L3 Endocrine Pathologies Flashcards
GHRH Loop
GHRH –> Growth hormone –> IGF in liver, other organs
Somatostatin Loop
SS –> Growth hormone –> IGF in liver, other organs
Thryotropin releasing hormone loop
TRH –> TSH –> T3 and T4 in thyroid
Corticotrophin-releasing hormone Loop
CRH –> ACTH –> Cortisol in adrenal cortex
Thyroid gland
at the base of the neck, wraps around the neck
composed of spherical follicles
each follicle contains one layer of epithelial cells, creating a space that is filled with thyroglobulin
synthesis of Thyroid hormone
Iodine is absorbed by the GI tract as iodide
Iodide is converted back to iodine and coupled to tryosine to form thyroglobulin
TSH stimulation causes thyroid hormones to be split from thyroglobulin
T4
prehormone
Thyroid gland secretes primarily T4
> 99% of T4 in blood is attached to TBG (higher affinity for it then T3)
T3
hormone
Thyroid secretes only small amount of T3, most is unbound
most physiologically active form
plasma concentration of free T3 is 10x higher than free T4
T4 is converted to T3
by the target tissues
Prehormone
hormone that is inactive until it is modified by the target cell
Mechanism of thyroid hormone action
Only the free form of T4 and T3 can enter target cells
T4 is converted to T3 inside target cells
T3 enters nucleus and binds to a nuclear receptor
Hormone receptor complex binds to specific section of DNA to activate specific genes
Stimulation of thyroid hormone secretion
TSH, TRH, increased TBG levels in pregnancy, thyroid stimulating immunoglobins in grave’s disease
Inhibitory factors of thyroid hormone secretion
iodine deficiency
Actions of thyroid hormone
Thyroid hormone acts on virtually every organ system
BMR
Metabolism
Growth
CV/Respiratory
CNS
Thyroid hormone impact on BMR
increases O2 consumption
increases activity of Na/K ATPase
Thyroid hormone impact on Metabolism
Increases glucose absorption from GI tract
increases the power of catcheolamines, glucoagon, and GH on gluconeogenesis, lipolysis, proteolysis
overall effect is catabolic
Thyroid hormone impact on growth
acts synergistically with GH and somatomedians to promote bone maturation
Thyroid hormone impact on CV and respiratory
increases CO by inducing the synthesis of cardiac beta 1 adrenergic receptors
induces synthesis of cardiac myosin and SR CaATPase
Thyroid hormone impact on CNS
essential for normal maturation of CNS. Perinatal lack of TH results in severe intellectual disability/delay
Hypothyroidism
Can be caused by lack/decrease in TRH or TSH, or inability to produce thyroid hormone (hashimoto, gland removal, lack of iodine)
Hashimoto’s thyroiditis
most common cause of hypthyroidism in the USA
AI disease in which antibodies attack thyroid galnd, resulting in an inability to produce sufficient TH
Hypothyroidism Goiter
when the cause of hypothyroidism is a defect in TH production in the thyroid gland, a goiter develops from the unrelenting stimulation of thyroid gland
if plasma TH is low, there is a lack of negative feedback to the anterior pituitary, which causes increased release of TSH, whcih leads to hypertrophy of thyroid gland
Causes of Hypothyroidism Goiter
defect in TH production
hashimoto’s hypothyrodism
iodine deficiency
Causes of Hyperthyroidism goiter
Grave’s disease
increased TRH or TSH
Clinical presentation of Hypothyroidism
Cretinism in infant
Low BMR
Myxedema
how you treat it: synthetic T4/Synthroid
Cretinism
untreated congenital deficiency of TH
presents as gross dwarfing, severe intellectual disability, all development milestones are delayed
Low BMR clinical presentation
weight gain, lethargy, slurred speech, constipation, decreased metal acuity, decreased heat production
Myxedema clinical presentation
usually due to long hypothyroidism. Accumulation of proteins/fluid in subcutaneous tissues
causes of Hyperthyroidism
Grave’s disease
Increased TRH
altered levels of TSH
excessive administration of thyroid hormone
Grave’s disease
autoimmune disorder characterized by increased levels of thyroid stimulating immunoglobulins
the antibodies stimulate the thyroid gland, causing increased TH secretion and gland hypertrophy
Dx of hyperthroidism
S/S and increased plasma levels of T3 and T4
TSH levels can be increased or decreased, depending on the cause of hyperthyroidism
If the cause is the gland–> tsh level will be decreased
If the cause is disorder of hypothalamus –> TSH will be increased
Clinical presentation of hyperthyroidism
weight loss
increased food intake
excessive heat production and sweating
rapid HR
nervousness/weakness
goiter (sometimes)
exopthalmos (grave’s)
Treatment of hyperthyroidism
radioactive iodine ablation , surgical removal of thyroid gland
TH replacement after
Stimuli and Inhibitory of Growth HOrmone
GHRH acts on anterior pituitary to stimulate GH synthesis/secretion
Somatostatin inhibits GH secretion by blocking action of GHRH on anterior pituitary cells
How is growth hormone secreted?
