Endocrine System Flashcards
What is the purpose of homeostasis?
The endocrine system is responsible for maintaining homeostasis. It maintains homeostasis via the actions of hormones
How does the nervous system interact with the endocrine system?
Release of hormones controlled by nervous system
Nervous system and hormones influence each other by feedback loops
How can hormones be classified into two main groups?
Lipid soluble:
Steroids (ex. Glucocorticoids)
Lipid soluble hormones require protein binding to pass through the plasma
Water soluble:
Amines (ex. Epinephrine, T3)
Peptides (ex. TSH, Human Growth Hormone)
Proteins (longer versions of peptide hormones)
Water soluble hormones require cell membrane receptors to move across cell membranes
What factors determine circulating levels of hormones?
Synthesis, secretion, transport
How are peptide hormones synthesized?
Peptide hormones are synthesized depending on the degree to which sections of DNA that code for hormones are being transcripted
How is amine and steroid hormone production controlled?
Their production is controlled by regulating enzymes and substrate availability
Are hormones further processed after synthesis?
Most hormones created as a larger polypeptide, requires conversion to final hormone molecule by an enzyme
How are hormones secreted?
Exocytosis: The cell will release hormones when it received a specific signal
Diffusion: The cells that produce these hormones will continuously secrete them. The rate of diffusion is changed by modification of enzymes or proteins involved in its production
Pulsating: These releases will cause a different effect compared to lower concentrations of hormone. Ex. Hormones released during puberty
What factors affect hormone transport in the blood?
Affinity of hormone for plasma protein carriers
Hormone degradation
Availability of receptors
Receptor binding
Hormone uptake
How does affinity of hormone for plasma protein carriers affect hormone transport?
Protects hormone from degradation or uptake
Allows for fine control over circulating levels
Prevents hormone from binding to unintended sites
Allows transport of lipid soluble hormones
What are some key hormones?
Thyroid, cortisol, parathyroid, vasopressin, mineralocorticoids, insulin
What realms of the body do hormones effect?
Extracellular fluid
Metabolism
Biological clock
Contraction of cardiac and smooth muscle
Glandular secretion
Some immune function
Growth and development
Reproduction
What exactly do hormones change once they bind with the target?
Synthesize new molecules
Change permeability of the membrane
Alter rate of reactions
Ex. Insulin once bonded to insulin sensitive tissues, increases glycogen synthase activity which in turn increases release of glycogen
What are the 3 main hormone actions?
Permissive:
Binding to a target cell allows a different hormone to have its full effect
Synergistic:
Two hormones act together to achieve a greater effect. Ex. Hormones involved in lactation
Antagonist:
Two hormones produce and opposite effect. Ex. Insulin and glucagon
What are some major endocrine glands?
Pineal gland
Hypothalamus
Pituitirtary gland (anterior)
Thyroid gland
Parathyroid gland
Thymus
Describe the pineal gland
The pineal gland is located in the epithalamus, but it’s is not a part of the brain
It produces melatonin (important for sleep due to its anti-excitatory effects)
Describe the action of melatonin
Melatonin binds to melatonin receptors causing anti-excitatory effects
Levels peak at 1-2 years of age, remain stable until puberty, then decline
Regulate sleep patterns (circadian and seasonal)
High levels of melatonin can inhibit puberty (concern in children for melatonin supplements)
Melatonin release is stimulated by darkness and inhibited by light
What is the main role of the hypothalamus?
It is a major integrating link between nervous and endocrine system
The hypothalamus receives input from the cortex, thalamus, lambic system, and other organs
Hormones released by the hypothalamus regulate almost all aspects of growth, development, metabolism, and homeostasis
The hypothalamus communicates with the pituitary gland to control homeostasis using the following hormones:
Growth hormone-releasing (+) and inhibiting (-) hormone
Somatostatin (-)
Dopamine (-)
Corticotropin-releasing hormone (+)
Thyrotropin-releasing hormone (+)
Gonadotropin-releasing hormone (+)
Oxytocin (+)
Vasopressin (+)
Hypothalamic hormones are generally inhibited by the production of target hormones
What hormones does the pituitary gland (anterior) release?
