Simplifying the Complexity of Primary Hyperparathyroidism Roseann P. Velez, DNP, FNP, Mary Donnelly-Strozzo, DNP, ANP-BC, and Julie Stanik-Hutt, PhD, GNP/ACNP-BC ABSTRACT
Primary hyperparathyroidism (PHPT) is a common but complex endocrine disorder. Historically, many PHPT patients have been diagnosed only after a protracted period of manifesting significant signs and symptoms. However, today, PHPT is often found during routine serologic screening or evaluation for decreased bone mass. Knowledge of PHPT is essential to ensure appropriate patient evaluation and treatment and to prevent adverse outcomes of chronic, untreated disease. Elevated serum calcium with subsequent elevated parathyroid hormone levels usually brings the diagnosis to light. The diagnosis of PHPT can be challenging and medical management is available, but surgery is the only cure. Keywords: fractures, hypercalcemia, hyperparathyroidism, parathyroid hormone, parathyroid surgery Ó 2016 Elsevier, Inc. All rights reserved.
INTRODUCTION
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yet patients may present asymptomatically with elevated Ca and PTH levels. Abnormalities in serum Ca and PTH levels often provoke questions from providers regarding the best approach to diagnostic testing and management. Prompt diagnosis and appropriate treatment of patients with parathyroid abnormalities is critical to mitigate adverse outcomes from unrecognized, chronic disease. Symptomatic patients with mild PHPT improve after parathyroidectomy.1 However, management of patients with mild, asymptomatic PHPT can be challenging. Although medical management is an option for patients with PHPT, surgery is indicated for patients who meet surgical criteria and is the only cure. The benefit of parathyroidectomy on body mass index, lifestyle, and psychological function as compared with no surgery is that surgery is a costeffective treatment with minimal risk for complication from a single procedure.4
atients with primary hyperparathyroidism (PHPT) have abnormally elevated calcium (Ca) and parathyroid hormone (PTH) levels with respect to each other. In the United States, PHPT is the most common cause of hypercalcemia encountered in ambulatory care.1 About 100,000 patients are diagnosed annually, producing an annual US incidence of < 10 per 100,000 and prevalence of up to 1%.2 Before middle adulthood, the prevalence of PHPT is similar in men and women but is more common after age 65. Postmenopausal women have the highest incidence of PHPT.2 PHPT can have significant, insidious effects on the body, most commonly increasing bone turnover and decreasing bone mineral density (BMD). Failure to correct bone abnormalities has a negative impact on fracture risk. Severe bone disease, known as osteitis fibrosa cystica (OFC), only occurs in < 3% of patients in the US.3 PHPT affects the central nervous, cardiac, renal, and gastrointestinal systems,
PARATHYROID GLANDS
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The parathyroid glands are pea-sized glands located behind the thyroid gland. Expected anatomic findings upon exploration of the neck reveal 4 parathyroid glands, but ectopic parathyroid glands can be
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found in the thyroid, high in the neck or carotid sheath, in the retroesophageal space, and within the thymus or mediastinum. Parathyroid glands produce PTH, also known as parathormone, or PTH-intact. All parathyroid glands that hypersecrete PTH are enlarged, sometimes to the size of a lima bean or larger. The parathyroid glands maintain levels of Ca and phosphorus. Ca plays an active role in metabolic processes, nerve impulse conduction, muscle contraction, and the clotting cascade. The vast majority of Ca is in bone, but it is also found in cells and fluids. Protein-bound and ionized, or free, Ca is carried in the plasma. When serum Ca levels fall, PTH is secreted and serum Ca increases through bone resorption, while Ca excretion from the distal tubule in the kidneys decreases. PTH secretion increases Ca absorption from the duodenum by increasing renal formation of 1,25-dihydroxycholecalciferol [1,25(OH)2D], the active form of vitamin D, from 25-hydroxycholecalciferol, the inactive form of vitamin D.5 Vitamin D‒deficient patients have increased bone turnover, more clinically significant disease, low BMD measurements, and more frequent fractures. PTH is negatively correlated with vitamin D; the lower the vitamin D level, the higher the PTH.6 When elevated PTH stimulates the renal tubular reabsorption of Ca, hypercalcemia ensues. The increase of Ca in the glomerular filtrate causes hypercalciuria. Nephrolithiasis is a