ANATOMY, PHYSIOLOGY & PATHOLOGY

NOTES OF THE

ENDOCRINE SYSTEM
FOURTH EDITION
PRE-SUMMARIZED FOR THE TIME-POOR
READY-TO-STUDY MEDICAL, PRE-MED,
HIGH-YIELD NOTES USMLE OR PA STUDENT

141 PAGES
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Table Of Contents:

What’s included: Ready-to-study anatomy, physiology and pathology notes of the endocrine system presented in
succinct, intuitive and richly illustrated downloadable PDF documents. Once downloaded, you may choose to either
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Anatomy & Physiology Notes:

• OVERVIEW OF THE ENDOCRINE SYSTEM
• THE HYPOTHALAMUS & PITUITARY GLAND
• THE PINEAL GLAND
• THE THYROID GLAND
• PARATHYROID GLANDS
• THE ADRENAL GLANDS
• THE ‘ENDOCRINE’ PANCREAS
• CALCIUM & PHOSPHATE HOMEOSTASIS
• FLUID & ELECTROLYTE HOMEOSTASIS
• ENDOCRINE REGULATION OF GROWTH
• PHYSIOLOGICAL RESPONSE TO STRESS
• REPRODUCTIVE ENDOCRINOLOGY

Pathology Notes:
• GENERAL OVERVIEW OF ENDOCRINE DISORDERS
• THYROID DYSFUNCTION:
o HYPOTHYROIDISM (INCL. HASHIMOTO’S DISEASE)
o HYPERTHYROIDISM (INCL. GRAVE’S DISEASE)
o DIAGNOSING THYROID DYSFUNCTION
o NON-TOXIC GOITRES
o THYROID NEOPLASMS
• GROWTH DYSFUNCTION:
o GROWTH HORMONE DEFICIENCY (AKA. PITUITARY DWARFISM)
o GIGANTISM/ACROMEGALY
• ADH DISORDERS:
o DIABETES INSIPIDUS
o SIADH
• ADRENAL CORTEX DYSFUNCTION:
o ADDISON’S DISEASE
o WATERHOUSE-FRIDERICHSEN SYNDROME
o CONGENITAL ADRENAL HYPERPLASIA
o CONN’S SYNDROME
o CUSHING’S DISEASE/SYNDROME
• PHAEOCHROMOCYTOMA
• DIABETES
• CALCIUM & PHOSPHATE BALANCE DISORDERS:
o PARATHYROID DISORDERS
• GONADAL DYSFUNCTION
• MULTIPLE ENDOCRINE NEOPLASIA SYNDROME
OVERVIEW OF THE ENDOCRINE SYSTEM
 OVERVIEW OF THE ENDOCRINE SYSTEM
Endocrinology:
- Endocrinology: The scientific study of Hormones (Chemical Messengers) and the endocrine organs.
- Endocrine system is critical for maintaining Homeostasis

What is a Hormone?
• Chemical signalling molecules secreted by endocrine glands into the extracellular fluids to exert an effect
elsewhere in the body
• Hormones travel in blood or lymph throughout the body
• BIOLOGICAL SPECIFICITY: Hormones Interact with specific receptors of specific cells of specific organs.

Hormones Are Either Steroidal or Non-Steroidal:

- Steroids Hormones:
o Sex Hormones – Eg: Testosterone (Androgens), Oestrogens, Progestogens.
o Adrenal Hormones – Eg: Glucocorticoids, Mineralocorticoids
o (Derived from Cholesterol)
- Non-Steroid Hormones:
o Amino Acid Derivatives:
§ Catecholamines (Eg: Adrenaline, Nor-Adrenaline & Dopamine) (Derived from Tyrosine)
§ Histamine (Derived from Histidine)
§ All Thyroid Hormones (Derived from Tyrosine)
o Proteins:
§ All Pituitary Hormones
o Fatty-Acid Derivatives:
§ Eg: Prostaglandins
§ Eg: Thromboxanes
o Purines:
§ Eg: Adenosine
o Dissolved Gases:
§ Eg: Nitric Oxide

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

Synthesis of Chemical Messengers:
- Steroidogenesis:
o All steroid hormones are derived from Cholesterol
o There are 5 Families of Steroids, each with their main physiological member:
§ Progestogens (Progesterone)
§ Androgens (Testosterone)
§ Mineralocorticoids (Aldosterone)
§ Glucocorticoids (Cortisol)
§ Oestrogens (Oestrogen)
- Protein/Peptide Synthesis & Processing:
o Synthesis of polypeptide hormones can be more complex than Transcription & Translation.
o Some Protein Hormones are initially synthesised as longer Pre-Prohormones
o These Pre-Prohormones are then cleaved, leaving Prohormones
o These Prohormones are then cleaved again, leaving active Hormones
§ Eg: Insulin:

