1st test endocrine Flashcards
Wolfram Syndrome
rare progressive degenerative transmited AR DNA
central diabtes insipidus DM optic atrophy - blindness neurosensorila deafness neuro/psch alterations
neurohipofisis
post pituitary
connected to hypothalamus via axons
secretes vasopressin and oxytocin
Nephrogenic Diabetes Insipidis
ADH is okay but its afunctional
rec is messed up
poor response of renal tube cells
classification in NDI
primary familiar congenital (AD X linked)
secondary NDI
tubulointersticial nephroamties
polycystic kidney, distal tubular acidosis, cistinosis, idiopathic hypercalciuria, renal amyloidosis
secondary tubularintersiticail nefropathy
litio
demeclocicline
DIC
altered conservation of body water as a consequence of inadequate ADH
large V of water eliminated in urine
poliruia
compensatory [plidipsia
psycogenic polydipsia or primary polidipsi
increased ingestion of water more than necessary –> physiological suppression of ADH due to over hydration and hypotony –> polyuria (sudden 10-12L), nicturia, polydipsia
hipoosmotic polyuria
hypovolemia and hypotension
hypertonic dehydration
astenia with sleep disorder
hipernatremia
PP seen in
young women
psychiatric px
fenotiazide (dry mouth) takers
hypothalamic lesions alteraing thirst center
normal urine
50cc/hr
cause of primary DIC
immunolocial
secondary cause of DIC
tumor qx trauma IC tumor = 3rd cause craneofaringeoma in kids lung breast CA metastasis in adults supraselar germinomas intraselar GI tumors via metastasis toxoplasmosis, herpes simplex, AIDS, qx truma Lawrence Moon Biedel Synrome
linfocitic hipofifis (infiltariotn)??
phases of DIC from head trauma
polyuria 4-5 days
secondary to transsphenoidal qx
2-3d after qx -> polyuria
this alters ADH liberation
oliguria 4-5d
(cell degeneration with liberation of preformed hormone into circulation)
polyuria and polydipsia (compensatory)
neurosecretory cell death causes Permanent ADH deficit
cx of Lawrence Moon Biedel syndrome
obesity, mental deficit, pigmental rhinitis…
dx DI
<1010 urine density
urine and serum electrolytes (one high one low)
hypernatremia
plasma osmolarity > 350 mOsm/L
urine osmolarity (lower)
prueba de depuracion aquosa - remove all diuretics, solutions, ingestion - (doesn’t have - oliguria - anuria) if they do will have polydipsia from IC liquid –> coma (2-4hr)
what is endocrinology
- Branch of internal medicine that studies regulatory functions of hormones
anatomy of hypothalamus
- Weight = 4gr
- 0.3-04cm
tx DI
desmopresin - agonist of ADH uniting with V2 rec of acuoporin –> tubular water reabsorption
VO/SC/Spray
1-2mg every 6hr, px responds within days
something about falcemics?
hydration
clorpropamid - increases ADH action - psychiatric use
carbamacepine - increases ADH liberation (high doses) > 1200mg/day
irrigation of hypothalamus?
?
- Primary capillary plexus Hypophysary arteries ant branches
limits of hypothalamus
- optic chiasm (ant)
- thalamus/3rd ventricle (sup)
- mamillary bodies (post),
- infundibulo tallo-hipofisario (int)
ADH is also produced where
adenohipofisis
periventricular nucleus
SSIADH
excessive persistend ADH secretion , not responding to inhibition -
retain water
low plasma osmolarity - dilution, high urine osmolality
edematized
oliguria
water retained
hyponatremia
nypoosmolarity
2 connections of hypothalamus hypofisis
- Sistema porta hipotalámico-hipofisario.
- Originates in eminencia media.
- retrógrado & anterógrado flow
- parvocelulare hypothalamic neurons (parvo = small [short axón -magnocelulares]) secrete hormones that reach AP
- Neuronas hipotalámicas magnocelulares send axons to NP.
○ Porta-hipotalamo-hipofisario = anterior (circulatory) • Eminencia media is where portal system is formed ○ Neuronas neurohipofisarias magnocelularesPosterior from hypothalamic neuronal axonal connection
MC of SSIADH
change personality irritable confusion hallucinate nausea vomit, extrapyrimadial signs
convulsion crisis, altered consciousness
DX criteria of SIADH
TABLE… fundamental
complentary
uricemia < 4mg/dL
BUN < 10mg/dL
FENa > 1%
functions of hypothalamus can be
endocrine or non endocrine
tx of SIADH
hydration - hypertonic saline ADH blockers (carbonate litium) loop diuretic
vaptan (conivaptan, tolvaptan, relcovaptan)
endocrine function of hypothalamus
1. parvocelular neurons secrete liberating facors or inhibitory that act at AP. Magnocelular neurons (supraóptico & paraventricular nuclei) send axons to NP, store these products
ADH does what
retains water
reabsorbs Na+
secretes K+
no endocrine function of hypothalmsu
Based in nuclei that regulate sleep, thirst, T, appetite, libido, weight.
hyperprolactinemia
incrased prolactin plasma levels > 20ng/mL in men
too much produced or liberated and systemic effects
> 25ng/mL in wommen
2 separate occations
amenorrea,/oligomenorrea galactrea
produced in lactotrope cells
What is hypothalamus?
- The hypothalamus controls theanteriorand posterior pituitary’s release of hormones differently.
substances that stimulate prolactine/etiology of hiperprolactinemia
TRH striadol GnRH AVP oxytocin Serotonin AcH glutamate
physiological : stimulation of pezon sex sleep ovulation pregnancy neonatal life ovulation lactancy ingesting AAs exercise emotional stress and physical Trauma qx Hipoglucemia IAM Convulsiones del lóbulo temporal Síncope Venopunción Deshidratación Dolor
DRUGS
sub that inhibit prolactin
dopamine opoid GABA GAP somatostanina, .........
first cuase of non tumoral hipoerprolactinemia from drugs
EXAM
cause 25-100ng/dl
metoclopramida, risperidona, fenotiazina à >200ng/mL)
if MC change tx -
stop for 3 days , reread levels to see if secondary to drug
Si la medicación no puede ser descontinuada y el inicio de la hiperprolactinemia no coincide con el inicio de la terapia, se recomienda MRI de hipófisis en busca de prolactinoma.
increased prolactin due to hypothalamic damage
tumors granulomatouse and infiltrative diseases cranial RT vascular cause seccion of tallo
also alterations of hypofisis
hyperprolactinemia from hypothyroidism
due to increased TRH –> secrete effect on lactotrope cells (more sensibile)
decrease sensibility of lactrotoope cells to dopamine
increased VIP
decrease in PRL wasting in circulation o aclaramiento renal (hipometabolic state lowers GFR) - more in plasma
hypofisiary hyperplasia (like puberty )
most cells in pituitary are…?
????
polyscystic ovary syndrome - PRL
hyperandrogen and estrogen –> lots of estradiol which stimulates prolactin liberation
increase number and size of lactotropes
decrease of dopamine hypothalamus
increased transcriptionfor PRL
resistence to dopamine acction
adrenal deisease PRL
increased transcription
increased lactotrophe cell differentiation
PRL increased secretion
liver disease PRL
cirrhosis decreased hepatic circulation of PRL
increases steroidogenesis - more estrogen/estradiol
decreased hypothalamic dopamine (dad)
Renal disease PRL
rests action nof dopamine
resists…..PRL
isiopathic hyperprolactimea
microprolactinomas?
