Chap 24- Endocrine System Flashcards
1
Q
classifications of hormones
A
- peptide or AA
- steroid hormones
2
Q
how do AA hormones work?
A
interact with cell surface receptors
3
Q
how do steroid hormones work?
A
diffuse across plasma membranes and interact with intracellular receptors
4
Q
pituitary gland
A
- made up of anterior and posterior lobes
- anterior lobe is 80% of gland
- controlled by hypothalamus
5
Q
anterior lobe of pituitary gland
A
- hormone production controlled by hypothalamus
- carried via portal vascular system
6
Q
posterior lobe of pituitary
A
- made of modified glial cells and axonal processes extending form hypothalamus
- oxytocin and ADH
7
Q
hormones that come from anterior pituitary
A
- TSH
- ACTH
- FSH
- LH
- GH
- Prolactin
- Endorphines
8
Q
hyperpituitarism
A
- most commonly anterior pituitary adenoma
- can be due to:
- proto-oncogene mutations
- loss of tumor suppressor genes
- proliferative pituitary cells
- epigenetic modifications
- other promoting factors
- clinical cours depends on hormones affected
9
Q
hypopituitarism
A
- decreased secretion of pituitary hormones
- due to diseases of hypothalamus or pituitary
10
Q
causes of hypopituitarism
A
- hypothalamic diseases caused by mass lesions, radiation, infections
- pituitary diseases caused by mass lesions, pituitary surgery, or pituitary radiation
11
Q
clinical features of hypopituitarism
A
- depends on what hormones are affected
- growth failure due to GH deficiency
- LH and FSH can cause amenorrhea, infertility, impotence, decreased libido
- hypothyroidism and hypoadrenalism
- failure of postpartum lactation
12
Q
what are the posterior pituitary syndromes?
A
- central diabetes insipidus
- SIADh
13
Q
central diabetes insipidus
A
- excessive urination due to inability of kidney to resorb water from urine
- cause- ADH deficiency
- mostly idiopathic cause
14
Q
SIADH
A
- syndrome of inappropriate ADH
- increased ADH
- resorption of too much water, results in hyponatremia
- Na in blood is “less” due to excessive dilution
- causes- ADH neoplasms, drugs that increase ADH secretion
15
Q
thyroid gland
A
- two lobes connected by isthmus
- two major cell types are follicular cells and C cells
- hormones cannot be produced without iodine
16
Q
thyroid follicular cells
A
- convert thyroglobulin into thyroxine (T4) and triiodothyronine (T3)
17
Q
Thyroid C cells
A
- synthesize and secrete calcitonin
18
Q
what is the role of calcitonin?
A
- promotes absorption of Ca in skeletal muscle
- inhibits resorption of bone by osteoclasts
19
Q
feedback control of thyroid hormones
A
- homeostasis is disturbed
- hypothalamus releases TRH
- pituitary releases TSH
- TSH effects thyroid and produces T3 and T4
- T3 and T4 increase basal metabolic rate
- levels raise is blood and homeostasis is restored
20
Q
hyperthyroidism
A
- hypermetabolic state due to increased levels of T3 and T4
21
Q
what is radioiodine uptake? (RAIU)
A
- test to see how reactive thyroid glands/ how much iodine they take
- active- take more iodine because it is required to produce T3 and T4
- near absent uptake indicates inflammation and destruction of thyroid tissue or extrathyroidal source of thyroid hormones
22
Q
hyperthyroidism with high radioiodine uptake cause
A
- autoimmune thyroid disease- graves
- autonomous thyroid tissue- multinodular goiter
23
Q
hyperthyroidism with near absent radioiodine uptake cause
A
- thyroiditis
- exogenous thyroid hormone intake
- ectopic hyperthyroidism
24
Q
graves disease
A
- triad: hyperthyroidism, goiter, eye disease (protruded eyes)
- hyperthyroidism is most common feature of graves
- cause- autoantibodies TRAb stimulate thyroid hormone production and thyroid growth
25
types of thyrotropin receptor antibodies (TRAb)
- stimulating- majority of pts with graves
- blocking- results in hypothyroidism
- neutral