‘Reactive’ Properties of Chemical Messengers:

- Biological Specificity: Certain Chemical Messengers will only fit into certain receptors
- Affinity: The degree to which a chemical is attracted towards a receptor
- Efficacy: The degree of effectiveness of the binding of the messenger to the receptor
- ‘Agonists’: Chemical Messengers with High Affinity & High Efficacy
- ‘Antagonists’: Chemical Messengers with High Affinity but Low Efficacy
Note: There are no Endogenous Receptor-Antagonists, Only Exogenous (Drugs)
- Hormone Binding Proteins: Proteins that inactivate hormones by binding to them, limiting Bioactivity
- Epitope: An Immunologically active binding site on a protein to which an antibody can attach

Endocrine Glands:
- Endocrine Glands are Ductless and secrete by Exocytosis into the Extracellular Fluid → Diffuses into Blood

Classical Endocrine Glands:

• Hypothalamus
• Pituitary gland
• Pineal gland
• Thyroid gland
• Parathyroid glands (dorsal aspect of thyroid gland)
• Thymus
• Adrenal glands
• Pancreas (has exocrine parts for digestion) (endocrine part secretes insulin)
• Gonads: Testes/Ovaries (also exocrine)
 OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

Long or Short-Range Signalling?

• Endocrine: Some signals are “broadcasted” throughout the entire body via bloodstream. → Hormones
(produced by endocrine cells) [TV]
• Autocrine: Signals that affect only cells of the same cell type as the emitting cell. [doctor conference]
• Paracrine: Signals (aka local mediators) that act on cells in the vicinity of the emitting cell but on different
cell types than the emitting cell. [Lecture]

CNX OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

2 Main Receptor Types: (Intracellular & Membrane-bound Receptors)
• Intracellular Receptors:
o Lipid-soluble hormones (steroid/thyroid hormones) & even gasses (nitric oxide-blood vessel dilation)
§ Steroid hormones bind to receptor proteins in the cytosol or the nucleus that regulate gene
expression.

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

• Plasma-Membrane-Bound-Receptors:
o Most signal molecules can’t cross the plasma membrane of the target cell.
o Most intracellular signalling proteins act as molecular switches activated by either phosphorylation
OR GTP-Binding (swapping a GDP for a GTP)
o 3 Types:
§ Ion-Channel-Linked Receptors
• Resulting signal is a flow of ions across the membrane – produces an electric current.
§ Enzyme-Linked Receptors
• When activated – act as enzymes or are associated with enzymes inside the cell.
§ G-Protein-Linked Receptors (more common)
• Binds to a class of membrane-bound GTP-Binding-protein (G-Protein) → becomes
activated and released to migrate across the membrane, initiating a cascade of other
effects.
• Some G-Proteins directly regulate ion channels in the plasma membrane.
• Other G-Proteins activate membrane-bound enzymes. Eg: adenylyl-cyclase →
increases the [second messenger (cyclic-AMP)] → activates an intracellular
signalling protein (eg: A protein kinase) OR turns on genes via activated Protein
Kinase ‘A’ (PKA).
OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons
Tissue Responsiveness:
- Receptor Downregulation:
o Where a decreased receptor density in the membrane decreases the responsiveness of that cell to
that receptor’s stimuli.
o This is achieved by Internalising the receptor-ligand complex, dissociating the ligand, and recycling
the receptor back to the surface.

- Receptor Desensitisation:
o Where a change in receptor structure decreases the responsiveness of that cell to that receptor’s
stimuli.
o Why? To prevent multiple, rapid stimulations.

Source: Unattributable
Regulation of Hormone Release:
- 3 Mechanisms:
o 1- Humoral:
§ Where the concentration of a solute in the blood (Eg: High Glucose/Low Calcium) is detected
by a specific gland, stimulating hormone release (Eg: Insulin/Parathyroid Hormone)
o 2- Neural:
§ Where the Nervous System Directly stimulates hormone release.
§ Eg: Sympathetic NS Activated → Stimulates Adrenal Medulla → Secretes Catecholamines.
o 3- Hormonal:
§ Where one hormone stimulates the release of another hormone from a different cell.
§ Eg: The Hypothalamus secretes hormones → Stimulate Ant. Pituitary → Secretes Hormones.
§ Eg: The Ant. Pituitary secretes Hormones → Stimulate other organs to secrete hormones.

