endo-all Flashcards
Mechanism of cortisol
Glucocorticoid receptor
Degradation enzyme of catecholamine that predominates in neuronal mitochondria
MAO
Biochemical diagnosis of pheochromocytoma
Catecholamine excess
Urinary fractionated metaphrenine or plasma free metaphrenine will predict size and location of tumor
In the absence of cortisol, GR stays I. Cytoplasm bound to molecular chaperone such as
Heat-shock protein 90
Cyclophilin
Regulation of aldosterone secretion
RAAS
Stimulators of aldosterone
Angiotensin II = increase STAR and cyp11b2 (potent vasoconstrictor)
Extracellular K
Acute elevated ACTH
Reaction 2 in modification of FC to cortisol
Pregnenolone to progesterone by 3B-HSD or
Pregnenolone to 17-OH-pregnenolone by CYP17 (hydroxylase func)
Results from continuous administration of aldosterone in 2-3days
Aldosterone escape
Synthesis of epinephrine
- Transport of tyrosine into chromaffin cells cytoplasm
- Hydroxylation of tyrosine into DOPA
- DOPA to dopamine
- Transport of dopamine into chromaffin granules (secretory vesicles)
- Dopa to norepi within chromaffin granules as chromogranins
- Norepi diffuses out of granule thru facilitated diffusion
- Methylation of norepi to epi
- Transport of epi back into granules
Imaging of choice in pheochromocytoma if there is metastasis, previous operation or for familial, multiple pheochromocytoma
MIBG - 1st choice, gets into cell but not metabolized in cell
PET scan - metabolized further in cell
Complex of N/NE with ATP, Ca and proteins inside the granules.
Chromogranins
Renin is produced by
Juxta glomerular cell
Tissue distribution and potency agonist:
B2 receptor
Liver
Epi>norepi
Zona glomerulosa is primarily regulated by
RAS
Extracellular K
ANP
Largest and most Steroidogenic zone in adrenal Cortex
Zona fasciculata
ACTH binds to what receptor in zona fasciculata
Melanocortin-2 receptor
Metabolism of catecholamine
Draw!
Steroidogenic pathways in zona glomerulosa
Pregnenolone to progesterone (3B-HSD) to 11-doc (cyp21b) to corticosterone to 18-OH-corticosterone to aldosterone (cyp11B2)
Rate-limiting enzyme in Steroidogenesis
Cyp11A1
Inhibitors of aldosterone
ANP (directly inhibits aldosterone production / indirectly inhibits renin release)
Chronic elevated ACTH
Mechanism of action of catecholamine
Exerted thru adrenergic receptor
Congenital adrenal hyperplasia usually due to
Cyp21
Zona glomerulosa is secondarily regulated by
ACTH
Important in biogenesis on secretory vesicles and organization of components within vesicles
Chromogranins
DHEAS/DHEA: has high affinity binding to albumin
DHEAS
Tissue distribution and potency agonist:
B3 receptor
Adipose tissue
Norepi>epi
How is blood collection done in diagnosis of pheochromocytoma?
Supine for 20min
Overnight fast
No nicotine, alcohol within 12hrs
Avoid acetaminophen, TCA and phrnoxybenzamine
Conn’s disease results in
K depletion Na retention Ms weakness Hypertension Polyuria
Reduces osmotic burden of storing individual molecule of epi with chromaffin granules
Chromogranins
Metabolic action of chronically elevated cortisol in healthy individuals
Increase cortisol
Increase insulin/glucagon ratio
Decrease epi and norepi
Reaction 4 in modification of FC to corticosterone
17-Oh-progesterone to 11-deoxycorticosterone by cyp21B
What happens when there is Hypervolemia
Hypervolemia means high Na level, this will inhibit the renin release which will lower aldosterone secretion resulting back to normovolemia
Reaction5 in modification of FC to corticosterone
11-deoxycorticosterone to corticosterone by cyp11B1
Degradation enzyme of catecholamine that is predominant
COMT
Primary hyperaldosteronism
Usually due to aldosterone- secreting tumor
Conn’s syndrome
Reaction 3 in modification of FC to cortisol
Progesterone to 17-OH-progesterone by cyp17(hydroxylase) or
17-OH-pregnenolone (^5) to 17-OH-progesterone(^4) by 3B-HSD
Unique features of zona glomerulosa
- Absence of cyp17
2. Presence of cyp11b2 (aldosterone synthase)
In pheochromocytoma, lability of Bp is caused by
Episodic catecholamine release
Impaired Symphathetic reflex
Unrecognized chronic volume expansion
Chronic effect of ACTH
- Increase transportation of genes encoding Steroidogenic enzyme and coenzyme
- Increase LDL and HDL receptor
Secretion of noepi and epi is regulated by
Descending sympa signals in response to stress.
Hypothalamus and brain stem send a chemical signal as ACTH to bind to nicotinic receptor in chromaffin cells which increases acty of tyrosine hydroxylase and B-hydroxylase in which stimulates exocytosis of granules
Imaging of choice in pheochromocytoma preferred for extra adrenal, pregnant, children and those allergic to contrast.
MRI
Tissue distribution and potency agonist:
a2 receptor
Adrenergic pre synaptic terminals
Norepi=epi
Zona glomerulosa has low affinity binding to transport proteins
True
Presence of this enzyme converts cortisol to cortisone (inactivates)
11B-HSD2
Steroidogenic pathway in zona reticularis
Pregnenolone to 17-OH-pregnenolone (CYP17) to DHEA (CYP17 -lyase) to DHEAS (SULT2A1) or
DHEA to aldrostenedione (3B-HSD)
DHEAS/DHEA: low affinity binding to protein
DHEA
Degradation enzyme of catecholamine that predominates as methylation of Norepi/epi in non-neuronal tissue
COMT
Reaction 4 in modification of FC to cortisol
17-OH-progesterone to 11-deoxycortisol by CYP21B
In pheochromocytoma, hypertension is mainly due to
Increased peripheral resistance
Tissue distribution and potency agonist:
B1 receptor
Heart
Epi=norepi
Increase ACTH due to any enzyme block decreasing cortisol synthesis.
May cause masculinization of female fetus or incomplete masculinization of male fetus
Congenital adrenal hyperplasia
Cortisone is converted back to cortisol in liver, skin and other tissues by
11B-HSD1
1st reaction in Steroidogenic pathway
Free cholesterol transported in inner mitochondria thru STAR protein, and converted into pregnenolone by CYP11A1
Cortisol serves as negative feedback thru
- Inhibition of pomc gen expression at corticotropes.
2. Inhibition of pro-CRH gene expression at hypothalamus
Clinical features of pheochromocytoma
Sweating Hypertension Headaches Anxiety/fear Forceful heartbeat with or without tachycardia Flushing Fatigue Tremors
Renin is release in response to
Low bp
Low Na delivery to macula densa
Zona reticularis begins to appear after birth at..
5 year old
Physiologic action of aldosterone in kidney
Increase NA reabsorption
Increase K and H secretion
Zona glomerulosa almost all inactivated by
Liver (conjugated to glucoronide)
Acute effect of ACTH
- Rapid transport of cholesterol to OMM
- Increase STAR protein gene expression
- Resulting to increase pregnenolone activity
2 primary degradation enzymes of catecholamine
- Monoamine oxidase MAO
2. Catechol-O-methyltransferae COMT
Tissue distribution and potency agonist:
a1 receptor
Adrenergic post synaptic nerve terminals
Norepi=epi
Pheochromocytoma is majorly bilateral/ unilateral?
90% unilateral and sporadic
Chromaffin cell tumor that produce, store, metabolize and secrete catecholamine (in excess).
Causing irregular secretion of epi and norepi leading to attacks of raised bp, palpitations, and headache.
