Bone/Parathyroid Case 3

A 67-year-old Caucasian woman with vitamin D deficiency presents for follow-up of osteopenia. She has no history of vertebral, radius, or pathological fracture or family history of osteoporosis. A recent DXA scan revealed a bone mineral density with a T-score of -1.7 in the spine, and -2.0 in the left femoral neck. She takes calcium and vitamin D supplementation. She denies bone pain, history of kidney stones, anorexia, change in concentration, peptic ulcer disease or pancreatitis in the past. 

Laboratory test results at the time of the visit:  

Serum calcium = 11.2 mg/dL (8.2-10.2 mg/dL) (SI: 2.8 [2.1-2.6 mmol/L]) 

Serum phosphate = 2.8 mg/dL (2.3-4.7 mg/dL) (SI: 0.9 [0.7-1.5 mmol/L]) 

Serum creatinine = 0.80 mg/dL (0.6-1.1 mg/dL) (SI: 70.7 [53.0-97.2 µmol/L]) 

Glomerular filtration rate (estimated) > 60 mL/min per 1.73 m2 

Serum 25-hydroxyvitamin D = 30 ng/mL (30-80 ng/mL [optimal] (SI 74.9 nmol/L [74.9-199.7 nmol/L]) 

Serum intact PTH = 85 pg/mL (10-65 pg/mL) (SI: 85 ng/L [10-65 ng/L]) 

Serum albumin = 4.0 g/dL (3.5-5.0 g/dL) (SI: 4.0 g/L [35-50 g/L]) 

Serum magnesium, normal 

Urinary calcium = 450 mg/24 h (100-300 mg/24 h) (SI: 11.2 [2.5-7.5 mmol/d]) 

Urinary creatinine = 1.2 g/24 h (1.0-2.0 g/24 h) (SI: 10.6 [8.8-17.7 mmol/d]) 

Urinary volume = 1600 mL/24 h  

Question 1

Which of the following is the correct next step in management?

A. Continue to monitor calcium, 25-hydroxyvitamin D, PTH every 3-6 months.
B. Increase vitamin D supplementation, repeat calcium, 25-hydroxyvitamin D, PTH in 3 months.
C. Refer to surgery for preoperative localization and parathyroidectomy.
D. Start cinacalcet 30 mg daily and repeat calcium, albumin, creatinine and PTH in 2 weeks.
E. Refer to medical genetics for assessment of Familial Hypocalciuric Hypercalcemia (FHH).
Incorrect!
Correct!
Correct Answer
C. Refer to surgery for preoperative localization and parathyroidectomy.

This patient presents with a clinical constellation of hypercalcemia, elevated PTH with a replete 25-hydroxyvitamin D level, that is suggestive of primary hyperparathyroidism. Additionally, she has clear evidence of hypercalciuria with a fractional excretion of calcium [FeCa] = 0.026; FeCa = (urine calcium x serum creatinine)/(serum calcium x urine creatinine), which further supports a diagnosis of primary hyperparathyroidism rather than familial hypocalciuric hypercalcemia (FHH). The fractional excretion of calcium, also termed the urine calcium to creatinine ratio, can be used to distinguish primary hyperparathyroidism and FHH. A FeCa < 0.01 in a vitamin D-replete individual is highly suggestive of FHH rather than primary hyperparathyroidism (ratio usually > 0.02 in primary hyperparathyroidism. In an analysis of five large studies combining 165 patients with FHH and 197 patients with primary hyperparathyroidism, a FeCa < 0.01 had a sensitivity for FHH of 85% and a specificity of 88% with a positive predictive value (PPV) of 85% (1-3). This effectively rules out answer E.  

This patient currently does not have any symptoms to suggest primary hyperparathyroidism, but does meet surgical criteria for parathyroidectomy. For asymptomatic individuals who meet the Fourth International Workshop on Asymptomatic Primary Hyperparathyroidism guidelines, surgical intervention is recommended as opposed to observation (4, 5). Therefore, answers A, B, and D are incorrect. 

Patients need to meet only one of the following criteria for surgery (with our patient’s findings in bold):  

  • Serum calcium concentration of 1.0 mg/dL (0.25 mmol/L) or more above the upper limit of normal 

  • Skeletal indications:  

  • Bone density at the hip, lumbar spine, or distal radius htat is more than 2.5 standard deviations below peak bone mass (T-score < -2.5) 

  • Previous asymptomatic vertebral fracture (by radiograph, computed tomography [CT], magnetic resonance imaging [MRI], or vertebral fracture assessment).  

  • Renal indications: 

  • Estimated glomerular filtration rate (eGFR) < 60 mL/min 

  • Twenty-four-hour urinary calcium > 400 mg/day (> 10 mmol/day).  

  • Nephrolithiasis or nephrocalcinosis by radiograph, ultrasound, or CT.  

