Endocrinology I Flashcards
What are the functions of endocrine glands?
Regulate concentration of blood fluid (haemostasis)
Regulate body temperature
Regulation of reproduction, development and metabolism
What are the three major classes of hormones?
Polypeptide - proteins and peptides (water soluble)
Amine - derived from amino acids (water soluble)
Steroid hormones (lipid soluble)
What is the HPA pathway for stress and circadian rhythm?
Stressful stimulus causes the hypothalamus to release CRH
CRH stimulates the pituitary gland to release ACTH
ACTH stimulates the adrenal cortex which releases cortisol and androgens > stress metabolism. Positive and negative feedback
How is hormone secretion regulated?
Positive feedback and negative feedback loops
Positive feedback loop: hormones act on anterior pituitary
Negative feedback long loops: hormones act on anterior pituitary and hypothalamus. Short loops from anterior pituitary to hypothalamus
What is the embryological origin of the pituitary gland?
Anterior lobe (adenohypophysis) - protrusion of the ectoderm from roof of mouth
Posterior lobe (neurohypophysis) - neuroectoderm
What is the difference between the anterior and posterior pituitary gland?
Anterior pituitary: synthesise and stores hormones
Posterior hormones: only stores and releases them
What are examples of hormones released by anterior lobe of pituitary gland? what cells release them?
GH by somatotrophs
TSH by thyrotrophs
ACTH by corticotrophs
FSH and LH by gonadotrophs
Prolactin by lactotrophs
What hormones are released by the posterior pituitary gland? what cells release them?
ADH and oxytocinby cell bodies of hypothalamic neurons, secreted by nerve terminals
Where do the problems lie in primary, secondary and tertiary endocrine disorders?
Primary - Thyroid gland, parathyroid gland
Secondary - Anterior pituitary
Tertiary - Hypothalamus
What may cause hypersecretion?
Hormone secreting tumours
Hyperplasia
Autoimmune stimulation
Ectopically produced peptide hormone - ACTH, ADH
What may cause hyposecretion?
Autoimmune disease
Tumours
Infection
Haemorrhage
What regulates GH release from the anterior pituitary?
GNRH from hypothalamus has positive feedback, stimulates GH release
Somatostatin from hypothalamus has negative feedback, inhibits GH release
What are the two functions of GH? How does it exert these functions?
Growth of skeletal and soft tissue
Metabolic on carbohydrate, lipid and protein metabolism
- Indirect - through hormone - IGF1/somatomedins
- Direct - through GH receptors in target tissue
When may GH secretion increase/decrease?
Increase: sleep, stress, young age
Decrease: old age, obesity
What are the direct actions of GH?
- Increased cartilage formation, bone growth
- Increaesd protein synthesis, cell growth and proliferation
What are the indirect actions of GH?
Increased lipolysis
Increased blood sugar
What can GH deficiency cause in children?
Pituitary dwarfism:
- Impaired pituitary GH secretion
- Decreased rate of growth and short stature
- Normal brain development
- Decreased plasma GH and IGF1
Laron dwarfism:
- Defective GH receptors in target tissue and defective IGF1 production
- Decreased plasma IGF1 but elevated plasma GH
What can GH deficiency cause in adults?
If GH deficiency occurs after epiphyseal fusion of long bones, height unaffected
- Increased body fat
- Reduced muscle mass
- Fatigue
- Decreased physical fitness
What does excess GH in children cause - before epiphyseal plates have fused?
Gigantism
Rapid increase in growth and weight
Can be due to tumour in pituitary that hypersecretes GH
- Large hands and feet
- Coarse facial features, frontal bossing, prognathism
- Headaches
- Excessive sweating
What can excess GH cause in adults - once epiphyseal plates have fused?
Acromegaly
Excessive skeletal, soft tissue and internal organ growth
Acral bony overgrowth ->
- Frontal bossing
- Increased hand and foot size
- Mandibular enlargement with prognathism
- Frontal bossing
- Headaches, sweating, increased BP, increased blood glucose
How may acromegaly be treated?
Somatostatin analogues - lanreotide, octreotide, pasireotide
What does prolactin do? 4
- Breast development
- Milk production
- Suppresses sex drive in both sexes
- Anovulation in ovary
What releases prolactin, and what causes increase in levels?
