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238
P. S. Sundaram et al.
a
c
Fig. 16.8 36-year-old patient with S.PTH 126.8 pg/mL and hypercalcemia (S.Ca of 11.2mg/dL).
Dual phase
with image: (a) Initial image at 15min post injection showing homogenous normal tracer uptake
in both lobes of thyroid gland; (b) 2-h delayed image showing focal abnormal tracer uptake in left
superior parathyroid region with washout from thyroid gland; (c) Non-contrast CT neck; (d)
SPECTCT image shows accurate localization of parathyroid adenoma at left superior region
99m
Tc MIBI parathyroid scintigraphy demonstrating left superior parathyroid adenoma
b
d
Certain specic features of the lesion such as size, cellularity, presence of
P-glycoprotein, and phase of cell growth affect the scan sensitivity. Oxyphil cell
rich parathyroid adenoma were found to show good
(Thallium) uptake. The sensitivity of
99m
Tc SestaMIBI scintigraphy was low in para-
99m
Tc SestaMIBI and
201
Tl
thyroid adenomas with P-glycoprotein or Multi Drug Resistance (MDR) gene
expression.
The sensitivity of
99m
Tc SestaMIBI is approximately 60% in detecting hyperplastic glands. The size, cellularity of the glands and the PTH level inuence
sensitivity and specicity of the scans. MIBI scans fail to localize the multi-glandular pathology.
16.6.5 False Positive andFalse Negative Results
99m
in
Tc-SestaMIBI Scan
False positive images are frequently associated with thyroid pathologies such as
nodules, thyroiditis, and with concurrent lymph node pathologies. Small size of
parathyroid lesions and multi-glandular diseases, and p-glycoprotein expression are
few conditions which lead on to negative scan results.
16 The Role ofNuclear Medicine inThyroid andParathyroid Disorders
239
16.6.6 Recent Advances inParathyroid Imaging Using PET
Many PET radiotracers have been used in parathyroid imaging. Methionine is a
precursor amino acid in PH synthesis and PET imaging using 11C-methionine
showed promising results. Since the half-life of the tracer is 20 min, images are
harvested immediately after the intravenous administration. The tracer is costly and
is not widely available. The sensitivity of the scan in localizing multi-glandular
lesions is low. 18F-FDG PETCT has poor sensitivity in unselected patients with
primary hyperparathyroidism but is useful in patients with parathyroid carcinoma in
assessing spread of lesion.
Choline is the precursor for cell membrane synthesis, thus being concentrated by
parathyroid adenoma and hyperplastic parathyroid glands. PET imaging with
11
C-Choline was found superior to
phy. 11C-Choline has been found to be superior in detecting parathyroid lesions.
However, limited availability of radiopharmaceutical as well as the shorter half-life
of the radiotracer remains the area of concern. 18F-Fluorocholine is a PET tracer
found promising results in parathyroid localization with a reported sensitivity and
positive predictive value of 93–100% and 90–100%, respectively. The sensitivity of
18
F-Fluorocholine PETCT was greater than that of 4D-CT regarding the number of
lesions (96% vs. 75%) and patients (85% vs. 63%), respectively. A meta-analysis of
11 studies on 18F-Fluorocholine PETCT found the rate of detection of lesions to be
97% in patient-based analysis and 94% in lesion-based analysis. 18F-Fluorocholine
PETCT is being considered as one of the imaging methods for parathyroid gland
visualization before invasive procedures in patients with persistent or recurrent disease with negative conventional imaging results.
Similarly, 18F-Fluorocholine PETMR, where anatomical imaging with CT is
being replaced by MRI, has also shown promising results. In 10 patients with negative or inconclusive results of ultrasonography and
18
F-Fluorocholine PETMR was performed after intravenous administration of 3
MBq/kg of 18F-Fluorocholine. The sensitivity and PPV of 18F-Fluorocholine
PETMR were found to be 90% and 100%, respectively.
