Endocrine Pathology Quiz

Introduction to Endocrinology (BMS200)

• Course taught by Dr. Lakshman, PhD on September 16th, 2023
• The course covers introductory endocrinology for BMS200 students.

Learning Outcomes

• Describe the functional anatomy of the vascular and non-vascular elements of the endocrine system (hypothalamus, pituitary gland, thyroid gland, and adrenal glands).
• Explain the regulation of the hypothalamic-pituitary-target gland axis, considering short and long feedback loops.
• Describe growth hormone synthesis, transport, function, and regulation, including diurnal rhythms of secretion.
• Analyze the regulation and biological actions of somatomedins in relation to growth hormone secretion.
• Predict complications associated with abnormal growth hormone production and function, such as acromegaly and gigantism.
• Describe the synthesis, regulation of secretion, and function of prolactin, including its role in cross-talk with other hypothalamic hormones.

Pre-Assessment

• How does negative feedback work?
• What do you recall about the functionality of growth hormone?

Hypothalamus Anatomy

• The hypothalamus is composed of different types of neurons combined in various nuclei.
• These neurons receive input from many receptors in the body regarding thirst, blood pressure, appetite, light-dark cycles, and temperature, etc.
• Hypothalamic neurons send outputs to the pituitary gland.

Hypothalamic Regulation

• The hypothalamus receives signals from the CNS and messengers traveling through the bloodstream.
• Specific regions within the third ventricle allow selective passage of signals from blood ventricular fluid (known as circumventricular organs).
• Signals can be detected by neurons in the hypothalamus nuclei.
• These nuclei can sense osmolarity, glucose, and signal peptides (short-loop feedback, appetite mediators).
• Extensive communication exists between the brainstem, limbic areas, and the cortex.

Magnocellular and Parvocellular Neurons

• Magnocellular neurons are located within the supraoptic and paraventricular nuclei and produce large quantities of neurohormones (oxytocin, vasopressin).
• Output from these neurons is released into systemic circulation via the posterior pituitary.
• Parvocellular neurons are smaller and are located within multiple nuclei.
• They produce various neurohormones (CRH, TRH, GHRH, GHIH, DA, GnRH/LHRH, PRH).
• Output from these neurons is released into systemic circulation via the portal vein to the anterior pituitary.

Hypothalamic-Pituitary System (AP)

• The hypothalamus secretes releasing or inhibiting hormones into a set of capillaries.
• These hormones travel to the anterior pituitary, modulating hormone secretion from those cells.
• Anterior pituitary hormones control various other endocrine glands (thyroid, adrenal gland, gonads, liver).
• Hypothalamic-pituitary hormones use a portal vein system for efficient transport.

Cranial Anatomy - Hypophyseal Fossa

• The pituitary gland is encased within a bony structure called the sella turcica.

Basic Function of Hypothalamic Neurohormones

• This section details the function of various hypothalamic hormones.
• Each hormone listed has a specific function (controlling uterine contractions, stimulate thirst, stimulate ACTH release, stimulate TSH release...).

Hypothalamus and Pituitary

• Posterior pituitary, composed of axon terminals from magnocellular neurons and arteries, releases AVP (ADH) and Oxytocin hormones into the systemic circulation.
• Anterior pituitary, composed of endocrine tissues producing ACTH, GH, TSH, etc., receives hypothalamic neurohormones through capillaries, and releases these hormones into systemic circulation.

Hypothalamic Regulation

• Receives input from the CNS, intestines, heart, and liver.
• Contains glucose-sensing neurons and receptors for substances such as osmolarity.
• It regulates the hypothalamus via feedback loops (positive and negative).

Hypothalamic & Pituitary Regulation (Definition)

• Long loop: target endocrine gland — hypothalamus or pituitary
• Short loop: pituitary — hypothalamus
• Ultra-short loop: discussed elsewhere

Review: Short and Long Feedback Loops

• A table summarizing short and long feedback loops for CRH, GHRH, TRH, and GnRH.

