week 6 Flashcards
endocrine control
endocrine system is a complex network of cells and glands that produce and release hormones, which are chemical messengers that travel through the bloodstream to regulate various physiological activities in the body
what controls the endocrine system
Hypothalamus
The anterior pituitary releases:
Thyroid-stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Growth hormone (GH)
Prolactin (PRL)
Gonadotropins (LH and FSH)
the hypothalamus produces hormones called
Thyrotropin-releasing hormone (TRH)
Corticotropin-releasing hormone (CRH)
Growth hormone-releasing hormone (GHRH)
Prolactin-releasing hormone (PRH)
Gonadotropin-releasing hormone (GnRH)
thyroid produces
T3 (triiodothyronine)
T4 (thyroxine)
parathyroid hormone, action
increases blood calcium levels, opposing calcitonin from the thyroid
Thymus Gland: role
production and maturation of immune cells including small lymphocytes that protect the body against foreign antigens. source of cells that will live in the lymphoid tissues and supports their maturation and proper function
Adrenal Glands release consist of a cortex and medulla
cortex releases cortisol and aldosterone, which help regulate metabolism and blood pressure
medulla produces adrenaline and noradrenaline, involved in the fight-or-flight response
Pancreas releases
insulin and glucagon to regulate blood glucose levels (opposing hormones)
kidneys release
renin, increases blood pressure, and erythropoietin, which stimulates red blood cell production
Mechanisms of Endocrine Hypofunction
Ageing: Hormone production can decline with age, affecting various endocrine glands
Autoimmune Conditions: certain autoimmune diseases can attack hormone-secreting cells, leading to reduced hormone levels
Infections and Inflammation: these can damage endocrine tissues, impairing hormone production
Drug Effects: Some medications can cause atrophy of hormone-producing cells, further reducing hormone levels
Causes of Endocrine Hyperfunction
Excess Hormone Production: This can result from: Hyperplasia or Hypertrophy
Tumours:
Autoimmune Disorder
hypothalamus role
maintaining homeostasis by regulating endocrine, autonomic, behavioral, and circadian functions
Anterior Nucleus (Preoptic area) function, impairment and mechanism
Function: Mediates heat dissipation via parasympathetic activation (e.g., vasodilation, sweating)
Impairment: Leads to hyperthermia or poor thermoregulation, especially in febrile states
Mechanism: Impaired central inhibition of heat-retention pathways
Posterior Nucleus function, impairment and mechanism
Function: Promotes heat conservation via sympathetic activation (e.g., vasoconstriction, shivering)
Impairment: Results in hypothermia and inability to respond to cold exposure
Mechanism: Disruption of descending sympathetic outflow from the hypothalamus
Ventromedial Nucleus (VMH) function, impairment and mechanism
Function: Satiety center; inhibits feeding behaviour
Impairment: Leads to hyperphagia and obesity—seen in lesions like craniopharyngioma
Mechanism: Leptin receptor–mediated appetite control is disrupted
Lateral Nucleus: function, impairment and mechanism
Function: Stimulates hunger and feeding behaviour
Impairment: Causes anorexia, weight loss, and failure to thrive, especially in paediatric populations
Mechanism: Disruption in orexin and melanin-concentrating hormone signaling pathways
Supraoptic Nucleus: Arcuate Nucleus: function, impairment and mechanism
Function: Key regulator of the tuberoinfundibular pathway, modulating dopamine (inhibitory to prolactin), GnRH, GHRH, and appetite-related peptides
Impairment: May result in hyperprolactinaemia, amenorrhea, growth delay and appetite dysregulation
Mechanism: Dysfunction of neuropeptide signaling and hypothalamic-pituitary communication
Paraventricular Nucleus (PVN): function, impairment and mechanism
Function: Produces oxytocin and CRH, and regulates autonomic output
Impairment: Causes decreased oxytocin (impacting parturition, lactation, and bonding) and dysregulated stress response via altered CRH secretion
Mechanism: Neuroendocrine axis impairment, particularly the HPA axis
Suprachiasmatic Nucleus (SCN): function, impairment and mechanism
Function: Acts as the central circadian pacemaker, synchronizing biological rhythms via light cues from the retina
Impairment: Leads to circadian rhythm disorders, such as sleep phase delay, insomnia, or irregular sleep-wake cycles
