Differentials
Familial hypocalciuric hypercalemia (FHH)
SIGNS / SYMPTOMS
Patients with FHH appear healthy. There may be a positive family history of other members with high serum calcium without objective symptoms of nephrolithiasis or bone disease.
INVESTIGATIONS
Renal calcium to creatinine clearance ratio is lower compared with patients with PHPT.
Diagnosis can be confirmed with genetic testing.
Humoral hypercalcemia of malignancy
SIGNS / SYMPTOMS
Positive history of solid tumor malignancy. Other manifestations of systemic signs of illness such as weight loss, fatigue, pain, and feelings of ill health.
Humoral hypercalcemia of malignancy occurs in patients with solid tumors of the lung, breast, kidney, ovary, and head and neck; there is typically no bone metastasis. This process is mediated primarily by PTH-related-protein/peptide (PTHrP). PTHrP also plays a role in the hypercalcemia associated with bone metastases and multiple myeloma.
INVESTIGATIONS
Serum intact PTH is appropriately low, but PTHrP would be elevated if the source is from a malignancy.
Mild hypokalemic hypochloremic alkalosis may be present.
CT scan of the thorax, abdomen, and pelvis is used to evaluate for malignancies.
Multiple myeloma
SIGNS / SYMPTOMS
There may be weight loss or back pain.
INVESTIGATIONS
Serum protein electrophoresis shows monoclonal gammopathy.
Presence of Bence-Jones protein in urine.
Bone x-ray may show lytic bone lesions, characteristic of multiple myeloma.
There may be anemia.
Milk-alkali syndrome
SIGNS / SYMPTOMS
History of excessive intake of antacids.
INVESTIGATIONS
Calcium levels are high, but serum intact PTH is low.
Sarcoidosis
SIGNS / SYMPTOMS
Can present with a dry cough, breathlessness, or tender red skin lumps.
INVESTIGATIONS
CXR shows thoracic lymphadenopathy and parenchymal lung disease.
Angiotensin-converting enzyme levels may be elevated.
May have eosinophilia or elevated erythrocyte sedimentation rate (ESR).
Calcium is high, but serum intact PTH is low.
Hypervitaminosis D
SIGNS / SYMPTOMS
History of excessive vitamin D intake (usually within the context of over-treated vitamin D deficiency or self-medication).
INVESTIGATIONS
25-hydroxyvitamin D level >100 nanograms/mL indicates hypervitaminosis D.
Calcium is high, but serum intact PTH is low.
Thyrotoxicosis
SIGNS / SYMPTOMS
Tachycardia, weight loss, nervousness, and anxiousness are present in thyrotoxicosis.
INVESTIGATIONS
TSH is low.
Calcium is high, but serum intact PTH is low.
Chronic or acute leukemia
SIGNS / SYMPTOMS
Infections, fever, weight loss, lymphadenopathy, and abnormal bleeding are present in acute or chronic leukemia.
INVESTIGATIONS
CBC may show anemia, leukocytosis, or leukopenia.
Calcium is high, as well as PTH-related-protein/peptide. PTH levels are low.
Immobilization
SIGNS / SYMPTOMS
Patients have a history of being bed-bound or hospitalized for long periods of time, but may be without specific hyperparathyroid symptoms (e.g., nephrolithiasis).
INVESTIGATIONS
Serum calcium levels are often high with a low serum intact PTH level.
Thiazide use
SIGNS / SYMPTOMS
Patients usually have a history of hypertension and are on thiazide diuretic therapy.
INVESTIGATIONS
Serum calcium levels should decrease when thiazide medication is discontinued. Serum intact PTH levels are low.
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