Adrenal Gland Fx Normal Dx Anatomy Multimodality Applied Anatomy

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The Adrenal Gland
A memory image reflecting its 3 major function. The wide eyes and dilated pupils reflect ffright fight and flight, water dripping from its mouth reflect water metabolism and salt spewing reflects salt metabolism . Ashley Davidoff MD TheCommonVein.com 140229-01.adrenal

2. Definition


The adrenal glands are paired endocrine organs located above the kidneys, part of both the endocrine and autonomic stress-response systems, acting as the body’s hormonal emergency centers.
  • Each gland has two functionally distinct regions: the cortex (steroid production) and medulla (catecholamine production).

  • They regulate metabolism, blood pressure, immune response, and acute stress adaptation.

  • Common diseases include Cushing’s syndrome, Addison’s disease, and pheochromocytoma.

  • Diagnosis involves hormonal assays, CT/MRI, and stimulation/suppression tests; treatment may be medical or surgical depending on etiology. |


Core Element Summary
Structure Bilateral glands with cortex (zona glomerulosa, fasciculata, reticularis) and medulla (chromaffin cells)
Function Receive hypothalamic-pituitary signals → produce corticosteroids and catecholamines → modulate homeostasis and stress
Common Diseases Addison’s disease, Cushing’s syndrome, pheochromocytoma
Diagnosis ACTH test, serum cortisol, plasma metanephrines, CT/MRI
Treatment Hormone replacement, tumor resection, medical suppression (e.g., ketoconazole)
Section/Subsection Content (Text + Insert Images Where Desired)
Title Applied Anatomy of the Adrenal Glands
 
Definition The adrenal glands (suprarenal glands) are paired endocrine organs located superior and medial to the kidneys. They are essential for life, synthesizing steroid

  • Most Unique Features
  • Dual structure and function:
    • cortex for steroids,
    • medulla for catecholamines.

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Adrenal Function Aldosterone is responsible for water and salt balance which in turn is intimately related to blood pressure control. Cortisol, is responsible for responding to physically stressful situations. Androgens are responsible for developing male characteristics. The medulla produces adrenaline which is responsible for urgent “fight or flight” situations. (Image courtesy of Ashley Davidoff M.D.) code adrenal anatomy physiology Davidoff art 39516 adrenals-0007

Adrenal Asymmetry As a paired organ you would think that they would be perfectly symmetrical, like the hands or feet, but in fact they look quite different, particularly in cross-section. The right tends to be long and thin and the left short and stout.Images Courtesy of: Ashley Davidoff, M.D. adrenals-0003

Structure and/or Function Cortex: Outer layer producing mineralocorticoids, glucocorticoids, and androgens. – Medulla: Inner core producing epinephrine and norepinephrine.
Composed Of (Major Parts/Units) – Capsule – Cortex: zona glomerulosa, zona fasciculata, zona reticularis – Medulla
Common Diseases – Addison’s disease (hypofunction) – Cushing’s syndrome (hypercortisolism) – Pheochromocytoma (catecholamine-producing tumor) – Adrenal incidentalomas (usually benign)
Diagnosis Most Common  
Clinical Presentation Addison’s: fatigue, hypotension, hyperpigmentation. Cushing’s: obesity, hypertension, purple striae. Pheochromocytoma: episodic hypertension, sweating, palpitations.
Imaging Characteristics CT: Masses characterized by size, attenuation (HU), washout. – MRI: Lipid content (chemical shift imaging); pheochromocytomas are T2 hyperintense.
Labs – Cortisol levels and ACTH stimulation test – Plasma and urinary metanephrines (pheochromocytoma) – Aldosterone/renin ratio (primary hyperaldosteronism)
Rx – Addison’s: Lifelong steroid replacement. – Cushing’s: Surgical resection. – Pheochromocytoma: Preoperative alpha-blockade then surgery.
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History Discovered in the 16th century by Eustachius; Addison in 19th century linked adrenal failure to clinical disease.
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Anatomy: Parts Cortex and medulla with functional and embryological differences.
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Size Length: 4–6 cm Width: 2–4 cm Thickness: ~1 cm Weight: ~4–5 grams
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Shape – Right adrenal: Pyramidal. – Left adrenal: Crescent-shaped.
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Position – Right: Posterior to liver, adjacent to IVC. – Left: Posterior to stomach and pancreas, adjacent to aorta.
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Character Yellowish cortex due to lipid content; reddish-brown vascular medulla.
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Time (Embryology) – Cortex: Derived from mesoderm. – Medulla: Derived from neural crest cells. Development begins around the 6th week of gestation.
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Blood Supply – Superior suprarenal arteries (from inferior phrenic) – Middle suprarenal arteries (from abdominal aorta) – Inferior suprarenal arteries (from renal artery)
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Venous Drainage – Right adrenal vein drains into the IVC. – Left adrenal vein drains into the left renal vein.
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Lymphatic Drainage Lymph flows into paraaortic (lumbar) lymph nodes.
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Nerve Supply – Preganglionic sympathetic fibers directly innervate medullary chromaffin cells, enabling rapid catecholamine release.
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Physiology The adrenal glands play a vital role in stress response, metabolism, blood pressure regulation, and sexual development.
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Receives Substrates for steroid and catecholamine synthesis via arterial blood and direct sympathetic innervation.
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Processes – Cortex: Converts cholesterol into corticosteroids and androgens. – Medulla: Synthesizes epinephrine and norepinephrine from tyrosine.
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Exports – Cortex: Cortisol, aldosterone, androgens into systemic circulation. – Medulla: Rapid release of catecholamines into bloodstream during stress.

3. Anatomy


Page 3 – Normal


🔹 Table 1 – U-SSPCT–C Structural Features

Category Element Description
Unit Subcomponents Cortex (zona glomerulosa, fasciculata, reticularis), medulla (chromaffin cells)
Size Volume and weight ~4–6 cm in length; ~4–6 grams per gland
Shape Contour and form Right: triangular; Left: crescent-shaped
Position Location and relations Retroperitoneal, superior to kidneys; embedded in perirenal fat
Character Tissue type and texture Cortex: firm, yellow; Medulla: soft, reddish-brown
Time Development and aging Arise from mesoderm (cortex) and neural crest (medulla); fully formed by birth; cortex involutes with age
Connections – Arterial Supply Arteries Superior, middle, and inferior suprarenal arteries (branches of inferior phrenic, aorta, and renal arteries)
Connections – Venous Drainage Veins Right adrenal vein drains to IVC; left adrenal vein drains to left renal vein
Connections – Lymphatic Drainage Lymphatics Drain to lumbar (para-aortic) lymph nodes
Connections – Nerve Supply Nerves Preganglionic sympathetic fibers innervate medulla; stimulate catecholamine release

🔹 Table 2 – Functional Model: Receive → Process → Export

Phase Component Description
Receive Hypothalamic and pituitary signals; sympathetic input ACTH stimulates cortex; sympathetic fibers stimulate medulla
Process Hormone synthesis Cortex: mineralocorticoids (zona glomerulosa), glucocorticoids (zona fasciculata), androgens (zona reticularis)
Medulla: epinephrine, norepinephrine    
Export Hormonal output Cortisol, aldosterone, DHEA, epinephrine, norepinephrine into systemic circulation to regulate stress, BP, metabolism, electrolytes

4. Disease and Diagnosis


Page 4 – Disease and Diagnosis (Finalized)


🔹 Table 1 – Disease Categories and Global Effects

Category Pathologic Process Global Anatomic Change
Inflammatory Autoimmune adrenalitis (Addison’s) Gland atrophy, cortex destruction
Infection Tuberculosis, fungal infections Caseating necrosis, gland calcification
Neoplasm – Benign Adrenal adenoma Small, well-defined non-invasive nodule
Neoplasm – Malignant Adrenocortical carcinoma, metastasis Large, irregular mass, invasive
Mechanical Mass effect from adjacent structures Compression or displacement of gland
Trauma Hemorrhage (e.g., in sepsis or injury) Swollen, heterogeneous glands
Metabolic Congenital adrenal hyperplasia (CAH) Bilateral enlargement, nodular cortex
Circulatory Infarction, venous thrombosis Hemorrhage, necrosis
Inherited CAH, MEN syndromes Hyperplasia or neoplasia depending on mutation
Infiltrative Amyloidosis, hemochromatosis Gland infiltration, structural degradation
Idiopathic Primary aldosteronism (idiopathic hyperplasia) Diffuse cortical thickening
Iatrogenic Chronic corticosteroid use Cortical atrophy from ACTH suppression
Functional Cushing’s, pheochromocytoma, Conn syndrome Hormonal excess ± structural change
Psychiatric N/A
Psychological N/A

