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1 Endocrine Surgery: Historical Pearls andHow toBest Prepare forCases
3
Fortunately, with advancements in modern technology such as intraoperative nerve
monitoring, improved preoperative imaging, adjuncts such as laryngoscopy, along
with the knowledge gained by our surgical predecessors, laryngeal nerve injury is a
relatively rare complication in our modern era.
Additional innovations in diagnostics (improved cytopathologic accuracy of
biopsies), preoperative risk stratication (via molecular testing and genetic analysis), and advancements in postoperative management and surveillance have only
further propelled the evolution of thyroid surgery. The introduction of minimally
invasive and remote access techniques, along with non-operative therapies such as
radiofrequency ablation and evidence-based surveillance protocols, has empowered
patients with an array of treatment options like never before.
Parathyroid
Sir Richard Owen, curator of the London zoological gardens, is credited with the
rst accurate description of the parathyroid gland around 1850in an Indian rhinoceros. The human corollary was described 40 years later by Ivor Sandström, a
Swedish medical student [3]. As mentioned previously, tetany (ofcially coined in
1879 by Lucian Corvisart) following thyroidectomy troubled even the most skilled
surgeons. The classic constellation of signs in tetany include [13]:
• Trousseau’s sign: carpopedal spasm (wrist, metacarpal, and thumb exion with
nger hyperextension) following ination of a blood pressure cuff above systolic
pressures).
• Erb’s sign: increased excitability of muscles.
• Chvostek’s sign: ipsilateral facial muscle contraction in response to tapping the
facial nerve anterior to the ear.
The association between tetany and the parathyroid glands was not appreciated
until 1891, when Eugène Gley observed that dogs undergoing thyroidectomy only
developed tetany (and death) when concomitant parathyroidectomy was performed [14].
Advancements in the anatomical understanding of the parathyroid glands were
made by Halsted and Evans, who in 1907 delineated the vascular supply of the
parathyroids, cautioning against the ligation of the inferior thyroid artery, and
instead proposed selective ligation of the distal parathyroid arterial branch [15]. In
1909 Halsted performed the rst parathyroid autotransplantation in canines, and
reported a 61% success rate in transplantations [16]. Felix Mendl is credited with
performing the rst parathyroidectomy in 1925in Vienna. The rst parathyroidectomy performed in the United States took place at Massachusetts General Hospital
and involved a sea captain named Captain Charles Martell with severe primary
hyperparathyroidism. His adenoma proved elusive, and he would go on to require
six more parathyroid explorations before being successfully treated. Edward
Churchill was ultimately successful in identifying the ectopic substernal adenoma,
performing the rst reported mediastinal parathyroidectomy in the process [3].
4
M. B. Mulder and W. T. Shen
The complex interplay between diseases of the parathyroids, skeletal system, and
kidneys was discovered following several pivotal discoveries. The rst was made by
Friedrich Daniel von Recklinghausen, who is credited with providing the initial
case report of a patient with recurrent atraumatic long bone fractures, brosis, cysts,
and brown tumors [17]. While von Recklinghausen failed to correlate causation
with the parathyroids, his description of this condition (later termed osteitis brosa
cystica of von Recklinghausen) provided the context for Friedrich Schlagenhaufer
to later propose a hyperactive parathyroid to be the inciting culprit of this patient’s
bone disease [17]. Jacob Erdheim’s ndings (who is credited with describing parathyroid hyperplasia in the setting of osteomalacia) further conrmed the parathyroid’s role in demineralizing bone disease [18]. Developments by Fuller Albright
and his team furthered the understanding of the link between parathyroid disease
and chronic kidney disease by distinguishing primary, secondary, and tertiary
hyperparathyroidism as separate entities [18].
Reports crediting authorship of the initial description of PTH vary. However,
Ramussen and Craig were the rst to isolate and purify PTH biochemically, a discovery that afforded Berson and Yalow to then develop an immunoassay capable of
quantitating PTH levels. As a result, they were awarded the Nobel Prize in 1977
[18, 19].
