia as a result of

ectopic vitamin D production by activated mononuclear cells (e.g., macrophages) of
lungs and lymph nodes. ALP levels may also be increased due to hepatic granuloma
formation. However, phosphate levels are usually normal, and this patient lacks
clinical features that would suggest sarcoidosis (e.g., dyspnea, lymphadenopathy,
iridocyclitis, skin plaques).

  b

Familial hypocalciuric hypercalcemia

Familial hypocalciuric hypercalcemia (FHH) would result in elevated calcium and mildly
elevated ALP levels. However, phosphate levels would be either normal or decreased.

  c
ImmobilizationS

Prolonged immobilization (e.g., following a vertebral fracture) can lead to increased bone
demineralization with mild hypercalcemia, hyperphosphatemia, and increased alkaline
phosphatase.

Disorders of calcium balance

  d

Parathyroid adenoma

The family history of multiple endocrine neoplasia might suggest a diagnosis of parathyroid
adenoma, which would result in hypercalcemia and mildly increased ALP levels (as a result
of primary hyperparathyroidism). However, patients with parathyroid adenoma would have
hypophosphatemia because PTH receptor activation in the proximal convoluted tubule
decreases renal phosphate reabsorption.

  e

Pseudohypercalcemia

Pseudohypercalcemia occurs in patients with increased serum protein concentration (e.g., due
to hyperalbuminemia in dehydrated patients or due to paraproteinemia in patients with
multiple myeloma) because approximately half of all serum calcium is bound to serum
proteins. This patient, however, has normal albumin and serum total protein levels.

  f

Paraneoplastic syndrome

Paraneoplastic production of the PTH-related peptide (PTHrP) by tumors (at this patient's
age, e.g., neuroblastoma, renal tumors, and leukemia) can result in hypercalcemia and mildly
increased ALP levels. Phosphate levels, however, would be decreased because PTH receptor
activation in the proximal convoluted tubule decreases renal phosphate reabsorption. This
patient also lacks any clinical feature that would suggest an underlying malignancy (e.g.,
weight loss, fatigue, bone pain, abdominal pain, hematuria).

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