99m
Tc SestaMIBI/
99m
Tc-pertechnetate scintigra-
99m
Tc-SestaMIBI imaging,
16.6.7 Gamma Probe Guided Parathyroidectomy [22]
Minimally invasive parathyroidectomy became popular after successful preoperative imaging, particularly with SestaMIBI scintigraphy and ultrasound. Radioguided
surgery using intraoperative gamma probe facilitates the surgical exploration,
reduces the operative time, and conrms the correct excision of the pathological
parathyroid tissue. The intraoperative gamma probe is a handheld radiation detector
device which gives both auditory signals and digital counts to guide the surgeon to
localize and dissect the radioactive target tissue. Minimally invasive radioguided
surgery (MIRS) (Fig.16.9) is recommended to reduce blood loss, intraoperative
surgical time, faster postoperative recovery (reduced hospital stay days) and cosmetic purpose to have a small scar. Patients undergo a prior SestaMIBI scintigraphy
240
P. S. Sundaram et al.
a
c
Fig. 16.9 MIRS, minimally invasive radioguided parathyroidectomy in a 56-year-old male with
history of left hemithyroidectomy. (a)
noma; (b) Exposing the adenoma intraoperatively based on Gamma probing; (c) Sterile draped
battery-operated hand-held Gamma probe showing count statics in neck at the site of adenoma; (d)
Collimated Gamma nder
99m
d
Tc MIBI concentrating right inferior parathyroid ade-
b
to identify the site of solitary parathyroid adenoma. On the day of surgery 2–3 mCi
of intravenous
99m
Tc SestaMIBI is injected 1h prior to surgery. This is done to minimize radiation exposure to surgeon and theatre staff. Gamma probe localizes the site
of adenoma by keeping the probe over the overlying skin surface, incision is made
accordingly and neck is exposed. This helps in complete excision of adenoma,
reducing the intraoperative time by 50% and also reduces the length of incision.
Studies also show less evidence of post-surgical hypocalcemia, less pain, and
complications.
16.7 Conclusion
Single isotope, dual phase
of choice for localizing parathyroid adenomas in patients with suspected hyperparathyroidism apart from high-denition US. MIRS has placed a greater
emphasis on preoperative localization of abnormal parathyroid glands. However,
there is no perfect imaging modality with widespread availability and high sensitivity, to localize all abnormal parathyroid glands. 18F-Fluorocholine PETMR
is another emerging technology especially used in those patients with negative
MIBI ndings for preoperative localization of abnormal parathyroid glands.
99m
Tc MIBI parathyroid scintigraphy is the procedure
16 The Role ofNuclear Medicine inThyroid andParathyroid Disorders
241
References
1. Mettler FA, Guiberteu MJ. Essentials of nuclear medicine imaging (Chapter 4). 6th ed.
Philadelphia: Elsevier, Inc; 2012.
2. Burrow GN, Fisher DA, Larsen PR.Maternal and fetal thyroid function. N Engl J Med.
1994;331:1072–8.
3. Gorman CA.Radioiodine and pregnancy. Thyroid. 1999;9(7):721–6.
4. Rubow S, Klopper J, Wasserman H, etal. The excretion of radiopharmaceuticals in human
breast milk: additional data and dosimetry. Eur J Nucl Med. 1994;21:144–53.
5. Robinson PS, Barker P, Campbell A, Henson P, Surveyor I, Young PR. Iodine-131in breast
milk following therapy for thyroid carcinoma. J Nucl Med. 1994;35(11):1797–801.
6. Intenzo CM, dePapp AE, Jabbour S, Miller JL, Kim SM, Capuzzi DM.Scintigraphic manifestations of thyrotoxicosis. Radiographics. 2003;23(4):857–69.
7. Martino E, Aghini-Lombardi F, Mariotti S, etal. Amiodarone iodine-induced hypothyroidism:
risk factors and follow-up in 28 cases. Clin Endocrinol. 1987;26:227–37.
8. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, etal. 2015
American Thyroid Association Management guidelines for adult patients with thyroid nodules
and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force
on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1–133.
9. Shanmuga Sundaram P, Padma S.Diagnostic utility of PETCT in thyroid malignancies: an
update. Ann Nucl Med. 2013;27:681–93. https://doi.org/10.1007/s12149- 013- 0740- 6.
10. Hales NW, Krempl GA, Medina JE.Is there a role for FDG PET/CT in cytologically indeterminate thyroid nodules? Am J Otolaryngol. 2008;29:113–8.
11. Silberstein EB, Alavi A, Balon HR, Clarke SE, Divgi C, Gelfand MJ, Goldsmith SJ, Jadvar
H, Marcus CS, Martin WH, Parker JA, Royal HD, Sarkar SD, Stabin M, Waxman AD.The
SNMMI practice guideline for therapy of thyroid disease with 131I 3.0. J Nucl Med.