20% of cases
MRI cortes
ateration /inactivation of dopamine rec
lesions of thorax wall PRL
toractomy masectom trauma mammoplasty dermatitis burns herpes zoster breast cyst nipple piercing
any stimulation of 4,5,6 intercostal nerve increases neuronal afferent stimulation postsynaptic increased serotonin liberation with stimulates TRH –> PRL increase
ectopic production of PRL
hypernefroma renal adenoCA bronchogenic CA uterine fibroma ovaric teratioma gonadotroma ovaric dermoid cyst Hodgkin linfoma and T cell linfoma
macroprolactinoma and med form before??
MC of hiper PRL
increases hypothalamus of dopamine and beta-endorphins
rec of PRL in GnRH cells
down regulation of GnRH (hypogonadism, galactorrea, hirsutism)
decreasd ovarian secretion of estradiol and progesterone (no LH, FSH for steroidogenesis at ovary_
decreased testosterone
decreased 5alfa-reductase (converts dihydro..to testosterone)
- Galactorrea: 80% hiperprolactinémicas, 30% hiperprolactinémicos.
- Hipogonadismo hipogonadotrópico. Hay ↓FSH, ↓LH, debido a que:
a. Neuronas de GnRH tienen receptores para PRLà ↓liberación de GnRH.
b. ↑PRL à ↑DA + ↑β-endorfinas en hipotálamo à ↓liberación de GnRH.
women Hipoestrogenismo à ¾ Amenorrea / oligomenorrea. ¾ ↓libido. ¾ ↓lubricación vaginal à Dispareunia ¾ Osteopenia/osteoporosis: ↓densidad ósea (-25% lumbar), irreversible ¾ Irritabilidad ¾ Oleadas de calor. Infertilidad.
men Hipoandrogenismo: PRL à ↓actividad 5α-reductasa à ↓dihidrotestosterona. ¾ Disfunción eréctil. ¾ ↓libido. ¾ Oligospermia à infertilidad. ¾ ↓volumen eyaculado. ¾ Ginecomastia. ¾ Osteopenia/osteoporosis.
la mujer.
¾ PRL à ↑producción ovárica de andrógenos y adrenal de DHEA-S (sulfato de dehidroepiandrosterona).
¾ PRL à ↓síntesis hepática de SHBG à ↑proporción de esteroides sexuales libres (biológicamente activos) en plasma.
Presentación clínica
2. Prolactinemia >200ng/mL.
3. Clínica: galactorrea, hipogonadismo hipogonadotrópico, hirsutismo, efecto de masa (neuroftálmicos, hipopituitarismo).
sampling in hiperPRL
2 separate occasions
1-2 hour after waking up
discart other causes (meds, liver, preg, renal failure, mammillary stimulation, sex)
macroprolactinemia in asymptomatic px (no galactorrea but elevated levels - sim hormones?)
drugs
1:100 dilution
dx evaluation of hiperprolactimea
hipofisary macroadeoma
measure PRL
below 200
1:100 dilution - discart hook effect if above ya tu sabe
if below 200 - pseudoprolactinoma (something else compressing, dopamine e obstructed)
more than 200 - macroprolatinoma1)
Tomar muestra adecuadamente:
¾ 2 muestras separadas por 20-40 minutos >1h después de haber despertado, sin tener sexo (coito, manipulación de mamas) o ejercicio.
¾ Diluir muestra 1:100 para evitar efecto hook.
¾ Excluir mediante historia clínica y examen físico: embarazo, uso de fármacos; mediante laboratorio: hipertiroidismo (T4 libre, TSH), IR (creatininemia), IH (transaminasas y fosfatasa alcalina).
Si nada de lo anterior es evidente o prolactinemia >100ng/mL:
2) MRI de hipófisis antes y después de administrar gadolinio.
¾ Si se confirma adenoma hipofisario à
û Evaluar función hipofisaria
û Campimetría visual computarizada (en particular si es un macroadenoma).
¾ Si no se confirma adenoma hipofisario à hiperprolactinemia idiopática.
tx of hiperprolactinmeia
dopamine agonsits
Tx de elección. Se unen a D2 en superficie de lactotropas normales y tumorales y producen inhibición de PRL, como lo haría la DA, restauran función gonadal y causan regresión tumoral en 80-90%. Se deben usar de por vida.
a) Bromocriptina. Aprobada por FDA.
b) Cabergolina. Aprobada por FDA. La más potente y se da 1-2x/semana.
c) Quinagolida.
d) Lisurida.
e) Pergolida.
qx - if px wont take drugs,
1. Tumorectomía transesfenoidal, indicada en:
¾ Intolerancia/resistencia a los agonistas de DA. ¾ No deseo de consumir agonistas DA por largo tiempo.
¾ Crecimiento de prolactinoma a pesar del uso de estos. ¾ Deseo de embarazo por parte de la paciente (aunque la mayoría no crece durante el embarazo: indicación relativa).
¾ Prolactinomas con componente quístico. ¾ Preferencia del paciente.
¾ No mejoría de los campos visuales tras 1-3 meses de agonistas DA
- Agonistas de DA. Tx de elección. Se unen a D2 en superficie de lactotropas normales y tumorales y producen inhibición de PRL, como lo haría la DA, restauran función gonadal y causan regresión tumoral en 80-90%. Se deben usar de por vida.
a) Bromocriptina. Aprobada por FDA.
b) Cabergolina. Aprobada por FDA. La más potente y se da 1-2x/semana.
c) Quinagolida.
d) Lisurida.
e) Pergolida.
Tumorectomía transesfenoidal, - Radioterapia hipofisaria. Fallo en tx médico y quirúrgico. 150-200 rads/día, 5x/semana por 5 semanas. Dosis total: 4,500-5,000rads. Alta probabilidad de desarrollar hipopituitarismo.
tx if drugs and qx don’t work for hiperPRL
- Radioterapia hipofisaria. Fallo en tx médico y quirúrgico. 150-200 rads/día, 5x/semana por 5 semanas. Dosis total: 4,500-5,000rads. Alta probabilidad de desarrollar hipopituitarismo.
2 types of hypothalamic cells
hypofisiotropic hypothalamic (liberators and inhibitors)
vs
neurohipofisiary hypothalamic (oxytosin and AVP/ADH)
liberators do what?
induce hormonal secretion
hypothalamic liberating hormones
TRH –> TSH and prolactin
CRH –> ACTH/corticotropin secretion @ suprarenal gland and proopiomelanocortin peptides (MSH, beta-endorphin)
GnRH –> LH and FSH (gonadotropins) @ genitals and Prolactin
GHRH/somatocrinin –> GH/somatotropin in pulses @ all organs
GH secretion is increased by
exercise
starvation (hypoglycemia)
Sleep
relationship between dopamine prolactin and TRH
Prolactin is under tonal dopamine inhibition, andexcess TRH levels suppress dopamine. Thus, prolactin levels will increase as dopamine decreases.