Pheochromocytoma
Imaging of choice for pheochromocytoma
CT scan
Regulation of cortisol production
Thru Hypothalmus-ant. Pituitary-adrenal axis
Reaction 5 in modification of FC to cortisol
11- deoxycortisol to cortisol by cyp11B1
Metabolic action of cortisol in response to stress
Increase cortisol
Decrease insulin/glucagon ratio
Increase epi and norepi from sympathoadrenal output
Adrenal androgens (DHEAS) appear in circulation at
6 year old
Mechanism of action of zona glomerulosa
Intracellular mineralocorticoid receptor
Regulation of menstrual cycle when there is high freq GnRH pulses
LH production
Normal internal genitalia but incomplete masculinized external genitalia - ambiguous genitalia. Mistaken for females at birth
5a reductase deficiency
Primary defect of PCOS
Inappropriate signals between HP axis and ovary
Loophole in male repro axis..
Intratesticular T level should be >100x more than circulating T level to maintain normal spermatogenesis
Short stature, webbed neck, low se tears, shield-shaped chest, short 4th metacarpals and sexual infantilism
Turner syndrome
Androgen negative feedback effect on FSH and LH ..more on
LH
Primary isolated gonadotropin deficiency due to inability of GnRH neurons to migrate to medico basal hypothalamus from nasal placode. With undescended testes (CRYPTORCHIDISM) and microphallus. Asso with anosmia
Kallmann syndrome
Most common cause of congenital hypogonadism
Gonadal dysgenesis or Turner syndrome
Genetic disorder in men with extra X chromosome.
Phenotypically male but with small testis and decreased germ cell
Klinefelter syndrome
Due to decreased DHT formation
5a reductase deficiency
Functional connections are established between GnRH neurons and portal system by
16wks AOG
Testosterone and DHT synthesis
Aldrostenedione to testosterone (17B-HSD) to DHT (5a-reductase)
Seminiferous tubular dysgenesis
Klinefelter syndrome
isoform of 5a-reductase:
Found in male urogenital tract, skin, hair follicles and Liver
For masculinization of ext genitalia in utero
Type 2
isoform of 5a-reductase:
Expression starts at puberty
Type 1
Regulation of development of external genitalia in female
Absence of DHT
GnRH neurons have been demonstrated in the feral hypothalamus by
9wks gestation
In adult male, LH is secreted in pluses approx every
2 hrs
Female repro cell which expresses LH receptor
Theca cells
60% of androgen is bound to
sex hormone binding globulin SHBG
Regulation of menstrual cycle when there is low freq GnRH pulses
FSH production
Chronically a ovulation women with high androgen, estrogen, and LH levels
PCOS
Regulation of development of internal genitalia in male
Wolffian duct-Testosterone and presence of MIS
Results from hereditary defect of X chromosome gene controlling androgen receptor expression
Phenotypically female but male internal genitalia
Male pseudo hermaphroditism
Androgen insensitivity syndrome
Characterized by a striking increase in amplitude of LH pulses with a lesser change in frequency
Puberty
Female repro cell which produces androgen (primarily androstenedione)
Theca cells
Granulosa cells expresses what enzymes
17b-HSD, cyp19
Theca cells expresses what enzyme
Cyp11a1, 3b-HSD, cyp17
Regulation of Sertoli cell function
Stimulated by both testosterone and FSH
Expresses FSH receptor
FSH stimulates synthesis of inhibin
Characterized by low amplitude GnRH secretionas mirrored by LH secretion
Childhood period
Regulation of development of internal genitalia in female
Mullerian duct - absence of MIS
Leydig cell produces estrogen peripherally. Effects…
Bone maturation
Insulin sensitivity
Improves lipoprotein profile (increase HDL)
Exogenous T level increases circulating T only
True
Regulation of development of external genitalia in male
Presence of DHT
isoform of 5a-reductase:
Found in skin - contributes to sebaceous gland activity and acne formation
Type 1
Female repro cell which expresses FSH receptor
Granulosa cells
Diagnosis of PCOS requires 2 out of 3 of
- Amenorrhea
- Evidence of excess androgen secretion (acne, hirsutism)
- Polycystic ovaries by ultrasound
Hormonal Rhythm with a 24hr cycle
Circadian rhythm
Type of secretory transport that involved release of neurohormone from axonal endings and regulation of nearby cell by diffusion
Neurocrine
Sites of impairment in dwarfism
Reduced GH secretion
Decreased IGF production
Deficient IGF action
Zone of adrenal cortex composed of straight cords of large cells with foamy cytoplasm which is filled with droplets representing stored cholesterol ester
Zona fasciculata
Pineal gland secretes what hormone?
Melatonin
ADH are synthesized as preprohormones:
Preprovasophysin - co secreted peptide - neurophysin I
Preprooxyphyxin - cosecreted peptide - neurophysin II
In embryology of hypothalamus. Division where the cells makes up almost all the adenohypophysis
Pars digitalis
Type of DI wherein there is normal ADH production but abnormal renal ADH response
Nephrogenic DI
Nursing stimulates PRL production and hence asso with decreased fertility during phase of nursing
Excess PRL in male results in testosterone deficiency and impotence
Eicosanoids
Prostaglandins
Leukotrienes
Thromboxanes
Prostacyclin
GH induce placenta to produce ___ .
By increasing maternal blood glucose and FA level! this increases the availability the nutrients for fetus.
Somatomammotropin
Steroid hormones are administered orally
Yes
Iodothyronines circulate the blood bound or unbound
Bound to serum binding proteins
Steroid hormone categories
- Progestins - progesterone
- Mineralocorticoids - aldosterone, 11-deoxycorticosterone
- Glucocorticoids - cortisol, corticosterone
- Androgens - testosterone, dihydrotestosterone
- Estrogen - estradiol-17B, estriol, secosteroid (vitD active metabolite)
Blood supply of testis
Testicular artery (from branches of internal spermatic artery)
Funnel shaped swelling superior to the infundibulum
Median eminence
Hypothalamic nuclei that func as:
Focal point of info processing
Dorsomedial nucleus
Iodothyronine have intracellular receptors
True
Hormonal rhythm with a 1/2 to 2 hr cycle
Pulsatile rhythm
Proteins or peptide hormones are administered orally
False
2 types of bv carrying blood from adrenal cortex to medulla
Medullary arterioles - provide high O2 and nutrient to chromaffin cells
Cortical sinusoids - into which cortical cells secrete steroid hormone
Pineal gland also contains other bio active peptides such as
TRH, GnRH, somatostatin, norepi
Component of pituitary gland composed mainly of neural cells and the site of release of neuro hormones.
Posterior pituitary or neuro hypophysis
Hyperprolactinemia is asso with amenorrhea and infertility.
Can have gynecomastia and galactorrhea.
May have visual disturbance (bite,portal hemianopsia) and decreased libido
True
Venous drainage of adrenal gland
R adrenal v - post aspect of IVC
L adrenal v - L renal v - IVC
Parafollicular cells are usually located where in the lobe?
Upper 2/3 of lobes
Age of gestation where rathke’s pouch arise
5th wk
Hypothalamic nuclei that func as:
Regulation of appetite
GNHR, GnRH, dopamine, somatostatin
Arcuate nucleus
In DI, they are unable to concentrate the urine normally, resulting in large volume of urine excreted.
True
Tropic hormone secreted of: Corticotrope Thyrotrope Gonadotrope Somatorope Lactotrope
Tropic hormone secreted of:
Corticotrope - adenocorticotropic hormone ACTH
Thyrotrope - thyroid stimulating hormone TSH
Gonadotrope - follicle-stimulating hormone FSH and leutinizing hormone LH
Somatorope - GH
Lactotrope - prolactin
Secretion of ACTH is pulsatile
True
Venous drainage of thyroid gland
Superior thyroid vein
Middle thyroid vein
Inferior thyroid vein
GH excess that occurs after puberty or after closure of epiphyses
Acromegaly
Hypothalamic nuclei that func as:
Magnocellular PVN: ADH, oxytocin
Parvicellular PVN: TRH, CRH, VIP
Paraventricular nucleus
PRL inhibitors
Dopamine agonist (bromocriptine)
Somatostatin
TSH
GH
4 cell types of adenohypophysis
Basophils:
Gonadotropes FSH, LH
Corticotropes ACTH
Thyrotropes TSH
Acidophils:
Lactotropes Prolactin
Somatotropes GH
GH excess that occurs before puberty
Gigantism
GH is a ___ aa peptide
191 aa
Metabolic actions of GH on lipids
Lipolytic
Keratogenic after long term admin’n
Hypothalamus is a dorsal/ventral derivative of neural tube.
