Endocrine 2 Flashcards
Describe the characteristics of water-soluble hormones
Transported unbound
Short half-life
Cleared fast
Bind to surface receptors on cells
Give some examples of water-soluble hormones
Where are these stored?
Peptides
Monoamines
Both stored in vesicles before secretion
Describe the characteristics of fat-soluble hormones
Transported bound to protein
Diffuse into cells
Long half-life
Cleared slowly
Give examples of fat-soluble hormones
When are they secreted?
Thyroid hormones
Steroids
Secreted upon demand
What does the endocrine system comprise of?
Pituitary gland
Thyroid
Parathyroid
Adrenal glands
Pancreas
Ovary
Testes
first lecture of endo
skipped to regulation of appetitie
How do you calculate BMI?
Weight (kg) / height squared (m2)
What are the ranges for BMI ?
< 18.5 underweight
18.5 - 24.9 normal
25 - 29.9 overweight
30 - 39.9 obese
> morbidly obese
Risks of obesity
Type II diabetes
HTN
Coronary artery disease
Stroke
Osteoarthritis
Obstructive sleep apnoea
Carcinoma - breast, endometrium, prostate, colon
What plays a central role in appetite regulation?
Hypothalamus
Why is the anatomy of the anterior pituitary unusual?
No arterial blood supply
Describe the HPA axis
Hypothalamus -> CRH
Pituitary -> ACTH
Adrenal cortex -> cortisol
Cortisol decreases the activity of Hypothalamus & Pituitary
∴ less CRH + ACTH produced
Describe the HPT axis
Hypothalamus -> ↑ TRH
Pituitary -> ↑ TSH
Thyroid gland -> ↑ T3 + T4
T3 + T4 decreases activity of Hypothalamus and Pituitary
∴ ↓ TRH + TSH produced
Describe the GH/IGF-I axis with the result of increasing GH
Hypothalamus -> ↑ GHRH
Pituitary -> ↑ GH
Liver -> ↑ IGF-I
IGF-I decreases activity of hypothalamus
∴ ↓ GHRH
Describe the GH/IGF-I axis with the result of decreasing GH
Hypothalamus -> ↑ SMS (inhibits GH production)
Pituitary -> ↓ GH
Liver -> ↓ IGF-I
IGF-I decreases production of GH
∴ ↓ IGF-I = ↑ GH
What is the mean age and mean duration of symptom presentation of Acromegaly?
mean age = 44 years
mean duration = 7 years
What are some co-morbidities of Acromegaly?
HTN and heart disease
Sleep apnoea
Arthritis
Insulin-resistant diabetes (type 2)
Cerebrovascular events & headaches
What are some questions you could ask to find out the clinical features of acromegaly?
Are rings still fitting you?
Is shoe size changing?
Teeth more separate?
When is acromegaly excluded?
(Clinical findings)
Random GH < 0.4 ng/ml
Normal IGF-I
Gold standard for Acromegaly
75gm Oral glucose tolerance test
Acromegaly excluded if :
IGF-I normal
and
OGTT nadir GH <1ng/ml
What are the aims of treatment in acromegaly?
Restoration of basal GH and IGF-I to normal
Symptom relief
Reverse of visual/soft tissue changes
Stop further skeletal deformity
Normalise pituitary function
Why can’t you rely on random GH to diagnose acromegaly?
Because GH has pulsatile secretion
What are some issues that make transsphenoidal pituitary surgery harder?
Large tumour
Invasiveness - if in cavernous sinus
How does the size of an adenoma (specifically when treating acromegaly) affect the surgical cure rate?
If < 1cm, cure rate ~90%
If > 1cm, cure rate ~ <50%
What are problems of radiotherapy when treating acromegaly?
Delayed response
Hypopituitarism
Rare 2ndary tumours
Bc close to eyes, could cause damage
What medication can be used to block GH and ∴ treat acromegaly?
Somatostatin analogues
Dopamine agonists
GH receptor antagonist
What are some advantages of dopamine agonists when treating acromegaly?
No hypopituitarism
Oral administration
Rapid onset
What are some disadvantages of dopamine agonists when treating acromegaly?
Relatively ineffective
Side effects
What are the advantages of using Cabergoline vs bromocriptine (both dopamine agonists used to treat acromegaly)?
Cabergoline is more potent, fewer side effects
Twice weekly
When are dopamine agonists especially useful in treating acromegaly?
When tumour is co-secreting GH and prolactin
What are some disadvantages of somatostatin analogues?
Injectable
Side effects
What are some determinants of efficacy of somatostatin analogues?
GH levels
Tumour size
SMS receptor expression
Describe the onset of acromegaly
Insidious
What are some effects of prolactin?
Menstrual irregularity
Infertility
Galactorrhoea
Low libido
Low testosterone in men
What type of visual defect can you get with a pituitary tumour?
Bi-temporal hemianopia
Describe the location of the pituitary
Sits within the sella turcica at the base of brain
Name some examples of hormones that are secreted from the anterior pituitary
Thyroid stimulating hormone (TSH)
Adrenocorticotrophic hormone (ACTH)
Prolactin
Growth hormone (GH)
Gonadotrophic hormones
Name some examples of hormones that are secreted from the posterior pituitary
Oxytocin
Anti-diuretic hormone (ADH)
Describe the blood supply of the anterior pituitary
No direct arterial blood supply
Receives blood through portal venous circulation from hypothalamus
Describe how prolactinoma may come about
Ant. pituitary enlarges
Impinges on hypothalamus
Hypothalamus produces less dopamine
∴ prolactin secreted is NOT suppressed
What can pituitary tumours cause?
