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Endocrinology

I. Hypothalamic-Pituitary Axis

A.        Introduction

1.         The “Master Gland”

a.          in “olden days

b.          Today

2.         Hypothalamus-Pituitary Connections

a.         To Anterior Pituitary (Adenohypophysis)

i.             Embryology

ii.           Hypothalamo-hypophyseal portal

iii.         Hormones

b.         To Posterior Pituitary (Neurohypophysis)

i.             Nature Of Posterior Pituitary

ii.           Hormones

iii.         Functions

c.          Intermediate Lobe

3.         Nature of Secretion

a.         Pulsative

b.         Daily Rhythms

c.          Longer Rhythms

B.        Hypothalamic Control

1.         General Mechanisms

a.         Nature

b.         Action

2.         The Hormones

a.         General Information

i.             Chemical Form

ii.           Peripheral Forms

iii.         Single Effect

b.         Specifics

i.             Thyrotropin-Releasing Hormone (TRH).

(a)      Structure

(b)      Major Target

(c)      Minor Target

ii.           Gonadotropin-Releasing Hormone (GnRH)

(a)      LH-RH

(b)      Structure

(c)      Targets

(d)      Effect of exogenous administration:

(i)    Pulsatile administration

(ii)  Continuous administration

a.    Long-acting versions

iii.         Growth Hormone-Releasing Hormone (GHRH)

(a)      Structure

(b)      Target

iv.        Somatostatin

(a)      Structure

(b)      Target

(c)      And Insulin

(d)      And TSH

v.          Corticotropin-Releasing Hormone

(a)      Structure

(b)      Target

3.         Hypothalamic Abnormalities

a.         Typical pathologies

b.         Results

i.             Specificity

ii.           General

C.        Anterior Pituitary Hormones

1.         Adrenocorticotrophic Hormone (ACTH; Corticotropin)

a.         Description

b.         CRH – ACTH – Adrenal Axis

2.         Glycoprotein Hormones

a.         Commonalities

b.         Thyroid-Stimulating Hormone (TSH)

c.          LH and FSH

i.             Stimulation

ii.           Suppression

iii.         Females

iv.        Males

3.         Growth Hormone (GH)

a.         Structure

b.         Control

c.          Action

i.             Somatomedin-C

ii.           Metabolic effects

(a)      Insulin-like

                        (b)      Longer-term

d.         Everyday importance

4.         Prolactin

a.         Cells

b.         Function

c.          Pituitary tumors

D.        Posterior Pituitary Function

1.         Introduction

a.         The Hormones

b.         Structure

c.          Synthesis

i.             Source

ii.           Synthesis

iii.         Storage

iv.        Release

d.         Clearance

2.         Hormone Actions

a.         ADH:

i.             Major Function

ii.           High concentration

iii.         Stimulus

(a)      Osmotic concentration

(b)      Decreased blood volume

(c)      Others

(d)      Inhibitors

(e)      Diabetes Insipidus

b.         Oxytocin:

i.             Targets:

(a)      Myoepithelial cells

(b)      Uterine Smooth Muscle

E.        Pituitary Disorders

1.         Generalized Hypopituitarism

a.         Causes

i.             Primary

(a)      Pituitary tumors

(b)      Infarction or ischemia

(c)      Inflammation

ii.           Secondary

(a)      Hypothalamic tumors

(b)      Inflammations

(c)      Trauma

(d)      Others

b.         Appearance

i.             Onset

ii.           Decreased LH and FSH

(a)      Females

(b)      Men

iii.         Decreased GH

iv.        Decreased TSH

v.          Decreased ACTH

vi.        Sheehan’s Syndrome

c.          Diagnosis

i.             Visualization of the pituitary/sella turcica.

(a)      Skull xrays, CT scans, MRIs, PET scans

(b)      Cerebral angiography

ii.           Visual Field Testing

iii.         Evaluation of Thyroid Function

(a)      TSH, T3/T4

(b)      Injection of synthetic TRH

iv.        Evaluation of ACTH Secretion

(a)      Testing “Pituitary Reserve”