Following stimulation by hormones released by the hypothalamus, the following hormones are released:
Human growth hormone
Thyroid-stimulating hormone
Follicle-stimulating and luteinizing hormone
Adrenocorticotrophic hormone
Melanocyte-stimulating hormone
Prolactin (only pituitary hormone that is controlled by an inhibitory pathway)
Secretion inhibited by production of target hormones
Describe the action of Human growth hormone
HGH is the most plentiful anterior pituitary hormone
Promotes synthesis o a protein insulin-like growth factor (IGFs)
Binds mostly to liver, skeletal muscle, cartilage, and bone
It is released in a pulsating manner during puberty, declines after
How is human growth hormone regulated?
Low blood sugar stimulates release of growth hormone releasing hormones (increases HGH release)
High blood sugar stimulates release of growth hormone inhibiting hormone from hypothalamus (decreases secretion of HGH)
What is the concern with excess HGH or deficiency?
Excess HGH can cause uncontrolled growth of bones and skeletal tissues. Increased body size puts strain on organs, so organ failure is more common
HGH deficiency can cause slow growth
Describe the interactions between hypothalamus hormones on pituitary gland hormones
Growth hormone-releasing hormone stimulates Human growth hormone
Thyrtropin-releasing hormone stimulates TSH
Gonadotropin-releasing hormone stimulates FSH and luteinizing hormone
Corticotropin-releasing hormone stimulates Adrenocorticotrophic hormone
Dopamine inhibits prolactin
Somatostatin inhibits HGH and TSH
Describe the anatomy and function of the thyroid gland
Butterfly-shaped endocrine gland in the front of the neck
Responsible for synthesis, storage and release of the two thyroid hormones (T3 and T4)
Describe the histology of the thyroid gland
The colloid is a collection of cells that synthesize and store T3 and T4
The follicular cells surround the colloid and they synthesize thyroglobulin and introduce iodine into the thyroid
The parafollicular cells produce calcitonin, a hormone that inhibits the effects of T3 and T4
Describe is the process of T3 and T4 synthesis
Synthesis and secretion of T3 and T4 is controlled by TSH, which is controlled by thyrotropin-releasing hormone
T3 and T4 synthesis requires iodide, thyroglobulin, and tyrosine
Iodine binds with tyrosine-thyroglobulin complex. One iodide attached to this complex forms MIT and two iodides make a DIT (mono or di-iodotyrosine respectively)
MIT + DIT = T3 and DIT + DIT = T4
The T3 and T4 are secreted into circulation
T3 is more potent because it fits active site better, but T4 serves as a good reservoir of T3 precursors (DIT).
What are the actions of T3 and T4 hormones?
Heart: chronotropic and inotropic (HR and contractility)
Adipose tissue: catabolic
Muscle: catabolic
Bone: Developmental (normal process of bone turnover)
Nervous system: development
Gut: metabolic
Other tissue: calorigenic
How are T3 and T4 levels regulated?
A negative feedback loop ensures that T3 and T4 levels do not get too high or low.
When T3 and T4 levels decrease, the hypothalamus is activated and releases thyrotropin-releasing hormone, which activates the pituitary gland. Following stimulation of the pituitary gland, it releases TSH. TSH stimulates the thyroid gland to release T3 and T4.
When T3 and T4 levels increase, these hormones inhibit the release of TSH by the pituitary gland. This inhibition prevents further stimulation of the thyroid gland
What is the role of the parathyroid gland?
The parathyroid gland is located on the posterior surfaces of the lateral lobes of the thyroid.
The parathyroid releases parathyroid hormone (PTH) to regulate to calcium and phosphate
PTH increases blood calcium through the following functions:
Stimulating the number and activity of osteoclasts
Increasing calcium and magnesium reabsorption from urine
Increasing synthesis of calcitriol, which increases calcium and magnesium absorption from GI
PTH decreases blood phosphate by increasing excretion from the kidneys
How do parathyroid hormone and calcitonin interact with each other?
The action of the parathyroid hormone is opposed by calcitonin.
Calcitonin has the following actions:
Secreted by follicular cells in the thyroid
Inhibits the activity of osteoclasts
Decreases reabsorption of calcium from urine
What is the importance of the thymus?
The thymus is downregulated after puberty, but it still has important functions
The thymus is critical in T cell development via the release of Thymosin a1, Thymulin, and Thymopoietin
What is the cause of hyperthyroidism?