Growth Hormone (GH)

• Similar in structure to prolactin.
• Produced by somatotrophs within the anterior pituitary.
• Released in pulses, major burst at night (nocturnal) during slow-wave sleep.
• Transported with a growth hormone-binding protein.
• Half-life is approximately 6-20 minutes.
• Stimulates insulin-like growth factor-1 (IGF-1) release from the liver.

GH Regulation: Stimulation & Inhibition

• GH secretion is stimulated by GHRH, hypoglycemia, arginine, catecholamines, and dopamine.
• GH secretion is inhibited by somatostatin (GHIH), hyperglycemia, increase in non-esterified fatty acids, and insulin-like growth factor-1 (IGF-1).

GH Secretion Patterns

• In the adult, GH levels are reduced due to smaller pulse width and amplitude rather than a decrease in the number of pulses.

GH Receptor

• Class 1 Cytokine Receptor Family
• Locations include liver, bone, kidney, adipose tissue, muscle, brain, and immune cells.
• Binding sites lead to dimerization and increased JAK activity which phosphorylates tyrosine residues and releases transcriptional factors.

GH Functions

• Affects bone growth, adipose tissue lipolysis, skeletal muscle growth, liver function, immune system function, brain function, and metabolism.

GH and IGF-1

• IGF-1 (somatomedin): regulated by GH, PTH and reproductive hormones in bone.
• Function is stimulating bone formation, protein synthesis, glucose uptake, neuronal survival, myelins synthesis, bone turnover, and collagen synthesis.
• Low at birth, increases during childhood/puberty, begins to decline in the third decade.

Too Much GH - What Would You Expect?

• Symptoms of significant excess growth hormone production.

Acromegaly

• Frequently caused by a somatotrope adenoma leading to excess GH secretion.
• Bone: acral bony overgrowth (frontal bossing), increased hand/foot size, mandibular enlargement, and wide spacing between incisor teeth.
• Soft tissue: increased heel pad thickness, enlarged shoe size, coarse facial features, and fleshy nose.
• Neoplastic, Metabolic, and Neurological complications.

Acromegaly – Complications

• Complications associated with Acromegaly, including neoplastic processes, metabolic issues, and neurological effects.

Acromegaly - Metabolic Complications

• Promoting gluconeogenesis.
• Reduction in insulin signaling pathway, and consequent Insulin Resistance.

Acromegaly - Neurologic Complications

• Impingement of the optic nerve (bitemporal hemianopsia), and increased intracranial pressure (causing headaches and impacting other cranial nerves).

Acromegaly and Cardiovascular Impact

• Cardiomyopathy with arrhythmias, left ventricular hypertrophy, decreased diastolic function, upper airway obstruction (due to sleep apnea), central sleep dysfunction, soft tissue laryngeal airway obstruction, diabetes.

Gigantism

• Elevated GH secretion prior to epiphyseal closure in children/adolescents leads to gigantism and nearly identical clinical presentations as acromegaly.

Prolactin

• Synthesized by lactotrophs (15-20% of anterior pituitary).
• Prolactin levels increase in response to estrogen (especially pregnancy).
• Secretion increases during sleep, decreases during wake hours,
• Prolactin stimulates development of mammary glands and milk production.
• Under tonic inhibition from dopamine released from the hypothalamus, bonding to D2 receptors on lactotrophs.
• Also regulated by somatostatin and GABA, which inhibit prolactin release from the hypothalamus.
• Suckling and increased estrogen stimulate prolactin release from hypothalamus, in addition to TRH, serotonergic, and opioidergic pathways.

Prolactin Function

• Develops mammary glands
• Milk synthesis
• Maintains milk synthesis.
• Prevents milk synthesis during pregnancy due to high progesterone levels.
• Inhibits GnRH.

What is the primary hormone responsible for stimulating both the synthesis and secretion of GH from somatotrophs?

• Growth Hormone-releasing hormone (GHRH).

What is the primary physiologic effect of growth hormone?