- some pts have mix of TRAb so clinical presentation depends on balance
26
pathogenesis of hyperthyroidism
- thyroid cells turn into antigen presenting cells (MHC Class II) due to insults like inflammation
- class II molecule expressen presents thyroid antigens to/activates autoreactive T cells
27
predisposing factors to graves disease
- association with certain alleles of HLA
- infections of thyroid gland itself
- stress induced immune suppression and rebound immunologic hyperactivity
- moderate levels of estrogen
- post-partum
28
clinical manifestations of graves
- eyes protrude outward due to adipogensis and hyaluronic acid production
- warm and smooth skin
- increased sweating
- onycholysis- softening of nails
- increased HR, contractility, LVEF, CO
29
autonomous thyroid tissues
- benign condition
- clinically present as single nodule that is hyperfunction or "hot" on scan
- caused by mutation in TSH
- most that are "hot" are benign
30
multinodular goiters
- most common benign thyroid tumors
| - main issue is whether they are cancerous, whether or not they cause thyroid dysfunction
31
goiter
- abnormal growth of thyroid gland
- can be diffuse or nodular
- diffuse- entire gland is big
- nodular- localized region of thyroid gland is enlarged
- can be nontoxic or toxic
32
etiology of goiter
- iodine deficiency is most common cause worldwide
| - mix of genetic and environmental factors
33
thyroiditis
- transient hyperthyroidism due to inflammation
| - can be acute, subacute, or chronic
34
acute thyroiditis cause
due to bacterial infection- staph aureus
35
subacute thyroiditis cause
- viral infection of the gland
36
chronic thyroiditis
- usually autoimmune disorder
37
thyroid storm
- rare but life threatening condition
- extreme/ exaggerated amount of hormones produced
- usually occurs in untreated thyrotoxosis who experience surgery, infection, or trauma
38
hypothyroidism
- thyroid function at suboptimal level
- primary- thyroid disease causes decreased T3 and T4, increased levels of TSH
- secondary- decreased TSH or decreased TRH
39
chronic autoimmune thyroiditis/ Hashimoto's
- most common cause of hypothyroidism in iodine sufficient parts of world
- caused by cell and antibody mediated destruction of thyroid
40
pathophysiology of hashimoto's
- compromised function of Treg cells and increased activity of follicular T helper cells
- DNA fragments and altered miRNA profile
- cells destroyed via destruction or apoptosis
41
risk factors for Hashimoto's
- more common in women
- most common cause of hypothyroidism in children
- polymorphism in genes for HLA
- genetic factors
42
graves disease vs. Hashimoto's
- graves- thryoid cells are overactivated
| - hashimoto's- cell death causes not enough thyroid hormone release
43
types of thyroid carcinomas
- papillary cancer- most common
- follicular cancer
- anaplastic (undifferentiated) cancer
44
pathogenesis of thyroid carcinoma
- due to accumulation of multiple genetic factors
- mutation in oncogenes and tumor suppressor genes -> differentiated thyroid follicle can cause well differentiated papillary or follicular carinomas -> poorly differentiated carinoma -> anaplastic carcinoma
45
papillary carinomas
- biggest risk factor- radiation exposure of thyroid during childhood
- family history is also cause
- usually asymptomatic
- first manifestation may be mass in cervical lymph node
- clinical features: hoarseness, dysphagia, cough, dyspnea
46
parathyroid glands
- made of two types of cells
- chief cells- mainly produce PTH
- oxyphil cells- unknown function
47
selective function of calcium ion
- bone mineralization
- muscle contraction
- co-factor for blood coagulation
48
selective function of phosphate ion
- formation of ATP
- important intracellular anion
- major components of DNA/ RNA and membrane bilayer
- bone mineralization
49
how are calcium and phosphate ions related?
