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Adrenal Gland Pathology
Diagnosis
Pathology of Adrenal Cortex Cushing Syndrome Pituitary Adrenal Ectopic
Adrenocortical Adrenocortical Adrenocortical Serum ACTH ↑ ↓ ↑
Hyperfunction Hypofunction Neoplasms ↓ Dose Steroid Not suppressed Not Suppressed Insensitive or Not
(Adrenocortical (No ↓ Urinary (No ↓ Urinary Suppressed
Insufficiency) Steroid Excretion) Steroid Excretion) (No ↓ in Urinary)
↑ Dose Steroid Suppressed Not Suppressed Insensitive or Not
Hypercorticolism 1° Adrenocortical Hyperplasia (Suppression of (No ↓ in Urinary Suppressed
(Cushing Syndrome) Insuffi ciency Adenoma Urinary Steroid) Steroid Excretion) (No ↓ in Urinary)
Hyperaldosteronism • Acute Carcinoma
Adrenogenital, Virilizing • Chronic
Syndrome 2° Adrenocortical
Insuffi ciency
Cushing Syndrome
Definition
Symptom complex is cau sed by ↑ Glucocorticoid levels
Exogenous Administration Endogenous
Most common type 1° Hypothalamic-Pituitary Diseases associated
with Hypersecretion of ACTH (70-80%)
Hypersecretion of Cortisol by
• Adrenal Adenoma
• Adrenal Carcinoma
• Adrenal Nodular Hyperplasia
Ectopic ACTH secretion by
Non-Pituitary Neoplasm
Definition Morphology
Uncommon syndrome
Characterized by
Chronic Exce ss of Aldosterone Secretion
Na+ Retention, K+ Excretion
Hypertension, Hypokalaemia
Types
Primary (1°) Secondary (2°)
Autonomous overprodu ction Anything that cause Kidney Conn Syndrome (Aldosterone Produ cing Adenoma)
of Aldosterone to perceive Almost always Single, Small (< 2cm diameter)
↓ ↓ Intravascular Volume Well-circums cribed lesion often buried within gland, no visible enlargement
Suppressed RAAS (Activation of RAAS) Bright Yellow is composed of Lipid Laden Cortical Cells
↓
↓ Adenoma does not suppress ACTH secretion
↓ Plasma Renin Activity Aldosterone Release (Cortex of Adjacent Adrenal Tissue, Opposite Glands are Not Atrophic)
↓ Renin ↑ Renin Rarely Carcinoma may be responsible
Adrenal Glands
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Adrenogenital Syndrome
Classification Definition
Primary Secondary Functional Adenomas are most commonly associated with
Primary Hypoadrenalism ↓ Stimulation of Adrenals • Hyperaldosteronism
Acute Chronic owing to ↓ ACTH • Cushing Syndrome
Adrenal Crisis Chronic Insu fficien cy Virilizing Neoplasm ↑ Likely to be Carcinoma
(Addison Disease) Functional, Non-Functional can be determined based on Clinical, Bioche mically
(Not on Morphologic Features)
Acute Primary Insufficiency (Adrenal Crisis) • Adenoma
Sudden ↑ Demand for Steroid • Carcinoma
(precipitated by any form of stress that requires an immediate ↑ in Steroid
Output from glands in patient with Chronic Adrenocortical Insufficiency) Adenoma
Rapid Withdrawal of Steroids in patients maintained on Exogenous Steroid
(due to inability of Atrophic Glands to produce Steroid Hormones)
Massive Adrenal Haemorrhage with Destruction of Adrenal Cortex
(as occurs in Newborns with prolonged, difficult delivery – Trauma, Hypoxia)
Patients with DIC
Waterhouse-Friderichsen Syndrome
Waterhouse-Friderichsen Syndrome (Un common but Catastrophic syndrome )
Overwhelming Bacterial Infection
Adrenocortical Ne oplasm (Adenoma)
(classically – Neisseria meningitidis septicemia)
Well-Circums cribed
(occasionally – pseudomonas, pneu mococci, H. In fluenzae, staphylococci)
Nodular Lesion up to 2.5 cm in diameter that Expands the Gland
Rapidly progressing Hypotension leading to Shock
Yellow → Yellow-Brown (due to Lipid within Tumour Cells)
DIC with widespread Purpura of Skin
Most are clinically silent
Rapidly Developing Adrenocortical Insufficiency with
Massive Bilateral Adrenal Hemorrhage
Waterhouse-Friderichsen Syndrome
Can occur at any age (Children ↑)
Adrenocortical Ne oplasm (Adenoma)
Direct Bacterial Seeding of Small Vessels in Adrenal
Compose d of Cells similar to Normal Adrenal Cortex
Development of Endotoxin -Indu ced Vasculitis, DIVC
Adrenals converted to Sacs of Blood Clots (obscuring all underlying detail)
Carcinoma
Histology – Haemorrhages starts within Medulla expanding into Cortex
Rare, occur at any age
Death can follow within Hours → Few Days (unless appropriate treatment)
↑ Likely to be Functional than Adenomas
Often associated with
Primary Chronic Insufficiency (Addison Disease)
Uncommon • Virilism
Resulting from Progressive Destruction of Adrenal Cortex • Features of Hyperadrenalism
Generally, Clinical Manifestation appear when
at least 90% Adrenal Cortex compromised
90% Caused by
Autoimmune Adrenalitis (most common – developed countries)
Infection (Tu berculosis)(common – developing countries)
Acquired Immune Defi ciency Syndrome (AIDS)
Metastatic Cancers