GH is secreted in a pulsatile manner, about every two hours. Largest burst happens within 1 hour of falling asleep
GH is the ______ hormone for normal ____
single most important, growth
GH secretion throughout life
Not constant throughout life
increases steadily from birth to early childhood
Puberty has huge GH bursts
Declines after puberty
Lowest levels in old age
Stimulatory Factors for growth hormone secretion
Increase in GHRH secretion
Exercise
Stress
Fasting (decreases FFA/Glucose)
Puberty
Deep Sleep
Inhibitory Factors of growth hormone
increase in somatostatin release
increase in GH release
increased glucose or FFA concentration
REM sleep
Old Age
Actions of growth hormone
most actions of GH are indirectly mediated through the production of somatomedins (insulin-like growth factors) by the liver
Some actions are due to the direct effects of GH on skeletal muscle, liver, adipose
Effects of growth hormone
REMEMBER–GH promotes growth in every organ/organ system by making fuel available
- Increase protein synthesis and organ growth (uptake of AA and synthesis of DNA)
- Increase Lipolysis
- Decrease glucose uptake and utilization of glucose by muscle and adipose tissue
- Increase linear growth
- Alter every aspect of cartilage metabolism
Results of decreased glucose uptake by GH
causes increased blood glucose and insulin levels (diabetogenic effect)
Growth Hormone Deficiency in Childhood
causes dwarfism
failure to grow
short stature
mild obesity
delayed puberty
treated with human GH replacement
GH Deficiency in Adulthood
considered that no overt clinical symptoms are evident
some clinicians now recognize somatopause –> obesity, decreased muscle mass, BMD< dyslipidemia, decreased CO
Growth Hormone Excess before puberty
GIGANTISM
long bones grow disproportionately
usually diabetic (GH brings glucose into blood)
Acromegalic features
TX: somatostatin analogues, which inhibit GH secretion
GH hormone after puberty
Acromegaly
short bone epiphyseal plates do not close
hands, feet, skull, lower jaw continue to grow
-coarsening of facial features
-increased organ size
-insulin resistance
Tx: somatostatin analogues
Adrenal Glands
each gland is compromised of 2 distinct endocrine glands
Adrenal medulla: secretes cathecholamines
Adrenal Cortex: secretes corticosteroids
Corticosteroids
cortisol, aldosterone, adrenal androgens
Cathecholamines
E, NE, Dopamine
Stimulatory Factors of cortisol secretion
Decreased plasma cortisol
Physical stress
chronic anxiety and psychological stress
sleep-wake transition (peaks as you wake)
heavy exercise
Inhibitory Factors of cortisol secretion
increased plasma (cortisol)
Actions of cortisol
anti-inflammtory/immunosuppression
stimulation of gluconeogenesis and lipolysis
maintenance of normal BP
inhibition of bone formation
Decreases Type 1 collagen formation
increases wake tine and decreases REM sleep
How does cortisol maintain normal BP?
permissive effect on NE/E can increase bp. Stimulates synthesis of alpha 1 receptors
Cortisol increases availability of _____ ______
energy sources
it is a catabolic hormone that is essential for fasting, breaks down proteins and fat.
MOA for cortisol
Most of cortisols effects are due to changes in gene transcription
- Decreases transcription of proinflammatory genes
- Increases gene transcription of proteins that decrease inflammation
Cortisol produces proteins that inhibit the production of phosphoplipase A, which decreases production of inflammatory mediators
Timeframe: hrs to days
Cortisol produces…
lipocortins/annexins, which are a group of proteins the body makes in response to cortisol release
Have same effect as predinisone
Cortisol deficiency is also known as
Addison’s disease
Addison’s disease
primary adrenocrtical insufficiency
usually caused by autoimmune destruction of ALL zones of adrenal cortex
Tx: cortisol and aldosterone replacement
S/S of Addison’s disease
S/S from loss of cortisol:
hypoglycemia, anorexia, weight loss, nausea & vomiting, weakness.