Ventral
Hormone that increases during pregnancy, promoting development of breast
PRL
Proteins /peptide hormones are stored in
Membrane-bound granules
Half life of oxytocin
3-5 min
Hypothalamus develops from lateral wall of diencephalon thru ventral extension to a groove in about __wk of gestation
5 1/2 wks
Type of secretory transport where in some peptides/amines secreted directly into the gut (ie somatostatin, GASTRIN, secretin, subs P)
Solinocrine
Weight of adrenal gland
8-10 gm
Nucleus of Mammillary region of hypothalamus
Posterior nucleus
Smaller,dendritic and well granulated cells of pancreas
Delta cell
Hormone that Stimulates breast myoepithelial cell to contracts thereby ejecting the milk that has been stored in breast
Oxytocin
Catecholamine are polar/non polar
Polar
SIADH is common in what disease
PTB, pulmonary Ca
In suppression test, the administration Of suppressor is to test the..
Autonomy of hormonal secretion
Venous drainage of hypothalamus
Majority of hypothalamus - ant.cerebral and basal vein
Dorsal portion - internal cerebral vein
Both reaching the great vein of Galen (rosenthal)
Sertoli cells forms these junctions with all stages of sperm cell, allowing sperm cells to be guided towards the lumen
Adherens-type junction
Gap junction
Endocrine hormones that do not have their own personal glands
Gastrin, secretin, cholecystokinin - by GI wall
Erythropoietin - kidney
Prostaglandin
LH in female stimulates ___ produces what hormone
Follicle Ovulation and maturation into corpus luteum
Produces estrogen and progesterone
Which is larger? Right or left lobe of thyroid gland?
Right lobe. 2x larger
Zona reticularis begins to appear after birth at
5 y/o
Aldosterone in zona glomerulosa is regulated primarily by
Renin-angiotensin system
Extracellular K and ANP
Aldosterone in zona glomerulosa is regulated secondarily by
ACTH
In embryology of hypothalamus. Division where the cells facing away from infundibulum.
Pars digitalis
Regulation of development of external genitalia in the presence of DHT
Male geniality is formed (penis, scrotum,prostate)
In stimulation test, the administration of specific stimulators to test the ..
Hormonal secretory reserve to the gland p
Hormones that secretes in an Ultradian rhythm
FSH
LH
Testosterone
FSH in female stimulates ___ produces what hormone.
Follicular growth
Produces estradiol
Two principal hormones of follicular cells
Thyroxine T4
Triiodothyronine T3
GH is stimulated during deep, slow-wave sleep (stages 3 and 4).
Sleep wake patterns
Pulsatile secretion
Metabolic actions of GH on IGF
Stimulates IGF production
Stimulates growth
Mitogenic
Exocrine function of Sertoli cells
Production of fluid to move immobile sperm put of testis towards epididymis
Production of androgen-binding protein (ABP)
Determination of release of spermatozoa from seminiferous tubules
Hormone that stimulates contraction of uterine myometrium
Oxytocin
TRH is inhibited by
Stress
Required for homeostasis of all cells
Influence cell differentiation growth and metab
Considered as a major metabolic hormone because they target virtually every tissue
T3 and T4
Seat of the soul
Pineal gland
In embryology of hypothalamus. Division which is the lower expansion of infundibular process. And becomes the posterior pituitary.
Pars nervosa
Steroid hormones are derived form
Cyclopentanoperhydrophenanthrine (CPPP) ring
The cells in adrenal cortex develops into
Steroidogenic cells (GC, MC, androgens)
Medullary arterioles and cortical sinusoids fuse into ___ of vessels that drains into suprarenal vein and into IVC
Medullary plexus
Importance of endocrine system
Allows normal growth and development of organism
Maintains internal homeostasis
Regulated the onset of reproductive maturity at puberty and the func of the repro system in adults
A cells of pancreas produces what hormone
Glucagon
Which extends higher and lower in the neck? Right or left lobe of thyroid gland?
Right lobe
Site of release of ADH and oxytocin
Neurohypophysis
The mass of islets of langerhans in pancreas differs with age. Is it greater in adult?
Greater in fetus and young
Cell pop in thyroid parenchyma
Follicular cells
Parafollicular C cells
Epithelial cells
Gf resistant due to genetic defect in the receptor (total absence of IGF response)
Laron dwarfs
PRL is stimulated by
Nursing or breast stimulation which promotes onset and maintenance of milk production
Iodothyronine is derived from what aa
Tyrosine
Neuroendocrine reflex stimulating the regulation of oxytocin
During labor, Stretching of vagina and cervix
LH in male stimulates ___ produced by ___ cell
Testosterone stimulation by leydig cells
Catecholamine are have short/long half life
Short half life (1-2min)
Age of gestation where pars nervosa arise.
8th wk.
The outer part of adrenal glands
Adrenal cortex (90%)
Iodothyronines can be administered orally
True
Organs which secrete subs in response to stimuli
Glands
Type of DI wherein there is destruction of pituitary or hypothalamus resulting to:
High urine volume and low urine osmolality
High plasma osmolality and low ADH levels
Neurogenic DI
Cell in peri tubular compartment that produces testosterone
Interstitial cells of leydig
Bld supply of hypothalamus
Terminal branches of circle of Willis: Internal carotid artery Ant.cerebral artery Post. Cerebral artery Ant. Comm. artery Post. Comm. artery Basilar artery
Catecholamine are stored in
Membrane soluble granules
2 types of neuron in hypothalamus
Magnocellular (large) neuron
Parvicellular (small) neuron
Columnar and caller cells of pancreas with granules
A cells
Precursor of Eicosanoids
Arachidonic acid
Nucleus of Tuberal region of hypothalamus
Arcuate nucleus
Dorsomedial nucleus
Ventromedial nucleus
Half life of ACTH
10 min
Polyhedral cells of pancreas arranged in tubes around capillary
B cells
Largest single organ specialized for hormone production
Thyroid gland
ADH and oxytocin are similar in structures but only differs in only 2 aa.
ADH - Phenylephrine (phe)
Oxytocin - isoleucine (ile)
Hyper or hypo secretion of a hormone due to tumor or disease of an endocrine gland itself.
Primary hypo or hyper function
Important in early vasodilators shock
Antidiuretic hormone
Neuron of hypothalamus with neuro peptides and biogenic amines
Parvicellular
Stimulation test is useful in diagnosing hypofunction/hyperfunction
Hypofunction
For detecting impaired secretory reserve
Regulation of secretion of ADH is inhibited by
Alcohol
Cortisol
Atrial natriuretic peptide ANP
Pp cells of pancreas produces what hormone
Pancreatic polypeptide
Proteins or peptide hormones has short/ long half life
Short half life
PRL stimuli
Stress and sleep
Largest and most Steroidogenic zone of adrenal cortex
Zona fasciculata
Catecholamines are synthesized by
Adrenal medulla
Neurons
Sertoli and sperm cells are located in what Component of testicular lobule
Intra tubular compartment
In embryology of hypothalamus. Division which is composed of thin layer of cells which wrap around the infundibular stalk
Pars tuberalis
Target endocrine gland of: Corticotrope Thyrotrope Gonadotrope Somatorope Lactotrope
Target endocrine gland of:
Corticotrope - zona fasciculata and reticularis of adrenal cortex
Thyrotrope - thyroid epith
Gonadotrope - ovary (theca&granulosa); testis (leydig&sertoli)
Somatorope - liver
Lactotrope - none (not part of endocrine axis)
Steroid hormones are polar/non polar
Nonpolar - not readily soluble in blood thus curculates bound to transport proteins
Adrenal androgen (DHEAS) appear in circulation at what age
6 y/o
Hyper or hypo secretion of a hormone produced by excessive or deficient stimulation from its tropic hormone or its physiologic stimulators: no disease of gland per se.
