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11 Interventional Endocrinology: Techniques, Indications, andPotential Complications
99
• For radiofrequency ablation, regrowth occurs after 2–3years with regrowth rates
varying from 20–30% [21, 32, 33].
• Following ablation, the incidence rate of overall complications is around 3%
while the major complication rate is less than 2% [15].
• The most common complications are [19, 34, 35]:
– Pain (reported in up to 24.6% of patients).
– Voice change.
– Hematoma.
– Vomiting.
– Nodule rupture.
– Skin burn.
– Thyrotoxicosis.
– Hypothyroidism.
– Edema.
– Fever.
References
1. Baek JH, Lee JH, Valcavi R, Pacella CM, Rhim H, Na DG.Thermal ablation for benign thyroid nodules: radiofrequency and laser. Korean J Radiol. 2011;12(5):525–40.
2. Hussain I, Zulqar F, Li X, Ahmad S, Aljammal J. Safety and efcacy of radiofrequency
ablation of thyroid nodules—expanding treatment options in the United States. J Endocr Soc.
2021;5(8):bvab110.
3. Tamhane S, Gharib H.Thyroid nodule update on diagnosis and management. Clin Diabetes
Endocrinol. 2016;2(1):1–10.
4. Li Y, Jin C, Li J, etal. Prevalence of thyroid nodules in China: a health examination cohortbased study. Front Endocrinol. 2021;12:676144.
5. Kuo JH, Lee JA.The adoption of ultrasound-guided radiofrequency ablation of thyroid nodules in the United States. Ann Surg. 2021;273(1):e10–2.
6. Haugen BR, Alexander EK, Bible KC, et al. 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. https://doi.org/10.1089/thy.2015.0020.
7. Deandrea M, Garino F, Alberto M, etal. Radiofrequency ablation for benign thyroid nodules according to different ultrasound features: an Italian multicentre prospective study. Eur J
Endocrinol. 2019;180(1):79–87.
8. Deandrea M, Sung JY, Limone P, etal. Efcacy and safety of radiofrequency ablation versus
observation for nonfunctioning benign thyroid nodules: a randomized controlled international
collaborative trial. Thyroid. 2015;25(8):890–6.
9. Garberoglio R, Aliberti C, Appetecchia M, etal. Radiofrequency ablation for thyroid nodules:
which indications? The rst Italian opinion statement. J Ultrasound. 2015;18(4):423–30.
10. Cheng Z, Liang P.Advances in ultrasound-guided thermal ablation for symptomatic benign
thyroid nodules. Adv Clin Exp Med. 2020;29(9):1123–9.
11. Jin H, Lin W, Lu L, Cui M. Conventional thyroidectomy vs thyroid thermal ablation on
postoperative quality of life and satisfaction for patients with benign thyroid nodules. Eur J
Endocrinol. 2021;184(1):131–41.
12. Kuo JH, Sinclair CF, Lang B, etal. A comprehensive review of interventional ablation techniques for the management of thyroid nodules and metastatic lymph nodes. Surgery. 2021;
13. Bernardi S, Palermo A, Grasso RF, Fabris B, Stacul F, Cesareo R.Current status and challenges of US-guided radiofrequency ablation of thyroid nodules in the long term: a systematic
review. Cancers. 2021;13(11):2746.
100
14. Cesareo R, Pasqualini V, Simeoni C, etal. Prospective study of effectiveness of ultrasoundguided radiofrequency ablation versus control group in patients affected by benign thyroid
nodules. J Clin Endocrinol Metabol. 2015;100(2):460–6.
15. Kim J-H, Baek JH, Lim HK, etal. 2017 thyroid radiofrequency ablation guideline: Korean
Society of Thyroid Radiology. Korean J Radiol. 2018;19(4):632–55.
16. Pacella CM, Bizzarri G, Guglielmi R, etal. Thyroid tissue: US-guided percutaneous interstitial
laser ablation—a feasibility study. Radiology. 2000;217(3):673–7.