Also S/S from loss of aldosterone (like hypotension)
Cortisol Excess
Cushings Syndrome
Cushings Disease
Cushings SYNDROME
(Too much cortisol)
1. Overproduction of cortisol by adrenal cortex
2. Systemic pharmacological administration of glucocorticoids
Tx if due to problem 1: drugs that block steroid hormone synthesis
Cushings DISEASE
(too much ACTH)
Excess of ACTH due to a pituitary tumor
Tx: surgical removal of ACTH secreting tumor
S/S of Cushing’s Syndrome
- Hyperglycemia
- Muscle Wasting
- Increased fat in face, trunk, between scapulae
- Striae
- Poor wound healing
- Hypertension
- Emotional changes
- Osteoporosis
- AVN of femoral head
Plasma Calcium Regulation
Requires 3 hormones and 3 organs
Hormones–PTH, Vitamin D, calcitonin
Organs–Large intestine, kidney, bone
PTH
secreted by parathyroid glands
acts on bones, kidneys, intestine to regulate blood
most important hormone in regulation of calcium level in blood
___% of calcium in the body is in the bones
99%
Remaining 1% is found in extracellular fluid
Ionized Ca is the only biologically active form
Normal Blood Ca level
10 mg/dl
Calcium homeostasis
1000 mg goes into the body
800 mg will go out into feces
200 mg will be excreted in the urine
Bone bank (calcium)
PTH causes more calcium to be withdrawn (reabsorbed)
Calcitonin causes more calcium to be deposited into the bone
Function of PTH
regulate the concentration of Ca in ECF/plasma
the amount of PTH secreted from the parathyroid gland depends on the amount of calcium in the blood
Low levels of blood calcium triggers an increase in PTH
PTH remains at a basal level with normal levels of calcium
What level of calcium triggers PTH release?
<7.5 mg/dl
Actions of PTH on Bone
Bone resorption (withdrawal). Delivers both Ca and phosphate to the blood
Actions of PTH on Kidney
inhibits phosphate reabsorption, which increases phosphate excretion into the urine, to allow for more ionized Ca
Increases Ca reabsorption in the DCT
Actions of PTH on Small Intestine
No direct effect on Ca absorption (the small intestine)
indirectly stimulates Ca absorption by activation of Vitamin D
Calcitonin
Synthesized and secreted by C cells in the thyroid gland
Secreted when plasma Ca is high
Inhibits osteoclast bone resorption to decrease Ca delivery to plasma (causes bone deposition)
Calcitonin does NOT regulate Ca minute to minute
Vitamin D
Promotes mineralization of new bone
Increases plasma concentrations of both Ca and phosphate
precursor is located in liver, active form is in the kidney
Actions of Vitamin D on Intestine, Kidney, Bone
Intestine/Kidney: Increases/stimulates Ca and phosphate absorption
Bone: stimulates osteoclast activity and bone resorption
Osteomalacia
softening of bones
Osteoporosis
weakening of bone
Rickets
soft bones
Dosage is _____
everything!
hormonal effects are very dependent on concentration
a deficit or excess of hormone produces pathological responses
Ergogenic aids
durgs or dietary supplements used to enhance performance
Doping
use of a drug or blood product to improve athletic performance
Most studies to assess the value of ergogenic aids
-include only conditioned athletes and young adults
-do not include children, adolescents
-are of poor quality
Survey of 21000 college athletes
almost half reported taking protein
Review of adolescent use of performance enhancing substances
Protein, creatine, and caffeine were most commonly used ingredients
athletes use more substances than nonathletes
Persons with most influence to taking ergogenic aids
coaches (65%)
dietitians
doctors
_____ knowledge about supplements is associated with ____ use
Greater
Less
Education regarding ergogenic aids
Refer to evidence based information regarding cost-benefit ratio
It is not within our scope to recommend or sell supplements. Education and recognition of ADRs is
Erythropoietin
Epo: hormone that is primary regulator of RBC formation
Clinical uses: chemo induced anemia, esrd induced anemia, HIV/AIDS
Reasons rHuEpo is abused
Improve aerobic power in endurance sports
ADRs of Epo abuse
peripheral vein varicosities
HTN
thrombotic events causing MI, CVA< PE
Anabolic Sterioids
most are versions of testosterone
Used clinically with HIV/AIDS, delay of growth syndromes
abused to increase strength
Results of anabolic steroid abuse
increase skeletal muscle surface area and strength
increases lipid profile, systolic BP, liver damage, acne, hair growth, psychological changes, mortality, genital alteration
Growth Hormone Abuse
Clinical uses: deficiency of GH that results in growth delay
Abused: to increase muscle mass, strength, and decrease fat mass
has not been proven to be an effective ergogenic aid
ADRs of Growth Hormone abuse
gigantism
large hands and feet
carpal tunnel syndrome
myopathic muscles
HTN
insulin resistance
Amphetamines/Stimulants
Related to NE/E/DA
Clinical uses: ADHD, narcolepsy
Commonly abused substances: caffeine, ephedrine, amphetamines, meth
Abused to increase endurance, weight loss
Amphetamines effectiveness
no increase in VO2 max, increased time to exhaustion
increased max torque, peak power, lung function
ADRs of Amphetamines
increased dysrhythmias, HTN, MI, CVA, GI disturbances, heat intolerance, anxiety, insomnia, dizziness, paranoia, hallucinations, death
Adrenal Medulla
secretes catecholamines in response to SNS stimulation
increases HR, sweat, decreased motility of GI
