W5 Growth hormone & Corticosteroid responsive conditions (SM) Flashcards
What is the pituitary gland?
What hormones (class) are secreted from this gland?
- A chickpea sized gland located in the skull
- An extension of the hypothalamus
- Separated into the Anterior and Posterior pituitary glands
- Responsible for growth, development, reproduction, metabolism in the body
- Peptide
- Anterior- glandular cells
- Posterior- neural cells
Which cell types are in the anterior pituitary gland?
Somatotrophs- Somatotropin, growth hormone (GH)
Corticotrophs- Corticotropin, adrenocarticotropic hormone (ACTH)
Lactotrophs- Prolactin
Thyrotrophs- Thyrotropin, TSH
Gonadotropins- Gonadotropins, leutinising hormone (LH), follicle stimulating hormone (FSH)
trope/trope: cells
trophic/tropin: hormone
Which hormones are stored/released in the posterior pituitary gland?
Oxytocin
ADH/Vasopressin
Pituitary tumours:
benign or malignant usually?
signs?
mri scan:
Pituitary tumours are mostly benign and slow-growing
not metastatic usually
Over/underproduction of hormones (hyper/hypo)
Local effects: pressure on surrounding structures
- headaches, visual disturbances
MRI images show the normal pituitary gland (solid white arrow) and a pituitary tumour (dashed white arrow)
The optic chiasm (where the optic nerves meet) is shown by the green arrows and is pushed up by the pituitary tumour (see slide)
Hypothalamic-releasing and anterior pituitary tropic hormones
Hypothalamus acts on anterior pituitary which acts on peripheral glands to release hormones
e.g. CRH in Hypothalamus —- ACTH in AP — Cortisol from Adrenal cortex
GHRH in Hyp— GH in AP— IGF-1 from Liver (HPA Axis)
somatostatin and dopamine suppress GH release in AP
Somatotropin, GH
Structure?
main role?
- GH is secreted by acidophilic cells of anterior pituitary glands.
- GH is a peptide hormone, 21.5 K Da single-chain polypeptide (190 AA) with 2
disulphide bridges - GH is stored in the cells as granules, and it is released as pulsatile
- Major role in growth (linear) and metabolism
GH, Functions
Direct?
Indirect?
Direct – on metabolism:
* Increase Blood Glucose
(anti-insulin effect)
* Increase Gluconeogenesis (Liver)
* Increase Protein synthesis (Muscle)
* Decrease Glucoseuptake (Muscle)
* Increase Lipolysis (Adipose)
* Decrease Glucose uptake (Adipose)
Indirect – growth:
* Insulin-like growth factors (somatomedins) from liver
Lean body Mass
* Increase Hypertrophy (cell size)
* Increase protein synthesis
Organ size- IGFs
* Increase Hyperplasia (cell number)
* Cell division
Linear growth
* Increase Skeletal growth
Influencers of GH release:
- Blood glucose, free fatty acids and amino acid levels influence GH release
- Sleep and exercise affect GH release
GH, disorders (Deficiency/Insufficiency)
What is the main example?
symptoms in adults?
symptoms in children
Dwarfism
(stunted growth)
* Congenital (genetic mutations or structural issues in the baby’s brain)
* Acquired (damage to the pituitary gland, injury, infection, radiation)
* Idiopathic (unknown cause)
Children:
Small face, impaired hair and nail growth, delayed tooth development, delayed puberty and low blood sugar
Adults:
* Malaise, excessive tiredness, anxiety and depression
* Osteoporosis and impaired hair growth
* Poor muscular tone, decrease in lean body mass
* Hypoglycaemia
* Increase in adipose tissue (especially around the waist)
GH, disorders (Deficiency/Insufficiency)
Treatment? (2)
- Hormone Replacement
Biological and Biosimilar medicine should be prescribed and dispensed.) - Somatropin (Recombinant Human Growth Hormone)
Used to treat growth failure in children and adults*
Used in Turner syndrome and Prader-Willi syndrome
Used in short bowel syndrome and to prevent weight loss in AIDSis
*Prescribed to adults only if the following criteria are fulfilled (NICE TA64)
* Severe GH deficiency, defined as a peak GH response of less than 9 mU/litre (3 ng/ml) during an insulin tolerance test or a cross-validated GH threshold in an equivalent test.
* Perceived impairment of quality of life (QoL), as demonstrated by a reported score of at least 11 in the disease-specific ‘Quality of life assessment of growth hormone deficiency in adults’ (QoL-AGHDA) questionnaire.
* Under treatment for other pituitary hormone deficiencies as required
GH, disorders (excess/hyper)
What are 2 examples?
Symptoms? (8)
- Gigantism in children
- Acromegaly in adults
Symptoms:
* coarsening of facial features
* enlarged hands and feet (arthritis)
* headaches, vision disturbance
* sleep apnoea, general tiredness
* hypertension, cardiomegaly
* glucose intolerance (diabetes)
* irregular or loss of periods (females); impotence (males)
* bowel polyps
GH, disorders (excess/Hyper)
Treatment:
Goals? (2)
Non-pharmacological? (2)
Drugs? (3)
- Reduce GH levels/block GH action
- Treat the symptoms and conditions (hypertension, diabetes, arthritis…)
- Surgery: Effective and can completely cure acromegaly. But, removing large
adenomas is a bit of a challenge. - Radiation: Stereotactic or conventional radiation methods
(require extreme care and hormonal replacement to maintain other pituitary
hormones)
Drugs:
1. Somatostatin analogues
Octreotide, Lanreotide, Pasireotide
2. Dopamine (D2) receptor agonist
Bromocriptine, Cabergoline
3. GH receptor antagonists
Pegvisomant
GH, disorders (Excess/Hyper)
Pharmacological treatment:
Drugs
* Somatostatin analogues: A monthly injection of either octreotide, lanreotide or pasireotide –slows down the release of GH and can sometimes also shrink tumours
* GH receptor antagonist: a daily pegvisomant injection –blocks the effects of growth hormone and can significantly improve symptoms
* Dopamine (D2) receptor agonist: bromocriptine or cabergoline tablets –can stop growth hormone being produced, but they only work in a small proportion of people
Hormones of Adrenal Gland? (4)
Steroidal:
* Aldosterone- Mineralocorticoids (Mineral Balance)
* Cortisol- Glucocorticoids (Glucose Metabolism)
* Dehydroepiandosterone- Androgens (Masculinisation)
Catecholamines (Sympathetic activation):
* Adrenaline/Noradrenaline
Adrenal gland sits on top of kidneys
Corticosteroids biosynthesis:
Zone-specific steroidogenesis
Differential expression of biosynthetic enzymes in the different zones of the adrenal cortex (no need to memorise the various enzymes and steps)
3 zones:
Zona glomerulosa, Zona fasciculata, zona reticularis