• Stimulation of postnatal longitudinal growth.

Which family of receptors do growth hormone cell surface receptors belong to?

• Class 1 cytokine receptors.

What is the primary physiologic role of prolactin in the mammary gland?

• Stimulation of milk production.

References

• All mentioned references are summaries regarding the cited texts, details can be found in cited materials, not provided in this response

Adrenal Pathologies (PAT-3.04, BMS 200)

• Course covering adrenal pathologies and their relationships to their respective clinical characteristics.

Learning Outcomes

• Describes the pathophysiology of Cushing's syndrome, relating it to clinical features.
• Describes the pathophysiology of Addison's disease and compares it to adrenal insufficiency.
• Describes the pathophysiology of Conn's disease and its relation to clinical features.
• Predicts pathological findings, clinical features, and complications associated with pheochromocytoma.
• Explains the pathophysiology of adrenal neoplasms and their correlation with clinical features.
• Describes the pathophysiology of congenital adrenal hyperplasia and its relationship to clinical features.
• Relates pathophysiology and clinical features of relevant endocrine disorders to diagnostic tests (e.g., insulin tolerance test, CRH test, etc.)

Terminology

• Tertiary: dysfunction at the hypothalamus
• Secondary: dysfunction at the pituitary gland
• Primary: dysfunction at the adrenal glands (final endocrine organ)

Pathologies of the Adrenal Glands

• Adrenal glands can have hyper- or hypofunction.
• Hyperfunction can involve raised cortisol and/or aldosterone levels and commonly result from secondary causes.
• Disorders that involve elevated androgens will usually also involve reduced levels of glucocorticoids and/or mineralocorticoids.
• The focus is on significant insufficiencies of the adrenal cortex.

Pathologies Covered Today

• Cushing's syndrome, hypercortisolism, hyperaldosteronism, and pheochromocytoma (hyperfunction)
• Adrenocortical insufficiency and congenital adrenal hyperplasia (hypofunction).

Cushing Syndrome

• A disorder caused by elevated glucocorticoid levels, which often stem from excessive cortisol levels.
• Four common sources are: Iatrogenic (drug-induced), hypothalamic-pituitary diseases (associated with ACTH hypersecretion), adrenal adenoma/carcinoma/nodular hyperplasia, or ectopic ACTH secretion by a non-endocrine neoplasm.

Hypersecretion of ACTH

• 70-80% of endogenous hypercortisolism cases involve an ACTH-producing pituitary microadenoma (Cushing Disease).

Ectopic ACTH Production

• Paraneoplastic syndrome involving tumors (e.g., small-cell lung cancer, renal adenocarcinoma).
• Rapid increases in ACTH levels, resulting in quick onset of clinical symptoms/signs.

ACTH-Independent Cushing Syndrome

• Primary Cushing syndrome (10-20% of cases) that arises from an adrenal adenoma (often well-differentiated and more common in women), with excess cortisol production being limited to one gland.

Adrenal Carcinoma

• Uncommon cause of primary Cushing syndrome.
• Typically a large mass that produces excess corticosteroids and androgens.

Iatrogenic Cushing Syndrome

• Most common cause is exogenous administration of glucocorticoids (hydrocortisone, prednisone, methylprednisolone, or dexamethasone).
• Systemic administration required to elevate serum glucocorticoid levels.
• Risks and potential long-term effects on the adrenal glands should be considered.

ACTH Dependent vs ACTH Independent

• Explains the difference in how ACTH secretion influences adrenal function. Visually summarized pathways of disease states.

Clinical Course of Cushing Syndrome

• Mnemonic to remember the associated features (Central Obesity, Cervical fat pads, etc.).
• Describes the clinical features and long-term effects of Cushing syndrome (stressors and long-term pathologies).
• Slow onset and subtle symptoms in early stages.
• Can be subtle until later in the progression, often involving hypertension and weight gain first.

