Week 4: Endocrine Flashcards
Major role of the endocrine system
Regulation and integration of body functions
Structure of the endocrine system
Made up of several glands which communicate using chemical messengers: hypothalamus, pituitary, pineal, adrenal, pancreas and sex organs
Basic features of the endocrine system
hormones are released from endocrine glands, travel through the blood and interact with a target organ
What does the chemical nature of hormones determine? (4)
their synthesis, release, transport and receptor site on the target site
What kind of hormones are water-soluble?
peptides and catecholamines
What kind of hormones are lipid-soluble?
steroid and thyroid hormones
Water-soluble hormones: Identify the structural classes, synthesis and storage, release, transport, receptor & type of cellular response
structural classes: Peptide and catecholamines
synthesis & storage: in advance and stored in vesicles
release: exocytosis with calcium signal
transport: without a carrier to the target tissue
receptor: on target cell surface
cellular response: second messenger systems
Lipid-soluble hormones: Identify the structural classes, synthesis and storage, release, transport, receptor & type of cellular response
structural classes: Steroid and thyroid hormones
synthesis & storage: On demand, cannot be stored
release: diffusion once made
transport: requires protein carrier to target tissue
receptor: inside cell in cytoplasm or nucleus
cellular response: alter gene transcription
What are the 3 causes of gland hypofunction? Give an example
- Congenital defect resulting in loss of gland or key enzyme
Example: congenital hypothyroidism - Destruction of the gland due to ischemia, infection, inflammation, autoimmunity, neoplastic growth
Example: Addison’s - Aging or atrophy of a gland
What are the 3 causes of gland hyperfunction? Give an example
- Excessive endogenous hormone production
Examples: Graves’, Cushing - Excessive administration of exogenous hormones
- Autoimmune stimulation of the gland
What are the 2 causes of alteration in target tissue responsiveness? Give an example
- Loss of receptors on a target tissue
Example: Diabetes Mellitus - Production of antibodies that block the ability of a hormone to bind to a receptor
What are the 3 functional alterations of glands?
- hypofunction
- hyperfunction
- alteration in target tissue responsiveness
Define and give an example of a primary endocrine disorder
definition: originates in the gland responsible for producing the hormone
example: hyperparathyroidism
Define and give an example of a secondary endocrine disorder
definition: caused by decreased hormone production or release from the pituitary
example: pituitary adenoma
Define and give an example of a tertiary endocrine disorder
definition: due to dysfunction of the hypothalamus
example: tumors and mass lesions of the hypothalamus
What are the diagnostic approaches to endocrine disorders? (5)
Blood tests: measure hormone levels
Urine tests: measure hormone levels or metabolites
Stimulation and suppression tests: hypofunction testing (stimulation); determine if negative feedback regulation is intact (suppression)
Genetic tests: identify genetic changes, screening
Imaging: scan for anatomical changes, density changes, uptake
What are the normal functions of growth hormone? (2 categories)
Structural: promotes growth of skeletal muscle and stimulates extension of the long bones before puberty by acting on the epiphyseal plate
Metabolic: stimulation of protein anabolism and fat catabolism while sparing glucose to maintain homeostasis
What is the most common cause of growth hormone excess?
Excess commonly caused by secretory pituitary adenoma, may occur in acute illness, chronic renal failure, cirrhosis
What is gigantism and how does it occur?
What is it: Symmetric excessive linear growth
How does it occur: Excess of growth hormone prior to closure of epiphyseal plates during childhood
What is acromegaly and how does it occur?