(i)    Problem

(ii)  Test Purpose

(iii)Best test: Insulin Tolerance

v.          Evaluation of Prolactin

vi.        Evaluation of GH

(a)      Routine

(b)      Measurement in children

(c)      Injection of GHRH

(d)      Subtlety

vii.      Evaluation of LH/FSH

(a)      Measurement of LH/FSH

(b)      Concentrations

(c)      Postmenopausal women

viii.    Combined Anterior Pituitary Function Test

ix.        Differentiating from other diseases

(a)      Anorexia nervosa

(b)      Alcoholic liver disease

(c)      Polyglandular Autoimmune Disease

                        (d)         Treatment      

2.         Selective Pituitary Deficiency.

a.         Introduction

b.         Isolated GH Deficiency

c.          Isolated Gonadotropin Deficiency

i.             Vs. Primary Hypogonadism

ii.           Exercise, Diet & Stress

iii.         Kallmann’s Syndrome

(a)      Description

(b)      Defects

(c)      Cause

d.         Isolated ACTH Deficiency

e.         Isolated TSH Deficiency

3.         Hyperpituitarism

a.         Gigantism & Acromegaly

i.             Introduction

ii.           Appearance

(a)      Before Epiphyseal Closure

(b)      After Epiphyseal Closure

(c)      Diagnostic Indicators

(i)    Radiographic Examination

(ii)  GH Radioimmunoassay

(iii)Somatomedin-C

(d)      Treatment

b.         Galactorrhea

i.             Definition

ii.           Cause

iii.         Appearance

iv.        Diagnostic Tests

4.         Posterior Pituitary Disorders

a.         Diabetes Insipidus

i.             Introduction

(a)      Definition

(b)      Nephrogenic DI

(c)      Water-Drinkers

ii.           Cause of DI

(a)      Hypothalamic Nuclei

(b)      Primary vs. Secondary

iii.         Appearance

(a)      Polyuria

(b)      Polydipsia

iv.        Diagnosis

(a)      Testing

(i)    Water Deprivation Test

a.    Pre-Test

b.    Collections

c.     Termination

d.    Vasopressin

e.    Evaluation

i.        Normal

ii.      Positive

iii.    Nephrogenic DI

(ii)  ADH Measurement

v.          Treatment

(a)      Hormonal

(i)    Vasopressin

(ii)  Synthetic Analog

(b)      Nonhormonal

(i)    Diuretics

(ii)  Reduced Na Intake

b.         Compulsive Water Drinkers

i.             Identity

ii.           Volume

(a)      Nocturia

(b)      Polydipsia

iii.         Hyponatremia

iv.        Treatment

II.                   Thyroid Disease

A.        Glandular Structure

1.         Formation

a.         Initiation

b.         Migration

c.          Appearance

B.        Hormone Synthesis

1.         Thryoglobulin

a.         Identity

b.         Location

2.         Iodine

a.         Capture

b.         Conversion

c.          Incorporation

i.             Organification

ii.           Result

iii.         Coupling

d.         Reabsorption

i.             Colloid Droplet

ii.           Lysosomes

iii.         Diffusion

C.        Thyrotropin (TSH)

1.         Thyrocyte Activity

2.         Mechanisms

a.         Binds to Receptors

b.         Activates Adenylate Cyclase

c.          Control

D.        Circulation of Thyroid Hormones

1.         Thyroxine-Binding Globulin

2.         Thryroxine-Binding PreAlbumin

3.         Free

4.         T4-to-T3 Conversion

E.        Hormone Actions

1.         Increased Protein Synthesis

2.         Increased Oxygen Concentration

F.         Euthyroid Goiter

1.         Definition

2.         Appearance

3.         Treatment

G.       Euthyroid Sick Syndrome

1.         Definition

2.         Causes

3.         Appearance

H.        Hyperthyroidism

1.         Definition

2.         Major Cause Categories

3.         Specific Causes

a.         Graves’ Disease

b.         Inappropriate TSH

c.          Elevated Concentrations of HCG

d.         Thyroiditis

e.         Iodine Ingestion

4.         Signs/Symptoms

a.         Many/Varied Signs

b.         Eye Signs

c.          Infiltrative Dermopathy

d.         Thyroid Storm

5.         Diagnosis

6.         Treatment

a.         Iodine Administration

b.         Propylthiouracil/Methimazole

c.          Radioactive Iodine

d.         Surgery

I.            Hypothyroidism (Myxedema)

1.         Definition

2.         Forms

a.         Primary

b.         Secondary

3.         Signs/Symptoms

4.         Diagnosis

a.         Primary Hypothyroidism

b.         Secondary Hypothyroidism

c.          TRH Test

d.         T3/T4

5.         Treatment

J.          Thyroiditis

1.         Definition

2.         Types

a.         Silent Lymphocytic Thyroiditis

b.         Hashimoto’s Thyroiditis

III.                 Endocrine Pancreas

A.        Normal Physiology

1.         Islets of Langerhans

a.         Description

b.         Cell Complement

2.         Hormone Secretion

a.         Fasting

i.             Description

ii.           Glucagon

iii.         FFA Utilization

b.         Feeding

i.             Description

ii.           Insulin

B.        Diabetes Mellitus

1.         Definition

2.         Classification

a.         Type I (IDDM; Juvenile Onset)

i.             Age at Onset

ii.           Prevelance

iii.         DKA

iv.        Insulin

v.          Genetics

b.         Type II (NIDDM)

