ENDOCRINE SYSTEM

Endocrine system

-maintains homeostasis

through glandular hormone regulation.

-Disruptions in hormone levels can lead to

disorders affecting overall body function.

Role of Hypothalamus & Pituitary

Drugs that interact with hypothalamic and

pituitary hormones are used to treat and replace

deficient hormones.

Growth Hormone-Releasing Hormone

GHRH

Thyrotropin-Releasing Hormone

TRH

Gonadotropin-Releasing Hormone

GnRH

Corticotropin-Releasing Hormone

CRH

Prolactin-Releasing Hormone

PRH

Somatostatin

Inhibits growth hormone release

PIF

Prolactin-Inhibiting Factor.

Growth Hormone-Releasing Hormone

Thyrotropin-Releasing Hormone

Gonadotropin-Releasing Hormone

Corticotropin-Releasing Hormone

Prolactin-Releasing Hormone

Stimulating Hormones (Releasing Factors):

Goserelin

Histrelin

Leuprolide and Nafarelin

Tesamorelin

Hypothalamic-Releasing Hormones:

Tesamorelin

Stimulates GH release,used in HIV-related lipodystrophy.

Leuprolide

Potent GnRH agonists.

Histrelin

GnRH as an antineoplastic agent.

Goserelin

Synthetic GnRH

Cetrorelix

Degarelix

Ganirelix Acetate

Hypothalamic Hormone Antagonists:

Cetrorelix

GnRH antagonist for fertility.

Ganirelix Acetate

GnRH antagonist.

Degarelix

Blocks GnRH for cancer treatment.

Goserelin, Histrelin, Leuprolide, Nafarelin

Used to suppress gonadotropin secretion and decrease sex hormones.

Tesamorelin

Stimulates GH release to decrease abdominal fat in HIV patients with lipodystrophy

Cetrorelix, Degarelix, Ganirelix

Block GnRH to treat conditions like prostate cancer and fertility disorders.

Nafarelin

is administered via nasal spray.

Hypothalamic-Releasing Hormones

●Hypersensitivity to the drug or its

components.

●Pregnancy and lactation due to potential

harm to the fetus or baby.

Increased Sex Hormones

Decreases sex hormone production.

Adverse Effects: Agonists (e.g., Goserelin,Leuprolide)

Male side effects: Decreased testosterone levels

Female Side Effects: Reduced sex hormones

Adverse Effects: Antagonists (e.g., Cetrorelix,Degarelix)

Role of the Anterior Pituitary

• Secretes hormones essential for growth,

metabolism, and reproductive function.

• Agents affecting pituitary hormones mimic or

antagonize the effects of these hormones.

Anterior Pituitary Hormones

Therapeutic Use

Used for replacement therapy (e.g., growth

hormone deficiency) and diagnostic purposes.

Growth Hormone (GH)

Luteinizing Hormone (LH)

Follicle-Stimulating Hormone (FSH)

Thyroid-Stimulating Hormone (TSH)

Adrenocorticotropic Hormone (ACTH)

Main Anterior Pituitary Hormones:

Linear skeletal growth

Growth of internal organs

Protein synthesis

Deficiency can lead to hypopituitarism and

dwarfism

Growth Hormone Agonists:

• Developmental abnormalities

• pituitary tumors

• circulatory disturbances

• trauma

• In adults: Often due to pituitary tumors or

treatment for childhood GH deficiency.

Common Causes of GH Deficiency:

Historical treatment

Modern treatment

Growth Hormone Replacement Therapy (GHRT):

Modern treatment

Somatropin (synthetic human GH), produced through recombinant DNA

(rDNA) technology.

Historical treatment

Originally extracted from cadavers,limiting supply and increasing cost.

Growth Hormone Replacement Therapy (GHRT)

• Primary used as GH replacement: Used in

children with short stature (d w arfi sm) and

adults with somatotropin deficiency syndrome

(S D S ).

• Other indications include growth failure in

children with GH deficiency and certain

conditions like HIV-related lipodystrophy.

Cytochrome P450 Interaction

GH may interact with drugs metabolized by the cytochrome P450 enzyme system, leading to altered metabolism of other medications.