FEEDBACK:
• Negative:
o Most common
o Where the Biological Response causes a Decreased Hormone Release.
o Maintains levels around a stable intrinsic/pre-set level.
o Involved in homeostatic control.
• Positive:
o Uncommon (Lactation & Parturition)
o Where the Biological Response causes an Increased Hormone Release
o Are therefore Unstable mechanisms
o Terminate upon removal of initial stimulus.

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

Levels of Feedback Loops:
- Feedback may occur at many different levels within an endocrine axis.
o Ultra-Short Loop:
§ The secreted hormone feeds back to the same tissue that secreted it.
• Eg: A Hypothalamic Hormone feeds back to the Hypothalamus.

o Short Loop:
§ The secreted hormone feeds back to the tissue that stimulated its secretion.
• Eg: The Hormone secreted by the Target Organ feeds back to the Pituitary.
• Or. The Hormone secreted by the Pituitary feeds back to the Hypothalamus.

o Long Loop:
§ The hormone secreted by the target organ feeds directly back to the Hypothalamus.

Source: Unattributable
Major Hormones & Their Functions:

Endocrine gland Associated hormones Chemical class Effect

Pituitary (anterior) Growth hormone (GH) Protein Promotes growth of body tissues

Pituitary (anterior) Prolactin (PRL) Peptide Promotes milk production

Thyroid-stimulating hormone Glycoprotein Stimulates thyroid hormone release
Pituitary (anterior)
(TSH)
Adrenocorticotropic Peptide Stimulates hormone release by
Pituitary (anterior)
hormone (ACTH) adrenal cortex
Follicle-stimulating hormone Glycoprotein Stimulates gamete production
Pituitary (anterior)
(FSH)
Luteinizing hormone (LH) Glycoprotein Stimulates androgen production by
Pituitary (anterior)
gonads
Antidiuretic hormone (ADH) Peptide Stimulates water reabsorption by
Pituitary (posterior)
kidneys
Oxytocin Peptide Stimulates uterine contractions
Pituitary (posterior)
during childbirth
Thyroxine (T4), Amine Stimulate basal metabolic rate
Thyroid
triiodothyronine (T3)
Calcitonin Peptide Reduces blood Ca2+ levels
Thyroid
Peptide Increases blood Ca2+ levels
Parathyroid Parathyroid hormone (PTH)
Aldosterone Steroid Increases blood Na+ levels
Adrenal (cortex)
Cortisol, corticosterone, Steroid Increase blood glucose levels
Adrenal (cortex)
cortisone
Epinephrine, norepinephrine Amine Stimulate fight-or-flight response
Adrenal (medulla)
Melatonin Amine Regulates sleep cycles
Pineal
Insulin Protein Reduces blood glucose levels
Pancreas
Glucagon Protein Increases blood glucose levels
Pancreas
Testosterone Steroid Stimulates development of male
Testes secondary sex characteristics and
sperm production
Oestrogens and Steroid Stimulate development of female
Ovaries progesterone secondary sex characteristics and
prepare the body for childbirth
THE HYPOTHALAMUS & PITUITARY GLAND
 THE HYPOTHALAMUS & PITUITARY GLAND

The Hypothalamus:
- Location:
o In the diencephalon @ base of the brain, just below the thalamus.
o ‘Hypo’-Thalamus = Below the Thalamus

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

- Functions:
o The Hypothalamus receives information from multiple higher brain centres, integrates it, decides on
a response, and orders the pituitary to secrete specific hormones to elicit the response.
§ Ie: Links the nervous system to the endocrine system via the pituitary gland.
o Controls body temperature, hunger, thirst, fatigue, anger, and cycles. Synthesizes & secretes
neurohormones (hypothalamic-releasing hormones) which stimulate or inhibit the secretion of
pituitary hormones.
- Inputs:
o RAS (Reticular Activating System/Substance) – Regulates drowsiness by releasing Serotonin.
o Thalamus – Plays a role in Pain Perception
o Neocortex & Limbic System – Emotional Centre
o Optical System – Vision

Source: Unattributable
 - Outputs:
o Anterior Pituitary
o Posterior Pituitary
o Brain-Stem (Autonomic NS)

- Hypothalamic Regulatory Hormones:

Abbreviation Full Name Stimulated/Inhibited Hormone

GHRH Growth-Hormone Releasing Hormone Stimulates Release of Growth Hormone
SS Somatostatin Inhibits Release of Growth Hormone & TSH
TRH Thyrotropin Releasing Hormone Stimulates Release of TSH & Prolactin
PRH Prolactin Releasing Hormone Stimulates Release of Prolactin
GnRH Gonadotropin Releasing Hormone Stimulates Release of Gonadotropins; FSH & LH
CRH Corticotrophin Releasing Hormone Stimulates Release of ACTH
PIH Prolactin Inhibiting Hormone Inhibits Release of Prolactin

https://www.ncbi.nlm.nih.gov/books/NBK551529/figure/article-692.image.f1/

The Pituitary Gland:

- Location:
o Just Anterior to Pons of the Brainstem
o Just Posterior to the Optic Chiasma
o Just Inferior to the Hypothalamus
o Connects superiorly to the hypothalamus (above it) via the Infundibulum
- Function:
o Secretes at least 9 hormones.
o Function is controlled by hypothalamus (which secretes releasing/inhibiting hormones)
Embryology of the Pituitary Gland:
- Q: Why is the Anterior Pituitary Endocrine, but the Posterior Pituitary Neuronal?
- A: Because they have different embryonic origins.
o Anterior Pituitary:
§ Arises from an upward out-pouching of the Oral-Ectoderm from the roof of the oral cavity
called Rathke’s Pouch. This pouch pinches off from the oral cavity and is later separated by
the sphenoid bone.
§ Consists of Epithelial/Glandular Tissue, & therefore Manufactures & Secretes Hormones.
o Posterior Pituitary:
§ Originates from a downward out-pouching of Neuro-Ectoderm from the brain in the floor of
the 3rd ventricle.
§ Consists of Neural Tissue, & therefore Secretes Neurohormones.

Source: Unattributable
Anterior Pituitary: (Adenohypophysis)
- Glandular Tissue (adeno = gland)
- Responsible for Producing:
o TSH (Thyroid Stimulating Hormone)
o FSH/LH (Follicle Stimulating Hormone; Luteinizing Hormone)
o PRL (Prolactin)
o ACTH (Adreno CorticoTropic Hormone)
o GH (Growth Hormone)
- Different Cell Types in the Anterior Pituitary Secrete Specific Hormones:
o Gonadotrophs: FSH & LH
o Corticotrophs: ACTH (Adreno-Cortico-Tropic Hormone)
o Thyrotrohps: TSH
o Mammotrophs: Prolactin
o Somatotrophs: Growth Hormone & Somatotropin
- Histology – Glandular structure:
o Clusters of acini surrounded by blood vessels
o Acini - mosaics of different cells:
§ (acidophils –red, basophils – dark blue, chromophobes - colourless)
§ Note: Pituitary Tumours may be from any of the 3 cells
o PLENTY of blood vessels (neither arteries or veins; but ‘Portal Vessels’ – Ie: Blood comes only from
the hypothalamus → carries the hypothalamic hormones.)

Mikael Häggström, M.D, CC0, via Wikimedia Commons

- Blood Supply:
o Arterial blood enters via Hypophyseal Branches of the Internal Carotid Arteries.
- Venous Drainage:
o Venous blood leaves via venules which drain into the Dural Sinuses.
OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons
Posterior Pituitary: (Neurohypophysis)
- Made of Nervous Tissue
- Is essentially an Extension of the Hypothalamus
- Supraoptic & Paraventricular Nuclei in the hypothalamus synthesize Oxytocin & ADH →Transport them to
their axon terminals in the Posterior Pituitary.
o Hormones released as needed via exocytosis in Post-Pituitary
§ ADH
§ Oxytocin
- Histology – Just like normal brain tissue. (Neural Origin)
o Note: NO neurones, but plenty of axons.
o Many supporting cells (Astrocytes, oligodendrocytes)
o Plus Blood Vessels (neither arteries or veins; but ‘Portal Vessels’ – Ie: Blood comes only from the
hypothalamus → carries the hypothalamic hormones.)

Jensflorian, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

 Pituitary Hormones:

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons
ACTH – Adrenocorticotropic Hormone:
- Secreted By:
o Corticotrophs in the Anterior Pituitary
- Primary Action:
o Stimulates adrenocortical cells in the Zona Fasciculata of the Adrenal Cortex to secrete
Glucocorticoids.
§ To reduce inflammation
§ To increase blood glucose levels
§ To increase lipolysis & proteolysis
- Release is Stimulated By:
o Corticotrophin Releasing Hormone (CRH)
o CRH is secreted by the Hypothalamus in response to:
§ Stress
§ Low blood glucose
§ Low glucocorticoid levels
§ Increased Sympathetic Activity
§ Normal Diurnal Rhythm
- Release is Regulated By:
o Negative feedback loop between Hypothalamus-Pituitary-Adrenal glands