Modern contributions including intraoperative PTH monitoring (which utilizes
interpretation of PTH decay dynamics in real-time to predict operative success) ,
improved preoperative localization studies, and intraoperative adjuncts (infrared
spectroscopy, exvivo parathyroid aspiration, intraoperative ultrasound) have revolutionized contemporary practice. As a result, minimally invasive, outpatient/sameday parathyroidectomy has become the preferred operation for the majority of
patients with primary hyperparathyroidism.
Adrenal
Historical references to the adrenal gland date back to ancient Greece. However,
Bartolomeo Eustachius in 1563 is credited with describing the adrenal gland as a
distinct entity, separate from the kidney. The preliminary correlation of the adrenals
with the nervous system was rst proposed by Thomas Wharton in 1656 when he
postulated the adrenals’ role in transferring substances from the nervous system into
circulation. His ndings catalyzed today’s understanding of the neuroendocrine
function of the adrenal medulla [20]. The adrenal medulla was distinguished from
the outer cortex in 1805 by Cuvier; however, the rst complete description of the
microscopic anatomy of the adrenal gland (including differentiation of the cortex
from the medulla) was provided by Albert von Kölliker in 1852 [21, 22].
A pivotal contribution establishing the adrenals’ central physiologic role was
published by Thomas Addison in 1855. Addison described the constellation of
symptoms of adrenal insufciency which Troisseau would later call Addison’s disease [21, 23]. In 1896, William Osler demonstrated temporary improvement in
1 Endocrine Surgery: Historical Pearls andHow toBest Prepare forCases
5
Addison’s disease using injectable adrenal extract [20]. While Addison described
the initial concept of hypercortisolism, Osler enhanced the description of the symptom complex ultimately named after Osler’s mentee Harvey Cushing [24]. Cushing
discovered the role of the adrenal cortex in hypercortisolism caused by pituitary
malfunction, providing the rst description of the classic features pathognomonic
for the eponymous disease [20]. Surgical attempts at treating Cushing’s syndrome
proved fatal without appropriate cortisol replacement therapy. Fortunately, the collaborative efforts of Mayo’s Edward Kendall and Phillip Hench and Zurich’s Tadeus
Reichstein led to the isolation of cortisone and its essential components by the late
1930s [20–22]. By 1950, cortisone was shown to be a successful replacement therapy following adrenalectomy for patients with Cushing’s syndrome [20, 22]. That
same year, Kendall, Hench, and Zurich were jointly awarded the Nobel Prize for
their discoveries [21].
The rst pheochromocytoma was described by Felix Fräenkel in 1886, although
the term wasn’t coined until 1912 by Ludwig Pick [20]. George Oliver and Edward
Sharpley-Schafer are credited with the discovery of a substance released by the
adrenal medulla that caused elevations in blood pressure. They named it adrenaline
and it was renamed epinephrine 2years later by John Abel [3, 22].
Like cortisol, the isolation of aldosterone was a collaborative effort again involving Reichstein along with Sylvia and Jim Tait in 1953. The syndrome of aldosterone
excess known as Conn’s syndrome was named after Jerome Conn who was the rst
to describe primary hyperaldosteronism in 1955 [3, 22].
The rst successful adrenalectomy (a 20-pound tumor later suspected to be an
adrenal cortical carcinoma) was performed by Knowsley Thornton in 1889. The
rst successful adrenalectomies for pheochromocytomas were performed in 1926
by Charles Roux in Switzerland and 7months later by Charles Mayo in the United
States [3, 22]. Early surgical approaches were transabdominal; however, posterior
and ank approaches were described in subsequent years. The development of laparoscopic surgery in the 1990s further advanced adrenalectomies with Michel Gagner
performing the rst successful laparoscopic adrenalectomy in 1992 [22]. The laparoscopic approach, both transabdominal and retroperitoneal, has been widely
adopted in the ensuing years and today is the preferred approach for most adrenal tumors.
