Primary hyperparathyroidism: Labs to order, Tx to consider

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Applied Evidence

Primary hyperparathyroidism: Labs to order, Tx to consider

J Fam Pract. 2018 November;67(11):E16-E21

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References

1. Griebeler ML, Kearns AE, Ryu E, et al. Secular trends in the incidence of primary hyperparathyroidism over five decades (1965-2010). Bone. 2015;73:1-7.

2. Melmed S, Polonsky, KS, Larsen PR, et al. Williams Textbook of Endocrinology: Hormones and Disorders of Mineral Metabolism, 12th ed. Philadelphia, PA: Elsevier Inc, 2011:1262-1263.

3. Assadi F. Hypercalcemia: an evidence-based approach to clinical cases. Iran J Kidney Dis. 2009;3(2):71-79.

4. Bilezikian JP, Cusano NE, Khan AA, et al. Primary hyperparathyroidism. Nat Rev Dis Primers. 2016;19;2:16033.

5. Roman S, Sosa JA. Psychiatric and cognitive aspects of primary hyperparathyroidism. Curr Opin Oncol. 2007;19:1-5.

6. Berkow JW, Fine BS, Zimmerman LE. Unusual ocular calcification in hyperparathyroidism. Am J Ophthalmol. 1968;66:812-824.

7. Carroll MF, Schade DS. A practical approach to hypercalcemia. Am Fam Physician. 2003;67:1959-1966.

8. Ong GSY, Walsh JP, Stuckey BGA, et al. The importance of measuring ionized calcium in characterizing calcium status and diagnosing primary hyperparathyroidism. J Clin Endocrinol Metab. 2012;97:3138-3145.

9. Silverberg SJ, Bilezikian JP. “Incipient” primary hyperparathyroidism: a “forme fruste” of an old disease. J Clin Endocrinol Metab. 2003;88:5348-5352.

10. Eastell R, Brandi ML, Costa AG, et al. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99:3570-3579.

11. Boudou P, Ibrahim F, Cormier C, et al. Third- or second-generation parathyroid hormone assays: a remaining debate in the diagnosis of primary hyperparathyroidism. J Clin Endocrinol Metab. 2005;90:6370-6372.

12. Carnevale V, Dionisi S, Nofroni I, et al. Potential clinical utility of a new IRMA for parathyroid hormone in postmenopausal patients with primary hyperparathyroidism. Clin Chem. 2004;50:626-631.

13. Jameson JL, De Groot L. Endocrinology: Adult and Pediatric. 7thed. Philadelphia, PA: Elsevier Inc, 2016:1109.

14. Tebben PJ, Singh RJ, Kumar R. Vitamin d-mediated hypercalcemia: mechanisms, diagnosis and treatment. Endocr Rev. 2016;37:521-547.

15. Shinall MC Jr, Dahir KM, Broome JT. Differentiating familial hypocalciuric hypercalcemia from primary hyperparathyroidism. Endocr Pract. 2013;19:697-702.

16. Castellano E, Attanasio R, Gianotti L, et al. Forearm DXA increases the rate of patients with asymptomatic primary hyperparathyroidism meeting surgical criteria. J Clin Endocrinol Metab. 2016;101:2728-2732.

24-hour urinary Ca²⁺

A 24-hour urinary Ca²⁺ excretion is used to assess the risk of renal stones and to differentiate PHPT from familial hypocalciuric hypercalcemia (FHH). Patients with FHH have an abnormality in Ca²⁺ receptor gene expression in parathyroid cells and renal tubular cells that could lead to parathyroid-mediated hypercalcemia and hypocalciuria. FHH is differentiated from PHPT by calculating a 24-hour urinary Ca²⁺/Cr ratio. A value of <0.01 is diagnostic of FHH; whereas values >0.02 indicate PHPT. The test can be more accurate when the patient is on a normal Ca²⁺ and salt diet, when the estimated glomerular filtration rate is >60 mL/min/1.73 m², and when the serum 25(OH) vitamin D level is >30 ng/dL.¹⁵ Adequate urine volume is necessary for the 24-hour Ca²⁺/Cr ratio to be valid.

Renal imaging

Kidney stones and high Ca²⁺ deposits in the kidneys are the common manifestations of PHPT. Renal X-ray, computed tomography (CT), or ultrasonography are recommended in the evaluation of patients with PHPT. An incidental finding of either kidney stones or high Ca²⁺ deposits in the kidneys is an indication for surgery.¹⁰

Bone density/DEXA (dual energy X-ray absorptiometry) scan with a vertebral fracture assessment (VFA)

Asymptomatic PHPT individuals with osteoporosis (T-score < 2.5) or vertebral compression fracture benefit from surgical management.¹⁰ It is essential to obtain densitometry at 3 sites: the lumbar spine, the hip, and the distal third of the radius. Due to differing amounts of cortical and cancellous bone at the 3 sites and the differential effects of PTH on the cortical and cancellous bone, measurement at all 3 sites allows a clear estimation of the severity of the hyperparathyroid process on the skeleton.¹⁶ Therefore, consider measuring serum PTH if the patient has severe osteoporosis or fragility fractures that cannot be explained or that are unresponsive to treatment.

Management

The primary modality of treatment in PHPT is parathyroidectomy. The benefits are many, including an increase in bone mineral density (BMD) and reduction in fractures and kidney stones.¹⁰ With modern imaging and intra-operative PTH measurement, the success of minimally invasive parathyroidectomy is high in experienced hands. Patients with PHPT should be referred to an endocrinologist before surgery.

Surgery

Consider surgery if the patient meets any one of the following criteria:

1) overt clinical manifestations (stones, fractures)

2) serum Ca²⁺ >1 mg/dL above the upper limit of normal

3) Cr clearance <60 mL/min

4) low BMD with a T score ≤2.5 at any site

5) age <50 years

6) uncertain prospect for follow-up.

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