classic renal manifestation of PHPT, and providers should consider parathyroid disease as a cause of nephrolithiasis.7 Based on a negative feedback loop, PTH secretion is decreased when Ca reaches normal levels. Hypercalcemia suppresses PTH secretion. Excess PTH can cause cortical demineralization, and severe, chronic hyperparathyroidism can cause diffuse demineralization, pathologic fractures, and OFC.3 Elevations in osteocalcin and alkaline phosphatase, which are biochemical markers of bone formation, are found in patients with OFC.3 Physiologic changes in bone structure through PTH influenced osteoblast activity are related directly to disease duration. Osteoblasts transport proteins and initiate bone mineralization.8 The osteoblasts induce osteoclastogenic cytokine RANKL (receptor activator of nuclear factor-kB ligand) and may not cause bone www.npjournal.org
changes in early PHPT disease states.2 As the disease progresses, morphologic changes occur in cortical bone as a result of increased PTH. Excess PTH thins cortical bone as a result of endosteal bone reabsorption, increasing periosteal apposition and bone diameter, which protects against risk of fractures.9 Bone loss in PHPT is studied based on fracture epidemiology, measurement of the shape or form of bone tissue, and BMD data.9 Early diagnosis and appropriate referral for treatment of PHPT can prevent irreversible bone damage. DEFINITION
Hyperparathyroidism occurs when serum PTH levels are elevated relative to serum Ca levels. Although hyperparathyroidism is associated with abnormal Ca metabolism, 2%-5% of patients are asymptomatic.1 The diagnosis may be made upon incidental finding of hypercalcemia during routine blood tests or when routine BMD testing is abnormal. Mild PHPT includes patients who have normal Ca levels with elevated PTH or elevated Ca levels with an inappropriately normal or high-normal PTH.1 The most common cause of PHPT is parathyroid adenoma, found in 80% of patients.10 Parathyroid hyperplasia occurs in 20% of patients with PHPT. It is an exceedingly rare cause of PHPT and occurs in < 1% of patients.1 What may challenge providers is when patients have normocalcemic primary hyperparathyroidism (NPHPT), as demonstrated by persistently high PTH levels, and normal Ca levels with no secondary causes of parathyroid disease.11 To make the diagnosis of NPHPT, secondary causes of elevated Table 1. Causes of Hypercalcemia Due to Medications Thiazide diureticsa Lithiuma Excessive amounts of antacids containing calcium and alkalia Excessive intake of vitamin Aa Excessive intake of vitamin Da Canagliflozin, an sodium-glucose linked transporter (SGLT2) inhibitorb Hormone therapy (estrogens, antiestrogens, androgens, progestins)c Theophylline a b c
From Endres.14 From Kaur and Winters.23 From the University of Michigan.24
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PTH must be ruled out including: medication effects (see Table 1); a glomerular filtration rate of < 60 mL/min; liver disease; and vitamin D insufficiency with plasma 25(OH)D levels of 50 mmol/L.1 Any disorder that results in hypocalcemia will elevate PTH and will produce secondary hyperparathyroidism (SHPT). In secondary hyperparathyroidism, another condition produces hypocalcemia and the parathyroid tissue produces PTH in response. The most common cause of SHPT is chronic kidney disease, whereby patients are unable to manufacture 1,25(OH)2D. These patients have a low serum Ca and extremely high PTH levels. Other causes of SHPT include cancers, hypervitaminosis, hyperthyroidism, immobilization, and medications, such as thiazide diuretics.12 Tertiary hyperparathyroidism results from hypertrophied parathyroid glands in patients with chronic renal failure. Even after successful kidney transplantation, which allows patients to achieve normal levels of vitamin D and normal to high Ca levels, very high PTH levels continue to be produced. CLINICAL PRESENTATION
In the US, approximately 15%-20% of patients with PHPT present with nephrolithiasis, a diagnosis often made in the primary care setting.13 Patients with PHPT may have no symptoms, but commonly mild symptoms. PHPT can be missed, even with expert history-taking skills and physical exam techniques. Normal physical findings can be seen in PHTH as 2%-5% of patients are truly asymptomatic.1 Symptoms of hypercalcemia include anorexia, nausea, constipation, insomnia, arthritis, polydipsia, and polyuria, and are more commonly seen in patients whose Ca level rises rapidly. If Ca levels rise slowly, patients may adapt to the subtle changes. The symptoms of PHPT correlate directly with the duration of elevated PTH. The mnemonic symptoms of “stones, bones, abdominal groans, and psychiatric moans” are commonly described by patients. These renal, musculoskeletal, gastrointestinal, and psychiatric symptoms result from the hypercalcemia caused by the inappropriately secreted PTH. The global prevalence of PHPT varies considerably. In geographic areas where low vitamin D is prevalent, symptoms of PHPT may include the 348
