Endocrinology Flashcards
All lectures. Not done with ENDO 3 or 4 yet as of 2/19
What are features of the endocrine system?
Provides “broadcast’ regulation of
many tissues; specificity due to
receptors
Slower but longer lasting responses
compared to the NS
What are the functions of hormones?
- Maintenance of homeostasis
- Growth and differentiation
- Reproduction
What are some specialized endocrine glands?
- Pituitary Gland
– Thyroid Gland
– Parathyroid Gland
– Adrenal Gland
– Pineal Gland
Can organs secrete hormones even if that’s not their purpose?
Yes
What are the classes of hormones?
- Proteins and Polypeptides
- Steroids
- Derivatives of Tyrosine
How are protein hormones first synthesized as?
Preprohormone
What is preprohormone converted into?
Prohormone
What happens to the prohormone?
Packaged into vesicles, then cleaved into active hormone
Where do steroid hormones come from?
Adrenal cortex, ovaries, and testes
What are steroid hormones synthesized from?
Cholesterol
What happens when a steroid hormone is needed?
Synthesized on demand (it is not stored)
What are amine hormones derived from?
Tyrosine
What are some examples of amine hormones?
Epinepherine and norepinepherine
Are amine hormones stored?
Yes, then released as needed
What do thyroid hormones bind to?
The protein thyroglobulin
How are epinepherine and norepinepherine secreted?
Stored in vesicles, then released by exocytosis
How can hormones circulate?
Freely or bound to carrier proteins
What are carrier proteins called?
Binding proteins
What are example of binding proteins?
Albumin, thyroxine-binding globulin
What are features of growth hormone excess?
Coarse facial features,
large fleshy nose,
frontal bossing, jaw
malocclusion.
What is growth hormone excess in children called?
Gigantism
What is growth hormone excess in adults called?
Acromegaly
What is the treatment for a Pituitary Microadenoma?
Surgical resection of the tumor (adenomectomy)
via transphenoidal approach followed by
medication (somatostatin (GHIH) receptor ligand
or GH receptor antagonist)
What are some of the oral manifestations of GH Excess?
Thick rubbery skin, enlarged nose,
and thick lips; Macrocephaly; Macrognathia; Disproportionate mandibular growth; Mandibular Prognathism; Generalized Diastemata; Anterior open bite and malocclusion (macrognathia and tooth migration)
Does GH Excess cause sleep apnea?
Yes, through hypertrophy of the pharyngeal and laryngeal tissues
What are some causes of GH deficiency?
Hypothalamic disorders
Mutations: GHRH receptor, GH gene, GH receptor, IGF-1 receptor
Combined pituitary hormone deficiencies (panhypopituitarism)
Radiation
Psychosocial deprivation
What are the clinical manifestations of GH deficiency?
slow linear growth rates
* normal skeletal proportions
* pudgy, youthful appearance (decreased lipolysis)
* in the setting of cortisol deficiency hypoglycemia
What is the most common form of dwarfism?
Achondroplasia
What is achondroplasia?
autosomal dominant condition
that results from a mutation of FGF-3 receptor in cartilage and brain. This mutation makes
the receptor overly active and it inhibits cartilage growth at growth plates so limb growth is reduced (growth of the trunk of the body is not impacted).
What are the oral manifestations of GH deficiency?
Disproportionate delayed growth of the skull & facial skeleton -> small facial appearance
Solitary Median Maxillary Central incisor
Eruption delayed
Prone to hygiene-related problems
What does the posterior pituitary secrete?
Antidiuretic/Vasopressin and Oxytocin
What is another term for the posterior pituitary gland?
Neurohypophysis
What type of hormones are the ones secreted by the Neurohypophysis?
Polypeptide
What does the Neurohypophysis contain?
~100,000 unmyelinated
axons of neurons whose cells
bodies are in the hypothalamus
(Paraventricular nucleus and
Supraoptic nucleus)
What does vasopressin do to the blood vessels?
Contraction of vascular
smooth muscle via V1
receptors
What does vasopressin do to renal tubules?
- Binds to V2 receptors in
the late distal tubule and
collecting duct.