hypothalamic nucleus/region for TRH
paraventricular (medial portion)
hypothalamic nucleus/region for CRH
paraventricular (anterior portion)
hypothalamic nucleus/region for GnRH
arcuate-preoptic (ant)
hypothalamic nucleus/region for GHRH
arcuate
Hypopfisis cell populations that produce for TSH
tirotrope cells
Hypopfisis cell populations that produce
Prolactin
lactotrope cells
Hypopfisis cell populations that produce
ACTH
corticotrope cells
Hypopfisis cell populations that produce
FSH and LH
gonadotrope cells
Hypopfisis cell populations that produce
GH
somatotrope cells
melanocyte inhibiting factor inhibits
release of MSH
which are the hypothalamic inhibiting hormones
dopamine (DA) - prolactin release inhibiting hormone - inhibits liberation of Prolactin and lactropes and TSH
somatostatin (SS) - inhibits liberation of PRL, TSH, GH
region/hypothalamic nucleus for dopamine
arcuate
region/hypothalamic nucleus for somatostatine
supraquiasmatic periventricular region (ant)
lactancy hormone that stimulates milk ejection
oxytocin
what do AVP/ADH do
stimulate reabsorption of water
non endocrine functions of the hypothalamus
○ Thirst, temperature, sexual desire, etc thorugh hypothalamic nuclei
anterior pituitary hormones are produced by what
parvocellular hypothalamic neurons
anterior pituitary hormones
ACTH LH, FSH GH TSH Prolactin MSH
weight of pituitary gland
0.5-0.9gr
blood flow of pituitary gland
very vascularized
0.8ml/gr/min
Situations in which Pituitary can double size:
- Pregnancy
- Puberty (especially girls)
- Primary hypothyroidism
- Primary hypogonadism
% gland of adeno vs neurohipofisis
75% adeno
25% neuro
embryological origin of adenohipofifis
Bolsa de Rathke (evaginación del techo de la orofaringe primitiva).
embryological origin of neurohipofisis
Evaginación del hipotálamo ventral y del piso del 3° ventrículo
irrigation of adenohipofisis
Arteria hipofisaria superior + sistema porta hipotalámico (0.8ml de sangre/g de tejido)
irrigation of neurohipofisis
Arteria hipofisaria media + Arteria hipofisaria inferior
Venous drainage of pituitary glland
cavernous senos –> sup and inf petrous senos –> yugular veins –> SVC –> RA
pituitary cell types
- Nulas - don’t secrete hormones, do secrete NTs
* Secretory - classified in 5 types
cx of somatotropic cells
@ lateral portions
acidofiles
50%
function of somatotropic cells in skeletal muscle
increases muscle mass
increases AA capitation
decreases proteolysis
decreases glucose capitation (CONTRAREGULATOR) –> hyperglucemiant
function of somatotropic cells in adipose tissue
decrease capitation of glucose increase lipolysis (degradation of TGs/FAs) -increases activity of hormonosensible/GH lipase
function of somatotrpic cells in liver
increase protein synthesis
increases gluconeogenesis (formation of glucose from lactate, pyruvate, glycerol, AAs)
increases IGF-1 synthesis (somatomedine C) –> which in turn increases bone lineal growth , muscle and visveral growth
what is IGF-1
a cofactor that helps GH functions/efficacy = NECESSARY
cx of lactotrpic cells
acidofiles
posterior
10-25%
function of lactotropic cells
in mammary glands increase milk production during lactancy
decreases GnRH (FSH LH) –> amenorrea
cx of corticotropic cells
basophils
15-20%
function of corticotropic cells
@ adrenal cortex
increase growth, development, vascularization
increase LPL capitation which increases synthesis and adrenal secretion of glucocorticoids (cortisol) and sex steroids (androgens and estrogens)
increases melanin synthesis
stimulate mineralocorticoids, sex hormones
increase CyP450 : cholesterol –> pregnenolone
decrease GnRH and GH
cx of gonadotropic cells
basophiles
anterior
10-15%
function of LH in women
theca cells: make androgens - testosterone and androstenedione by theca cells in ovaries that by diffusion pass to granulouse cells (through aromatase converts androgens to estrogens)
ovaric follicle: rupture causing ovulation
function of LH in men
Leydig intersticial cells of testicle: synthesis and secretion of testosterone
decreases hypothalamic secretion of GnRH and pituitary secretion of FSH and LH by RAN
function of FSH in w0men
acitmates aromatase
androstenedione –> estrone (E1)in adipocytes
testosterone –> estradiol (E2)
growth and follicular development
dominant foliculo selection
production of inhibine by granous cells in ovaries which cause less secretion of FSH from pituitary
estrogen byexcellence
estradiol
function of FSH in men
proliferation of seminiferous tubes
principal determinant of testicular volume
spermatogenesis
production of inibine thru sertoli cells in the testicle –> decreases pituitary FSH secretion
cx of tirotropic cells
anterolateral
anteromedial
10%
function of tirotropic cells in thyroid
stimulate vascularity and thyroid growth
stimulate production of T3 and T4
morphological changes causing pseudopod formation increases iodine trapping and bone reabsorption
(that’s why hyperthyroidism causes early osteoporosis)
decreases colloid, fotitias of IC colloid
stimulates tiroglobulin hydrolysis
- Iodine metaoblism phases stimulation
- Increases mRNA of tiroglobulin and thyroid peroxidase
- Increases 5’ deyodase I (T4–>3 peripheral)
- Glucose captation, O2 consumption and CO2 production +
hormones that share alfa subunits
LH
FSH
TSH
80% of somatomelina C / IGF-1 produced where?
liver
but it acts in the muscle
=
how can IGF-1 lead to microsomal children
mothers pancrease stimulates insulin also stimulating IGF-1
which homones are glucoproteins
TSH
LH
FSH
share homology
which are somatotropins
PRL
GH
irrigation of hypothalamus
thru superior hypophyseal artery
TFs involved in development of adenohipofisary cells
- POU1F1 (Pit-1): lactotropas, somatotropas y tirotropas.
- Prop-1: gonadotropas. (promiscuous)
- T-pit: corticótropas.
TSH also stimulates
estrogen
ADH nucleus
is a nonapeptide that is synthesized predominately in thesupraoptic nucleusof the hypothalamus, and secreted from theposterior pituitaryupon stimulation of these cell bodies.
primary stimulus for ADH secretion
The primary stimulus for antidiuretic hormone (ADH) secretion is anincrease in serum osmolarity. A loss of intracellular water from hypothalamic osmoreceptor neurons bathed by hyperosmolar blood will stimulate ADH release. Other factors thatincreaseADH secretion include: • Pain/stress • Hypoglycemia • Nausea • Volume contraction • Nicotine and opiates • Angiotensin II
2 primary functions of ADH
- Regulate serum osmolarity
- Maintain (increase)blood pressure
- Increases water reabsorption in renal colector tubules
- Modualtes BP by increasing SM arterial tone
Stimulates liberation of ACTH by hypofisary corticotrope cells
oxytocin nucleus
Oxytocin is a nonapeptide that is primarily produced by theparaventricular nucleiwithin thehypothalamus, and secreted from the posterior pituitary
how does oxytocin travel to posterior pituitary
Like ADH, oxytocin travels to the posterior pituitary via carrier proteins calledneurophysins.
stimulus for oxtocin secretion
The major stimulus for oxytocin secretion issuckling. Other positive stimuli includedilation of the cervixandorgasm, Bconfidence , memory, conection and empathy.
effects of oxytocin
The primary effects of oxytocin aremilk ejection@ lactation anduterine contraction @ labor.
adverse effects of oxytocin
- Hyponatremia and seizures(due to anti-diuretic properties similar to antidiuretic hormone)
- Subarachnoid hemorrhage
- Uterine rupturein pregnant patients
irrigation of hypothalamus
MCA of ICA
function of thyroid hromones
Thyroidhormones: • induce central nervous system maturation during growth • increase basal metabolic rate • increase cardiac output • promote bone growth
what stimulates TRH
cold
what inhibits TRH
stress
what inhibits TSH
DA, SS, cortisol, GH, T3 y T4 thyroxine
TSH does what
stimulates T3 and T4 secretion from thyroid and - neg feedback to decrease TRH and TSH
@ thyroid increase growth and vascularity, capitation of I- inorganic,
increases oxidation of Inorganic I- creating more reactive yodant species (EIRs)
4) ↑Incorporación de EIR en residuos tirosina de la tiroglobulina[4] à ↑formación de yodotirosinas: MIT[5] y DIT[6].
increases formation of thyroid peroxidase
6) ↑Acoplamiento de yodotirosinas: MIT + DIT = T3, DIT + DIT =T4.