Mechanism: Disruption in melatonin regulation and clock gene expression
Supraoptic Nucleus: function, impairment and mechanism
Function: Produces vasopressin (ADH) for water balance
Impairment: Leads to central diabetes insipidus with polyuria, polydipsia, and hypernatraemia
Mechanism: Loss of AVP synthesis and axonal transport to the posterior pituitary
Aetiology of Hypothalamus dysfunction
Intracranial masses
Vascular events
Trauma or surgery:
Medications
Inflammatory and infectious processes
hypothalamic peptides directly affect
functions of the thyroid gland, the adrenal gland, and the gonads as well as influencing growth, milk production and water balance
infundibulum connects what
hypothalamus and pituitary gland
how does the hypothalamus comunicate with the Anterior Pituitary Gland
through a blood supply
how does the hypothalamus comunicate with the posterior Pituitary Gland
via nerve signals, allowing for direct hormonal release without the need for blood transport
Hypopituitarism
efers to decreased secretion of pituitary hormones, which can result from either disease of pituitary gland or hypothalamus
Aetiology of hypopituitarism
Pituitary Disorders: impair secretion of one or more hormones commonly due to mass lesions, infarction or iatrogenic e.g., from pituitary adenoma surgery, radiation)
Clinical manifestations of hypopituitarism
Depend upon the cause as well as the type and degree of hormonal insufficiency
Patients may be asymptomatic or present with symptoms related to hormone deficiency or a mass lesion, or nonspecific symptoms such as fatigue
where is the growth hormone produced in what cell
pituitary somatotroph cells
growth hormone role
growth and metabolism
- Hyperfunction: excessive hormone production of endocrine function causes
- Excessive stimulation and hyperplasia or hypertrophy of the endocrine gland
- Hormone-producing tumour of the gland
- Ectopic hormone secretion
- Medication
- Decrease negative feedback
anterior pituitary hormones impoertant ones to know secreted here are
growth hormone
thyroid hormone and
Adrenocortictropic
Causes of multi-hormone pituitary disruptions
- Tumours
- Pituitary surgery or radiation
- Lesions and head trauma
- Infection or inflammation
- Autoimmune disease
Clinical manifestations of hypopituitarism
- Headache
- Altered mental state
- Postural hypotension
- Being chronically unfit
- Weakness and fatigue
- Growth failure
Growth hormone excess and deplition excretion
- Excess – gigantism (children), acromegaly (adults)
- Depletion – dwarfism (children)
ADH excess and deplition excretion
- Excess – SIAHD
- Depletion – Diabetes insipidus
ACTH excess and deplition excretion
- Excess – Cushing’s
- Depletion – Addison’s
Growth hormone hyposecretion - children
delayed puberty
* Delayed skeletal maturation
* Results in short stature or dwarfism
* Disrupts normal blood glucose levels
* Decreased muscle mass
* Increased subcutaneous fat
Growth hormone hyposecretion - adult
- Reduced bone density
- Alterations in physical and mental well-being
- Cardiac function and metabolic parameters
- Lower levels of energy and libido
Growth hormone hypersecretion - children
- Results in increased linear bone growth – Gigantism
- Thickening of fingers, jaw, forehead, hands and feet
- Decreased bone density
Growth hormone hypersecretion - adults
- Overgrowth of the cartilaginous parts of the skeleton
- Enlargement of the heart and other organs of the body
- Metabolic disturbances resulting in altered fat metabolism and impaired glucose tolerance
main function of adrenal gland
Stress responsiveness
Sugar (glucose) availability
Salt balance
Sexual balance and maintenance
Adrenal Medulla
part of the sympathetic nervous system
when stimulated releases adrenaline and noradrenaline
Primary Adrenal Insufficiency (Addison’s Disease)
adrenal cortex (outer layer of adrenal gland). Leads to ↓ cortisol, ↓ aldosterone, and ↓ adrenal androgens
Aetiology Primary Adrenal Insufficiency
Autoimmune adrenalitis (most common) - autoimmune process that destroys the adrenal cortex; evidence of both humoral and cell-mediated immune mechanisms directed at adrenal cortex
infection
Haemorrhagic/Infarction
genetics
drugs
Epidemiology Primary Adrenal Insufficiency
2500 australians with 100 new dx each year
B. Seconday Adrenal Insufficiency is problem in
pituitary gland (↓ACTH). Aldosterone is preserved.
