The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 7 2384-2386
Copyright © 1998 by The Endocrine Society
Secondary Hyperparathyroidism in a Patient with Eight Parathyroid Glands
Oscar Joe Hines and
H. Earl Gordon
Department of Surgery, University of California Los Angeles School
of Medicine, Los Angeles, California 90095-6904
Address all correspondence and requests for reprints to: H. Earl Gordon, M.D., Division of General Surgery, UCLA School of Medicine, Box 956904, Los Angeles, California 90095-6904.
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Abstract
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The etiology of secondary hyperparathyroidism is multifactorial, and as
many as 10% of patients will ultimately require surgical intervention.
This condition is most commonly caused by four-gland hyperplasia. We
describe a patient who presented with secondary hyperparathyroidism and
symptoms of memory loss, pruritus, constipation, and bone and joint
pain. These complaints could not be controlled with conventional
therapy. Over a three-year period, the patient underwent three neck
explorations, with complete and persistent relief of his symptoms
following the last parathyroidectomy. A total of eight parathyroid
glands were removed during these three procedures. Although recurrence
of hyperparthyroidism can be caused by seeding at the time of
operation, the glands removed during the second and third procedures
were not the typical miliary seeding seen with this complication. These
glands were solid and hypertrophied and were found in areas not
previously explored. A discussion of the possible causes of this
unusual presentation is included.
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Introduction
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PAPPENHEIMER and Wilens were the first to
recognize that an enlargement of the parathyroid glands is a common
autopsy finding in patients dying of chronic uremia (1). The
pathogenesis of hyperparathyroidism, in the face of uremia, is complex
and multifactorial (2) and can be documented in as many as 67% of
uremic patients if left untreated (3). Management with
1,25(OH)2D3, calcitriol, and calcium
supplementation can aid in the prevention of symptoms and any resulting
renal osteodystrophy (4, 5, 6). However, a patient with established
secondary hyperparathyroidism and continuing symptoms can be difficult
to manage pharmacologically. As many as 5–10% of renal failure
patients will ultimately require surgery to control progression of
their hyperparathyroid disease, and of these, as many as 14% will
require reoperation for persistent or recurrent disease (7).
We describe a patient with secondary hyperparathyroidism who, because
of persistence of symptoms, required three neck explorations over 3 yr.
Eight separate parathyroid glands were ultimately removed.
Supernumerary parathyroids have been described, but none as extensive
as the current case has been reported in the literature.
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Subject and Methods
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The patient initially presented in 1986, at age 61 yr, because
of symptoms that eventually lead to the diagnosis of renal failure, the
etiology of which was unclear. One year later, in 1987, he required
peritoneal dialysis. In 1988, he underwent a kidney transplant, which
eventually failed (6 yr later, in 1994). He was begun on hemodialysis.
However, the patient complained of memory loss, pruritus, constipation,
and bone and joint pain. At that time, the serum calcium level was 10.6
mg/dL (normal 8.4–10.0 mg/dL) (Fig. 1
),
and the PTH level was 735 pg/mL (10–55 pg/mL). A diagnosis of
secondary hyperparathyroidism was made, and the patient underwent a
neck exploration in November, 1994. At the time of surgery, three
hyperplastic parathyroid glands were identified. The two superior
glands were excised and two-thirds of the right inferior parathyroid
was removed. Postoperatively, the patient’s calcium never normalized
(10.3–12.0 mg/dL), and the PTH remained elevated (916 mg/dL). The
patient’s symptoms persisted. He was maintained on vitamin D
supplementation and calcitonin.
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Figure 1. Serum calcium values (normal 8.4–10.0
mg/dL) from 1990 to present. Arrows indicate operative
exploration and parathyroidectomy.
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Almost 1 yr later (in October, 1995), the patient was referred to us
for further evaluation. An ultrasound of the neck was obtained,
revealing a mass lateral to the left carotid artery, and a lesion in
the right midneck region was also noted. A sestamibi scan confirmed the
presence of bilateral parathyroid tissue (Fig. 2). The serum calcium measured 11.4
mg/dL, and the PTH level was 711 pg/mL. The patient underwent a second
operation, and a 4.1-g parathyroid was found high in the left neck,
lateral to the carotid artery. The remnant right inferior gland also
was identified. Both of these were removed, in addition to a fifth
parathyroid discovered in the right tracheoesophageal groove. To
maintain calcium homeostasis, the patient had the right inferior
remnant transplanted to the right forearm. A total of 5.5 g of
parathyroid tissue was removed at this second operation, after which
the patient’s preoperative symptoms were dramatically relieved.
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Figure 2. Sestamibi scan before second exploration.
The scan demonstrates increased uptake bilaterally in the neck,
suggesting remaining hyperplastic parathyroid tissue.
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Three months after this second operation, the patient’s serum calcium
level measured 8.1 mg/dL. The PTH level began to rise, however, and
differential PTH levels were obtained in each arm to determine whether
the transplanted parathyroid tissue was the etiology of this elevation.
