Clinical Radiology (2005) 60, 953–959

PICTORIAL REVIEW

Embryology of the adrenal glands and its relevance

to diagnostic imaging
T.D. Barwicka,*, A. Malhotraa, J.A.W. Webba, M.O. Savageb, R.H. Rezneka

Departments of aDiagnostic Radiology, and bPaediatric Endocrinology, St Bartholomew’s Hospital, London,

UK

Received 20 October 2004; received in revised form 20 March 2005; accepted 6 April 2005

KEYWORDS An understanding of the embryology of the adrenal glands is necessary to appreciate

Adrenal gland, the location of adrenal ectopic, or rest, tissue which can occur anywhere along the
abnormalities; Adre- course of gonadal descent. This tissue usually has no clinical significance, but may
nal gland, hyperplasia; become hyperplastic in patients with primary or secondary adrenal pathology. In
Kidney, abnormal- congenital adrenal hyperplasia, hyperplastic rest tissue may present as a soft-tissue
ities; Paediatrics mass, particularly in the gonads and retroperitoneum, and may be mistaken for
tumour. The adrenal in the neonate is proportionately much larger than in the adult;
in renal ectopy or agenesis the ipsilateral adrenal is normally sited and may be
mistaken for a kidney because of its size. This review article illustrates the
embryology of the adrenal with particular emphasis on the relevance of embryology
to pathology.
Q 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights
reserved.

Embryology of the adrenal glands
The adrenal gland has a dual embryological origin.
The adrenal cortex arises from the coelomic
mesoderm of the urogenital ridge, and the medulla
arises from neural crest tissue (Figs. 1 and 2).1,2
During the 5th week of fetal development,
mesothelial cells from the posterior abdominal
wall, between the root of the bowel mesentery
and developing mesonephros/gonad (urogenital
ridge), proliferate and form the fetal or primitive
cortex of the adrenal. In the 6th week, a second
wave of mesothelial cells surrounds the primitive
cortex and later forms the adult or definitive
cortex.1,2 By 8 weeks, the cortical mass separates
from the rest of the mesothelial tissue and is
surrounded by connective tissue.3
* Guarantor and correspondent: T.D. Barwick, Department of
Radiology, St Bartholomew’s Hospital, West Smithfield, London
EC1A 7BE, UK. Tel.: C44 2076018329.
E-mail address: tara.barwick@btinternet.com
(T.D. Barwick).
The adrenal medulla arises from neural crest
tissue in the adjacent sympathetic ganglion at the
level of the coeliac plexus (Fig. 1).1–4 These neural
crest cells, which stain yellow or brown with
chrome salts, are called chromaffin cells and
migrate towards the adrenal cortex at 7 weeks.
They gradually invade the medial aspect of the
cortical tissue along its central vein to gain a
central position.
Complete encapsulation of the medulla does not
occur until late fetal development. The adrenal
cortex differentiates fully into the three zones by 3
years of age (Fig. 2).1,3 The zona glomerulosa and
zona fasciculata are present at birth, but the zona
reticularis develops later.
Anatomy
At birth the adrenals are 10 to 20 times larger than
adult glands relative to body weight, and approxi-
mately one third the size of the neonatal kidney.1
The fetal and neonatal adrenal gland consist

0009-9260/$ - see front matter Q 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.crad.2005.04.006
954 T.D. Barwick et al.

Figure 1 Fetus at 7 weeks. Transverse sections at level of the adrenals show developing gonads and adrenal cortex
within urogenital ridge. Migration of neural crest cells from sympathetic ganglion forms adrenal medulla.

predominately of cortex which has an active role in
the synthesis of glucocorticoids, precursor steroids,
sex steroids, oestrogens and progesterone in the
third trimester and the first 3 months after birth. On
US, the neonatal adrenal characteristically has a
thin reflective core surrounded by a thick transonic
zone (Fig. 3).5 The gland rapidly decreases in size as
the fetal cortex regresses; the size of the adult
adrenal is approximately 8% that of the kidney.
The right adrenal lies between the liver, inferior
vena cava and right crus of the hemidiaphragm and
superior to the upper pole of right kidney. The left
adrenal lies between the left crus of the hemi-
diaphragm and the tail of the pancreas, and is
superomedial to the upper pole of left kidney.4,6 On
CT, the adrenal typically has an inverted “y” or “v”
shape on the left and a linear or inverted “v” on the
right, depending on the level of section.7 The 95th
percentile maximum width of the body of the
normal adrenal is less than 1 cm, and that of each
limb is less than 5 mm.8 The normal length should
be less than 4 cm.9