Secondary hyper or hypofunction
Most abundant cell type in pancreas
Beta cells
Type of glands which secretes salts, water, immunoglobulin and enzymes conveyed to a major lumen via a duct
Exocrine gland
Most abundant circulating hormone in young male adult (negligible to female)
Androgen
Domain in follicular cell that faces the follicle lumen (colloid) with micro villi and pseudopods
Apical domain
Iodothyronines have short or long half life
Long half life
Neural crest-derived cells of adrenal ,medulla asso with sympathetic ganglia
Chromaffin cells
GnRH is released in pulsatile secretion
True
Nurse cell
Sertoli cells
Blood supply of pituitary gland
Internal carotid arteries branches:
Superior hypophysial arteries
Middle and inf hypophysial arteries - supplies pituitary stalk and post pituitary
Bld supply of thyroid gland
Superior thyroid arteries
Inferior thyroid arteries
Thyroid ima arteries
Pineal gland secretes melatonin in response to
Hypoglycemia and darkness
Axonal swelling in neuro hypophysis due to storage of secretory granules.
Herring bodies
Protein bound fraction of hormone are physiologically inactive fraction
Free or unbound fraction of hormone are physiologically active fraction
Steroid hormone is synthesized by
Adrenal cortex
Ovaries
Testes
Placenta
In embryology of hypothalamus, the rathke’s pouch may persist and becomes
Craniopharyngioma
Catecholamine circulates in the blood in unbound/bound form
Both
Major difference in between male and female repro tract:
Testosterone exerts neg feedback on secretion of pituitary FSH and LH
Estrogen exerts neg and pos feedback
Major difference in between male and female repro tract:
M: activity does not show rhythm
F: activity based on monthly menstrual cycle or length of pregnancy
Contributes to __% active androgen in males for axillary and pubic hair growth and libido
50%
Inability to initiate postpartum lactation
PRL deficiency
GHRH has a diurnal pattern
Peak - early morning
Valley - day
In embryology of hypothalamus. Division where the cells on the side of the rathke’s punch facing the infundibulum.
Lost in adult.
Pars intermedia
Target cell of ADH
Cells lining Distal renal tubule
Principal cells of collecting duct
Eicosanoids are short lived compound formed from
Polyunsaturated fatty acids
Parafollicular cells produces what hormone
Calcitonin
Which plays minimal role in Ca metab
Regions of hypothalamus
Chiasmatic (preoptic region)
Tuberal region
Mammillary region
In gigantism, it may be due to pituitary tumor which may compress the anterior pituitary
In acromegaly, Appositional growth occurs instead of lengthening of long bones.
“Acro” means end/extremity
“Megaly” means enlargement
Hypertension, hypokalemic alkalosis are found in excess/deficient ACTH
Excess ACTH (Cushing’s disease)
The outer cortex of ovary is composed of densely cellular stroma, and within resides ovarian follicles which is covered by
Tunica albuginea
Ovarian surface epith cells
Functional unit of ovary
Ovarian follicle
Type of secretory transport that secretes hormones to regulate its cell of origin thru membrane receptor
Autocrine
Regulation of development of external genitalia in the absence of DHT
female genitalia is formed (labia majora,minora, clitoris, lower 2/3 of vagina)
Milk let down
Oxytocin
Endocrine axis
Hypothalamus Releasing hormone Endocrine cell type Tropic hormone Peripheral endocrine gland (adrenal,thyroid, gonads, liver) Peripheral hormone Physiologic response
Type of secretory transport which is the production of an intracellular hormone that binds to an intracellular receptor without leaving the cell
Intracrine
Infundibulum + pars tuberalis
Pituitary stalk
Proteins/peptide hormones are polar/nonpolar
Polar
Hypothalamic nuclei that func as:
Thermoregulation (heating center)
Posterior hypothalamus
Steroid hormones have intracellular receptors
True
ACTH has a diurnal pattern
Peak - early morning
Valley - late afternoon
Hormones that have intracellular Receptors
Steroid hormones and Iodothyronines
Hypothalamic nuclei that func as:
Thermoregulation (cooling center)
Regulation of thirst
Anterior hypothalamus
Regulation of secretion of ADH is released in response to
Cellular dehydration
- Increase ECF osmolality
- Decrease blood vol and pressure
- Na, sucrose, mannitol
- Drugs: barbiturates, nicotine, opiates
- Nausea (protective effect)
Hormone that maintains the normal osmolarity of body fluids and blood vol
Antidiuretic hormone
Effects of SYndrome of inappropriate secretion of ADH
High urine osmolality
Hyponatremia
Low serum osmolality
Type of neurocrine wherein the msgr is carried to local or distant site of action via ECF or blood
Nonsynaptic neurocrine
Proteins or peptides are synthesized as
Prehormones or preprohormones
Catecholamine are derived from what aa
Tyrosine
Primary hypothalamic regulator of: Corticotrope Thyrotrope Gonadotrope Somatorope Lactotrope
Primary hypothalamic regulator of: Corticotrope - corticotropin-RH Thyrotrope - thyrotropin-RH Gonadotrophs - Gonadotropin-RH Somatorope - Growth hormone-RH Lactotrope - dopamine and prolactin-RH
Hypothalamic nuclei that func as:
Somatostatin
Periventricular nucleus
Inhibin in males is produced by what cell and cause decrease/increase FSH or LH
Inhibin in males is produced by Sertoli cells which decreases FSH
GH is under dual control by hypothalmus. It is stimulated and inhibited by..
Stimulation by GHRH
Inhibition by somatostatin
Biochemical classification of hormones
Proteins and peptides
Catecholamines
Steroid hormones
Iodothyronines (aa derivatives)
Chemical msgr/signals secreted into the blood stream to act on distant tissues
Hormones
Neural down growth
Infundibulum
Weight of pituitary gland (hypophysis)
400-800 mg
Metabolic actions of GH on proteins
Increase tissue aa uptake
Increase incorporation into proteins
Decrease urea production
Produces positive Nitrogen balance
Normal GH level but lack normal rise in IGF during puberty
Partial IGF response
African pigmy
Half life of ADH
15-20 min
Stress also triggers CRH release
True
Hormone that Stimulates development of breast duct system, breast fat deposition and breast stroma
Estrogen
TRH has a diurnal pattern.
Peak - overnight
Valley - dinner time
Weight of thyroid gland
15-25 gm
Hypothalamus originates from
Embryonic basal plate
Endocrine function of Sertoli cells
Expression of androgen receptor and FSH-receptor
Production of mullerium-inhibiting subs (MIS)
Aromatic action of testosterone to estradiol-17B
Produce inhibin (keeps FSH level within specific range)
Hypotension, hyperkalemic acidosis are found in excess/deficient ACTH
Deficient ACTH (Addison’s disease)
If PRL suppress GnRH release
Lactational amenorrhea
Domain in follicular cell that faces extracellular matrix (blood) which contains (+) TSH and NIS
Basal domain
Iodothyronines are stored in
Follicle (part of thyroglobulin)
FSH in male stimulates ___ produced by ___ cell
Facilitates spermatogenesis
Produced by Sertoli cells
Major difference in between male and female repro tract:
m: gametes contiguous with repro tract
F: gamers not contiguous with repro tract
Major difference in between male and female repro tract:
m: gametic reserve replenished throughout life
F: finite gametic reserve, exhausted by menopause
Adrenal medulla synthesize
Catecholamine:
Epi (80%)
Norepi (20%)
Supportive function of Sertoli cells
Maintaining, breaking and reforming multiple junctions with developing sperm
Maintaining blood-testis Barrier
Phagocytosis
Transfer of nutrients and other subs from blood to developing sperm cells
Expression of paracrine factors and receptors for sperm-derived paracrine factors
Leydig cells synthesize and stores
Cholesterol as cholesterol esters
Hormone that keeps FSH level within specific range.
Inhibin
Proteins or peptide hormones have cell membrane receptors (2nd msgr)
True
TSH is heterodimer. What subunit is common to TSH, FSH and LH
Alpha-Glycoprotein subunit
PRL is a ___ aa peptide
199 aa
Hormone that Stimulates development of breast glandular tissue, the secretory structure of the breast
Progesterone
Sertoli cells contains major secretory products such as
Protease and protease inhibitors.
