PATHOPHYSIOLOGY,

EVALUATION, AND MEDICAL

MANAGEMENT OF
ADRENAL DISORDERS
Lt Col Hafizur Rashid
Classified Specialist- Surgery
Post Fellowship Training in Urology
CONTENT
 ADRENAL ANATOMY AND EMBRYOLOGY
 ADRENAL PHYSIOLOGY
 ADRENAL DISORDERS
 Increased Adrenal Function
 Cushing Syndrome
 Primary Aldosteronism (Conn syndrome)

 Pheochromocytoma

 Disorders of Decreased Adrenal Function

 Adrenal insufficiency (Addison disease)
 Disorders of Abnormal Adrenal Function
 Congenital Adrenal Hyperplasia
 ADRENAL LESIONS
 Malignant
 Benign
 ADRENAL INCIDENTALOMA
ADRENAL ANATOMY AND
EMBRYOLOGY
 Paired retroperitoneal
 Cortex and medulla

 4 to 5 g each

 4 to 6 cm in length and 2 to 3 cm in width

 Right is triangular, left crescent-shaped

 The cortex is derived from the intermediate mesoderm of

the urogenital ridge
 Medulla is derived from neural crest cells, from adjacent
sympathetic ganglia
ADRENAL ANATOMY AND
EMBRYOLOGY
ADRENAL PHYSIOLOGY
 Adrenal cortex
 Zona glomerulosa> Mineralocorticoid> angiotensin II &
serum potassium levels.
 Zona fasciculata > Glucocorticoid> ACTH
 Zona reticularis > Androgen> ACTH, Circadian

 Adrenal Medulla
 Partof the autonomic nervous system
 Epinephrine (80%)
 Norepinephrine (19%)
 Dopamine (1%)
ADRENAL DISORDERS- INCREASED FUNCTION-
CUSHING SYNDROME

 Cushing Syndrome
 Hypercortisolism secondary to excessive production of
glucocorticoids by the adrenal cortex
 Non ACTH dependent- 25%
 Cushing Disease- ACTH (Pituitary) dependent- 75%
ADRENAL DISORDERS- INCREASED FUNCTION-
CUSHING SYNDROME
ADRENAL DISORDERS- INCREASED FUNCTION-
CUSHING SYNDROME
ADRENAL DISORDERS- INCREASED FUNCTION-
CUSHING SYNDROME

 Diagnosis
S Cortisol> Circadian rhythm, Globulin Binding> Less
sensitive
 24-hour urinary free cortisol (UFC) evaluation > free
bioavailable cortisol.
 Overnight LD-DST- 1mg dexamethasone> serum cortisol
next morning > glucocorticoid negative feedback system >
ACTH-independent Cushing syndrome and ectopic ACTH
secretion fail to suppress cortisol > Cushing syndrome.
ADRENAL DISORDERS- INCREASED FUNCTION-
CUSHING SYNDROME
ADRENAL DISORDERS- INCREASED FUNCTION-
CUSHING SYNDROME

 Identifying the Cause of Cushing Syndrome

 Serum ACTH >
 High> Pituitary Imaging
 Low> Abdominal imaging

 Ectopic ACTH syndrome for patients who have high serum

ACTH levels, Normal pituitary
 Direct measurements of ACTH in a downstream venous
plexus —the inferior petrosal sinus—after CRH stimulation
has become the gold standard approach for distinguishing
ectopic ACTH production from Cushing disease.
ADRENAL DISORDERS- INCREASED FUNCTION-
CUSHING SYNDROME

 Treatment
 Exogenous Cushing Syndrome- Gradual withdrawal
 Cushing Disease- trans-sphenoidal surgical resection, failed-
bilateral adrenalectomy
 Ectopic ACTH Syndrome- Resection of the primary ACTH-
producing tumor, if not possible- bilateral adrenalectomy
 ACTH-Independent Disease- Surgical resection of diseased
Adrenal
 Medical Treatment of Hypercortisolism- if surgery fails/
impossible- metyrapone, aminoglutethimide trilostane,
ketoconazole, and etomidate
ADRENAL DISORDERS- INCREASED FUNCTION-
PRIMARY ALDOSTERONISM

 Primary Aldosteronism
 Primary- aldosterone secretion is independent of the RAAS,
and plasma renin levels will be suppressed.
 Secondary- elevated renin levels are the cause of elevations
in aldosterone secretion
ADRENAL DISORDERS- INCREASED FUNCTION-
PRIMARY ALDOSTERONISM
ADRENAL DISORDERS- INCREASED FUNCTION-
PRIMARY ALDOSTERONISM
ADRENAL DISORDERS- INCREASED FUNCTION-
PRIMARY ALDOSTERONISM
 Investigation
 Screening test
 Morning (between 8 and 10 AM) Plasma Aldosterone Concentration (PAC)
 Plasma Renin Assay (PRA) or Direct Renin Concentration (DRC)