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severe clinical “bone and stone” disease, including lower extremity bone pain, pathologic fractures, and muscle weakness with hyporeflexia.3 In the Western world, providers may encounter postmenopausal women with asymptomatic vertebral fractures as an early manifestation of PHPT. Musculoskeletal symptoms in younger patients may include manifestations of genetic disease.2 Vague symptoms of weakness, paresthesias, muscle cramps, and fatigue are frequently reported by patients with undiagnosed PHTH, and neurologic exam findings may include diminished deep tendon reflexes. Cardiovascular abnormalities of PHPT include hypertension and palpitations. Ventricular hypertrophy, prolonged PR interval, shortened QT interval, and bradyarrhythmias may be seen on electrocardiogram. Echocardiography may reveal diastolic dysfunction. Digitalis sensitivity, insulin resistance, type II diabetes mellitus, hyperuricemia, gout, and pseudogout may be seen in patients with more severe cases of PHPT.10 Patients may report itchy skin, inability to focus, mental fatigue, irritability, and depression. Many of these symptoms are reported by family members rather than the patients themselves. Patients who present with such symptoms should alert providers to check Ca levels when other etiologies are excluded. LABORATORY DATA
The 2 laboratory tests used to determine serum Ca levels are total serum Ca or an ionized serum Ca.14 In the serum, 40% of Ca is bound to serum proteins, predominantly albumin, so serum albumin levels must be considered in the interpretation of a serum Ca level.15 If a patient’s serum albumin level is low, then the associated total serum Ca level is also low, as there is less protein to which Ca can bind. If the patient’s albumin levels are below normal, a mathematical calculation is used to “correct” the serum Ca value before interpretation. When major shifts in serum protein or pH are present, it is most prudent to measure directly the ionized Ca level to determine the presence of hypercalcemia.15 When patients have an elevated serum Ca, providers should always check the previous serum Ca level. If serum Ca had been raised, PTH should be ordered in conjunction with a repeat serum Ca. The Volume 12, Issue 5, May 2016
Ca and PTH levels should be obtained simultaneously to assure accurate diagnosis because individual Ca and PTH levels fluctuate quickly. The diagnosis of PHPT rests on Ca and PTH levels with respect to one another. When dealing with normal parathyroid tissue and a high Ca level, the PTH should be negligible. Only with abnormal parathyroid tissue will the Ca elevate in conjunction with an elevated PTH hormone level. If serum Ca had not been elevated in the past, repeating just the serum Ca level would be prudent. Two different assays are available to measure PTH levels. Both assays aid in determining whether hypercalcemia is parathyroid-mediated, as up to 20% of PHPT patients may be normocalcemic.16 In the presence of hypercalcemia, an intact PTH level of > 25 pg/mL is considered abnormal when the normal range is 10-65 pg/mL. Patients with PHPT who take vitamin B7 supplements may have unusually low PTH concentrations, so interpretation of laboratory data must consider patients’ pharmacologic therapy. Parathyroid hormone is negatively correlated with vitamin D; the lower the vitamin D level, the higher the PTH.6 Serum 25(OH)D, which identifies vitamin D deficiency, should be ordered to predict disease severity because vitamin D‒deficient patients have increased bone turnover. Serum creatinine may demonstrate renal insufficiency. A 24-hour urine calcium is usually very low with a calcium creatinine clearance ratio of < 0.010, but the urinary calcium can be normal (100-300 mg/day) or elevated.16 Patients’ dietary intake of Ca should be normal on 24-hour urine testing to allow for accurate interpretation of results. The phosphaturic effect of PTH on the renal system causes hypophosphatemia. Other laboratory findings include moderate anemia, magnesium abnormalities, acid-base imbalance, and monoclonal gammopathy.3 Patients with nephrolithiasis typically have stones that are composed of Ca oxalate. Renal and urinary tract ultrasound should be ordered if there is a suspicion for nephrolithiasis.
