What are the phases of growth in humans?
Prenatal growth
Postnatal growth - infantile phase (first three years of life), childhood growth (3 to puberty) and pubertal growth spurt
Growth velocity of infantile phase of growth
Rapidly decelerating
Largely dependent on nutrition, genetics and endocrine hormones
Childhood growth velocity
Slowly decelerating
Regulated by genetic factors and GH
Pubertal growth spurt
28cm males, 25 cm females
Dependent upon sex steroids and GH
Where are GH receptors present?
In most tissues of the body, particularly liver
Weight gain velocity during infancy
Rapid (birth weight triples by 1 year)
Peak bone mineral velocity during puberty
Lags behind peak growth velocity by about 1 year. Causes a transient declie in mone mineral per bone volume, leading to an increased susceptibility of fractures
Pituitary fossa
Depression on upper surface of sphenoid bone
Sellar diaphragm
Sheet of dura that stretches over the clinoid processes. The centre has a small opening where the pituitary stalk sits
What is on the floor of the cavernous sinus?
V2, V ganglion, V3
Where does the carotid plexus distribute its fibres?
Deep structures (eye and LPS)
Origin of the neurohypophysis
Floor of diencephalon
Origin of adenohypophysis
Roof of the embryonic pharynx
What are the three “pars” of the anterior pituitary?
Pars distalis (most of AP) Pars intermedia (internediate part between AP and PP) Pars tuberalis (sheath extendig from pars distalis and wrapping around the pituitary stalk)
What does prolactin do in males (normally)?
It increases testosterone binding in the prostate and formation of androgen receptor complexes
B FLAT
Basophilic cells of the AP: FSH, LH, ACTH, TSH
Where are oxytocin and vasopressin made?
The hypothalamus
Supraoptic and paraventricular nuclei
Vascular supply of the PG
Branches of the ICA
Superior hypophyseal arteries - infindubulum, which connects to AP via hypophyseal portal system
Inferior hypophyseal arteries - neural lobe of AP
Hypophyseal portal system
Venules connecting capillaries in the median eminence
Does the AP receive a direct blood supply?
No. It depends on the hypophyseal portal system
Microadenoma
<1cm diameter
Macroadenoma
> 1cm diameter
What is known about mutations in pituitary adenomas?
Evidence of monoclonality, oncogene activation, G protein mutations (for non-functioning pituitary adenomas)
When do pressure effects of the tumour occur?
When the tumour is a macroadenoma
What symptoms result from compression or invasion of adjacent structures by the tumour?
headache (stretching of dura)
CSF obstruction & hydrocephalus (large tumours)
visual disturbances (optic compression)
CSF rhinorrhoea (erosion of sella turcica)
III, IV or VI palsies
How is GH release co-ordinated?
GH secretion is co-ordinated by a synchronous decrease in somostatin tone and release of GHRH from the hypothalamus.
Presenting symptoms of a prolactinoma in men
Men usually present with impotence or symptoms of hypogonadism. Galactorrhoea occurs in about 20%.
What types of prolactinomas (micro or macro_) are common in (a) men and (b) women?
The majority of prolactinomas in women are microadenoams, whereas in men they are more frequently macroadenomas
When would coma occur as a presenting symptom of raised ICP?
This is usually a late stage presentation, but occasionally a rapid herniation of the brain can cause coma as the first presentation.
How does a tumour cause hypopituitarism?
If normal pituitary tissue is destroyed by the tumour
Iatrogenically, as a consequence of Tx
Compression of the pituitary stalk, causing disruption of delivery of hormones from HTH
What is the order of loss of pituitary hormone secretion?
Prolactin, Gonadotophins, GH, TSH, ACTH
Carniopharyngioma
Arises from remnants of Rathke’s pouch (roof of mouth that gives rise to AP). A congenital malformation which grows at variable rates, forming cysts as they enlarge.