Monitoring Required

Careful monitoring is needed when combining GH therapy with other drugs affecting liver enzymes

Growth Hormone Replacement Therapy (GHRT)

Peak levels: Reach peak within 7 hours after injection.

Growth Hormone Replacement Therapy (GHRT)

Contraindications

●Known allergy to somatropin or its

ingredients

●Closed epiphyses (in children whose

growth plates have fused)

●Cranial lesions, abdominal surgery, and

acute illness (e.g., complications

post-heart surgery)

Growth Hormone Replacement Therapy (GHRT)

Antibody formation to GH, leading to inflammation and autoimmune-type reactions (swelling, joint pain)

Endocrine Effects: Hypothyroidism and insulin resistance

Swelling and joint pain are common in some patients

Growth Hormone Hypersecretion

●Caused mainly by pituitary tumors

• Can occur at any age, leading to

hyperpituitarism

In Children (Before Epiphyseal Plate Closure)

In Adults (After Plate Closure)

Effects of GH Hypersecretion:

Acromegaly

Linear growth stops

In Adults (After Plate Closure)

Gigantism

In Children (Before Epiphyseal Plate Closure)

Surgical and Radiation Therapy

Drug Therapy

Treatment Options Of Growth Hormone Hypersecretion:

Dopamine agonists

Somatostatin analogues

GH analogue

Drug Therapy Of Growth Hormone Hypersecretion:

GH analogue

(e.g., Pegvisomant)

Somatostatin analogues

(e.g.,Octreotide acetate, Lanreotide)

Dopamine agonists

(e.g.,Bromocriptine)

Somatostatin Analogs Somatostatin

• Naturally inhibits GH release from thehypothalamus

• Not used directly for GH excess due to multiple

effects (inhibits gastrin, glucagon, insulin)

Octreotide acetate and Lanreotide

More potent than somatostatin in inhibiting GH

Lanreotide

Given as monthly subcutaneous injection

Dopamine Agonists

• A semisynthetic ergot alkaloid that inhibits GH secretion

• Increases somatostatin release from the hypothalamus

• May be used alone or in combination with radiation therapy for acromegaly

Dopamine Agonists

In normal individuals, ___________ can increase GH release (opposite effect).

GH Analogues

Mechanism of Action

• Pegvisomant is a GH analogue that binds to GH receptors on cells, blocking GH's effects

• Used for patients who don’t respond to other

treatments (surgery, radiation, octreotide)

• Administered daily via subcutaneous injection

Octreotide

Rapidly absorbed, widely distributed; excreted 30% unchanged in

urine.

Lanreotide

Depot form, slow release, half-life of 25-30 days

Bromocriptine

• Administered orally, absorbed from the

GI tract, extensively metabolized in the

liver

●Excreted in bile

Pegvisomant

• Subcutaneous injection; peak effect

within 33-77 hours

●Half-life of 6 days, excreted in urine

Bromocriptine

Contraindicated in pregnancy and lactation due to effects on the fetus and

lactation inhibition

Octreotide, Lanreotide, and Pegvisomant

No adequate studies in pregnancy or lactation; use only if benefits outweigh

risks

Diabetes

Thyroid dysfunction

Caution in endocrine disorders ___________ , as GH antagonists may worsen

these conditions

Octreotide & Lanreotide

●GI complaints: Constipation, diarrhea,

nausea, flatulence

●Serious effects: Acute cholecystitis,

biliary tract obstruction, pancreatitis

●Cardiac effects: Sinus bradycardia,

arrhythmias

●Injection site reactions: Pain,

discomfort, inflammation

●Blood glucose changes: Monitor glucose

levels, especially with Lanreotide

Bromocriptine

●GI disturbances: Nausea, constipation

●Dopamine-blocking effects: Drowsiness,

postural hypotension

●Lactation inhibition

Pegvisomant

●Injection site pain and inflammation

●Liver function changes, increased

infection risk, nausea, and diarrhea

Bromocriptine

• Increased toxicity with erythromycin

(avoid combination)

● Decreased effectiveness with

phenothiazines (monitor closely)

Pegvisomant

May require higher doses if used with opioids (mechanism unclear)

