Adrenal Glands

The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. The outer zona glomerulosa secretes mineralocorticoids (primarily aldosterone); the middle zona fasciculata secretes glucocorticoids (primarily cortisol); and the innermost zona reticularis secretes androgens. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. The medullary cells function more like neurosecretory postsynaptic neurons rather than traditional endocrine cells. The adrenal glands have a rich vascular supply and complex relationships with their surrounding organs.

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Overview

Location

There are 2 adrenal glands in the body and each gland is in close association with a kidney. The adrenal glands are:

  • Retroperitoneal structures
  • Located on the superomedial aspect of each kidney
  • Within the renal fascia and perirenal fat
  • Separated from the kidneys by a fibrous tissue
Adrenal gland

Adrenal gland located on the superior medial aspect of each kidney

Image by Lecturio.

Borders/anatomic relations

  • Inferior to both glands is the kidney.
  • Right adrenal gland:
    • Anteromedial: inferior vena cava
    • Lateral: liver
    • Posterior: diaphragm
  • Left adrenal gland:
    • Anteriorly:
      • Tail of the pancreas
      • Spleen
      • Stomach
    • Medially: abdominal aorta
    • Inferiorly: splenic vein and artery
    • Posterior: diaphragm

Development

  • Adrenal cortex:
    • Derives from the mesoderm
    • The primitive fetal cortex develops from the mesothelial cells on the dorsal wall of the primitive coelom.
    • Fetal cortex:
      • Actively produces steroids during gestation
      • Involutes after birth
    • Definitive cortex (with mature cortical zones) develops slowly after birth.
  • Adrenal medulla:
    • Derived from neural crest cells (neuroectoderm)
    • Migrates to the medial portion of the developing gland → encapsulated by the developing cortex
  • Changes in size:
    • At birth: The adrenal gland is ⅓ the size of the kidney.
    • Adulthood: The adrenal gland is 1/30th the size of the kidney.

Gross Anatomy

General structure

The adrenal glands are composed of 2 functionally separate layers: the adrenal cortex and the adrenal medulla. Each layer has its own embryologic origins, anatomy, histology, and functions.

  • Right: triangular in shape
  • Left: semilunar in shape

Adrenal cortex

  • Outer portion of the gland
  • Makes up 80%‒90% of the gland by volume
  • More fat → yellow color
  • Firm consistency
  • Fine granular surface

Adrenal medulla

  • Central portion of the gland
  • Only about 10%‒20% of the gland by volume
  • Red-brown in color

Microscopic Anatomy

Adrenal cortex

The adrenal cortex has 3 distinct zones, and each zone has its own regulation and secretory products. These 3 zones (from external to internal) are:

  • Zona glomerulosa:
    • Secretes mineralocorticoids (mainly aldosterone)
    • Cells are arranged in circular clusters.
  • Zona fasciculata:
    • Secretes glucocorticoids (mainly cortisol)
    • Cells are arranged in columns.
  • Zona reticularis:
    • Secretes androgens (e.g., dehydroepiandrosterone (DHEA) and androstenedione)
    • Cells are in a reticular arrangement.

Adrenal medulla

  • Cells within the medulla are modified postganglionic sympathetic neurons that form synapses with preganglionic sympathetic nerve fibers.
  • Made up of chromaffin cells:
    • Neurosecretory “postsynaptic” cells (thought to be kept in a state of incomplete differentiation by cortisol)
    • Secrete catecholamines:
      • Epinephrine and norepinephrine
      • Responsible for the fight-or-flight response
    • Can be described as an endocrine sympathetic ganglion (lack axons)

Neurovasculature

Arterial supply

Adrenal glands are highly vascular organs.

  • Blood supply (to both the cortex and medulla): about 50‒60 branches from the following 3 major arteries entering the glands:
    • Superior suprarenal artery from the inferior phrenic artery
    • Middle suprarenal artery from the aorta
    • Inferior suprarenal artery from the renal artery
  • Medullary blood supply:
    • Some capillaries pass through all 3 layers of the cortex and into the medulla. The medulla can be influenced by secretions of the cortex (especially glucocorticoids).
    • Some arteriole branches go straight from the capsule into the medulla.
  • Blood flow: approximately 10 mL/min
  • Adrenocorticotropic hormone (ACTH) increases blood flow to the adrenal glands.
  • Adrenal capillaries are fenestrated → better absorption of secretary products

Venous drainage

  • Typically drain via a single vein on each side: suprarenal (adrenal) veins
    • Right suprarenal vein → inferior vena cava
    • Left suprarenal vein → left renal vein → inferior vena cava
  • Specialized characteristics of suprarenal veins:
    • Lack a tunica media in some segments → chromaffin cells are present right next to the tunica intimasecrete their content quickly/directly into the blood
    • Smooth muscle of the tunica media is arranged longitudinally → can contract and expel its content quickly
Vascular supply to the adrenal glands

Vascular supply to the adrenal glands

Image by Lecturio.

Lymphatic drainage

  • Drained via 2 lymphatic plexuses:
    • 1 in the medulla
    • 1 deep in the adrenal capsule
  • Drains into:
    • Lateral aortic lymph nodes
    • Paraaortic nodes near the origin of the renal artery
    • Thoracic duct (some lymphatics traverse the diaphragm)

Innervation

  • Visceral fibers (traversing the retroperitoneal autonomic ganglia) from:
    • Vagus nerve
    • Phrenic nerve
    • Greater and lesser splanchnic nerves
  • Preganglionic sympathetic fibers synapse directly with cells in the adrenal medulla.