🔹 Table 2 – Anatomic-Pathologic Correlation and Imaging

Disease Example U-SSPCT–C Changes Imaging Appearance
Addison’s disease Unit: Cortex affected Size: Atrophic Shape: Flattened Character: Homogeneous, small Time: Chronic Connections: Loss of ACTH stimulation; TB may cause calcification CT/MRI: Bilateral small glands; may show calcifications (if infectious)
Adrenal adenoma Unit: Solitary cortical nodule Size: <4 cm Shape: Round/oval Character: Lipid-rich, homogeneous Time: Incidental/slow-growing Connections: Well-demarcated CT: <10 HU, rapid contrast washout MRI: Signal drop on out-of-phase imaging
Pheochromocytoma Unit: Medullary tumor Size: 2–6+ cm Shape: Irregular Character: Hypervascular, heterogeneous Time: Intermittent symptoms Connections: Sympathetic innervation MRI: T2 bright (“light bulb”); avid enhancement CT: Enhancing mass
Adrenocortical carcinoma Unit: Infiltrative tumor Size: >6 cm Shape: Lobulated Character: Heterogeneous, necrotic Time: Rapid growth Connections: May invade IVC, kidney CT/MRI: Irregular mass with necrosis, delayed washout, possible vascular invasion
CAH Unit: Bilateral cortical hyperplasia Size: Enlarged Shape: Lobulated Character: Thickened cortex Time: Congenital onset Connections: HPA axis dysregulation CT/MRI: Bilateral irregular gland enlargement
Adrenal hemorrhage Unit: Hematoma-filled gland Size: Enlarged (acute) Shape: Irregular Character: Hyperdense (acute phase) Time: Evolves over days Connections: Disruption of venous outflow CT: Hyperdense acute hemorrhage MRI: Signal varies with hematoma age

🔹 Table 3 – Diagnostic Tools

A. Clinical Signs and Symptoms

Symptom Interpretation
Fatigue, weight loss, hyperpigmentation Addison’s disease
Hypertension, hypokalemia Primary aldosteronism (Conn syndrome)
Paroxysmal headache, sweating, tachycardia Pheochromocytoma
Cushingoid appearance (moon face, striae) Cushing’s syndrome
Early virilization in children CAH (21-hydroxylase deficiency)

B. Imaging Modalities

Modality Use When/Why Used
CT (non-contrast + washout) Evaluate adrenal mass (size, HU, washout) First-line for incidentalomas or hormone-producing tumors
MRI Characterize mass (lipid, hemorrhage, T2 signal) Preferred for pheochromocytoma, indeterminate CT
PET/CT Functional and metastatic assessment Useful in ACC and metastatic pheo
MIBG scan Neuroendocrine tumor imaging Functional assessment of pheochromocytoma

C. Laboratory Tests

Test Purpose When Used
AM cortisol, ACTH Assess adrenal insufficiency Suspected Addison’s or secondary causes
Plasma metanephrines Pheochromocytoma screening High sensitivity
Aldosterone:renin ratio Hyperaldosteronism screening Hypertension + hypokalemia
Dexamethasone suppression test Cushing’s diagnosis Determine cortisol autonomy
17-hydroxyprogesterone CAH screening Neonatal or virilization evaluation

D. Other Diagnostic Tools

Tool Use Indication
ACTH stimulation test Evaluate adrenal reserve Confirm Addison’s
Adrenal venous sampling Localize aldosterone production Distinguish unilateral adenoma from bilateral hyperplasia
Genetic testing Identify CAH or MEN mutations Family history or syndromic findings

5. History and Culture


Page 5 – History, Culture, and Art (Final Format)


🔹 1. History of Anatomy

Era / Contributor Milestone
1563 – Bartholomeo Eustachio First described and illustrated the adrenal glands
19th century Recognition of adrenal cortex and medulla as distinct zones
20th century Detailed zonal anatomy: zona glomerulosa, fasciculata, reticularis, and chromaffin cells

🔹 2. History of Physiology

Era Discovery
1850s – Thomas Addison Identified adrenal insufficiency as cause of a deadly disease
Early 20th century Adrenaline (epinephrine) discovered and synthesized
Mid-20th century Cortisol and aldosterone roles identified; development of steroid therapy
Modern era HPA axis and feedback loops fully characterized; link to stress, immunity, metabolism, and emotion

🔹 3. History of Disease

Era Milestone
1855 – Addison Described adrenal failure and skin pigmentation (Addison’s disease)
20th century Cushing syndrome and pheochromocytoma pathophysiology clarified
Modern era Genetic syndromes (e.g., CAH, MEN) and adrenal incidentalomas studied via imaging and endocrine testing

🔹 4. History of Diagnosis

Tool / Test Milestone
Clinical signs (hyperpigmentation, hypertension) Classic indicators of dysfunction
ACTH stimulation test Tests adrenal reserve in suspected Addison’s
24-hour urine cortisol Diagnoses Cushing syndrome
Plasma metanephrines Detects pheochromocytoma with high sensitivity

🔹 5. History of Imaging

Modality Use
CT/MRI Visualize tumors (e.g., adenomas, pheochromocytomas), hemorrhage, and hyperplasia
Nuclear medicine (I-131 MIBG, PET) Functional imaging for pheochromocytoma, metastases
Ultrasound Less commonly used; limited by retroperitoneal location

🔹 6. History of Laboratory Testing

Test Purpose Use
Serum cortisol Assess adrenal output Morning and stress levels
ACTH Differentiate primary vs secondary adrenal disease  
Aldosterone/renin ratio Screens for primary hyperaldosteronism  
Plasma/urine metanephrines Screen for catecholamine-secreting tumors  

🔹 7. History of Therapies

Therapy Era Details
Cortisone replacement 1940s Life-saving in adrenal insufficiency
Steroids (prednisone, dexamethasone) Mid-20th century Used in inflammatory and endocrine diseases
Adrenalectomy Surgical removal of tumors; may be open or laparoscopic  
Alpha blockers Pheochromocytoma pre-treatment before surgery  
Hormone suppression and replacement Ongoing management for CAH, Addison’s, etc.  

🔹 8. Cultural Meaning

Culture Symbolism
Modern psychology Adrenal = stress gland; associated with “fight or flight” response
Popular culture “Adrenaline rush” symbolizes excitement, risk, survival
Holistic medicine Seen as central to “adrenal fatigue” (a non-evidence-based but widely discussed concept)
Mythology Often metaphorically linked to courage and reaction to danger

🔹 9. Artistic Representations

Medium Example Meaning
Visual metaphors Lightning bolt to kidneys Symbolizes adrenaline surge and power
Holistic body maps Energy pathways include adrenal meridians Emphasize their role in balance and vitality
Abstract sculpture Hormonal cascades as spirals or feedback loops Represent endocrine integration with emotion

🔹 10. Literary References

Author / Source Reference Theme
Scientific literature “Adrenaline-fueled decisions” Emotion and urgency tied to hormones
Popular media “Pumped with adrenaline” Common idiom reflecting stress chemistry
Historical fiction Descriptions of fainting, bronze skin Possibly unrecognized adrenal insufficiency (Addison’s)

🔹 11. Music and Performing Arts

Context Representation Notes
Performance stress Linked to adrenal surge Musicians and actors experience heightened cortisol and epinephrine pre-performance
“Adrenaline music” Fast tempo and rhythm Used to evoke urgency, risk, thrill (e.g., in film scores)
Physical performance Stress hormones support vocal projection Needed in intense emotional expression or stage tension