This disease is caused by excess synthesis and secretion of thyroid hormones (T3 and T4). The negative feedback loop that would normally keep T3 and T4 levels in check shuts down
Can drugs alone cure hyperthyroidism?
No, all drugs related to hyperthyroidism are temporary solutions in preparation for surgery or radioactive iodine treatments
What are some common forms of hyperthyroidism?
Toxic diffuse goiter (Graves disease)
Toxic multi-nodular goiter (Plummers disease)
Acute phase of thyroiditis
Toxic adenoma
Describe Toxic diffuse goiter (Graves disease)
Most common cause of hyperthyroidism
Autoimmune disorder
More common in younger, female patients (ages 20-50)
The immune system creates antibodies against the TSH receptors located on the thyroid gland. The activities of these antibodies cause hyperplasia of the thyroid gland. The enlargement of the thyroid gland is even across the gland, leading to a goiter
Describe Toxic multi-nodular goiter (Plummers disease)
The second most common cause of hyperthyroidism
Iodine deficiency is the most common trigger for thyroid nodule enlargement (decreased iodine –> less T4 prod. –> thyroid cells enlarge –> TSH receptors mutate –> thyroid is continually active
This disease develops slowly over several years (decades to fully develop)
Describe Toxic adenoma
Benign tumours growing on the thyroid gland
The tumours become active and act just like other thyroid cells. They secrete T3 and T4, but toxic adenomas do not respond to negative feedback.
Describe the Acute phase of thyroiditis
It causes inflammation and damage to the thyroid gland. The damage causes the excess hormone to be released. Once hormone supplies within the thyroid are depleted, hypothyroidism develops
What is the clinical presentation of hyperthyroidism in general?
Most symptoms are characteristic of someone who is over-stimulated
Tremor in hands
Diarrhea
Heat intolerance
Unintentional weight loss
Weakness
Tachycardia
Amenorrhea (absence of menstruation)
What is the clinical presentation of toxic diffuse goiter?
Exophthalmos (excess T3 and T4 causes tissues to form around the eyes in way that eyes appear to be bulging)
Peri orbital edema (eye irritation)
Diplopia
Diffuse Goiter
Pre-tibial myxedema (waxy discolouration of the skin on the shin)
What are some treatments available for hyperthyroidism?
Pharmacotherapy:
Thioamides (PTU and MMI)
Beta-blockers
Radioactive Iodine
Surgery
What are some thioamides available in hyperthyroid treatment?
Propylthiouracil (PTU) and Methimazole (MMI)
These drugs are not used life-long, they will usually become ineffective within 3 years of use
Main purpose of using these drugs is to reduce severity of hyperthyroidism to prepare a patient for curative therapy
What is the mechanism of action for thioamides?
Thioamides inhibit the production of T3 and T4 by preventing iodine from incorporating with the tyrosine residue on thyroglobulin (directly inhibits the enzyme responsible (thyroid peroxidase)).
What additional mechanism of action does propylthiouracil have compared to methimazole?
In addition to general thioamide action, PTU also inhibits peripheral conversion of T4 into T3 (more potent form)
How should dosing for thioamides look like?
Start with an initial high dose, followed by lower maintenance doses
Titrate every 4-6 weeks based on lab data
Decrease the dose gradually as the thyroid returns to normal size because it now has a lower production rate, therefore inhibition rate can also go down
What are some common side effects of thioamides?
Side effects are relatively mild but become more of a concern for long-term therapy
GI upset
Rash
Arthralgia (joint pain across multiple joints)
What are some serious, but rare side effects of thioamides?
Agranulocytosis (lowered WBC count):
It affects 0.3-0.4% of patients using thioamides (higher in PTU users)
Abrupt onset and associated with fever, malaise, and sore throat
Neutropenia (low neutrophil count):
Prevents the immune system from properly mounting a response
Can be life-threatening if illness or fever occurs while neutropenic
Hepatoxicity:
It affects 0.1-0.2% of patients using thioamides (higher in PTU users)
MMI poses concerns about obstructive jaundice
PTU poses concerns about allergic-type hepatocellular damage
Vasculitis:
More common in PTU users
Auto-immune process
Damages vascular tissue causing inflammation and destruction of blood vessels (organ system affected determines exact presentation)
Polyarthritis:
It affects 1-2% of patients using thioamides
High degree of pain and swelling in many joints
How is hyperthyroidism treated in pregnancy?