7) ↑formación de la gota de coloide.
8) ↑Liberación de T3 y T4.
what increases TSH
TRH and estradiol
difference between types of hypothyroidism
a. Primary: damage to thyroid gland: ↑TSH + ↓T3 y T4.
b. Central: ↓TSH (o inapropiadamente normal) + ↓T3 y T4.
Secundary: damage/disfunción of tirotrpic cells that makeTSH.
Terciario: damage /disfunción to hypothalamic neuronas that produce TRH.
2° y 3° son bioquímicamente indistinguibles.
- Pirmary = @ thyroid gland ○ High tsh ○ Low T4 - Secondary ○ Both low - Tertiary ○ Both low
90% of T3 in circulation comes from
T3 circulante (forma biológicamente activa) se deriva de la T4.
feedback of increased cortisol
less hypothalamic secretion of CRH and hypofisary secretion of ACTH (por RAN)
what increases ACTH
CRH and AVP
Stress, trauma , int. qx, infections, hypoglicemia (similar to GH contraregulatory hormones)–> ACTH and catecolamines @ adrenal gland
cortisols effect on hormones
AVP, ↓CRH, ↓ACTH, ↓GnRH.
what is cortols made from
cholesterol and needs cytochrome p450
cx of cortisol
- Catabolic - hyperglucemic
- Anabolic only I liver –> + cytocrome p450
- Antiinflammatory
- Immunosuppressor
different types of hypoadrenalism
c. Primary (Addisons disease): damage to adrenals ↑ACTH + ↓cortisol + hiperpigmentación of skin and mucus due to RAN deficit).
d. Central: ↓ACTH (o inapropiadamente normal) + ↓cortisol.
Secundary: damage/disfunción in corticotropas cells that produce ACTH
Terciary: damage/disfunción hipotalámic neurons that produce CRH.
Primary Adrenal Insuff
- ACTH up - Low cortisol
Secondary @ corticotrope cell lesion
- Both down
Hypofisis trurmor of ACTH
- Both up
Adrenal tumor that secretes cortisol
- Low ACTH - High cortisol
circadian rhythm of cortisol secretion
- Different quantitites @ different times
- máxima @6:00-8:00am;
- mínima @12:00am.
how to know if there is a loss of cortisol circadian rythm
- Para determinar si hay pérdida de este ritmo circadiano (propio del Síndrome de Cushing Endógeno) se mide cortisolemia @8:00am (5-25μg/dL) y @4:00pm (suele estar al 50% respecto a 8:00am, es decir, 2.5-12.5μg/dL)
GnRH pulse
Hipotálamo produce GnRH en pulsos de 60/90-120 minutosà sistema porta va a gonadotropas adenohipofisarias à ↑FSH (end) y ↑LH. (beginning)
different types of masculine hypogonadism
primary (hypergonadotropic) damage , testicular dysfunction - ↑FSH + ↑LH + ↓testosterona + ↓inhibina.
Central (hypogonadotropic) - ↓FSH + ↓LH + ↓testosterona + ↓inhibina
…secondary - damge corticotropes that produce FSH and LH
…tertiary - damage to hypothalamic neurons that produce GnRH
aromatase
- Testosterone to estradiol (E2) -↓hipotalámic secretion of GnRH and pituitary FSH y LH (por RAN),
when secreción is >200pg/mL during >40-50h will be ↑secreción hipotalámica of GnRH (por retroalimentación positiva [RAP]) à↑↑↑LH (pico de LH) à ovulación.
○ Estradiol negative feedback vs LH, FSH, GnRH
- Androstenediona à estrona (E1). ¾ Also pulsatilie - If > 200mg/dl > 40-50hr --> negative feedback - more than this time --> postiive feedback --> dominant follicular rupture --> primary oocyte = OVULATION ¾ Andrógenos à ↓secreción hipotalámica de GnRH e hipofisaria de FSH y LH (por RAN). ¾ Inhibina? - Can only inhibit FSH - not LH
feminine hypogonadism
- Primary (hipergonadotrópic): damage disfunción of ovary: ↑FSH + ↑LH + ↓estradiol + ↓inhibina.
- Central (hipogonadotrópico): ↓FSH + ↓LH + ↓testosterona + ↓inhibina
Secundario: damage/disfunción en corticotropas productoras de FSH y LH.
¾ Terciario: damage/disfunción de hipotalámic neurons that produce GnRH.
where is the Kiss1 gene
in hypothalamus (núcleos anteroventral periventricular [AVPV] y arcuato), placenta and oncocytes --> produces 145 AA protein that is cleabed into 4 peptides: (Kisspeptines - ligands of Kiss1-R (GPR54 linked to G protein expressed in productor neurons of GnRH) ○ Discovered in philadelphia - hersheys kisses
- Kp54 (metastine), Kp14, Kp13, Kp10
function of kisspeptins
Sex steroids increase Kiss1 gene expresion in AVPV nucleus and degrease it inn arcuate nucleus –> LH peak
Stimulate GnRH liveration
Initiate puberty
¾ Regulation of ovulation (neuroendocrine)
¾ Initiation, maintenance, and regulation of fertility
3 circulation forms of prolactin
- native PRL (de 23.5 kDa). the one that is normally secreted in 6-14 pulsos during the day(60% while sleeping).
- Big-PRL (de 50kDa).co secreted in small quantities
- Big-Big-PRL (de 150kDa). also cosecreted in small quantities
macroprolactina
all 3 PRL + 1 IgG
immunoreactive
low biological activity
dx macroprlactinemia
measure prolactin precipitación inpolietilenglicol o cromatografía . gel
when to suspect macroprolactinemia
Suspect macroprlactinemia? - fem, high prolactin, no drugs that stimualte , no galactorrea - at expense of macroprolactins, also inhibit GnrH
in asymptomatic px with hyperprolactinemia
inhibitors of PRL secretion
Dopamina[1][2] Somatostatina GABA (ácido γ-aminobutírico). GAP (péptido asociado a GnRH) Calcitonina.
stimulators of PRL secretion
Estradiol[3] TRH GnRH AVP Oxitocina VIP Serotonina Bombesina
Galanina Histamina Neuropéptido Y Sustancia P Angiotensina II Neurotensina Péptido histidina-metionina
Physiological factors that liberate PRL (date night)
stimulación de las mamas Coito, especialmente en mujeres Sueño Ovulación Embarazo Vida neonatal Lactancia Ingesta de aminoácidos Ejercicio
ACTH does what @ adrenals
increases growth and development of adrenal cortex
increases adrenal capture of lipoproteins (cholesterol is substrate for adrenal steroidogenesis)
increases activity for CyP450scc, enzyme that transforms (cutting lateral chain) cholesterol –> pregnenolone
increases stimulation of MSH alfa-R –> which increases synthesis of melanin by melanocytes
action of kisspeptines in hypothalamus
increases secretion of GnRH to begin puberty
neuronendocrine control of ovulation
initiation, maintenance, metabolic regulation of fertility
Prolactin function
stimulates production of maternal milk during latency
differentiating types of hyperthyroidism
Hyperthyroidism - Primary ○ Low TSH ○ High T4 - With levated TSH and T4
Hipergonadotropic Hipogonadism
- High LH and FSH
- Low estradiol , low testosterone
Hipogonadotropic Hipogonadism
- Both low
cx of hypofisary adenoma
- Benign tumors of hypofisial gland
- 10-15% of IC neuplasias
- 3rd cause + Fc
- 90% of hypofisial neoplasias
% of hipofisary adenomas that are prolactinoma
45%
□ Inhibit GnRH can call a combined syndrome
epi cx of prolactinoma
○90% Micro in women, 60% macro in men
○ 3rd decade women
○ Men older
(Son 8 veces más frecuentes en mujeres y se suelen diagnosticar entre 20-40 años.