demineralization and pathologic fractures usually seen in the long bones of the extremities. Subperiosteal bone erosions of the distal phalanges and lateral aspects of the middle phalanges and a saltand-pepper appearance of the skull are radiologic findings consistent with severe PHPT.3 Screening for osteoporosis facilitates earlier diagnosis of PHPT. Although fractures are not common in PHPT, patients are at increased risk of distal forearm and pelvic fractures and, less commonly, vertebral fractures. Plain X-rays and BMD tests are the primary imaging studies used in the evaluation of PHPT. Orders for BMD tests should request examination of the lumbar spine, bilateral hips, and distal third of the radius. The radius is included as it is a site of cortical bone and is a measurement of skeletal disease in PHPT. The skeletal system remains an end-organ in PHPT, and BMD shows decreased skeletal density at the forearm and hip. High-resolution peripheral quantitative computed tomography detects microstructural skeletal features in PHPT. A recent technological advancement, trabecular bone score, an adaptation of the lumbar spine dual-energy X-ray absorptiometry image, was recently approved for clinical use in the US and Europe as a tool to predict major osteoporotic fractures.3 Neck imaging may be helpful for surgical planning, but negative imaging searching for parathyroid abnormalities does not rule out disease. Ultrasound, computed tomography, and nuclear imaging are used to identify abnormal parathyroid tissue. Various studies, such as 99m-technetium-sestamibi scans, have greatly enhanced skilled parathyroid surgeons’ ability to identify those patients with mild PHPT and should be ordered by the surgeon to alleviate redundant and unnecessary testing.13 Sestamibi scintigraphy scan is the most commonly used localization study but can miss abnormal glands when more than 1 gland is affected. Because a variety of factors can affect interpretation, and use of multiple tests can quickly increase costs, choice of imaging is best left to the surgeon. MEDICAL TREATMENT
RADIOGRAPHY
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Controversy exists regarding treatment for the 2%-5% of patients who have biochemically confirmed PHPT but lack overt signs and symptoms.13 Medical The Journal for Nurse Practitioners - JNP
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management of these patients includes scheduled monitoring, as well as therapies to eliminate excess Ca, maintain hydration, and prevent loss of bone mass. Scheduled monitoring should include biannual serum Ca measurement, annual assessment for overt signs or symptoms of hyperparathyroidism, serum creatinine measurement, and BMD testing.16 Calcimimetics, drugs that “mimic” the effects of Ca, can be used to treat, but do not cure, hypercalcemia with PHPT.17 Cinacalcet is the only drug in this class found to reduce serum Ca to normal levels and even reduce PTH in patients with PHPT.18 Cinacalcet should not be used in patients with low Ca levels or in those with seizures, due to its effect on lowering the seizure threshold.19 Patients require close monitoring of serum Ca levels when receiving cinacalcet due to its significant adverse effects on QT prolongation, arrhythmias, heart failure, and hypotension. There are many drug-drug interactions with cinacalcet, so monitoring of hepatic function is essential. The starting dose for cinacalcet is 30 mg/ day, and the dose can be titrated up by 30 mg slowly every 2-4 weeks to a maximum dose of 180 mg/day. Although there are indications for medical management of parathyroid disease, pharmacologic therapies have not been cost-effective and are not curative.4 There is no need to recommend a reduction in daily Ca intake to below the recommended daily amount of 1,000 mg/day for adults and 1,200 mg/day for postmenopausal woman and men > 70 years old, but excessive Ca intake should be avoided.18 In addition to dairy foods, Ca is found in collard greens, kale, bok choy, broccoli, sardines, salmon, shrimp, almond, rice or soy milks, orange and other fruit juices, tofu, frozen waffles, oatmeal, and other cereals. Patients should read package labels to identify foods with high levels of Ca so that their diet meets but does not exceed the recommended daily amount. Loop diuretics should be substituted for thiazide diuretics. Because lithium increases Ca, patients’ should consult with their mental health providers about alternative treatments to lithium. After medications are discontinued, serum Ca can be rechecked in 3 months.1 In patients with documented low levels of 25(OH)D, repletion using 600-1,000 IU of cholecalciferol may be given while monitoring serum 25(OH)D. A goal of > 50 and up to 75 mmol/L is 350