Type of gland that are ductless to which it secretes hormones directly into the circulation.
Endocrine gland
Primary endocrine cell of testis
Leydig cells
There is no cortisol/androgen synthesis if this particular enzyme is..
Absence of CYP17
Neuron of hypothalamus with arginine vasopressine and oxytocin
Magnocellular
This enzyme catalyzes the last 3 reactions from DOC to form aldosterone
Presence of CYP11B2 (aldosterone synthase)
Catecholamine have cell membrane receptors
True
Stage of ovarian follicle growth where that start of ovarian hormone production
Growing antral (tertiary) follicle
Cell bodies producing ADH and oxytocin located in what nucleus
Supra optic (SON) and paraventricular nucleus (PVN)
Effect of ADH
Decrease urine flow
Increased urine osmolality
Increased mesangial cell contraction - decrease GFR
Inhibits renin release
Iodothyronines are polar or nonpolar
Polar
Peripheral hormone involved in negative feedback of: Corticotrope Thyrotrope Gonadotrope Somatorope Lactotrope
Peripheral hormone involved in negative feedback of:
Corticotrope - cortisol
Thyrotrope - T3
Gonadotrope - estrogen, progesterone, testosterone, inhibin
Somatorope - IGF-1
Lactotrope - none
Delta cells of pancreas produces
Somatostatin
B cells produces what hormone
Insulin
Nucleus of Chiasmatic region of hypothalamus
Suprachiasmatic
Supra optic
Paraventricular nucleus
Anterior nucleus
Isthmus crosses the trachea between rings”
Tracheal rings I and II
PRL is under tonic inhibitory control by hypothalamus by
Dopamine
Hormone that Stimulates milk secretion into the alveoli in pregnancy and nursing
PRL
Normal gametogenesis and development and physiology of male and female repro tract are absolutely dependent on gonadal endocrine func
True
GH deficiency
Dwarfism
GnRH is a ___ aa peptide
10aa
Incrd Skin pigmentation may occur in Addison’s disease if
The disease is not of pituitary origin
Component of testicular lobule composed of seminiferous tubules
Intratubular compartment
Classes of hormones based on structure: glycoproteins
FSH
LH
TSH
HCG
The inner part of adrenal glands
Adrenal medulla (10%)
Hypothalamic nuclei that func as:
Hunger center
MCH, anorexins
Lateral hypothalamus
GH excess
Gigantism and acromegaly
Regulates salt and volume homeostasis
Zona glomerulosa
Aldosterone
GH indirectly induce liver to produce
Somatomedin
Proteins/peptide hormones circulate the blood in bound/unbound form
Unbound
what are the dopamine agonist drugs that cause shrinkage of prolactinomas?
Bromocriptine
Cabergoline
“BRO, you call ur TITS a CAB”
ACTH is a ___ aa peptide
39 aa
Type of neurocrine wherein the msgr traverses a structure synaptic space
Synaptic neurocrine
Suppression test is useful in diagnosing hypofunction/hyperfunction
Hyperfunction
Hyperfunctioning gland is not operating under normal control mechanism
Type of secretory transport that involves secretion of hormone from endocrine cell, its diffusion into capillaries and regulation of distant cells
Hemocrine/ endocrine
Cell in thyroid parenchyma where it could be the origin of subset of papillary thyroid Ca
Epithelial cells
Inhibin in females is produced by what cell and cause decrease/increase FSH or LH
Inhibin in females is produced by corpus luteum and causes decrease in FSH and LH
Beta cells of pancreas are found in
Body
Tail
Anterior portion of head
Steroid hormones are stored in
Endocrine gland
Deficiency in ADH production
Diabetes insipidus
The last 3 reactions from DOC to aldosterone
11-hydroxylation: DOC to corticosterone
18-hydroxylation: corticosterone to 18-hydrocorticosterone
18-oxidation: 18-hydrocorticosterone to aldosterone
ANS modulates islet hormone secretion. What stimulation increases insulin, glucagon and PP?
Cholinergic and beta-adrenergic stimulation
Blood supply of adrenal gland
Inf suprarenal artery (from renal artery)
Middle suprarenal artery (from aorta)
Superior suprarenal artery (form inf phrenic artery)
Hyperprolactinemia is secondary to post/ant pituitary tumor
Anterior pituitary
Receptor of: Corticotrope Thyrotrope Gonadotrope Somatorope Lactotrope
Receptor of: Corticotrope - melanicortin-2 receptor MC2R Thyrotrope - TSH receptor Gonadotrope - FSH and LH receptor Somatorope - GH receptor Lactotrope - prolactin receptor
Hypothalamic nuclei that func as:
Regulator of circadian rhythm and pineal function.
Suprachiasmatic nucleus
Metabolic actions of GH on carbohydrates
Increase blood glucose
Des peripheral insulin sensitivity
Increase hepatic output of glucose
Admin’n results in increased serum insulin levels
Component of testicular lobule that represents true epithelial cells of seminiferous epith and surrounds the sperm cells
Peritubular compartment
Components of testicular lobule
Intra lobular compartment
Peritubular compartments
A cells of pancreas are found in
Body
Tail
Catecholamine
Norepi, epi, dopamine
Type of DI common in compulsive water drinkers
Psychogenic DI
Hypothalamic nuclei that func as:
ADH: osmoregulatioh
Oxytocin: regulation of uterine contraction and milk ejection
Supraoptic nucleus
Major difference in between male and female repro tract:
Testis reside outside abdominal cavity
Ovaries reside within abdominal cavity
Major difference in between male and female repro tract:
M: Continuous release of gametes from gonads
F: release of gametes occurs once a month
Basic roles of gonadal hormone in male
Support of spermatogenesis
Maintenance of male repro tract and semen production
Maintenance of secondary sex characteristics
Maintenance of libido
Dwarfism occurs after or before puberty
Before puberty
F or PP cells of pancreas are found in
Post or ventral part of head
TSH stimulate the proliferation of Tg synthesizing cuboidal cells of thyroid follicles. Thus an excess TSH will cause enlarged thyroid or..
Goiter
Causes of retarded growth in children
GH deficiency Thyroid deficiency Insulin deficiency Malnutrition / under nutrition Physical growth retardation Constitutional delay Chronic disease Genetic disorders charac by short stature Cortisol excess
Major difference in between male and female repro tract:
Testosterone always the primary gonadal steroid
Estrogen is the primary steroid in first half of cycle, progesterone in 2nd half
Major difference in between male and female repro tract:
M: repro system does not prepare for NB
F: prepare for NB with breast development and milk production
Hormonal rhythm with periodicity <24 hr
Ultradian rhythm
Hyperprolactinemia may occur with excess TRH production stimulates PRL secretion in addition to TSH secretion
True
Hypothalamic nuclei that func as:
Satiety center
GHRH, somatostatin
Ventromedial nucleus
Component of pituitary gland composed mainly of epithelial cells with 5cell types excreting 6 hormones.
Anterior pituitary or adenohypophysis
Hypothalamus is composed of gray/white matter
Gray mater
Type of secretory transport that release hormone into ECF and its regulation of surrounding cells by diffusion
Paracrine
Functional unit of thyroid gland
Follicular cells
Hypothalamic nuclei that func as:
Few GnRH neurons
Preoptic nucleus
Circulating ab in graves disease
TRAbs
Metabolic effects of T3
- Lipolysis- FA + glycerol
- expression of lipogenic enzymes
- cholesterol catabolism into BA
- Rapid removal of LDL from plasma
- Carbohydrate and protein catabolism
T3/4: Produced only in thyroid gland
T4
During first trimester, ___ is at its highest conc and can stimulate thyroid cells to produce new thyroid hormones.
B-HCG
Most frequent cause thyrotoxicosis in iodine-sufficient countries
Graves disease
Indication for radioactive iodine treatment
Female planning a pregnancy in the future
Pts with increase ping surgical risk
Pts previously operated or externally irradiated neck
Pts with CI to ATD
In some pts with HAshimoto’s thyroiditis, they may stay hypothyroid because of inability to escape this effect
Wolff-chaikoff effect
TSH level and T4 level of:
True hyperthyroidism
Low TSH
High T4
Thyroid hormone is critical for normal bone Growth and development
T3 regulates sk maturation at growth plate.
