I, Bardet S, Reznik Y, Clarisse B, Aide N: F18-choline PET/CT guided surgery in primary hyperparathyroidism when ultrasound and MIBI SPECT/CT are negative or inconclusive: the APACH1 study. Eur J Nucl Med Mol Imaging 2018;45:658–666.
36Ajmi S, Sfar R, Trimeche S, Ben Ali K, Nouira M: Scintigraphic findings in hungry bone syndrome following parathyroidectomy. Rev Esp Med Nucl 2010;29:81–83.
37Wilhelm SM, Wang TS, Ruan DT, Lee JA, Asa SL, Duh QY, Doherty GM, Herrera MF, Pasieka JL, Perrier ND, Silverberg SJ, Solórzano CC, Sturgeon C, Tublin ME, Udelsman R, Carty SE: The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg 2016;151:959–968.
38Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, Potts JT Jr: Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab 2014;99:3561–3569.
39Orr-Walker BJ, Evans MC, Clearwater JM, Horne A, Grey AB, Reid IR: Effects of hormone replacement therapy on bone mineral density in postmenopausal women with primary hyperparathyroidism: four-year follow-up and comparison with healthy postmenopausal women. Arch Intern Med 2000;160:2161–2166.
40Cesareo R, Di Stasio E, Vescini F, Campagna G, Cianni R, Pasqualini V, Romitelli F, Grimaldi F, Manfrini S, Palermo A: Effects of alendronate and vitamin D in patients with normocalcemic primary hyperparathyroidism. Osteoporos Int 2015;26:1295–1302.
41Rubin MR, Lee KH, McMahon DJ, Silverberg SJ: Raloxifene lowers serum calcium and markers of bone turnover in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab 2003;88:1174–1178.
42Peacock M, Bolognese MA, Borofsky M, et al: Cinacalcet treatment of primary hyperparathyroidism: biochemical and bone densitometric outcomes in a five-year study. J Clin Endocrinol Metab 2009;94:4860–4867.
Bart L. Clarke, MD
Mayo Clinic E18-A
200 1st Street SW
Rochester, MN 55905 (USA)
E-Mail [email protected]
Brandi ML (ed): Parathyroid Disorders. Focusing on Unmet Needs.
Front Horm Res. Basel, Karger, 2019, vol 51, pp 23–39 (DOI: 10.1159/000491036)
______________________
Normocalcemic Hyperparathyroidism
Sabrina Corbetta
Endocrinology and Diabetology Service and Laboratory of Experimental Endocrinology, Department of Biomedical Sciences for Health, University of Milan, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
______________________
Abstract
Parathyroid hormone (PTH) disorders are characterized by a wide spectrum of clinical and biochemical presentations. The increasing use of serum PTH assay in the set of the diagnostic workout in patients with osteoporosis has identified patients with features of surgically confirmed primary hyperparathyroidism (PHPT) associated with persistent normal serum calcium levels, which has been recognized as a distinct entity from hypercalcemic PHPT (HPHPT) by the last international consensus. Normocalcemic PHPT (NPHPT) affects about 6–8% of PHPT patients. Although hypercalcemia is absent, patients with NPHPT experience kidney, bone, and cardiovascular impairments similar to those observed in HPHPT, suggesting that NPHPT may significantly affect the health of patients. Diagnosis of NPHPT requires an intensive diagnostic workup aimed to: (1) exclude all causes of secondary hyperparathyroidism, and (2) evaluate the occurrence of PTH-related diseases. The management of NPHPT is controversial in part due to lack of solid data about the natural history as well as the effects of surgical or medical treatments. Nonetheless, a clinical and biochemical follow-up is recommended in order to detect potential progression. When hypercalcemia and/or PTH-related disorders arise, parathyroidectomy can be considered. When surgery is not advisable, medical treatment aimed to increase bone mineral density may be a therapeutic option.
© 2019 S. Karger AG, Basel
Parathyroid hormone (PTH) is generating great interest as it is a master regulator of the bone metabolism and a marker of cardiometabolic risk. Though PTH has often been used as a marker for the differential diagnosis of hypercalcemic disorders, nowadays it is widely measured in normocalcemic subjects in the set of the diagnostic workflow for osteoporosis and bone metabolic diseases. In this context, most individuals have been diagnosed with normocalcemic primary hyperparathyroidism (NPHPT).
Fig. 1. Spectrum of parathyroid disorders according to serum calcium and PTH levels. ↑, increased; ↓, decreased; ◆, hypercalcemic disorders; ○ (small circles), normocalcemic disorders; ■, hypocalcemic disorders; ○ (large circle), NPHPT. SHPT, secondary hyperparathyroidism; hypo-PTH, hypoparathyroidism; hyper-PTH, hyperparathyroidism; pseudohypo-PT, pseudohypoparathyroidism; N, normal serum PTH levels. Dashed lines indicate the thresholds of serum PTH levels for the diagnosis of hypoparathyroidism (40.0 pg/mL) and hyperparathyroidism (65 pg/mL).
Primary hyperparathyroidism (PHPT) is sustained by autonomous PTH release from one or more parathyroid glands and includes a wide spectrum of clinical presentations (Fig. 1). Besides severe symptomatic and sometimes life-threatening hypercalcemia, PHPT often occurs with mild asymptomatic hypercalcemia. Symptoms related to hyperparathyroidism span throughout the different clinical presentations (Fig. 2). This wide spectrum includes NPHPT, which was firstly recognized in 2008 by the panel of experts of the Third International Workshop on Asymptomatic Primary Hyperparathyroidism [1], who positively answered the question: “Is normocalcemic hyperparathyroidism, which is defined as normal serum calcium with raised PTH in the absence of any common cause of secondary normocalcemic hyperparathyroidism, part of the diagnostic spectrum?”
Fig. 2. Spectrum of PHPT clinical presentations according to serum calcium levels; kidney and bone diseases are transversal to the different clinical presentations. The serum calcium threshold suggested as an indication for parathyroidectomy in asymptomatic PHPT by the most recent guidelines is reported. PTX, parathyroidectomy; eGFR, estimated glomerular filtration rate; FHH, familial hypocalciuric hypercalcemia; *, according the most recent guidelines [25].
Definition
NPHPT is defined as persistent fasting normocalcemia associated with an increased serum PTH concentration.
Fasting Normocalcemia
The diagnostic criteria for NPHPT include consistently normal albumin-adjusted total serum calcium and normal