A 53-year-old white woman was referred for the evaluation of
osteoporosis. She had no complaints at the time of initial evaluation and was
not taking any medications besides a multivitamin. She did not smoke cigarettes
or use an excess of alcohol. She has been physically active with good sun
exposure as a physical activity teacher and coach. She is very flexible and has
had multiple bilateral shoulder subluxations and dislocations since her
childhood but no history of fractures or loss of height. She had a surgical
menopause after oophorectomy for bilateral ovarian cysts when aged 45 years
with no estrogen replacement therapy. She did not have a history of renal
stones or a family history of osteoporosis.
Exam revealed a thin woman (BMI, 21) with remarkable hyperextensibility
of her joints and cubitus valgus. She did not have blue sclera or kyphosis. Lab
testing revealed an inappropriately elevated parathyroid hormone of 103 pg/mL
relative to other normal tests including a serum calcium of 9.3 mg/dL, ionized
calcium 5 mg/dL, phosphorous 2.9 mg/dL, 25 OH vitamin D 41 ng/mL, blood urea
nitrogen 21 mcg/dL and creatinine 0.8 mcg/dL. Her 24-hour urine calcium was 197
mg with a normal calculated fractional calcium excretion of 1.3%. Her urinary
N-terminal telopeptide was at the upper limit of normal at 63 nM BCE/mM. A
clinical diagnosis of Ehlers-Danlos syndrome (EDS; hypermobility type) was
made. Causes of her osteoporosis were defective bone mineralization from the
EDS, excessive bone resorption from her postmenopausal state and an elevated
PTH level. The perplexing finding of an elevated PTH despite normocalcemia,
normal 25 OH vitamin D and renal function was investigated further.
Kishore M. Lakshman
Stephanie L. Lee
A neck ultrasound in endocrine clinic with a high resolution linear
probe did not detect any masses suggestive of a parathyroid adenoma. A
Technetium (Tc)-99m sestamibi scintigraphy with single-photon emission CT
imaging was not suggestive of parathyroid gland enlargement (figure 1). Next, a
4D-CT scan of the neck was performed (figure 2). After a bolus IV contrast
injection, multiple axial images were obtained after a 22-second, 52-second and
82-second delay. The scan revealed a 0.6 cm x 0.3 cm mass located posterior to
the superior aspect of the right thyroid gland and medial to the internal
carotid artery. This oblong-shaped mass was slightly hypodense to muscle on
noncontrast phase, then initially hyperenhancing and subsequently relatively
hypoenhancing on later post-contrast images (figures 2A, B, C). The patient was
referred for parathyroidectomy. The surgeon located a 130-mg right superior
parathyroid adenoma at the site indicated by the 4D-CT scan. The intraoperative
PTH values dropped from 1,192 pg/mL to 121 pg/mL, reflecting a 90% decrease,
and the final pathology corroborated an adenoma.
The last decade has witnessed the development of unilateral minimally
invasive parathyroidectomy that relies on accurate preoperative localization of
the parathyroid lesion. After biochemical confirmation of primary
hyperparathyroidism, the initial imaging modality to locate a parathyroid
adenoma is typically a parathyroid nuclear scintigraphy scan often with Tc-99m
sestamibi scintigraphy or a neck ultrasound; their sensitivities are debated
and are in the 60% to 80% range for Tc-99m and 30% to 70% for neck ultrasound.
The sensitivity is lower in challenging situations such as multigland disease,
ectopic parathyroid glands, supernumerary glands and previous neck exploration.
In this particular case, the parathyroid adenoma was located deep and posterior
to the superior pole of the thyroid, a location not easily seen by
Tc-99m sestamibi parathyroid planar scan. Anterior view of the neck and
chest performed five minutes (early) and two hours (late) after injection of
isotope. There was symmetric uptake of isotope in the thyroid in the early scan
and uniform washout of tracer without area of retention on the delayed (late)
image or by SPECT images. This imaging test did not reveal the location of the
right upper 130 mg parathyroid adenoma.
Photos courtesy of: Stephanie L.
Figure 2. Axial 4D - CT
scan. A. Initial non-contrast enhanced axial image of the upper neck at the
level of the upper pole of the right thyroid gland (T) shows the normal neck
anatomy including right internal jugular vein (JV), tracheal (TR) and carotid
artery (c). The parathyroid adenoma indicated by the green arrow is not readily
apparent. B. Axial early (~20 seconds) post contrast-enhanced image shows the
characteristic hyperenhancing right parathyroid adenoma (green arrow), medial
to the right internal carotid artery (c) and posterior to the superior pole of
the right thyroid lobe (T). C. After a delay of ~50 seconds, the enhancement of
the mass (green arrow) is diminished but persists typical of a parathyroid
4D-CT, also referred to as multidimensional CT, is emerging as a
second-line localization technique. It has the same capacity as a 3D-CT in
demonstrating anatomical detail, but the fourth dynamic dimension of contrast
enhancement with time improves the sensitivity to detect small parathyroid
adenomas. Parathyroid adenomas typically enhance avidly on early-phase imaging,
and the hyperenhancement persists despite a long delay after contrast
administration. The degree of early enhancing and slow washout of contrast
correlates with metabolic activity of the parathyroid adenoma. This
characteristic gives 4D-CT the double advantage of demonstrating gland
functionality and excellent anatomy of the gland and its surrounding
structures. One studys results demonstrated that 4D-CT had improved
sensitivity (88%) vs. sestamibi imaging (65%) and ultrasound (57%) in
localizing hyperfunctioning parathyroid glands. A disadvantage of the technique
is the radiation exposure from the multiple series of images of the neck.
A potential challenge while interpreting a 4D-CT includes
differentiating parathyroid adenomas from normal lymph nodes and vascular
structures. Lymph nodes do not show hyperenhancement and are most often
isoenhancing relative to adjacent muscles. Vascular structures can be
identified by carefully tracking them in the CT performed during early arterial
phase enhancement. A direct advantage of 4D-CT vs. parathyroid sestamibi scans
is its ability to detect smaller parathyroid adenomas and parathyroid
hyperplasia, especially in the postoperative neck. The location of parathyroid
adenomas missed by conventional methods and detected by 4D-CT include ectopic
adenomas and those located in the tracheoesophageal groove, carotid sheath and
mediastinum. 4D-CT is a valuable modality with the ability to detect small
parathyroid adenomas or hyperplastic glands with a high sensitivity, and to
provide precise anatomical localization to plan the best surgical approach. The
4D-CT scan is highly recommended in challenging cases of hyperparathyroidism
when conventional imaging with neck ultrasound and parathyroid sestamibi are
Kishore M. Lakshman, MD, MPH, is a Fellow in Endocrinology, Section
of Endocrinology, Diabetes and Nutrition, and Stephanie L. Lee, MD, PhD, is
Associate Chief, Section of Endocrinology, Diabetes and Nutrition, and
Associate Professor of Medicine, both at Boston Medical Center.
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