How toBest Prepare forCases
• Preoperative Preparation: Extensively review the patient’s clinical history, with
the key components outlined below:
– History:
Patient’s initial presentation (if symptomatic).
Time course of symptoms (diagnosis to treatment) or changes.
Diagnostics/workup to establish the diagnosis.
6
M. B. Mulder and W. T. Shen
– Imaging results:
Size, proximity to critical structures, locoregional or distant metastasis or
invasion?
Features associated with malignancy?
– Biopsy results:
For thyroid be sure to review the Bethesda classication and the implications of the results.
(Relatively rare for parathyroids or adrenals to undergo biopsies).
– Labs:
Thyroid: TSH/thyroid function panel, calcium.
Parathyroids: PTH, calcium, vitamin D, phosphate, renal function.
Adrenals: variable depending on the type of lesion.
– Patient-specic factors that could complicate or alter the surgical plan:
Comorbidities.
Body habitus: Short neck, central obesity, etc., may inuence the approach
and operative strategy.
Medications:
Anticoagulants? (Endocrine organs are highly vascular).
Preoperative regimens? i.e., Lugol’s for Graves, alpha/beta-blockade
for pheochromocytomas, etc.
Previous operations or interventions (including anterior cervical surgery
for neck operations and history of radiation).
– **If the patient is presenting with recurrence:
Biopsy results, initial pathology, genetic testing if concerned for familiar
or syndromic association, evaluation of the lateral and central neck, vocal
cord evaluation.
– Familiarization with the critical steps in the operation, including review of the
pertinent anatomy.
– Practice (knot tying, suturing, etc.) and bring your muscles! (you may be
requested to assist in retracting).
• Perioperative Preparation:
– Introduce yourself to staff prior to the case.
– Obtain your gloves for the scrub tech.
– Teamwork!
– Standout students help the circulator or resident with tasks to optimize patient
care and safety and efciently begin the case.
– Intraoperative nerve monitoring, ultrasound, or energy devices may be used
so familiarity with setup and the general principles of use may be helpful.
1 Endocrine Surgery: Historical Pearls andHow toBest Prepare forCases
7
References
1. Sarkar S, Banerjee S, Sarkar R, Sikder B.A review on the history of “Thyroid Surgery”. Indian
J Surg. 2016;78(1):32–6.
2. Haddad FS.Abulcasis. Abbottempo. 1968;3:22–5.
3. Brunicardi FC, Andersen DK, Billiar TR, Dunn DL, Kao LS, Hunter JG, et al., editors.
Schwartz’s principles of surgery. 11th ed. NewYork, NY: McGraw-Hill Education; 2019.
p.3179.
4. O’Malley CD, de Saunders CM, editors. Leonardo on the human body. Mineola, NY: Dover
Publications; 1983.
5. Liston R.Lectures on the operations of surgery: and on diseases and accidents requiring operations. Philadelphia, PA: Lea and Blanchard; 1846.
6. Gross SD.A system of surgery v.1, vol. 1. Philadelphia, PA: HC Lea’s son; 1882.
7. Halsted WS.The operative story of goiter. Johns Hopkins Hos Rep. 1920;19:175.
8. Becker WF.Presidential address: pioneers in thyroid surgery. Ann Surg. 1977;185(5):493–504.
9. Haeger K.The illustrated history of surgery. London: Harold Starke; 1998.
10. Ord WM. On Myxœdema, a term proposed to be applied to an essential condition in the
“Cretinoid” affection occasionally observed in middle-aged women. Med Chir Trans.
1878;61:57–78.5.
11. Kocher T.Ueber Krophfexstirpation und ihre Folgen. Arch Klin Chir. 1883;29:254–337.
12. Kaplan EL, Salti GI, Roncella M, Fulton N, Kadowaki M.History of the recurrent laryngeal
nerve: from Galen to Lahey. World J Surg. 2009;33(3):386–93.