MC of prolactinoma in men
disfunción eréctil, disminución volumen testicular y del eyaculado, oligospermia, ginecomastia., glactorrea, low libido, infertility, azoospermia
what is prolactinoma
○ Tumor of lactotrope cell line mostly in adenohipofifsis ‘
○ Cosecretion of hormones and PRL level hyperprolactinemia --> decreased secretion GnRH --> decreased LH and FSH
pseudoprolactinoma
effecto de tallo - too much prolactin from compression of tallo
macroadenomas even if they aren’t prolactinomas cause hyperprolactinemia < 200ng/mL due to effecto de tallo
MC of prolactinoma in women
amenorrea, oligomenorrea, disminución lubricación vaginal, dispareunia, oleadas de calor, osteopenia/osteoporosis. Falla en menarquia, regular period with short lutea fase, infertility, low libidio, galactorrea
i. Inhhibition of GnRH
MC of prolactinoma common to both sexses
decresed libido, infertlility e. Reduction of bone mass and osteoporosis
mass effect MC of prolactinoma
i. Loss of vision
ii. Headache
iii. Convulsions
iv. Hydrocefaly
v. Unilateral exoftalmo
vi. Paralysis of craneal nerves
○ Neurological/oftalmological ○ Headache, IC HTN, convulsions, apoplejia, compression of quiasm
Hook Effect - de cancho
results in elevated PRL levels which interfere with immunoradiometric ensayo and arrojan a abnormally low cifra (20-200ng/ml) what would lead one to believe its a nonsecreting macroadenoma
to aboid this sample should be diluted 1:100 if there is a pituitary macroadenoma and prolactinemia < 200
if its still in 20-200 range its a pseudo prolactinoma
i. >200ng/dl
ii. Interference with radioimmunoensayo
iii. Low PRL
before samplimg for prolactinoma what is important to consider
i. Take prolacin 1-2hr at wake up to aboid false +
ii. 2 separate elvated tests
iii. Discard hyperprolactinemia (pregnancy meds 25-100ng/ml, hypothyroidism, renal insuff, or hepatic insuff)
hipofisial adenoma 20%
somatotropoma
○ High GH
○ Gigantism , acromegaly
hipofisial adenoma 10-12%
corticotropoma ○ High ACTH
○ Cushingnhibit GnRH
® So these we cause combined sydrome
hipofisial adenoma 1-2%
tirotropoma ○ High TSH
○ Bocio and hyperthyroidism
hipofisial adenoma 15%
gonadotropoma
○ High FSH, LH ○ No clinical syndrome
hipofisial adenoma 5-10%
tumor of celulas nulas
what is hypopituitarism
○ Low hormonal secretion (2 or more)
○ Can be total
Syndrome –> decrease/absence of 1 or more hormones of pit. Gland
mechanisms for hypopituitarism
§ Tumor compresses hypothalamus - decreasing § Compressing pit. Gland § Compression of THH § Decrease of pit. Irrigation § Necrosis of hipofisis
what is combined syndrome
- Combined syndrome of hypersecretion of 1 hormone associated to decrease in secretion of 1 o more adenohipofisial hormones
microadenoma
< 10mm
what is corticotropoma
hypersecretion of ACTH –> hyperproduction of adrenal cortisol –> decreased GnRH –> decreased LH, FSH, GH
examples of microadenomas
prolactinoma
corticotropoma
macroadenoma
> 10mm
○ More in adults
○ Mechanical compression of hypothalamus, hypofisis, infundibulo, portal vessels --> focal pituitary necrosis ○ (craniofaringioma in kids)
neurological MC of hypopituitarism??
- Cefalea. 4. Epilepsia del lóbulo temporal. 7. Alteración de conciencia (somnolencia, estupor y coma).
- Parálisis de NC III, IV, VI (compresión senos cavernosos). 5. Rinorrea de LCR (si destruye piso de silla turca). 8. Defectos de campos visuales (hemianopsia bitemporal; por compresión del quiasma óptico).
- Hidrocefalia obstructiva (compresión 3° ventrículo). 6. Obstrucción vía aérea nasal. 9. Disminución agudeza visual y ceguera (compresión del nervio óptico y de las cintillas).
hipofisial apoplejia
Spontaneous Infarto/hemorrage of hypophysary adenoma (10-15%) clinically in 66%.
local consequences of hipofisial apoplejia
Signos de irritación meníngea: cefalea, Kernig, Brudzinski.
Parálisis ocular, diplopía, proptosis, defectos de campos visuales.
Alteración de la conciencia
Alteración de autorregulación simpática
Dolor facial
Hidrocefalia obstructiva
systemic consequences of hipofisial apoplejia
Hipopituitarismo: 1. Insuficiencia suprarrenal secundaria aguda: hipotensión y choque. 2. Hipotiroidismo central. 3. Hipogonadismo secundario. Silla turca vacía
wermer syndrome
(Múltiple Endocrine Neoplasia 1, las 3 P). HAD, coexistence of 2/3of the following:
1. Pituitary adenoma.
a. In 60% of NEM1, generally prolactinomas (60%), somatotropomas y corticotropomas, y generally are macroadenomas.
2. Primary Hiperparatiroidism (from hiperplasia or multiple adenomas).
a. Initial clínica-bioquímica presentation.
b. 60-90% of NEM1.
3. pancreáticos y duodenales neuroendocrinos tumors: insulinomas, glucagonomas, gastrinomas, VIPomas, somatostatinomas.
gigantism vs acromegaly
excessive secretion of GH that if before closure of hipofisis is gigantism (prominent lineal growth of long bones)
if after closure = acromegaly (exaggerated growth of bland tissues, bones of hands, feet, mandible, internal viscera)
etiology of gig/acro
somatotropoma 1. Somatotropoma productor de GH (99%). 65% son macrosomatotropomas.
- Secreción ectópica de GH: in pancreatic and lung cancer
3. excessive secretion of GHRH Eutópica: gangliocitoma o hypothalamic coristoma . b. Ectópica: Tumores islotes pancreáticos. ¾ Carcinoides bronquial, intestinal o tímico. ¾ CA microcítico de pulmón. ¾ CA medular de tiroides. ¾ Feocromocitoma. ¾ Adenoma adrenal.
general MC of gig/acro
Fatiga Intolerancia al calor Ganancia de peso Diaforesis Hiperhidrosis palmoplantar
osteomegalia in gig/acro
Prognatismo: aumento de espacios interdentales maloclusión.
Dedos engrosados y elongados (acropaquia)[1].
Rasgos faciales grotescos[2].
Crecimiento de manos y pies[3]
Tórax en tonel[4]
Dermatolomegalia ig/acro
Engrosamiento cutáneo por depósito de glucosaminoglucanos.
Hipersecreción sebácea: piel oleosa, acné, quistes sebáceos.
Hipertricosis (50%). Cutis verticis gyrata[6]
Hiperpigmentación (40%) Papilomas
Acantosis nigricans[5] (10%) Moluscos fibrosos
organomegalia acro/gig
Laringomegalia y apnea del sueño Parotidomegalia Nefromegalia Hepatomegalia Macroorquidismo Cardiomegalia (15%) asociada a ICC/ cardiomiopatía hipertrófica.
endocrinological metabolopathies in acro/gig
HTA (25%) Intolerancia a glucosa (50%) DM (25%) Hiperfosfatemia[7] Hipocalcemia por hipercalciuria[8] Nefrolitiasis Hipopituitarismo[9] Hiperprolactinemia[10]
neuropathy in acro/gig is due to
comprisive effect
neuroatropathies in acro/gig
Neuropatía periférica por compresión de nervios periféricos por osteomegalia.