- Pressure on local structures - optic nerve ∴ bitemporal hemianopia
- Pressure on normal pituitary ∴ hypopituitarism
- Could be a functioning tumour
e.g. prolactinoma, acromegaly, cushing’s
Describe symptoms if a pituitary tumour puts pressure on local structures
Could go up and stretch the dura, causing headaches
Visual field defects (bitemporal hemianopia)
Could go sideways into medial temporal lobe, cause cranial nerve palsies and seizures
If goes down through bone, CSF fluid leakage
Describe hypopituitary signs
Pale
No body hair
Central obesity
Why is a benign adenoma NOT a differential for diabetes insipidus?
Bc diabetes insipidus is caused by dysfunctional posterior pituitary and benign adenomas only are found anteriorly!
What is a carcinoid tumour?
Type ofneuroendocrine tumourthat grows from neuroendocrine cells
What are the 3 layers of the adrenal cortex and what do they produce?
GFR makes good SEX*
Zona glomerulosa - mineralcorticoids - aldosterone (AM)
Zona fasciculata - glucocorticoids - cortisol (GC)
Zona reticularis - androgens - sex hormones
What is the difference between Acromegaly and Gigantism?
Gigantism-XS GH productioninchildren BEFORE fusionof theepiphysesof thelong bones
Acromegaly-XS GHinadults
Describe a bitemporal hemianopia
Loss of vision on outer half of both eyes
What inhibits the release of GH?
Somatostatin !
Dopamine
High levels of glucose
Where is prolactin secreted from?
Anterior Pituitary
What inhibits the release of of prolactin?
Dopamine
Where is dopamine produced?
Hypothalamus
What is prolactin?
Hormone produced by lactotrophs in ant. pituitary gland
Define prolactinoma
Lactroph cell tumour of the pituitary
Define microadenoma
Tumour < 1cm
Define macroadenoma
Tumour > 1cm
What is a circadian rhythm?
Physical, mental and behavioural changes that follow a daily cycle
What is 1° adrenal insufficiency also called?
Addison’s disease
What is 2° adrenal insufficiency also called?
Hypopituiritarism
What is the most common cause of primary adrenal insufficiency worldwide?
TB
What is the most common cause of primary adrenal insufficiency in the UK?
Addison’s (autoimmune adrenalitis)
Aldosterone acts on the kidney to :
Increase sodium reabsorption from distal tubule
& increase potassium excretion from distal tubule
What is the fun key phrase to remember for Addison’s?
Tanned, Toned (fit and ready), Tired, Tearful
If Hypothalamus releases TRH,
What does the pituitary release?
What is the target organ?
What does the target organ release?
What is the effect of the hormones?
TSH
Thyroid
T3 + T4
Metabolism
If Hypothalamus releases CRH,
What does the pituitary release?
What is the target organ?
What does the target organ release?
What is the effect of the hormones?
ACTH
Adrenal cortex
Cortisol
Fat metabolism
If Hypothalamus releases GnRH,
What does the pituitary release?
What is the target organ?
What does the target organ release?
What is the effect of the hormones?
FSH/LH
Gonads
Oestrogen/Testosterone
Menstrual cycle, Sex
If Hypothalamus releases GHRH,
What does the pituitary release?
What is the target organ?
What does the target organ release?
What is the effect of the hormones?
GH
Liver
IGF-I
Growth & development
If Hypothalamus releases Dopamine,
What does the pituitary release?
What is the target organ?
What does the target organ release?
What is the effect of the hormones?
Inhibits prolactin
Breast
/
Milk production
What inhibits TSH?
Somatostatin
When treating adrenal insufficiency, what must you remember?
Double dose of steroids if infection, trauma, surgery or nightshift work
What is the cause of Goitre?
Iodine deficiency
If a patient presents with weight loss, heat intolerance, palpitations, sweating, anxiety etc, what should you be thinking?
and ∴ what should you do?
Problem with thyroid
∴ order a TSH test (cheap, doesn’t take long and can quickly determine the problem)
What are T3/T4 necessry for?
3 M’s :
Movement, Mentation & Metabolism
Where and when is Parathyroid hormone secreted?
By Chief cells in response to hypocalcaemia
Describe the action of Parathyroid hormone
↑ Osteoclast activity (∴ release Ca2+ & phosphate from bone) -> RAPID!
↑ Intestinal calcium absorption -> slow & indirect !
↑ Ca2+ & ↓ phosphate reabsorption in kidney
↑ Vitamin D production
Overall, ↑ Ca2+ & ↓ Phosphate
What is calcitriol release stimulated by?
↓ Plasma Ca2+
↓ Plasma phosphate
Parathyroid hormone (PTH)
What is the role of Vitamin D / Calcitriol / 1, 25-dehydroxycholecalciferol ?
↑ Ca2+ & Phosphate absorption in gut
Enhanced bone turnover by ↑ osteoclasts
↑ Ca2+ and phosphate reabsorption in kidneys
Inhibits PTH release - neg feedback
What is calcitriol?
The active form of Vitamin D
Where is calcitonin made?
In C-cells of thyroid
What effect does calcitonin have on plasma Ca2+ and phosphate?
↓ Ca2+ and phosphate
What does HYPOcalcaemia cause?
Paraesthesia
Muscle spasms
Seizures
Basal ganglia calcification
Cataracts
ECG abnormalities (Long QT)
Osteomalacia - vit D def
CHVOSTEK’S SIGN
How do you look for Chvostek’s sign?
Tap facial nerve and look for facial spasm
What are paraganglia cells?
Chromaffin cells that secrete adrenaline
