BRIEF CLINICAL REPORT

Parathyroidectomy for Osteoporosis

More Complex Than We Thought?
Jessica M. Fazendin, MD, Brenessa Lindeman, MD, and Herbert Chen, MDY
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(version 25; IBM Corp, Armonk, NY). Chi-squared analysis and

P rimary hyperparathyroidism is a common disorder that can lead
to the undesirable sequelae of nephrolithiasis, gastrointestinal
abnormalities, cognitive impairment, and deleterious skeletal
t tests were used where appropriate.

effects.1 The classic biochemical profile of primary hyperparathy- RESULTS

roidism is well understood with elevated calcium in the setting of From November 2000 to October 2018, 2053 patients under-
inappropriately normal or elevated parathyroid hormone (PTH). went parathyroidectomy for primary hyperparathyroidism. The mean
More recently, a variant of primary hyperparathyroidism in which age was 60  0 and the majority (77.8%) were female. Mean calcium
calcium levels are normal in the setting of elevated PTH has and parathyroid hormone preoperatively were 10.9 mg/dL and
been well described.2 Lim et al3 reported that in addition to positive 127  2.9 pg/mL, respectively. Patients were categorized based on
family history, low vitamin D, and glomerular filtration rate < 60, the presence or absence of bone disease. Patient demographics are
normocalcemic primary hyperparathyroidism patients were more listed in Table 1. In total, 694 (34.2%) of patients exhibited osteo-
likely to have multigland disease as compared with the classic porosis, osteopenia, or admitted to a history of pathologic fracture.
biochemical profile. In contrast, they found no correlation between Patients with skeletal effects were older and more likely to be female
the presence of kidney stones or osteoporosis and multigland hyper- (P < 0.0001). Mean preoperative calcium and PTH levels were lower
parathyroidism.3 in the bone disease group [(10.8 vs 10.9 mg/dL, P ¼ 0.0009) and (121
Studies have shown that parathyroidectomy for biochemically vs 130 pg/mL, P ¼ 0.037), respectively]. Patients with bone disease
classic primary HPT is effective in treating nephrolithiasis and were more likely to have multigland disease compared with patients
decreasing the incidence of pathologic fractures.4 Surgical cure is without bone disease (33.2% vs 27.9%, P ¼ 0.014).
the only effective measure to achieve a significant improvement in
bone mineral density and risk reduction of fractures, but has variable DISCUSSION
effects on bone mineral density at various sites.5 To better charac- It is well understood that surgical cure of primary hyperpara-
terize this observation, we review our institutional experience in thyroidism results in numerous clinical benefits for patients. Inci-
patients with bone disease and primary hyperparathyroidism. dence of renal calculi, musculoskeletal, and gastrointestinal
manifestations can all improve in addition to asymptomatic man-
METHODS ifestations such as bone loss.1 We know that many asymptomatic
To perform this study, we utilized a prospective database of all patients are often diagnosed with primary hyperparathyroidism after
patients undergoing parathyroidectomy for primary hyperparathy- undergoing routine bone density evaluation with DEXA scans, and
roidism from November 2000 to October 2018 for 2 surgeons, across they often have biochemical abnormalities with either elevated
2 institutions (UAB Institutional Review Board-Approved). Patients calcium or parathyroid hormone, but not always both.3,4 Parathy-
were diagnosed with primary hyperparathyroidism based on serum roidectomy has not only been shown to be effective for fracture risk
calcium, serum PTH, and vitamin D levels. PTH lab platforms were reduction, but to also be more cost-effective as compared with
validated across both institutions throughout the study period. Bone observation alone. Unfortunately, this disease remains both
disease was categorized based on bone mineral density designation
of osteoporosis or osteopenia or history of pathologic fracture.
Patient-reported history was used to distinguish pathologic versus TABLE 1. Patient Characteristics With Percentages in Paren-
traumatic fractures. Multigland disease was defined by one or more theses [No. (%)] and the Standard Error of the Mean (SEM),
abnormal parathyroid glands found at the time of operation. Defini- Along With Confidence Interval Shown
tion of abnormal gland included visual inspection by the surgeon
Bone Disease No Bone Disease
(color, shape, size) and diagnosis reinforced ex-vivo with elevated n ¼ 694 n ¼ 1336
counts detected by gamma probe. It is both surgeon’s practice to use Demographics (34.2%) (65.8%) P Value
the gamma probe for at every operation, except those for which it is
contraindicated (ie, pregnancy, lactation). Intraoperative PTH sam- Sex
M 78 (11.2) 373 (27.9) P < 0.0001
ples at 5, 10, and 15 minutes were used to confirm a successful
F 616 (88.8) 963 (72.1)
procedure. Statistical analysis was performed using SPSS software Age (years) 65  0.4 57  0.4 P < 0.0001
CI 64, 66 CI 57, 58
Preoperative Ca mg/dL 10.8  0.03 10.9  0.02 P ¼ 0.0009
CI 10.7, 10.8 CI 10.8, 11.0
From the Department of Surgery, University of Alabama at Birmingham, Birming- Preoperative PTH pg/mL 121  6.3 130  2.9 P ¼ 0.037
ham, AL. CI 108, 133 CI 124, 135
hchen@uabmc.edu. Pathology
The authors report no conflicts of interest. Single adenoma 464 (66.8) 963 (72.1) P ¼ 0.014
Copyright ß 2020 Wolters Kluwer Health, Inc. All rights reserved. Multigland disease 230 (33.2) 373 (27.9)
ISSN: 0003-4932/20/27301-0e19
DOI: 10.1097/SLA.0000000000003978

