What is the hypothalamus analogous to in business?
The CEO
What is the pituitary gland analogous to in business?
The managers
What is the target gland analogous to in business?
The workers
Describe negative feedback regulation for the thyroid
Hypothalamus detects free thyroxine and when the hormone is low, the
hypothalamus releases TRH.
TRH stimulates the anterior pituitary,
which releases TSH.
TSH stimulates the thyroid gland to release thyroxine
List the anterior pituitary hormones
ACTH
TSH
LH
FSH
GH
Prolactin
What test do we use to detect GH deficiency?
IGF
Describe the GH suppression test
A 100-g glucose load is given to a patient after a baseline GH level is assessed. Glucose should suppress GH. If it doesn't then there is an unregulated source of GH somewhere in the body.
Name the disease of excess GH before the epiphyseal plates fuse
Gigantism
Name the disease of excess GH after the epiphyseal plates fuse
Acromegaly
What is prolactin used for physiologically?
Milk production
What is GH used for physiologically?
Growth
What is the diagnostic test of choice for prolactinomas?
MRI
What molecule inhibits the production of prolactin?
Dopamine
What is the clinical sign of a prolactinoma?
The lateral fields of vision are diminished, it's like looking through a tunnel
Name the posterior pituitary hormones
ADH (vasopressin) and oxytocin
Name the tropic hormones of the anterior pituitary
ACTH
TSH
LH
FSH
Cause the subsequent release of a hormone
GH
Prolactin
Cause a direct cellular change
What hormone in our bodies is regulated by positive feedback?
Oxytocin
What two things is oxytocin related to physiologically?
Milk letdown and uterine contraction/childbirth (parturition)
What's another positive feedback loop in the body besides oxytocin?
Coagulation
What is the other name for ADH?
Vasopressin
What are the two functions of ADH?
Cause vasoconstriction of arterioles and reabsorb free water (without Na)
What disease is associated with a too much ADH?
SIADH (Syndrome of inappropriate ADH) which basically means that you don't pee a lot and retain too much water
What disease is associated with not enough ADH or an insensitivity at the receptors?
Diabetes insipidus
What is the function of the gonads?
To produce sperm/oocytes
Identify the results for hypergonadotropic hypogonadism
high FSH/LH
low testosterone/estrogen
Identify the results for hypogonadotropic hypogonadism
low FSH/LH
low testosterone/estrogen
What is a primary ovarian failure going to look like on lab tests?
High FSH
low estrogen
What is primary testicular failure going to look like on lab tests?
High FSH/LH
low testosterone
What is the giveaway clinical finding for Kallmann syndrome?
Anosmia, or lack of the sense of smell. This would also show a hypogonadotropic hypogonadism-like panel
What is the FSH level in the follicular phase of the menstrual cycle?
Elevated FSH
What is the FSH level in the luteal phase of the menstrual cycle?
Dropping FSH
What is the LH level in the follicular phase of the menstrual cycle?
Low LH
What is the LH level in the Ovulation phase of the menstrual cycle?"
LH spike"
What is the estrogen level in the ovulation phase of the menstrual cycle?
Elevated estrogen due to LH spike
What is the progesterone level in the ovulation phase of the menstrual cycle?
Slowly rising progesterone
What is the progesterone level in the Follicular phase of the menstrual cycle?
Low progesterone
What is the progesterone level in the Luteal phase of the menstrual cycle?
High progesterone
What does the uterine lining do during the luteal phase?
Becomes soft and cushy, ready for an embryo to implant in its walls
What does the uterine lining do during the follicular phase?
It is being sloughed off at the beginning, but begins to grow prior to ovulation.
What gonadotropin is associated with ovulation?
LH
Describe precocious sexual development in girls
Pubic/axillary hair development, breast development, or onset of menses prior to age 8.
Describe precocious sexual development in boys
Facial/pubic/axillary hair development, elongation of the penis prior to age 9
What is the age range for normal puberty for girls?
8-14
What is the age range for normal puberty for boys?
9-15
What hormones are produced in the adrenal cortex?
Aldosterone
Cortisol
Testosterone
What does the zona glomerulosa produce
aldosterone
What does the zona fasiculata produce
cortisol
What does the zona reticularis produce
testosterone
What is an easy way to remember the order that these are produced in?GFR -
Salt, Sugar, Sex
How is estrogen formed from the hormone testosterone?