2012;53(10):1633–51.
12. Andrade VA, Gross JL, Maia AL.The effect of methimazole pretreatment on the efcacy of
radioiodine therapy in Graves’ hyperthyroidism: one-year follow-up of a prospective, randomized study. J Clin Endocrinol Metab. 2001;86:3488–93.
13. Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, Tennvall J, Bombardieri E,
European Association of Nuclear Medicine (EANM). Guidelines for radioiodine therapy of
differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2008;35(10):1941–59.
14. Luster M, Lippi M, Jarzab B, Perros P, Lassmann M, Reiners C, Pacinie F. rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review.
Endocr Relat Cancer. 2005;12(1):49–64.
15. Tuttle RM, Sukhjeet A, Avram AM, etal. Controversies, consensus and collaboration in the use
of I-131 therapy in differentiated thyroid cancer: a joint statement from the American Thyroid
Association, the European Association of Nuclear Medicine, the Society of Nuclear Medicine
and Molecular Imaging, and the European Thyroid Association. Thyroid. 2019;29:461–70.
16. Padma S, Sundaram PS.Radioiodine as an adjuvant therapy and its role in follow-up of differentiated thyroid cancer. J Can Res Ther. 2016;12:1109–13.
17. Samuel AM, Rajashekharrao B, Shah DH.Pulmonary metastases in children and adolescents
with well-differentiated thyroid cancer. J Nucl Med. 1998;39(9):1531–6.
18. Fugazzola L, Elisei R, Fuhrer D, Jarzab B, Leboulleux S, Newbold K, Smit J. 2019
European Thyroid Association guidelines for the treatment and follow-up of advanced
radioiodine- refractory thyroid cancer. Eur Thyroid J. 2019;8:227–45. https://doi.
org/10.1159/000502229.
19. Smith JR, Oates ME.Radionuclide imaging of the parathyroid glands: patterns, pearls, and
pitfalls. RadioGraphics. 2004;24:1101–15.
20. Kukar M, Platz TA, Schaffner TJ, et al. The use of modied four-dimensional computed
tomography in patients with primary hyperparathyroidism: an argument for the abandonment
242
of routine sestamibi single-positron emission computed tomography (SPECT). Ann Surg
Oncol. 2015;22(1):139–45.
21. Taillefer R, Boucher Y, Potvin C, Lambert R.Detection and localization of parathyroid adenomas in patients with hyperparathyroidism using a single radionuclide imaging procedure with
Tc-99m sestamibi (double phase study). J Nucl Med. 1992;33:1801–7.
22. Norman JG.Minimally invasive radioguided parathyroidectomy: an endocrine surgeon’s perspective. J Nucl Med. 1998;39:15N–24N.
P. S. Sundaram et al.
Surgery oftheParathyroid Gland
17
AravindanNair andP.BalajiViswanath
17.1 Introduction
From the time of Sir Richard Owen’s rst description in 1850 of the parathyroid
glands, the clinical features, diagnosis, and treatment of parathyroid disorders have
changed dramatically over the past 150 years. Advances in diagnosing, imaging,
and improvements in surgical techniques have made parathyroid surgery safe and
hardly with any morbidity. In many institutions, minimally invasive parathyroid
surgery under local anesthesia has become a daycare procedure.
17.2 Anatomy oftheParathyroid
Generally, there are four parathyroid glands, one pair of glands on each side located
on the posterior border of the thyroid. Approximately 3% have <4 glands and 5–10%
have more than 4 glands. Sine thymus and inferior parathyroid gland share embryological origin from third pharyngeal pouches the inferior pair have close relation
with thymus or even migrate along with it to the mediastinum. Frequently, islets of
parathyroid tissue are seen in the thymus which gains signicance in Multiple
Endocrine Neoplasia and secondary hyperparathyroidism.