13. Moftt HC.Tetany in adults. J Am Med Assoc. 1911;57(6):452–8.
14. Kokenge F. The history of the parathyroid glands—a contribution to the history of the
parathyroid glands, their anatomy, function and their diseases. Laryngorhinootologie.
2022;101(8):646–51.
15. Halsted WS, Evans HM.I. The parathyroid Glandules. Their blood supply and their preservation in operation upon the thyroid gland. Ann Surg. 1907;46(4):489–506.
16. Halsted WS.Auto- and isotransplantation, in dogs, of the parathyroid glandules. J Exp Med.
1909;11(1):175–99.
17. Eknoyan G.A history of the parathyroid glands. Am J Kidney Dis. 1995;26(5):801–7.
18. Kalra S, Baruah MP, Sahay R, Sawhney K.The history of parathyroid endocrinology. Indian J
Endocrinol Metab. 2013;17(2):320–2.
19. Sosa JA, Udelsman R.The parathyroid glands. In: Townsend C, editor. Sabiston textbook of
surgery. 19th ed. Amsterdam: Elsevier; 2012. p.925.
20. Papadakis M, Manios A, Schoretsanitis G, Trompoukis C.Landmarks in the history of adrenal
surgery. Hormones. 2016;15:136–41.
21. Yeh M, Duh Q-Y. The adrenal glands. In: Townsend C, editor. Sabiston textbook of surgery.
19th ed. Amsterdam: Elsevier; 2012. p.963.
22. Fleming B. History of adrenal surgery. 2010. http://www.endocrinesurgery.net.au/
adrenal- history.
23. Pearce JMS.Thomas Addison (1793–1860). J R Soc Med. 2004;97(6):297–300.
24. Cushing H.William Osler, the man. Ann Med Hist. 1919;2(2):157–67.
Part I
Thyroid
Chapter 2
Thyroid Gland Anatomy andPhysiology
FrederickThurstonDrake
Introduction
In-depth knowledge of the embryology and anatomy of the thyroid gland, and, in
particular its relationships with nearby nerves and blood vessels, is crucial to performing safe surgery on this organ. Moreover, thyroid gland physiology is uniquely
related to surgical decision-making and the pre- and post-operative care of patients
with operative thyroid disease.
Embryology [1]
• The primordial thyroid appears at day 22 of gestation and is the rst endocrine
gland to develop.
• Initially, the lateral and medial components of the thyroid develop separately.
• The medial component begins in the pharynx as an epithelial proliferation at the
border of the rst and second pharyngeal pouches. Following initial development, the thyroid detaches from the pharynx and descends to arrive in its ultimate position on the anterior surface of the trachea.
• The two lateral parts arise from the fourth and fth pharyngeal pouches, and their
cell of origin is the neural crest (ultimately to become parafollicular C cells). The
lateral components descend and fuse with the medial aspect of the thyroid by the
fth week of gestation.
F. T. Drake (*)
Boston University Chobanian and Avedisian School of Medicine, Boston Medical Center,
Boston, MA, USA
e-mail: Frederick.Drake@bmc.org
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_2
11© The Author(s), under exclusive license to Springer Nature
12
tilage
Th
stemum
F. T. Drake
• The thyroglossal duct connects the base of the tongue to the thyroid, but in most
people, this obliterates later in gestation.
• In the second month of gestation, thyroid follicles begin to appear, and colloid is
apparent within them by the end of the third month. The fetal thyroid begins to
secrete thyroid hormone sometime within 10–12weeks of gestation.