Aromatase enzyme in the peripheray
What would you expect to find in a patient with 21-hydroxylase deficiency?
low aldosterone
low cortisol
high testosterone
What would you expect to find in a patient with 17 hydroxylase deficiency?
high aldosterone
low cortisol
low testosterone
If a patient is deficient in aldosterone, what would you expect for Na values?
low Na
f a patient has an excess of aldosterone, what would you expect for Na values?
high Na
If a patient has an excess of aldosterone, what would you expect for K values?
low K
If a patient is deficient in aldosterone, what would you expect for K values?
high K
How does the RAAS system work?
Angiotensin I is created from the liver
Angiotensin converting
enzyme (ACE) is present in the lungs and converts Angiotensin I into
Angiotensin II
Angiotensin II causes synthesis of Aldosterone in
the adrenal glands
What is the negative feedback loop for aldosterone?
hypothalamus - CRH
pituitary - ACTH
adrenal gland - aldosterone
How does aldosterone help regulate blood pressure?
Water follows Na reabsorption
What is Conn syndrome?
Hyperaldosteronism
What electrolyte findings would you expect to see in Conn syndrome?
high Na
low K
Metabolic alkalosis
What is the treatment of hypoaldosteronism?
fludrocortisone (aldosterone replacement therapy)
What is Cushing syndrome?
hypercortisolism
What is Addison disease?
hypocortisolism
What is Cushing disease?
A pituitary adenoma causing hypercortisolism
What laboratory results would you expect to see in Cushing disease?
ACTH high
Cortisol high
What laboratory results would you expect to see in Cushing syndrome?
ACTH low
Cortisol high
What laboratory results would you expect to see in Addison disease?
ACTH high
Cortisol low
What clinical sign can be a giveaway for Addison disease?
dark complexion and dark creases/folds on the skin
(think John F Kennedy)
If you don't have enough cortisol, what will your blood sugar do?
Blood sugar will fall
If you have too much cortisol, what will your blood sugar do?
Blood sugar will rise
What is the diurnal rhythm for ACTH?
steadily decreases during the day and then begins to increase overnight peaking around 6am
What is the clinical consequence of excess androgens in our blood?
masculinization
What is the clinical consequence of excess estrogens in our blood?
Feminization
What analyte do we use to assess for excessive adrenal androgens?
DHEA and DHEA-S
What metabolite of DHEA do we test for in the urine?
17-ketosteroids
What does the adrenal medulla secrete?
Catecholamines
What two amino acids are involved in the creation of Dopamine?
tyrosine and phenylalanine
What is the epinephrine-producing tumor called?
pheochromocytoma
What enzyme breaks down catecholamines in neural tissues?
MAO
What enzyme breaks down catecholamines in non-neural tissues?
COMT
What are the three catecholamines?
Dopamine, epinephrine an norepinephrine
What is precursor protein is produced by the follicular cell of the thyroid?
thyroglobulin
What amino acid residue is present on the thyroglobulin molecule?
tyrosine
What enzyme oxidizes iodine in the colloid?
Thyroid peroxidase (TPO)
How many oxidized iodine molecules can a tyrosine residue hold?
2
What happens in conjugation?
adjacent thyroxine molecules are stacked on to each other
Before the hormone can be released into circulation, what must happen first?
The thyroglobulin must be destroyed
What is the most active form of thyroid hormone in the body?
Free T3, Triiodothyronine (T3)
What is the circulating form of thyroid hormone in the body?
Bound T4
What percentage of thyroxine is protein bound?
99.97%
What proteins primarily bind to thyroxine?
Albumin, TBP
What is a clinical sign of hypo- hyperthyroidism?
Goiter
What are the symptoms of hyperthyroidism?
anxiety
weight loss
bulging eyes (Graves'
disease)
excessive sweating
What are the symptoms of hypothyroidism?
slow cognition
weight gain
cold
dry skin
What results would you expect in primary hypothyroidism?
T4 low
TSH high
TRH high
What results would you expect in secondary hypothyroidism?
T4 low
TSH low
TRH high
What results would you expect in tertiary hypothyroidism?
T4 low
TSH low
TRH low
What results would you expect in primary hyperthyroidism?
T4 high
TSH low
TRH low
What results would you expect in secondary hyperthyroidism?
T4 high
TSH high
TRH low
What results would you expect in tertiary hyperthyroidism?
T4 high
TSH high
TRH high
What is non-thyroid illness? (euthyroid sick syndrome)
A chronic illness that affects your ability to produce a lot of hormone. Remember, if you're chronically sick, your body doesn't want to use it's resources for growth and development, it's more worried about survival.