The superior parathyroids have a more or less xed location on the posteromedial aspect of the superior pole of the thyroid lobe close to the trachea esophageal
groove. The inferior parathyroids are less constant inlocation and are usually found
on the posterolateral aspect of the thyroid lobe in a circular area with a radius of
around 2.5cm with the center being the point of contact between RLN and inferior
thyroid artery. The average parathyroid measures 5×3×1mm and weighs about
35–40 mg. The adult gland is yellow and almost pear-shaped with a tuft of
A. Nair (*) · P. BalajiViswanath
Department of General and Endocrine Surgery, Naruvi Hospitals, Vellore, Tamil Nadu, India
© The Author(s), under exclusive license to Springer Nature Singapore Pte
Ltd. 2024
C. G. Nair, S. J. Abraham (eds.), Surgical Management of Thyroid and
Parathyroid Diseases, https://doi.org/10.1007/978-981-97-3774-1_17
243
244
A. Nair and P. BalajiViswanath
normal-looking fat attached to it. The symmetry inlocation and size of the superior
parathyroid glands is around 80% whereas it is about 70% for the inferior glands [1].
The parathyroid glands have variable relations with the thyroid gland and may be
placed within the brous capsule or outside it. The intracapsular parathyroid gland
remains within the connes of the thyroid gland even after undergoing pathological
changes. Extracapsular parathyroid tends to take a path of least resistance when the
volume increases and can be seen from the cricothyroid junction up to the posterior
mediastinum or in the superior mediastinum.
At operation, the parathyroid glands are globular or oblong and soft in consistency (unlike a thyroid nodule or a lymph node). They are quite vascular and usually
have what is known as the oating sign, the gland is seen to move within its fatty
capsule when gentle pressure is applied. The superior glands are usually seen posterior to the nerve and the inferior glands are seen anterior to the nerve.
Parathyroid glands receive the blood supply from the inferior thyroid on the
majority of occasions but in about 15% superior thyroid artery directly or through
the posterior anastomotic channel supply superior parathyroids.
17.2.1 Variations
Since parathyroid glands originate from 3rd and 4th pharyngeal pouches and
migrate to their usual locations close to the thyroid gland and since they share an
embryological origin with other organs, ectopia is not rare. Approximately 10–15%
of parathyroid glands may be ectopically placed. Ectopic locations include the
thyro- thymic tract, trachea-esophageal groove, retro esophageal space, intrathyroidal, carotid sheath, and mediastinum. Supernumerary glands are recorded in different frequencies varying from 2.5% to 22% of the population. Most often they are
located in the thymus or relation to the thyro-thymic tract. Parathyroid glands are
described from Type A to G based on embryological development and regional
anatomy. Understanding this helps inlocalization during surgery.
Type A: Adherent to posterior thyroid capsule with normal superior gland location
Type B: Tracheo-esophageal groove
Type C: Tracheo-esophageal groove inferior to the lower end of the thyroid lobe
Type D: Directly over recurrent laryngeal nerve
Type E: Close to the inferior thyroid pole (normal inferior parathyroid location)
Type F: within the thyro-thymic ligament
Type G: Intra thyroidal
17.3 Calcium Metabolism
The adult human body contains approximately 1kg of calcium of which only 1% is
in the extracellular uid. Total calcium in the blood is maintained within relatively
narrow ranges of 8.5–10.2 mg/dl (2.2–2.5 mmol/L) and 55% of this is protein
17 Surgery oftheParathyroid Gland
245
bound. Calcium remains in three forms in blood as ionic form, complexed form, and
protein-bound form. About 90% of protein-bound calcium is attached to albumin
and the rest to a variety of globulins. A portion of total calcium that forms ion couplets with anions such as bicarbonate and/or citrate is known as complexed calcium.
Ionic form and complexed form constitute the diffusible portion of serum calcium
which can pass through biological membranes. A diffusible portion of serum calcium is a determinant factor in calcium metabolism.
Traditionally serum total calcium is measured but this includes all three forms of
circulating calcium. Calcium levels are corrected (serum corrected calcium) based
on serum albumin, by the fraction of 0.8mg/dl decrease for 1mg/dl decrease in
albumin, which represents the diffusible portion of calcium. Estimation of ionic
calcium levels is not routine.
Cycle of calcium metabolism
The ionized calcium levels are inversely affected by the pH of the blood. One
unit of rising in the PH of blood will decrease the calcium by 0.36mmol/L.
Calcium homeostasis is regulated mostly by parathyroid hormone (PTH) synthesized and secreted from the parathyroid glands. Serum ionized calcium controls
the release of PTH from parathyroid glands by a negative feedback mechanism.
