Endocrine Pathology

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

Approach to Endocrine Pathology

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 ProductionEnvironment Utilization, Storage

Types of Endocrine Hormones

Steroid Hormones Cortisol

Peptides Insulin

Amino AcidsEpinephrine

Interaction of Hormones

1 Hormone Multiple Actions

Spermatic GenesisTestosterone Muscle Growth

Prostatic Hyperplasia

Hormone Interaction

1 Function, Multiple Hormones

Glucose GlucagonEpinephrineCortisolGrowth 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” glandso far

Hypothalamic Trophic (Stimulating) Hormone Interactions

HypothalamicTrophic or Releasing

Hormone (RH)

Anterior PituitaryTarget

Cell/Hormone

Peripheral TargetOrgan/Hormone

Thyroid (TRH) Thyrotroph/TSH Thyroid/T4&T3

Corticotropin (CRH) Corticotroph/ACTH Adrenal/Cortisol

Gonadotropin (GnRH) Gonadotroph/LH &FSH

Gonads/Estrogen/Progesterone/Test-osterone

Growth Hormone(GHRH)

Somatotroph/GH Growth/Metabolic

Hypothalamic Suppressor Hormone Interactions

Hypothalamic Anterior PituitaryTarget Cell/Hormone

Somatostatin Somatocyte/GrowthHormone

Dopamine 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 Prolactin, ACTH,

GH, TSH, Etc.

Mass Effect 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

AmenorrheaProlactin Galactorrhea

Libido LossInfertility

Pregnancy Prolactin Amenorrhea

Hypothyroidism Galactorrhea

Hypothalamic Libido Loss

Supracellular Mass Infertility

Other Causes of Hyperprolactinemia

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

Urine - Na

Serum Osmotic Pressure

Serum H2O Serum Na+

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 LungCVA/CNS TumorsTrauma: 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)

Convulsions (Na < 115)Coma/Death

SIADH - Rx

Remove Offending Cause (e.g. malignancy, medication)

Trauma - Usually Resolves Fluid Restriction ADH Antagonist