Week 3 - Hormones Flashcards
Outline the management of a patient with a GH-secreting tumour.
- Surgery (transsphenoidal hypophysectomy)
- Medical tx (if surg fails)
- Irradiation (last resort)
What types of medical therapy can be given to a patient to treat GH-secreting tumours?
Best option = Somatostatin analogs (Octreotide, sandostatin)
Next best option = DA agonists (bromocriptine, cabergoline)
Last resort = GH Receptor blocker (pegvisomant – VERY expensive)
What are the three types of hormones secreted from the anterior pituitary?
- and what hormones are in each group?
Somatomammotrophins = GH & Prolactin
Corticotrophins = ACTH, Beta-lipotropin
Glycoprotein hormones = TSH, LH, FSH
The highest levels of prolactin are associated with what?
Prolactinomas
How does hypothyroidism lead to high prolactin?
Low T3/T4 –> Hyopthalamus increases secretion of TRH –> TRH stimulates both TSH AND prolactin release from pituitary.
What are the main treatment options for a prolactin-secreting tumour?
- Medical: DA agonists (bromocriptine, cabergoline)
2. Surgical: transsphenoidal hypophysectomy (2nd choice)
What disorder is characterized by high ACTH (tumour secreting ACTH)?
Cushing’s Disease
What type of capillaries are found in the pituitary & why?
Fenestrated capillaries - allow releasing hormones to enter (primary plexus) & exit (secondary plexus) the blood
All hypothalamic releasing hormones bind what type of receptor?
- do they bind intracellularly or extracellularly?
Extracellular receptors:
G-protein coupled receptors
What hormones are secreted in a pulsatile pattern? What is this pattern called?
GH, LH, FSH
“ultradian rhythm” (varies over the day)
In what region of the hypothalamus are GHRH neurons present?
Arcuate nucleus
What is present in the Periventricular nucleus of the hypothalamus?
Somatostatin neurons.
What is Cushing’s disease?
Hypercortisolism due to excess pituitary secretion of ACTH
What type of receptor does GH bind to?
- describe the cascade after GH binds.
Tyrosine Kinase receptor.
- GH binds –> phosphorylation of JAK –> cross phosphorylation of receptor –> STATs bind R –> phosphorylation of STATs –> moves to nucleus –> regulates gene expression
GH effects on growth are mediated by what?
IGF-1
What is the most common reason for dwarfism?
Lack of GHRH
What is Cushing’s syndrome?
High cortisol
- either caused by pituitary, adrenals, or other source
What is Hashimoto’s disease?
Autoimmune disease of the thyroid leading to hypothyroidism
What is the most common cause of hyperthyroid disease? – what happens to hormones
Grave’s disease
- increased T3/T4
- complete suppression of TSH
What is the order of the most common causes of pituitary tumour? (ie. which hormones are most likely to be increased from pituitary tumour?)
- Prolactin
- GH
- ACTH
What is the agent responsible for negative feedback from the testis to FSH?
Inhibin
What is the order of hormone loss in loss of pituitary function?
- GH
- FSH & LH
- TSH
- ACTH
What is a craniopharyngioma?
Tumour derived from embryonic pituitary tissue.
aka. Rathke pouch tumour.
What is the insulin tolerance test?
- what is it used for?
Used when looking for GH deficiency.
- administer insulin
- glc should decrease (to 10 micro g/L
**test is often avoided b/c of hypoglycemia complications
What is required for a definitive dx of GH, enough to justify GH replacement therapy?
- Lack of GH response to low glc
- Low IGF-1
- Symptoms: short stature, growth failure
Diabetes Insipidus is due to what?
Deficiency of ADH
- failure to concentrate urine
What would you expect Na+ levels to be in Diabetes Insipidus?
- and if it’s different than you expect?
Expect high Na+ levels because kidneys cannot concentrate urine, so get excessive water loss and not an equal Na+ loss.
- if Na+ is low, that suggests psychogenic DI
What is the main complaint in a patient with Diabetes Insipidus?
Polyuria & polydipsia
What happens to K+ & Ca++ in Diabetes Insipidus?
Hypokalemia (b/c K+/Na+ exchange doesn’t work in kidneys?)
Hypercalcemia (why?…)
What are some symptoms of Cushing’s disease?