 PRA/DRC value be set at 0.2 ng/mL/h

 Confirmatory Testing
 2 L of 0.9% sodium chloride IV over 4 hours, in the morning after an
overnight fast while the patient is in a recumbent position. PAC is measured;
a level greater than 5 ng/dL is diagnostic of primary aldosteronism, and
levels greater than 10 ng/dL are suggestive of aldosterone producing
adenomas
 Captopril suppression test, Furosemide-upright test and ACTH
stimulation test – low sensitivity
ADRENAL DISORDERS- INCREASED FUNCTION-
PRIMARY ALDOSTERONISM
ADRENAL DISORDERS- INCREASED FUNCTION-
PRIMARY ALDOSTERONISM

 Treatment and Prognosis

 Surgically correctable subtype of primary aldosteronism can
be offered unilateral adrenalectomy
 Other patients can be managed effectively with medical
therapy- The aldosterone receptor antagonists spironolactone
and eplerenone are agents of choice
ADRENAL DISORDERS- INCREASED FUNCTION-
PHEOCHROMOCYTOMA

 Pheochromocytoma is a tumor of the catecholamine-

producing cells of the adrenal medulla
 Among patients with incidental adrenal masses,
approximately 5% will have a pheochromocytoma
 “10% tumor”: 10% extra-adrenal, 10% familial, 10%
bilateral, 10% pediatric, and 10% malignant
ADRENAL DISORDERS- INCREASED FUNCTION-
PHEOCHROMOCYTOMA
ADRENAL DISORDERS- INCREASED FUNCTION-
PHEOCHROMOCYTOMA

 Clinical presentation
 Paroxysmal hypertension
 The triad of headache, episodic sudden perspiration, and
tachycardia is a classic hallmark of pheochromocytoma
 Hereditary pheochromocytomas- younger age and multifocal
and/or bilateral at presentation
 Malignant Pheochromocytoma- Metastatic disease is much
more common in extra-adrenal lesions, larger (>5 cm);
ADRENAL DISORDERS- INCREASED FUNCTION-
PHEOCHROMOCYTOMA
ADRENAL DISORDERS- INCREASED FUNCTION-
PHEOCHROMOCYTOMA

 Diagnostic Tests
ADRENAL DISORDERS- INCREASED FUNCTION-
PHEOCHROMOCYTOMA

 Cross-Sectional Imaging
 CT/ MRI- well-circumscribed lesions. Given their rich
vascularity and low lipid content, pheochromocytomas typically
measure an attenuation of greater than 10 HU on unenhanced CT
(mean approximately 35 HU).
 FDG PET Scan- Gold standard imaging modality
 MIBG Scan- Metaiodobenzylguanidine Scintigraphy
ADRENAL DISORDERS- INCREASED FUNCTION-
PHEOCHROMOCYTOMA
ADRENAL DISORDERS- INCREASED FUNCTION-
PHEOCHROMOCYTOMA

 Treatment
 Complete resection
of the tumor is
advised whenever
possible
ADRENAL DISORDERS- INCREASED FUNCTION-
PHEOCHROMOCYTOMA

 Treatment of Metastatic Pheochromocytoma:

 Current therapy for metastatic pheochromocytoma is largely
palliative.
 Systemic treatment of metastatic disease with radioactive 131I-
MIBG may be instituted
 Chemotherapy regimen for malignant cyclophosphamide,
vincristine, and dacarbazine (CVD).
ADRENAL DISORDERS- INCREASED FUNCTION-
PHEOCHROMOCYTOMA

