{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T22:54:12Z","timestamp":1767912852529,"version":"3.49.0"},"reference-count":130,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cCarol Davila\u201d University of Medicine and Pharmacy, PhD research \u201cPrimary hyperparathyroidism: cardio-metabolic, osseous and surgical aspects\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Non-classical manifestations such as neuropsychiatric manifestations in primary hyperparathyroidism (PHPT) have long been documented as symptoms of PHPT and are commonly reported by these patients, despite this connection still being a matter of debate, and they (per se) do not represent an indication of parathyroidectomy. Objective: We aimed to overview the most recent findings regarding the link between depression and\/or anxiety (D\/A) in subjects confirmed with PHPT, including the impact of the surgery in improving their outcome. Methods: This was a comprehensive review of English-based original studies published between January 2020 and October 2024. Results: The studies (n = 16) included a total of 10,325 patients and an additional 152,525 patients with hypercalcemia (out of whom 13,136 had a PHPT diagnosis and 45,081 were at risk of PHPT diagnosis). Out of these subjects with PHPT, 10,068 underwent parathyroidectomy. Female prevalence was between 62.5 and 92%. Most individuals were over 50, with the youngest studied population having a mean age of 52.7 \u00b1 13.8 years, and the oldest had a median of 71. Depression was documented based on ICD-10 codes (n = 3) and patients\u2019 records (n = 2), Depression Anxiety Stress Scales (DASS) (n = 2), Beck Depression Inventory (BDI) (n = 3), BDI-II (n = 3), Symptom Check List 90-revised (SCL) (n = 1), Hamilton Depression Rating Scale (HAM-D) (n = 2), HADS (n = 2), Patient Health Questionnaire-9 (n = 1), and European Quality of Life 5 Dimensions 3-Level Version (EuroQOL-5D-3L) (n = 1). Patient records\u2019 (n = 1) and ICD-10 codes (n = 2) were also used for anxiety. Most studies used questionnaires to identify anxiety in PHPT: DASS (n = 2), SCL90R (n = 1), Generalized Anxiety Disorder-7 (n = 1), HADS (n = 2), EuroQOL-5D-3L (n = 1), and State\u2013Trait Anxiety Inventory (n = 1). Depression prevalence varied from 20\u201336.6% to 65.7% (scale-based assessment) and to 10.5% upon ICD-10. A rate of newly onset depression was reported of 10.7% and of 0.2% with concern to the prevalent suicidal ideation (an incidental rate of 0.4% after a median follow-up of 4.2 years). Most studies identified a moderate depression (when assessing its severity), affecting approximately one third of the surgery candidates. The prevalence of anxiety in PHPT varied between 10.4% and 38.6% (n = 8). Discordant results were generated when applying distinct questionnaires for the same population, and this might come as a potential bias. Other confounding factors are generated by the sub-population referred for surgery that typically displays a more severe parathyroid condition or non-endocrine overlapping conditions (e.g., related to the social or familial status). Conclusion: The modern approach of the patient with PHPT should be complex and go beyond the traditional frame. D\/A had a high prevalence in the mentioned studies, associated with increased medication use. Yet, the underlying pathogenic mechanisms remain incompletely elucidated. No correlations between D\/A and serum calcium levels were confirmed, while PTH had a slight positive correlation with depression. Parathyroid surgery appears to be beneficial for D\/A as it improves the scores, prevalence, and severity. Cinacalcet might reduce depression scores, although more evidence is needed. Women are prone to both PHPT and D\/A. The optimal method of D\/A screening in PHPT remains to be determined, and the current scales need validation and perhaps adjustment for this specific population sub-group, while PHPT management should be refined upon D\/A identification.<\/jats:p>","DOI":"10.3390\/diseases13020054","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T03:41:57Z","timestamp":1739331717000},"page":"54","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Analysis of Primary Hyperparathyroidism in Association with Depression or Anxiety"],"prefix":"10.3390","volume":"13","author":[{"given":"Ana-Maria","family":"Gheorghe","sequence":"first","affiliation":[{"name":"PhD Doctoral School of \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-5666","authenticated-orcid":false,"given":"Claudiu","family":"Nistor","sequence":"additional","affiliation":[{"name":"Department 4-Cardio-Thoracic Pathology, Thoracic Surgery II Discipline, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Thoracic Surgery Department, \u201cDr. Carol Davila\u201d Central Military University Emergency Hospital, 010242 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1028-0618","authenticated-orcid":false,"given":"Aurelian-Emil","family":"Ranetti","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, \u201cDr. Carol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Endocrinology Department, \u201cDr. Carol Davila\u201d Central Emergency University Military Hospital, 010825 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-3835","authenticated-orcid":false,"given":"Mara","family":"Carsote","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, \u201cDr. Carol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Clinical Endocrinology V, \u201cC.I. Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3580","DOI":"10.1210\/jc.2014-1415","article-title":"Current issues in the presentation of asymptomatic primary hyperparathyroidism: Proceedings of the Fourth International Workshop","volume":"99","author":"Silverberg","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jocd.2012.11.008","article-title":"Nontraditional manifestations of primary hyperparathyroidism","volume":"16","author":"Walker","year":"2013","journal-title":"J. Clin. 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