What is it:
-Tissue thickening and growth on hands, feet, nose and mandible
- Arthritis due to growth of joint cartilage and increased bone absorption
- General systemic disorder of the lungs, liver, spleen and kidneys, enlargement of intestines
- Hypertension, coronary artery atherosclerosis, CHF
How does it occur: excess of GH during adulthood
What are the consequences of growth hormone deficit in adults (4) vs. children (5)?
adults: normal height, increased body fat, decreased lean body mass, decreased bone mineral density
children: short stature, obesity, immature appearance/voice, delay in skeletal maturation, hyperlipidemia
What are the clinical manifestations of congenital growth hormone deficit? (6)
Short stature, obesity, immature appearance/voice, delay in skeletal maturation, hyperlipidemia, normal intelligence
What is the cause and what are the clinical manifestations (4) of acquired growth hormone deficit?
cause: abnormalities of the hypothalamus and pituitary
CM: Obesity, delayed skeletal maturation, increased cardiovascular mortality, other syndromes
Which two hormones are involved in endocrine regulation of calcium balance?
Two hormones regulate calcium levels: calcitonin & parathyroid hormone
Where does calcitonin come from and what is it’s general action?
released from thyroid gland when calcium levels are high - stimulates uptake of calcium
Where does parathyroid hormone come from and what is it’s general action?
released from parathyroid gland when levels are low - promotes release of calcium and phosphate into the blood
What are the 3 specific actions of parathyroid hormone?
- Stimulates osteoclasts to promote release of calcium and phosphate
- Stimulates enzymes in liver and kidney to produce an active form of vitamin D which increases calcium absorption in the GI tract
- Stimulates renal tubules to promote calcium reabsorption and decrease phosphate reabsorption
What is hypoparathyroidism?
decreased secretion of PTH or decreased hormonal response to PTH in the tissues
What is the cause and major consequence of hypoparathyroidism?
cause: due to removal or autoimmune destruction of parathyroid gland
consequence: decreased calcium levels which leads to increased neuromuscular activity and tetany
What are the symptoms of hypoparathyroidism (5)?
tetany, chvostek sign, trousseau sign, parasthesias, prolonged QT interval
What is the definition of hyperparathyroidism?
enhanced activity of parathyroid gland
What are the causes of primary hyperparathyroidism? (3)
adenoma, hyperplasia, carcinoma of parathyroid glands
What are the causes of secondary hyperparathyroidism? (2)
chronic renal failure, renal phosphate retention
What are the symptoms of hyperparathyroidism? (5)
Fatigue, hypertension, constipation, renal stones, bone pain
What is the normal function of thyroid hormone (5)?
major metabolic hormone, important for growth and development
- Permissive for growth-promoting actions of GH
- Essential for development of the nervous system
- Increases protein synthesis of many types of cells
- Regulates the rate of oxidative phosphorylation
- Controls O2 consumption and the production of heat, which determines the BMR
What are the two hormones produced by the thyroid?
thyroid hormone & calcitonin
What is the normal function of calcitonin?
reduces plasma calcium levels by causing calcium to be deposited into the bone
Which hormones comprise thyroid hormone? Which is the major form of TH? Which is the most potent form of TH?
Thyroid hormone includes thyroxine (T4) and triiodothyronine (T3)
Major/most potent form & active form = T3
Normal feedback loop for thyroid hormone?
- Hypothalamus stimulated (by sleep, cold temperature, stress) releases thyrotropin-releasing hormone or TRH
- TRH stimulates the pituitary gland to produce TSH
- TSH stimulates the thyroid gland to secrete TH
- When level of hormones reaches a certain threshold, the hormones communicate with the hypothalamus to stop the hormone cascade
What is a permissive hormone, and how does thyroid hormone function as one?
Permissive hormone = exert profound effects on the ability of cells to respond to other hormones
TH increases cellular responsiveness to catecholamines
Define hypothyroidism. How is it diagnosed?
deficiency of thyroid hormone
In children = cretinism
Adults = myxedema
TSH & TH levels -TSH will be elevated & TH decreased in primary hypothyroidism; both decreased in secondary hypothyroidism
Define hyperthyroidism
overproduction of TH
Causes of hypothyroidism
congenital or acquired, almost always primary, may be secondary
Most common cause = Hashimoto’s disease
S/S of hypothyroidism (child (2) vs. adult (8))
Child or infant - mental retardation, growth deficiencies
Adult - generalized and consistent with overall decrease in metabolism; weakness & fatigue, cold intolerance, dry skin, bradycardia, delayed deep tendon reflexes, anemia, hyponatremia and depression
What is the common cause of hyperthyroidism? What is it’s etiology?
