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Endocrine Pathology

Approach to Endocrine Pathology


Some

Definitions
Some Anatomy & Histology (Morphology)
Some Biochemistry (Chemical Measurements)
Some Physiology (Regulation)
The Pathology (Morphology)
The Laboratory Diagnosis

What

is the Endocrine System?


Highly Integrated & Distributed Organs

What

is its purpose?
Maintain Homeostasis Between Organs

How

does it fulfill its purpose?


Through Hormones or Chemical Messengers

Reproduction

Growth/Development

Hormone & Effects

Types of Endocrine Hormones


Steroid Hormones

Cortisol

Peptides

Insulin

Amino Acids

Epinephrine

Interaction of Hormones
1 Hormone

Multiple Actions
Spermatic Genesis

Hormone Interaction
1 Function, Multiple Hormones

Classification of Endocrine Diseases


Hyperfunction

(Excess)

Hypofunction

Impaired synthesis or release (deficiency)


Abnormal target tissue interaction (resistance)
Abnormal target tissue response (resistance)
Mass

Lesions (Neoplasia)
Non-functioning (No hormone)
Functioning (Hormone)

Etiology of Endocrine Deficiency &


Resistance Syndromes
Hormone Deficiency
Autoimmune
Hypothyroidism (Hashimotos)
Type I Diabetes Mellitus
Post Surgical
Hypoparathyroidism
Hypothyroidism

Etiology of Endocrine Deficiency &


Resistance Syndromes
Hormone Deficiency
Inflammation, Neoplasia
Granulomatous
Non-Functioning Adenoma
Receptor Defect/Resistance
Type II Diabetes Mellitus

Hypothalamus
The true master gland
so far

Hypothalamic Trophic (Stimulating)


Hormone Interactions
Hypothalamic
Anterior Pituitary Peripheral Target
Trophic or Releasing
Target
Organ/Hormone
Hormone (RH)
Cell/Hormone
Thyroid (TRH)
Thyrotroph/TSH
Thyroid/T4&T3
Corticotropin (CRH)

Corticotroph/ACTH Adrenal/Cortisol

Gonadotropin (GnRH)

Gonadotroph/LH &
FSH

Growth Hormone
(GHRH)

Somatotroph/GH

Gonads/Estrogen/
Progesterone/Test
-osterone
Growth/Metabolic

Hypothalamic Suppressor
Hormone Interactions
Hypothalamic
Somatostatin

Dopamine

Anterior Pituitary
Target Cell/Hormone
Somatocyte/Growth
Hormone
Prolactocyte/Prolactin

Pituitary Diseases
Hyperpituitarism
Adenoma
Sella Turcica
Visual Field 's
IC Pressure

Hypopituitarism
Destructive Processes
Ischemic Injury
Radiation
Inflammation

Pituitary Adenomas Associations & Tendencies


In General:
10% of Cranial Neoplasms
4th - 6th Decade
3% of MEA-I

Pituitary Adenomas Associations & Tendencies


Functioning
Microadenomas
(<1cm)
Early Sxs

Non-Functioning*
Macroadenomas
(>1cm)
Late Sxs

* Null Cell (~20%)

Pituitary Adenomas Associations & Tendencies


Hormone Effect
Prolactin (~25%)
Growth Hormone
(~15%)
ACTH (~15%)

Can Have Mass Effect

Mass Effect*
Visual Field Changes
Increased Cranial
Pressure - Headache,
N&V
Hypopituitarism can
Occur
* Null Cell (20%)

Pituitary Adenomas - Clinical


Hormone Effect

Mass Effect

Prolactin, ACTH,
GH, TSH, Etc.
Sella Turcica Erosion
Visual Field Defects
Intracranial Pressure

Pituitary Adenomas & Hormonal


Syndromes
Hormone Secreted

Growth Hormone
Prolactin
ACTH

Gigantism & Acromegaly


Galactorrhea & Amenorrhea
Cushing's Syndrome
Nelson's Syndrome

Prolactinomas

Most Common Hyperfunctioning Pituitary


Adenoma
F (microadenomas) > M (macroadenomas)
Microscopically - Chromophobe or Weakly
Acidophilic
Hyperprolactinemia (>200 ug/L)
Detection Depends on Clinical Status

Prolactin Effects
Prolactin

Amenorrhea
Galactorrhea
Libido Loss

Other Causes of Hyperprolactinemia

Pregnancy
Prolactin
Hypothyroidism
Hypothalamic
Supracellular Mass

Amenorrhea
Galactorrhea
Libido Loss
Infertility

Prolactinoma - Rx
1.
2.
3.

