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
Internal Energy Production
Environment Utilization, Storage
Types of Endocrine Hormones
Steroid Hormones Cortisol
Peptides Insulin
Amino Acids Epinephrine
Interaction of Hormones
1 Hormone Multiple Actions
Spermatic Genesis
Testosterone Muscle Growth
Prostatic Hyperplasia
Hormone Interaction
1 Function, Multiple Hormones
Glucose Glucagon
Epinephrine
Cortisol
Growth Hormone
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 (Hashimoto’s)
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 & Gonads/Estrogen/
FSH Progesterone/Test
-osterone
Growth Hormone Somatotroph/GH Growth/Metabolic
(GHRH)
Hypothalamic Suppressor
Hormone Interactions
Hypothalamic Anterior Pituitary
Target Cell/Hormone
Somatostatin Somatocyte/Growth
Hormone
Dopamine Prolactocyte/Prolactin
Pituitary Diseases
Hyperpituitarism Hypopituitarism
Adenoma Destructive Processes
Sella Turcica Ischemic Injury
Visual Field 's Radiation
IC Pressure Inflammation
Pituitary Adenomas -
Associations & Tendencies
In General:
10% of Cranial Neoplasms
4th - 6th Decade
3% of MEA-I
Pituitary Adenomas -
Associations & Tendencies
Functioning Non-Functioning*
Microadenomas Macroadenomas
(<1cm) (>1cm)
Early Sxs Late Sxs
* Null Cell (~20%)
Pituitary Adenomas -
Associations & Tendencies
Hormone Effect Mass Effect*
Prolactin (~25%) Visual Field Changes
Growth Hormone Increased Cranial
(~15%) Pressure - Headache,
ACTH (~15%) N&V
Can Have Mass Effect Hypopituitarism can
Occur
* Null Cell (20%)
Pituitary Adenomas - Clinical
Hormone Effect Prolactin, ACTH,
GH, TSH, Etc.
Mass Effect Sella Turcica Erosion
Visual Field Defects
Intracranial Pressure
Pituitary Adenomas & Hormonal
Syndromes
Hormone Secreted
Growth Hormone Gigantism & Acromegaly
Prolactin Galactorrhea & Amenorrhea
ACTH 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
Amenorrhea
Prolactin Galactorrhea
Libido Loss
Infertility
Other Causes of Hyperprolactinemia
Pregnancy Prolactin Amenorrhea
Hypothyroidism Galactorrhea
Hypothalamic Libido Loss
Supracellular Mass Infertility
Prolactinoma - Rx
1. Treated with bromocriptine
(dopamine receptor agonist)
2. Surgery
3. 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 Gigantism
Closure (Prepubertal) Body Size
Long Legs/Arms
After Epiphyseal Acromegaly
Closure (Adults) 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 BP
(~5% to 10%)
Urine Volume Serum H2O
Urine - Na Serum Na+
Serum Osmotic Pressure
ADH Deficiency
(Diabetes Insipidus)
Clinical Lab
Polyuria Large Volumes of Dilute
Thirst (Polydipsia) Urine
Dehydration Sp Gr
U/Na+
No hyperglycemia
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