Most common presentation of craniopharyngioma
Increased ICP
Usually present in middle childhood
What are the main pituitary tumours
From most common to least common: Non-functioning adenoma Prolactinoma Combined GH/prolactin producing adenoma Thyrotrope adenoma
Non-functioning adenomas can stain positive for what?
Glycoprotein hormones, e.g. gonadotrophins, LH/FSH/TSH (the beta-subunit) BUT they are either non-secretory or only secrete biologically inactive hormones (i.e. subunits)
What do you need to remember about secretory tumours and other hormones?
A secretory adenoma can cause a deficiency of the other pituitary hormones
Gigantism
Caused by GH secreting adenoma in childhood, before epiphyseal closure
Gonadotrope adenomas
Women have no symptoms
Men may have sexual dysfunction or gynacomastia
Children may have precocious puberty
What is the classic triad of increased ICP that could possibly be due to a brain tumour (or other space occupying lesion)?
Headaches, vomiting, papilloedema
In children, when might the visual problems associated with increased ICP be drawn to one’s attention?
When they are having trouble in school
Children might not complain about vision problems until they are nearly blind
Papilloedoema
Transmission of ICP along the optic nerve sheath, causing venous congestion and swelling
Headache
Due to tension on dura or blood vessels
Headache tends to increase gradually ove time and is worst on waking when ICP is highest
Vomiting
Distortion/ischaemia in areas of the medulla involved with vomiting (area postrema). More common in children, and may be very sudden in onset
Can ICP be high in the absence of papilloedema?
Yes. The anatomy of the optic sheath may not allow for the transmission of pressure
What are the late signs in increased ICP?
Disturbances of consciousness, oculomotor function disturbances (suggests that intracranial adaptive capacity has become exhausted)
Other signs of intracranial masses
Disturbed function of the structures involved in the tumour
e.g. reduced pituitary function
If cortex is involved, focal or generalised epilepsy may occur
Severe short stature is associated with which diseases?
Primary disorders of bone (e.g. achondroplasia) or bone metabolism (osteogenesis imperfecta)
Psychological consequences of short stature?
There is a positive correlation between lack of self-esteem, depression, underachievement and shortness of stature
BUT recent studies show few psych consequences in children and adolescence and sometimes health professionals rate child as having more problems than the child demonstrates
Things that a short child might do
Elicit behaviours more appropriate for their “height age” than actual age.
Coping with teasing by clowning around/joking
Self-sufficiency and independence may suffer (unless physical environment is adjusted to height level)
Effect of early maturation in girls
May benefit in contrast to the late-maturing girl
Effect on late maturation in boys
Less poised, less relaxed, more restless
What is normal short stature?
Short stature that is not a consequence of endocrine disorder. Endocrine therapies are not necessary
Is blood pressure affected at normal levels of vasopressin release?
No
What can diabetes insipidus be caused by?
Destruction of cell bodies in hypothalamus
Mutation in vasopressin gene
Results in increased secretion of ADH
NB destruction or removal of the pituitary will not remove the source of vasopressin
What happens if the thirst mechanism is disrupted?