T3 participates in osteoblasts differentiation and proliferation and chondrocytes maturation loading to bone ossification.
Patients undergoing surgery (thyroidectomy) should be rendered
Euthyroid
RAI therapy or RAI ablation:
Low dose
RAI therapy
Major extrathyroidal T4 conversion site for production of T3
Liver
Some occurs in liver and other tissue
Half life of t3
One day
Myxedema is due to
Accumulation of hyaluronic acid which alter the composition of the subs of the dermis and other tissue
PTU / MMI:
More binding to albumin
PTU
Half life of t4
7 days
Severe hypothyroidism in infancy with irreversible mental and grocery retardation
Cretinism
Iodine intake not more than
1100 ug/d
Indications for thyroidectomy
Planning for pregnancy (<4-6 mos) Thyroid malignancy Large goiter (>80gms) Low RAIU Coexisting hyperparathyroidism
Thyroxine therapy must be considered in subj (age) if TSH is ___ and/or TPO ab is (present/absent)
<65 yrs old if TSH >10mU/L and/or TPO ab is present
During pregnancy, there is an increased Renal iodine clearance, therefore..
Increased 24-hr RAIU
Hallmark of classic HAshimoto’s disease
Goiter
TSH level, T3 or t4 level in subclinical hypothyroidism
High TSH
Normal t4 and t3
3-8x more potent
T3
During pregnancy, there is an decreased plasma iodine and placental iodine transport to the fetus, therefore..
In deficient women, decreased T4, increases TSH then leads to goiter formation
Treatment of choice in HAshimoto’s disease and /or large goiter
Levothyroxine
Mechanism of action of ATDs
Inhibition of organification (iodine binding to Tg)
Inhibition of coupling of Iodothyronines
Inhibition of T4 to T 3 conversion (PTU)
Possible immunosuppressive effects (MMI)
Potential complication of thyroidectomy
Hypoparathyroidism
Hypothyroidism
Vocal cord paralysis
AOG when fetus is completely dependent on maternal thyroid hormones
First 3 mos
Pathologic feature of HAshimoto’s thyroiditis
Presence of both mononuclear cells and thyroid follicle destruction
During pregnancy, there is an increased serum TBG, therefore..
Increased total T3 and T4
T3 is derived from 2 processes
- 80% of circulating T3 comes from deiodination of T4 on peripheral cells
- 20% comes directly from thyroid secretion.
PTU / MMI:
Lower conc in breast milk
PTU
T4 is converted to T3 by
5-deiodination of outer ring of T4
Main ag in graves disease
TSHR
Life threatening clinical condi in pts with long standing severe untreated hypothyroidism
Myxedema coma
ATD that is used in all patients
MMI
Except those in 1st tri in pregnancy, treatment for thyroid storm
Little or no placental transfer
TSH
PTU / MMI:
With peculiar toxicity - aplastic cutis embryopathy
MMI
Excess iodine
Wolff chaikoff effect
Jodbasedow phenomenon
Conditions that increase TBG
Pregnancy Infectious/chronic active hepatitis HIV infection Biliary cirrhosis Acute intermittent porphyria Genetic factors
TSH level and free T4 level of:
Secondary or central hypothyroidism
Low TSH
Low T4
Most common cause of hyperthyroidism
Graves disease
TPO uses ___ as the oxidant to activate I- to hypoiodate the iodination species
H2O2
PTU / MMI:
Less placental passage
PTU
Thyroid hormone stimulates mitochondrial activity in most tissue
T3 increases basal metabolic rate, body heat production and O2 consumption.
PTU / MMI:
Blocks thyroid hormone production and secretion
Both
RAIU level in thyrotoxicosis
Decreased
Mechanism of action do radioactive iodine
Destroys the thyroid and stops the excess production of hormone
First line therapy for hyperthyroidism or graves disease
Radioactive iodine
During pregnancy, there is an increased O2 consumption, therefore..
Increased BMR
During pregnancy, there is an increased plasma type 3 deiodinase, therefore..
Accelerates rates of t3 and T4 degradation and production.
Thyroid hormones that appear in fetal serum
TSH
T4
TSH level and RAIU level of:
TSH-secreting pituitary tumor
TH hormone resistance
Elevated or normal TSH
Dietary iodine reaches the circulation as
Iodide anion
DIT plus DIT
Tetraiodithyronine or T4
RAI is used by elderly and cardiac pts
True.
TSH level and RAIU level of: Graves disease Toxic multinodular goiter Toxic adenoma Gestational hyperthyroidism
Low TSH
High RAIU
Iodination of tyrosyl residues then forms monoiodotyrosine and diiodotyrosine which are then coupled to form either T3 or T4. Both reactions are catalyzes by
Thyroperoxidase
It functions as iodide concentrating mechanism that enables iodide to enter the thyroid for hormone biosynthesis
NIS
TSH level and T4 level of:
Sick euthyroid syndrome
Low TSH
Low T4
There is transient low TSH during 1st trimester due to increased thyroid hormone production.
True
Thyroid hyperfunction induced by excess iodine ingestion in pts with various thyroid disorder (grave’s disease)
Jod-basedow phenomenon
Normal circulating concentration of t3
60-180 ng/dl
Lab diagnosis for thyrotoxicosis and hyperthyroidism
Suppressed TSH <0.1 mU/L
Elevated T4
RAIU
Major regulator of mitochondrial activity
T3
Decrease or increase TBG effects on total serum T3 and T4 level and free T3 and T4.
Decrease or increase TBG will decrease/increase total serum T3 and T4 level.
While free T3 and T4 remain unchanged
PTU / MMI:
Blocks peripheral conversion of T4 to T3
Porpylthiouracil
Pregnancy must be postponed for at least ____ after RAI therapy
6 mos
Anti thyroid drugs
Methimazole
Propylthiouracil
Carbimazole
Thiamazole
TSH level and T4 level of:
Graves disease
Low TSH
High T4
Graves disease is a syndrome characterized by
Hyperthyroidism
Ophthalmopathy
Dermopathy
Pretibial myxedema
Thyroid hormone is a major regulator of mitochondria activity
T3 induces early transcription and increases TFA expression.
T3 stimulates O2 consumption.
In cases wherein TSH <10mU/L and/or TPO ab is absent, thyroxine therapy still might be warranted in individual with high background for
Cv risk, pregnancy and infertility
Reserved for disorders that results from sustained overproduction of hormone by the thyroid gland itself
Hyperthyroidism
Indispensable component of thyroid hormone comprising 65% of T4 and 58% of T3’s weight.
Iodine
DIT plus MIT
Triiodothyronine T3
Treatment of choice for recurrent hyperthyroidism after ATD therapy
RAI
During pregnancy, there is an increased plasma volume, therefore..
Increased T3 and T4 pool size
T3/T4 which is biologically active responsible for the majority of thyroid hormone effects
T3
Increased thyroid hormone requirements during pregnancy
Increase free TH binding to TBG - marked fall in serum free T4 - if no compensatory increase in thyroid secretion leads to hypo.
Transplacental transfer of T4 - placental degradation of T4 - if no compensatory increase in thyroid secretion leads to hypo.
Signs and symptoms in hypothyroidism
Constipation Puffy eyes Muscle weakness Weigh loss gain Bradycardia Cold intolerance Dry, patchy skin Heavy period
Hairloss Tiredness Forgetfulness Depression Elevated cholesterol
Goiter Hoarseness Infertility Irritability Dry/sore throat Dysphagia
AOG when fetal pituitary gland differentiates
10-12 wks
Pro hormone for T3
T4
Iodide must be first ___ to be able to iodinate tyro sly residues of Tg
Oxidized
Most common cause of thyrotoxicosis
Thyroiditis
Most common case of hypothyroidism in areas wherein dietary iodine is sufficient
HAshimoto’s thyroiditis
To liberate t3 and t4, Tg is resorted into follicular cells in the form of ___ which fuse with lysosomes to form phagolysosome
colloid droplets
Thyroid hormone influences cv hemodynamics by
Increase HR and decrease systemic vascular resistance thus increase CO = improve cardiac performance Elevate blood volume Local vasodilators Decrease diastolic blood pressure Cardiac chronotropy and inotropy
T3/4: 80% are from peripheral conversion
T3
T3/4: only free hormones are active
T4
Excess iodine with transient shut down of thyroid hormone production (normally).
