Endocrinology Flashcards
What determines whether a cell membrane will be responsive to a hormone?
The amount of hormone
*this is because receptors are usually present in excess
What determines whether the cell (cytoplasm) or nucleus will respond to a hormone?
The number of receptors
Why are most hormones given via injection?
They are Peptide hormones (and as such don’t cross membranes easily)
poorly absorbed
catabolized in GI tract
short half life
A kinase…
A phosphatase…
attaches phosphate
removes phosphate
What are the 2 main types of cell-surfaces receptors for hormones?
Receptor Kinases
(act through tyrosine kinase)
G-Protein Coupled Receptors
(2nd messengers cAMP, IP3, Ca to activate protein kinases)
Name 4 things 2nd Messengers have effects on.
Cellular traffic
Enzyme Action
Membrane effects
*DNA transcription/mRNA synth > protein synth
T/F
Steroid hormones cross membranes easily
True
How do steroid hormones often work in the cell?
Cross membrane, bind receptor
Steroid/Receptor complex enters nucleus, acts directly with DNA to alter transcription and protein synth
Normally an excess of hormones will _______ receptors and a hormone deficiency will ________ receptors.
down-regulate
up-regulate
How is an imbalance in hormones usually assessed?
considering both the endocrine gland from which they came and their target tissues
T/F
Endocrine issues are more common in women.
True
T/F
Endocrine issues are often auto-immune and run in families
True
What connects the pituitary gland to the hypothalamus?
Pituitary Stalk
Which lobe of the pituitary is larger?
Anterior
Which part of the pituitary is considered to be an extension of the nervous system?
Posterior Pituitary
Where are the hormones in the Posterior Pituitary made?
Hypothalamic nuclei
How do hormones made in the hypothalamus travel to the posterior pituitary for storage/release?
Travel down axons
What are the 2 Posterior Pituitary hormone?
ADH (antidiuretic hormone)
Oxytocin
What is the function of ADH?
Concentrates urine
inhibits diuresis - urine output
What is the function of Oxytocin?
Controls uterine contractions and breast milk let down
T/F
The Anterior Pituitary is made up of one cell type.
False.
Contains several cell types that make and release different hormones
How are Anterior Pituitary hormones regulated?
through Hypothalamic hormones
What connects the hypothalamus to the Anterior Pituitary?
a Portal Venous system in the pituitary stalk
Aside from being the hormones of the Posterior pituitary, what do ADH and Oxytocin have in common?
Both only 9 AA long
What type of hormones are made in the hypothalamus?
Peptide hormones
How are hypothalamic hormones secreted?
in pulses
What stimulates the release of hormones from the hypothalamus to the Anterior Pituitary?
higher brain centers
*can be affected by stress
Are hypothalamic hormones measurable?
No. Too invasive.
What are the 4 Stimulatory hypothalamic hormones?
TRH - thyrotropin releasing hormone
CRH - corticotropin releasing hormone
GnRH - gonadotropin releasing hormone
GHRH - growth hormone releasing hormone
What 2 substance inhibit hypothalamic hormones?
dopamine
somatostatin
What are the 5 cell types of the Anterior Pituitary and what Hormones do they produce?
thyrotrophs TSH - thyroid-stimulating hormone
corticotrophs ACTH - adrenocorticotropic
gonadotrophs LH and FSH
somatotrophs GH - growth hormone
lactotrophs prolactin
What 2 Pituitary hormones have both stiumulatory and inhibitory effectors?
Growth Hormone - stimulated by GHRH and inhibited by Somatostatin
Prolactin - stimulated by TRH (thyrotropin releasing hormone) and inhibited by Dopamine
What two hormones does TRH (thyrotropin releasing hormone) stimulate?
TSH and Prolactin
Name 6 Anterior Pituitary Hormones and their targets.
TSH thyroid ACTH adrenal cortex FSH ovary or testis LH ovary or testis GH liver, all tissues Prolactin breast
Outline the Thyroid feedback loop.