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targeted to avoid ensuing hypercalcemia and decreased urinary excretion from exogenous cholecalciferol.18 Estrogen replacement therapy in postmenopausal women with low BMD may decrease bone resorption, but it does not affect serum Ca or PTH levels in PHPT.18 Patients receiving ERT are at risk for the adverse effects of estrogen, including cardiovascular, cerebrovascular, and malignancies. Bisphosphonates are a better option for patients with PHPT and low BMD. Although there are no data on fracture improvement, alendronate has been shown to improve lumbar spine and hip density in these patients.18 SURGICAL TREATMENT
Surgery is the only known cure for PHPT. Four consensus meetings to address the surgical management of asymptomatic PHPT have been held, with the most recent workshop in 2013 (see Table 2). The guidelines recommend surgery for patients with biochemically confirmed PHPT and overt signs and symptoms. Parathyroid surgery is also recommended for asymptomatic individuals who meet specific laboratory or radiology thresholds.20 Even when there is no specific indication for surgery, parathyroidectomy is an accepted, appropriate course of action because Table 2. 2013 Guidelines for Parathyroid Surgery in Patients With Asymptomatic Primary Hyperparathyroidism Measurement Age
Indication for Surgerya,b < 50 years
Serum calcium > 1 mg/dL (> 0.25 mmol/L) above upper limit of normal
a
Bone mineral density
(a) t-score of 2.5 (osteoporosis) (b) Vertebral fracture on imaging study
Creatinine clearance
(a) Reduced to < 60 mL/min (b) 24-hour urine for calcium > 400 mg/ day and increased stone risk by biochemical stone risk analysis (c) Nephrolithiasis or nephrocalcinosis on imaging study
Surgery is also indicated for patients who are unwilling or unable to undergo
medical surveillance. b Patients need to meet only 1 of these criteria to be advised to have parathyroid surgery. Reprinted with permission from John Wiley & Sons. Callender GG, Udelsman R. Surgery for primary hyperparathyroidism. Cancer. 2014;120(23):3602-3616.
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surgery is the only cure.13 Providers should consider early referral to a head and neck surgeon to determine the most effective treatment. Parathyroid surgery is safe, effective, and improves symptoms and quality of life when performed by a skilled parathyroid surgeon.21 The goal of surgery is to remove the abnormal parathyroid tissue and leave the patient with normal parathyroid function, without surgical complications. A minimally invasive approach is used with local or general anesthesia. Once the gland is enlarged, levels of PTH should decrease rapidly. Serum PTH levels can be checked, but it can take up to 15 minutes to obtain results. Patients generally receive injections of the radioactive tracer, 99mTc-sestamibi, before surgery and during the procedure to identify the hyperactive gland or glands. Typically, the suspected hyperactive gland is the first to be isolated and excised. It is immediately scanned in the operating room using the gamma probe, to confirm high radiotracer counts. The 3 remaining parathyroid glands are then identified. If any gland is obviously enlarged, it is excised and scanned to confirm the high counts. In any normal-appearing glands, a tiny section is excised and scanned as well to confirm lower counts. In this way, the surgeon is able, during the procedure, to determine that all abnormal glandular tissue is removed and that remaining parathyroid tissue is not hyperactive.22 Patients are usually able to be discharged home within 2 hours of surgery.3 Patients who require extensive neck exploration or excision of all 4 parathyroid glands may require overnight admission to monitor Ca levels. All patients are instructed to increase their oral Ca intake and to monitor themselves for symptoms of hypocalcemia, such as tetany. Patients typically follow-up with the surgeon in 1-2 weeks, and serum Ca and PTH levels are rechecked.3 The benefit of surgery versus medical therapy is that not only is surgery curative and costeffective, but that it is a single-procedure cure with an overall low complication rate.4 IMPLICATIONS FOR PRIMARY CARE NPS
For patients who are not candidates for parathyroidectomy, primary care providers can recommend supportive preventive measures with www.npjournal.org
appropriate monitoring.7 Patient education should include medication reconciliation, avoidance of volume depletion, and education regarding Ca intake. Physical activity prevents bone resorption, and 400-600 IU of vitamin D daily may prevent PTH secretion and bone resorption. Nephrolithiasis may be minimized by adequate water intake. Bisphosphonates, calcimimetics, and selective estrogen receptor modulators such as raloxifene may be indicated.1 CONCLUSIONS
