Primary hyperparathyroidism: Labs to order, Tx to consider

,; ,; ,

Applied Evidence

Primary hyperparathyroidism: Labs to order, Tx to consider

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

By

Padmaja Sanapureddy, MD

Vishnu Vardhan Garla, MD

Mallikarjuna Reddy Pabbidi, DVM, PhD

Unexplained kidney stones, osteoporosis, or certain subtle clues may point to hyperparathyroidism. These tests and imaging options can help you to be sure.

PDF Download

PRACTICE RECOMMENDATIONS

› Evaluate suspected cases of primary hyperparathyroidism (PHPT) with serum total calcium, parathyroid hormone (PTH), creatinine, and 25-hydroxy vitamin D levels. A

› Consider 24-hour urine measurement of calcium and creatinine in patients undergoing evaluation for possible PHPT. A

› Obtain bone densitometry at the spine, hip, and distal radius in patients with PHPT. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

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.

Since the advent of multichannel serum chemistry screening in the 1970s, large numbers of asymptomatic cases of primary hyperparathyroidism (PHPT) have been discovered. The clinical spectrum of the disease has changed from the classic “moans, groans, bones, and stones” to an asymptomatic and subtle presentation of hypercalcemia.^1,2 PHPT and malignancy are the most common causes for hypercalcemia, accounting for 90% of cases.³ In the United States, the estimated incidence of PHPT between 1998 and 2010 was about 50 per 100,000 person-years. Most patients with PHPT are older women (ages >50 years) who are asymptomatic at the time of diagnosis.¹

Vigilance needed in primary care. PHPT is slowly progressive, and the patient might accept symptoms as a process of aging. Therefore, it is essential that primary care physicians (PCPs) be aware of the diagnostic and management options. A systematic approach to the diagnosis of PHPT helps differentiate the causes of hypercalcemia (TABLE²; FIGURE²). But before we discuss PHPT diagnostic clues, it’s helpful to quickly review the workings of the parathyroid glands.

How the glands work, what can go wrong

Parathyroid hormone (PTH) is secreted by 4 pea-sized parathyroid glands located posterior to the thyroid. PTH regulates the levels of calcium (Ca²⁺) and phosphorous and controls the conversion of 25(OH) vitamin D to 1,25(OH)₂ vitamin D by activating the enzyme 1 alpha-hydroxylase.

PHPT is regarded as an abnormal secretion of PTH that does not correlate with the levels of Ca²⁺ in the blood.¹ Eighty percent of PHPT is due to a solitary adenoma in one of the parathyroid glands, 2% to 4% is secondary to multiple parathyroid adenomas, 15% is due to parathyroid hyperplasia, and 0.5% due to parathyroid carcinoma.⁴

Nonspecific symptomsare subtle clues of PHPT

Patients with PHPT can present with nonspecific symptoms, such as weakness, fatigue, anorexia, polyuria, polydipsia, bone and joint pain, mild depression, and mild cognitive or neuromuscular dysfunction.⁵ A careful history is essential to elicit these symptoms, as the patient may attribute these to aging or other causes. PHPT should also be considered when patients present with kidney stones, unexplained osteoporosis, or fragility fractures. A physical examination is seldom helpful, as parathyroid adenomas are hardly ever palpable. A slit-lamp examination may reveal corneal diseases in rare cases of hypercalcemia.⁶

Which lab tests, imaging should you order?

Serum Ca²⁺

Repeat measurements of serum Ca²⁺ to confirm hypercalcemia. Volume depletion, underlying malignancy, medications such as hydrochlorothiazide, lithium, and excess intake of Ca²⁺ carbonate can cause hypercalcemia.⁷ Therefore, a review of the patients’ home medications and dietary preferences in the evaluation of hypercalcemia is essential. The 2 most common causes of hypercalcemia are hyperparathyroidism and hypercalcemia of malignancy.

For hypercalcemia, establish a differential diagnosis by measuring intact PTH. An increased serum Ca²⁺ level along with an elevated PTH concentration should suggest PTH-dependent hypercalcemia, whereas hypercalcemia with suppressed or low-normal PTH values should suggest PTH-independent hypercalcemia (granulomatous disorders, hypercalcemia of malignancy).

Continue to: Hypercalcemia of malignancy is due to...