– Aquaporin-2 (AQP-2)
proteins are then
inserted into the apical
membrane of tubular
epithelial cells, allowing
for water reabsorption
(along with AQP-3 and
AQP-4 on the
What stimulates ADH secretion?
Decreased Blood Volume (Isotonic)
Increased Osmolarity (Isovolemic)
Decreased Blood Pressure
What is hypodypsia?
Decreased or absent feeling of thirst, which results in
reduced intake of water and can cause Hypernatremia
Who gets hypodipsia?
A common problem in elderly people, but is also
associated with lesions in the hypothalamus (thirst
center), head trauma, occult hydrocephalus or
subarachnoid hemorrhage.
What is diabetes insipidus?
ADH imbalance, causes large output of urine
What are the two types of DI?
Neurogenic/Central
– Nephrogenic/Peripheral
What is Neurogenic/Central?
Reduced ADH secretion
What is Nephrogenic/Peripheral?
Lack of kidney response to ADH
What is syndrome of inappropriate ADH?
High levels of ADH, inappropriately elevated
What does oxytocin do?
Stimulates contraction of the
uterus towards the end of gestation.; Causes milk ejection from the breasts in lactation
What is a sign of a disease?
objective evidence
of disease that can be seen or
measured (ex. enlarged
hands, polyuria, tachycardia,
etc.)
What is a symptom of a disease?
measured (they are
subjective) but are reported
by the person
Which thyroid hormone is more potent?
T3 is more potent than T4
What do thyroid hormones do?
impact metabolism
and growth/development. They also
have permisive action on
catecholamines
What are the two active thyroid hormones?
T3 and T4
Which thyroid hormone is secreted more?
93% is T4; 7% is T3
What is the active form of hormone (in relation to binding proteins)?
The free or unbound form
What kinds of hormones circulate freely?
The majority of amines, peptides, and protein hormones
What hormones circulate bound to binding proteins?
Steroid and thyroid hormones
What can affect someone’s plasma hormone levels that is NOT hormone-production related?
Liver deficiency causing problems with binding proteins
Are hormone level stagnant throughout the day?
NO, circadian rhythms… other fluctuations
What is a circadian rhythm?
Rises and falls based off time of day
What is pulsatile secretion?
They “pulse” with their release
What binds to plasma membrane receptors?
Polypeptide, Protein and Amine
Hormones
What binds to nuclear receptors?
Thyroid and steroid hormones
What features do the ligand/receptor demonstrates?
Specificity, affinity and saturation
What determines the location of the hormone receptor?
The properties of the hormone
What are examples of plasma membrane hormone receptors?
- G-protein Coupled
- Tyrosine Kinase: Insulin
- Serine Kinase
- Cytokine: Leptin
What are examples of G-Protein Coupled receptors?
β Adrenergic, Calcitonin,
ACTH, Glucagon, TSH, Vasopressin
What second messenger do Gs-pro c receptors produce?
cAMP
What second messenger do Gq-pro c receptors produce?
P3, DAG and Ca2+
How are receptors distributed throughout the body?
Vary greatly across target tissues to specify tissue activation; however, some are distributed widely (like insulin receptors)
Why do you think these receptors
are more broadly distributed?
They hormones causes a response in more tissue
What are nuclear hormone receptors?
A large family of receptors that are located either in the cytoplasm or
nucleus. All act to increase or decrease gene expression.
What does the hormone receptor complex bind to?
hormone responsive element in the
promoter region of a gene, which leads to
either activation or repression of
transcription.
What are the three types of hormone interactions?
– Antagonism
– Synergistic
– Permissiveness
What are tropic hormones?
hormones that have other endocrine
glands as their targets
What is a primary disorder?
Abnormality in the last
endocrine organ secreting the
hormone leading to either
hypo- or hyper-secretion.
What are some examples of primary hyposecretion?
(1) Partial destruction of the gland
(2) Dietary Deficiency
(3) Enzyme deficiency required for
hormone synthesis
What is a cause of primary hypersecretion?
A tumor in an endocrine gland
What is a secondary disorder?
Abnormality in tropic hormone
leading to either hypo- or
hyper-secretion
What can cause secondary hyposecretion?
A lack of sufficient tropic hormone
What can cause secondary hypersecretion?