🔹 12. Athletics and Performance

Context Role of Adrenal Glands Examples
Fight-or-flight Immediate stress response Epinephrine mobilizes energy, increases heart rate
Endurance sports Cortisol regulates energy balance Overtraining may suppress adrenal function
Adrenal disorders in athletes Addison’s or Cushing’s impact stamina and metabolism Requires careful hormonal management and monitoring

🔹 13. Culinary and Nutritional Use

Use Context Details
Adrenal gland meat Rarely consumed Occasionally found in organ meat dishes (e.g., sweetbreads)
Traditional medicine Used in glandular extracts Not widely supported by evidence but promoted in alternative medicine
“Adrenal support” supplements Commercial use Marketed for “fatigue” though medically unsupported

🔹 14. Notable Individuals with Adrenal Disease

Name Condition Note
John F. Kennedy Addison’s disease Managed with corticosteroids throughout presidency
Eugene Floyd Pheochromocytoma Rare tumor publicly discussed in medical advocacy
Floyd Patterson Boxer with adrenal issues Rumored medical management for stress and stamina

🔹 15. Famous Quotes and Sayings

Quote Context
“Adrenaline junkie” Someone who seeks excitement and risk
“Running on adrenaline” Surviving stress or fatigue through hormonal momentum
“Pumped full of adrenaline” State of readiness or extreme alertness
“Stress kills” Modern interpretation of prolonged adrenal overdrive (cortisol excess)
 

7. MCQ's


Page 6 – Multiple Choice Questions (MCQs)


🔹 MCQ 1 – Basic Science

Which of the following hormones is produced by the zona glomerulosa of the adrenal cortex?

A. Cortisol
B. DHEA
C. Aldosterone
D. Epinephrine


Correct Answer Table

Correct Answer Explanation
C. Aldosterone The zona glomerulosa produces mineralocorticoids, primarily aldosterone, which regulates sodium and potassium balance.

Incorrect Answer Table

Option Reason It Is Incorrect
A. Cortisol Produced by the zona fasciculata
B. DHEA Produced by the zona reticularis
D. Epinephrine Produced by the adrenal medulla, not cortex

🔹 MCQ 2 – Basic Science

The adrenal medulla is derived from which embryologic tissue?

A. Endoderm
B. Mesoderm
C. Neural crest
D. Ectoderm


Correct Answer Table

Correct Answer Explanation
C. Neural crest Chromaffin cells of the adrenal medulla originate from neural crest and secrete catecholamines.

Incorrect Answer Table

Option Reason It Is Incorrect
A. Endoderm Gives rise to gut and respiratory linings
B. Mesoderm Gives rise to adrenal cortex, not medulla
D. Ectoderm Forms skin and nervous system but not adrenal medulla

🔹 MCQ 3 – Clinical

A 34-year-old woman has episodes of headache, palpitations, and hypertension. Plasma metanephrines are elevated. What is the most likely diagnosis?

A. Cushing’s disease
B. Pheochromocytoma
C. Addison’s disease
D. Conn syndrome


Correct Answer Table

Correct Answer Explanation
B. Pheochromocytoma Classic triad of headache, palpitations, and episodic hypertension with elevated catecholamine metabolites indicates pheochromocytoma.

Incorrect Answer Table

Option Reason It Is Incorrect
A. Cushing’s disease Causes weight gain, central obesity, not episodic hypertension
C. Addison’s disease Causes hypotension, not hypertension
D. Conn syndrome Causes sustained hypertension, not paroxysmal symptoms

🔹 MCQ 4 – Clinical

Which finding is most consistent with primary adrenal insufficiency (Addison’s disease)?

A. High cortisol and low ACTH
B. Hypertension and hypokalemia
C. Hyperpigmentation and hyponatremia
D. Cushingoid appearance


Correct Answer Table

Correct Answer Explanation
C. Hyperpigmentation and hyponatremia Primary adrenal insufficiency leads to low cortisol and aldosterone, resulting in low sodium and high ACTH (which stimulates melanocytes).

Incorrect Answer Table

Option Reason It Is Incorrect
A. High cortisol Cortisol is low in Addison’s
B. Hypertension Addison’s typically causes hypotension
D. Cushingoid appearance Seen in cortisol excess, not deficiency

🔹 MCQ 5 – Radiologic

Which imaging feature is most typical of a lipid-rich adrenal adenoma on CT?

A. High attenuation (>30 HU) on non-contrast scan
B. Slow contrast washout
C. Low attenuation (<10 HU) on non-contrast scan
D. Bright signal on T2-weighted MRI


Correct Answer Table

Correct Answer Explanation
C. Low attenuation (<10 HU) Lipid-rich adenomas typically have <10 Hounsfield Units on non-contrast CT and show rapid washout.

Incorrect Answer Table

Option Reason It Is Incorrect
A. High attenuation Suggests malignancy or hemorrhage
B. Slow washout Malignant tumors wash out slowly
D. T2 brightness Seen in pheochromocytomas, not adenomas

🔹 MCQ 6 – Radiologic

Which MRI feature is most characteristic of pheochromocytoma?

A. Isointensity on T1 and T2
B. Hypointensity on all sequences
C. Bright signal on T2-weighted imaging
D. Low signal on out-of-phase imaging


Correct Answer Table

Correct Answer Explanation
C. Bright signal on T2-weighted imaging Pheochromocytomas are typically T2-hyperintense (“light bulb sign”) due to their high water and vascular content.

Incorrect Answer Table

Option Reason It Is Incorrect
A. Isointense Not typical of pheochromocytomas
B. Hypointense Seen in hemorrhage or calcified lesions
D. Out-of-phase signal loss Suggests lipid-rich adenoma, not pheochromocytoma

🔹 MCQ 7 – Radiologic

Which condition is most likely to cause bilateral adrenal enlargement in a child?

A. Adrenal adenoma
B. Pheochromocytoma
C. Congenital adrenal hyperplasia
D. Adrenocortical carcinoma


Correct Answer Table

Correct Answer Explanation
C. Congenital adrenal hyperplasia CAH leads to bilateral cortical hyperplasia due to enzymatic deficiency (most commonly 21-hydroxylase).

Incorrect Answer Table

Option Reason It Is Incorrect
A. Adenoma Usually unilateral and well-circumscribed
B. Pheochromocytoma Usually unilateral and medullary in origin
D. Carcinoma Typically unilateral and large with necrosis/invasion

8. Memory Image


The Adrenal Gland A memory image reflecting its 3 major function. The wide eyes and dilated pupils reflect ffright fight and flight, water dripping from its mouth reflect water metabolism and salt spewing reflects salt metabolism . Ashley Davidoff MD TheCommonVein.com 140229-01.adrenal

9. Other


Applied Anatomy of the Adrenal Glands

Learning Objectives[ps2id id=’01’ target=”/]

Recognize the basic anatomy of the adrenal glands.
Be able to locate this organ within the abdominal cavity and identify the main structures of the adrenal gland utilizing cross sectional medical imaging.
Describe the adrenal gland’s function and its relation to the other organs in the abdominal region.
Differentiate the role of radiographic examination, CT, US, and MRI in imaging studies of the adrenal glands.
Introduction:

Two Boys Fishing
Imagine two young boys with straw hats fishing by the river.
The boy in red is napping and has his hat on his forehead – the left adrenal.
The other boy in blue is wide awake and has his hat atop his head – the right adrenal.
This is how the adrenals are positioned relative to the superior poles of the kidneys.
Ashley Davidoff MD 2018
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adrenals-0015

Definition

 

The adrenals are paired endocrine glands secreting catecholamines (norepinephrine and epinephrine) from the inner medulla, and steroid hormones from the outer cortex. The medulla is controlled by the neuroendocrine axis, while the cortex is controlled mostly by the pituitary gland. The adrenals are located retroperitoneally at the upper poles of the kidneys. They mainly help the body in its response to stress as well as play a role in maintaining blood pressure and salt balance. When faced with a stressful situation, the medulla of the adrenal glands secrete epinephrine (adrenaline) causing an “adrenaline rush” preparing the body for “fight or flight”.