●Chorionic Gonadotropin

• Cosyntropin

• Pasireotide

• Thyrotropin Alpha

Drugs Affecting the Anterior Pituitary Hormones

Chorionic Gonadotropin (Chorex)

Mechanism of Action:

●Acts like Luteinizing Hormone (LH)

• Stimulates testosterone production in males and

progesterone production in females

Chorionic Gonadotropin (Chorex)

Male: Treatment of hypogonadism, to stimulate testosterone production

Female: Used in fertility treatments to support ovulation

Pasireotide

Administration:

Drugs Affecting the Anterior Pituitary Hormones

• Available in long-acting release (LAR) form for

monthly injections

Thyrotropin Alpha (Thyrogen)

Mechanism of Action:

• A synthetic version of TSH (Thyroid-Stimulating

Hormone).

• Stimulates the thyroid to produce thyroid hormones

Chorionic Gonadotropin Alpha (Ovidrel)

Related Drug of chorionic Gonadotropin:

Chorionic Gonadotropin Alpha (Ovidrel)

Used as a fertility drug to induce ovulation in women

Cosyntropin

Mechanism of Action:

●A synthetic form of ACTH (Adrenocorticotropic Hormone).

• Stimulates the adrenal glands to produce

cortisol

Cosyntropin

Indications:

●Diagnostic use to test adrenal function and adrenal gland responsiveness

• Not used therapeutically

• Rapid onset, short duration of action

Pasireotide (Signi for, SigniforLAR)

Mechanism of Action:

• A somatostatin analog that inhibits the release of ACTH from the pituitary

• Acts on somatostatin receptors in the adrenal gland

Cushing's Disease

Acromegaly

Indications: Of Pasireotide:

Acromegaly

Suppresses GH in patients who do not respond to other therapies

Thyrotropin Alpha (Thyrogen)

Indications:

• Adjunctive treatment for radioiodine ablation of thyroid tissue

• Used in patients who have undergone near-total to total thyroidectomy for thyroid cancer

• Helps locate thyroid remnants by stimulating iodine uptake

Cushing's Disease

Reduces ACTH secretion in patients with Cushing’s disease

Chorionic Gonadotropin

Used in fertility treatments for both men (testosterone stimulation) and women

(ovulation induction).

Cosyntropin

Used for diagnostic testing of adrenal function

Pasireotide

Treats Cushing's disease and acromegaly

Thyrotropin Alpha

Aids in post-thyroidectomy management and radioiodine ablation

Chorionic Gonadotropin

• Administered intramuscularly (IM)

●Half-life: Several hours, depending on

the formulation

Cosyntropin

• Administered IV for diagnostic purposes

• Short duration of action

Pasireotide

• Available in long-acting injectable (LAR)

●Half-life of 12-15 hours

Thyrotropin Alpha

• Administered IM or subcutaneously (SC)

●Half-life of 24 hours

Chorionic Gonadotropin

Contraindicated in pregnancy and active ovarian cysts

Cosyntropin

• Use cautiously in patients with adrenal

insufficiency

●Contraindicated in severe cardiovascular

disease

Pasireotide

• Contraindicated in pregnancy and

lactation

●Caution with liver dysfunction, as it may

cause liver enzyme changes

Thyrotropin Alpha

• Contraindicated in patients with iodine

allergy

●Caution in patients with cardiovascular

issues or hyperthyroidism

Chorionic Gonadotropin

Adverse Effects:

• Headache, fatigue, irritability

●Possible ovarian hyperstimulation

Cosyntropin

Adverse Effects:

Fluid retention, hypokalemia, increased

blood pressure

●Hyperglycemia in diabetic patients

Pasireotide

Adverse effects:

• GI symptoms: Nausea, diarrhea,

abdominal discomfort

●Elevated liver enzymes, glucose

intolerance

●Fatigue and headache

Thyrotropin Alpha

Adverse effects:

• Injection site reactions

●Flu-like symptoms (e.g., fever, chills)

Chorionic Gonadotropin

Clinical Considerations:

● Monitor ovarian response during fertility

treatment

●Ensure proper timing for ovulation

induction

Cosyntropin

Clinical Considerations:

Only used for diagnostic testing of adrenal insufficiency

Pasireotide

Clinical considerations:

Regular monitoring of liver function and glucose levels is essential