Annals of Surgery  Volume 273, Number 1, January 2021 www.annalsofsurgery.com | e19

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Fazendin et al
under-recognized and undertreated, with lost opportunities for
improved clinical outcomes and a deleterious financial effect on
the health care system.6 In a study of over 600 patients at a major
academic center, only one-third of patients who met 1 or more
consensus guidelines were referred for and eventually underwent
parathyroidectomy.7
Not unexpectedly, patients with bone disease included in this
study had lower preoperative calcium than their counterparts free
from bone disease. They also exhibited a milder biochemical form of
hyperparathyroidism with lower preoperative PTH values. We
found that more patients with skeletal complications secondary
to hyperparathyroidism exhibited multigland disease. While there
are statistically significant differences in preoperative calcium
(0.1 mg/dL) and PTH (9 pg/mL) between groups, this may be
difficult to identify on an individual basis for the clinician in
practice. We acknowledge this and suggest that the clinician has
a higher index of suspicion for multigland disease when bony
abnormalities are present.
Whereas postoperative patients with classical primary
hyperparathyroidism (elevated calcium in the setting of inappro-
priately normal to elevated PTH), have excellent musculoskeletal
outcomes, it is unclear why patients with varying biochemical
profiles may not experience the same benefit. In a 2018 study of 71
surgically-treated patients with normocalcemic primary hyperpara-
thyroidism, persistently elevated PTH levels were seen in 46.5% of
patients at 6 months despite an appropriate drop in ioPTH levels.8
We know that patients are more likely to have single-gland disease
in classical primary hyperparathyroidism at 80% to 85%, and that
the incidence of multigland disease increases with milder biochem-
ical profiles.3,9
Every effort should be made to achieve surgical cure of
hyperparathyroidism at first operation to achieve maximal clinical
benefit and to be most cost-effective. While localization studies may
help drive minimally-invasive parathyroidectomy, these may be most
appropriate in biochemically classic hyperparathyroidism.10 As we
have seen, patients with bone disease are more likely to exhibit
multigland pathology, and would likely best be served with a 4-
gland exploration.
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Annals of Surgery  Volume 273, Number 1, January 2021
CONCLUSION
Because multigland disease patients are more likely to exhibit
bone disease, it is all the more important to achieve a biochemical
cure to prevent deleterious skeletal effects over time. Varying
improvement in bone mineral density and fracture risk reduction
in this population underscores a likely systemic process seen in
multigland hyperparathyroidism. Surgeons should suspect multig-
land disease in patients with lower calcium and PTH levels and have
a low threshold for a 4-gland exploration in the attempt to achieve a
cure at first operation.
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ß 2020 Wolters Kluwer Health, Inc. All rights reserved.