Labs - Cushing Syndrome

• How serum ACTH levels help differentiate primary Cushing's disease from ACTH-dependent forms (based on expected cortisol and ACTH levels in tests).

Adrenal Labs

• Dexamethasone suppression tests (low and high dose).
• In a healthy person, the suppression test determines if endogenous glucocorticoids are being suppressed, indicative of Cushing's disease.
• No suppression indicates ectopic ACTH-dependent Cushing's.

Adrenocortical Insufficiency

• Can be primary or secondary, acute or chronic.
• Primary involves destruction of adrenal cortex, whereas secondary involves a problem with hypothalamic-pituitary axis.
• Chronic cases include autoimmune disease, Tuberculosis, or AIDS.
• Acute cases can arise from rapid cessation of glucocorticoid therapy, or precipitating conditions like shock, injury, surgery, infection, etc.

Adrenal Insufficiency

• Caused by primary adrenal disease or decreased stimulation of adrenals due to ACTH deficiency.
• Possible patterns: primary acute (adrenal crisis) and primary chronic (Addison's Disease), secondary.

Primary Acute Adrenocortical Insufficiency

• In patients on exogenous corticosteroids, rapid withdrawal of steroid doses or failure to increase doses in response to acute stress.
• Common cause in newborns following prolonged/difficult births.
• Pathologies like anticoagulant therapy, disseminated intravascular coagulation (DIC), Waterhouse-Friderichsen syndrome (rare).
• Symptoms include hemodynamic instability, abdominal pain, nausea, vomiting, fever, hypoglycemia, and hyponatremia.

Acute Adrenal Insufficiency

• Life-threatening emergency.
• Clinical features: hemodynamic instability, severe postural hypotension, abdominal pain, nausea, vomiting, fever, decreased level of consciousness, and various physiologic stressors.

Addison Disease (Chronic Primary Adrenal Insufficiency)

• Uncommon; usually progressive destruction of the adrenal cortex.
• Diagnosable when 90% of adrenal cortex is compromised.
• 90% of cases result from autoimmune destruction of the adrenal cortex (60-70% in developed countries), Tuberculosis (less common), AIDS, or sarcoidosis.

Addison Disease - Pathogenesis (Autoimmune Causes)

• Autoimmune Polyendocrine Syndrome (APS) type 1 (rare, autosomal recessive): AIRE gene mutation.
• APS type 2 (More common than type I, begins in early adulthood - between 20 and 40) Autoimmune attack of multiple endocrine organs.
• Idiopathic.

Addison Disease - Clinical Course

• Progressive destruction of adrenal cortex, leads to weakness, and easy fatigability.
• GI disturbances (anorexia, nausea, vomiting, weight loss, and diarrhea)
• Hyperpigmentation, hypokalemia, hyponatremia, and volume depletion.
• Can be triggered/exacerbated by physical stress, infection.
• Adrenal Crisis can occur rapidly unless corticosteroid therapy is started.

Secondary Adrenocortical Insufficiency

• Involves problems with the hypothalamic-pituitary axis, causing reduced ACTH output.
• Possible causes include metastatic cancer, infection, infarction, and/or irradiation.
• Patients typically do not experience hyperpigmentation and the lack of normal aldosterone levels is absent.
• Cortisol & androgen output are reduced, while aldosterone remains normal.
• Insulin tolerance test helps diagnose possible deficiency.

Labs - Adrenal Insufficiency

• Describes how serum ACTH and cortisol levels can distinguish between primary and secondary adrenal insufficiency.

Primary Hyperaldosteronism

• Chronic excess aldosterone secretion.
• Indicates an autonomous overproduction of aldosterone, leading to sodium retention, potassium excretion, hypertension, and hypokalemia.
• Etiologies: often involve a single aldosterone-secreting adenoma (Conn Syndrome), or bilateral adrenal hyperplasia).

Primary Hyperaldosteronism

• Location of dysfunction: often an adrenocortical neoplasm localized to the adrenal gland (i.e., a solitary aldosterone-secreting adenoma, Conn Syndrome, or bilateral adrenal hyperplasia).