When increasing doses of iodide inhibit organification and hormonogenesis of thyroid hormone.
Wolff chaikoff effect
TSH level, T3 or t4 level in subclinical hyperthyroidism
Low TSH
Normal t4 and t3
Asymptomatic
Required daily intake of iodine in 7-12y/o.
120 ug/d
Environmental triggers of graves disease
Stress
Tobacco use
Infection
Iodine exposure
Normal disposition of T4
41% is converter to T3
38% is converter to rT3
21% is metabolized via other pathways (conjugation on liver and excretion in bile)
RAI therapy or RAI ablation:
With intention to destroy all thyroid remnant and metastasis in well diff Ca
RAI ablation
Required daily intake of iodine in teenager and adults
150 ug/d
Primary secretory product of thyroid gland
T4
RAI has no effect on fertility, no increased incidence of congenital malformation and no increased risk of cancer
True
T4 is biologically inactive in target tissues
True. Until converted to T3
AOG when fetal thyroid begins to conc iodine and synthesize Iodothyronines
10-12wks
Signs and symptoms of hyperthyroidism
Freq bowel movement Bulging eyes Sudden paralysis Weigh loss / gain Tachycardia Heat intolerance Warm, moist palm Light period
Increase sweating
Insomnia
Nervousness, tremors
Goiter Hoarseness Infertility Irritability Dry/sore throat Dysphagia
What would be given in immediate preop period in thyroidectomy
Potassium iodide
To diminish vascularity to suppress the thyroid hormone production becoz patients undergoing surgery should be rendered euthyroid.
Iodide trapping by the aid of
NIS
Placental transfer without difficulty
Iodide
Thionamides
Thyroid ab
TRH
Biosynthesis of T3 and T4
- Dietary iodide ingestion by follicular cells
- Active transport and uptake of iodide into colloid by thyroid gland
- Oxidation of I and iodinatiob of Tg tyrosine residues
- Coupling of Iodotyrosine residues (MIT & DIT) to form T3 and T4
- Proteolytic of Tg with release of T3 and t4 into circulation
Thyroid secretes approximately how many grams of thyroxine daily
70-90 ug/d
TSH level and T4 level of:
T3 thyrotoxicosis
Sub clinical hyperthyroidism
Low TSH
Normal T4
Rare disorder of chronic sclerosing thyroiditis
Riedel’s thyroiditis
Normal circulating concentration of t4
4.5-11 ug/dl
Thyroperoxidase Catalyzes oxidation steps involved in:
I- activation
Iodination of Tg tyrosyl residues
Coupling of iodotyrosyl residues
Required daily intake of iodine in pregnant and lactating women
25o ug/d
Decreased thyroid hormone concentration may lead to alteration of ___. May develop impairment of attention, slowed motor function, and poor memory
cognitive function.
Dermopathy in graves disease
Plummer's nail Hyperpigmentation Hyperhidrosis Alopecia Acropachy (triad of digital clubbing, soft tissue swelling of hands and feet and periosteal new bone formation)
Drugs that increase TBG
Oral contraceptives Methadone Clofibrate 5-fluorouracil Heroin Tamoxifen
PTU / MMI:
Long half life
MMI
Refers to classic physiologic manifestations if excessive quantities of the thyroid hormones
Thyrotoxicosis
Lab diagnosis to differentiate thyrotoxicosis and hyperthyroidism
RAIU
During 1st tri in pregnancy, there is an increased HCG, therefore
Increased free T4 and T3
Decreased basal TSH
Thyroid hormone influences the female repro system
Hypothyroidism may be asso with menstrual disorder, infertility, risk of miscarriage and other complications of pregnancy.
RAI therapy or RAI ablation:
To destroy some thyroid tissue in graves disease or toxic nodules.
RAI therapy
Total daily production rate of t3
15-30 ug/d
RAI is contraindicated during
Lactation and pregnancy
More than 99% of circulating T3 and t4 is bound to plasma protein Carrier proteins which are
TBG 75%
Transthyretin TTR / thyroxine-binding prealbumin TBPA 10-15%
Albumin 7%
HDL 3%
Drugs that decrease serum t3 and t4 by decreasing binding
Antiseizure medications
Salicylates
Required daily intake of iodine in 0-7y/o.
90 ug/d
Graves disease is an autoimmune disease with a strong familial disposition more common in male/female.
Female
Atrial fibrillation is characteristically manifested in what thyroid disorder
Graves disease
Self limited anti-inflammatory disorder of thyroid and the most common cause of pain from thyroid origin
Subacute thyroiditis
TSH level and RAIU level of: Iodine induced hyperthyroidism Amiodarone- induced hyperthyroidism Struma ovarii Metastatic thyroid Ca Thyroiditis
Low TSH
Low RAIU
Drugs that decrease serum t3 and t4 by decreasing TBG conc
Glucocorticoids Androgens L-asparaginase Mefenamic acid Furosemide
Some placental transfer
T3
T4
Iodide active transport by thyroid Is mediated by this membrane protein
Sodium-iodide symporter or NIS
Primary stimulating signal of PTH
Low circulating Ca level
Hormones and minerals found in bones
PTH Vit D Calcitonin Calcium Phosphorus
Inhibits bone resorption
Calcitonin
As decreases Ca and Pi
PTH receptor that is abundant in bones (osteoblasts) and kidneys (prox and distal convoluted tubules)
PTH1R
Circulating forms of calcium
Ionized - 50%
Protein-bound - 40%
Complexed with anion - 10%
Major regulator of calcium and phosphorus metabolism
PTH
Calcitonin is produce by what cell
Parafollicular C cell
Calcitonin release is stimulated by
Vit D
Ingestion of food due to GASTRIN
Effect of PTH to phosphate and Ca level
Increase Ca
Decrease phosphate
Low Ca stimulates renal 1a-hydroxylase thru increased PTH
High Ca inhibits 1a-hydroxylase thru CaSR in proximal tubule
Hypoparathyroidism is due to PTH and vitD deficiency. It has high/low Ca and high/low Pi.
Low Ca and high Pi
The most important effect of PTH is to increase/decrease plasma calcium level
Increase plasma calcium level
PTH decrease /increase plasma phosphate
Decrease plasma phosphate
As in chronic renal disease with high Pi and low Ca due to high PTH and low vit D
Renal osteodystrophy
Vit D3
Cholecalciferol
Calcitonin excess does not produce hypocalcemia (MTC).
Calcitonin deficiency does not produce hypercalcemia (post total thyroidectomy for thyroid Ca )
Calcitonin plays a very minimal or negligible physiologic role in Ca and phosphate homeostasis
PTH receptor that does not bind to PTHrP
PTH2R
Very active vit D preparation
Calcitriol
Percentage of active vit d that circulates as free steroid
0.4%.
Other binds to DBP from liver
What kind of receptor is vit D receptor
Nuclear receptor
PTH stimulation
Phosphodieasterase inhibitors Epinephrine Dopamine Histamine Lithium Thiazides diuretics
High Mg level inhibits PTH
True
Useful histo chemical marker for MEdullary thyroid Ca
Calcitonin
Calcitonin is regulated by
CaSR and high Ca level
PTH inhibition
A-adrenergic agonists
Prostaglandins
Aluminum
Chromogranin
Normal calcitonin plasma level
10-20pg/mL
Any increase In plasma Ca by 1mg/dl will result to 2-10fold acute rise in calcitonin
Low circulating Ca level is sensed by principal cells thru
Ca-sensing receptor (CaSR)
VitD deficiency leads to defective bone mineralization in adults
Osteomalacia
Major stimulus of calcitonin
Hypercalcemia
Larger, mitochondria-rich, eosinophilic cell type of parathyroid gland
Oxyphil cell
PTH decrease plasma phosphate by
Inhibiting renal tubular phosphate reabsorption
Rate limiting enzyme in vit d synthesis
1a-hydroxylase (CYP1a)
Vit D synthesis
7-dehydrocholesterol -(skin UV light)- cholecalciferol - (liver vitD 25-hydroxylase)- 25hydroxycholecalciferol -(kidney 1a-hydroxylase)- 1,25dihydroxyvitamin D
Effect of vitD to phosphate and Ca level
Increase Ca
Increase phosphate
Hyperparathyroidism is an excessive production of PTH that is usually due to single adenoma. It has high/low Ca and high/low Pi.
