Parathyroid Disorders. Группа авторов

patients. Unilateral temporary recurrent laryngeal nerve injury was observed in 0.9% of the elderly patients and in 0.1% of the younger patients (p > 0.05). No differences were seen in cervical hematomas, mortality, or major cardiovascular, neurological, respiratory or metabolic postoperative complications. All the patients reported improvement in their quality of life. Bone mineral density increased after surgery in 85.6% of the elderly and 79.8% of the younger patients, without significant differences between symptomatic and asymptomatic patients. The study concluded that parathyroidectomy in elderly patients with PHPT is safe, with benefits and morbidity similar to what is seen in younger patients.

Parathyroid surgery is best performed by experienced surgeons because of variability in location of the abnormal gland(s). In major medical centers, preoperative localization of parathyroid adenomas before initial neck exploration may be considered unnecessary because of extremely high cure rates (95–98%) with standard neck exploration. Patient or physician interest in minimally invasive parathyroidectomy typically leads to parathyroid imaging studies, including ultrasonography, ^99mTc-sestamibi scanning, ^99mTc-sestamibi-¹²³I subtraction scanning, 4D-CT scanning, MRI, or ¹⁸F-choline-PET/CT scanning [35] of the neck before surgery. ^99mTc-sestamibi subtraction scanning is capable of detecting as many as 90% of single parathyroid adenomas before surgery. False-negative and false-positive imaging results, however, are relatively common. During standard neck exploration, patients with single or more adenomas should undergo resection of the tumor or tumors and identification of the remaining normal glands. Patients with 4-gland hyperplasia should typically undergo removal of 3.5 glands, with an alternative approach being removal of all 4 parathyroid glands, followed by auto-transplantation of part of 1 gland in the forearm, neck, or chest wall.

In patients cured of their hyperparathyroidism, the serum calcium concentration promptly normalizes, often after a brief period of asymptomatic relative hypocalcemia. “Hungry bones” syndrome, with rapid skeletal mineral uptake postoperatively, may develop in patients with bone disease [36].

      Reoperation for persistent or recurrent PHPT is technically difficult. Most surgeons require preoperative imaging as described above to attempt to localize the parathyroid tumor before a second surgery.

The American Association of Endocrine Surgeons developed evidence-based guidelines to enhance the appropriate, safe, and effective practice of parathyroidectomy [37]. Based on a literature review, these guidelines recommend that initial evaluation include the measurement of serum 25-hydroxyvitamin D and 24-h urine calcium, dual-energy X-ray absorptiometry, and supplementation for vitamin D deficiency. Parathyroidectomy is recommended for all symptomatic patients, and should be considered for most asymptomatic patients, as surgery is more cost-effective than observation or pharmacologic therapy. These evidence-based recommendations were created to assist clinicians in the optimal management of patients with persistent or recurrent PHPT.

      Nonsurgical Management

Medical options are limited for patients with asymptomatic hypercalcemia who are unable or unwilling to undergo a surgical procedure [38]. Patients not undergoing surgery should maintain adequate hydration and remain physically active. Use of thiazides and lithium should be avoided. Dietary calcium intake of 800–1,000 mg/day is advised to minimize bone loss and avoid aggravation of hypercalcemia or hypercalciuria. Dietary calcium intake of less than 600 mg/day may stimulate physiologic hyperparathyroidism. Oral or intravenous administration of phosphate should be avoided because of the risk of precipitation of ectopic calcification. Estrogen replacement therapy may help normalize serum calcium levels and prevent bone loss in postmenopausal women, although PTH and phosphate levels do not change [39]. Orally and intravenously administered bisphosphonates may be beneficial, but oral etidronate and intravenous clodronate and pamidronate infusions have not shown any long-term benefit. Alendronate, risedronate, raloxifene, and salmon calcitonin administered by nasal spray or injection have not been extensively investigated for this indication, although reports indicate that alendronate [40] or raloxifene [41] may help decrease serum calcium levels. The CaSR agonist (calcimimetic) cinacalcet HCl has been shown to decrease serum calcium and maintain normal levels of serum calcium for as long as 5 years without changing bone mineral density [42], and to improve serum calcium levels in patients with intractable PHPT or parathyroid carcinoma. Asymptomatic patients with PHPT who do not have parathyroidectomy tend to do well, although as many as a quarter of these patients may develop progression of disease, defined as development of at least one new indication for surgery, over 15 years of follow-up, and younger patients less than 50 years old tend to have a higher incidence of progressive disease.

      Conclusion

      Asymptomatic PHPT is the most common presentation of PHPT seen in Europe and North America, and an increasingly common presentation in other parts of the world. Diagnosis depends on classical biochemical changes including increased serum calcium and PTH levels, with normal renal function and vitamin D sufficiency, and lack of symptoms related to the disorder. Some patients may have hypercalciuria, calcium-containing kidney stones, or osteoporosis, but not yet be symptomatic. The most recent guidelines recommend imaging for kidney stones or nephrocalcinosis, bone density testing of the lumbar spine, hips, and nondominant 1/3 distal radius, and measurement of 24-h urine calcium and creatinine to look for complications of the disorder in otherwise asymptomatic patients. As many as 25% of asymptomatic patients may develop indications for parathyroidectomy when followed over up to 15 years. Patients who remain asymptomatic should be monitored periodically for the development of complications that would justify surgery. Patients who become symptomatic should have surgery when recognized. Recent studies suggest that surgery may improve quality of life even in patients who remain asymptomatic. Medical options for therapy in patients with PHPT who cannot have or decline surgery are limited, with cinacalcet the only approved therapy at present.

      References

1Khan AA, Hanley DA, Rizzoli R, Bollerslev J, Young JE, Rejnmark L, et al: Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus. Osteoporos Int 2017;28:1–19.

2Callender GG, Udelsman R: Surgery for primary hyperparathyroidism. Cancer 2014;120:3602–3216.

3Fraser WD: Hyperparathyroidism. Lancet 2009;374:145–158.

4Clarke BL, Brown EM, Collins MT, Jüppner H, Lakatos P, Levine MA, Mannstadt MM, Bilezikian JP, Romanischen AF, Thakker RV: Epidemiology and diagnosis of hypoparathyroidism. J Clin Endocrinol Metab 2016;101:2284–2299.

5Wermers RA, Khosla S, Atkinson EJ, et al: The rise and fall of primary hyperparathyroidism: a population-based study in Rochester, Minnesota 1965–1992. Ann Int Med 1997;126:433–440.

6Silverberg SJ: Primary hyperparathyroidism; in Rosen CJ (ed): Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, ed 8. Washington, American Society for Bone and Mineral Research, 2013, pp 543–552.