This drawing reveals the intimate relationship between the adrenal glands (a.k.a. suprarenal glands) with the kidneys. Although they are paired, they usually appear quite different on cross sectional imaging.
Courtesy of: Ashley Davidoff, M.D.

The anatomy of the adrenal glands appears to have been described first in 1563 by Bartholomeo Eustachius as the “glandulae renis incumbentes” in his Tabulae Anatomicae. Ideas about the function of the adrenal glands lagged behind. Thomas Bartholin proposed that these “capsulae atrabilariae” purified black bile that eventually drained into the renal veins.In 1714 Lancisius Emil Huschke first differentiated the two layers of the adrenal gland, the cortex and the medulla, anatomically. Edme F.A. Vulpian demonstrated the differential staining of the two regions histologically.

In 1716 the Academie des Sciences de Bordeaux offered a prize for the answer to the question, “What is the purpose of the suprarenal glands?” Charles de Montesquieu, judging the responses, found the essays so unsatisfactory that he was unable to award the prize, concluding that “Perhaps some day chance will reveal what all of this work was unable to do.”

Evidence for a central physiological role for adrenal glands came from clinical observation. On March 15, 1849, Thomas Addison presented a paper to the South London Medical Society entitled, “On anaemia: disease of the supra-renal capsules,” a result of his interest in idiopathic, or pernicious, anemia. Three of the patients he described had adrenal disease at autopsy, and it was the only abnormality that was identified in two of them.

Harvey Cushing began his career at the Massachusetts General Hospital and is considered a pioneer of Neurosurgery, making several fundamental discoveries about the pituitary gland and its relation to the adrenals. Due to his extensive work, Cushing’s disease and syndrome are named after him.

Image collage courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Overview

The adrenal glands are small and mighty. They are tucked away in the back of the abdomen, just below the chest cavity, and literally have their finger on the pulse as they sit alongside the highway systems of the aorta, vena cava, and autonomic nerve chains. They sit on top of the waterworks in close contact with the kidneys, and within the functional loop of the renin – angiotensin – aldosterone hormonal system that controls blood pressure, volume and salt metabolism. Some of the most dramatic responses of the body originate in these small and sometimes hidden glands.The adrenals have a reputation in the imaging world of being hard and difficult. Neither of these statements is true. First, they are so soft that they get pushed around by all the other organs that surround them. Secondly, like so many things that appear difficult initially, with appropriate attention, the structural complexity and eccentricities unfold.

This image combines the coronal view with the axial view and reflects the intimate relationships that the adrenals have with the kidneys as well as the great vessels of the abdomen. They literally have their fingers on the pulse of the aorta (red overlay)and the inferior vena cava (IVC) (blue overlay).

As a paired organ you would think that they would be perfectly symmetrical, like the hands or feet, but in fact they look quite different, particularly in cross-section. The right tends to be long and thin and the left short and stout.
Images courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Normal Frontal View

The adrenal glands are located retroperitoneally in the abdomen. They sit on the upper poles of the kidneys on the posterior abdominal wall and extend roughly from the level of the 11th thoracic rib to the first lumbar vertebrae.The right adrenal is slightly more lateral than the left. Since the adrenals sit on top of kidneys, and the right kidney is usually lower than the left, the right adrenal is usually more inferior.

This reconstructed CT scan reveals the intimate relationship between the adrenal glands (a.k.a. suprarenal glands) with the kidneys. Although they are paired, they usually appear quite different on cross sectional imaging.Courtesy of: Ashley Davidoff, M.D.

 

Anatomy and Physiology of the Adrenal Glands: Normal Transverse View

The adrenals can be found just lateral to the crus of the diaphragm. They have a ‘wishbone’ shape, or upside down ‘y’ shape and are surrounded by fat. In general the right adrenal is the long and thin one of family, and the left the short and chubby one.Often the lateral limb of the right adrenal gland is pressed against the liver and cannot be clearly seen. Since the limbs are soft, compressible, and malleable, they often are distorted by normal surrounding structures producing “bends” in them. This sometimes results in difficulty distinguishing cases of abnormal nodules and hyperplasia (increased size) from normal distortion.

The crura of the diaphragm (maroon overlay) can be seen as muscle bundles alongside the vertebral body and surrounding the aorta. The limbs of the adrenal gland (yellow overlay)should not be thicker than the crura. In this instance, the right adrenal gland is normal. The knobbly appearance of the left gland is also normal. At first glance it does appear thickened and concerning, but when the bend of the medial limb is recognized as a structural consequence of compression, the appearance becomes less concerning. The distinction between “knobbly normal” and “knobbly hyperplasia” is sometimes difficult.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Size

The adrenals can vary in weight anywhere between 4 to 14 grams, but the average weight is between 3 to 6 grams. Only about 10% of the gland’s weight is from the medulla (inner portion).The average adrenal dimensions are:

·         20-30 mm. in width

·         40-60 mm. in length

·         3-6 mm. in thickness

The left adrenal is slightly larger than the right.

As previously stated, the limbs of the adrenal glands should be as gracile and as thin as the crura. In many instances however the gland gets distorted by surrounding structures and becomes thicker than the crus as seen by distortion of the left adrenal gland in this case.Courtesy of: Ashley Davidoff, M.D.  .Courtesy of: Ashley Davidoff, M.D.

In this case the normal medial limb of the right adrenal gland is elongated. This is a normal variant. The lateral limb is pushed against the liver.Courtesy of: Ashley Davidoff, M.D.

In this instance the adrenal size is clearly abnormal. The abnormal areas of metastatic disease are overlayed in green. The thickening of the medial limb of the right and the mass on the left result in an increased size of the each of adrenal glands.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Size – small and large

The tiny subcentimeter green nodule at the apex of the left adrenal is a surgically proven aldosteronoma, which is a benign tumor that produces excessive aldosterone and causes hypertension. If left untreated devastating effects of hypertension result.

This massive adrenal carcinoma (in green overlay) occupies almost the entire left side of the abdomen, and is so bulky that it has literally pushed the left kidney (red overlay)down to the pelvis, and rightward to the right kidney. Sometimes adrenal carcinomas produce hormones with functional effects relating to the type of hormone they produce.Images courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Shape

In general the adrenals have a ‘wishbone‘, or upside down ‘y’ shape, but they are not usually symmetrical. Although they are naturally asymmetric structures, part of their shape discrepancy relates to the variability in their surroundings. Since they are in different relative positions they have different surroundings.When there is a paucity of fat or the surrounding structures push on them, they tend to distort. The right adrenal gets pushed against the liver, and elongates, while the left becomes irregular and “knobbly”. Thus in general, the right is long and thin and the left short and stout. When there is a large amount of retroperitoneal fat they tend to look more alike in cross section.

In general the adrenal glands are triangular in shape and are reminiscent of the shape of the “wishbone” or the breast bone of the chicken.Courtesy of: Ashley Davidoff, M.D.

The right adrenal gland, in this case, looks exactly like the inserted drawing of the “wishbone”. This represents the typical appearance of the glands – the right long and thin, and the left short and stout. The bright red overlays represent some of the branches of the adrenal arteries.Courtesy of: Ashley Davidoff, M.D.

The adrenal glands should be well defined, and be free of nodularity, such as seen in this normal case. The distinction between “knobbly normal”, and “knobbly hyperplasia” (disease) as stated previously, is a difficult but very important distinction to make.Courtesy of: Ashley Davidoff, M.D.

This case shows bilateral nodularity caused by bilateral adrenal adenomas. The abnormal areas are overlayed in green and the normal adrenal outlined in yellow.Images courtesy of: Ashley Davidoff, M.D.

 Position

Two Boys Fishing
Imagine two young boys with straw hats fishing by the river.
The boy in red is napping and has his hat on his forehead – the left adrenal.
The other boy in blue is wide awake and has his hat atop his head – the right adrenal.
This is how the adrenals are positioned relative to the superior poles of the kidneys.
Ashley Davidoff MD 2018
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Now take a look at the straw hats as they are positioned on the kidneys. The left adrenal lies more medial and is therefore more compressed by surrounding structures including the medially positioned spine. The right adrenal is more able to take on its naturally triangular shape.Courtesy of: Ashley Davidoff, M.D.