17. Lubner MG, Brace CL, Hinshaw JL, Lee FT Jr. Microwave tumor ablation: mechanism of
action, clinical results, and devices. J Vasc Interv Radiol. 2010;21(8):S192–203.
18. Esnault O, Franc B, Monteil J-P, Chapelon J-Y.High-intensity focused ultrasound for localized
thyroid-tissue ablation: preliminary experimental animal study. Thyroid. 2004;14(12):1072–6.
19. Bo X-W, Lu F, Xu H-X, Sun L-P, Zhang K.Thermal ablation of benign thyroid nodules and
papillary thyroid microcarcinoma. Front Oncol. 2020:2233.
20. Kim J-h, Baek JH, Sung JY, et al. Radiofrequency ablation of low-risk small papillary
thyroidcarcinoma: preliminary results for patients ineligible for surgery. Int J Hyperth.
2017;33(2):212–9.
21. Negro R, Trimboli P.Thermal ablation for benign, non-functioning thyroid nodules: a clinical
review focused on outcomes, technical remarks, and comparisons with surgery. Electromagn
Biol Med. 2020;39(4):347–55.
22. Jung SL, Baek JH, Lee JH, etal. Efcacy and safety of radiofrequency ablation for benign
thyroid nodules: a prospective multicenter study. Korean J Radiol. 2018;19(1):167–74.
23. Deandrea M, Trimboli P, Garino F, etal. Long-term efcacy of a single session of RFA for
benign thyroid nodules: a longitudinal 5-year observational study. J Clin Endocrinol Metabol.
2019;104(9):3751–6.
24. Dobnig H, Amrein K.Monopolar radiofrequency ablation of thyroid nodules: a prospective
Austrian single-center study. Thyroid. 2018;28(4):472–80.
25. Vuong NL, Dinh LQ, Bang HT, Thuy TTM, Bac NH, Vy TT.Radiofrequency ablation for
benign thyroid nodules: 1-year follow-up in 184 patients. World J Surg. 2019;43(10):2447–53.
26. Cho SJ, Baek SM, Lim HK, Lee KD, Son JM, Baek JH. Long-term follow-up results of
ultrasound- guided radiofrequency ablation for low-risk papillary thyroid microcarcinoma:
more than 5-year follow-up for 84 tumors. Thyroid. 2020;30(12):1745–51.
27. Zhang M, Tufano RP, Russell JO, et al. Ultrasound-guided radiofrequency ablation versus
surgery for low-risk papillary thyroid microcarcinoma: results of over 5 years' follow-up.
Thyroid. 2020;30(3):408–17.
28. Ding M, Tang X, Cui D, etal. Clinical outcomes of ultrasound-guided radiofrequency ablation
for the treatment of primary papillary thyroid microcarcinoma. Clin Radiol. 2019;74(9):712–7.
29. Suh CH, Baek JH, Choi YJ, Lee JH.Efcacy and safety of radiofrequency and ethanol ablation
for treating locally recurrent thyroid cancer: a systematic review and meta-analysis. Thyroid.
2016;26(3):420–8.
30. Zhang M, Luo Y, Zhang Y, Tang J.Efcacy and safety of ultrasound-guided radiofrequency
ablation for treating low-risk papillary thyroid microcarcinoma: a prospective study. Thyroid.
2016;26(11):1581–7.
31. Kim HJ, Cho SJ, Baek JH, Suh CH. Efcacy and safety of thermal ablation for autonomously functioning thyroid nodules: a systematic review and meta-analysis. Eur Radiol.
2021;31(2):605–15.
32. Sim JS, Baek JH.Long-term outcomes of thermal ablation for benign thyroid nodules: the
issue of regrowth. Int J Endocrinol. 2021;2021
33. Bernardi S, Giudici F, Cesareo R, etal. Five-year results of radiofrequency and laser ablation
of benign thyroid nodules: a multicenter study from the Italian minimally invasive treatments
of the thyroid group. Thyroid. 2020;30(12):1759–70.
