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Chapter 17
Adrenal Gland Anatomy andPhysiology
AlexisL.Woods andClaireE.Graves
Introduction/Overview
The adrenal glands were rst described in 1552 but their function was a mystery
until 1855 when Thomas Addison described, and Brown-Séquard’s experiments the
following year showed, that they were essential to life [1]. The adrenals are golden
yellow retroperitoneal organs, laying just superior to the kidneys (hence “suprarenal
glands”) at the level of T11-12 [1]. They’re highly vascularized organs, with two
distinct components that have separate functions, the cortex and medulla. The cortex produces mineralocorticoids, glucocorticoids, and androgens. Mineralocorticoids
play an important role in regulating blood pressure and electrolyte balance.
Glucocorticoids modulate the immune system, blood sugar, and metabolism through
the hypothalamic-pituitary-adrenal (HPA) axis, while androgens are important for
developing secondary sexual characteristics. The medulla produces norepinephrine
(NE) and epinephrine (Epi), which activate alpha- and beta-adrenergic receptors.
Anatomic Relationships [1–3]
• Adrenal glands are located superior and slightly medial to the kidneys on both
sides (see Fig.17.1).
• The left is crescent-shaped, and the right is pyramidal-shaped.
• The right adrenal is bounded by the retrohepatic vena cava and right lobe of liver
anteriorly and the psoas and diaphragm posteriorly.
A. L. Woods · C. E. Graves (*)
Department of Surgery, University of California Davis, Sacramento, CA, USA
e-mail: alwoods@ucdavis.edu; cegraves@ucdavis.edu
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_17
155© The Author(s), under exclusive license to Springer Nature
156
A. L. Woods and C. E. Graves
Inferior vena cava
Right inferior phrenic artery
Right adrenal vein
Right adrenal gland
Right inferior
adrenal artery
Right kidney
Abdominal aorta
Right renal artery
Fig. 17.1 Adrenal anatomical location and blood supply
Right renal vein
Middle adrenal arteries
Left inferior phrenic artery
Left adrenal gland
Left renal vein
Left renal artery
Left inferior
phrenic vein
Left adrenal
vein
Left kidney
Left inferior
adrenal artery
• The left adrenal lies between the kidney and the aorta. The tail of the pancreas,
stomach, and splenic hilum are anterior to the gland, with the psoas and diaphragm posterior.
• Adrenals are surrounded by a capsule (see Fig.17.2) and then surrounded by fat
and Gerota’s (perirenal) fascia with the kidneys.
Adrenal Gland Anatomy [2, 4]
Adrenal Cortex
• Outer zone composes 80–85% of adrenal tissue.
• Three distinct layers, secreting adrenocortical steroid hormones (see Fig.17.2).
– Outer—Zona Glomerulosa: produces mineralocorticoids (aldosterone)—
thin layer.
– Middle—Zona Fasciculata: produces mostly glucocorticoids (cortisol)—
most prominent layer.
– Inner—Zona Reticularis: produces mostly androgens (deoxyhydroepiandros-
terone [DHEA], androstenedione).
17 Adrenal Gland Anatomy andPhysiology
Fig. 17.2 Adrenal gland
pathology slide
(underlying image
obtained from public
domain and modied by
authors)
– *Mnemonic: layers from outside to in acronym: GFR: Salt, Sugar, Sex -the
layers from outside to in make salt (mineralocorticoids), sugar (glucocorticoids), and sex hormones (androgens).
157
Adrenal Medulla
• The inner zone, approximately 15–20% of the tissue (see Fig.17.2).
• Secretes the catecholamines Epi and NE.
Embryology [1, 2]
Adrenal Cortex
• Cortex is of mesodermal origin.
• By gestational week 8, adrenal cortex differentiates. Produces fetal adrenal ste-
roids throughout intrauterine life.
• After birth, the fetal adrenal cortex involutes and the three-layered adult cortex
replaces it by age 10–20years old.
Adrenal Medulla
• Medulla is of neuroectodermal origin.
• Neural crest cells migrate and differentiate into chromafn cells.
158
• Epi is present by third month of life.
• Ectopic medullary tissue along abdominal aorta or sympathetic chain are called
organs of Zuckerkandl.
A. L. Woods and C. E. Graves
Vascular Supply andDrainage (See Fig.17.1) [1, 3, 4]
• Arterial supply is from three vessels.
– Superior adrenal arteries from inferior phrenic arteries.
– Middle adrenal arteries from aorta, near celiac plexus.
– Inferior adrenal arteries from renal arteries (most prominent).
– Anatomic variants also include branches from intercostal, left ovarian, or left
internal spermatic arteries.
– Arteries are typically so small that they are often not distinctly identied dur-
ing adrenalectomy.