Secondary Hyperaldosteronism

• Aldosterone release triggered by renin-angiotensin system activation.
• Caused by decreased perfusion to the kidneys, arterial hypovolemia/edema (CHF, cirrhosis, nephritic syndrome), and pregnancy.
• Plasma renin levels typically elevate in response to these conditions.

Clinical Course of Hyperaldosteronism

• Symptoms include hypertension, hypokalemia (manifesting as neuromuscular issues).
• Diagnosing via aldosterone: renin ratio.

Congenital Adrenal Hyperplasia (CAH)

• Autosomal recessive defect in enzymes involved in cortisol synthesis pathways.
• Most commonly involves 21-hydroxylase deficiency, leading to mild to complete lack of cortisol production.
• Different types exist, including those with salt-wasting, simple virilizing, and non-classic features.

Congenital Adrenal Hyperplasia (CAH) - Classic Forms

• Salt-wasting: Lack of aldosterone; can be fatal if untreated; virilization of female infants.
• Simple virilizing: Reduced 21-hydroxylase function, leading to ambiguous genitalia in female infants at birth.

Congenital Adrenal Hyperplasia (CAH) - Non-Classic

• Late-onset.
• No abnormalities at birth; symptoms appear during puberty.
• Mimics PCOS in women; hirsutism, acne, and menstrual irregularities are common.
• Men are often asymptomatic.
• Diagnosis involves measuring 17-OHP levels.

Pheochromocytoma

• Rare tumor of chromaffin cells in the adrenal medulla; often, but not always, benign.
• Secretes elevated quantities of catecholamines.
• The most common triggers are sporadic cases, while hereditary syndromes can also cause this disease state.
• Majority arises in adrenal medulla, although ~10% can originate in other locations (i.e., carotid bodies).
• Malignant in ~10% of cases; this will lead to tissue invasion.

Pheochromocytoma (continued)

• Clinical features: hypertension (often episodic), catecholamine-induced hypertension (usually in response to physical and/or emotional stress and/or sudden changes in posture), symptoms similar to cerebrovascular accidents (strokes), acute heart failure, and heart hypertrophy.

Adrenals Labs Summary

• Summarizes increased/decreased cortisol levels, along with associated disease states.

Adrenal Physiology (PHY-3.02, BMS 200)

• Course focusing on adrenal physiology for BMS 200 students.

Outcomes for Today

• Contrast the histology, regulation, and secretions of adrenal gland zones.
• Explain the synthesis of steroid hormones, including significant enzymes and transport/metabolism.
• Discuss the physiological roles of glucocorticoids (impact on carbohydrate, protein, lipid metabolism, immune system modulation, and responses to autonomic nervous system and vasopressors).
• Explain the role of mineralocorticoids in sodium and fluid homeostasis.

Outline

• General anatomy of adrenal glands (microscopic/macroscopic, vasculature, embryology).
• Glucocorticoids (synthesis/regulation/effects).
• Mineralocorticoids (synthesis/regulation/effects).
• Catabolism of glucocorticoids and mineralocorticoids.
• Catecholamines (synthesis/regulation/effects/catabolism).

General Roles of the Adrenal Glands

• Key components of the endocrine system.
• Major hormones include: glucocorticoids, mineralocorticoids and catecholamines (primarily epinephrine and norepinephrine).

Adrenal Glands – General Anatomy

• Location: superior to each kidney
• Comprised of the cortex (steroid hormones), and the medulla (catecholamines).
• Adrenal vasculature is extensive.
• Rich blood supply from superior, middle, and inferior suprarenal arteries; Blood drains into a central vein to the vena cava or renal vein.
• Surrounded by a fat pad.

Adrenal Glands – Embryology

• Adrenal Medulla: arises from neural crest cells during embryonic development.
• Adrenal Medulla - functions similar to a large sympathetic ganglion.
• Adrenal Cortex: arises from mesoderm.

Adrenal Glands – Functional Histology & Anatomy, four major zones.

