Depressive Disorder in Primary Hyperparathyroidism and Effects of Surgery in Elderly Patients: Case Series

Introduction

Primary hyperparathyroidism (PHPT) is a common endocrinological disorder characterized by chronic elevation of parathyroid hormone (PTH) and serum calcium concentrations. The incidence of PHPT is approximately 21 cases per 100,000 person/year, with the disorder typically caused by a solitary parathyroid adenoma [1]. PHPT is a disease with multisystemic and heterogeneous manifestations. The usual presentation is observed in less than 15% of PHPT cases [2], and neuropsychiatric symptoms such as psychosis and, less commonly, depressive symptoms may occur [3, 4, 5, 6]. Parathyroidectomy is the treatment of choice for patients with physically symptomatic PHPT. However, it remains unclear whether parathyroidectomy is indicated solely for its psychiatric manifestations [7].

The aim of this case series was to assess the role of surgery in management of primary hyperparathyroidism associated with psychiatric disorders in elderly. Written informed consent was obtained from all patients.

Discussion

Primary hyperthyroidism (PHPT) is a complex endocrinopathy involving parathyroid glands which produces high amounts of parathyroid hormone and consequently high calcium serum level. Classic manifestations of PHPT include renal and skeletal disorders that are associated with significant depletion in bone mineral density. Elderly patients are particularly susceptible to bone-related diseases and the risk of fractures. In cases of “fragile patient” with PHPT, non-specific complaints are reported; among these, depression is a common psychiatric manifestation, found in about 33% of PHPT sufferers. Although the pathogenesis of psychiatric disorders in PHPT is unclear, it appears that calcium plays a central role in the onset of disorders by interacting with monoamine metabolism, thereby modifying neurotransmission and resulting in mood and cognitive alterations [8]. We concur with several studies indicating that patients with PHPT who undergo parathyroid surgery could experience improvements in mood and neuropsychological functioning [2, 3, 5, 9, 10, 11, 12, 13]. When serum parathyroid hormone levels are lowered, a decrease in severe depressive symptoms is noted [3]. A systematic review published in 2023 by Desai et al. explored the results of 1227 patients from 11 studies; 833 patients suffered from hyperparathyroidism, and the remaining were from control groups. Of the 1227 patients, 499 were reviewed for the improvement of neuropsychiatric symptoms after parathyroidectomy and 334 were reviewed for the effects of increased PTH on their neurocognitive behaviours. They concluded that there is a significant correlation in patients with hyperparathyroidism between high serum calcium level, high serum parathyroid hormone level, high serum alkaline phosphatase level, and depressive symptoms [3]. The presence of a long-standing depressive disorder unresponsive to medical therapy should suggest an organic disorder such as chronic hypercalcemia, which may be secondary to PHPT. Surgical intervention in these selected cases can assist medical therapy in the improvement of depressive symptoms. This is in accordance with Liu JY, et al. [14] who in 2020 published a comparative study of 244 patients who underwent parathyroidectomy and 161 who underwent thyroidectomy. They observed improvement in neuropsychiatric symptoms after parathyroidectomy (6.2 [5.0-7]).

The diverse neuropsychiatric manifestations observed in patients with Primary Hyperparathyroidism (PHPT) could potentially lead to a high rate of misdiagnosis. Increasing awareness of this correlation could facilitate earlier diagnosis of PHPT. There is a need for more randomized controlled trials to evaluate the effectiveness of treatments for depression in patients with hyperparathyroidism.

Our case series on elderly patients above show reversibility of psychiatric symptoms with correction serum calcium levels by parathyroidectomy and transient effect on noninvasive treatment. As already described in some reports, it is still unclear whether the degree of psychotic symptoms is directly proportional to the severity of hypercalcaemia. It is also possible that elderly patients have a lower tolerance to changes in serum calcium levels and therefore present more severe symptoms in the presence of small changes in serum calcium levels. The prevalence of primary hyperparathyroidism (PHPT) increases with age. They are more likely to present with vague neuropsychiatric complaints, which can be mistakenly attributed to their age rather than PHPT. The only cure for PHPT is  surgery, but referral for parathyroidectomy in patients over the age of 70 is often limited due to comorbidities and perceived surgical risks. However, the cure rate in the elderly, as measured by surgical success, has been shown to be equivalent to that of younger patients, with minimal increased risk of postoperative complications. As the life expectancy of the population increases, elderly patients with PHPT are at an increased risk of developing sequelae from this disease. In conclusion, we described three cases of PHTP in elderly. A consideration by our case series, as described in similar reports, patient age should not be the reason for abstaining from a surgical referral in cases of PHTP. Surgery remains an effective treatment to prevent PHPT-associated complications and improve the quality of life for symptomatic patients.

In addition, when dealing with elderly patients presenting with recent complaints of depressive or psychiatric disorder, hypercalcemia must be considered among the causes of the symptoms presented. Appropriately designed future studies are needed to confirm these findings and definitively compare outcomes to conservative approaches

Authors’ Contributions

GB-AS wrote the manuscript. AS supervised the project. AM, DP, ST, and FB critically revised the manuscript. LZ external endocrinological revision. All authors read and approved the final manuscript.