TRH > TSH > T4, T3 (thyroxine, triiodothyronine)
T4/T3 either provides feedback through TSH or directly onto TRH in hypothalamus
What is the main function of the thyroid hormones?
Energy expenditure
Outline the Adrenal feedback loop:
CRH > ACTH > Cortisol
Cortisol either provides feedback through ACTH or CRH directly
Outline the Gonad Feedback loop:
GnRH > FSH/LH > Estrogen/Testosterone
with feedback at either tertiary (hypothalamic) or secondary level
*Kisspeptin starts this cascade
What effects GnRH directly and is regulated by higher brain centers?
Kisspeptin
What is Kisspeptin coded by and where is it made?
KISS1 gene
mainly hypothalamus
Outline the Growth feedback loop:
GHRH > GH > IGF-1 (insulin like growth factor1)
feedback at secondary or tertiary (hypothalamic) level
What 3 hormones possibly effect the expression of Growth Hormone?
IGF-1 (through regulation feedback loop)
GHRH (stimulation from hypothalamus)
Somatostatin (inhibition)
Outline Prolactin feedback:
No suckling > Dopamine > Prolactin inhibited > no milk
Suckling > inhibits dopamine > Prolactin > milk
What might cause a hormone deficiency?
What might cause hormone excess?
Hypothalamic lesion
Tumors
What are the 3 main questions to address with a pituitary tumor in making a diagnosis?
Tumor produce hormones?
Pituitary mass effects?
Other pituitary hormones affected?
What does excess GH cause?
acromegaly or gigantism
What does excess ACTH cause?
excess cortisol (Cushing disease)
What does excess TSH cause?
hyperthyroidism
*very rare
In what 3 ways does excess Prolactin manifest?
breast milk, no menses, infertility
What does excess FSH/LH cause?
no disease
What are some pituitary tumor mass effects?
headache from stretched dura
optic damage (peripheral)
cranial nerve defects
sinus invasion
What are the 3 main treatments for pituitary pathologies?
Tumor Mass - surgery/radiation
Hormone excess - Antagonist
Hormone deficiency - replacement of target hormone or pituitary hormone
Individual cell type failure in the pituitary or the failure of the entire gland (panhypopituitarism) can be caused by:
tumor
infiltration (Fe deposits)
infection (TB)
auto-immune
What is the usual progression of loss in the pituitary when a mass is present?
GH, FSH, and LH first
TSH and ACTH second
Why would a mass cause prolactin to increase?
Pressure on the pituitary stalk prevents dopamine inhibition from the hypothalamus
How would pituitary failure present at the target tissues?
*low ACTH/cortisol - can’t handle medical stress
low TSH/thyroid hormones - hypothyroidism
low FSH, LH, sex hormones - no menses, infertility, etc
low prolactin - no lactation
low GH/IGF-1 - growth failure in children
Name 6 causes of high prolactin:
Tumor Stalk damage Chest wall trauma Kidney failure Antipsychotics (suppress dopamine) Hypothyroidism (high TRH from hypothalamus)
*remember TRH affects both TSH and prolactin
What is an effective treatment for a pituitary tumor causing high prolactin output?
Dopamine or agonist
this inhibits prolactin and causes tumor to shrink
What does high levels of prolactin suppress?
Kisspeptin
- so bad for gonad function/fertility
What cause fits these metabolic conditions:
increased FA mobilization
Insulin resistance
More protein synth
Tumor producing GH
What does too much GH cause if the onset is before/after puberty?
before - gigantism
after - Acromegaly
What is one of the first signs of excessive Growth Hormone?
enlarged sweat glands
What is a useful test for Acromegaly?
a GH increase after an oral glucose load
no one knows why this works
What is an appropriate treatment for Acromegaly?
Somatostatin (suppresses GH)
GH antagonist
*remember, goal is to suppress GH and get IGF-1 normal
What are 4 main tools to use in endocrinology?