C. Tertiary Adrenal Insufficiency
is problem in the
hypothalamus (↓CRH) or functional suppression of Hypothalamic-Pituitary-Adrenal axis
aeitology of Tertiary Adrenal Insufficiency
Most common - Exogenous glucocorticoids
Long-term steroid therapy (oral, inhaled, topical, intra-articular)
Abrupt cessation of steroids without tapering
Hypothalamic tumours or trauma
Clinical manifestations of Primary Adrenal Insufficiency (Addison’s Disease)
fatigue, weakness, nausea, anorexia and weight loss, abdominal pain, darkening of the skin or mucous membranes
chronic hypotension, hypoglycaemia, decreased heart size
Zona glomerulosa (outer) adrenal cortex, hormone produced and its function
Mineralocorticoids (mainly aldosterone) Regulates sodium and potassium balance via the RAAS
Zona fasciculata (middle) adrenal cortex, hormone produced and its function
Glucocorticoids (mainly cortisol)
Controls metabolism, immune response, and stress response. Secretion is regulated by the hypothalamic-pituitary-adrenal axis via ACTH
Zona reticularis (inner) adrenal cortex, hormone produced and its function
Androgens (e.g., DHEA)
Contributes to secondary sexual characteristics, especially in females
Negative feedback in Adrenal Medulla
High cortisol inhibits both CRH and ACTH production
Subclinical/Partial adrenal cortex
Mild or absent symptoms; often normal cortisol at rest but inadequate during stress
Compensated/Chronic adrenal cortex clinical manifestations
Progressive fatigue, anorexia, weight loss, postural hypotension, hyperpigmentation
Acute Adrenal Crisis
life-threatening hypotension, shock, vomiting, abdominal pain, hypoglycaemia
Cushing Syndrome
characterised by elevated cortisol levels in the blood, which can arise from various causes, including both exogenous and endogenous factors
Exogenous Cushing Syndrome Aetiology
cortisol is introduced from outside the body, commonly through long-term use of steroid medication
Endogenous Cushing Syndrome
results from the body producing excess cortisol.
Pathogenesis Cushing Syndrome
involves the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Normally, the hypothalamus releases corticotropin-releasing hormone (CRH), stimulating the pituitary gland to secrete ACTH, which in turn prompts the adrenal glands to produce cortisol
In Cushing syndrome, this regulatory mechanism is disrupted, leading to abnormally high cortisol levels
clinical manifestations of Cushing syndrome
Muscle Wasting
Skin Changes
Bone Health
Addison’s Disease is compared to ushing Syndrome
Addison’s Disease (Primary Adrenal Insufficiency)
Cushing Syndrome (Glucocorticoid Excess)
Addison’s Disease (Primary Adrenal Insufficiency) cause, hormonal deficientcies and clinical features
Cause: Autoimmune destruction of the adrenal cortex (autoimmune adrenalitis), infections (e.g., TB, CMV), hemorrhage, infiltrative disease, or medications
Hormones Deficient: ↓ Cortisol, ↓ Aldosterone, ↓ Androgens
Clinical Features: fatigue, weight loss, nausea, vomiting, postural hypotension, hyperpigmentation
Cushing Syndrome (Glucocorticoid Excess)
cause, hormonal deficientcies and clinical features
Cause: Prolonged exposure to excess cortisol
Exogenous steroids (most common)
Endogenous: Pituitary adenoma (Cushing disease), adrenal tumor, ectopic ACTH
Hormones Elevated: ↑ Cortisol (± ACTH depending on source)
Clinical Features: central obesity, moon face, buffalo hump, muscle wasting, skin thinning, purple striaem hypertension, glucose intolerance, osteoporosis