Although there was a mild differential in the PTH level, the patient
was asymptomatic, and the serum calcium was normal, so further
evaluation of the PTH elevation was not pursued.
In August, 1996, 10 months after the second operation, the patient
complained of recurrence of severe pain in both upper extremities and
aggravation of his Paget’s disease in the lower extremities. These
symptoms became severely disabling. Although the patient’s serum
calcium level had remained within the normal range during most of the
10 months after the second operation, it rose to 10.8 mg/dL in August,
1996, with a corresponding PTH of 1520 pg/mL. A repeat sestamibi scan
was performed, which revealed two foci of parathyroid tissue in the
left neck/upper mediastinal region (Fig. 3). An ultrasound revealed a 1-cm mass,
just inferior to the left lobe of the thyroid gland. Although an
magnetic resonance scan failed to identify any abnormality, using the
information of the first two tests, a third neck exploration was
performed. At the time of operation, no disease was discovered in the
neck, and the upper mediastinum was explored through the same collar
incision. Three glands were identified in the thymus, measuring 1.4,
1.0, and 0.6 cm in diameter, respectively, and weighing a total of
1.0 g. Postoperatively, the patient’s symptoms resolved, and his
serum calcium and PTH levels normalized.
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Figure 3. Sestamibi scan before third operation. The
scan demonstrates two foci of uptake in the left lower neck/upper
mediastinal region, not seen on the prior exam (Fig. 2 ).
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Results
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In summary, this patient underwent three operations, during which
a total of eight parathyroid glands were removed (Fig. 4). Pathologic confirmation of each gland
was obtained at the time of operation, and by permenant section,
following the procedure (Fig. 5). To
date, the patient remains asymptomatic. His forearm parathyroid
transplant has been functioning, with his serum calcium and PTH levels
remaining normal, with no calcium supplementation.
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Discussion
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Whereas only 2–6% of all patients are found to have
supernumerary parathyroid glands, this anomaly may be found in as many
as 25% of uremic patients (8, 9, 10). In most patients, this is caused by
a fifth gland. In our patient with chronic renal failure, a total of
eight parathyroid glands were ultimately removed. Although cases of
supernumerary parathyroids have previously been described, none as
extensive as the current case has been reported in the literature.
Reoperation for secondary hyperparathyroidism is well described (7, 11, 12). In addition to the beneficial effects on bony pathology, the
surgical treatment of advanced hyperparathyroidism also results in an
improvement of cardiac performance, insulin secretion, phagocyte
function, sexual dysfunction, and pruritus (13, 14). The manifestations
of this patient’s disease were controlled each time an adequate
procedure was performed. It is likely that subsequent exacerbation of
the patient’s symptoms correlated with growth of the remaining
parathyroid tissue.
Imaging studies, to identify and localize unrecognized
parathyroid disease, should be performed before reoperation is
considered. This may include ultrasound, nuclear medicine scan,
computed tomography scan, magnetic resonance imaging, angiography,
venous sampling, or percutaneous aspiration. The most specific and
sensitive noninvasive imaging technique seems to be sestamibi scan,
with virtually no false-positive results reported (15). This patient
demonstrated abnormal parathyroid tissue, by sestamibi and ultrasound
before each reexploration (but not by magnetic resonance, a less
sensitive test).
The etiology underlying this patient’s enormous propensity for
multiple parathyroid glands is unclear. Although unlikely, it is
possible that the additional glands seen in this patient stemmed from
seeding at the time of operation. However, the mediastinum was not
explored in the first two operations. Furthermore, recurrence caused by
seeding is characterized by a miliary appearance, with each nodule
measuring a few millimeters. The glands found in our patient were
solid, hypertrophied organs, which suggests that they represented
ectopic parathyroid tissue.
The concept of parathyroid rests, or parathyromatosis, was
introduced in 1977 by Marx, who proposed that during ontogenesis,
branchial pouch tissue may scatter throughout the neck and mediastinum
(16). The stimuli of hypocalcemia, hyperphosphatemia, and
1,25(OH)2D3 deficiency in renal failure may
then ultimately result in parathyroid cell hyperplasia.
At the molecular level, the sequence of events underlying parathyroid
cell proliferation is just now being unraveled. In the uremic state,
parathyroid cell proliferation seems to initially be a polyclonal
event. Uremic patients have a diminished ability for DNA repair (17),
which may increase the likelihood of parathyroid gland clonal
transformation and inactivation of a tumor supressor gene, which leads
to a monoclonal proliferation (18, 19). Clinically, the end result is
hyperparathyroidism, unresponsive to medical therapy.
Our patient has demonstrated a remarkable propensity for
symptomatic hyperparathyroidism. We speculate that had
monoclonal cells been transplanted to his forearm at the second
operation, he would have returned with recurrent symptoms of
hyperparathyroidism that would have required an additional local
procedure on the forearm graft.
Received December 18, 1997.
Revised March 12, 1998.
Accepted March 18, 1998.
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Abstract
Introduction