34. Lim JY, Kuo JH. Thyroid nodule radiofrequency ablation: complications and clinical follow
up. Tech Vasc Interv Radiol. 2022;25(2):100824. ISSN 1089–2516. https://doi.org/10.1016/j.
tvir.2022.100824.
35. Kim J, Sun Z, Cummins M, etal. Implications of radiofrequency ablation in patients undergoing thyroid surgery for benign disease in the United States. Surgery. 2022;171(1):160–4.
R. A. Collins and J. H. Kuo
Part II
Parathyroid
Chapter 12
Parathyroid Anatomy andPhysiology
MandakiniVenkatramani andSeanM.Wrenn
Overview
• There are four parathyroid glands that classically reside posterior to the thy-
roid gland.
• The embryology of the parathyroid glands allows for anatomic variability in
parathyroid location.
• Parathyroid glands regulate calcium homeostasis by detecting hypocalcemia and
secreting parathyroid hormone. This affects calcium resorption, reabsorption,
and absorption in the bone, kidneys, and gastrointestinal tract.
Embryology
• The thyroid, parathyroid, and thymus originate from the embryonic pharyn-
geal region.
• During the sixth week of fetal development, parathyroid glands develop from the
endoderm of the third and fourth pharyngeal pouches (Fig.12.1).
– Inferior parathyroid glands originate from the third pharyngeal pouch (as
does the thymus).
– Superior parathyroid glands originate from the fourth pharyngeal pouch.
M. Venkatramani
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center,
New York, NY, USA
S. M. Wrenn (*)
Department of Surgery, Division of Surgical Oncology, Rush University Medical Center,
Chicago, IL, USA
Switzerland AG 2024
R. M. Gartland, J. A. Lee (eds.), Endocrine Surgery Clerkship, Contemporary
Surgical Clerkships, https://doi.org/10.1007/978-3-031-62091-1_12
103© The Author(s), under exclusive license to Springer Nature
104
I
Develops into tonsils
II
Develops into inferior PTG & thymus
III
Develops into superior PTG
IV
M. Venkatramani and S. M. Wrenn
Thyroid gland
Thymus
Fig. 12.1 Parathyroid embryology. The superior parathyroid glands (PTG) develop from the endoderm of the fourth pharyngeal pouch. The inferior PTG and thymus develop from the third pharyngeal pouch [1, 2], https://link.springer.com/chapter/10.1007/978- 3- 031- 07418- 9_2/gures/2
• Parathyroid glands develop high in the neck and travel caudally to their nal
anatomic locations. As a result, it is not uncommon to see parathyroid glands in
atypical places along their path of descent.
• Inferior glands must travel farther than superior glands and thus end up in ectopic
locations more often.
• Inferior glands originate and travel with the thymus, making the thymus a com-
mon location for an ectopic inferior gland.
Anatomy
• There are typically four parathyroid glands: right superior, left superior, right
inferior, and left inferior (Fig.12.2).
• Supernumerary glands have been found in up to 13% of autopsies.
• Ectopy of parathyroid glands is relatively common.
• The most common location for an ectopic superior parathyroid gland is in the
tracheoesophageal groove or retroesophageal space.
or
12 Parathyroid Anatomy andPhysiology
Fig. 12.2 Parathyroid
glands. There are four
parathyroid glands, two
superior and two inferior.
They are located on the
posterior aspect of the
thyroid gland [3], https://
www.researchgate.net/
gure/
Anatomical- location- ofthe- parathyroid- glandsposterior- view- modiedby- F- netter_
g2_342298993
Left superior
parathyroid
Left inferior
parathyroid
Right superior
parathyroid
Right inferi
parathyroid
105
• The most common location for an ectopic inferior parathyroid gland is in the
anterior mediastinum and cervical thymus.
Location
• Parathyroid glands usually lie on the posterior surface of the thyroid within a
connective tissue capsule and surrounded by fatty tissue.