- inverse relationship
| - Ca goes up and phosphate goes down, vice versa
50
role of vitamin D in Ca and phosphate concentrations
- increases absorption of Ca in gut
| - increases release of Ca and phosphate from bones
51
role of PTH in Ca and phosphate concentrations
- increases release of Ca and phosphate from bones
- increases Ca reabsorption
- phosphate excretion by kidneys
- increased production of active vit d can inhibit PTH
52
FGF 23 role in Ca and phosphate concentrations
- increase phosphate excretion by kidneys
53
hyperparathyroidism
- caused be elevated parathyroid hormone (PTH)
| - primary, secondary, or tertiary
54
primary hyperparathyroidism
- autonomous overproduction of PTH
- caused by adenoma in most cases
- can also be caused by hyperplasia or parathyroid carcinoma
- important cause of hypercalcemia
55
secondary hyperparathyroidism
- compensatory hypersecretion of PTH in response to prolonged hypocalcemia
- due to chronic kidney failure
56
tertiary hyperparathyroidism
- persistent hypersecretion of PTH
| - happens even after hypocalcemia is corrected i.e. after renal transplant
57
altered calcium sensing on PTH secretion
- determination of serum calcium
- mutation in calcium receptor- can either activate or inactivate
- decreased sensitivity to calcium
58
causes of hypercalcemia
- primary hyperparathyroidism *
- secondary and tertiary hyperparathyroidism
- hypercalcemia of malignancy
59
hypercalcemia in primary hyperparathyroidism
- PTH mediated activation of osteoclasts -> increased bone resorption
- intestinal Ca absorption is increased
60
hypercalcemia of malignancy
- most common tumor causes- breast Ca, multiple myeloma, lymphoma, squamous cell cancers
- tumor secretion of parathyroid hormone related proteins (PTHrP)
- osteolytic metastases and cytokine release
- tumor production of 1,25 dihydoxy vit D
61
clinical course of primary hyperparathyroidism
- usually asymptomatic
- identified on routine blood chemistry profiles
- painful bones, renal stones, abdominal groans, psych moans
- excessive resoprtion of Ca -> osteopenia
- increased excretion of Ca in urine -> kidney stones
62
most common cause of secondary hyperparathyroidism
- renal failure most common cause aka chronic kidney disease- mineral and bone disorder
- results in chronic hypocalcemia
63
manifestation of secondary hyperparathyroidism
- hypocalcemia
- phosphate retention
- increased FGF23 -> increased excretion of phosphate from kidneys
- decreased vit D
- abnromal bone turnover, mileralization, growth, strength
- extraskeletal calficifaction
64
what is extraskeletal calcification?
- calcification of arteries
- increased levels of phosphate changes SMC to osteoblasts
- happens in secondary hyperparathyroidism
65
hypoparathyroidism
- PTH not made
- caused by destruction of gland, abnormal development, or altered regulation of PTH
- usually is aquired due to surgical or autoimmune damage
66
clinical features of hypoparathyroidism
- related to severity and chronicity of hypocalcemia
- tetany
- test with Chvostek sign and trousseau sign
67
Chvostek's sign
- mechanical stimulation of motor fibers in facial nerve
| - tap near PTs ear and they will twitch
68
Trosseau's sign
- increased excitability of nerves in arm and forearm
- caused by hypocalcemia
- occlude brachial artery with pressure cuff -> anaerobic metabolism -> increased excitability
69
components of adrenal glands
- adrenal cortex- outer layer
- adrenal medulla- middle layer
- chromaffin cells- produce catecholamines
70
types of steroids synthesized in adrenal cortex
- glucocorticoids- cortisol
- mineralcoricoids- aldosterone
- sex setroids- estrogens and androgens
71
feedback in adrenal glands
sense glucocorticoids are low -> signal hypothalamus -> release CRH -> goes to adrenal gland -> release glucocorticoids
72
functions of cortisol
- break down of adipose tissue
- reduces bone formation
- glucose generation in liver
- decrease AA uptake in muscles
- counteracts insulin
73
overproduced hormones in hyperadrenalism
- excess cortisol -> cushing's syndrome
- excess aldosterone -> hyperadolsteroneism
- excess androgens -> adrenogenital syndromes
74
what is the purpose of the circadian clock system?
