Adrenal gland

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• Adrenal gland
• Normal
• Anatomy
• Cortex and Medulla
• Weight 4gm/gland
• Stress related changes
• ACUTE STRESS ?wt. ( loss of lipid)
• Chronic stress ? wt. ( hypertrophy
  Hyperplasia)
• Cortex G F - R
• F -75 of cortex
• Medulla chromaffin cells secrete
  catecholamines ( epinephrine)
• Emergencies
• Stressful states infection, trauma, surgery,
  sudden withdrawal of steroid administration

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DISEASES OF ADRENAL CORTEX

• Hyperfunction (hyperadrenalism)
• Cushings syndrome
• (? cortisol)
• Hyperaldosteronism (? aldosterone)
• Adrenogenital syndromes
• (?androgenic steroids)

• Hypofunction
• (hypoadrenalism)
• Acute
• massive hemorrhage of adrenal glands
• (Waterhouse- Friderichsen)
• Chronic
• Primary (adrenal defect)- (Addisons disease)
• Secondary (Pituitay defect)
• Tertiary (Hypothalamus defect)

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• Pathology
• Hypercortisolism (Cushings syndrome)
• Etiology
• Exogenous cause
• MCC Corticosteroid therapy
• Endogenous causes
• 1. ACTH secreting Pituitary Micro adenoma MCC
• Cushings disease not Cushing's syndrome
• Age/ Sex 25yrs., females
• Skin pigmentation POMC ( only in Cushing's
  disease)
• Adrenal nodular cortical hyperplasia
• Lab ? ACTH, ? cortisol
• 2. Primary adrenal causes Adenoma, Hyperplasia,
  Carcinoma
• ACTH independent Cushing's syndrome or adrenal
  Cushing's syndrome
• Age/ Sex female, Adenoma ( Adult child 11),
  carcinoma (?children)
• Wt. of gland adenoma lt30 gm. carcinoma
  gt300gms., hyperplasia 40 gms.
• Lab ? ACTH, ? cortisol
• Adrenal atrophy of uninvolved side

4

• Pathology
• Hypercortisolism (Cushings syndrome)
• Endogenous causes contd
• 3. Ectopic ACTH secreting conditions Small cell
  Carcinoma of Lung (MC)
• Age/ sex Male, 5oyrs.
• Adrenal bilateral hyperplasia
• Lab ? ACTH, ? cortisol ( same as Cushing's
  disease)
• Morphology pituitary adrenal changes
• Pituitary (same in all types) Crooke hyaline
  change (?intermediate keratin)
• Adrenal cortex depends on the specific type

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CUSHINGS SYNDROME
Pituitary ? Cushing disease (not syndrome)
MC ENDOGENOUS cause
MC EXOGENOUS cause
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Prognosis Adenomas are curable by surgery.
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• Pathology
• Hypercortisolism (Cushings syndrome)
• Clinical course common to all types
• Early HTN, ?wt., (obesity central or
  Truncal), moon faces, Buffalo hump
• Skeletal muscle Type 2 atrophy, ? muscle mass
  ( limb weakness)
• Metabolism carbohydrate
• Hyperglycemia Glucosuria (? gluconeogenesis) ?
  secondary DM
• Bones Resorption ( due to loss of collagen), ?
  osteoporosis ( pain , fracture)
• Skin thin, fragile, easily bruised ( poor wound
  healing, striae)
• Others infections (? immune response), altered
  mental status ( mood disturbances, depression,
  frank psychosis), hirsutism, menstrual
  abnormalities,
• Lab Diagnosis
• 24 hr. urine free cortisol levels
• Dexamethasone suppression test

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• Pathology
• Hyperaldosteronism ? aldosterone secretion
• Very important surgically correctable cause of
  HTN (like in Pheochromocytoma)
• Causes Primary secondary
• Rx surgery (adenoma), Drugs ( hyperplasia),
  underlying causes ( in Secondary)

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• Pathology
• Adrenogenital syndrome excess sex steroids
• Etiology
• Part of Cushing's disease (?ACTH? Androgen)
• Primary adrenocortical neoplasms (carcinoma
  common),
• produce mixed syndromes ( virilizing and
  Cushing's)
• Congenital adrenal Hyperplasia (AR, Enzyme
  deficiencies)
• Congenital adrenal Hyperplasia
• Cause MCC 21- hydroxlase ( 90 of cases)
• Age variable ( depends on severity of enzyme
  deficiency)
• Ethnicity Hispanics Ashkenazi Jews (? carrier
  rate)
• Genetics CYP21A (pseudo gene- inactive
  homologous gene)
• replaces CYP 21B (active gene)
• Clinical types 3 syndromes (classic, Simple
  Non- classic)
• Classic salt wasting, adrenal hyperplasia
• Deficiency no mineralocorticoid, ?
  Glucocorticoid, ?androgen activity
• Clinical salt wasting (?Na, ?K), acidosis,
  ?BP, CVS collapse ? death
• Phalloid organ (female), normal male at birth but
  develop salt wasting syndrome a week later
• Simple without salt wasting, adrenal
  hyperplasia