• Superior parathyroid glands classically lie on the posterior aspect of the thyroid,
near the tracheoesophageal groove, 1cm above the intersection of the recurrent
laryngeal nerve and the inferior thyroid artery.
• Inferior parathyroid glands are classically on the posterior aspect of the inferior
pole of the thyroid gland.
• Relation between parathyroid and recurrent laryngeal nerve (Fig.12.3).
– Superior glands lie posterior to the nerve.
– Inferior glands lie anterior to the nerve.
• Parathyroid anatomy can be variable [4]. Other locations for glands include:
– Above the superior pole.
– Retropharyngeal or retroesophageal space.
– Thyrothymic ligament.
– Cervical thymus.
– Anterior mediastinum.
– Carotid sheath.
– Intrathyroidal.
106
M. Venkatramani and S. M. Wrenn
Superior
thyroid
artery
Inferior
thyroid
artery
Recurrent
laryngeal
nerve
Fig. 12.3 Relative location of parathyroid glands. The superior parathyroid glands are usually
1–2cm above the intersection of the recurrent laryngeal nerve and inferior thyroid artery. Superior
parathyroid glands lie posterior to the recurrent laryngeal nerve. The inferior parathyroid glands
have a variable location, but are often found near the inferior portion of the thyroid lobes and lie
anterior to the recurrent laryngeal nerve [5], https://www.uptodate.com/contents/image?imageKey
=SURG%2F56752
0.8%
2%
12%
80%
4%
0.2%
Area of
distribution
of superior
parathyroid
gland
0.8%
1%
1%
6%
2%
17%
44%
26%
2%
0.2%
Area of
distribution
of inferior
parathyroid
gland
Blood Supply
• Arterial blood supply to the parathyroid [6].
– Superior and inferior parathyroid glands typically get their blood supply from
branches of the inferior thyroid artery.
– However, they can also get their blood supply from the superior thyroid artery
and esophageal or muscular arterial branches.
– Most of the time, a single artery supplies a parathyroid gland.
– Generally, the superior pedicles are shorter than the inferior pedicles.
• Venous drainage of parathyroid glands.
– Parathyroid glands drain into superior, middle, and inferior thyroid veins.
• The shared blood supply and close proximity to the thyroid gland put the parathyroid glands at risk for damage or ischemia from thyroid surgery procedures
potentially leading to post-surgical hypoparathyroidism.
12 Parathyroid Anatomy andPhysiology
107
Gross Appearance
• Normal parathyroid glands are typically spherical or ovoid bodies that are somewhat attened.
• Normal glands measure 4–6mm in length, 3–4mm in width, and weigh about
35–40mg.
• A normal parathyroid gland is approximately the size of a grain of rice.
• The color of the gland varies with age:
– Newborn—gray/semi-transparent.
– Children—light pink.
– Adult—yellow/tan/brown.
Histology
• Parathyroid glands consist of:
– Chief cells—the primary cell, synthesizes and secretes parathyroid hor-
mone (PTH).
– Oxyphil cells—unclear function, quantity of oxyphil cells increases with age.
– Fibrovascular stroma—gives form to the gland, contains capillaries for
blood supply.
– Adipose tissue—fat cells, quantity increases with age [7].
Physiology
• The function of the parathyroid gland is to regulate calcium homeostasis [8].
• Parathyroid chief cells have calcium-sensitive receptors (CaSR) which detect
decreased serum calcium levels. This prompts secretion of parathyroid hormone (PTH).
• PTH works in a multifaceted way to increase serum calcium (Fig.12.4).
– Resorption—Bones.
PTH binds to osteoclasts which causes release of RANK ligands and
M-SCF. This then prompts osteoclasts to break down bone and release
both calcium and phosphate into the blood.
– Reabsorption—Kidney.
PTH causes increased calcium reabsorption at the distal convoluted tubule
and collecting duct.