Figure 2 Fetal adrenal development. Diagram of fetal adrenal cortex and medulla, showing encapsulation of medulla
and differentiation of adrenal cortex into three layers.
Embryology of the adrenal glands and its relevance to diagnostic imaging
Figure 3 Normal neonatal adrenal gland. US shows
right adrenal gland with thin echogenic core (arrowheads)
and thick transition zone (arrowed). Note “y” shape and
large size relative to right kidney (RK); L, liver.
Developmental abnormalities of the
adrenal
Developmental abnormalities of the adrenal gland
can be divided into ectopic or accessory tissue and
heterotopia.
Ectopic or accessory adrenal tissue, known as
adrenal rest tissue, occurs when fragments of tissue
break off during development. The adrenal rests
may contain cortical tissue only or other cortical
and medullary tissue, depending on whether the
fragments break off before or after migration of
neural medullary tissue into the cortex. Thus,
accessory adrenal tissue close to the original
position of the adrenal may contain medulla; but
more distant accessory adrenal tissue, which
usually migrates with the developing gonad, con-
tains cortex only.10,11
Ectopic adrenal cortical tissue is found in up to
50% of neonates4,12 and usually atrophies, so that it
only occurs in 1% of adults.13 Most ectopic adrenal
tissue is found in the vicinity of the adrenals around
the coeliac axis.10,13 However, since the adrenal
cortex and gonads both arise from the urogenital
ridge, in early embryogenesis adrenal cortical
tissue can migrate with the descending gonads
(Fig. 4). Adrenal rests have been described within
the retroperitoneum, broad ligament, ovaries,
inguinal region and testis4,10,11,13–16 and occur
along the path of testicular descent in up to 50%
of newborns.10 Adrenal rests within the testis occur
in 7.5% to 15% of neonates and normally regress in
955
early infancy. The rests are usually an incidental
finding at surgery or autopsy, rarely greater than 3
to 5 mm in size and usually of no clinical
significance. However, they may become important
if there is excess adrenocorticotrophic hormone
stimulation resulting in hyperplastic change with
excessive hormone production, or associated neo-
plastic change occurs.10,11,14 Ectopic adrenal tissue
should be considered in the differential diagnosis of
soft-tissue masses closely related to the urogenital
system or to the course of gonadal descent.13
Adrenal heterotopia occurs very rarely, when
accessory adrenal tissue is incorporated into
adjacent organs such as kidney or liver because of
incomplete separation of primitive adrenal cortical
cells from the coelomic mesothelium (meso-
derm).10,15–18 Adrenal heterotopia may be complete
or partial, depending on whether none or a portion
of the adrenal remains in its normal position.
Although rare, death from adrenal insufficiency
following excision of heterotopic adrenal gland has
been reported.4
The adrenals and adrenal rest tissue in
congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) describes a
group of autosomal recessive disorders character-
ized by enzyme defects in the pathway of cortisol
synthesis. Deficient cortisol production leads to
increased ACTH production and hyperplasia of the
adrenal cortex (Figs. 5 and 6).19 In patients with
untreated CAH, there is typically bilateral diffuse
enlargement of the adrenals with preservation of
the normal configuration, but occasional nodular or
mass-like transformation may occur. 20 The
enhancement pattern of the adrenal gland on CT
in persons with CAH has not been documented. In
our own limited experience, the bilateral adrenal
masses enhance inhomogeneously, with foci of non-
enhancement and foci of marked enhancement
often simulating an adrenal tumour (Fig. 5). In CAH,
sustained elevation of ACTH stimulates any adrenal
rest tissue, which becomes hyperplastic and may be
functionally active. The rest tissue may be a
presenting feature or a sign of poor hormonal
control, and can be found anywhere along the
course of testicular descent.15,21,22
Retroperitoneum
Rest tissue in the retroperitoneum, particularly at the
level of the coeliac axis, is well documented.10,13,23
The presence of this rest tissue is not usually
956 T.D. Barwick et al.

Figure 4 Development of gonads and adrenals. Anterior views showing origin of kidney and gonadal tissue from
urogenital ridge. Note ascent of kidneys to upper lumbar region and descent of gonads. Adrenal rest tissue may migrate
with gonads along the course of their descent.

manifest unless hyperplasia secondary to ACTH

stimulus occurs.21 There are no specific features
of the retroperitoneal mass that result from
hyperplasia of this rest tissue, and it is indistin-
guishable from other types of retroperitoneal mass
(Fig. 7).