The setpoint at which the release of PTH is initiated is serum ionic calcium level
of 1.1–1.2mM (4.41–4.81mg/dl) which corresponds to serum total calcium level
of 2.2–2.4 mM (8.82–9.62mg/dl). Calcium sensing receptors in the parathyroid
gland detect the changing levels of calcium in the blood and modulate the synthesis
and release of parathyroid hormone by the chief cells. PTH favors osteoclastic
activity in bone, renal reabsorption of calcium, and synthesis of 1,25, OHD in kidneys. 1,25, OHD enhances gastrointestinal absorption of calcium. Serum levels of
inorganic phosphate and vitamin D are other determinants of serum calcium level.
Calcitonin produced by the parafollicular cells of the thyroid in response to
increased calcium levels inhibits bone resorption thus reducing calcium levels. Its
role in humans is not very clear when calcitonin levels are constantly very high as
246
A. Nair and P. BalajiViswanath
in medullary carcinoma thyroid. Salmon calcitonin has been useful in reducing
serum calcium in patients with high calcium levels.
17.4 Pathology ofHyperactive Parathyroid Glands
17.4.1 Adenoma
Parathyroid adenomas are usually single but multiglandular lesions are seen in about
10–15% of instances. The parathyroid gland contains chief cells, oxyphil (oncocytic)
cells, brovascular stroma, and adipose tissue. An adenoma could be monoclonal or
polyclonal and is an encapsulated lesion, tan brown with occasional hemorrhagic and
cystic areas. The majority of adenomas are of chief cell origin but oncocytic and
mixed cell adenomas are infrequently detected as a histological surprise. The adenoma differs from hyperplasia by the presence of a rim of compressed normal tissue.
17.4.2 Hyperplasia
Hyperplasia is usually multiglandular and could be part of multiple endocrine neoplasias, and secondary hyperparathyroidism. Nodular hyperplasia is rarely found in
sporadic primary hyperparathyroidism. Unlike adenoma, the lesion does not have a
thick capsule or a rim of compressed normal tissue.
17 Surgery oftheParathyroid Gland
247
17.4.3 Carcinoma
Parathyroid carcinoma is rare and accounts for about 1% of primary hyperparathyroidism. Most of the parathyroid carcinomas are functional and used to express high
disease severity indices such as serum PTH and calcium. Parathyroid carcinoma
presents as an ill-dened mass, usually palpable with adherence to surrounding tissues. The cut surface is nodular, rm, and has a gray tan appearance. Microscopically
it shows atypical neoplastic parenchymal cells with mitotic gures interspersed
with thick brous bands showing capsular and vascular invasion.
17.5 Hyperparathyroidism
Customarily hyperparathyroidism is categorized into three different forms primarily
based on the pathophysiology of the disease.
1. Primary
2. Secondary
3. Tertiary
17.5.1 Primary Hyperparathyroidism
Primary hyperparathyroidism is the third most common endocrine disorder after
diabetes mellitus and thyroid disorders. One or more parathyroid glands undergo
neoplastic changes or hyperplasia and continue to function autonomously. A single
adenoma is the etiology of PHPT in approximately 85% of cases and 2–5% of cases
are due to double adenomas. Hyperplasia and parathyroid carcinoma are the
other causes.
Occasionally more than one member of the family suffers from PHPT but evidence of germline mutation is not available. Mutation in the MEN1, CDC73, or
CASR gene was detected in some cases.
17.5.2 Secondary Hyperparathyroidism
Secondary hyperparathyroidism is seen in the setting of dialysis-dependent endstage renal disease and is associated with persistent vitamin D deciency. In Chronic
Kidney Disease (CKD), there is renal wastage of calcium and accumulation of
PO4in blood and this hypocalcemia induces PTH secretion. In renal failure, there
is hyperphosphatemia which induces Fibroblast Growth Factor 23 (FGF-23) from
bone resulting in the decreased renal conversion of 25–hydroxy cholecalciferol to
1,25–dihydroxycholecalciferol. Thus, intestinal absorption of calcium is decreased.
Both these effects cause hypocalcemia which stimulates PTH secretion and parathyroid hyperplasia sets in. Secondary hyperparathyroidism is a multiglandular disease and usually reverts to normality when CKD is corrected by transplant.