 Treatment of Hereditary Pheochromocytoma

 Risk for malignancy is low
 Partial cortical-sparing adrenalectomy has been advocated
 Life-threatening addisonian crisis can also occur despite close
postoperative monitoring
ADRENAL DISORDERS- DECREASED
FUNCTION- ADRENAL INSUFFICIENCY
 Addison disease
 Aldosterone secretion by the adrenal glands does not
depend on ACTH, the zona glomerulosa continues to
function appropriately in patients with secondary adrenal
insufficiency.
 Mineralocorticoid deficiency is therefore present only in
patients with primary Addison disease
ADRENAL DISORDERS- DECREASED
FUNCTION- ADRENAL INSUFFICIENCY
ADRENAL DISORDERS- DECREASED
FUNCTION- ADRENAL INSUFFICIENCY
ADRENAL DISORDERS- DECREASED
FUNCTION- ADRENAL INSUFFICIENCY
 Addisonian Crisis
 Acute adrenal insufficiency, or adrenal crisis, is a life-
threatening condition often preceded by hypotension
unresponsive to fluid resuscitation.
 Patients are easily and often misdiagnosed with an acute
abdomen, whereas abdominal pain, nausea, vomiting,
and fever frequently accompany hypovolemia in these
individuals.
 Pediatric patients can exhibit hypoglycemic seizures
ADRENAL DISORDERS- DECREASED
FUNCTION- ADRENAL INSUFFICIENCY
 Addisonian state
 Adrenal insufficiency (an addisonian state) after
adrenalectomy in the setting of a normally functioning
contralateral adrenal gland is unlikely, but possible.
 Adrenalectomy for a cortisol-secreting lesion, because
functionality of the contralateral gland can be suppressed
 Patients with contralateral partial or radical nephrectomy, the
integrity of the adrenal gland on the side of previous surgery
may be compromised, or that gland may be altogether absent.
ADRENAL DISORDERS- DECREASED
FUNCTION- ADRENAL INSUFFICIENCY
 Diagnostic Tests
 Primarily made on clinical grounds, with a high index of suspicion
 Morning serum cortisol and ACTH
 Exhibit abnormal aldosterone and renin levels
 Confirmatory testing involves assessing the adrenal response to
ACTH stimulation in the form of the corticotropin test.
ADRENAL DISORDERS- DECREASED
FUNCTION- ADRENAL INSUFFICIENCY
 Treatment
 The treatment of Addison disease involves adrenal hormonal
repletion.
 Cortisol is replaced with hydrocortisone or with cortisone acetate
 Mineralocorticoid replacement is required only for patients with
primary adrenal insufficiency and is achieved with fludrocortisone
ADRENAL DISORDERS- DECREASED
FUNCTION- ADRENAL INSUFFICIENCY
ADRENAL DISORDERS- ABNORMAL ADRENAL
FUNCTION- CONGENITAL ADRENAL HYPERPLASIA
 Low cortisol production caused by a metabolic
enzymatic abnormality in the cholesterol-steroid
biosynthesis pathway
 Autosomal recessive

 Deficiency in the enzyme 21-hydroxylase

 ACTH production by the pituitary gland is increased,

resulting in hyperplasia of the adrenal cortex and
overproduction of adrenal androgens
 High propensity for developing benign adrenal cortical
adenomas, but not malignancy
CONCLUSION
Question?
Thank you
ADRENAL LESIONS- MALIGNANT-
ADRENAL CARCINOMA
 Adrenal Carcinoma
 Rare
 Bimodal age distribution that peaks in children during the
first decade of life and in adults during the fourth to fifth
decades of life
 Slight female predominance of 1.5 to 2.1
 Hereditary- Li-Fraumeni syndrome and Beckwith-
Wiedemann syndrome
ADRENAL LESIONS- MALIGNANT-
ADRENAL CARCINOMA
 Clinical Characteristics
 Symptomatic presentation resulting from hypersecretion of
adrenal hormones occurs in 40% to 60% of patients
 30% of patients present with symptoms of abdominal pain or
fullness,
 Incidentally detected
ADRENAL LESIONS- MALIGNANT-
ADRENAL CARCINOMA
ADRENAL LESIONS- MALIGNANT-
ADRENAL CARCINOMA
 Needle biopsy
 Usually not performed before surgical excision because there
is a clinically unacceptable risk for needle-tract seeding
 Surgically resectable disease, the information obtained from
biochemical and radiographic evaluation should be enough to
justify excision
 Indication for needle biopsy is in cases of unresectable,
locally advanced, or metastatic disease to confirm the
diagnosis before systemic medical therapy.
ADRENAL LESIONS- MALIGNANT-
ADRENAL CARCINOMA
ADRENAL LESIONS- MALIGNANT-
ADRENAL CARCINOMA
 Management
 Despite aggressive surgical resection, adrenal carcinoma is
associated with a high rate (60% to 80%) of recurrent disease
 Unfortunately, the majority of patients with ACCs have
advanced disease on presentation
 Thus, local and systemic adjuvant therapy is often
administered, in spite of the lack of clear evidence
demonstrating improved survival.
ADRENAL LESIONS- MALIGNANT-
ADRENAL CARCINOMA
 Surgery
 Laparoscopic< 6cm> Open
 Metastatic- cytoreductive removal of the primary tumor and
debulking metastasectomy should be considered if more than
90% of the disease burden can be removed, others should not
be operated.
 CT/RT
 Mitotane alone/ combination
 Radiation therapy remains the treatment of choice in the
management of bone and CNS metastasis
 Adjuvant RT- Increasing
ADRENAL LESIONS- MALIGNANT-
METASTASES
 Melanoma  Basal cell carcinoma,
 Lung  Pancreatic tumors,