Compresión de médula espinal.
Síndrome del túnel carpiano
Artropatía.
dx of gig/acro
Medir IGF-1 (somatomedina C, (+: >1ng/mL) o GH (+: >1ng/mL) en sangre a los 0, 30, 60, 90, 120 minutos.
2) MRI de hipófisis con gadolinio à
a. adenoma hipofisario: evaluación hormonal + campimetría visual computarizada
b. No adenoma hipofisario: GHRH en plasma, MRI de tórax, TAC de abdomen.
tx of gig/acro
1) Extirpación transesfenoidal. Cura 70% de microadenomas y 50% de macroadenomas.
2) Análogos de la somatostatina: lanreótido, octreótido. Inhiben síntesis de GH hasta en un 90% por somatotropas y reducen tamaño tumoral.
3) Pegvisomant. Bloquea unión a GH-R.
4) Agonistas dopaminérgicos: bromocriptina, cabergolina, quinagolida, lisurida y pergolida a dosis mayores que las usadas para prolactinomas.
5) Radioterapia hipofisaria, con el riesgo de producir hipopituitarismo. Tx dura 6 meses a 20 años, pero normaliza los niveles en 90% de casos.
Etiology of CUshing syndrome
deberse a:
¾ Exógeno. Forma más frecuente. Por el uso a dosis excesivas o prolongadas de glucocorticoides (estados inflamatorios crónicos).
Endógeno. Por tumor productor de ACTH,
endogenous causes of Cushing are classified into
ACTH dependent (excess produced due to tumor which increases cortisol production by suprarenals)
and ACTH independent (excess cortisol produced by adrenal hyperplasia/tumor)
Cortisol causes RAN on ACTH
ej of ACTH dependent causes
§ Corticotropoma hipofisario (“Enfermedad de Cushing”). 68% de casos de síndrome de Cushing endógeno en adultos.
Secreción ectópica de ACTH por tumor extrahipofisario. 12% de casos de síndrome de Cushing endógeno en adultos.
acute presentation of ACTH dependent causes of cushing
CA de pulmón 75%.
chronic presentation cushing (ACTH dependent)
v Carcinoides bronquial, intestinal o del timo.
v Tumores de células de los islotes pancreáticos, especialmente insulinomas.
v CA medular del tiroides.
v Feocromocitoma.
§ Síndrome de secreción ectópica de CRH por tumor extrahipotalámico. <1% de los casos de síndrome de Cushing endógenos en adultos.
v CA medular del tiroides.
v Carcinoide bronquial.
v CA de próstata metastásico.
ej of ACTH independent causes of cushing
§ Adenoma/CA productor de cortisol.
§ Hiperplasia micronodular/macronodular.
general MC of cushing
Obesidad centrípeta
Cefalea
Psicopatías
Miastenia proximal
cutaneuous MC of cushing
Estrías purpúricas >1cm de diámetro @ abdomen, flancos, MS, MI. Adelgazamiento cutáneo. Fragilidad capilar (equimosis o moretones espontáneos o por traumas mínimos) Hiperpigmentación (en ACTH dependiente). Cara redonda. Acné. Hirsutismo. Plétora Acantosis nigricans Micosis Pobre cicatrización
endocrinological metabolic MC of cushing
Alcalosis hipocalémica Retraso de crecimiento óseo Oligomenorrea/amenorrea. Alteración libido/ disfunción eréctil. HTA (80%) Intolerancia a glucosa y DM Hipercalciuria con Nefrolitiasis
Leucocitosis neutrofílica.
Osteopenia/osteoporosis.
Hiperlipidemia.
Poliuria.
dx of cushing
confirm biochemically dx of cushing (confirm endogenous hiperorisolism)
distinguish between ACTH dependent vs independent
distinguish between corticotropoma vs ectopic secretion
how to biochemically confirm cushing
a. Cortisol libre en orina de 24h 2-4x mayor del límite superior.
b. Prueba de Nugent: supresión con 1mg de dexametasona:
¾ 1° día de la prueba: 1mg VO de dexametasona a las 11pm.
¾ 2° día de la prueba: medir cortisolemia @ 8am y si es <1.8 μg/dL se excluye.
c. Medir cortisol salival a las 11pm: >145 ng/dL (>4nmol/L).
d. Cortisolemia >1.8 μg/dL @12nm con paciente dormido (no tiene aplicabilidad clínica).
e. Prueba de dexametasona-CRH.
how to distinguish between ACTH dependent vs independent
Determinar ACTH en plasma:
a. ACTH bajo à ACTH independiente à hacer TAC de suprarrenales.
ACTH normal (10 pg/mL) /alto à ACTH dependiente
how to distinguish between corticotropoma and ectopic secretion
MRI de hipófisis con gadolinio à (neg) à MRI de tórax + TAC de abdomen + perfil hormonal:
¾ Insulinemia à insulinoma.
¾ Catecolaminas en suero y orina de 24h + metanefrinas à feocromocitoma.
¾ Ácido 5-OH-indol-acético en orina de 24h à tumor carcinoides.
¾ Calcitonina à CA medular de tiroides.
tx for cushing
- Extirpación transesfenoidal. Cura 80%, 10-30% tiene recurrencia à 30-50% no son curados.
- Radioterapia hipofisaria. 40% son curados (85% si son <18años). El 60% no es curado pero está protegido contra el síndrome de Nelson (crecimiento excesivo de un corticotropoma + defectos de campos visuales + hiperpigmentación cutánea [cuando tx inicial es adrenalectomía bilateral])
- Mitotane (adrenolítico: destructor de adrenales) + inhibidor de la síntesis adrenal de cortisol. 80% se cura.
- Inhibidores de enzimas adrenales de la síntesis del cortisol (ketoconazol, metirapona).
- Adrenalectomía bilateral total.
10% of prolactinomas cosecrete
GH
cx of macroprolactinoma in men
estos producen prolactinemia >200ng/mL).
dx evaluation of prolactinoma
1) Tomar muestra adecuadamente:
¾ 2 muestras separadas por 20-40 minutos >1h después de haber despertado, sin tener sexo (coito, manipulación de mamas) o ejercicio.
¾ Diluir muestra 1:100 para evitar efecto hook.
¾ Excluir mediante historia clínica y examen físico: embarazo, uso de fármacos; mediante laboratorio: hipertiroidismo (T4 libre, TSH), IR (creatininemia), IH (transaminasas y fosfatasa alcalina).
Si nada de lo anterior es evidente o prolactinemia >100ng/mL:
2) MRI de hipófisis antes y después de administrar gadolinio.
¾ Si se confirma adenoma hipofisario à
û Evaluar función hipofisaria
û Campimetría visual computarizada (en particular si es un macroadenoma).
¾ Si no se confirma adenoma hipofisario à hiperprolactinemia idiopática.
psychopharmacological drugs that cause hyperprolactinemia
drugs
psychodrugs - decrease tono hypothalamic of dopamine
Fenotiazinas (40-90%, clorpromazina y demás)
Butirofenonas (haloperidol y demás, 40-90%)
Risperidona (100%).