• Zona Glomerulosa: smallest zone; mineralocorticoid secretion.
• Zona Fasciculata: largest zone; glucocorticoid secretion.
• Zona Reticularis: androgen secretion.
• Medulla: catecholamine secretion.

Regulation of Glucocorticoid Secretion

• Corticotrophin releasing hormone (CRH) released from hypothalamus.
• CRH stimulates ACTH release.
• ACTH acts on the adrenal gland, increasing synthesis of cortisol within the zona fasciculata.
• Negative feedback mechanisms regulate HPA Axis; prevents overproduction/underproduction of hormones.

Regulation of Glucocorticoid Secretion

• ACTH binds to a G-Protein coupled receptor in the zona fasciculata cells.
• Binding activates G-protein inside the cell, resulting in dissociation of the alpha-subunit (Gs) and cAMP increase.
• Activation of adenylyl cyclase increased cAMP
• Increased cAMP activates protein kinase A, which phosphorylates various target proteins.
• This leads to specific cellular responses

Synthesis of Adrenal Steroids

• Cholesterol stores are used for synthesis upon activation.
• Cholesterol mobilizatuon: PKA stimulates release from intracellular stores (lipid droplets).
• StAR (steroidogenic acute regulatory protein): facilitates transport of cholesterol to the inner mitochondrial membranes.
• Enzymes convert cholesterol to pregnenolone via steps.
• Further steps convert pregnenolone into glucocorticoids (cortisol).

Glucocorticoid Synthesis Regulation

• ACTH upregulates steps such as LDL receptor expression, activity of CEH and StAR, and side-chain cleavage enzymes
• ACTH is tropic for adrenal gland, increasing gland growth.

Regulation of Glucocorticoid Synthesis

• Circadian rhythm in ACTH and glucocorticoid levels with higher levels in the mornings/early mornings.
• Negative feedback regulates CRH and ACTH release (Cortisol).
• Stress triggers increases in CRH and ACTH secretion.

Effects of Glucocorticoids (Intracellular)

• Glucocorticoid receptors are found in the cytosol and bind to glucocorticoid response elements (HRE).
• Binding of steroid hormones (via displacement of HSP) leads to translocation, dimerization of hormone-receptor complexes, nucleus entry, and stimulating gene transcription at HRE.

General Effects of Glucocorticoids on Metabolism and Fighting Stress

• Increases energy availability by inhibiting DNA/protein synthesis and accelerating protein catabolism; increasing hepatic gluconeogenesis by stimulating gluconeogenesis enzymes (PEPCK and G-6-phosphatase), increased hepatic responsiveness to glucagon, and increasing hepatic and adipose lipolysis.
• Decreases glucose uptake in muscle and adipose tissue and increasing appetite.
• This leads to increase blood sugar, free fatty acids, and overall increase in cellular energy.

General Effects of Glucocorticoids on Other Tissues

• Fetus: steroid hormone synthesis is important in fetal lung development.
• Bone: regulates bone formation via multiple pathways (osteoblast inhibition and osteoclast overactivation).
• Healing tissue: physiologic levels are beneficial for healing, while elevated levels can suppress fibroblast function.
• Nervous systems: can cause mood irregularities, varying from euphoria to irritability, and depression.

General Effects of Glucocorticoids on Other Tissues (continued)

• Increase effectiveness of catecholamines at peripheral vessels or heart.
• Increases salt and water retention at higher concentrations.
• Influences CNS function and behavior, with significant changes in supraphysiologic conditions.

General Effects of Glucocorticoids on the Immune System

• Physiologic elevations increase neutrophil number and activity, as well as monocyte and eosinophil diapedesis.
• Chronic elevations reduce macrophage activity, impair lymphocyte production, reduce antibody production, inhibit phospholipase A2 activity, and impair healing after damage
• Immune function impacts vary based on stressor quantity and type

Synthesis of Mineralocorticoids

• Initial steps in mineralocorticoid synthesis are the same as those for glucocorticoids, beginning with cholesterol and following the same enzymatic cascade leading to pregnenolone.
• Unique steps convert corticosterone to aldosterone.
• Aldosterone synthase is expressed in the zona glomerulosa and is integral for the process.