A tumor (either in an endocrine gland
that secretes tropic hormones or in
non-endocrine tissue (lung)) can
secrete hormones
What kind of tests are run to diagnose endocrine disorders?
Plasma hormone levels, autoantibodies, suppression tests, imaging, urine tests
Is the anterior pituitary gland a true endocrine hormone?
Yes
What does the posterior pituitary gland contain?
axon terminals of hypothalamic neurons
What does the anterior pituitary gland secrete?
Growth Hormone
* Adrenocotricotropin (ACTH)
* Thyroid-Stimulating
Hormone (TSH)
* Follicle-Stimulating
Hormone (FSH)
* Luteinizing Hormone (LH)
* Prolactin
What does the posterior pituitary gland secrete?
Antidiuretic Hormone
(ADH)/Vasopressin
* Oxytocin
What do somatotrophs secrete?
secrete GH (30-40% of cells)
What do corticotrophs secrete?
ACTH (20% of cells)
What do thyrotrophs secrete?
(3-5% of cells
What do gonadotrophs secrete?
LH and FSH (3-5% of cells)
What do mammotrophs secrete?
Prolactin (3-5% of cells)
How is anterior pituitary secretion regulated?
Neurons in the hypothalamus
synthesize and secrete
hypothalamic releasing and
inhibiting hormones that
control the endocrine cells in
the anterior pituitary
Where are the hypothalamic hormones released into?
primary capillary plexus in the median
eminence
What do Hypothalamic-Hypophyseal
Portal Blood Vessels do?
carry the hypothalamic hormones to the
sinuses of the anterior pituitary
gland
What are hypothalamic releasing and inhibiting hormones?
Thyrotropin Releasing Hormone
Gonadotropin Releasing Hormone
Corticotropin Releasing Hormone
Growth Hormone Releasing Hormone
Prolactin Releasing Hormone (PRH)
Prolactin Inhibiting Hormone (PIH
GHIH
What is growth hormone?
a peptide hormone,
acts directly on target
tissues and as a tropic
hormone to the liver,
which releases insulin-
like growth factor-1 (IGF-1)
What are normal concentrations of GH in adults?
1.6-3 ng/ml
What does acute stress, sleep, and hypoglycemia do to GH?
Increase secretion
What does aging, disease, and glucose do to GH?
Decrease secretion
What does GH secretion look like?
Pulsatile secretion; lower
concentrations during the day
with highest levels a few hours
after sleep.
What is GH stimulated by?
starvation
(protein deficiency), fasting
(hypoglycemia), stress,
exercise, and excitement
When is GH secretion high (over a lifetime)?
High secretion in neonatal
period but decreases in
childhood. Peak levels during
puberty and then they decline
with age.
Many of the growth and metabolic effects of GH
are mainly produced by…
IGFs (aka somatomedins)
IGF-1 is produced…
in most
tissues and acts on
neighboring cells in a
paracrine manner
Where is the site of major synthesis of IGF-1?
the LIVER (i love the liver)
How many different types of IGF are there?
6
What does IGF do in terms of growth?
in nearly all tissues in the body (increased size of cells, mitosis
and differentiation of bone and muscle cells) mainly via IGF-1
What does IGF do in terms of protein?
Amino acid uptake and protein synthesis in most cells.
What does IGF do in terms of glucose?
Reduced glucose utilization- decreased uptake, increased hepatic
glucose production and increased insulin secretion (insulin resistance;
diabetogenic)
What does IGF do in terms of adipose?
Mobilization of fatty acids from adipose tissue (lipolysis) resulting in
increased FFA in blood and use of FFA for energy
What hormones stimulate chondrogenesis?
Before fusion of the epiphyseal plates,
GH and IGF-1
What do GH and IGF do before the epiphyseal growth plates fuse?
stimulate chondrogenesis
and widening of the epiphyseal plates,
followed by bone matrix deposition
stimulating linear growth
What does GH and IGF do in adults?
Increases bone turnover (by activating both osteoblasts and osteoclasts)
What is a diabetes insipidus presentation?
Polyuria, (hypotonic and tasteless)
What is a diagnostic test of diabetes insipidus?
dehydration test in a controlled
environment.