- regulate glucocorticoid secretion based on environmental changes
75
parts of circadian clock
- central master clock- aka SCN in hypothalamus
| - adrenal peripheral clocks in all organs and tissues
76
what does the circadian clock regulate?
- central clock controls HPA axis
- creates diurnal oscillation of hormones and cortisol
- HPA axis adjusts daily rhythms of glucocorticoids
- synchronizes other peripheral clocks
77
functions of glucocortioids
- synchronization of circadian clocks
- decrease immune and inflammation
- congition
- increase depression and anxiety
- decrease growth and reproduction
- increase CV tone
- increase gluconeogensis, lipolysis, and proteolysis
78
Cushing's syndrome
- hypercortisolism
| - either endogenous or exogenous
79
types of endogenous cushing's syndrome
- ACTH dependent
| - ACTH independent
80
ACTH- dependent Cushing's syndrome
- no up and down of cortisol levels, remains high
- usually due to pituitary adenoma
- ACTH secretion not regulated by hypothalamus
- increased ACTH -> hyperplasia and hypersecretion of cortisol -> normal circadian rhythm lost
81
possible mechanism of Cushing's disease
- abnormalities in gluccocorticoid receptor
- abnormal expression of enzyme that converts cortisol to cortisone
- inappropriate repression/ expression of certain genes i.e. POMC gene
82
what is the most common cause of hypercortisolism?
ingestion of prednisone, usually for non-endocrine reasons
83
clinical features of Cushing's syndrome
- weight gain
- moon face
- buffalo hump
- stretch marks on skin due to inhibition of collagen synthesis
- neuroskeletal defects
- neuropsych abnormalities
84
Cushing's syndrome and diabetes
- glucoccorticoids effect insulin sensitivity
- tissues become unresponsive to insulin
- insulin secretion also impaired
- causes hyperglycemia
85
primary aldosteronism
- type of hyperadrenalinism
- caused by too much aldosterone
- too much aldosterone -> Na retention -> HTN
- cause is usually idiopathic, adenoma, or increased sensitivity of aldosterone in kidney
86
adrenal insufficiency
- destruction of adrenal cortex and reduction of adrenal hormones
- primary insufficiency- Addison's autoimmune disease
- Secondary insufficiency- inadequate pituitary or hypothalamic stimulation of adrenal glands
87
pathogenesis of adrenal insufficiency
- humoral immunity: presence of antibodies in serum
- cellular immunity: T cells produce interferon gamma, cytotoxic T cells and activated macrophages cause destruction of adrenal cortex
- genetic susceptibility strongly associated with HLA
88
Symptoms of Addison's disease
- hyper pigmentation due to excess ACTH secretion which stimulates melanocytes
- hypotension due to volume depletion from aldosterone deficiencty
89
adrenal crisis
- sudden worsening of adrenal insufficiency sx
- main feature- shock
- can be caused by infection, major stress, after bilateral adrenal infarction, pt who abruptly stop doses of glucocorticoids
90
pheochromocytoma
- excess catecholamines due to tumor
- neoplasm of chromaffin cells
- concentration of DA, NE, and E varies based on tumor
91
clinical features of pheochromocytoma
- triad:
- headaches
- palpitations
- sweating
- results in life threatening hypertensive emergencies
92
Sustained hypertension in pheochromocytoma
- continuous release of NE -> constant vasoconstriction
| - pts experience orthostatic hypotension
93
paroxysmal hypertension in pheochromocytoma
- sporadic, sudden release of E that is unpredictable
| - can happen due to physical stress, emotional stress, smoking, etc.
94
pineal gland
- made of pineocytes
- photosensory and neuroendocrine fns
- main product- melatonin
95
melatonin
- made from AA tryptophan
- serotonin is intermediate between tryptophan and melatonin
- secreted into blood and cerebrospinal fluid
- transfers signals to the brain about sleep and circadian rhythms
96
melatonin physiology
- daylight- serotonin is stored
- darkness- release NE and causes stored serotonin to become accessible
- NE activates enzyme that converts serotonin to melatonin
- melatonin levels rise in blood and diffuse across BBB
- shows circadian rhytm