Treated with bromocriptine


(dopamine receptor agonist)
Surgery
Radiaton

Growth Hormone (Somatotroph)


Adenoma
Second (2nd) most common functioning adenoma
Macroscopically - May be larger when detected
Microscopically:
+/- granulated acidophilic/chromophobic cells
Immunoreactive for GH and +/- PRL

GH - Secreting Adenoma
Before Epiphyseal
Closure (Prepubertal)

Gigantism
Body Size
Long Legs/Arms

After Epiphyseal
Closure (Adults)

Acromegaly
Prognathism
Enlarged Hands/Feet

Acromegaly - Other Clinical Findings

Abnormal GIT risk of cancer


Diabetes Mellitus
Hypertension
Arthritis
Osteoporosis
Congestive Heart Failure (CHF)

Corticotroph Cell Adenomas


Microadenomas (<1cm)
Microscopically:
Basophilic or Chromophobic
PAS Positive
Immunochemically (+) for ACTH

Corticotroph Adenomas - Clinically


ACTH

Cortisol

Cushing's Disease
Weight Gain
BP
Truncal Obesity
Muscle Mass
Diabetes Mellitus

Nelson's Syndrome
Pre-Existing Corticotroph Adenoma
Adrenalectomy Removes Feed Back,
hipercortosolism does not develop.
Aggressive Enlargement of Adenoma,
produces Mass Effect and Invasion
ACTH precursor molecule on
melanocyte hyperpigmentation

Pituitary Adenomas - The "Others"


Null Cell (~20%)

"Mass Effect"

Gonadotroph (~10%-15%)

"Mass Effect"
Libido

Thyrotroph (~1%)

Rare (<1%)

Hypopituitarism
(Anterior Pituitary-AP)
Loss or Absence of > 75% of AP
Most Common Causes:
Nonsecretory Pituitary Adenomas
Ischemic Necrosis (Sheehan's Syndrome)
Ablation by Surgery or Radiation

Hypopituitarism
(Anterior Pituitary-AP)
Loss or Absence of > 75% of AP
Less Common Causes:
Hypothalamic Tumors
Empty Sella Syndrome
Inflammation Trauma
Metastatic Disease

AP - Hypofunction - Clinical

Usually slow in onset


Growth hormone
Pallor ( MSH)
LH & FSH (Gonadal Atrophy)
TSH - life threatening
ACTH - life threatening
Prolactin

Sheehan's Syndrome
Most Common Cause of Ischemic Necrosis
Normal in AP in Pregnancy
Ischemia During Delivery (Hypotension)
Posterior Pituitary Spared

Posterior Pituitary
Is composed of modified glial cells (pituicytes) and
axonal processes extending from nerve cell bodies
in the supraoptic & paraventricular cells of the
hypothalamus.

Posterior Pituitary Hormones


Antidiuretic Hormone------------> Absorption
(ADH) Renal Free H2O
Vasopressin U-Vol/ U-Na+
S-Vol/ S-Na+
Blood Pressure
Oxytocin---------------------------->Some contraction
of
uterus and
lactiferous ducts
during pregnancy

ADH (Vasopressin)
Osmotic Pressure----> ADH----> Reabsorption
(>280)
RT-H20

Blood Volume
(~5% to 10%)
Urine Volume
Urine - Na

BP

Serum H2O
Serum Na+
Serum Osmotic Pressure

ADH Deficiency
(Diabetes Insipidus)
Clinical
Polyuria
Thirst (Polydipsia)
Dehydration
No hyperglycemia

Lab
Large Volumes of Dilute
Urine
Sp Gr
U/Na+

Serum Sodium
Serum Osmolality
( Serum Na+)

ADH Deficiency (Diabetes Insipidus)


Etiologies:
Autoimmune Neoplasia (Ectopic)
Traumatic Spontaneous
Hypothalamic Lesions
Rx:
Access to Water
Desmopressin (DDAVP)

Syndrome of Inappropriate ADH (SIADH)


ADH Excess Occurs With Inappropriate Stimulis
(e.g. hyperosmolality)
Concentrated Urine
Dilute Serum

Syndrome of Inappropriate ADH


(SIADH)
ADH
by Small Cell (Oat Cell) Ca of Lung
CVA/CNS Tumors
Trauma: Medications
ADH---> Renal H2O Tubular --> U-H20
Reabsorption
U-Na+/Osm
S-H20
S-Na+/Osm

SIADH
Body Water But No Edema

Overhydration of Brain Cells

Confusion (Na < 125)


(Na < 115)
Convulsions
Coma/Death

SIADH - Rx
Remove Offending Cause (e.g. malignancy,
medication)
Trauma - Usually Resolves
Fluid Restriction
ADH Antagonist