108
M. Venkatramani and S. M. Wrenn
Fig. 12.4 Physiologic
effect of parathyroid
hormone (PTH). Calciumsensing receptors detect
decreased extracellular
calcium levels, which
prompts secretion of
(PTH). This in turn has
downstream effects on the
bone, kidney, and intestine
which, through distinct
mechanisms, help restore
normal extracellular
calcium levels [9], https://
entokey.com/
parathyroid- physiologyand- molecular- biology/
PTH causes decreased phosphate reabsorption at the proximal convoluted
tubule (PTH=phosphate trashing hormone).
PTH stimulates production of 1-alpha hydroxylase in the kidney, which
allows for the conversion of inactive 25 Vitamin D to 1.25 active vitamin D.
Bone
resorption
++
Ca
efflux
Bone
++
Ca
CaSR
PTH
Kidney
1,25 Dihydroxycholecalciferol
++
Ca
reabs.
reabs.
PO
4
++
Ca
Intestine
Ca
reabs.
PO
reabs.
++
4
– Absorption—GI tract.
Active Vitamin D acts on the GI tract to increase intestinal calcium
absorption.
– All together these effects increase extracellular calcium levels when they
are low.
• Negative feedback—Calcium-sensitive receptors in the parathyroid gland sense
normalization of calcium levels, and then turn off or downregulate serum PTH
secretion.
• Serum half-life of PTH is approximately 3min, and PTH is quickly removed
from the serum by the kidney and liver. This physiology allows for intraoperative
parathyroid hormone monitoring during parathyroidectomy.
• Chronic states of elevated PTH serum activity are called hyperparathyroidism,
and can be primary, secondary, or tertiary in nature. Underactive or low parathyroid hormone activity is called hypoparathyroidism.
12 Parathyroid Anatomy andPhysiology
109
References
1. Rosen RD, Bordoni B.Embryology, parathyroid. [updated 2022 may 8]. In: StatPearls [internet]. Treasure Island (FL): StatPearls Publishing; 2022.
2. Sakr MF. Embryology of the parathyroid glands. In: Parathyroid gland disorders. Cham:
Springer; 2022. https://doi.org/10.1007/978- 3- 031- 07418- 9_2.
3. Casarim A.Parathyroid glands and hyperparathyroidism: a general overview. 2020 https://doi.
org/10.5772/intechopen.92785.
4. Noussios G, Anagnostis P, Natsis K.Ectopic parathyroid glands and their anatomical, clinical
and surgical implications. Exp Clin Endocrinol Diabetes. 2012;120(10):604–10. https://doi.
org/10.1055/s- 0032- 1327628. Epub 2012 Nov 22
5. Lyden ML, Wang T, Sosa JA.Surgical anatomy of the parathyroid glands. In: UpToDate.
2022. https://www.uptodate.com/contents/surgical- anatomy- of- the- parathyroid- glands?sea
rch=locaiton+of+parathyroid+gland&source=search_result&selectedTitle=1~150&usage_
type=default&display_rank=1. Accessed 10 Jan 2023.
6. Ilahi A, Muco E, Ilahi TB.Anatomy, head and neck, parathyroid. [updated 2022 Aug 8]. In:
StatPearls [internet]. Treasure Island (FL): StatPearls Publishing; 2022.
7. Greeneld LJ, Mulholland MW, Doherty G.Parathyroid glands. In: Greeneld’s surgery: scientic principles and practice. LWW; 2012.
8. Clark OH, et al. Parathyroid embryology, anatomy and pathology. In: Textbook of endocrine surgery. 3rd ed. New Delhi, India: Jaypee Brothers Medical Publishers (P) Ltd; 2016.
p.627–36.
9. Hall J.Parathyroid hormone, calcitonin, calcium and phosphate metabolism, vitamin D, bone
and teeth. In: Guyton and Hall textbook of medical physiology. Chapter 79. 11ed. Philadelphia:
Saunders-Elsevier; 2011. Philadelphia 955–972.