Endocrine disorders I Flashcards
hormone
- a chemical messenger that travels from one cell to another.
- biologically active substances released in one part of the body, travel in the blood stream and have an effect on other part (often remote) of the body.
- helps different parts of the human body to communicate with each other and integrate body functions
Chemical structure of hormones
Amino Acid Derivatives
Peptides
Proteins
Steroid
amine hormone
derived from the modification of single amino acids such as tryptophan, tyrosine
Examples of Amine Hormones
Melatonin (pineal gland) regulates circadian rhythm (synthetic form taken as tablets)
Thyroid hormones (thyroid gland) -metabolism- regulating thyroid hormones
Catecholamines (adrenals) such as epinephrine, norepinephrine play a role in the fight-or-flight response,
Dopamine (hypothalamus) inhibits the release of certain anterior pituitary hormones
Peptide and Protein Hormones
consist of multiple amino acids linked to form an amino acid chain.
synthesized like other body proteins: DNA is transcribed into mRNA, which is translated into an amino acid chain
Peptide hormones
shortest chain of amino acids
Peptide hormones
Antidiuretic hormone (ADH) -pituitary -important in fluid balance
Atrial-natriuretic peptide (ANP)- heart - reduced blood pressure
Protein Hormones
Protein hormones - longer polypeptides
Growth hormone (pituitary gland)
Follicle-stimulating hormone (FSH) – pituitary - glycoprotein (attached carbohydrate group) - stimulate the maturation of eggs in the ovaries and sperm in testes
Steroid hormones
Derived from the lipid cholesterol
Examples of Steroid Hormones
Testosterone and the estrogens (testes and ovaries)
Aldosterone (adrenal) involved in osmoregulation
Cortisol (adrenals) - regulates metabolism
Steroid hormones characteristics
Not soluble in water - they are hydrophobic
Blood is water-based - steroid hormones require a
transport protein (eg Sex Hormone Binding Globulin)
This complex structure extends the half-life (time required for the half of the hormone to be degraded) of steroid hormones much longer than that of hormones derived from amino acids.
Cortisol has a half-life of approximately 60 to 90 minutes
Epinephrine has a half-life of one minute
Mode of action of Non-Steroid hormones
amino acid, peptides, protein hormones
water soluble & lipid insoluble - cannot pass through the cell membrane
act through second messengers – bind to receptors on cell membranes
Mode of action - Steroid hormones
lipid soluble and can pass through the cell membrane directly enter the cell.
Thyroid hormones that are amine derivatives but are lipid soluble
Non-steroid Hormone action
Effects target tissues by binding to the receptors - specific for a hormone
Receptors are extra cellular (surface) protein molecules in the cell membrane associated with G-proteins (GDP) and Adenyl cyclase
Hormones (First messenger) bind to the receptor and produces Second Messengers with the help of receptors
Hormone bind to receptor causing activation of G-protein which further activates Adenyl cyclase that converts ATP to Cyclic AMP (Adenosine monophosphate). This causes a signaling pathway.
The cAMP activates the Kinase enzyme which triggers specific intracellular biochemical changes like enzyme activation, secretion, ion channel changes etc.
Steroid Hormone Action
Diffuse through the cell membrane of the target cell
Bind to intracellular receptors in either the cytoplasm or within the nucleus creating hormone-receptor complex which moves to the cell nucleus and binds to a particular segment of the DNA
It triggers transcription of a target gene to mRNA, which moves to the cytosol and directs protein synthesis.
These proteins promote specific to hormones metabolic reactions in the cell.