Thyroid gland secrete what 3 hormones
Thyroxine (T4)
Triiodothyronine (T3)
Calcitonin
Thyroid disorders Epidemiology
not readily known
Hypothyroidism Aetiology
Primary hypothyroidism is due to inadequate production of thyroid hormone caused by disease of the thyroid gland
central hypothyroidism is more rare, and refers to thyroid hormone deficiency due to a disorder of the pituitary, hypothalamus, or hypothalamic-pituitary portal circulation,
Hyperthyroidism Aetiology
Increased thyoid hormone synthesis:
Exogenous thyroid hormone use
Increased release of preformed throid hormone:
Thyroid storm
rare but severe presentation of hyperthyroidism characterised by an acute exacerbation of symptoms
clinical manifestations of thyroid storm
Anxiety and irritability
Sweating and heat intolerance
Tachycardia
Weight Loss
Fatigue
Frequent Loose Stools
Describe the role of thyroid hormones in metabolism
Increase Basal Metabolic Rate
Carbohydrate Metabolism
Lipid Metabolism
Protein Metabolism
Clinical presentations of hypothyroidism include:
Weight Gain
Fatigueadequate rest
Dry Skin and Hair Loss
Constipation
Hyperthyroidism Clinical features include
Weight Loss
Anxiety and Irritability
Tachycardia
Frequent Loose Stools
parathyroid glands secrete what hormone and what is its function
parathyroid hormone (PTH) which is a major regulator of calcium balance
Hypoparathyroidism
Aetiology
Post-surgical
autoimmune destruction
Genetic causes
Infiltrative diseases
Hypoparathyroidism Pathophysiology
deficient secretion or action of parathyroid hormone (PTH).
↓ serum calcium levels due to decreased bone resorption and reduced calcium reabsorption in kidneys
There is also low or inappropriately normal active form of Vitamin D levels, and this leads to less intestinal calcium absorption
Clinical manifestations Hypoparathyroidism
Neuromuscular irritability e.g., muscle cramps, facial twitching, paraesthesias
Psychiatric symptoms
Chronic: dry skin, brittle nails, hair loss, basa
Primary Hyperparathyroidism Aetiology
Autonomous overproduction of PTH, typically due to:
Parathyroid adenoma (most common)
Hyperplasia
Rarely, parathyroid carcinoma
Primary Hyperparathyroidism
Hypercalcaemia via increased bone resorption, increased calcium reabsorption from kidneys, and increased intestinal absorption as there is an increase conversion of Vitamin D to its active form
Hypophosphataemia (increased renal excretion of phosphate)
Bone demineralisation over time
Secondary Hyperparathyroidism Aetiology and Pathophysiology
Chronic kidney disease (CKD) → impaired vitamin D activation and phosphate retention
Vitamin D deficiency or malabsorption
Clinical manifestations of Hyperparathyroidism
Skeletal: Osteopenia/osteoporosis
Renal: Nephrolithiasis (calcium stones)
Gastrointestinal: Constipation, nausea
Neuromuscular: Fatigue, weakness
Psychiatric: Depression
Cardiac: Shortened QT interval, arrhythmia
Diabetes Mellitus
condition marked by high levels of glucose (sugar) in the blood.
Type 1 diabetes
- Characterised by extensive damage to the pancreatic beta islet cells
- Insulin production and release is reduced
Development of Type 1A Diabetes
- Genetic predisposition
- Immunologically mediated beta cell destruction
- Insulin antibodies or islet antibodies
Idiopathic Type 1B Diabetes
- Those cases of beta cell destruction in which no evidence of autoimmunity is present
- Only a small number of people with type 1 diabetes fall into this category
- Strongly inherited.