The adrenal glands are usually difficult to find. Since the left kidney is slightly more superior than the right, the left adrenal is usually more superior. The left adrenal can be found when the splenic vein crosses behind the pancreas from the spleen to the portal vein, and the right adrenal can be found when the IVC frees itself from its intrahepatic portion inferiorly. The gland must be identified superiorly and inferiorly until no part of the gland remains, since exophytic tumors off the gland are not uncommon.The adrenals or adrenal like tissue can be found in places other than its normal position. This is termed ‘ectopic’ adrenal tissue.

In these images, the right adrenal is best seen as the IVC (blue overlay) emerges from the liver. Parts of the left adrenal are visualized as the splenic vein (blue overlay) courses behind the pancreas to the portal vein.Courtesy of: Ashley Davidoff, M.D.

Structural

The adrenal gland consists of 2 main parts:1. an outer cortex which secretes several classes of steroid hormones;
2. an inner medulla which is the source of the catecholamines epinephrine and norepinephrine.The adrenal also has a thin outer fibrous capsule which can vary in thickness from gland to gland, and in some cases, even within the same gland.

The outer cortex has separate embryological origin and is distinct in its function and structure. The hormones produced by the cortex have a steroid infrastructure. The inner medulla which only accounts for 10% by weight produces catecholamines.Courtesy of: Ashley Davidoff, M.D.

When the adrenal gland is reviewed under the microscope, three different layers are identified in the cortex and one layer in the medulla. In the following images the yellow and orange layers represent the cortical layers and the red represents the medulla.

This image shows the relative volume of cortex (in yellow and orange) to the lesser volume of medulla (red).Courtesy of: Ashley Davidoff, M.D.

The cortex is divided into the 3 zones based on the arrangement of cells.

zona glomerulosa is the outer most rounded groups of cell.
zona fasciculata, is the middle column of cells and arranged radially.
zona reticularis is the innermost irregularly arranged cylindrical masses of cells.
“GFR” is a good pneumonic to remember. It stands for glomerular filtration rate but also stands for the three layers, from outer to inner, – glomerulosa, fasciculata, and reticularis.

The outermost of the three layers of cortex is the zona glomerulosa which consists of rounded groups of cells. The middle and largest layer is the zona fasciculata, in which the cells are radially arranged. The zona reticularis, is the innermost layer and is made of irregularly arranged cylindrical masses of cells. Remember the pneumonic “GFR” = from outer to inner glomerulosa, fasciculata, and reticularis.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Parts – Functional

The outermost layer, the zona glomerulosa produces aldosterone. The middle layer of the cortex produces cortisol, and the inner layer produces androgens. The medulla produces adrenaline, a type of catecholamine.Courtesy of: Ashley Davidoff, M.D.

Aldosterone is responsible for water and salt balance which in turn is intimately related to blood pressure control. Cortisol, is responsible for responding to physically stressful situations. Androgens are responsible for developing male characteristics. The medulla produces adrenaline which is responsible for urgent “fight or flight” situations.Courtesy of: Ashley Davidoff, M.D.

 

Anatomy and Physiology of the Adrenal Glands: Parts – Imaging

In imaging it is usually not possible to differentiate between the cortex and the medulla, and we divide the adrenal into the medial and lateral limbs which are joined together at the apex of the gland.

In this image we have been able to identify each of the four limbs that make up the two adrenal glands. Each has a medial and a lateral limb joined together at the apex. The left adrenal vein is noted as the blue overlay.Courtesy of: Ashley Davidoff, M.D.

In this early arterial phase, there appear to be a number of layers in the left adrenal. We have interpreted them as the cortex and medulla as seen in the yellow and red overlay. With the advancing multidetector technology, the distinction between cortex and medulla may be uncovered. This is an exciting prospect!Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Character-Normal

The normal adrenal gland is soft and friable. It is usually surrounded by fatty tissue and is encapsulated. The surface appears corrugated or nodular and is usually not smooth.

The normal color is a golden yellow color which can be distinguished from the more pale surrounding fat. The capsule is a thin fibrous structure surrounding the gland attached by many fibrous bands which penetrate into the gland.

When the adrenal is cut, the outer cortex and the inner medulla can be distinguished by color. The cortical (outer) layer appears golden yellow while the inner medulla appears more flattened and a darker reddish/brown.

The outer cortex has separate embryological origin and is distinct in its function and structure. The hormones produced by the cortex have a steroid infrastructure. The inner medulla which only accounts for 10% by weight produces catecholamines.The cortical (outer) layer appears golden yellow while the inner medulla appears more flattened and a darker reddish/brown.Courtesy of: Ashley Davidoff, M.D.

The adrenal glands behave like other parenchymal organs on CT scanning in that they are of soft tissue density. Under physically stressful situations, they may enhance significantly more than other organs due to their rich blood supply.Courtesy of: Ashley Davidoff, M.D.

On T1-weighted imaging, the intensity of the adrenals is less than that of the surrounding liver and spleen. While on T2-weighted imaging, the adrenal is usually close to the intensity of the liver.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Capsule

Each gland is encased in a thin layer of loose areolar connective tissue and a thick fibrous capsule. The capsule is attached by fibrous bands extending into the substance of the gland.

The fibrous capsule (white) surrounds the gland and is fixed to the gland by multiple fine strands of fibrous tissue that extend into the gland. (highlighted in red).Courtesy of: Ashley Davidoff, M.D.

This is an artist’s rendition of thin fibrous strands of the capsule penetrating the cortex.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Arterial Supply – Extra – Adrenal Anatomy

The adrenal gland is very vascular, receiving an estimated 6 to 7 ml/g per minute, or about 25ml/minute in the resting state. Why does it have such a large blood supply? The body’s second to second need to respond to crisis situations requires enough blood to pass by the adrenals to circulate important and necessary hormones.

The blood supply of the adrenal gland is derived from three adrenal arteries: the superior artery is a branch of the inferior phrenic artery; the middle artery arises directly from the aorta; and the inferior artery arises from the renal artery.

The primary blood supply of the right adrenal comes from the superior and inferior adrenal arteries, whereas the left adrenal is supplied primarily by the middle and inferior adrenal arteries. The three arteries branch, and each gland may have up to 50 small arterial branches enter the perimeter, supplying a gland that obviously commands a tremendous blood supply.

This coronal T1-weighted image has been overlayed with the arterial anatomy of the adrenal. Each gland receives arterial blood from three arteries – the superior, middle and inferior adrenal arteries.
Courtesy of: Ashley Davidoff, M.D.

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There are three adrenal arteries – the superior that arises from the inferior phrenic artery, the middle that arises directly off the aorta and the inferior that arises from the renal artery usually as a branch of the capsular artery. This schematic only shows 3 branches per vessel, but in reality there is extensive branching before each artery actually enters the gland.
Courtesy of: Ashley Davidoff, M.D.

This image shows a schematic of the histologic distribution of the adrenal arterial supply and venous drainage. The dominant area of arterial supply is the cortex, and the dominant area of venous drainage is the medulla.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Arterial Supply – Intra- Adrenal Anatomy

Up to 50 to 60 small feeder vessels penetrate the anterior and posterior surfaces of the glands and form a plexus beneath the capsule. Cortical arteries supply the cortex from the subcapsular plexus, which drains centripetally toward the medulla. Medullary arteries pass through the cortex and supply the medulla directly. In the zona reticularis, the capillaries coalesce to form progressively larger venous sinuses that drain centrally.

Medullary capillaries form venous channels, which eventually forms a single adrenal vein that usually drains into the vena cava on the right and into the renal vein on the left.

This image shows a schematic of the histologic distribution of the adrenal arterial supply and venous drainage. The dominant area of arterial supply is the cortex, and the dominant area of venous drainage is the medulla.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Arterial Supply – Imaging

This image reflects the right renal artery with the capsular branch arising from within 2 cm. from the aortic origin. The inferior adrenal artery is overlayed in red and can be seen terminating in a tuft of vessels at the adrenal gland.Courtesy of: Ashley Davidoff, M.D.