- cervical fat pad
- proximal muscle wasting
- progressive & central obesity
- striae on trunk
When during the day does cortisol peak?
- what is the clinical relevance of this?
Peak in morning.
- therefore, if expecting a disease with low cortisol, there is no point to test in a.m. b/c it will be higher than average.
What are the three hallmark symptoms of low Testosterone?
- loss of sex drive
- loss of am erections
- low volume/delayed ejaculations
How is hypogonadism diagnosed in younger men?
- all three hallmark symptoms of low testosterone, plus a lab test showing low testosterone.
What is PADAM?
Partial Androgen Deficiency in the Aging Male
What happens to a patient who is given continuous LHRH?
Stops producing LH
(but FSH is unaffected)
What happens to a patient who is given pulsatile LHRH?
They produce LH leading to increased testosterone production.
What happens to a patient who is given GnRH antagonist?
Stop producing FSH and LH
What are some causes of hypogonadism?
- brain (pit. tumour –> check FSH, LH, prolactin)
- chronic debility, alcoholism, HIV
- drugs (corticosteroids, opiates)
Why are testosterone blood tests usually unhelpful in women?
- when might it be used?
Testosterone is produced within the cell, used in the cell, then degraded in the cell, so doesn’t usually get into the blood stream.
- may be used to look for high testosterone (in case extra is being produced and leaks into the blood).
What can high testosterone in women cause?
- how is this different from males?
Females:
- upper abdominal obesity
- increased risk of CVD
Males show these symptoms with low testosterone
What is the main thing to determine before assessing/treating low testosterone in men?
Is it primary or secondary?
ie. is the problem in the testis or the brain?
What is the lab test for diagnosing hypogonadism?
9am testosterone
In females, what regulates ovarian testosterone?
LH & FSH (which are regulated by testosterone & progesterone feedback)
In females, what regulates adrenal testosterone?
Cortisol
What drug can be given to patients with central diabetes insipidus? & what does it do?
For mild deficiency: Chlorpropamide - enhances ADH action
For severe deficiency: ddAVP - ADH analog
What is the treatment of nephrogenic diabetes insipidus?
Dietary: Na+ restriction
Meds: diuretics (decrease Na+ absorption); prostaglandin synthase inhibitors - enhance water resorption
Under what value does the Na+ level have to get in order to present with neurologic symptoms of hyponatremia?
Na+ < 120mmol/L
What are some complications of steroid abuse? (explain mechanism)
When lots of anabolic steroids are given, a lot of testosterone gets converted to estrogens..
- leads to gynecomastia, decreased testicular size, infertility, erythrocytosis
Other toxic effects: CVD, Hepatotoxicity, Psychological problems
How does exercise affect hormones?
Exercise (a stressor on the body) decreases GnRH;
- can lead to amenorrhea/oligomenorrhea in women.
- variable effect in men.
What is testosterone metabolized into?
DHT (more active form of testosterone)
What does aromatase do?
Converts Androstenedione (pre-testosterone molecule) and testosterone into estrogens.
What do 5-alpha-reductase inhibitors do?
Prevent conversion of testosterone into DHT
- lessens male-pattern balding
- lessens BPH
What are the symptoms of low T in men?
- low libido
- decreased am erections
- low volume & delayed ejaculation
What hormones are produced by the acidophils?
GH & Prolactin
What are the 3 parts of the anterior pituitary?
- anterior lobe (pars distalis)
- intermediate lobe
- pars tuberalis
What are the two parts of the posterior pituitary?
- posterior lobe (pars nervosa)
- infundibular stalk
What is another name for the anterior pituitary?
Adenohypophysis
Histologically, where are posterior pituitary hormones stored?
Herring bodies (terminal ends of axons in the pituitary)
What connects the hypothalamus to the posterior pituitary?
Hypothalamohypophyseal tract
Where are ADH & oxytocin synthesized?
Hypothalamus (then travel through neurons to the posterior pituitary)
What is secreted by basophils in the pituitary?
**an easy way to remember this?
FSH
LSH
ACTH
TSH
(the base is FLAT)
What is produced by cells in the pineal gland?
- what is its action?
Melatonin
- regulates circadian rhythm
What is “brain sand”?
Concretions in the pineal gland; increase in number with increasing patient age.
(extra knowledge: scientific name is “corpora aranacea”)