Actions are slower but last longer
Regulation of hormone release
humoral
hormonal
neural
in a negative feedback loop
humoral
changes in ion/nutrient level in the blood
hormonal
changes in hormone levels that initiate or inhibit the secretion of another hormone
neural
a nerve impulse prompts the secretion or inhibition of a hormone
What are the man endocrine glands?
hypothalamus/pituitary axis
thyroid gland
adrenals
pancreas
gonads - ovaries and testes
Hypothalamus
Part of limbic system in the brain
Body homeostasis
Controls the release of hormones from the anterior and posterior pituitary
Hypothalamus – hormones
Corticotropin-releasing hormone (CRH)
Gonadotropin-releasing hormone (GnRH)
Thyrotropin-releasing hormone (TRH)
Growth Hormone Releasing Hormone (GHRH)
Antidiuretic hormone/Vasopressin (ADH)
Oxytocin
Corticotropin-releasing hormone (CRH)
stimulates production of ACTH activating cortisol axis
Gonadotropin-releasing hormone (GnRH)
stimulates production of LH/FSH stimulating further gonads – ovaries and testis
Thyrotropin-releasing hormone (TRH)
stimulates production of TSH stimulating thyroid hormone production
Growth Hormone Releasing Hormone (GHRH)
stimulates GH production
Antidiuretic hormone/Vasopressin (ADH)
increases how much water is absorbed into the blood by the kidneys
Oxytocin
release of a mother’s breast milk, moderating body temperature, and regulating sleep cycles
Two parts of Pituitary
anterior and posterior
Anterior Pituitary Hormones
Thyroid Stimulating Hormone (TSH)
Adrenocorticotropic Hormone (ACTH)
Growth Hormone (GH)
Follicle Stimulating Hormone (FSH)
Luteinizing Hormone (LH)
Prolactin (Prl)
Posterior Pituitary
Antidiuretic hormone - Vasopressin (AVP)
Oxytocin
Prolactin
major function of prolactin is milk production – oxytocin stimulates ejection
release is tonically inhibited by dopamine from hypothalamus
Inhibits gonadal function (nature’s contraceptive!)
Posterior Pituitary - where are hormones synthesised?
Hormones synthesized in the hypothalamus (neurons) are transported down the axons to the endings in the posterior pituitary
Where are posterior pituitary hormones stored?
Hormones are stored in vesicles in the posterior pituitary until release into the circulation
What are the principal hormones in posterior pituitary?
Antidiuretic hormone & Oxytocin
Antidiuretic Hormone (ADH)- Antidiuretic actions
V2 receptors
- increases
permeability of the collecting ducts to water
– retaining water
Antidiuretic Hormone (ADH) - Vasopressor actions
V1 receptors
- constricts vascular smooth muscle cells
Oxytocin
Breast-feeding
- Promotes milk ejection as a reflex to baby cry
Childbirth (parturition)
- in late pregnancy, uterine smooth muscle (myometrium) becomes sensitive to oxytocin
- positive feedback
Thyroid gland
- Small gland in the neck
What hormones does thyroid release?
- Release thyroid hormones: * Thyroxine (T4)
- Triiodothyronine (T3)
What are Tyrosine based hormones comprised of?
Partially composed of iodine
- Increases Basal Metabolic Rate and thermogenesis
- Increases sympathetic nerve activity
LH - men
acts on Leydig cells to stimulate Testosterone production
FSH -men
with Testosterone act on Sertoli cells to stimulate spermatogenesis
Testosterone
produced in Testes (Leydig Cells) and adrenal glands (zona reticularis)
LH - women
Stimulates androgen and progesterone production
Stimulates ovulation
FSH - women
stimulates oestrogen production
Oestrogen
Endometrial Proliferation
Breast Development
Progesterone
Increases Body temperature
Secretory endometrium
Where is insulin produced?
Beta cells in the islets of Langerhans produce insulin in response to rising glucose/food.
Promote the storage of glucose in fat, muscle, liver and other body tissues
What do alpha cells produce?
Alpha cells produce glucagon in response to lowering glucose
What do beta cells produce?
insulin
Hypopituitarism
Progressive loss of Anterior Pituitary function: FSH/LH and GH; TSH; ACTH.
What disease does cortisol excess in central lead to?
Cushing’s Disease
Cushing’s Disease
Excess cortisol in the blood due to an ACTH
secreting pituitary tumour
High cortisol, high ACTH
What disease does cortisol excess in adrenal lead to?