In this instance the middle and superior adrenal arteries can be seen supplying the right adrenal gland.(yellow overlay)Courtesy of: Ashley Davidoff, M.D.

 

 

Anatomy and Physiology of

This image depicts the relationship of the middle and superior adrenal arteries with the adrenal gland and the superior pole of the right kidney.
Courtesy of: Ashley Davidoff, M.D.

Adrenal Glands: Arterial Supply – Abnormal

In this injection of the middle adrenal artery, a mass is apparent in the right adrenal gland. The branches of the artery are distorted and, rather than a triangular shape as seen on previous image, we see a rounded mass. There is evidence of early venous filling (blue overlay) reflecting an arteriovenous shunt, characteristic of a hypervascular tumor.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Venous Drainage

The venous drainage of the adrenals occurs via a single vein that emerges from the anterior surface of each gland.

The dominant portion of the adrenal vein arises in the medulla of the gland.  Courtesy of: Ashley Davidoff, M.D.

Adrenal venous drainage is usually through the right and left adrenal veins.

The right adrenal vein exits the apex of the gland and enters the posterior surface of the inferior vena cava. This vein is short (1-5 mm.), fragile, and the most common source of troublesome bleeding during right adrenalectomy.

The left adrenal vein is a bit longer (2-4 cm. in length) and usually drains into the left renal vein, either directly or after being joined by the left inferior phrenic vein. Smaller emissary veins may drain into the inferior phrenic, renal, and rarely the hepatic portal veins.

Not well recognized is the left inferior phrenic vein, which usually communicates with the adrenal vein which courses medially. This can be injured during dissection of the medial edge of the gland.

In this coronal view the shorter right adrenal vein can be seen entering the IVC, and the longer left vein, drains into the left renal vein. This information is very important for the angiographer who sometimes needs to sample the veins for hormonal levels. Note that the long and thin right adrenal gland has the short adrenal vein that enters directly into the IVC, while the short and stout left gland has a long vein that enters into the left renal vein.Courtesy of: Ashley Davidoff, M.D.

Remember – the tall and thin one of the family (right adrenal) has the short vein, while the short and stout one (left adrenal) has the long vein. Note also that the vein of the right gland enters directly into the IVC, while the vein of the left gland enters into the left renal vein.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Venous Drainage – Venography

This series of three images reflects a study called “adrenal vein sampling” which requires the simultaneous catheterization of the adrenal veins. This procedure is used to identify relative and absolute concentrations of hormone secretion from the glands to distinguish between normal, bilateral hyperplasia, and unilateral adenoma.

The first image shows the catheters in each of the adrenal veins. The second image is a venogram of the right adrenal vein, and the third a venogram of the left. The venogram is mainly performed to confirm that the catheter is in the correct position, because the veins, particularly the right, may be difficult to find and other small veins coming into the IVC may masquerade as adrenal veins. It is absolutely essential to be in the “right place at the right time” for this test.Courtesy of: Ashley Davidoff, M.D.

This image is an overlay and an enlarged version of the first image above. It shows the right catheter entering the short right adrenal vein, exiting from above the right gland, and entering the IVC. The left adrenal vein, which is longer, exits from below the left gland and enters into the left renal vein. The insert of the “duel” is a reminder of the short vein on the right and the long vein on the left.
Courtesy of: Ashley Davidoff, M.D.

This image is an overlay and an enlarged version of the second image from the initial series above. It shows the right catheter entering the shorter right adrenal vein, exiting from above the right gland, and entering the IVC. The yellow overlay is an approximation of the right adrenal gland.Courtesy of: Ashley Davidoff, M.D.

This image is an overlay and an enlarged version of the third image of the initial series. It shows the left adrenal vein, which is relatively long, exiting from below the left gland, and entering the left renal vein. The yellow overlay is an approximation of the left adrenal gland.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Venous Drainage – Imaging CT

The left adrenal vein is almost always seen in cross sectional imaging lying at the apex of the gland. In this case both adrenal veins are identified (blue overlay). We have reviewed this case before which represents an aldosteronoma of the left adrenal gland. (green nodule)Courtesy of: Ashley Davidoff, M.D.
Anatomy and Physiology of the Adrenal Glands: Lymphatics

The left adrenal vein is almost always seen in cross sectional imaging lying at the apex of the gland. In this case both adrenal veins are identified (blue overlay). We have reviewed this case before which represents an aldosteronoma of the left adrenal gland. (green nodule)
Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Lymphatics

Lymphatic vessels arise from a plexuses deep within the capsule and in the medulla only. The lymph vessels follow the central vein and the main venous tributaries throughout the medulla of the adrenal gland. Lymphatic plexuses drain to para-aortic and renal lymph nodes.

There is no lymphatic supply to the cortex of the adrenal.

Anatomy and Physiology of the Adrenal Glands: Lymphatics
Lymphatic vessels arise from a plexuses deep within the capsule and in the medulla only. The lymph vessels follow the central vein and the main venous tributaries throughout the medulla of the adrenal gland. Lymphatic plexuses drain to para-aortic and renal lymph nodes.
There is no lymphatic supply to the cortex of the adrenal.

Anatomy and Physiology of the Adrenal Glands: Nerve Supply

The adrenal glands receive nerves from the lower thoracic (T10 – T12) and upper lumbar (L1 – L2) nerve plexuses. The nerves travel with the arteries. The nerve supply forms a plexus of medullated and non medullated nerves on the capsule of the gland primarily on the posterior aspect. The nerves enter the gland with the arterioles and help regulate the high adrenal blood flow.

The nerves to the adrenal gland,(colored in white) travel with the arteries. The neuroendocrine axis has to respond very rapidly to urgent, and sometimes emergency situations, and so the nerve supply is quite rich, and the interaction and intimate relationship with the arterial system is appropriately intimate and rich. Plexuses of the autonomic system (white overlay) course in a para aortic position and connect with each other as well as the organs that they supply.
Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Relations

The anatomic location of the adrenals, sandwiches them between several organs, and on the border between two major cavities. The adrenals are positioned differently in relation to the kidneys and to other asymmetric organs such as the liver, pancreas, and spleen.

These coronal MRI images show the adrenals surrounded by retroperitoneal fat, padded by the liver on the right and the spleen on the left, and displaced from the superior aspect of the kidneys by a “mop” of fat.Courtesy of: Ashley Davidoff, M.D.

 

This is a larger and more colorful version of the previous set. Note the relationship of the tail of the pancreas (in light pink) to the left adrenal and the medial relationship of the great vessels (“finger on the pulse”) and crura.(slithers of maroon extending from the hemidiaphragms).Courtesy of: Ashley Davidoff, M.D.

This embedded cross section reflects the true relationship of the great vessels to the adrenals. The IVC really is positioned anterior to the right adrenal while the aorta lies medial to the left adrenal gland .Courtesy of: Ashley Davidoff, M.D..

Anatomy and Physiology of the Adrenal Glands: Relations – Right adrenal

The right adrenal is framed by the following:·         anteriorly – the inferior vena cava and the caudate lobe of the liver

·         posteriorly – the diaphragm

·         superiorly – the bare area of the right lobe of the liver, diaphragm and chest cavity

·         inferiorly – the superior pole of the right kidney

·         medially – the crus of the diaphragm and the spine

·         laterally – the bare area of the right lobe of the liver

This cross sectional image shows the crus of the diaphragm (maroon), IVC (blue), and the liver (purple), surrounding the right adrenal (yellow).Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Relations – Left adrenal

The left adrenal is framed by the following:·         anteriorly – the end of stomach above and the pancreas below and branches of the splenic artery and vein

·         posteriorly – the left kidney, spleen, and the diaphragm

·         superiorly – the diaphragm and chest cavity

·         inferiorly – left kidney

·         medially – left crus of the diaphragm, aorta, and spine

·         laterally – the spleen and left kidney

This cross sectional image of the superior aspect of the left upper abdomen shows the spleen (dark pink), splenic artery and vein in the splenic hilum, the pancreas (light pink), crus of the diaphragm (maroon), aorta (red), and the spine surrounding the left adrenal (yellow).Courtesy of: Ashley Davidoff, M.D.