High Ca and low Pi
Bone cell type for production of matrix
Osteoblast
Predominant parenchymal cell type and a primary endocrine cell of parathyroid gland
Chief/principal cell
Facilitates absorption of Ca in duodenum and jejunum
Vit d
Ergocalciferol, secosteroid produced in plants. Enters the liver for hydroxylation via portal circulation and chylomicrons
Vit D2
PTH receptor that activates adenylyl cyclase and PLC
PTH1R
VitD deficiency leads to secondary increase in PTH
Osteoporosis
Parathyroid cell type that secretes PTH
Chief cell
Calcitonin is expressed in
Osteoclast (inhibits bone resorption)
Nephrons (inhibits Ca and Pi reabsorption)
Effect of calcitonin to phosphate and Ca level
Decrease Ca and decrease phosphate
Rare familial disorder charac by tissue resistance to PTH.
Pseudo hypoparathyroidism
Pty receptor that bonds both PTH and PTHrP
PTH1R
Inhibitors of calcitonin
Low vit D
Somatostatin
Bone is not affected in hypoparathyroidism
True
PTH receptors
PTH1R (hPTH/PTHrP)
PTH2R
CPTH
Mechanism of action of PTH in kidneys
Stimulates Ca reabsorption
Inhibits Pi reabsorption
Stimulates conversion to 1,25 dihydroxy vitamin D
High Ca and low Pi in hyperparathyroidism is due to
Bone demineralization
High GI Ca absorption
High renal Ca reabsorption
There is high PTH secretion, low Ca and congenital defects of skeleton.
Pseudo hyperparathyroidism
The most important effect of PTH is to increase plasma Ca level by
Stimulate bone resorption
Increase renal tubular reabsorption
Stimulate renal 1,25 dihydroxy- D synthesis
VitD deficiency leads to defective bone mineralization in children
Rickets
Mg and Ca in vit D deficiency
Low mg and Ca
Bone cell type for resorption of matrix
Osteoclasts
The low Ca and high Pi in hypoparathyroidism is due to
Impaired GI Ca absorption
Decreased renal reabsorption
Decreased bone Ca mobilization
Results in bone deformities due to increase bone resorption ff by increase bone formation.
It has high alkaline phosphatase, osteocalcin and urinary hydroxyproline.
It produces pain, bone deformation and bone weakness.
Paget’s disease
Bone remodeling is regulated by
PTH
PTH receptor that reacts with the carboxylate terminal rather than amino terminal of PTH
CPTH
Primary target of PTH
Bone
Kidneys
PTH receptor that is found in brain, placenta and pancreas
PTH2R
Secosteroid (class of steroid with 1 open cholesterol ring)
Vit D3
Calcitonin is primarily inactivated in what organ
Kidney
Insulin receptor has a and B subunit. Which subunit spans the cell membrane.
Beta subunit
Insulin receptor has a and B subunit. Which subunit contains hormone binding site?
Alpha subunit
Somatostatin has 2 forms
Somatostatin-14
Somatostatin-28
Insulin receptor has a and B subunit. Which subunit is external to cell membrane?
Alpha subunit
IRS phosphorylation leads to activation of..
Protein kinase B (PKB) dependent pathway
Resulting to metabolic effects of insulin.
Insulin mechanism of action
Insulin binds to IR
Initiates series of phosphorylation reaction and gene expression
Glut-4 transports glucose from outside to inside
Glycogen, lipid and protein synthesis
Termination of Insulin/IR signaling
- Insulin down- regulates own receptor by receptor-mediated endocytosis and degradation pathways
- Inactivation of IRS protein by serine/threonine protein kinase
- Activation of “suppressor cytokines signaling” SOCS which reduces acty levels of IR and IRS proteins.
Biphasic phase of insulin that involves release of newly formed insulin.
2nd or late phase
Insulin is catabolic/anabolic
Catabolic
Insulin is catabolic/anabolic
Anabolic
Biphasic phase of insulin that is short lived and prompt.
1st (early phase )
Regulation of insulin
Glucose enters Bcells by glut-2 Glucose to G6P by glucokinase Send signals to increase ATP/ADP ratio Closes K channel Depolarize Opens Ca channel CA entry Stimulates insulin secretory granule Release insulin thru exocytosis
Secreted in equinolar amts as insulin.
Measured in the blood to quantify endogenous insulin production
C-peptide
Insulin receptor has a and B subunit. Which subunit contains tyrosine kinase on cyto solid surface?
Beta subunit
Importance of somatostatin is not clearly established but..
It can inhibit insulin and glucagon secretion thru paracrine mechanisms depending in what the body needs
Major stimulus of glucagon
Low blood glucose
Pancreatic polypeptide is stimulated by
Various GIT hormone
Vagal stimulation
Determines net flow of hepatic metabolic pathway
Insulin/glucagon ratio
Primary target organ of glucagon effect
Liver
Insulin action
Promotes protein synthesis Inhibits protein degradation Ptromotes TGL synthesis Inhibits lipolysis Has effects on satiety
Glucose sensor of B cells
Glucokinase
Somatostatin is also found in
Hypothalamus and GIT
Primary site of degradation of glucagon
Liver
80% in single pass
Stimulates glucagon secretion
Low blood glucose High aa (arginine, alanine)
Sympa NS stimulation (B2 adrenergic)
Stress
Exercise
Peak of first or early phase
5 min
Insulin is stored in secretory granules in Zn-bound crystals. It is released by exocytosis of granule contents ff by endocytosis. It has 2 biphasic release
1st (early phase)
2nd (late phase)
Primary stimulus and regulator of insulin
Glucose
Glucagon circulates in bound/ unbound form
Unbound form
Thus has short half life of 6min
Duration of 2nd phase
10 min - 1 hr
Insulin is degraded by what enzyme found in liver, kidney and other tissue
Insulinase
Biphasic phase of insulin that is responsible to peak insulin secretion after meal
First or early phase
Entry kg glucose into B-cells is facilitated by
Glut-2 transporter
Action of insulin
*Glucose uptake (by GLUT-4 availability in ms and fats)
*Glucose use
Glycogenesis
*Glycolysis
Decrease glycogenolysis
Specific in liver FA synthesis and VLDL decrease gluconeogenesis Decrease x Decrease urea cycle activity
Specific in ms
Aa uptake
Protein synthesis
Decrease proteolysis
Specific in adipose tissue
Production of a-glycerol phosphate
Esterification of fats
Decrease lipolysis
Glucose is phosphorylated into G6P by what enzyme
Glucokinase
Half life of insulin
5-8min
Glucagon is a primary counter regulatory hormone by
Increase bld glucose thru hepatic glucose output
Increase glucose production thru (increase glycogenolysis, gluconeogenesis, and decrease glycolysis, glycogenesis and inhibits FFA synthesis from glucose)
Insulin + receptor results to cross phosphorylation of B subunits leading to recruitment of adaptor proteins such as..
IRS (insulin-receptor substrates)
SHC protein
APS protein
Biphasic phase of insulin that involves release of preformed insulin.
First or early phase
Inhibits glucagon secretion
Somatostatin
Insulin
High blog glucose
Primary counter regulatory hormone of insulin
Glucagon
Biphasic phase of insulin that is slower onset and maintained for considerable periods
2nd or late phase
Insulin is responsible for maintaining the upper limit of blood glucose and FFA by
Promoting glucose uptake and utilization by muscle and adipose tissue
Increase glycogen storage in liver and ms
Decrease glucose output by liver