Aetiology of T1DM
- Autoimmune Origin- caused by immune-mediated destruction of pancreatic β-cells
- Genetic Susceptibility
- Environmental Triggers- Viruses, Diet, Toxins, Immunotherapy
Epidemiology of T1DM
most common chronic diseases in childhood
Approximately 13,200 children and young adults aged 0–19 were living with type 1 diabetes in 2021
first nations children= a lot more common
Pathogenesis of T1DM
a lack of endogenous insulin secretion from the pancreatic β-cells
stages of T1DM
Autoimmunity Begins
Early Glucose Changes
Clinical Diabetes
Clinical manifestations of T1DM
increased urinary glucose excretion
enhanced thirst
Weight loss
Acute visual disturbances
Complications of T1DM
developing eye damage
developing nervous system damage
developing kidney disease
being diagnosed with a second autoimmune disease
Type 2 Diabetes Mellitus
characterised by hyperglycaemia, insulin resistance and defective insulin secretion
Type 2 Diabetes Mellitus Aetiology
- Genetic Predisposition
- Lifestyle and Environmental Factors
T2DM Epidemiology
In Australia, there are over 1.2 million (4.6%) people were living with type 2 diabetes
T2DM Pathophysiology
multifactorial- may have:
insulin resistance in muscle, adipose tissue, and liver
defective insulin secretion
Impaired insulin processing in T2DM
a greater proportion of secreted insulin remains as proinsulin
This suggests that the processing of proinsulin to insulin in the β-cells is impaired in T2DM
Clinical manifestations of T2DM
increased urinary glucose excretion, blurred vision, fatigue or feeling tired and weight loss
Definition Metabolic syndrome
cluster of common abnormalities, including insulin resistance, impaired glucose tolerance, abdominal obesity, reduced high-density lipoprotein (HDL)-cholesterol levels, elevated triglycerides, and hypertension.
Diagnostic Criteria (≥3 of 5 components) of Metabolic syndrome (MetS)
abdominal obesity
elevated triglycerides: ≥150 mg/dL
reduced HDL-C
elevated blood pressure
hyperglycaemia
Aetiology Metabolic syndrome
Visceral adiposity and ectopic fat accumulation
Adipose tissue dysfunction
Genetic susceptibility
Sex-based hormonal differences
Socio-environmental drivers
Pathogenesis of metabolic syndromes
are as yet unknown hw some inc
At the core of these processes are visceral fat accumulation, insulin resistance and chronic low-grade inflammation which together lead to widespread metabolic and organ dysfunction.
Clinical manifestations of metabolic syndrome
obesity-related conditions
hypertension-related signs:
insulin resistance signs: fatigue
dyslipidaemia
Overweight and Obesity Aetiology
Biological and Genetic Factors- Heritability& hormonal response to weight loss
Behavioral and Environmental Factors: High caloric intake, ultra-processed foods, sedentary lifestyles and reduced sleep contribute significantly
Developmental Origins- Foetal overnutrition, maternal obesity and early-life exposures can induce long-lasting changes in metabolism
Iatrogenic Factors- certain meds
Phases of metabolism
Anabolism
Catabolism
Metabolites
Health risk for obesity
- Gallbladder disease, infertility
- Sleep apnoea and pulmonary dysfunction
- Cancer
- Bone and joint problems
Hypertension
Epidemiology of obesity
Adults: 66%
children and Adolescents (2–17 years): 26%
Pathogenesis Overweight and Obesity
body defends its equilibrium fat stores through evolutionarily conserved mechanisms—triggered by reduced leptin and gut hormones—that increase hunger and lower energy expenditure during weight loss, maintaining a brain-regulated set-point even at unhealthy levels of adiposity.
Metabolic Consequences of obesity
This raises the workload on pancreatic β-cells
Cardiovascular Effects of obesity
Link between obesity and CVD is complex due to overlapping risk factor
Upper airways and respiratory system due to obesity
Physical effects of increased intra-abdominal and central adiposity on diaphragmatic compliance and lung function can also contribute to breathlessness
Musculoskeletal due to obesity
Weight-related metabolic and inflammatory factors contribute to direct mechanical