Mineralocorticoid Secretion Regulation

• Mineralocorticoid synthesis is primarily regulated by angiotensin II within the RAAS and serum potassium levels (K+).

Signaling in the RAAS - the basics

• Decreased perfusion to the kidney stimulates renin release.
• Renin converts angiotensinogen to angiotensin I
• Angiotensin I is converted to angiotensin II (causing vasoconstriction).
• Angiotensin II increases sodium and water reabsorption via the kidney.
• Angiotensin II also increases aldosterone secretion.

Aldosterone - Effects

• The major effects of aldosterone are increased sodium reabsorption and enhanced potassium secretion from the kidneys.
• Stimulates sodium reabsorption, which leads to water retention and an increased ECF volume.
• Decreases potassium reabsorption within the Gl tract, and increase in sodium/potassium pump activity in some cells.
• Glucocorticoids have some aldosterone-like effects (albeit weaker)

How are these hydrophobic steroid hormones carried in the circulation?

• Cortisol and aldosterone will bind somewhat to albumin
• The majority of cortisol is carried by cortisol binding protein (CBG).
• Aldosterone circulates predominantly unbound in circulation, with a much more rapid clearance than cortisol.

How are adrenal steroids metabolized?

• Both cortisol and aldosterone undergo glucuronidation by the liver before excretions by kidneys via a conjugation process to make them more soluble in the kidneys.
• Removal from the body - occurs via urinary excretion.

Synthesis of Catecholamines

• Catecholamines are synthesized from tyrosine, a primary amino acid.
• The adrenal medulla is the primary organ for epinephrine production (NE can also be produced).
• Epinephrine differs from norepinephrine primarily in having a methyl group added.
• Alpha and beta receptors impact stimulation.

Regulation of Catecholamine Synthesis

• Sympathetic stimulation, ACTH, and cortisol all stimulate catecholamine synthesis.

Catecholamine Synthesis

• Sympathetic stimulation leads to exocytosis of norepinephrine and epinephrine from adrenal medulla chromaffin granules.
• A surge in stress triggers the cascade.
• ACTH and Cortisol are also involved in chronic regulation.

Catecholamine Synthesis (acute regulation via neuronal signaling)

• Catecholamine production is triggered by acetylcholine binding to receptors on chromaffin cells, which increases calcium (Ca2+) levels in the cell.
• This increase in calcium facilitates exocytosis, releasing norepinephrine and epinephrine into the blood.

Catecholamine Synthesis (Inside Chromaffin Cells)

• Tyrosine is converted into DOPA then dopamine then norepinephrine then epinephrine via enzymatic pathways.
• Cortisol facilitates conversion of NE to Epi.
• Catecholamines are stored within neurosecretory granules until needed.

Actions of Catecholamines

• Heart: higher contractile force, elevated heart rate
• Vessels: vasoconstriction in skin, visceral tissues (limited in skeletal muscle and cardiac muscle), and potentially vasodilation.
• Energy Metabolism: Increase in blood glucose levels, gluconeogenesis, glycogenolysis, and ketogenesis, and increase of lipolysis..
• Lungs: dilation (bronchodilaiton), decreased mucus production.

Catabolism of Catecholamines

• Epinephrine and norepinephrine are degraded primarily in the liver and kidneys.
• Enzymes convert catecholamines to intermediates, eliminating them from the body to avoid overstimulation.
• The catabolism process produces metabolites, like VMA, that can be measured in the urine to evaluate catecholamine levels.

Test your knowledge on endocrine pathologies with this quiz. It covers key concepts such as primary dysfunction, adrenal insufficiency, Cushing's syndrome, and Conn's disease. Dive deep into the mechanisms and diagnostic evaluations associated with these conditions.