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