Carbohydrate counting
Growth charts
DXA scan
FRAX test
Describe the thyroid feedback system:
TRH > TSH > T4/T3
What do the thyroid hormones do?
Regulates energy expenditure, growth, etc
What are the hormones released from the thyroid?
T4 and T3
thyroxine and triiodothyronine
*T3 is active form
What is unique about the thyroid hormones?
They contain iodine
What transports iodide from the blood into the thyroid cells?
sodium-iodide symporter
What enzyme oxidizes iodide to iodine to by used in T4/T3?
Thyroid peroxidase
How is iodine stored in the thyroid?
In thyroglobulin in colloid. Added to tyrosine and then makes T4/T3
What amounts of T4/T3 does the thyroid secrete?
85% T4 (inactive)
15% T3 (active)
What is the blood carrier for T4/T3?
thyroid binding globulin
Does T3 act more like a peptide or steroid hormone?
Steroid.
enters nucleus - changes DNA expression
What are some functions of T3?
Increase metabolic rate (oxygen, heat, protein, fat, cholesterol synth/degradation)
*increases sympathetic nervous system tone
What is usually the most valuable test for the thyroid system?
TSH
What does TSI stand for?
Thyroid Stimulating Immunoglobulin
What can a radioactive iodine scan tell you?
Thyroid enlargment
iodine distribution
hot/cold nodules
Is Radioactive iodine useful for hypothyroidism?
no
What are the T4/T3 and TSH levels in Hyperthyroidism?
High T4/T3
Low TSH
(high TSH may be present in very rare TSH producing pituitary tumor)
What condition entails lid lag and Proptosis?
Hyperthyroidism
Graves for Proptosis
What condition entails constipation?
Hypothyroidism
What condition entails slow relaxation of muscle on reflex test?
Hypothyroidism
What causes Graves disease?
TSI antibodies mimic TSH and overstimulate thyroid gland
TSH low
T4/T3 high
What is the difference between a multinodular goiter and a hot nodule?
Multi-nodular escapes TSH control
Hot nodule has mutation in TSH receptor that kicks out more T4/T3.
What thyroid condition has a negative scan for iodine uptake and is often transient?
Thyroiditis
*here, the inflamed gland releases stored hormone and causes a temporary hyperthyroidism
What might be the cause of hyperthyroidism with a negative iodine scan without any noticable inflammation of the gland?
Exogenous T4/T3
What does high levels of TSH suggest?
Tumor
*very rare
What is a major cause of hyperthyroidism that is familial and 10x more common in women?
Graves disease
*autoimmune (usually), TSI
What infiltrates the eye muscles in Graves disease?
mucopolysaccharides and lymphocytes
*effects are worse in smokers
What usually happens after radio-active iodine treatment for hyperthyroidism?
Hypothyroidism
What are the 3 usual treatments for hyperthyroidism?
Radio-active iodine
Anti-thyroid drugs
Surgery
What are some causes of primary hypothyroidism?
Autoimmune destruction (Hashimoto thyroiditis)
Congenital defects
Radioactive iodine/surgery for hyperthyroidism
Anti-thyroid drugs
What would the T4/T3 levels and TSH levels be in primary hypothyroidism?
Low T4,T3
High TSH
What would the thyroid hormone levels be in a secondary pathology?
low T4,T3
low TSH
What would the thyroid hormone levels be in a tertiary pathology?
low T4,T3
low TSH
In what ages are the effects of hypothyroidism reversible?
Childhood and Adult
*dwarfism and low IQ from newborn/3rd trimester irreversible
Can a goiter be present in hypothyroidism?
yes. High TSH may cause this.
Why is Thyroxine (T4) increased slowly in dosage to treat hypothyroidism?
easier on the heart
What causes a goiter in hyperthyroidism?
Hypothyroidism?
Hyper - TSI (Grave’s), multinodular (growth factor outside TSH control), inflammation (thyroiditis)
Hypo - High TSH stimulates growth, but still low T4
