Pathophysiology
P-I-13. Menopause & osteoporosis, Case 1
閉経と骨粗鱬症 症例1
A 56-year-old woman is complaining of fatigue, which has been gradually increasing for approximately half a year. Three months ago high blood pressure was detected, for which she is taking ACE-inhibitors. A gastroscopy that was performed because of her stomach pain showed focal erosion in different areas of the gastric mucosa, for which a proton pump inhibiting treatment was recommended. A negative result for Helicobacter pylori was obtained from a histological sample. The patient’s anamnesis also contained an episode of nephrolithiasis.
Physical examination: Height: 162 cm. Weight: 50 kg. RR: 142/90 Hgmm.
Blood:
- ESR: 20 mm/h
- CRP: 6 mg/L
- RBC: 4.68 T/L
- haemoglobin: 144 g/L
- haematocrit: 0.42
- Na⁺: 142 mmol/L
- K⁺: 4.1 mmol/L
- Ca²⁺: 2.8 mmol/L
- PO₄³⁻: 0.6 mmol/L
- albumin: 38 g/L
- 25(OH) vitamin D level: 34 ng/mL (20-40 ng/mL)
- creatinine: 122 µmol/L
- eGFR: > 90 ml/min
- ASAT: 30 U/L
- ALAT: 22 U/L
- ALP: 450 U/L
- GGT: 40 U/L
Urine:
- protein: negative
- glucose: negative
- specific gravity: 1018 g/L
Urine sediment:
- WBC: 2/hpf
- RBC: 4/hpf
- star-shaped crystals
DEXA scan:
- lumbar spine T-score: -2.8
- hip T-score: -2.5
Key Quotes & What They Tell Us
| Quote / Value | Interpretation |
|---|---|
| Ca²⁺ 2.8 mmol/L (high); PO₄³⁻ 0.6 mmol/L (low) | Hypercalcaemia with hypophosphataemia — the biochemical signature of primary hyperparathyroidism (PTH drives Ca up, phosphate down) |
| ALP 450 U/L (high) | Increased bone turnover/resorption from excess PTH |
| “episode of nephrolithiasis”; urine “star-shaped crystals” | Hypercalciuria → calcium-containing kidney stones |
| “focal erosion … of the gastric mucosa” with negative H. pylori | Hypercalcaemia stimulates gastrin/acid → peptic erosions (“abdominal groans”) |
| “fatigue”; newly detected hypertension (RR 142/90) | Non-specific hypercalcaemia symptoms; hypercalcaemia can contribute to hypertension |
| 25(OH) vitamin D 34 ng/mL (normal); eGFR > 90 | Normal vitamin D and renal function exclude deficiency/CKD as the cause → points to primary, not secondary, hyperparathyroidism |
| DEXA lumbar T -2.8, hip T -2.5 | Osteoporosis (T ≤ -2.5) from chronic PTH-driven bone resorption |
Key Points
- Diagnosis: Primary hyperparathyroidism (excess PTH, typically a parathyroid adenoma).
- Biochemistry: Hypercalcaemia + hypophosphataemia + raised ALP, with normal vitamin D and renal function.
- Classic triad: “Stones, bones, and abdominal groans” — kidney stones, osteoporosis/bone pain, and peptic/GI symptoms.
- Pathophysiology: PTH increases bone resorption, renal calcium reabsorption, and vitamin-D activation → hypercalcaemia and bone loss.
- Contrast: Differs from postmenopausal osteoporosis (normal calcium) and secondary hyperparathyroidism (low calcium, renal failure).
一問一答
▶What is the biochemical signature of primary hyperparathyroidism?
Hypercalcemia with hypophosphatemia (PTH drives calcium up and phosphate down).
▶What is the classic clinical triad of primary hyperparathyroidism?
Stones, bones, and abdominal groans — kidney stones, osteoporosis/bone pain, and peptic/GI symptoms.
▶What are the three main actions of PTH that produce hypercalcemia?
Increased bone resorption, increased renal calcium reabsorption, and increased vitamin-D activation (boosting gut calcium absorption).
▶Why is ALP elevated (450 U/L) in Case 1?
Increased bone turnover/resorption from excess PTH raises alkaline phosphatase.
▶In the Case 1 patient (high Ca²⁺, low PO₄³⁻, osteoporosis, kidney stones), what is the diagnosis?
Primary hyperparathyroidism (excess PTH, typically from a parathyroid adenoma).
▶Why does the patient develop kidney stones in Case 1?
Hypercalciuria from hypercalcemia promotes calcium-containing kidney stones (seen as star-shaped crystals).
▶Why does the patient have gastric erosions despite negative H. pylori?
Hypercalcemia stimulates gastrin and acid secretion, causing peptic erosions (the 'abdominal groans').
▶How do normal vitamin D and eGFR help localize the diagnosis in Case 1?
They exclude vitamin D deficiency and CKD, pointing to primary (not secondary) hyperparathyroidism.
▶What DEXA T-score defines osteoporosis, and what were the patient's values?
T-score ≤ -2.5 defines osteoporosis; lumbar T was -2.8 and hip T was -2.5.
▶How does primary hyperparathyroidism cause bone loss?
Chronic excess PTH drives sustained osteoclastic bone resorption, reducing bone density.
▶How does the calcium/phosphate pattern of primary hyperparathyroidism differ from secondary?
Primary: high calcium, low phosphate. Secondary (CKD): low/normal calcium, high phosphate.
▶What is the most common cause of primary hyperparathyroidism?
A solitary parathyroid adenoma.
▶What general (non-specific) symptoms of hypercalcemia did the Case 1 patient have?
Fatigue, and contributory hypertension.
▶Why does PTH lower serum phosphate?
PTH reduces renal phosphate reabsorption (phosphaturic effect), lowering serum phosphate.
▶How does primary hyperparathyroidism differ from postmenopausal osteoporosis on labs?
Primary hyperparathyroidism has hypercalcemia; postmenopausal osteoporosis has normal calcium.
▶What confirmatory hormone test is expected in primary hyperparathyroidism?
An inappropriately elevated (or non-suppressed) PTH level in the face of hypercalcemia.
▶What is the definitive treatment for symptomatic primary hyperparathyroidism?
Surgical removal of the overactive parathyroid gland (parathyroidectomy).
▶Why might calcium be measured alongside albumin in hypercalcemia workup?
Because calcium is partly protein-bound; albumin is needed to correct/interpret total calcium.
▶What is the cardinal cause of nephrolithiasis in hyperparathyroidism?
Hypercalciuria leading to calcium-based stone formation.
▶Why can hypercalcemia cause neuropsychiatric and GI symptoms?
Elevated calcium depresses neuromuscular excitability and alters GI/CNS function, causing fatigue, constipation, and peptic symptoms.