This coned down cross-sectional image, more inferiorly, shows the left kidney (bright red), the tubular wisps of the splenic artery and vein anterolaterally, the pancreas (pink), crus of the diaphragm (maroon), aorta (red), and the spine surrounding left adrenal (yellow).Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Embryology

Each adrenal consists of two functionally distinct endocrine glands within a single capsule. The cortex derives from mesenchymal cells of the coelomic cavity lining, adjacent to the urogenital ridge. The fetal adrenal gland is recognizable by the second month of gestation when it is invaded by neuroectodermal cells that will form the medulla.The adrenal becomes quite vascular, increases rapidly in size and is actually larger than the kidney at midgestation. By the second trimester, the thin, outer definitive zone that will form the adult cortex becomes distinct. The inner fetal zone comprises most of the adrenal mass and still represents three quarters of the cortex at birth.

The fetal zone degenerates rapidly after birth, accounting for only one quarter of the cortical mass at 2 months and vanishing by 1 year. The total adrenal weight declines until age 2 to 3 months, and the growth from this point on parallels growth of the body. The zona reticularis develops during the first year of life.

This anatomic specimen reflects the relatively large size of the right fetal adrenal (yellow) in relation to the kidneys (bright red). The left adrenal has been removed. The ridges in the kidneys are known as fetal lobation which is a normal variant that may persist even into adulthood.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Abnormal Gland

Adrenal gland abnormality can vary from subtle thickening of the limbs as seen in hyperplasia, to small subcentimeter adenomatous nodules, to multiple tiny nodules of hyperplasia, to 6cm. (or more) masses. Attention to detail and imaging technique is key to the diagnosis of the abnormal gland.

The tiny subcentimeter green nodule at the apex of the left adrenal is a surgically proven aldosteronoma, which is a benign tumor that produces excessive aldosterone and causes hypertension. If left untreated devastating effects of hypertension result.

This case shows bilateral nodularity caused by bilateral adrenal adenomas. The abnormal areas are overlayed in green and the normal adrenal outlined in yellow.Images courtesy of: Ashley Davidoff, M.D.

This massive adrenal carcinoma (in green overlay) occupies almost the entire left side of the abdomen, and is so bulky that it has literally pushed the left kidney (red overlay)down to the pelvis, and rightward to the right kidney. Sometimes adrenal carcinomas produce hormones with functional effects relating to the type of hormone they produce.Images courtesy of: Ashley Davidoff, M.D.

Masses can be classified according to their size.

Conditions producing small masses less than 4 cm. include:

adenoma
hyperplasia
metastasis
pheochromocytomas

Conditions with larger masses greater than 4 cm. include:

cysts
hematomas
metastasis (especially from breast and lung cancers)
myelolipomas
pheochromocytomas belonging to the MEN syndrome

When a mass is greater than 6cm., the most likely diagnosis is a primary carcinoma.

Anatomy and Physiology of the Adrenal Glands: Incidentaloma

An “incidentaloma” is the most common adrenal tumor. It represents a small benign adenoma, (“oma” = tumor) of no functional significance, which is found incidentally, and hence its name. A nodule that is less than 3cm. with a density of less than 10 HU on CT, is diagnostic of the “incidentaloma”. The characteristic finding on MRI is a darkening in the “out of phase” T1 sequence of the tumor .

In this CT scan, the green overlay is a soft tissue nodule that was found incidentally.Courtesy of: Ashley Davidoff, M.D.

 

The nodule is oval, with smooth borders, measures less than 3cm., (left image) and has a density of 2.6 HU. (right image) It is a classical “incidentaloma” or benign adenoma. No further workup is needed.Courtesy of: Ashley Davidoff, M.D.

Anatomy and Physiology of the Adrenal Glands: Bilateral Adrenal Masses

In a patient with a known malignancy, particularly in lung or breast carcinomas, the finding of bilateral adrenal masses most likely represents metastatic disease. However, documenting the entity of metastatic adrenal disease is sometimes a decision focus for the type of treatment a patient may receive. In these circumstances, an adrenal biopsy must be performed .


The finding of bilateral masses (green overlay), in a patient with a known malignancy most likely represents metastatic disease. This patient has known lung carcinoma and bilateral masses with peripheral enhancement, which almost certainly represents metastatic disease.Courtesy of: Ashley Davidoff, M.D.

The most common causes of bilateral adrenal enlargement include:

metastases (especially lung and breast)

bilateral adenomas,

hemorrhage; spontaneous,: (particularly in infants),

traumatic, and bleeding disorders.

Less common causes include:

·         histoplasmosis and tuberculosis

·         neuroblastoma

·         pheochromocytoma

Additionally, rare causes include:

·         Addison’s disease

·         amyloidosis

·         lymphoma


This is a rare case of bilateral adrenal enlargement in a patient with end stage lymphoma.Courtesy of: Ashley Davidoff, M.D.

Calcification in the Adrenal Glands

 

 

This coned down plain film of the abdomen details bilateral adrenal calcification. Note that in this instance, the right adrenal gland is slightly higher than the left.
Courtesy of: Ashley Davidoff, M.D.

The most common cause of adrenal calcification is:

hemorrhage (occurring in the perinatal period) or

trauma.

Other less common entities producing calcifications in the adrenal include:

·         histoplasmosis

·         neuroblastomas

·         tuberculosis

Uncommon causes include:

·         Addison’s disease

·         amyloidosis

·         Cushing’s syndrome

·         cysts

·         neoplasms

·         pheochromocytomas

The idiopathic causes have no known etiology.

Anatomy and Physiology of the Adrenal Glands: Cyst in the Adrenal

Cysts in the adrenal are not uncommon and they may be quite large. Adrenal cysts are fluid containing structures enclosed by a thin smooth wall. In general, adrenal cysts have no functional or clinical significance. MRI is the best method of confirming their make up and morphology.

This MRI scan through the upper abdomen shows a fairly large mass in the left adrenal that is dark on T1-weighting, and is as bright as CSF on the T2-weighted image. These findings are characteristic of a benign cyst. No further workup is needed. Note how the right adrenal is compressed against the liver with only the medial limb in view.Courtesy of: Ashley Davidoff, M.D.

 

CT Imaging of the Adrenal Glands: Overview

The adrenal gland is surrounded by a natural contrast agent – retroperitoneal fat. The soft tissue density (grey) of the adrenal is easily identified in marked contrast to the black background of the fat. CT is a powerful tool that is well equipped to define the morphology of the gland, but it falls short of MRI in the characterization of a few lesions including cystic lesions and pheochromocytoma.Intravenous contrast is generally not required to define the morphology of the gland. It is particularly important not to use contrast when there is a question of pheochromocytoma, since the contrast can induce a fatal hypertensive crisis.
Optimal collimation is key when studying the adrenal. The adrenals are best visualized with contiguous 3mm. sections (sometimes retrospectively viewed at 1.5mm collimation)through the entire gland.Adrenal CT is included in the staging evaluation of a variety of tumors, particularly bronchogenic carcinoma. Thus the technologist should ensure that both the adrenals are visualised with appropriate collimation in their entirety in cancer staging examinations. In fact, if you “pick up” an unsuspected lung mass on any CT scan, it would be very helpful to include the adrenals using 3mm collimation.

It is also important to know that some tumors are exophytic, meaning they hang off the edges of the main gland. Seeing a normal gland on one cut does not mean the gland is normal. The glands have to be examined from top to bottom.

CT Imaging of the Adrenal Glands: Normal Character on CT Scan

The adrenal gland is of soft tissue density on non contrast scan, measuring between 10 and 30 HU on the non contrast study. Because of its rich blood supply, a contrast study will enhance the gland significantly, particularly in stressful situations where blood flow to the gland is increased.

The adrenal glands behave like other parenchymal organs on CT scanning in that they are of soft tissue density. Under physically stressful situations, they may enhance significantly more than other organs due to their rich blood supply.Courtesy of: Ashley Davidoff, M.D.

