Endocrine extras Flashcards
Hormone classes (by chem nature) Tyrosine derived? Peptide? Proteins? Steroids?
Tyr - NE, epi, DA
Peptides - Hypothalamic, also Growth Hormone
Protein - Insulin, (GH?), PRL
Steroids - Gluco, Mineralo, Sex Steroids (HAVE LONGER HALF LIVES IN BLOOD, BUT NOT STORED IN CELL)
G protein mechs, and the Hypothalamic peptides that use them:
Gs –> incr cAMP (TRH, CRH, GHRH)
Gi –> drops AC so drops cAMP and activates K+ channels (SST, PIH (DA))
Gq –> PKC –> IP3, DAG (GnRH GHRH)
Receptors for hormone classes For steroids? Who binds GPCR? Who binds cytokine? WHo binds EGF?
Steroids: enter nucleus and bind HRE –> gene transcription
Surface GPCR: Hypothalamic peptides (so not DA!)
Surface Cytokine: GH, prolactin (JAK/STAT - activation transcription)
Surface EGF family: insulin (binds and activates protein kinase)
Posterior and Anterior pituitary (anatomical relation to hypothalamus?)
PP is continuation of Hypo
AP is epithelial in original (from pharyngeal epithelium - Rathke’s pouch)
Effect of GH on insulin?
Counters action of insulin - i.e. it gets everything ready for growth rather than storage - increases availability of glucose ready for growth
BUT for GH to release IGF-1 you NEED NORMAL INSULIN LEVELS
Laron’s dwarfism vs African pygmies
Laron’s normal GH but bad receptors
Pygmies: normal GH but bad IGF-1 receptors
Tertiary, Secondary, Primary
Tertiary is Hypo, Secondary is Pit (BOTH CENTRAL)
Primary is target organ (PERIPHERAL)
Scant pubic hair?
Central adrenal insuff!
Order for loss of pit hormones
1) GH and LH/FSH
2) TSH/ACTH
3) finally PRL
reflects importance of each (except PRL)
ADH defic common in which tumors?
Common in metastatic tumors but NOT in pituitary adenomas
Made in adrenal cortex?
steroids! (gluco-, mineralo-, sex-)
has 3 zonas
Zona glomerulosa
outermost adrenal cortex makes aldosterone (a mineralo)
Zona fasciculata
middle of adrenal cortes makes cortisol (a gluco)
Zona reticularis
inner adrenal cortex
makes adrenal androgens
Made in adrenal medulla?
Epi and NE (both tyrosine derived) - the catecholamines
Made from chromaffin cells
Epi works on what adrenergic receptors?
a1 –> Gq –> IP3/DAG
a2 –> Gi/o –> decr AC and thus dec cAMP, & open K+
B1-3 –> incr cAMP
Permissive affect of cortisol …
Incr epi release and incr B-adrenergic activity (by producing and inserting B-receptors)
Sx unique to primary adrenal defic
vitiligo, pigmentation, HYPERkalemia
APS-1
autoimmune polyglandular syndrome
INVOLVING AUTOIMMUNE REGULATOR GENE
hypoPARATHYROIDism and mucocutaneous candida
both have adrenal defic (Addi.) and T1DM
ADPS-1
autoimmune polyglandular syndrome
HLA ASSOCIATED
hypoTHYROIDism (Hashimoto)
both have adrenal defic (Addi.) and T1DM
Cortisol levels for Adrenal insuff?
100 = primary (small adrenal glands on CT for autoimmune or metabolic, large on all others)
ACTH LOW or nl = Secondary (with path on pit MRI)
Primary aldosteronism (two types and who to screen)
1) Aldosterone producing ademoma (APA) 34% - SURG poss (likely if age 160/100 (severe) or RESISTANT (2 drugs), HTN under 20 y/o, adrenal incidentaloma, IF UNDER 40, HYPOkalemic) give aldost antagonists
2) Idiopathic hyperaldosteronism (IHA) 66% - give aldost antagonists WITH BP meds, IF OVER 40
3 parts of Ant Pit & functions?
1) pars distalis (makes and secretes hormone)
2) pars tuberalis (round the infundibulum)
3) pars intermedia (between distalis and pars nervosa of post pit) FOLLICLES HERE
Ant pit derived from?
RATHKE’S POUNCH oral/pharyngeal ectoderm (completely separates and wraps around stalk)
Post pit derived from?
neuroectoderm (its an extension of the brain) - still attached to neurons - an evagination of the diencepalon (3rd ventrilce)
2 parts of Post Pit & functions?
1) pars nervosa (releases ADH/vaso and oxytocin) HUGE AXON BUNDLE from hypothalamus (herring’s bodies)
2) median eminence and infundibulum (has portal veins connecting to AP par distalis - nerves here regulate hormone secreting cells of AP’s pars dsitalis
Blood supply and flow
Superior hypophyseal arteries: supply blood to (top part) median eminence, pars, tuberalis, and infundibulum.
Inferior hyphophyseal arteries: blood to pars nervosa (bottom part).
Pars distalis gets it blood form the hypophyseal portal veins that get it form the superior hypophyseal artery
Then LEAVES through hypophyseal veins
Rule of 10 for Pheochromocytoma
Familial, Extra-adrenal, malignant, bilateral
Pheochromocytoma screen?
Metanephrines >1300 in urine, urine catecholamine (2 fold increase)
LOTS OF POSSIBLE FALSE POSITIVES
Treat pheochromoctyoma
- a-blockers first
- then B-blockers
OR CCBs by themselves
THEN adrenalectomy surgery
High Lipid-Low Hounsfeld?
Low Lipid-High Hounsfeld?
Benign
Malignant
FOR adrenal incidentalomas (REMOVE if >4.5, growing, secreting hormone, if not MONITOR)
Most common mutation in thyroid cancer?
BRAF
What deiodinase is in the fetal brain?
And where are the others?
TYPE 2 in the fetal brain (large rise in TSH 30 min after birth so by 24 hours after birth increase in T3 and T4)
Type 1 is in liver and kidney
Type 3 is in the placenta and brain
Spiky hair kid?
Bamforth Lazarus, TITF2, congenital, also has cleft palate
Pendred’s syndrome?
Deafness and goiter, PEDNRIN mutation, SCL26A4
PAX8 mutation?
RENAL AGENESIS
Low T3 uptake and low T4 (same direction)
hypothyroidism
Hi T3 uptake and low T4 (opposite direction)
TBG defic
Eval of worrisome growth
Check bone age with XRay and book (L hand and wrist)
Labs: BMP, CBC (anemia in chronic dz and skeletal dysplasia)
UA, karytope (for Turner’s)
TSH and T4 (hypothyroid)
IGF-1
Nutritional: ESR (IBD), TTG & IgA (celiac),
MEN2A
Pheo, Medullary Thyroid carcinoma, HYPERPARATHYROIDISM
MEN2B
Pheo, Medullary Thyroid carcinoma, MUCOSAL NEUROMAS
Receptor involved in Germline MEN mutations?
RET receptor
Most common malignant thryoid nodule?
Papillary Carcinoma BUT GOOD PROGNOSIS
Large pale nuclei ORPHAN ANNIE (looks like curly hair)
Diagnx by Nuclear Features
Effect of Rathke Cleft Cyst?
Diabetes Insipidus
Brown Crooke cells indicate?
Elevated cortisol from ACTH producing adenoma
Craniopharyngoma
KIDS, beta-catenin mutations, squish everything
Basophilic pit tumors produce?
ACTH