i.             Age at Onset

ii.           Characteristics

iii.         DKA

iv.        Obesity

v.          Treatment

vi.        Genetics

vii.      Cells

viii.    Hyperglycemia

3.         Signs/Symptoms

a.         Initial Presentation

i.             Type I

ii.           Type II

b.         Symptomatic Hyperglycemia

i.             3 P’s

ii.           Others

c.          Late Complications

i.             And Hyperglycemia

ii.           Microvascular

iii.         Macrovascular

iv.        Retinopathy

v.          Nephropathy

vi.        Polyneuropathy

vii.      Foot ulcers/Joint problems

4.         Diagnosis

a.         National Diabetes Data Group

i.             FBG

ii.           OGTT

iii.         Impaired Glucose Tolerance

b.         American Diabetes Association

5.         Treatment

a.         Insulin

i.             Human

ii.           Absorption Rate

b.         Complications of Treatment

i.             Hypoglycemia

ii.           Dawn Phenomenon

iii.         Local Allergy

iv.        Generalized Allergy

c.          Oral Hypoglycemics: Sulfonylureas

i.             Action

ii.           Examples

iii.         Complication

d.         Anti-Hyperglycemics

i.             Biguanides

ii.           Alpha-Glucosides

iii.         Thiazolidinediones

6.         Diabetic Ketoacidosis

a.         Definition

b.         Mechanism

i.             Shift to Fat Catabolism

ii.           Produces Ketone Bodies

iii.         Disposal of Acids

iv.        Acetone

v.          Ventilation

vi.        Ratio Change

c.          Signs/Symptoms

d.         Diagnosis

e.         Treatment

7.         Hypoglycemia

a.         Definition

b.         Pathophysiology

i.             Neuron Fuel

ii.           Insulin and the CNS

iii.         CNS Monitor

iv.        Glucagon

c.          Classification

i.             Drug-Induced

(a)      Frequency

(b)      Drugs

(c)      Alcohol

(d)      Others

ii.           Non-drug Induced

(a)      Fasting Hypoglycemia

(i)    Introduction

(ii)  Causes

a.    Liver

b.    Fatty Acid Oxidation

c.     Islet cell Adenomas

d.    Mesenchyme Tumors

e.    Renal Failure

(b)      Reactive Hypoglycemia

(i)    Causes

d.         Signs/Symptoms

i.             Patterns

(a)      Adrenergic Symptoms

(b)      CNS Symptoms

ii.           Other Information

e.         Diagnosis

i.             Requirements

ii.           Glucose Concentrations

iii.         Associations

f.            Treatment

i.             Oral Carbohydrate

ii.           IV Glucose

iii.         Glucagon

IV.               Adrenal Glands

A.        Anatomy

1.         Components of the Glands

a.         Steroidogenic Tissue

b.         Chromaffin Tissue

2.         Origination

a.         Steroid-producers

b.         Catecholamine-producers

3.         Description

4.         Histology

a.         Cortical Layers

b.         Cell Appearance

5.         Fetal Cortex

B.        Cortical Hormones

1.         Introduction

a.         Categories

i.             Mineralcorticoids

ii.           Glucocorticoids

iii.         Androgens

2.         Synthesis

a.         And Cholesterol

b.         Formulae

c.          Concentrations & Activities

3.         Binding

a.         Cortisol

b.         Aldosterone

c.          Reservoir

4.         Degradation

a.         Site

b.         Elimination

C.        Mineralcorticoid Function

1.         Mineralcorticoid Deficiency

2.         Aldosterone Activity

a.         Major Role

b.         Excess Aldosterone

i.             Sodium Retention

ii.           Sodium Concentration

iii.         Total Result

iv.        And Potassium

(a)      Excess Aldosterone: Hypokalemia

(b)      Deficient Aldosterone: Hyperkalemia

v.          And H+

c.          Aldosterone and Other Secretions

i.             Sweat and Salivary Glands

ii.           Intestinal Secretion

3.         Cellular Mechanism of Aldosterone

a.         Entry

b.         Receptor

c.          Result

d.         Timing

4.         Regulation of Aldosterone Secretion

a.         Major Controllers

i.             Increased [K+]

ii.           Renin-Angiotensin System

b.         Minor Controllers

D.        Glucocorticoid Function

1.         Introduction

a.         Absence

b.         Activity

2.         Carbohydrate Metabolism

a.         Gluconeogenesis

b.         Decreased Utilization

c.          “Adrenal Diabetes”

3.         Protein Metabolism

a.         Decreased Cellular Protein

b.         Increased Plasma Proteins

c.          Effects on Amino Acids

4.         Fat Metabolism

a.         F.A. Mobilization

b.         Obesity

5.         Stress Resistance

a.         Introduction

 

 

 

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