What are causes of polyuria that aren’t diabetes insipidus?
- Primary ingestion of excess fluid: Primary Polydispia
- Increased metabolism of ADH (ex. pregnancy)
What can cause syndrome of inappropriate ADH?
surgery, pain, stress, temperature changes,
tumor, TB, Pneumonia, positive pressure breathing,
Hydrocephalus, Meningitis, HIV, etc
What is syndrome of inappropriate ADH?
Increased and uncontrolled secretion of ADH that causes volume expansion and hyponatremia
What does oxytocin do?
Stimulates contraction of the uterus towards the
end of gestation.
Causes milk ejection from the breasts in lactation.
What are the two parts of the adrenal glands?
The outer cortex and the inner medulla
How many zones are in the adrenal cortex?
3
What does the adrenal cortex secrete?
Corticosteroids (ex. Cortisol)
Mineralocorticoids (ex. Aldosterone)
Sex hormones (ex. DHEA)
How much of the gland does the adrenal medulla make up?
20-30% of gland tissue
What does the adrenal medulla secrete?
epinephrine & norepinephrine in
response to Sympathetic NS stimulation
Is the adrenal medulla essential for life?
No, but its helpful
Is the adrenal cortex essential for life?
Yes
What are the hormones that the adrenal cortex secretes made from?
Cholesterol
What are the layers of the cortex (from superficial to deep)?
Zona glomerulosa, zona fasiculata, zona reticularis
What is the largest cortex zone?
Zona fasiculata
What does the zona glomerulosa secrete?
Mineralcorticoids
What regulates the secretion of mineralcorticoids?
Secretion regulated by the renin-
angiotensin-aldosterone system
(RAAS).
What does the zona fasiculata secrete?
Glucocorticoids
What regulates the secretion of glucocorticoids?
hypothalamic-pituitary-adrenal
axis (HPA) – CRH, ACTH
What does the zona reticularis secrete?
Androgens
What regulates the secretion of androgens?
the HPA
What does the adrenal medulla secrete?
Catecholamines
What do chromaffin cells secrete?
catecholamines epinephrine (EPI) and
norepinephrine (NE) into the blood.
What is the adrenal medulla related to?
Sympathetic nervous system
Where do the reactions for synthesis of steroid hormones occur?
in either the mitochondria or the endoplasmic
reticulum
What does aldosterone do?
Increases renal tubular reabsorption of Na+ and secretion of K+.
Leads to an increase in EC fluid volume and Mean Arterial Pressure.
What stimulates aldosterone secretion?
Angiotensin II
increased K+
decreased Na+
Aldosterone has a similar effect on…
sweat glands and salivary glands as renal tubules
What does aldosterone do in gland ducts?
greatly increases reabsorption of sodium
and secretion
Why is aldosterone’s effect on sweat glands important?
to conserve body salt in
hot environments
Why is aldosterone’s effect on salivary glands important?
conserves sodium during high
rates of salivary secretion
What releases renin?
cells in the kidneys
Where is angiotensis converting enzyme produced?
Endothelium
What is the RAAS system (overview)?
Angeiotensinogen gets turned in to angiotensis I by renin
Angiotensis I gets turned into Angiotensin II by ACE
What does angiotensin II do?
Vasoconstriction, ADH secretion, thirst stimulation, and aldosterone secretion
What causes primary hyperaldosteronism?
adrenal adenoma (benign), adrenal hyperplasia, adrenal carcinoma
(malignant)
What are signs and symptoms of hyperaldosteronism?
- Hypertension
- Hypernatremia
- Headaches
- Potassium depletion
- Weakness
- Fatigue
- Polyuria
- Hypokalemic alkalosis
- Low plasma renin
What are the treatment options for primary hyperaldosteronism?
– Surgical removal of the tumor or most of the adrenal tissue when hyperplasia is the cause.
– Pharmacological antagonism of the mineralocorticoid receptor (ex. spironolactone) is
another option.
What is secondary hyperaldosteronism caused by?
– CHF
– Cirrhosis
– Nephrosis
– Renal artery stenosis (high plasma renin activity)
What are signs and symptoms of secondary hyperaldosteronism?