Secreted by lactotrophs
Inhibited mainly by hypothalamic dopamine in male and female
Level very low in male and female
Increases inly during pregnancy and breast feeding
What are prolactinomas?
Tumour in pituitary gland that causes excess secretion of prolactin
What are the symptoms of prolactinomas in men? 4
Men:
- Low sperm count
- Erectile dysfunction
- Low testosterone
- Gynaecomastia
What are the symptoms of prolactinomas in women? 3
Women:
- Loss of menstruation
- Anovulation
- Galactorrhoea
What are the symptoms found in both men and women with prolactinomas? 5
- Loss of libido
- Headache
- Infertility
- Secondary hypogonadism
- Osteoporosis
What synthesises and releases oxytocin?
Synthesised by paraventricular nucleus in hypothalamus
Stored and released by posterior pituitary
What is the action of oxytocin?
- Stimulates Myoepithelial cells of the mammary gland -> milk ejection
- Stimulates Myometrium -> expulsion of foetus and placenta
Both positive feedback mechanism
What synthesises and releases ADH?
Synthesised by supraoptic nuclei of the hypothalamus
Stored and released by posterior pituitary
What are the actions of ADH?
- Increases water permeability of principal cells in late DCT and CT in kidney
- Acts via V1 receptors in vascular smooth muscles to cause contractions
What stimulates ADH secretion?
- Increased body fluid osmolality
- Decreased blood volume
- Decreased blood pressure
- Angiotensin II
- Pain/stress
- Nausea and vomiting
What inhibits ADH secretion?
- Decreased body fluid osmolality
- Increased blood volume
- Increased blood pressure
- Atrial natriuretic peptide
- Ethanol
- Diuretic
What can decreased ADH cause?
Decreased ADH action > diabetes insipidus (DI)
- Neurogenic DI
- Nephrogenic DI
What causes neurogenic (central) DI?
(Decreased ADH secretion)
- Hypothalamus, pituitary tumour
What causes nephrogenic DI?
(Failure to respond to circulating ADH)
- Polycystic kidneys
- Chronic pyelorephritis
- Lithium in drugs
- Mutation in V2 receptor gene
What are the symptoms of DI?
- Polyuria
- Nocturia
- Polydipsia
- Passage of large volumes of dilute urine
- Marked dehydration
- Anorexia and epigastric fullness
- Hypernatremia
- Fatigue
What investigatory tests are used to diagnose DI?
- Serum osmolality
- Serum electrolyte level
- Urine osmolarity
- Water deprivation test followed by vasopressin test
What are the treatments for the different types of DI?
Central: synthetic AVP analogue desmopressin (DDAVP)
Nephrogenic: adequate fluid intake; salt restriction
What disorders can occur with increased ADH?
- Small cell lung cancer
- Severe brain trauma
- Sepsis or infection of the brain (meningitis)
What are the signs and symptoms of increased ADH?
- Plasma ADH abnormally high
- Physiologic ADH regulation not working
- Highly concentrated (hypertonic) urine
- Hyponatremia and osmolality
- Normal or high BP
What is the treatment for increased ADH?
Stop fluid and
Treatment of underlying cause
Where are gonadotrophins released from and what is there function?
FSH and LH released from gonadotropic cells of anterior pituitary
FSH:
- stimulate production of gametes
LH:
- female: matures follicles, trigger ovulation, stimulate release of estrogen and progesterone
- male: stimulate production of testosterone
Sex hormones have key role in bone metabolism
What is the release of GnRH like?
What is the HPG affected by?
What eventually happens to HPG axis over time in males vs females?
GnRH secretion is pulsatile
HPG axis affected by: stress, weight loss, excercise
In time:
Deregulation of HPG leads to menopause in females
HPA activity in males decreases over time
What is hypopituitarism and panhypopituitarism?
Hypopituitarism: deficiency of one or more hormones of the pituitary gland
Panhypopituitarism: absent production of all anterior pituitary hormones
What may cause hypopituitarism?
Congenital or acquired defects
Compression (tumour), gene mutation, tumours, ischaemia, iatrogenic or chronic inflammation