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

GH – Growth Hormone:
- Secreted By:
o Somatotrophs in the Anterior Pituitary
- Primary Actions:
o ↑Proportion of LEAN BODY MASS:
§ ↑Muscle Mass
§ ↓Adipose Tissue
o Stimulates cell metabolism, growth and division throughout the body
§ Stimulates Protein Synthesis
§ Decreases Protein Breakdown
§ Stimulates Bone Osteoblast activity
o Also has anti-insulin-like effects:
§ Stimulates Gluconeogenesis (Liver)
§ Stimulates Glycogenolysis (Liver)
§ Increases tissue insulin resistance
§ Stimulates Lipolysis (Adipose tissue)
o Indirect Actions (Via Somatomedins/IGF’s):
§ Linear Bone Growth (↑Collagen & Protein Synthesis)
§ Tissue Growth (↑Protein Synthesis & Gene Replication/Transcription)
- Release is Stimulated By:
o Growth Hormone Releasing Hormone (GHRH)
o GHRH is secreted by the Hypothalamus in a diurnal manner & in response to low GH levels
o Also stimulated by Ghrelin from the stomach
- Release is Regulated By:
o Negative feedback loop between Hypothalamus & Pituitary gland

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

TSH - Thyroid Stimulating Hormone:
- Secreted By:
o Thyrotrophs of the Anterior Pituitary
- Primary Action:
o Stimulates Thyroid Gland Growth
o Stimulates Thyroid Hormone Synthesis
o Stimulates Thyroid Hormone Release
- Release is Stimulated By:
o Thyrotropin-Releasing Hormone (TRH)
o TRH is secreted by the Hypothalamus in response to:
§ Low T3/T4 Blood Levels
§ Decreased metabolism
§ Cold stress
§ High-energy-use situations
- Release is Regulated By:
o Negative feedback loop between Hypothalamus-Pituitary-Thyroid glands:

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

FSH/LH – Follicle Stimulating Hormone & Luteinizing Hormone:
- Secreted By:
o Gonadotrophs of the Anterior Pituitary
- Primary Action:
o Important in Puberty → Development of Sexual Characteristics:
§ Primary Sex Characteristics (Genital Development)
§ Secondary Sex Characteristics (Eg: Pubic hair, voice changes, breast development)
o Important for Gamete Production
§ Males: LH → Leydig Cells → Produces Testosterone
§ Males: FSH → Sertoli Cells → Produce Sperm
§ Females: LH → Ovarian Follicles & Progesterone/Oestrogen Synthesis
§ Females: FSH → Recruits Ovarian Follicles early in menstrual cycle
- Release is Stimulated By:
o Gonadotropin-Releasing Hormone (GnRH)
- Release is Regulated By:
o Negative feedback loop between Hypothalamus, Anterior Pituitary & Gonads:

OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons

PRL – Prolactin:
- Secreted By:
o Lactotrophs in the Anterior Pituitary
- Primary Action:
o Targets Breast Tissue:
§ → Stimulates growth of glandular breast tissue during pregnancy
§ → Stimulates Breast Milk Production after birth
- Release is Stimulated By:
o Prolactin-Releasing Hormone (PRH)
- Release is Regulated By:
o Complex feedback loop involving dopamine, suckling stimuli, and other sex hormones

https://calgaryguide.ucalgary.ca/feedback-loop-prolactin-prl/
ADH – Anti-Diuretic Hormone (AKA: “Vasopressin”):
- Secreted By:
o Posterior Pituitary
- Primary Action:
o Regulates Blood Pressure & Blood Volume
§ V1 Receptors → Arteriole Constriction → Increased Systemic Vascular Resistance
§ V2 Receptors → Increases water reabsorption in the Renal Collecting Ducts
- Release is Stimulated By:
o Low blood volume
o Increase of serum osmolality
o Angiotensin-II
- Release is Regulated By:
o Feedback mechanism between Plasma osmolality & Osmoreceptors in Hypothalamus, Total body
water, and the Renin-Angiotensin System

https://www.amboss.com/us/knowledge/General_endocrinology
Oxytocin:
- Secreted By:
o Posterior Pituitary
- Primary Action:
o Progression of Labour
o Let-Down Reflex in Breastfeeding
- Release is Stimulated By:
o Baby Suckling (Breastfeeding)
o Fetal head pushing against cervix (During Labour)
- Release is Regulated By:
o Positive Feedback Mechanisms:
o Birth:

OpenStax, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons

o Breastfeeding:
OpenStax College, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons
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