CT Imaging of the Adrenal Glands: Abnormal Adrenal on CT scan

CT is a highly sensitive modality, although slightly less specific than MRI. The CT may be able to see a disorder, but often cannot exactly define the disorder. However, the CT can easily identify fat, which is present in conditions such as incidentaloma and myelolipoma. If an incidentaloma is suspected, non-contrast study is indicated. CT is more sensitive to the presence of calcification than MRI.It is very important for the radiologist to make a distinction between unilateral disease and bilateral disease. Cushing’s disease, for example, affects both adrenal glands and treatment may relate to surgical excision of a tumor of the pituitary gland. A unilateral nodule in Conn’s syndrome would require excision only of the affected adrenal gland.

In adrenal hemorrhage, serial CT examination will reveal evolution and usually resorption, and hence a progressive decrease in the size of the gland. The issue of adrenal mass or hemorrhage arises in the neonatal setting as well as following trauma in the adult.

 

MR Imaging of the Adrenal Glands: Overview

MRI is slightly more specific than CT but less sensitive to morphologic disorder. It is well suited to characterize fat, hemorrhage, and cystic changes, and MRI is the study of choice in patients with suspected pheochromocytoma or adrenal cysts. The advantage of being able to acquire images in many planes enables the radiologist and referring physicians to have a different perspective that sometimes provides relevant clinical information.MRI of the pituitary is superior to CT imaging, which has relevance in adrenal disease that is secondary to pituitary disease. Hence, in planning trans-sphenoidal surgery of the pituitary in patients with pituitary adenoma and resultant Cushing’s disease, it would be important to visualise the optic chiasm, the optic nerves, and the cavernous sinuses. This evaluation is best performed by MRI.

If a study of the adrenals is required during pregnancy, MRI is the diagnostic option of choice.

Visualization of calcification and bony structures is limited on MRI. On the other hand, MRI is very useful for defining vascular structures and the perfusional nature of adrenal lesions.

 

MR Imaging of the Adrenal Glands: Normal Character on MRI

Because the normal adrenal gland is surrounded by retroperitoneal fat, the relatively low intensity of the gland is seen in sharp contrast to the fat, particularly on T1 weighted images. MRI is best used in the characterization of adrenal gland masses.

The T1-weighted sequence is performed to optimize the morphology of the gland and the “in-phase” and “out-of-phase” techniques are also useful in defining the incidentaloma. The T2-weighted sequence enables the characterization of lesions with high water content as well as pheochromocytomas.

These “in-phase” and “out-of-phase” T1-weighted images focus on the normal right gland. The left gland cannot be visualised on these images. On the “in-phase” sequence (first image), the adrenal is almost isointense with the liver while on the “out-of-phase” sequence, the gland darkens slightly.Courtesy of: Ashley Davidoff, M.D.

 

These images reflect a normal right adrenal gland showing the difference between the normal T1-weighted and T-2weighted images. On T1-weighted images, (first figure) the intensity of the adrenals is almost isointense with the liver, while on T2-weighted image, (second figure) the adrenal is brighter than the liver.Courtesy of: Ashley Davidoff, M.D.

The above images are fat suppressed T1-weighted fat suppressed images of the right adrenal gland. Note the progressive and rapid gadolinium enhancement of the right adrenal gland. In this case, the adrenal gland enhances to the same extent as the spleen and slightly less than the kidneys.Courtesy of: Ashley Davidoff, M.D.

MR Imaging of the Adrenal Glands: Abnormal Adrenal on MRI

MRI is very useful in the relatively frequently asked indication to “rule out pheochromocytoma”. It is said that the adrenal gland is like a “lightbulb” on T2-weighted imaging in patients with pheochromocytoma – meaning of course that it is very bright. This is not always the case in pheochromocytoma, but if you really want to see a lightbulb, take a look at the adrenal cyst. It will hurt your eyes.

“In-phase” and “out-of-phase” T1 sequences are sensitive to the presence of steroidal fat present in the incidentaloma, and MRI competes well with CT for the diagnosis of this condition. Characterization of another fatty lesion called the myelolipoma is also easily solved by fat sensitive MRI sequences.

This MRI scan through the upper abdomen shows a fairly large mass in the left adrenal that is dark on T1-weighting, and is as bright as CSF on the T2-weighted image. These findings are characteristic of a benign cyst. No further workup is needed. Note how the right adrenal is compressed against the liver with only the medial limb in view.Courtesy of: Ashley Davidoff, M.D.

US Imaging of the Adrenal Glands: Overview

Ultrasound is quick, and a relatively inexpensive technology, but it has significant limitations in adrenal scanning. The adrenal glands are difficult to examine by ultrasound because of their small size, their location high in the abdomen under the rib cage, and the presence of retroperitoneal fat and bowel gas. In thin patients, the normal adrenal may be identified.An anterior or lateral approach may be necessary, particularly for the right adrenal gland, which occasionally can be seen through the liver. Bowel gas often impairs visualization of the left adrenal gland. A variety of patient positions and scanning windows are often required to adequately examine the glands.

Since CT and MRI have so many diagnostic advantages, ultrasound is not used as the primary modality for the adrenal glands. Ultrasound can help in the characterization of large adrenal masses, as well as to define whether a suprarenal mass originates from the kidney or the adrenal.

 

This is a case of neonatal hemorrhage, showing a complex mass with both solid and cystic components.Courtesy of: Ashley Davidoff, M.D.

This image represents a solid mass that is half the size of the kidney below the mass. A mass of this size typically indicates a primary carcinoma, however, this case represents a large pheochromocytoma.Courtesy of: Ashley Davidoff, M.D.

Conclusion: Final Thoughts

The adrenal glands are small and mighty. We started this module with that as the opening statement and we end with the same statement. Hidden in the depths of the body – these seemingly insignificant structures play an essential role. One only has to witness or read of the dire consequences of an “adrenal crisis”, the manifestations of the Waterhouse-Frederichsen syndrome or the “Addisonian crisis” to know and understand the part these two little glands play and what happens when they fail.The glands are often difficult to find on imaging. The left gland is best found on the axial cuts showing the splenic vein, and the right is found on the axial cuts showing the IVC emerging from the liver. Once a wisp of the gland is seen it should be followed up and down till it can no longer be seen. Nodules and masses of the adrenals are notorious for hanging out of the gland (exophytic) and a gland cannot be considered normal until its full extent has been scanned up and down.

The incidentaloma, or benign adenoma, is the most common mass of the adrenal and proof of a lipid substrate in the tumor makes a significant contribution to diagnosis and patient management. A pheochromocytoma crisis may be precipitated by administration of iodinated contrast, and although CT is our preferred modality for the adrenals, pheochromocytoma is best evaluated by MRI or MIBG nuclear scan.

The distinction between the cortex and medulla has eluded conventional imaging. Multidetector scanning is enabling better vascular imaging, and since the cortex is an arterial part of the gland and the medulla, dominantly a venous structure, the arterial phase should enable identification of the enhanced cortex and unenhanced medulla. We are looking forward to the possible potential of the advancing technology to unfold the mysteries that still hide in the adrenals.

References: Reference Material

·         Abeloff. (2000). Clinical Oncology (2nd ed.). New York: W. B. Saunders.

·         Brenner, & Rector. (2000). The Kidney (6th ed.). New York: W. B. Saunders.

·         Cotran. (1999). Robbins Pathologic Basis of Disease (6th ed.). New York: W. B. Saunders.

·         Goldman. (2000). Cecil Textbook of Medicine (21th ed.). New York: W. B. Saunders.

·         Gray’s Anatomy (38th ed.). (1995). Churchill Livingstone.

·         Moore. (1999). Clinically Oriented Anatomy (4th ed.). Lippincott, Williams & Wilkins.

·         Townsend. (2001). Sabiston Textbook of Surgery (16th ed.). New York: W. B. Saunders.

·         Walsh. (1998). Campbell’s Urology (7th ed.). New York: W. B. Saunders.

·         Wilson. (1998). Williams Textbook of Endocrinology (9th ed.). New York: W. B. Saunders.

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