Circulatory collapse - this can be fatal
Actions of oxytocin
Uterine contractions at birth (neuroendocrine reflex), milk let-down (suckling), coitus, behavioural effects
Germinoma
Tumour of germ cell origin
A child is more likely to have a tumour of germ-cell origin or a low-grade astrocytoma from an adjacent structure than a ptiuitary adenoma
Investigations: alphafoetoprotein and beta HCG in CSF/serum as markers of germ-cell origin tumour
Treatment of pituitary macroadenomas - options
Surgery, radiotherapy, drugs
Must be treated because they have demonstrated they have a capacity to grow
Radiation therapy
Used in patients with recurrent or incompletely excised tumours
Surgery
Mostly trans-sphenoidal surgery
Trans-cranial if they have extended into other parts
Drugs
Prolactinoma: cabergoline (DA Agonist)
GH adenoma: octreotide (somatostatin analogue)
ACTH: ketoconazole (usually reserved for patients unsuitable for surgery or with recurrent tumours after radiation)
Circadian rhythms
Endogenously produced biological rhythms Repetitive oscillations (1 cycle per 24 hours) Maintained under constant conditions
Circadian system
Co-ordinates physioloigcal and behavioural activities of brain and body
Activities influenced by the circadian system
Sleep-wake timing, thermoregulation, respiratory function, CV function, alertness, neurocognitive performance, immune function, endocrine function, GIT function, renal function
The circadian system is a wake-promoting system that works in opposition to the …
… homeostatic sleep system
Where is the “circadian pacemaker”
suprachiasmatic nuclei of anterior HTH
Zeitberger
Environmental cue
Strongest is the light-dark cycle
Retinohypothalamic tract
Involved in phototransduction from retina to suprachiasmatic nucleus
Zeitbergers other than light
Melatonin, exercise, social cues
Circadian disruption
Occurs due to misalignment in timing of circadian system relative to environmental light-dark cycle
Melatonin
Secreted by the pineal gland
Modulated by sympathetic innervation from the pineal gland
How is melatonin synthesis stimulated at night?
Neurons in SCN receive (absence of) light info from retina, and synthesise melanin
How is melatonin synthesis suppressed during the day?
Suppression of sympathetic neurons in SCN
Is melatonin affected by sleep deprivation?
No. Melatonin secretion occurs independent of sleep-wake status
Measuring melatonin
Blood and saliva
Primary metabolite is excreted in urine
Must be determined in dim lights because it is sensitive to light exposure
Can melatonin promote regulation of sleep?
Yes. Nightly onselt of melatonin occurs around the same time as the nightly increase in sleepiness and sleep propensity.
Administration of melatonin during the day makes a person sleepy
Cortisol is different from melatonin as it is influenced by …
the circadian system
sleep-wake behaviour AND
stress
What is the morning peak in cortisol related to?
Sleep termination. When sleep offset is delayed, so is the peak in cortisol. So during 24 hour sleep deprivation, cortisol levels tend to be elevated compared to normal
Circadian rhythms
Endogenously produced biological rhythms Repetitive oscillations (1 cycle per 24 hours) Maintained under constant conditions
Circadian system
Co-ordinates physioloigcal and behavioural activities of brain and body
Activities influenced by the circadian system
Sleep-wake timing, thermoregulation, respiratory function, CV function, alertness, neurocognitive performance, immune function, endocrine function, GIT function, renal function
The circadian system is a wake-promoting system that works in opposition to the …
… homeostatic sleep system
Where is the “circadian pacemaker”
suprachiasmatic nuclei of anterior HTH
Zeitberger
Environmental cue
Strongest is the light-dark cycle
Retinohypothalamic tract
Involved in phototransduction from retina to suprachiasmatic nucleus
Zeitbergers other than light
Melatonin, exercise, social cues
Circadian disruption
Occurs due to misalignment in timing of circadian system relative to environmental light-dark cycle
Melatonin
Secreted by the pineal gland
Modulated by sympathetic innervation from the pineal gland
How is melatonin synthesis stimulated at night?
Neurons in SCN receive (absence of) light info from retina, and synthesise melanin
How is melatonin synthesis suppressed during the day?
Suppression of sympathetic neurons in SCN
Is melatonin affected by sleep deprivation?
No. Melatonin secretion occurs independent of sleep-wake status
Measuring melatonin
Blood and saliva
Primary metabolite is excreted in urine
Must be determined in dim lights because it is sensitive to light exposure
Can melatonin promote regulation of sleep?
Yes. Nightly onselt of melatonin occurs around the same time as the nightly increase in sleepiness and sleep propensity.
Administration of melatonin during the day makes a person sleepy
Cortisol is different from melatonin as it is influenced by …
the circadian system
sleep-wake behaviour AND
stress
What is the morning peak in cortisol related to?
Sleep termination. When sleep offset is delayed, so is the peak in cortisol. So during 24 hour sleep deprivation, cortisol levels tend to be elevated compared to normal