Abstract
Primary hyperparathyroidism (PHPT) predominantly affects older adults, and parathyroidectomy can achieve definitive cure in symptomatic PHPT and asymptomatic meeting surgical criteria. As the population continues to age, the treatment of PHPT in octogenarians and nonagenarians presents a clinical conundrum. This case series presents the management of eight patients 85 years of age and older diagnosed with PHPT. A retrospective chart review of patients diagnosed with primary hyperparathyroidism were identified in a single institution. Those patients 85 years of age and older who were followed up for over one year were included in this case series. The literature on treatment options for this age group was also reviewed. Eight cases of PHPT patients aged 88 ± 2.5 years old with a follow-up average of 5.6 ± 4.4 years were reported in our case series. Six PHPT patients were medically managed and two PHPT patients underwent parathyroid resection. Most of the medically managed PHPT patients except for one had long-term stability of disease for over five years. The treatment of PHPT diagnosed in patients over 85 years of age presents a clinical challenge for which there is no clear consensus guideline. Our case series supports that medical therapy is a feasible option for PHPT patients over 85 years old.
1. Introduction
Primary Hyperparathyroidism (PHPT) is a common disease that increases in prevalence with advancing age. Prevalence peaks in women around 70–79 years of age (492 per 100,000) and in men over 80 years old (264 per 100,000) [1]. Most patients with PHPT initially present with asymptomatic hypercalcemia. Those that are symptomatic present with axial and extremity fractures, nephrolithiasis, and psychiatric disturbance [2]. Surgical resection of the involved glands is the standard of care for young or symptomatic patients with PHPT. Medical management is used as a bridge to surgery or in patients who refuse or cannot safely undergo surgery. Strategies include hydration with expectant management, stopping offending agents such as calcium supplementation and medications (thiazides, lithium) and using diuretics, bisphosphonates, selective estrogen receptor modulators, and cinacalcet [2]. Expectant management involves serial monitoring for worsening of symptoms without specific therapeutic intervention [3, 4].
Most of the literature on the treatment of PHPT is not age-specific. About 1.5% of patients over the age of 70 have PHPT [5]. As our population continues to age and as average life expectancy increases, the proportion of elderly patients with PHPT will also grow. Though the standard of care to manage PHPT is surgery to achieve cure, the role of surgery is less clear in the very elderly. The objective of our study is to report eight cases of PHPT patients over 85 years of age who were managed using medical or surgical treatment to elucidate differences in prognosis and outcomes.
2. Cases Presentation
We conducted a retrospective chart review of PHPT patients evaluated at Robert Wood Johnson University Hospital from January 2000 to September 2016. Our institution’s IRB provided approval for our investigations. There were 556 patients diagnosed with PHPT during this time. The diagnostic criteria of PHPT included: (1) intact PTH > 65 pg/mL (normal range: 10–65 pg/mL) or inappropriately normal levels in the presence of elevated serum calcium, (2) serum calcium > 10.6 mg/dL (normal range: 8.5–10.4 mg/dL), and (3) 24-hour urinary calcium > 100 mg/day (normal range: 100–250 mg/day). Eight PHPT patients aged 85 years and older with follow-up duration longer than one year were included for this study. Patient demographics, baseline characteristics, clinical presentation and overall clinical follow-up were examined.
Eight patients diagnosed with PHPT at the age of 85 years or older were included. The average age at diagnosis was 88 ± 2.5 years old. The average follow-up duration was 5.6 ± 4.4 years. The average calcium was 11.3 ± 0.78 mg/dL, iPTH was 166 ± 154 pg/mL and 24-hour urine calcium was 183 ± 35.5 mg at the time of diagnosis. All eight patients met guidelines [2, 5] for surgery by the serum calcium levels >1 mg/dl upper limit of normal, creatinine clearance <60 cc/min or T-score <2.5 (Table 1). Six PHPT patients were medically managed for one to eight years and two PHPT patients underwent parathyroid resection. The surgical group had a pre-operative serum calcium of 12.3 mg/dL while the medically managed group had an average of 10.9 mg/dL. For two patients treated surgically, one patient was cured with normal calcium and PTH levels but was only followed up for two years. One patient had recurrence of PHPT five years after surgery and required medical management with cinacalcet, loop diuretic, and bisphosphonate for ten years. Six patients were managed medically for an average of 5.2 years with minimal complications. Only one of the six patients experienced PHPT-related mortality. This patient had severe dementia, was on medical treatment for eight years, and passed away on hospice after a hip fracture. Of the other medically managed patients, three patients were managed with pharmaceutical therapy, one with bisphosphonate and two with cinacalcet. Two other patients were treated with nonpharmaceutical expectant management, which included oral hydration, discontinuation of HCTZ and maintaining physical activity. They had favorable outcomes after three to six years.
Patient vignettes are demonstrated in Table 1.
3. Discussion
The Endocrine Society consensus guidelines recommend parathyroidectomy for both symptomatic and asymptomatic PHPT. Surgery is readily offered for biochemical cure in younger, symptomatic or asymptomatic patients with PHPT meeting surgical criteria [2]. The benefits of parathyroidectomy include advantages in survival, increased bone density, reduced fatigue, and other subjective measures [6, 7].
Much of the current literature advocates for more aggressive surgical therapy for the elderly. However, the benefit of surgery at achieving cure for octogenarians and nonagenarians is less straightforward than for the young. There is increased risk for complications, prolonged operation time and increased length of stay in hospitals for patients over the age of 80 years [7, 8]. As our understanding of PHPT has evolved, different phenotypes of the disease have been recognized, the symptoms of which can be confounded by the aging process in this population [9]. Studies have shown that medically managed patients with PHPT could have stable disease for over ten years [9, 10]. Our expanded case series supports medical management as a reasonable option in the very elderly, especially those with comorbidities.
Literature in favor of medical management of the very old shows promise despite its smaller scope. Khan et al. [4] and Marcocci et al. [11] reviewed the rationale and evidence behind medical management and expectant monitoring. They found that medical management can be effective, and that patients’ quality of life can be similar to those treated surgically. Jacobs et al. [3] described four patients with PHPT aged 79 to 87 years treated with medical management as a bridge to surgery or as sole therapy in poor surgical candidates or those refusing surgery. They employed saline hydration, pamidronate and cinacalcet. Medical therapy was a successful bridge to surgical cure with parathyroidectomy for two patients after two weeks to two months of treatment. Medical therapy was not tolerated for another and pursued indefinitely for the final patient. Wong reported two PHPT patients over the age of 90 treated with oral rehydration, bisphosphonate or cinacalcet. They experienced no PHPT related complications or fractures in a follow-up duration of seven months to four years [12].
The limitations of our study include small sample size and short duration of follow-up. One patient had baseline dementia, and 3 nonagenarian patients passed away after 6–10 years follow up, we did not have the data and therefore cannot compare quality of life, cognitive and muscle function before and after intervention.
In summary, our data suggest that medical therapy is a reasonable option for PHPT patients over 85 years old. As life expectancy increases and more patients are diagnosed with PHPT later in life, further consensus guidelines may need to specifically address treatment recommendations for patients over the age of 85 years. Studies with larger patient populations and randomized controlled trials are needed to support our findings.
Conflicts of Interest
The authors declare that they have no conflicts of interest.