Hypercalcemia

Case Presentation

A 58-year-old man is referred to your outpatient clinic by his primary care physician for evaluation of elevated serum calcium. The referral notes report a slight fatigue over the past six months, which prompted a thorough medical workup, including the calcium measurement. His past medical history includes hypertension and a conservatively managed episode of urolithiasis three years ago. He is currently taking Lisinopril 10 mg daily for blood pressure control and no other medications.

Laboratory test 2 months ago

Serum calcium level: 11.8 mg/dL (Reference Range: 8.5–10.2 mg/dL) or 2.94 mmol/L (Reference Range: 2.20 - 2.55 mmol/L)

Serum albumin: 41 g/L (Reference Range: 34-50 g/L)

Serum creatinine: 75 µmol/l (Reference Range 45 - 84 µmol/L)

eGFR: > 90 ml/min/1.73 m² (Reference Range >59 ml/min/1.73 m²)

Laboratory test 1 month ago

Serum calcium level: 11.9 mg/dL (Reference Range: 8.5–10.2 mg/dL) or 2.97 mmol/L (Reference Range: 2.20 - 2.55 mmol/L)

Referral & Emergency Evaluation

To make optimal use of the patient’s history, we will first review the possible etiologies of this patient’s hypercalcemia.

History

The patient denies any history of fractures or bone pain. Urolithiasis was managed conservatively 3 years ago without any subsequent episodes. The stone was not examined. He denies any respiratory symptoms like dyspnea and cough, as well as B-Symptoms like weight loss or nighttime sweating. Regarding his medication history, he confirms that he is not taking any diuretics, lithium, or excessive amounts of calcium or vitamin D supplements. Additionally, there is no known family history of endocrine disorders, jaw tumours or disorders associated with multiple endocrine neoplasia.

Clinical Exam

On examination, his vital signs are within normal limits, with a blood pressure of 124/78 mmHg and a heart rate of 76 bpm. He appears well-hydrated, with no immediate signs of distress. No lymphadenopathy is noted. Cardiopulmonary examination is uneventful as well as clinical examination of the neck and skin.

Diagnosis

Results of the patient

Ionized Calcium: 6.2 mg/dl or 1.55 mmol/L (Reference Range: 4.4-5.2 mg/dL or 1.10-1.30 mmol/L)

PTH: 105 pg/ml (Reference Range: 15–65 pg/mL)

Phosphate: 0.82 mmol/L (Reference Range: 0.81 - 1.50 mmol/L)

25OHD: normal

Serum creatinine: 75 µmol/l

eGFR: > 90 ml/min/1.73 m²

Management

The neck ultrasound reveals a hypoechoic, well-circumscribed lesion measuring approximately 1.3 x 0.8 cm, located posterior to the inferior pole of the right thyroid lobe. The lesion appears distinct from the thyroid gland, with increased vascularity predominantly at the periphery and polar regions on Doppler imaging, suggestive of a parathyroid adenoma. No significant cervical lymphadenopathy is observed, and the thyroid gland itself appears normal in size and echotexture.

Follow-up imaging with 18F-fluorocholine PET/CT demonstrates a metabolically active nodule at the corresponding site. No additional hypermetabolic foci are identified in the remaining parathyroid glands, and there is no evidence of ectopic parathyroid tissue.

The patient agrees with a referral to a parathyroid surgeon. The following are knowledge checkpoints, questions, and exercises designed to strengthen understanding and clinical management of patients with primary hyperparathyroidism. After that we will revisit our patient’s case.

The patient’s bone mass density (BMD) shows T-scores of -0.8 at the lumbar spine, -1.0 at the femoral neck, and -1.6 at the distal one-third of the radius.

Renal function is normal. The 24-hour urinary calcium excretion is 280 mg/day

Kidney ultrasound revealed a 2 mm stone in the upper segment of the renal calyx, without signs of ureteral stones, kidney congestion, or hydronephrosis.

You conclude, that this patient does not meet the criteria for targeted genetic testing of hereditary primary hyperparathyroidism.

The patient decides to undergo parathyroidectomy. A parathyroidectomy of the right inferior parathyroid gland is planned.

The suspected adenoma located posterior to the right inferior thyroid lobe was identified during surgery. The parathyroid gland posterior to the right superior thyroid lobe was also visualized, showing no signs of adenomatous tissue. Intraoperative PTH levels dropped to 22 pg/ml, indicating successful removal of the hyperfunctioning gland with no evidence of additional overactive tissue.

PTH is measured at 11 pg/ml with total Calcium levels at 8.4 mg/dl (2.1 mmol/L) three hours after surgery with without any symptoms of hypocalcemia.

Clinical examination of the surgical site revealed no evidence of postoperative hematoma. The patient reported no changes in voice quality, and fiberoptic laryngoscopy confirmed intact laryngeal nerve function without signs of nerve injury.

Histopathological analysis confirmed a well-circumscribed, encapsulated lesion composed of uniform chief cells arranged in nests and trabeculae, with reduced adipose tissue and no capsular or vascular invasion, consistent with a parathyroid adenoma.

The patient was started on treatment with 1 g of calcium carbonate twice daily and calcitriol 0.25 mcg twice daily. Subsequent calcium levels remained stable, and the patient was discharged.

Seven days after surgery, the patient reports no symptoms of hypocalcemia. PTH is 13 pg/ml and calcium levels are within the normal range. You decide to continue the current treatment and schedule a follow-up in three weeks. At that visit, PTH rises to 20 pg/ml with calcium remaining normal, and the patient remains asymptomatic. You reduce calcitriol to 0.25 mcg once daily and reinforce education on hypocalcemia symptoms. Subsequent calcium levels remain stable, and PTH increases to 30 pg/ml, permitting a gradual tapering and eventual discontinuation of both calcium and calcitriol supplementation.

Clinical and biochemical follow-up after six months and one year shows the following results:

Six months post surgery:

PTH: 31 pg/ml, (Reference Range: 15–65 pg/mL)

Total Calcium: 8.93 mg/dl or 2.23 mmol/L (Reference Range: 8.5–10.2 mg/dL or 2.20 - 2.55 mmol/L)

Ionized Calcium: 4.55 mg/dl or 1.14 mmol/L (Reference Range: 4.4-5.2 mg/dL or 1.10-1.30 mmol/L)

Phosphate: 1.2 mmol/L (Reference Range: 0.81 - 1.50 mmol/L)

One year post surgery:

PTH: 28 pg/ml,

Total Calcium: 9 mg/dl or 2.25 mmol/L

Phosphate: 1.1 mmol/L

You inform the patient that their primary hyperparathyroidism has been successfully treated. However, continued monitoring for recurrence is recommended.

A DXA scan performed two years postoperatively demonstrates improvement in bone mineral density:

• Initial T-scores: Lumbar spine -0.8; Femoral neck -1.0; Radius (1/3 distal) -1.6

• Current T-scores: Lumbar spine -0.6; Femoral neck -0.9; Radius (1/3 distal) -1.2
  
  

Overall Interpretation:
One year after surgery, the patient remains in full symptomatic remission with stable biochemical parameters. The two-year DXA scan confirms improved bone density, consistent with the expected skeletal recovery following parathyroidectomy.

Ongoing follow-up is planned with annual clinical and biochemical assessments. A repeat DXA scan is scheduled in five years, assuming biochemical stability and no new risk factors for osteoporosis emerge.

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