The evaluation and medical management of patients with hypercalcemia is challenging. Mild or lessthan-obvious symptoms of PHPT can delay diagnosis and treatment. Once the diagnosis is confirmed, surgery improves quality of life and bone health. The current surgical guidelines should be applied early in the disease process to prevent progression of the disease, even in those patients who continue to be normocalcemic.11 Consideration of PHPT is essential in the differential diagnosis of patients with abnormal Ca and PTH levels, low BMD values, vague symptoms, nephrolithiasis, and with certain fractures. Consultation with an experienced parathyroid surgeon can enhance the chance for a cure. References 1. Applewhite MK, Schneider DF. Mild primary hyperparathyroidism: a literature review. Oncologist. 2014;19:919-929. 2. Wei S, Siegal GP. A 23-year-old woman with a right femoral neck fracture. JAMA. 2011;306(21):2385-2386. 3. Bandeira F, Cusano NE, Silva BC, Cassibba S, Almeida CB, Bilezikian JP. Bone disease in primary hyperparathyroidism. Arq Brasil Endocrinol Metabol. 2014;58(5):553-561. 4. Niederle B, Wemeau JL. Is surgery necessary for “mild” or “asymptomatic” hyperparathyroidism? Eur J Endocrinol. 2015;173(3):D13-20. 5. Hall JE. Guyton and Hall Textbook of Medical Physiology. 13th ed. Philadelphia: Elsevier; 2016. 6. Alarcon T, Gonzalez-Montalvo J, Hoyas H, Otero A, Mauleon J. Parathyroid hormone response to two levels of vitamin D deficiency is associated with high risk of medical problems during hospitalization in patients with hip fracture. J Endocrinol Invest. 2015;38:1129-1135. 7. 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 Metabol. 2014; 99(10):3580-3594. 8. Corrarino JE. Bisphosphonates and atypical femoral fractures. J Nurse Pract. 2015;11(4):299-396. 9. Cormier C. Fracture risk in hyperparathyroidism. Joint Bone Spine. 2012;79: 216-218. 10. Papadakis MA, McPhee SJ, eds. Current Medical Diagnosis and Management. New York: McGraw-Hill; 2015. 11. Bandiera F, Cassibba S. Hyperparathyroidism and bone health. Curr Rheum Rep. 2015;17:48. 12. Culpepper R, Barkley T, Myers C. Fluid, electrolyte, and acid-base imbalances. In: Barkley T, Myers C, eds. Practice Considerations for Adult‒Gerontology
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Acute Care Nurse Practitioners. West Hollywood, Ca: Barkley & Associates; 2015:764-787. Callender GG, Udelsman R. Surgery for primary hyperparathyroidism. Cancer. 2014;120(23):3602-3616. Endres DB. Investigation of hypercalcemia. Clin Biochem. 2012;45(12):954-963. Goltzman D. Approach to hypercalcemia. In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al., eds. Endotext: the FREE Complete Source for Clinical Endocrinology. South Dartmouth, Mass: MDText.com; 2013. Cusano NE, Bilezikian JP. Parathyroid hormone in the evaluation of hypercalcemia. JAMA. 2014;312(24):2680-2681. Nemeth EF, Goodman WG. Calcimimetic and calcilytic drugs: feats, flops, and futures. Calcif Tissue Int. 2015 [epub ahead of print]. Marocci C, Bollerslev J, Khan A, Shoback D. Medical management of primary hyperparathyroidism: Proceedings of the Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2014;99(10):3607-3618. Burcham JR, Rosenthal LD. Lehne’s Pharmacology for Nursing Care. 9th ed. St. Louis, Mo: Elsevier Saunders; 2016. Noureldine S, Gooi Z, Tufano R. Minimally invasive parathyroid surgery. Gland Surg. 2015;4(5):410-419. Lee F, Lee JJ, Liu TP, Cheng SP. Parathyroidectomy improves fracture nonunion in hyperparathyroidism. Am Surg. 2015;81(1):E36-E37. Norman J, Lopez J, Politz D. Abandoning unilateral parathyroidectomy: why we reversed our position after 15,000 parathyroid operations. J Am Coll Surg. 2012;214(3):260-269. Kaur A, Winters SJ. Severe hypercalcemia and hypernatremia in a patient treated with canagliflozin. Endocrinol Diabetes Metab Case Rep. http://dx.doi. org/10.1530/EDM-15-0042. University of Michigan Health System. Hypercalcemia. https://www.med .umich.edu/intmed/endocrinology/patients/Hypercalcemia.htm/. Accessed February 2, 2016.
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Roseann Velez, DNP, FNP, is an instructor at Johns Hopkins University School of Nursing and practices at Greater Baltimore Medical Associates in Hunt Valley, MD. She can be reached at
[email protected]. Mary Donnelly-Strozzo, DNP, ANPBC, is an instructor at Johns Hopkins University School of Nursing and Site Supervisor Wald Community Nursing Center. Julie StanikeHutt PhD, GNP/ACNP-BC, is a professor at the University of Iowa College of Nursing. In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest. 1555-4155/16/$ see front matter © 2016 Elsevier, Inc. All rights reserved. http://dx.doi.org/10.1016/j.nurpra.2015.12.017
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Volume 12, Issue 5, May 2016