Atrophy of Adrenal Gland
↓ Aldosterone
↓ Cortisol
Hyponatraemia (No Aldosterone)
Hyperpigmentation
(↑ ACTH but nowhere to go → Stimulate Melanocytes → Skin Adrenocortical Ne oplasm (Carcinoma)
Hyperpigmentation especially sun exposed areas, pressure points) Large
Hyperkalemia, Hypotension Invasive
Hypoglycaemia (due to ↓ Cortisol – Impaired Gluconeogenesis) Exceeding 20cm in Diameter
Variegated areas of Necrosis, Haemorrhage
Secondary Adrenocortical Insufficiency Cystic Change
Disorder of Hypothalamus, Pituitary (Smaller, Better Circumscribed Lesions are difficult to differentiate f rom adenoma)
(Metastatic Cancer, Infection, Infarction, Irradiation) Tendency to Invade
↓ ACTH Output → Syndrome of Hypoadrenalism • Adrenal Vein (common)
Prolonged Exogenous Steroid Administration • Inferior Vena Cava (IVC) (common)
(Suppress Adrenal Function) • Lymphatics
Hyperpigmentation is lacking Metastasis to Regional, Periaortic Nodes are common
(Melanotrophic Hormone Levels ↓) Distant Metastasis – Lung, other Viscera (Bone is Unusual Site)
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Adrenal Medulla
Neuroblastoma
Brown Discoloration (Foci of Old Haemorrhage)
Sharply demarcated with a Fibrous Pseudocapsule
Pheochromocytomas P=Parents Infiltrative Invading Kidneys, Renal Vein, Vena Cava
Uncommon Neoplasm Soft Grey-Tan Brain Like Tissue
Pheochromocytoma Areas of Necrosis, Cystic Changes, Haemorrhage (Large Tumours)
Most common tu mour in Adrenal Medulla in Adults Size range Minute Nodules → Masses (> 1kg)
Chromaffin Cells secrete
• Epinephrine
• Norepinephrine
Give rise to Surgically Correctable Hypertension
(Hypertension becomes fatal in unrecognized pheochromocytoma )
May cause Cushing Syndrome or other endocrinopathy
(when produce other steroids, peptides)
5 P’s (Pain, Pressure, Palpitations, Perspiration, Pallor)
(Sympathetic Over Expression)
Rule of 10’s Neuroblastoma
10% Malignant (90% Benign) Tumour variably Mature to
Neuroblastoma
10% Bilateral (90% Unilateral)
Small, Blue, Round Cell Tumour • Ganglio-Neuroblastoma
10% Extra-Adrenal (90% Adrenal)
Arrange in Solid Sheets (Ganglion Cells Mixed with
10% Kids (90% Adults) Mitosis, Nuclear Breakdown, Primitive Neuroblasts)
10% Familial (90% Non-Familial) Pleomorphism • Ganglioneuroma
Associated with Faint Pink Fibrillary Material (No or Minimal Neuroblasts with
• MEN2A (Background) Mature Ganglion Cells in
• MEN2B Rosettes (Tumour Cells surroundi ng background of Schwann Cells,
• Other Familial Syndromes a central space filled with neuropil) Fibroblasts with their processes)
Clinical
Young Childre n <2 y/o Older Children
Abdominal Masses Metastasis
Fever Bone, Liver, Lung, Bone Marrow
Weight ↓
Tumour Produce Catecholamines (90%)
Hypertension (↓ Frequent)
Course – Extremely Variable
Pheochromocytoma (Adrenal Medulla) Prognosis affected by Clinical, Histologic, Molecular, Biochemical Factors
Surrounded by a Narrow Rim of Outstreched Yellow Cortical Tissue Indicators - Age, Stage of Tumour
Lobular pattern (richly vascularised fibrous trabeculae pass through tumour) Excellent Prognosis – Infants < 1 y/o (regardless of stage)
Yellow-Tan
Haemorrhage, Necrotic, Cystic (Larger Lesions) MENs
Range (Small Circumscribed lesion confined to Adrenal Gland → Large Group of Genetically Inherited Disease
Haemorrhagic Mass weighing in kg) Result from Proliferative Lesions (Hyperplasia, Adenoma, Carcinoma)
MEN Rule
Occur at younger age than in sporadic cancers
Arise in Multiple Endocrine Organs
• Metachronously (Different Time)
• Synchronously (Same Time)
If occur in One Organ – often Multifocal
Preceded by Asymptomatic Stage of Endocrine Hyperplasia (progress to cancer)
↑ Aggressive, Tend to Recur
MEN Syndromes
MEN 1 MEN 2A MEN 2B
Pheochromocytoma (Adrenal Medulla) Pituitary Adenoma
Parathyroid Hyperplasia+++ Hyperplasia+
Polygonal → Spindle Shaped Chromaffin Cells
Adenoma+
Zellballen (small nests, alveoli) Pancreatic Islet Hyperplasia++
Richly Vascular Adenoma++
Carcinoma+++
Round → Ovoid Nu clei (Chromatin Stipled Salt, Pepper)
Adrenal Cortical Hyperplas ia Pheochromocytoma++ Pheochromocytoma+++
Moderate → Abundant Finely Granular Cytoplasm Thyroid C-Cell Hyperp lasia+++ C-Cell Hyperp lasia+++
Uncommonly the dominant cell type is Spindle or Small Cell Medullary Carcin oma+++ Medullary Carcin oma+++
No single histologic critera that can reliably predict clinical behaviour Extraendocrine Mucosal
Changes Ganglioneuroma
Definitive diagnosis for malignancy is based on presence of Metastasis Marfanoid Habitu s
Lab Diagnosis – Demo ↑ Urinary Excretion of Free Catecholamines Mutant Gene Locus MEN 1 RET RET
and metabolites (Vanillymanelic acid (VMA), Metanephrines)