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• Pathology
• Adrenogenital syndrome excess sex steroids
• Congenital adrenal Hyperplasia
• 3. Non- classic more common, asymptomatic (or
  only hirsutism)
• Clinical presentation
• A neonate (female) with ambiguous genitalia,
  vomiting, dehydration, salt wasting
• A male child with precocious puberty, enlarged
  genitalia
• An young adult female with late menarche,
  oligomenorrhea,/hirsutism
• Treatment
• Glucocorticoids (?ACTH, ?androgen activity)
• Mineralocorticoids
• Adrenocortical insufficiency
• Causes MCC is secondary (Iatrogenic sudden
  withdrawal of corticosteroids in cases of
  long-term steroid therapy)
• Primary (? adrenal activity ,? ACTH) / Secondary
• Acute / Chronic Clinical until 90 of cortical
  damage,
• Early progressive weakness, easy fatigability
• GIT- Anemia, Nausea, vomiting, wt. loss
  diarrhea
• ACTH- pigmentation ( not in secondary causes)
• ? Glucocorticoids hypoglycemia ( intractable
  vomiting, abdominal pain, ?BP, coma, death

• Exogenous ACTH- no ?in cortisol (primary) ?in
  cortisol (secondary)

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Adrenocortical insufficiency
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Waterhouse-Friderichsen syndrome

• Common in children with meningococcemia
• Basis for the adrenal hemorrhage uncertain
• Histology hemorrhage starts within medulla later
  into cortex

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• Pathology
• Adrenocortical Neoplasms
• Functional / nonfunctional
• Adenomas/ carcinoma
• How to know functional or not lab tests only (
  not by biopsy)
• Other lesions cystic lesions ,
• Myelolipoma ( Myelo hematopoiesis, Lipo
  adipose tissue)

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Adrenocortical adenoma
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Adrenocortical carcinoma
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• Pathology
• Adrenal Medulla
• Normal
• Specialized neural crest (neuroendocrine) cells
  or chromaffin cells
• Chromaffin cells brown-black color after
  exposure to potassium dichromate
• Paraganglion system in an extra-adrenal
  Neuroendocrine cells
• synthesize and secrete catecholamines (mainly
  -Epinephrine or adrenaline)
• Pathology
• Neoplasms most important lesions

Neoplasms
Pheochromocytomas (chromaffin cells)
neuronal
Mature Ganglioneuromas
Immature Neuroblastomas
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• Pheochromocytoma Uncommon tumors
• Synthesize and release catecholamines (more
  norepinephrine unlike normal gland)
• surgically correctable forms of Hypertension (?
  Other conditions)
• "rule of 10s"
• 10 - in association with familial syndromes
• 10 - extra-adrenal
• 10 - are bilateral
• 10 - biologically malignant
• 10 - arise in childhood
• Morphology average weight - is 100 gm
• Light Microscopy
• Zellballon pattern
• Cells in small nests or alveoli surrounded by a
  rich vascular network
• "salt and pepper" chromatin
• Electron microscopy membrane-bound,
  electron-dense granules
• Immunoreactivity
• neuronal markers (chromogranin and
  synaptophysin, NSE) in the chief cells
• Sustentacular cells S-100 protein (marker for
  schwann cells)

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• Pheochromocytoma contd
• Criteria for determining malignancy
• No single histologic feature can predict
  clinical behavior
• Definitive diagnosis of malignancy presence of
  metastases
• Clinical Course
• 1. Dominant feature Hypertension
• Classic type of HTN Abrupt elevation in BP with
  tachycardia, palpitations, headache, sweating,
  tremor, and a sense of apprehension
• Also associated with pain in the abdomen or
  chest, nausea, and vomiting
• But most common type (two-thirds of patients)
  chronic hypertension
• Paroxysms precipitated by emotional stress,
  exercise, changes in posture, and palpation
• 2. Catecholamine Cardiomyopathy
• myocardial instability and ventricular
  arrhythmias
• Laboratory diagnosis
• ? urinary free catecholamines
• Or their metabolites metanephrines, (VMA)
• Paragangliomas
• Carotid body tumor
• Chemodectomas Jugulotympanic body

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ADRENAL MEDULLAPheochromocytoma
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• Multiple Endocrine Neoplasia Syndromes (MEN)
• Proliferative lesions (hyperplasia, adenomas,
  and carcinomas) of multiple endocrine organs
• Distinct features
• more aggressive and recur
• multiple endocrine organs
• multifocal
• asymptomatic stage of endocrine hyperplasia
• younger age
• Treatment in MEN 2 types prophylactic
  thyroidectomy
• MEN- TYPE 1
• MC organ involved Primary hyperparathyroidism
• MC cause of morbidity and mortality tumors of
  the pancreas
• MC site of gastrinoma duodenum
• Other associated lesions carcinoid tumors,
  thyroid and adrenocortical adenomas, and Lipoma
• Familial Medullary thyroid cancer
• In 20 of familial pts. (older age)

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Multiple Endocrine Neoplasia Syndromes (MEN)