Antidepresivos (IMAO, tricíclicos, IRSS)
Benzodiacepinas
Sulpirida
Amoxapina
antiHTN drugs that cause hyperprolactinemia
Antihypertensives Metildopa y reserpina (disminuyen producción DA) Verapamilo Clonidina Labetalol Atenolol
antiemetics that cause hyperprolactinmia
Antiemetics Metoclopramida Domperidona Cisaprida Bloquean receptores D2 de DA en lactotropas
hormonal prepared drugs that cause hyperprolactinemia
hormonal preps Estrógenos. Disminuyen tono dopaminérgico, aumentan # y tamaño de lactotropos y aumentan síntesis de PRL. AO GABA Progesterona Serotonina (5-HT) Testosterona Noradrenalina (NE) Endorfinas TRH
toxic drugs that cause hyperprolactinemia
narcoticsCocaína Morfina y heroína Anfetaminas Metadona Nicotina Cerveza Codeína
antihistaminic H2 drugs that cause hyperprolactinemia
H2 histamine blockersCimetidina
Ranitidina
Miscellanious drugs that cause hyperprolactimeia
miscelanious Inhibidores de proteasas (SIDA) Fenitoína (anticonvulsivante) Isoniazida (antituberculoso) Piridostigmina (colinérgico) Medroxalol (antiadrenérgico)
causes of hyperprolactinemia that are related to damage of hypolathamus or infundible
Tumores: a. Craniofaringiomas. b. Germinomas. c. Meningiomas d. Metástasis a hipotálamo. e. Extensión supraselar de AH Enfermedades granulomatosas Enfermedades infiltrativas Radioterapia craneal Vasculopatías. Sección infundibular
causes of hypofisiopathy that are related to hipofiospathy
Prolactinomas (AH más frecuente). En mujeres suelen ser micro (90%, 100-200ng/mL) y en hombres macro (60%, >200ng/mL). 8x más frecuente en mujeres, edad de dx más frecuente: 20-40 años.
Macro-AH, por “efecto de tallo” (<200ng/mL).
Hipofisitis linfocítica.
Quiste intraselar.
Quiste de hendidura de Rathke.
Silla turca vacía
Acromegalia (50% de somatotropomas coproducen PRL
causes of hyperprolactinemia associated with primary hipothyroidism
Produce híper-PRL en 10-40%. Se da por:
- ↑TRH hipotalámica à ↑PRL
- ↑sensibilidad a TRH de lactotropas
- ↑VIP à ↑PRL.
- ↓DA hipotalámica
- ↓metabolismo PRL à ↓eliminación PRL
causes of hyperprolacinemia associated with polycystic ovary
Produce híper-PRL en 10-30%. Estado hiperandrogénico o hiperestrogénico (ver atrás)
causes of hyperprolactinemia associated with organ failure
Suprarrenal: ↓cortisol à ↑expresión gen PRL.
Renal: produce híper-PRL en 20-75%. ↓depuración.
Hepática: Produce híper-PRL en 5-20%. ↓depuración hepática, acumulación de estradiol.
causes of prolactinemia associated with thoracic wall , medular lesions
Toracotomía, mastectomía, traumatismo, mamoplastía, dermatitis, quemaduras, herpes zoster, brassiere ajustado, quiste mamario, mesotelioma, esofagitis, piercings en pezones, lesión, cirugía o tumor de médula espinal.
Por estimulación nervios costales 4°-6° produce galactorrea por estimulación del SNA.
causes of prolactinemia associated with ectopic prodcution
CA broncogénico (secreción VIP) Hipernefroma AdenoCA renal. Teratoma ovárico Gonadoblastoma Leucemia mielógena aguda Linfoma de Hodgkin y de células T
causes of prolactinemia associated with - miscellanous
Encefalitis Neurofibromatosis Pseudotumor cerebral Seudociesis Porfiria
causes of prolactinemia associated with macroprolactienmia
Autoanticuerpos anti-“big-big” PRL. Sospechar ante hiperprolactinémicos asintomáticos, pues estas moléculas tienen muy poca actividad biológica.
Se presenta hasta en el 40% de las detecciones de híper-PRL.
causes of prolactinemia associated with - idiopathic
20% de los hiperprolactinémicos. Puede ser por mínimas dimensiones. Se piensa en resistencia de lactotropos a la DA o poca actividad de sus receptores. Se normalizan espontáneamente en 30%.
for hyperprolactinemia when is transesfenoidal tumorectomy ndicated
¾ Intolerancia/resistencia a los agonistas de DA. ¾ No deseo de consumir agonistas DA por largo tiempo.
¾ Crecimiento de prolactinoma a pesar del uso de estos. ¾ Deseo de embarazo por parte de la paciente (aunque la mayoría no crece durante el embarazo: indicación relativa).
¾ Prolactinomas con componente quístico. ¾ Preferencia del paciente.
¾ No mejoría de los campos visuales tras 1-3 meses de agonistas DA
what are somatotropoma
tumor of somatotropes that secrete GH
what is cosecreted in 20-25% in somatotropomas
PRL
65-80% of somatotrpomas are
macroadeomas
MC of somatotropomas
gigantism /acromegaly in 99%
mass effect
mass effect in somatotropma
(hipopituitarismo, hiperprolactinemia y neurooftalmopatías
< 1% of gigantism and acromegaly is due tu
ectopic secretion of GH
excessive secretion of GHRH
- Eutópica (hipotalámico): gangliocitoma o coristoma.
- Ectópica: tiroides (CA medular), timo (carcinoide), bronquio (carcinoide), pulmón (CA microcítico), intestino (carcinoide), páncreas (CA de islotes), adrenales (adenoma o feocromocitoma).
Dx of somatotropoma
- Confirmación bioquímica:
a. IGF-1 (somatomedina C) elevado.
b. Prueba de sobrecarga oral de glucosa midiendo GH (SOG-GH). Medir GH en ayuna y cada 30mins durante 2h después de la sobrecarga con 75g glucosa VO. Confirmación: GH > 1ng/mL por lo menos en 1 de las muestras tomadas post-administración de glucosa. - MRI de hipófisis con gadolinio …
¾ Positivo à
a. Campimetría visual computarizada.
b. Evaluación hipofisaria.
¾ Negativo à
c. GHRH en plasma.
d. TAC tórax y abdomen.
what are corticotropomas
tumors of corticotropas that secrete ACTH producing CUSHINGS disease
what is cushings diesase
a state of hypercortisolism due to hyperstimulation of adrenal gland
cortico tropoma is responsible for what percent of endogenous cushing in adults
68%
90% are microadinomas
biochemical confirmation of corticotropoma
a. Cortisol urinario libre de 24h. Positivo: 2-4x > límite superior.
b. Prueba de supresión con 1mg nocturno de dexametasona. Se administra 1mg de dexametasona @11pm del primer día y se mide cortisolemia a la mañana siguiente. Positivo: >1.8μg/dL.
c. Cortisol salival @11pm. Positivo: >145ng/dL
least frequent AHs 1-2%
tirotropmas
most invasice AHs
tirotropmas
% of tirotropomas that are macroadenomas
85% are macroadenomas causeing mass effect ontop of hormonal effects (bocio, hiperhyroidism with increased TSH
¾ Cosecretan GH (16%), PRL (11%), LH/FSH (1.4%) y subunidad α[2].