Cushing’s Syndrome
Cushing’s Syndrome
Excess cortisol in the blood due to
overproduction of cortisol in the adrenals
High Cortisol, low ACTH
Principles of endocrine investigation
Based on negative feedback – the hormone suppresses its own production
Administer supra-physiologcal levels of hormones – eg 1mg Dexamethasone
Healthy response – endogenous cortisol low - suppressed
Abnormal response – cortisol not suppressed suggesting lack of physiological control
Overnight Low Dose Dexamethasone Suppression Test
Dexamethasone 1mg is given at 11pm the night before
Cortisol is measured at 8am the next morning
Cortisol suppression to <50nmol/l is normal
Cortisol above 100nmol/l suggests autonomous cortisol production – likely Cushing’s
Posterior Pituitary - Diabetes Insipidus
Excretion of a “large” volume (usually >4 L/d) of hypotonic urine in absence of glycosuria.
Test for Posterior Pituitary - Diabetes Insipidus
water deprivation test
Hypothyroidism
Low thyroid hormones T4/T3 and high TSH (periphery cause)
Hypothyroidism - Clinical Features
Insidious onset, tiredness, lethargy, cold intolerance, constipation, weight gain, bradycardia, loss of hair/eyebrow, slow relaxing reflex
Hypothyroidism - Treatment
Thyroxine replacement
Hyperthyroidism
High thyroid hormones T3/T4, Low TSH, Thyroid antibodies positive
Hyperthyroidism - Clinical features
Excess sweating, weight loss, diarrhoea, heat intolerance, palpitations, atrial fibrillation (irregular Heart rate), heart failure, anxiety, eye signs, goitre
Hyperthyroidism - Treatment
surgery, radioactive iodine,
Carbimazole – prevents iodinating tyrosine by thryroid peroxidase reducing levels of hormones
Addisons Disease
Autoimmune destruction of adrenal cortex
Low cortisol, aldosterone, high ACTH
Addisons Disease - Clinical Features
Pigmentation – from ACTH excess
Lethargy, malaise, weight loss
“salt wasting” - hyponatraemia (low sodium),
hyperkalemia (high potassium which could be potentially
life-threatening)
Hypoglycaemia, vomiting, low blood pressure along
with
hyponatraemia and hyperkalemia = Addisonian Crisis – Medical emergency
Female infertility - amenorrhea - Central
Pituitary Destruction – tumour, trauma
Hyperprolactinaemia – high prolactin inhibits LH/FSH
Genetic syndromes - Kallman’s Syndrome
Anorexia Nervosa
Female infertility - amenorrhea - Ovarian
Polycystic Ovarian Syndrome
Ovarian Failure – tumour, trauma
Ovarian dysgenesis – genetic syndromes
Male infertility - Central
Pituitary Destruction
– tumour, trauma
Hyperprolactinaemia
– high prolactin inhibits LH/FSH
Genetic syndromes
- Kallman’s Syndrome
Anorexia Nervosa
Male infertility - Testicular
Tumour, torsion, varicele, orchitis, trauma
Testicular dysgenesis due to genetic disorders
Diabetes Mellitus
Chronic diseases characterised by abnormalities of metabolism (carbohydrate, fat and protein) resulting from either
What is one of the common diseases in the world and one of the major health burdens on the NHS?
Diabetes Mellitus
type 1
Deficiency of insulin
type 2
Resistance to the actions of insulin
type 2
Damage to pancreas
Diagnosis of diabetes
HbA1c (glycolated haemoglobin) cut point of ≥6.5% (48mmol/mol)
Type 1 diabetes
- requires insulin from the moment of diagnosis
- no insulin production due to a combination of genetic, environmental and immunological factors leading to β-cells destruction
- Onset “dramatic” and insulin required to sustain life
Type 2 treatment focus
Metformin
GLP-1 analogues
SGLT2 inhibitors
Insulin at later stages
Diabetes is dangerous due to two complications
Microvascular complication
- Retinopathy
- Neuropathy
- Nephropathy
Macrovascular Complication
- stroke
- myocardial infarction
- peripheral vascular disease
Type 2 diabetes
- Combination of cell secretary defect and insulin
resistance - Late Onset, usually in adulthood
- Insulin resistance
- Risk factors include:
Obesity especially central (abdominal) obesity
Lack of exercise
Family history
Insulin resistance syndromes
