European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders

Abstract

This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders (PARAT) in 2019, were discussed during two virtual workshops in 2021, and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosing to familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represent areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT, need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborns children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed for a broader clinical audience, and were developed with focus on endocrinologists in training.

Figure 1

Alterations in calcium metabolism caused by familial hypocalciuric hypercalcemia (FHH). Hypercalcemia arises due to an increase in the parathyroid set-point for parathyroid hormone (PTH) release and possibly also from decreased renal calcium excretion (11, 12). Alterations in bone metabolism are not usually observed in FHH (13).

Figure 2

A clinical approach to patients with confirmed normocalcemic primary hyperparathyroidism. ^aReference range > 4 mg/kg/day, >250 mg/day in females, and >300 mg/day in males. ^bEvaluate for these disorders and manage as appropriate. 25(OH)D, serum 25-hydroxyvitamin D; Ab-TGA, anti-tissue transglutaminase antibodies; eGFR, estimated glomerular filtration rate; FGF-23, fibroblast growth factor-23; HPT, hyperparathyroidism; IBD, inflammatory bowel disease; iSGLT2, sodium-glucose cotransporter-2 inhibitors; PHPT, primary hyperparathyroidism; PPI, proton pump inhibitor; PTH, parathyroid hormone;

Figure 3

Pathophysiology of hypoparathyroidism. PTH, parathyroid hormone.

Figure 4

Perioperative management of patients at risk of postoperative hypoparathyroidism. 25(OH)D, 25-hydr oxyvitamin D; HypoPT, chronic hypoparathyroidism; PTH, parathyroid hormone.

Figure 5

Overview of calcium homeostasis and calciotropic hormones in pregnancy. Parathyroid hormone-related protein (PTHrP) production in the placenta will gradually decrease endogenous parathyroid hormone (PTH) secretion (4, 5). PRL, prolactin; RANKL, receptor activator of nuclear factor kappa-Β ligand.

Figure 6

Overview of calcium homeostasis in primary hyperparathyroidism during pregnancy. Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) will counterbalance the equilibrium hypercalcemia (5, 25, 158). PRL, prolactin; RANKL, receptor activator of nuclear factor kappa-Β ligand.

Figure 7

Overview of calcium homeostasis in chronic hypoparathyroidism during pregnancy. PTH, parathyroid hormone; PTHrP, parathyroid hormone-related protein; PRL, prolactin; RANKL, receptor activator of nuclear factor kappa-Β ligand.