title: The phenotype of primary hyperparathyroidism with normal parathyroid hormone levels: how low can parathyroid hormone go?
abstract: BACKGROUND
  While normocalcemic hyperparathyroidism is well recognized in primary hyperparathyroidism (PHP), less is known about patients with high calcium but normal intact parathyroid hormone (iPTH). We aimed to describe this entity and designated it normohormonal primary hyperparathyroidism (NHPHP).
  
  
  METHODS
  From a prospectively maintained database of patients undergoing bilateral parathyroid exploration for PHP, we identified and compared those with preoperative iPTH levels below (NHPHP) and above (typical PHP) normal reference peak (60 pg/mL).
  
  
  RESULTS
  NHPHP occurred in 46 of 843 patients (5.5%) undergoing initial parathyroidectomy for PHP. All had hypercalcemia (11.1 mg/dL). Regarding preoperative iPTH, 7 patients (15%) had values <40 pg/mL, 19 (41%) had values <60 pg/mL; and 20 (44%) had intermittent values >60 pg/mL. Unlike patients with elevated iPTH, nearly all NHPHP patients had additional testing delaying the operation. Imaging correctly localized NHPHP parathyroid disease in 80%. At the time of operation, 74% of NHPHP patients had single adenomas. Intraoperatively postmobilization, using the same assay that was used preoperatively, 82% had PTH levels >60 pg/mL (mean, 279 pg/mL). During the follow-up period, iPTH levels remained lower among NHPHP patients (21 pg/mL) compared to 41 pg/mL for patients with preoperative iPTH 60 to 100 pg/mL and 56 pg/mL for patients with preoperative iPTH 100 to 200 pg/mL (P < .0001).
  
  
  CONCLUSIONS
  Lower PTH set points may exist in some patients with otherwise typical PHP features. Although high normal iPTH is inappropriate for hypercalcemia and should suggest PHP, this disorder may occur with iPTH levels as low as 5 pg/mL. Awareness of the unusual phenotype of NHPHP may facilitate earlier diagnosis and surgery.
authors.affiliation: Department of Endocrine Surgery, Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Lucy B
authors.initials: LB
authors.lastname: Wallace
authors.forename: Rikesh T
authors.initials: RT
authors.lastname: Parikh
authors.forename: Louis V
authors.initials: LV
authors.lastname: Ross
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mazzaglia
authors.forename: Christina
authors.initials: C
authors.lastname: Foley
authors.forename: Joyce J
authors.initials: JJ
authors.lastname: Shin
authors.forename: Jamie C
authors.initials: JC
authors.lastname: Mitchell
authors.forename: Eren
authors.initials: E
authors.lastname: Berber
authors.forename: Allan E
authors.initials: AE
authors.lastname: Siperstein
authors.forename: Mira
authors.initials: M
authors.lastname: Milas
mesh_terms: D000236:Adenoma / Q000150:complications / Q000175:diagnosis; D000368:Aged; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000209:etiology; D049950:Hyperparathyroidism, Primary / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D016105:Parathyroidectomy; D010641:Phenotype; D011446:Prospective Studies; D013964:Thyroid Neoplasms / Q000150:complications / Q000175:diagnosis
chemical_list: D010281:Parathyroid Hormone