What is the most likely diagnosis for a patient with hypercalcemia, hypophosphatemia, slightly elevated parathyroid hormone (PTH) levels, and low 25-Hydroxy Vitamin D3 levels, presenting with generalized muscle and bone ache, abdominal cramps, and relief with cold milk?

Diagnosis: Primary Hyperparathyroidism

The most likely diagnosis is C. Primary hyperparathyroidism, based on the constellation of hypercalcemia (2.85 mmol/L), elevated ionized calcium (1.9 mmol/L), hypophosphatemia (0.71 mmol/L), inappropriately elevated PTH (5.5 pmol/L, just above upper limit of 5.3), and low vitamin D (15 mol/L). 1

Diagnostic Reasoning

Why Primary Hyperparathyroidism

• The key diagnostic feature is the inappropriately elevated or normal PTH in the presence of hypercalcemia, which defines primary hyperparathyroidism biochemically 2, 3
• In this case, PTH is 5.5 pmol/L (reference range 1.1-5.3), which is elevated despite significant hypercalcemia—a normal parathyroid gland would suppress PTH completely in the face of calcium levels this high 1
• The parathyroid glands are autonomously secreting PTH despite elevated calcium, which is the hallmark pathophysiology of primary hyperparathyroidism 1
• Hypophosphatemia (0.71 mmol/L) is characteristic, as PTH increases renal phosphate excretion 4
• The low vitamin D (15 mol/L) is expected because hypercalcemia suppresses PTH-driven conversion of 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D 1

Why NOT the Other Options

A. Milk-Alkali Syndrome:

• This diagnosis requires PTH to be suppressed (low), not elevated 1
• Milk-alkali syndrome occurs from excessive calcium and alkali intake, causing hypercalcemia that should shut down PTH production completely
• The elevated PTH (5.5 pmol/L) definitively excludes this diagnosis 2

B. Idiopathic Hypercalcemia:

• This is not a standard diagnostic entity in adults
• Any hypercalcemia requires identification of the underlying mechanism—elevated PTH points directly to primary hyperparathyroidism 1

D. Secondary Hyperparathyroidism:

• Secondary hyperparathyroidism presents with hypocalcemia or normal calcium, never hypercalcemia 5
• In secondary hyperparathyroidism, PTH is appropriately elevated in response to low calcium (from vitamin D deficiency, renal disease, or malabsorption) 5
• This patient has hypercalcemia, which excludes secondary hyperparathyroidism by definition 5

Clinical Context Supporting Primary Hyperparathyroidism

• Generalized muscle and bone ache are classic symptoms of moderate hypercalcemia 1
• Abdominal cramps are consistent with gastrointestinal manifestations of hypercalcemia 6
• The symptom relief with cold milk is likely coincidental or related to temporary gastric soothing, not diagnostic 1

Critical Diagnostic Pitfall to Avoid

• Vitamin D deficiency can coexist with primary hyperparathyroidism and must not be misinterpreted as causing secondary hyperparathyroidism 1
• The presence of hypercalcemia with elevated PTH confirms primary hyperparathyroidism, regardless of vitamin D status 1
• Vitamin D deficiency in this context is a consequence of the hypercalcemia suppressing PTH-mediated vitamin D activation, not the cause of PTH elevation 1

Next Steps After Diagnosis

• Confirm diagnosis by repeating calcium and PTH measurements to document persistence 1
• Measure 24-hour urinary calcium to exclude familial hypocalciuric hypercalcemia (calcium-to-creatinine clearance ratio <0.01 would suggest this rare genetic condition) 2
• Assess for surgical candidacy: corrected calcium >1 mg/dL above upper limit, impaired kidney function (eGFR <60), osteoporosis, nephrolithiasis, or age <50 years 1
• Refer to endocrinology and an experienced parathyroid surgeon for evaluation 1
• Do not order parathyroid imaging until biochemical diagnosis is confirmed—imaging is for surgical planning, not diagnosis 1