Anatomy
The word “thyroid” comes from the Greek word for “shield.” The thyroid gland is
comprised of two lateral lobes which are joined by an isthmus that bridges the two
lobes across the anterior surface of the trachea (Fig.2.1). A pyramidal lobe sometimes protrudes superiorly from the isthmus. Small case series have suggested that
Hyoid bone
Superior
thyroid artery
yroid cartilage
of larynx
Superior
thyroid vein
Common
carotid artery
Right lobe of
thyroid gland
Middle thyroid
vein
Thyrocervical
trunk
Trachea
Outline of
clavicle
Outline of
Internal
jugular vein
Cricoid car
of larynx
Left lobe of
thyroid gland
Isthmus of
thyroid gland
Inferior
thyroid artery
Inferior
thyroid
veins
Fig. 2.1 The thyroid gland and associated blood vessels. Source: Stathatos [11]. (*Note this image
is already reprinted from: Anatomy of the thyroid gland. Martini etal. [12])
2 Thyroid Gland Anatomy andPhysiology
a pyramidal lobe is present in 43–55% of patients, with a slight left-sided predominance [1].
The thyroid gland is bounded by the following anatomic structures when consid-
ered in a cross section of the transverse orientation [1, 2] (Fig.2.2):
• Laterally, the thyroid is bordered by the carotid sheath on each side.
• The posteromedial aspect of the right and left lobe is bounded by the trachea and
esophagus. More laterally, deep to the lobes of the thyroid gland, is the prevertebral layer of deep cervical fascia, which overlies the longus coli muscles and
cervical vertebrae.
• Anteriorly (supercially), the sternothyroid and sternohyoid muscles cover the
gland and are themselves covered by the platysma.
• The thyroid gland itself is covered in the pretracheal layer of deep cervical fascia,
a condensation of which connects the thyroid to the trachea at the rst and second tracheal rings and is known as Berry’s ligament.
13
Arterial Blood Supply [1] (Fig.2.1)
• Superior thyroid artery—rst branch of the external carotid artery.
• Inferior thyroid artery—a branch of the thyrocervical trunk, which arises from
the subclavian artery bilaterally.
• The thyroidea ima artery has a variable origin and is found in a small minority
of cases.
• The rich plexus of blood vessels within the thyroid gland itself allows left-right
vascular communication via the isthmus.
Venous Drainage [1] (Fig.2.1)
• Superior, middle, and inferior thyroid veins.
• Left/right variability is common, for example, one side may have a middle thy-
roid vein, but this may be absent for the contralateral lobe.
• The inferior thyroid veins commonly form a single trunk to drain into either the
left brachiocephalic vein (approximately 61%) or the right brachiocephalic vein
(approximately 26%).
14
St
Trachea
Vertebral a.
F. T. Drake
Platysma
Recurrent
laryngeal n.
Esophagus
Inf. thyroid a.
ernocleidomastoid
Sympathetic
trunk
Phrenic n.
Cervival n. V
Middle and
posterior scalene
Fig. 2.2 Thyroid gland and associated structures in the transverse view. Source: Amdur and
Mazzaferri [2]
Sternohyoid
Cervical
vertebra VII
Sternothyroid
Thyroid gland
Common carotid a.
Vagus n.
Int. jugular v.
Ant. scalene
Cervical n. VI
Longus colli
Nerves
• Recurrent laryngeal nerve (RLN): a branch of the vagus nerve, the RLN inner-
vates the intrinsic muscles of the larynx; it enables motor control of the vocal
folds and thus phonation. The right RLN courses around the subclavian artery
and enters the neck at a more lateral position compared to the left RLN, which
courses around the aortic arch at the ductus arteriosa. The RLN may branch prior
to entry into the larynx, and surgeons may identify a small esophageal and/or
pharyngeal branch coursing posteriorly. The anterior branch is thought to carry
the motor bers to the intrinsic laryngeal muscles [1, 3].
• Most commonly, the RLN passes deep (posterior) to the inferior thyroid artery or
its terminal branches, but this is highly variable. It is almost always deep to the
middle thyroid vein [1].
• RLN injuries [3]
– Unilateral injury most commonly causes hoarseness and, less often, swallow-
ing problems.
– Bilateral injury can cause airway loss if both vocal folds are paralyzed in the
paramedian position.