- High plasma renin activity
- Hypernatremia w/extracellular volume expansion
- Edema
- Decreased cardiac output
- Similar clinical findings as Primary Hyperaldosteronism-hypertension etc.
What does cortisol do?
Causes mobilization of energy stores and
suppresses the immune response
What causes secretion of cortisol?
Stress of any kind
What kind of stress causes cortisol release?
- Trauma of almost any type
- Infection
- Intense heat or cold
- Injection of norepinephrine
- Surgery
- Hypoglycemia
- Psychological stress
- Almost any debilitating disease
When does cortisol secretion peak?
In the morning (circadian rhythm)
Go over regulation of glucocorticoid secretion (slide 11 of endo 4)
Too conceptual for flashcards :/
What has similar affinity for the mineralcorticoid receptor as aldosterone?
Cortisol
How much more cortisol is circulating than aldosterone?
1000 fold- could cause symptoms of mineralcorticoid excess
What does 11BHSD2 do?
converts cortisol to cortisone in aldosterone-responsive tissues
How well does cortisone bind to the GC or MR receptors
not as high of an affinity as cortisol
What causes Apparent Mineralocorticoid Excess?
A Genetic deficiency of 11-HSD
What does Glycyrrhetinic acid, a compound of licorice, inhibit?
the activity of 11β-hydroxysteroid dehydrogenase
What can overwhelm the 11B-HSD2 enzyme?
HIGH circulating cortisol levels (such as in Cushing’s Syndrome)
What does cortisol stimulate in terms of CHO?
gluconeogenesis and glycogenolysis in liver (increase plasma glucose)
Cortisol has an anti-______ reaction
insulin: decreases glucose uptake in muscle and fat but not brain and heart
How does cortisol affect diabetes?
Makes diabetes worse by increasing glucose levels, lipid levels, ketone body
formation and insulin secretion
What does cortisol do to protein synthesis?
Inhibits it
What does cortisol do to protein in skeletal muscle
Increases proteolysis
What does cortisol excess do to protein (symtpomatically)?
muscle weakness, pain due, thin skin and abdominal striae due
to protein catabolic effec
What does cortisol do to lipids?
Promotes lipolysis; shifts energy system from utilization of glucose to fatty acids in
times of stress.
Causes lipid deposition in certain areas (abdomen, interscapular “buffalo hump” and a
rounded “moon face”.
What does low glucocorticoid levels do to energy sources?
prevents mobilization of energy sources
(glucose & free fatty acids) during stress & can result in fatal hypoglycemia.
What does absence of cortisol do to the vasculature?
contributes to circulatory failure due to
loss of permissive action of catecholamines on blood vessels
What are the anti-inflammatory actions of cortisol?
- Stabilizes the lysosomal membrane
- Decreases capillary permeability
- Decreases WBC migration and phagocytosis
- Suppresses T lymphocytes proliferation
- Decreases IL-1 secretion from WBCs
Who uses glucocorticoids to reduce inflammatory processes?
patients with diseases/conditions that involve
an inflammatory process like RA
How do glucocotricoids cause osteoporosis?
1) Stimulates bone resorption (via
increase RANK-L expression)
2) Inhibits osteoblastic maturation and
activity
3) Promotes apoptosis of osteoblasts and
osteocytes
When does the zona reticularis secrete adrenal androgens?
begins to secrete adrenal androgens around
age 8 (adrenarche) peaking in the
early 20s and then falling with age
What are the adrenal androgens?
- Dehydroepiandrosterone (DHEA)
- Androstenedione
- Testosterone
How do adrenal androgens affect males?
Weak effects
How do adrenal androgens affect females?
50% of active androgens
What do adrenal androgens do?
Growth of the pubic and axillary hair and libido in females are due to adrenal androgens
What are conditions result from excess adrenal androgens?
– In pre-pubertal boys, it can cause precocious pseudopuberty (not due to
the hypothalamic- pituitary-adrenal axis)
– 21-hydroxylase deficiency can result in virilization in newborn females
and pseudo-hermaphroditism
– Androgen secreting tumors producing excess androgen result in virilization
and precocious pseudopuberty in females