• Venous drainage.
– Left adrenal vein is approximately 2cm long and joins left inferior phrenic
vein, and they collectively drain into the left renal vein.
– Right adrenal vein is short (0.5cm) and typically drains directly into the infe-
rior vena cava (in 20% drains into accessory right hepatic vein).
– Veins are always identied, isolated, ligated, and divided during
adrenalectomy,
Lymphatics [1]
• Two plexuses, one in medulla and one just deep to capsule.
• Drainage usually via the lateral aortic lymph nodes (LNs) and para-aortic LNs.
• Lymphatics can also go through diaphragm to thoracic duct or posterior medias-
tinum; in adrenal cortical cancer, metastases can be found in these locations.
Innervation
Adrenal Cortex [1, 5]
• Function mediated by both hormonal and synaptic stimulation.
• Receives vasomotor sympathetic nerve supply on subcapsular arteriolar plexus.
• The subcapsular plexus and zona glomerulosa also are innervated by nerves
releasing vasoactive intestinal polypeptide and neuropeptide Y.
17 Adrenal Gland Anatomy andPhysiology
159
Adrenal Medulla
• Innervated by myelinated cholinergic preganglionic nerve bers (type B) from
T5-T8 segments, which become the greater splanchnic nerve after bypassing the
sympathetic trunk.
• Some greater splanchnic nerve bers go to celiac ganglion, which then inner-
vates the arteries supplying the adrenal gland.
• Some greater splanchnic nerve bers directly synapse on the muscarinic recep-
tors on chromafn cells in the medulla.
Biochemistry [1, 2, 4]
Adrenal Cortex
• Zona Glomerulosa: produces mineralocorticoids (aldosterone).
– Needs ACTH for rst step of steroid synthesis (cholesterol desmolase) but
after is regulated by the renin-angiotensin system and blood potassium levels.
– Renin-angiotensin-aldosterone system:
Decreased renal perfusion pressure (hypovolemia or low Na+ to distal convoluted tubule) stimulates release of renin from renal juxtaglomerular
apparatus.
Renin converts angiotensinogen (made in liver) to angiotensin
I. Angiotensin- converting enzyme (ACE, in lungs) converts angiotensin
I to II.
Angiotensin II (via IP3 mechanism) acts on zona glomerulosa by increasing conversion of corticosterone to aldosterone (see Fig.17.3).
Aldosterone increases renal Na+ reabsorption and H+/K+ secretion (see
Table17.1).
Angiotensin II also increases SVR, increases ADH release and H20
reabsorption.
– Hypokalemia suppresses renin and decreases aldosterone release, therefore
decreasing K+ secretion and restoring K+ levels.
• Zona Fasciculata: produces mostly glucocorticoids (cortisol, corticosterone).
– Secretion oscillates in a 24-h period, with levels highest just before waking
(~8a.m.) and lowest in the evening (~midnight) [4].
– Regulated by the hypothalamic-pituitary axis. CRH released from hypothala-
mus stimulates ACTH release from the anterior pituitary. ACTH then works
via cAMP mechanism, stimulating cholesterol desmolase and increasing steroid hormone synthesis in all zones of adrenal cortex through conversion of
cholesterol to pregnenolone (see Fig.17.3).
160
A. L. Woods and C. E. Graves
Fig. 17.3 Adrenal corticosteroid synthesis pathway (Adapted from Costanzo Physiology, 5th Edition)
17 Adrenal Gland Anatomy andPhysiology
Table 17.1 Actions of adrenocortical steroids (heavily adapted from Costanzo Physiology, 5th
Edition)
Mineralocorticoids Glucocorticoids Adrenal androgens
⇑ H+ and K+
secretion
⇑ Na+ reabsorption ⇓ insulin sensitivity, glucose
⇑ lipolysis, proteolysis,
gluconeogenesis
utilization
Inhibit inammatory and immune
responses
⇑ glomerular ltration rate
Inhibit bone formation
⇓ REM sleep
⇑ vascular response to
catecholamines
Has same effect as testosterone in
males
Stimulates axillary and pubic hair
growth in females
Stimulates libido in females
161
– Cortisol has negative feedback on CRH and ACTH secretion (see Fig.17.4).
– Cortisol is required for the stress response and increases gluconeogenesis,
glycogen depletion, insulin resistance. Also increases lipolysis (see
Table17.1).
– Glucocorticoids also have anti-inammatory properties by inhibiting prosta-
glandins and leukotrienes upstream. They also inhibit the release of histamine
and serotonin from platelets and mast cells.
– Cortisol increases vascular responsiveness to catecholamines through upregu-
lation of receptors on arterioles.
– Glucocorticoids are used as transplant anti-rejection medications because
they suppress immune response through inhibition of T lymphocytes and IL-2
production.
