Forestalling Hungry Bone Syndrome after Parathyroidectomy in Patients with Primary and Renal Hyperparathyroidism

Hungry bone syndrome (HBS), severe hypocalcemia following parathyroidectomy (PTX) due to rapid drop of PTH (parathormone) after a previous long term elevated concentration in primary (PHPT) or renal hyperparathyroidism (RHPT), impairs the outcome of underlying parathyroid disease. Objective: overview HBS following PTx according to a dual perspective: pre- and post-operative outcome in PHPT and RHPT. This is a case- and study-based narrative review. Inclusion criteria: key research words hungry bone syndrome and parathyroidectomy; PubMed access; in extenso articles; publication timeline from Inception to April 2023. Exclusion criteria: non-PTx-related HBS; hypoparathyroidism following PTx. We identified 120 original studies covering different levels of statistical evidence. We are not aware of a larger analysis on published cases concerning HBS (N = 14,349). PHPT: 14 studies (N = 1545 patients, maximum 425 participants per study), and 36 case reports (N = 37), a total of 1582 adults, aged between 20 and 72. Pediatric PHPT: 3 studies (N = 232, maximum of 182 participants per study), and 15 case reports (N = 19), a total of 251 patients, aged between 6 and 18. RHPT: 27 studies (N = 12,468 individuals, the largest cohort of 7171) and 25 case reports/series (N = 48), a total of 12,516 persons, aged between 23 and 74. HBS involves an early post-operatory (emergency) phase (EP) followed by a recovery phase (RP). EP is due to severe hypocalcemia with various clinical elements (<8.4 mg/dL) with non-low PTH (to be differentiated from hypoparathyroidism), starting with day 3 (1 to 7) with a 3-day duration (up to 30) requiring prompt intravenous calcium (Ca) intervention and vitamin D (VD) (mostly calcitriol) replacement. Hypophosphatemia and hypomagnesiemia may be found. RP: mildly/asymptomatic hypocalcemia controlled under oral Ca+VD for maximum 12 months (protracted HBS is up to 42 months). RHPT associates a higher risk of developing HBS as compared to PHPT. HBS prevalence varied from 15% to 25% up to 75-92% in RHPT, while in PHPT, mostly one out of five adults, respectively, one out of three children and teenagers might be affected (if any, depending on study). In PHPT, there were four clusters of HBS indicators. The first (mostly important) is represented by pre-operatory biochemistry and hormonal panel, especially, increased PTH and alkaline phosphatase (additional indicators were elevated blood urea nitrogen, and a high serum calcium). The second category is the clinical presentation: an older age for adults (yet, not all authors agree); particular skeleton involvement (level of case reports) such as brown tumors and osteitis fibrosa cystica; insufficient evidence for the patients with osteoporosis or those admitted for a parathyroid crisis. The third category involves parathyroid tumor features (increased weight and diameter; giant, atypical, carcinomas, some ectopic adenomas). The fourth category relates to the intra-operatory and early post-surgery management, meaning an associated thyroid surgery and, maybe, a prolonged PTx time (but this is still an open issue) increases the risk, as opposite to prompt recognition of HBS based on calcium (and PTH) assays and rapid intervention (specific interventional protocols are rather used in RHPT than in PHPT). Two important aspects are not clarified yet: the use of pre-operatory bisphosphonates and the role of 25-hydroxyitamin D assay as pointer of HBS. In RHPT, we mentioned three types of evidence.

Automated summary

Hungry bone syndrome (HBS) is a severe hypocalcemia that occurs after parathyroidectomy (PTX), resulting from the rapid drop in PTH (parathormone) levels. It is commonly seen in primary hyperparathyroidism (PHPT) or renal hyperparathyroidism (RHPT) patients and can have negative effects on the outcome of parathyroid disease.