In 1st trimester: use propylthiouracil (more concerned with fetal health)
In 2nd and 3rd trimester: switch to methimazole (more concerned with mother’s health)
How are beta blockers useful in hyperthyroidism treatment?
Reduces symptoms of hyperthyroidism related to cardiac over-stimulation (due to T3 and T4):
Palpitations
Tachycardia
Tremors
Anxiety
Heat intolerance
Avoid pindolol and acebutylol because they will also increase CO
How is thyroidectomy useful in the treatment of hyperthyroidism?
This is the most popular curative treatment in Europe, and it involves the removal of thyroid tissue. This procedure leads to permanent hypothyroidism.
How is radioactive iodine useful in the treatment of hyperthyroidism?
This is the most popular curative treatment in North America, and it involves the absorption of radioactive isotopes of iodine which ablate the gland. The procedure eventually results in hypothyroidism
Is thyroidectomy better compared to radioactive iodine in terms of their efficacy?
No, both are equally effective, but both pose risks and concerns
What is thyroid storm?
This is the sudden release of T3 and T4, a life-threatening situation due to liver damage, CVD collapse, and shock. It is characterized by severe manifestations of hyperthyroidism.
Often triggered by acute events like:
Thyroid surgery
Trauma
Infection
Childbirth
How is thyroid storm treated?
PTU is preferred and iodine is also given (initial short-term use of iodine can inhibit T3 and T4 secretion)
Other interventions involve:
Supportive care (oxygen, ventilator, IV fluids)
Administer beta-blockers to reduce symptoms of over-stimulation
Steroids can be used to block the conversion of T4 to T3
What is hypothyroidism?
A condition of thyroid hormone deficiency caused by a defect anywhere on the HPA axis.
The most common cause of hypothyroidism (99%) is chronic autoimmune thyroiditis (Hashimoto’s disease). In this disease, antibodies bind to TSH receptors and directly destroy thyroid cells
What are the symptoms of hypothyroidism?
Most symptoms are characteristic of someione who is not receiving enough stimulation:
Weight gain
Fatigue
Sluggishness
Bradycardia
Constipation
What are some treatment options for hypothyroidism?
Involves replacement of thyroid hormone
This includes the following:
Desiccated thyroid (Damm doesn’t like this option)
Liothyronine
Levothyroxine
Combined T3/T4
Why is desiccated thyroid a useful treatment option for hypothyroidism?
Desiccated thyroid (dried pills of animal thyroid):
It contains T3 and T4, but a greater proportion of T3 than seen naturally in humans. More T3 can overcorrect hypothyroidism back into hyperthyroidism as long as the drug is in effect
Why is liothyronine useful for treating hypothyroidism?
It contains T3 alone, does not affect T4 levels
Causes wide fluctuations in serum levels. Therefore it is not routinely recommended unless the patient has issues with the conversion of T4 into T3 (rare condition)
Why is levothyroxine useful for treating hypothyroidism?
It is a T4 analogue, and it is the 1st line therapy choice for hypothyroidism. Conversion into T3 is managed by the body, preventing over-stimulation.
Describe the dosing and administration regimen for levothyroxine?
The average dose is 1.6 mcg/kg/day for levothyroxine. Patients are most often given 100 mcg as a starting dose if exact condition is not known yet.
Adminsier on empty stomach, 30 min before meals or 1 hour after, every morning
What are the side effects of levothyroxine?
Should be very minimal as long as the drug is dosed properly. In severe cases, cardiac risk increases, aggravating existing CVD, and bone marrow density is declining
What are some drug-drug interactions with levothyroxine?
Antacids/H2 blockers/PPIs
Iron
Calcium
Calcium/mineal supplements
Cholestyramine
Raloifene
Manage drug-drug interactions by taking pills 2 hours before and 4 hours after taking these medications.
How do labs measure thyroid function?
TSH levels are the most important to accurately measure thyroid activity.
High TSH = low T3 and T4
Low TSH = high T3 and T4