• Zona Reticularis: produces mostly androgens (DHEA, DHEA-S, andro-
stenedione).
– Regulated by ACTH, through same pathway as above. Zona reticularis has
17,20-lyase, cleaving the 21-carbon precursors and creating 19-carbon DHEA
or androstenedione (see Fig.17.3).
– DHEA/androstenedione are weakly androgenic but converted to testosterone
in the testes. Testes also make de novo testosterone and adrenal androgens are
not required.
– Small amounts of testosterone and 17β-estradiol are also produced.
• Arenal Corticosteroid Synthesis (see Fig.17.3).
– Cholesterol enters cortex cells from bloodstream (cortex also produces a
small amount de novo), undergoes oxidative reactions catalyzed by cytochrome p450, and creates different enzymes in different cortical
layers [2].
– All layers contain cholesterol desmolase and which is the rate-limiting
enzyme in the pathway.
162
Fig. 17.4 Hypothalamicpituitary- adrenal (HPA)
axis feedback loop
(Adapted from Costanzo
Physiology, 5th Edition)
A. L. Woods and C. E. Graves
Adrenal Medulla [1, 2, 4, 6]
• Specialized ganglion of the sympathetic nervous system, where preganglionic
(greater splanchnic) bers synapse on chromafn cells.
• Chromafn cells synthesize and release catecholamines into blood stream (Epi,
NE, and dopamine).
• The rate-limiting step of catecholamine synthesis is the hydroxylation of tyro-
sine (see Fig.17.5).
• Phenylethanolamine N-methyltransferase (PNMT) is only in chromafn cells of
organ of Zuckerkandl and adrenal medulla and this converts NE to Epi (only
places Epi is made, sympathetic neurons only make NE).
• Cortisol drives the expression of PNMT.
• Basal secretion is low. Stress (e.g., surgery or trauma) signicantly increases Epi
secretion.
• Output from medulla is ~80% Epi and 20% NE.
• Epi and NE both activate α1 causing arterial and venous vasoconstriction, and α2
receptors in multiple locations with varied effects.
• Epi activates β1 receptors (increasing contractile force and HR) and β2 (smooth
muscle relaxation), NE activates β1 only.
• Epi and NE are inactivated by monoamine oxidase and catechol-0-
methyltransferase to vanillylmandelic acid (VMA).
17 Adrenal Gland Anatomy andPhysiology
Fig. 17.5 Epinephrine
synthesis (heavily adapted
from Textbook of
Endocrine Surgery, 3rd
Edition)
163
References
1. Clark OH, Duh Q-Y, Kebebew E, Gosnell JE, Shen WT.Textbook of endocrine surgery. JP
Medical Ltd; 2016.
2. Costanzo LS. Chapter 7, endocrine physiology. In: Physiology board review series. 5th ed.
Philadelphia, PA: Saunders/Elsevier; 2013. p.235–42.
3. Netter FH.Atlas of human anatomy, professional edition E-book: including NetterReference.
com access with full downloadable image Bank. Elsevier Health Sciences; 2014.
4. Yeh MW, Livhits MJ, Duh QD.Chapter 39: the adrenal glands. In: Townsend B, Evers M,
editors. Sabiston textbook of surgery: the biological basis of modern surgical practice.
Elsevier; 2016.
5. Megha R, Werle CJKS, Leslie SW.Anatomy, abdomen and pelvis, adrenal glands (suprarenal
glands). StatPearls; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482264
6. Motiejunaite J, Amar L, Vidal-Petiot E. Adrenergic receptors and cardiovascular effects of
catecholamines. Ann Endocrinol (Paris). 2021;82:193–7.
Chapter 18
Adrenal Incidentaloma: Differential
Diagnosis andWorkup
BenjaminJames andNataliaChaves
Overview [1, 2]
• Adrenal incidentalomas are present in approximately 2% of the general
population.
• 10% of patients present with autonomous secretion of adrenal hormones.
• Management of patients with adrenal incidentalomas should involve a multidis-
ciplinary team including endocrinologists, surgeons, radiologists, and
pathologists.
• For most surgical indications, minimally invasive adrenalectomy is the gold
standard.
General Information [1–3]
• Adrenal incidentalomas (AI) are adrenal masses that are >1cm discovered dur-
ing abdominal imaging performed for reasons other than suspected adrenal
disease.
• Incidence has been increasing and approaches 8.7%.
• Prevalence varies by diagnostic approach and patient’s age:
B. James (*)
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
Harvard Medical School, Boston, MA, USA
e-mail: bjames1@bidmc.harvard.edu
N. Chaves
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
e-mail: nchaves1@bidmc.harvard.edu
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_18
165© The Author(s), under exclusive license to Springer Nature