hpo vs pan
decreased or no of one or more pit hromes
pan is all > 90% of mass
causes of hypopituitarism (one or more hormons)
8Is
A
direct or indirect
tumoral invasion (meningioma, glioma, ) pit infarct infiltration of hipofisis infection in this region injury in this region - postqx, RT, trauma iatrogenic immunological idiopathic isolated - deficit of just one hormone
types of tumors that cause hipopituitarism
hipofisiary adenoma
compression
hypothalamic tumor cystic lesion (craneofaringoma, Rathke, aracnoidoceles)
metastasis
vascular lesions (necrosis) - no cells to produce hormenes
adenomas and hipoputuitarism
compress hypothalamus and pituitary and THH (tallo)
decrease pit irrigation
increase intrasellar pressure
prolactinoma (PRL inhibits GnRH)
corticotropoma (ACTH inhibits GnRH)
so two hormones are down thru RAN
down FSH, LH, testerone men, estradiol women
pituitary infart
apoplejia don’t know if hemorrhage or infart acute
both caus epituitary infarct (10-15% adenomas inernal hemorrhage??, autocorrection)
local MC:cefalea, meningeal irritation, visual signs, altered conscieness, facial pain
(due to increase in ICP - blood irritates calls cytokines and proinfalmmatory factors causing headache by VD)
altrered sympathetic regulation
obstructive hydrocefaly
systemic: hypopituitarism
empty silla turca syndrome
pathogenesis of apoplejjia
adenoma of pituitary grows fast
mass compresses superior pit artery , less perfusion, necrosis
can also cause its own vascular anomalies
all 3 of these conditions cass perfusion insuff and causes isquemic necrosis –> death of pit cell death
pituitary infract, Sheehan syndrome
@ post partum
blood loss in labor causes less blood flow up
which is already big (pit) due to preg
necrosis
failed lactancy, failed reinico of menstruation, massive labor hemorrhage (PRL inhibits GnRH - after nipple stimulation) cells dead anyway no PRL or GnRH
infiltrations and infections for hipopituitarism
infiltrative: amyloidosis sarcoidosis histocitiosis X hemochromatosis (destroynormal tissue that's there)
infection: micosis (coccido, crypto) Tb sifilis AIDS pituitary abcess
(hipofisisits linfocitica px ej?)
cranial injury hipopituitarism
trauma can be direct to brain
indirect.....causes of pituitary infarct cerebral edema (compresses)
hemorrhage or fracture of cranium (blood irritative ,and proinflammatory)
cerebral hypoxia
iatrogenic causes of hipopituiraism
qx of pit gland due to hypothalamic lesion
cranial RT (gammaknife) - waves destroy the mass/lesion but its not selective just like the surgery
hipofisitis –> hypopituitarism can be
primary or secondary
primary hipofisitis
linfocitic (1A)
granulomatous
xantomarous
secondary hipofisitis
local lesion (germinoma) systemic enf (saroidis)
isolated hypopituitarism ca n have 3 MC cx
isolated FSH LH down (without corticotropoma, hiperPRL)
- kallman syndrome (anosmia –> hipogonadismo hippanotropica??)
FSH alone
hyperprolactimea
TSH down alone
(IRC, linfocitic hipofisitis, pseudohipoparatiroidism)
ACTH down alone
(hipofisitis linfocitic, Sheehan, cranial trauma, Tpit gene mutation)
tpit gene
transcription for??
empty silla turca cause
partial or toal
deficiency in sella diaphragm and LCR infiltrates
compresses pit gland
clinical empty silla turca
oftalmologica (hemaniopsia bitemporal, blurry, blind, papilledema), neurological (cefalea, increased pressure, convulsions, paraplejias), endrological (hipo) 50%
@ def GH
neonates: hipoglicemia, hiperbilirrubinemia, convulsions
(confused with kernicterus)
short stature - infantile, delayed denticion, facial mcizo hypoplasia, frente oprominente, small mouth, occipital prominence
@ def ACTH
tired, less quality sleep, less muscular
dislipidemia
def gonadotropins
no cx sexuals ni 1 or secondary
criptoquidia micropene delayed puberty small testicles little pubic hair gynecomastia
adults: less libido less energy, less EPO, less testicle, heat waves, dyspareunia (SSAME AS MENOAPAUSE) amenorrea, dry vaginal, osteopenia
TSH def
HIPOTHYROIDISM MC weak dry skin palpebral edema adinamia, somnolencia hair falls cold skin thin nails striated bradipsiquia, bradilalia attention deficit memory loss depression, psycosis disfonia
def ACTH
depression weight loss postural hypotension (why) epigastric pain nausea vomit hipoglicemia (no contrareg_ hipnatremia anemia, linfocitosis
def GH
hipoglicemia induced with insulin
GH < 10ng/ml in ALL samples
give insulin (0.05-0.15 unidades/kg) to induce hipoglicemia
take basal glicemia (84mg/dl ej) 0
measure glicemia, GH, cortisol
0, 15, 30, 45, 60, 90, 120
well done to dx if glicemia is < 40mg/dl or half of what px had a basal if (43 CANT USE)
GH should be increasing
> 10 is no deficit - GH
this test measures somatotrope and corticotrope RESRERVES
to say px has GH deficit has to be 9 and down (1 at 10 = healthy)
cortisol should go up and if not its a def in reserve of corticotrope cells (cut off is = 18, healthy below deficit) In all samples
contraregulating hormones
cortisol
GH
glucagon
catecolamines
@ hypoglycemia these hormones go up
masculine hypogonadism dx
infertile
measure serum testosterone at 8 and 11am (nadir times)
if < 300ng/dl = confirmation
primary or secondary
(gonadotripinas )
in primary will be one elevated??
secondary hipo hipo
hipogonisms in women
amenorrea
measure LH, FSH, E2…. also prolactin
E2 down , LH, FSH up - primary (karyotype, precoz menopause, autoimmune ooforitis) = menopause if > 50
E2 down, LH, FSH down
secondary hypogonadism
MRI hipsifis, evaluate hipo function, central?
discart preg and hiperprolactinemia
insuff suprarenal dx
measure cortisol 8am (5-25) and 4pm (half)
Cortisol in morning @ insuff should be < 3
if < 18 = falla adrenal
if > 18mcg/dl = sano
if 3-18 - short ACTH stimulation test - inject 250microg of ACTH or 0.25mg - cortisol up N, doesn’t if sick (<18 = ADRENAL FAILURE)
hormone replacement tx GH
give GH in kids 0.035mg/kg/d SC
hormone replacement tx ACTH
give hydrocortisone - 20-30mg/d VO
Prednisina 5-7.5mg/d VO
Cortisone 25-37.5 mg/d VO
hormone replacement tx TSH
levoritoxine - 1.6-1.8mcg/kg/d VO
LH FSH
men - testerone esters 250mg C/3wk
2.5-7.5mg/d
5-10 gel/24hr
women
estrogen 1-2mg/d
estrogen and progestogens 25-100ug/24hrs (combined birth control)
craneofaringioma
tumors atht originate in remnants of cells from Rathke sac and can cause hipopit in kids
most common cause of hipopit in kids
2-3% of IC tumors
seen in 2 peaks of life
between 2-25yr or > 65yr
25% cause hypothalamic alterations
5% @ hypofisis
both @ 70%
25-30% mixed
15% solid
55-60% cystic
usually > 1cm = macroadenomas, mass effect –> hipopit
highly invasice with hypothalamic extension
MC of craneofaringoam
neuro MC
- headache, visual camp deficit, hydrocephaly, convulsions
hipopituiartism (tumba ADH) - 80% deficit MC delayed puberty DI
hyperprolactinemia
- tallo effect
<100ng/dl
dx of craneofaringeoma
MRI of hypofisis with gadolinio - fine, cortes, if small can catch it most are big (cant see calcifications which cystic lesions do become)
CT craneo (can see calcifications)
Xray (calcification, other lesion, silla turca issues)
campimetric deficits
altered III, IV, VI
less visual acuity
measure prolactin in plasma, FSH LH, estradiol,
FSH LH testosterone
RSH T4 free
GH, IGF1
Cortisol ACTH
hipoglicemia induced by insulin test (FOR LAS RESERVAS) -
tx craniofaringioma
qx
hormone replacement therapy
post qx complications for craneofaringioma
DI - 16-66%
adrenal insuff 40%
panhipopituitarism 23%
hipotiroidism 28%