Function

Functions of the adrenal cortex hormones

The adrenal cortex secretes hormones that are involved in the regulation of fluids, electrolytes, available energy, and inflammation, and in the development of sexual characteristics.

  • Mineralocorticoids: aldosterone
    • ↑ Blood pressure (↑ water reabsorption from the kidneys)
    • ↑ Serum Na+ (↓ urinary excretion of Na+)
    • ↓ Serum K+ (↑ urinary excretion of K+)
    • ↑ Serum pH (↑ urinary excretion of H+)
  • Glucocorticoids: cortisol, corticosterone
    • ↑ Immediate available energy through:
      • Fat and protein catabolism → ↑ amino acid and lipid levels in blood
      • Gluconeogenesis
      • Appetite stimulation
    • ↑ RBCs
    • ↑ Serum calcium from bone resorption (leads to ↓ bone mineral density over time)
    • Anti-inflammatory effects:
      • ↓ Inflammation
      • ↓ Blood vessel permeability
      • Long-term exposure suppresses the immune system.
  • Androgens: DHEA and androstenedione
    • Important for the development of secondary sex characteristics
    • Stimulates axillary, pubic, and male-pattern facial hair

Functions of the adrenal medulla hormones

The adrenal medulla secretes the catecholamines epinephrine and norepinephrine, which stimulate the fight-or-flight response. The effects include:

  • ↑ Blood pressure
  • ↑ Heart rate
  • ↑ Circulation to skeletal muscles
  • ↑ Respiration and bronchodilation
  • ↑ Blood glucose levels by:
    • Stimulating glycogenolysis
    • Stimulating gluconeogenesis
    • Inhibiting insulin release
  • ↓ Digestion

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Clinical Relevance

Several clinical conditions can result from abnormalities of the adrenal hormones. The most important conditions include:

  • Pheochromocytoma: rare catecholamine-secreting tumors that arise from the chromaffin cells of the adrenal medulla. Individuals typically present with treatment-resistant hypertension, episodic headaches, sweating, and tachycardia. Diagnosis is made via adrenal imaging studies and laboratory assessment that shows elevated serum catecholamines. About 90% of cases are benign, and surgical resection is the only curative treatment.
  • Adrenal insufficiency: inadequate production of glucocorticoids, mineralocorticoids, and adrenal androgens. Diagnosis is made by measuring cortisol and ACTH levels and with ACTH stimulation testing. Management involves glucocorticoid and mineralocorticoid replacement therapy.
    • Addison’s disease (primary adrenal insufficiency): Some of the etiologies include autoimmune disease, infections, and malignancy (among others).
    • Secondary and tertiary adrenal insufficiency: conditions resulting from the decreased production of ACTH within the pituitary gland. Secondary and tertiary adrenal insufficiency can also occur due to prolonged glucocorticoid therapy.
  • Congenital adrenal hyperplasia: a group of autosomal recessive disorders that cause a deficiency of an enzyme (most commonly 21-hydroxylase deficiency) needed for cortisol, aldosterone, and androgen synthesis. Clinical manifestations include ambiguous genitalia in genotypic females, salt wasting, and hypoglycemia. A less severe form known as nonclassical congenital adrenal hyperplasia also exists, which typically presents in puberty. Lifelong glucocorticoid replacement is needed.
  • Cushing’s syndrome: a condition resulting from chronic exposure to excess glucocorticoids. Etiologies include chronic glucocorticoid intake, increased adrenal secretion of cortisol, or increased pituitary or ectopic secretion of ACTH. Typical clinical features include central obesity, thin and bruisable skin, abdominal striae, secondary hypertension, hyperglycemia, and proximal muscle weakness. Diagnosis is by urinary and/or salivary cortisol testing along with a low dose dexamethasone-suppression test, determination of ACTH levels, and imaging.
  • Hyperaldosteronism: increased secretion of aldosterone from the adrenal cortex. Hyperaldosteronism may be primary (resulting from autonomous secretion (Conn syndrome)) or secondary (resulting from physiologic secretion due to stimulation of the RAAS) and presents with hypertension, hypokalemia, and metabolic alkalosis. Diagnosis involves measuring plasma aldosterone and renin activity along with imaging to identify hormone-secreting tumors. Management involves the use of aldosterone receptor antagonists and surgical excision of any aldosterone-secreting tumors.
  • Hypoaldosteronism: a condition resulting from low levels of aldosterone. Hypoaldosteronism can be caused by decreased aldosterone production or peripheral resistance to aldosterone. When hypoaldosteronism occurs as a result of an acquired decrease in renin production from the kidneys, the condition is referred to as renal tubular acidosis (RTA) type 4. Most cases are asymptomatic and diagnosed when routine lab evaluation reveals hyperkalemia and mild hyperchloremic metabolic acidosis, prompting further work-up.

References

  1. Roman, S. (2020). Surgical anatomy of the adrenal glands. UpToDate. Retrieved Aug 16, 2021, from https://www.uptodate.com/contents/surgical-anatomy-of-the-adrenal-glands 
  2. Megha, R. (2021). Anatomy, Abdomen and pelvis, adrenal glands (suprarenal glands). StatPearls. Retrieved Aug 16, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/666/ 
  3. Ovalle, W., Nahirney, P. (2020). Netter’s Essential Histology: With Correlated Histopathology (Netter Basic Science) (3rd ed.). Elsevier.

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