What is thyroid hormone's primary objective?
Growth and development
What results would you expect for non-thyroidal illness (euthyroid sick syndrome)
T4 low
TSH normal or low
What is the hallmark antibody for Graves' disease?
TSHRAb
What is the hallmark antibody for Hashimoto thyroiditis?
TPOAb
Is nonthyroidal illness a dysfunction of the hypothalamus, pituitary,
or the thyroid
gland?
It appears that euthyroid sick syndrome is a central phenomenon.
There are also
many different factors to take into consideration.
A great percentage (99.97%) of
thyroid hormone binds to proteins,
and only the free hormone is able to exert its
effect on the
target tissues. With prolonged illness, it appears that
the
thyroxine-thyroxine binding globulin bond becomes less
stable, so a higher
percentage is unbound and circulating in the
free (unbound) form, able to elicit its
effect. Basically, when
we test, we are assessing Total thyroxine
concentration,
including bound and unbound hormone. The raw
number of free thyroxine might
stay the same in chronic
illnesses, because the percentage of free hormone will
increase,
even though the total thyroxine value has decreased. It just means
that
less of it is being carried by TBG or albumin, which is in
the inactive form
anyway. So, physiologically, it doesn’t have
much of an effect
What is the initial test that should be performed to assess for a euthyroid state?
TSH
What would be the symptoms of a 21-hydroxylase deficiency?
Salt wasting at the level of the kidney, hypoglycemia, and masculinization
A 16-year-old female lives a normal, dehydrated life and doesn’t
drink a lot of
water because she says that cake tastes better.
What would you expect her
serum potassium level to be?
Low. It would probably be between 3.0 and 3.8 mg/dL. Dehydration
is
the most common cause of a low potassium. Be aware of how the
Na/K
exchange pump works in the kidneys because it will help you
elucidate many
pathologies on your exams. Remember, Aldosterone
causes Na retention and
K excretion, the lack of aldosterone
causes K sparing and Na excretion. This
effect can be seen in
potassium-sparing diuretics (i.e. Amiloride, Triamterene,
and Spironolactones).
What are the renal effects of aldosterone?
Reabsorption of Na and water with a loss of K
What is the test used to diagnose Cushing disease?
Overnight dexamethasone suppression test, NOT a plasma cortisol, that
would
only diagnose Cushing syndrome, but it won’t tell you where
the cortisol is
coming from
Why do hyperandrogenic males have high levels of estrogen?
The aromatase enzyme converts testosterone into estrogen
What is the diagnostic test for pheochromocytoma?
There are two, we use free metanephrines and a 23-hour
fractionated
metanephrines and catecholamines test
Testosterone and Estrogen help to develop what reproductive cells?
Spermatogonia and Oogonia
In menopause, the ovaries fail to produce adequate estrogen to
continue with the
reproductive life of a female. What would you
expect the level of FSH to be?
Extraordinarily high. This is a hallmark of menopause, FSH will be through the roof
What Estrogen levels would you expect in a female patient with low GnRH
levels?
Low Estrogen levels. Her low GnRH level will not induce secretion of
FSH or LH,
which will, in turn, not stimulate production of
Testosterone or Estrogen
What is the gonadotropin which is associated with ovulation?
LH. Remember, the “LH spike” is the cause of ovulation and estrogen
increases
along with it.
Precocious sexual development is considered before what ages?
Before age 8 in girls and before age 9 in boys
Elevated T4 will lead to what changes in negative feedback inhibition?
Decreased TRH and TSH
What are the two trophic hormones in the anterior pituitary?
GH and PRL
What is the definitive test for GH excess?
Oral glucose suppression test
A 28-year-old female is no longer menstruating and has noticed her
field of vision
getting smaller. What do you tell her?
She should get checked for a prolactinoma
What is another positive feedback loop in the blood?
Blood clotting. This is a rather important thing to keep
throughout
evolution; the ability to keep all that red fluid
inside of you … well … inside of
you, and circulating. Many
processes that are of the utmost importance to life
are
controlled by positive feedback mechanisms. Coagulation factors
function
by accelerating the reaction until the stimulus has
ended. In this case the
stimulus for coagulation is fibrin, and
the stimulation of the cascade ends when
a scab is formed. This
process is very tightly regulated by antithrombotic
factors as well.
A patient has diabetes insipidus, what is it caused by?
NOT blood sugar, but the insensitivity of the cells in the kidney to Antidiuretic
Hormone.