 RCC  Cholangiocarcinoma,

 Breast cancer,  Urothelial carcinoma,

 Medullary thyroid  Squamous cell carcinoma,

carcinoma,  Seminoma,
 Contralateral ACC,  Thymoma,
 Gastrointestinaln  Chronic myelogenous
malignancies, leukemia, and
 Prostate adenocarcinoma,  Other malignancies
 Cervical cancer,
ADRENAL LESIONS- MALIGNANT-
METASTASES
 Adrenal incidentaloma if discovered in patients with a
known malignancy, 50% are metastasis.
 Melanoma and non–small cell lung carcinoma, a survival
benefit has been suggested in patients who undergo
resection of an isolated adrenal metastasis
 RCC can involve the adrenal gland by direct invasion or
systemic metastases, but excision is only for
radiographically abnormal or a tumor thrombus extends
to the level of the adrenal vein
ADRENAL LESIONS- MALIGNANT-
METASTASES
 Treatment of metastatic disease of the adrenal glands in
patients with nonurologic malignancies requires a
multidisciplinary approach.
 The urologist must work closely with the patient’s
primary medical oncologist regarding the surgical and
biologic prudence of resection
ADRENAL LESIONS-BENIGN-
ADENOMA
 Most common neoplasms of adrenal gland
 Most often associated with the cortex.

 Most are metabolically silent rarely cortisol and

aldosterone
 Initially metabolically inert are unlikely to gain function

 Non Contrast CT is very helpful

 Attenuation of less than 10 HU on unenhanced CT is

“strongly suggest benign adrenal adenoma”
 Metabolically active, larger than 6 cm should undergo
resection
ADRENAL LESIONS-BENIGN-
OTHERS
 Other benign lesions

 Oncocytoma
 Myelolipoma
 Ganglioneuroma
 Adrenal Cysts
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE
 Adrenal incidentalomas are unsuspected adrenal masses
greater than 1 cm in diameter identified on cross-
sectional imaging performed for seemingly unrelated
causes.
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE- IMAGING
 Ultrasonography.
 Ultrasonography is a suboptimal imaging modality for
detecting and fully characterizing adrenal lesions.
 less sensitive in identifying left-sided adrenal lesions than
those in the right gland
 CT and MRI
 Permit cross-sectional and reconstructed anatomic image
 Characterization of the adrenal glands and serve as the
cornerstone
 Unenhanced CT scan is the first, and perhaps single best, and
most easily interpreted test for intracellular lipid and
therefore can diagnose an adrenal adenoma in more than 70%
of cases.
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE- IMAGING
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE- SIZE AND GROWTH
 Size > 4cm > evaluation
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE- BIOPSY
 The role of adrenal biopsy has been limited for the
following reasons:
 modern imaging in the context of clinical characteristics
affords superb diagnostic capabilities,
 histologically, adenomas cannot be reliably differentiated
from adrenal carcinomas,
 adrenal biopsy is not without risk

 When used to differentiate benign from metastatic

disease, adrenal biopsy carries favorable test
characteristics.
 Always exclude the possibility of pheochromocytoma
before performing biopsy.
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE- BIOPSY
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE- FUNCTIONALITY
 Testing for Cortisol Hypersecretion

 LD-DST,
 A late-night
salivary cortisol test
 24-hour UFC evaluation.
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE- FUNCTIONALITY
 Testing for Aldosterone Hypersecretion
 Today the screening test of choice for Conn syndrome is the
ratio of morning plasma aldosterone (ng/dL) to renin (ng/
mL/h).
 An ARR of 20 (some suggest 30) along with a concomitant
aldosterone concentration above 15 ng/mL is indicative of
Conn syndrome
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE- FUNCTIONALITY
 Testing for Adrenal Sex Steroid Hypersecretion
 Routine testing of incidentalomas for sex hormones is
currently not recommended except suspected adrenal
carcinoma
 S. testosterone and/or 17-ketosteroids
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE- FUNCTIONALITY
 Testing for Catecholamine Hypersecretion
 Freefractionated plasma metanephrines
 24-hour urinary fractionated metanephrine test
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE- FOLLOW-UP PLAN
EVALUATION OF ADRENAL LESIONS IN
UROLOGIC PRACTICE- SURGERY
CONCLUSION
Question?
Thank you