Testes

Some patients with CAH develop testicular masses

secondary to hypertrophy of testicular rest tissue.
The testicular masses atrophy under the influence
of high doses of glucocorticoids.15,17,21 In CAH,
hyperplastic adrenal rest tissue within the testis has
been described at US in 24% to 27% of cases,24,25 but
recently it has been suggested that the prevalence
of testicular rest tissue may be much higher, up to
94% at US and MRI.26
Typically, ultrasonography shows bilateral,

Figure 5 Congenital adrenal hyperplasia due to 21 Figure 6 Congenital adrenal hyperplasia. T2-weighted
hydroxylase deficiency in 37-year-old. Contrast-enhanced axial MR image in 46-year-old with 21 hydroxylase
CT shows massive adrenal hyperplasia bilaterally. Area of deficiency, showing massive adrenal enlargement typi-
necrosis is arrowed on left. cally of high inhomogeneous signal intensity (arrows).
Embryology of the adrenal glands and its relevance to diagnostic imaging 957

Figure 7 Retroperitoneal adrenal rest tissue. Three-year-old boy with severe genital virilization, rapid growth and an
abdominal mass. (a) Axial T2-weighted MR image shows bilateral smooth adrenal enlargement (arrows) consistent with
hyperplasia. Signal intensity of adrenals is uniform and intermediate compared with liver. (b) Axial T1-weighted image
shows retroperitoneal mass (arrowed) of intermediate signal intensity encasing aorta and origin of renal arteries. (c)
After 18 months of hydrocortisone replacement treatment, T2-weighted axial MR image shows normal adrenals
bilaterally and (d) complete resolution of retroperitoneal mass, suggesting adrenal rest tissue. The normal aorta (arrow)
and right crus of diaphragm (curved arrow) are clearly seen.

multifocal, intratesticular masses of reduced
reflectivity,22,24–26 which may be associated with
acoustic shadowing (Fig. 8).27 The MR features of
testicular adrenal rest tissue are similar to those of
normal adrenal glands. Most of the masses are
isointense to muscle on T1-weighted images,
hypointense on T2-weighted images and enhance
diffusely after contrast administration.25,26 Unfor-
tunately, both US and MR features are indistinguish-
able from testicular tumours without an
appropriate clinical history and endocrine profile.26
Although the clinical features of CAH are usually
present, occasionally the testicular lesion may be
the only clinical finding at presentation.15,24 There-
fore CAH must be excluded in any child presenting
with bilateral testicular masses and precocious
puberty.16 Recognition of hyperplastic adrenal
rest tissue as a cause of intratesticular masses in
patients with CAH means that unnecessary biopsy or
even orchidectomy can be avoided.21,25 The
presence of bilateral adrenal masses and reduction
in size of the testicular masses with glucocorticoid
treatment is diagnostic. In difficult cases, or if the
mass is unresponsive to steroid treatment, percu-
taneous sampling of the gonadal veins for adrenal
precursor steroids may be helpful.15,25,28
958
Figure 8 Adrenal rests in testes. A 31-year-old with
uncontrolled congenital adrenal hyperplasia presented
with hard, craggy testes. US showed intratesticular
masses of reduced reflectivity and reflective focus with
associated acoustic shadowing on left (arrowed). In view
of this and the history, hormonal treatment was tried and
masses decreased in size.
The adrenals in renal agenesis/ectopia
The adrenals and kidneys have separate embryolo-
gical origins. Like the adrenal cortex, the kidneys
develop from mesenchymal tissue. However, they
develop in the pelvis and ascend to the upper
lumbar region, where they meet the adrenals at 8
weeks of fetal life (Fig. 4).1 In renal agenesis, the
ipsilateral adrenal is usually present and normally
sited,29–31 appears enlarged and flattened and has
been described as discoid.30,32 This is thought to
relate to the absence of pressure from the kidney
which usually gives the adrenal the normal “y” or
T.D. Barwick et al.
Figure 9 Left renal agenesis. Contrast-enhanced CT
showing linear left adrenal gland (arrowed), normally
located, despite left renal agenesis. Note tail of pancreas
lying in left renal fossa.
“v” configuration.5,7,30 In persons who do not have a
normally sited kidney, the disc-shaped adrenal
appears linear on CT (Fig. 9).30 In renal agenesis in
the neonate, where the adrenal is relatively large
(Fig. 3), care must be taken not to mistake it for
kidney.30,31,33
Conclusion
Hyperplasia of adrenal rest tissue is a rare but
important manifestation of conditions with exces-
sive adrenocorticotrophic hormone stimulation,
such as CAH. Knowledge of the embryology of the
adrenal glands is essential to appreciate the
location of this rest tissue. In males with CAH,
the radiological features of testicular rest tissue
help in the differentiation from tumour, thereby
avoiding unnecessary biopsy or even orchidectomy.
In neonates with renal ectopia or agenesis, the
normal relatively large adrenal should not be
mistaken for kidney.
Acknowledgements
Figs. 1, 2 and 4 were prepared by D. McLean.
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