Graves’ disease
Etiology: Involves autoimmune production of an antibody against the TSH receptor that continually stimulates TSH action leads to excess TH and goiter
What are the consequences of Graves’ disease (5)?
- Hypermetabolism: weight loss, muscle weakness, increased ventilation to meet O2 demand, increased heat production
- Increase in SNS activity
Treatment of Graves’ disease
surgery or radioactive iodine to ablate part of the thyroid; thiouracil to block TH synthesis, lithium to block TSH secretion and iodine to block the additional production of TH
- What is thyrotoxicosis? 2. If left untreated, what can it give rise to?
- Characterized by increased synthesis and secretion of T3 and T4 which gives rise to increased metabolic rate
- Thyroid storm
What is goiter?
enlargement of thyroid gland
How can goiter occur in hypothyroidism?
thyroid gland enlarges in an attempt to produce more thyroid hormones
How can goiter occur in hyperthyroidism?
thyroid enlarges due to overstimulation
Is Hashimoto’s Thyroiditis hypothyroidism or hyperthyroidism? What is it?
Primary hypothyroidism
autoimmune destruction of the thyroid gland at the thyroid peroxidase, thyroglobulin and TSH receptors
Tx of Hashimoto’s
replacement of thyroid hormone
What is myxedema?
presence of non-pitting mucus type edema caused by an accumulation of hydrophilic mucopolysaccharide substance in the connective tissues
What is congenital iodine deficiency syndrome (cretinism)?
hypothyroidism due to decrease in iodine after birth
Structure of the adrenal gland
two bean-shaped glands on the top of the kidneys
two regions: medulla (inner portion) & cortex (outer portion)
Normal function of the two regions of the adrenal gland
Adrenal Medulla: produces catecholamines released after sympathetic stimulation: epinephrine & norepinephrine
Adrenal Cortex: produces three steroid hormone types: mineralocorticoids, glucocorticoids, sex hormones
What are the general functions of the hormones released by the adrenal medulla?
Released in response to sympathetic stimulation - occurs in response to short-term stress
What are the general functions of the hormones released by the adrenal cortex?
Mineralcorticoids: regulation of minerals - sodium and potassium (eg. Aldosterone)
- Stimulate sodium and water retention to maintain fluid and electrolyte homeostasis
Glucocorticoids: promotion of cellular metabolism and response to long-term stress by regulating glucose levels (eg. Cortisol)
- Protect against hypoglycemia by promoting gluconeogenesis & glycogenolysis
Sex hormones: androgens and some estrogens
What is the normal feedback loop for cortisol?
- Stress stimuli
- Hypothalamus stimulates pituitary gland by releasing CRH
- Pituitary gland secretes ACTH
- Adrenal glands release cortisol
Define adrenal insufficiency
reduction of one or more hormones secreted from the adrenal complex
Define primary adrenal insufficiency and give an example. Why does hyperpigmentation occur?
Primary adrenal insufficiency: damage to adrenal cortex
Example: autoimmune diseases and TB
Hyperpigmentation: increased ACTH stimulates melanocytes (this does not occur in a diminished level of ACTH)
Define secondary adrenal insufficiency and give an example.
occurs when there is a lack of ACTH from anterior pituitary
Example: exogenous glucocorticoid therapy or pituitary or hypothalamic tumor
What causes adrenal crisis and what are the s/s (7)?
Cause: Occurs due to insufficient glucocorticoids (rapid withdrawal of exogenous glucocorticoids or Addison’s)
S/S: confusion, headache, N/V, muscular weakness, hypotension, dehydration, vascular collapse
What is Addison’s disease?