  • Age less than 50 years 

This patient currently has primary hyperparathyroidism by lab studies, and has two indications for parathyroidectomy. It is important to note that she does not have any contraindications to surgery that are mentioned in the question stem, therefore, cinacalcet (answer D) would not be the most appropriate next step in management.  

References: 

1. Sywak MS, Knowlton ST, Pasieka JL, et al. Do the National Institutes of Health consensus guidelines for parathyroidectomy predict symptom severity and surgical outcome in patients with primary hyperparathyroidism? Surgery 2002;132:1013.  

2. Walker MD, McMahon DJ, Inabnet WB, et al. Neuropsychological features in primary hyperparathyroidism: a prospective study. J Clin Endocrinol Metab 2009;94:1951.  

3. Walker MD, Silverberg SJ. Parathyroidectomy in asymptomatic primary hyperparathyroidism: improves “bones” but not “psychic moans”. J Clin Endocrinol Metab 2007;92:1613. 

4. Bilezikian JP, Brandi ML, Eastall R, et al. Guidelines for the management of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J Clin Endocrinol Metab 2008;93:3462. 

5. Silverberg SJ, Clarke BL, Peacock M, et al. Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop.  J Clin Endocrinol Metab 2014;99:3580.  

This patient presents with a clinical constellation of hypercalcemia, elevated PTH with a replete 25-hydroxyvitamin D level, that is suggestive of primary hyperparathyroidism. Additionally, she has clear evidence of hypercalciuria with a fractional excretion of calcium [FeCa] = 0.026; FeCa = (urine calcium x serum creatinine)/(serum calcium x urine creatinine), which further supports a diagnosis of primary hyperparathyroidism rather than familial hypocalciuric hypercalcemia (FHH). The fractional excretion of calcium, also termed the urine calcium to creatinine ratio, can be used to distinguish primary hyperparathyroidism and FHH. A FeCa < 0.01 in a vitamin D-replete individual is highly suggestive of FHH rather than primary hyperparathyroidism (ratio usually > 0.02 in primary hyperparathyroidism. In an analysis of five large studies combining 165 patients with FHH and 197 patients with primary hyperparathyroidism, a FeCa < 0.01 had a sensitivity for FHH of 85% and a specificity of 88% with a positive predictive value (PPV) of 85% (1-3). This effectively rules out answer E.  

This patient currently does not have any symptoms to suggest primary hyperparathyroidism, but does meet surgical criteria for parathyroidectomy. For asymptomatic individuals who meet the Fourth International Workshop on Asymptomatic Primary Hyperparathyroidism guidelines, surgical intervention is recommended as opposed to observation (4, 5). Therefore, answers A, B, and D are incorrect. 

Patients need to meet only one of the following criteria for surgery (with our patient’s findings in bold):  

  • Serum calcium concentration of 1.0 mg/dL (0.25 mmol/L) or more above the upper limit of normal 

  • Skeletal indications:  

  • Bone density at the hip, lumbar spine, or distal radius htat is more than 2.5 standard deviations below peak bone mass (T-score < -2.5) 

  • Previous asymptomatic vertebral fracture (by radiograph, computed tomography [CT], magnetic resonance imaging [MRI], or vertebral fracture assessment).  

  • Renal indications: 

  • Estimated glomerular filtration rate (eGFR) < 60 mL/min 

  • Twenty-four-hour urinary calcium > 400 mg/day (> 10 mmol/day).  

  • Nephrolithiasis or nephrocalcinosis by radiograph, ultrasound, or CT.  

  • Age less than 50 years 

This patient currently has primary hyperparathyroidism by lab studies, and has two indications for parathyroidectomy. It is important to note that she does not have any contraindications to surgery that are mentioned in the question stem, therefore, cinacalcet (answer D) would not be the most appropriate next step in management.  

References: 

1. Sywak MS, Knowlton ST, Pasieka JL, et al. Do the National Institutes of Health consensus guidelines for parathyroidectomy predict symptom severity and surgical outcome in patients with primary hyperparathyroidism? Surgery 2002;132:1013.  

2. Walker MD, McMahon DJ, Inabnet WB, et al. Neuropsychological features in primary hyperparathyroidism: a prospective study. J Clin Endocrinol Metab 2009;94:1951.  

3. Walker MD, Silverberg SJ. Parathyroidectomy in asymptomatic primary hyperparathyroidism: improves “bones” but not “psychic moans”. J Clin Endocrinol Metab 2007;92:1613. 

4. Bilezikian JP, Brandi ML, Eastall R, et al. Guidelines for the management of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J Clin Endocrinol Metab 2008;93:3462. 

5. Silverberg SJ, Clarke BL, Peacock M, et al. Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop.  J Clin Endocrinol Metab 2014;99:3580.