Primary adrenal insufficiency - atrophy of adrenal glands due to autoimmune response
What are the consequences of Addison’s on adrenal function?
- Loss of 90% of adrenal cortices resulting in an insufficiency of tissue required to produce hormones
- Decrease in adrenal secretion of cortisol and increase in ACTH release
S/S of Addison’s (13)
- Hyperpigmentation: increased ACTH stimulates melanocytes
- Hypoglycemia
- Hypotension
- Decrease in cardiac size
- Decreased mineralcorticoid activity - fluid and electrolyte imbalances, changes in WBC
- Weakness, fatigue, anemia, anorexia, vomiting, diarrhea, muscle and joint pain
Treatment of Addison’s
replacement of missing hormones
Hydrocortisone to counter the loss of mineral and glucocorticoids
What is Cushing’s syndrome?
physical and physiologic manifestation of overproduction of cortisol
What is the cause of Cushing’s?
excess production of ACTH from pituitary tumor
S/S of Cushing’s (9)
- Fat redistribution: moon face or buffalo hump
- Altered protein metabolism: muscle wasting particularly in extremities
- Accelerated bone metabolism - osteoporosis, renal calculi
- Altered glucose metabolism - presents like DM
- Loss of immune cell activity - increased risk of infection
- Increased androgens - hirsutism, acne, irregular menstruation
Treatment of Cushing’s
depends on underlying cause: surgery, radiation or medicine
Insulin: where is it released from, when is it released, consequences of release on blood glucose levels
Where is it released: Beta-islet in pancreas
When is it released
- in response to high BG levels
- in response to parasympathetic stimulation (eating)
- In response to hormones produced by GI tract when food is being metabolized
Consequences of release on BG levels
- Causes recruitment of glucose transporters to the cell surface
- Insulin takes glucose into cells, lowering BG levels
- Glucose used for energy metabolism, converted to glycogen or fats for storage or used to synthesize proteins
Glucagon: where is it released from, when is it released, consequences of release on blood glucose levels
Where is it released: Alpha-islet in pancreas
When is it released
- in response to low BG levels
- Strenuous exercise when fuel requirements are increased
Consequences of release on BG levels
- Raises BG levels by converting glycogen into glucose
- Stimulation of glycogenolysis, lipolysis and gluconeogenesis
Define: glycolysis; glycogenesis; glycogenolysis; gluconeogenesis
glycolysis: breakdown of glucose, occurs in response to increased glucose levels
glycogenesis: glycogen synthesis, occurs during rest periods and in response to high glucose levels
glycogenolysis: catabolism of stored glycogen in liver to raise BG levels - occurs when BG levels decrease
gluconeogenesis: formation of glucose from sources other than carbohydrates when carbohydrates are unavailable
Type I DM: cause, underlying impact on insulin release, consequences and treatment
Cause: autoimmune, viral or genetic destruction of B-islet cells coupled with an environmental trigger
Underlying impact on insulin release or action: complete or near absence of insulin
Consequences: high plasma glucose levels, DKA (fats used in the absence of insulin, results in formation of ketones)
Treatment: exogenous insulin
Type II DM: cause, underlying impact on insulin release and treatment
Cause: genetic component but obesity
Underlying impact on insulin release or action: decreased responsiveness to insulin due to decreased receptor number or sensitivity, high BG levels
Treatment: dietary changes and exercise, may need exogenous insulin, medication therapy
Which type of diabetes is more common? (1)
Which type is more likely to experience DKA? (2)
- Type II
2. Type I
Long-term consequences of diabetes (4)
Microvascular disease - thickening of arterioles and capillaries; ischemia can damage vulnerable tissues such as in the eye
Atherosclerosis: increased r/f plaque formation which can lead to coronary artery disease and stroke
Neuropathies: often seen with changes in Schwann cells
Infection: loss of sensation, decreased perfusion and increased glucose fosters microbial growth + impaired WBC
