Pituitary Flashcards
Gold standard test for Growth hormone deficiency
Insulin tolerance test
Normal subjects response to insulin induced hypoglycemia
Peak Gh secretions more than 5 ug/L
Definition of severe GHD
Peak Gh response to hypoglycemia of less than 3 IG/L
Direct precursor of testosterone
Androstenedione
Chiari frommel syndrome
Post partum galactorrhea
Amenorrhea
Utero ovarian aropthy
Inhibitors of prolactin
Dopamine
Endothelin
Calcitonin
Tgf B2
Gold standard test for GHD
GH deficiency
GH replacement dose
0.2-0.3 mg/day
When to treat with growth hormone
Clinical features if hyposomatotropism
Evoked GH <3 ug/L
IGF 1 low
How to monitor response to GH
Measure IGF levels after 1 month
Toteate dose to normalize IGF levels after 1 month
Stop if no clinical reaoinse aft
Adrenal insufficency dx
Serum cortisol morning levels
<3 ug/dL suggests acth deficiency
>18 ug/dL normal acth reserve
Normal acth values in am
8-25 ng/L
Dynamic testing for acth
Hypothalamic ITR
Pituitary CRH or AVP
Adrebal ACTH
How to do insulin tolerance test for ACTH reserve
Insulin 0.1-0.15 U/kg IV after an overnight fast
Achieve symptomatic hypoglycemia and glood glucose less than 40
Normal reaponse:
Cortisol more than 20 ug/dL
Venous samples collect 0.,15,30,45,60,90,120
Glucose acth and cortisol
Recommended dose hydrocortisone adrenal steroid replacement
15-20 ug/day
Half lifr cortisol
Less than 2 hrs
How to test for gonadotropin
Single bolus of GnRH 25-100 ug
Evoke LG and FSG within 20-30 mins
GH hormone therapy effect on lipids
Improved HDL and chole ratio
No change in Tg
Range of morning plasma ACTHlevels
8 to 25 ng/L
Cortisol values as a normal response to hupoglycemia
Higher than 20 ug/dL
Mechanism of action Metyrapone
Blocks 11 B hydroxylase
An activin binding protein (gnrh) which inhibits activin action by inhibiting activin binding to its receptor
Follistatin
Autoimmune inflammatory condition occuring during or shortly after parturition
Lymphocytic hypophysis
What is ipilimumab?
Antibody that blocks the cytotoxic T lymphocyte antigen 4 which is also expressed by the pituitary
RX lymphophtcytic hypophysis
Replace pit deficits spontaneous resolution of inflammatory mass followed
Lab findings in lymphophtcytic hypoglycemia hysis
ESR elevated
(+) abx to 49 kda cytosolic protein in 70%
Characteristic for abscess on Mri
Isointense central cavity with surrounding ring enhancement
Pituitary mass
(+) vimentiun
S100 protei.
Glial fibrillat acidic protein
Pituicytoma
Most common carcinoma that metastasizes to pituitary
Breast
Then
Lung, prostate, renal
Features of ipilimumab induced hypophysitis
Central hypothyroidism in 100 AI In 50-84 Hyponat up to 5O% Low prolactin Low testosterone
Inability to nurse and
Post partum amenorrhea
Sheehans syndrome
Pituitary necrosis due to vasopasn due to hupovolemic shock
Gene locus MEN 4
CDKN 1B
Female to male ratio of microprolactinpmas
20:1
PRL levels steongly suggestive of a MICROPROLACTINOMA
> 200 ug/L
Pathognomonic >500
The most common potuitary tumors associated with men 1
Prolactinomas
% pf patients with acromegaly with elevated PRL
50%
AE of dopamine agonists
Heart valve regurgitation
Management of patients with prolactinomas planning pregnancies
MACROADENOMA ?
DC bromocriptine
Periodic visual field examinations
Post partum MRI after 6 weeks
MICROADENOMA
Surgery before pregnancy
Ensure bromocriptine sensitivity before pregnancy
Monitoring visual fields expectantly if need bromocriptine resumption
High dose steroids for threatened vision/ adenoma hemprrhage occurs
Anti hypertensives that cause hyperprolactinemia
“LVR”
Labetalol
Verapamil
Reserpine
What are the physiologic causes of hyperprolactinemia?
Exercise Coitus Stress Sleep Suckling Pregnancy
ECSSSP
Reason why prolactin is moderately elevated in patients with chronic renal failure and those on HD
Mean 28
Decreased glomerular filtratoon rate
This may cause sexual dysfunction
Weight of the adult pituitary
600 mg (rang 400-900)
5 distinct hormone secreting cell types in the mature anterior pituitary gland
Corticotroph cells Somatotroph cells Thyrotroph cells Gonadotroph cells Lactotroph cells
Blood supply of hypothalamus
Superior hypophyseal arteries (branch of ICA)
Blood supply of anterior pituitary gland
Long and short hupophyseal portal arteries (from infundibar plexuses and stalk)
Blood supply of posterior pituitary
Inferior hypophyseal arteries
Rathke’s pouch formation
4-5th week gestation
Where is the pituitary formed from?
Anterior - rathke’s puth
Posterior neural ectoderm assoc with 3rd ventricle development
Required tor the initial pouch invagination for pituitary morphoenesis
BMP4
When does the anterior pituitary under major cell differentiation?
12 wks
When are corticotrophs identifiables
6 wks
Somatotroph- 8 wks
Thyrotroph- 12 weeks
Lactotroph-24 weeks
Directs corticotroph cell commitment
Tpit protein
Determines subsequent developemebt if POUF1F1 and gonadotroph cell lineages
PROP1
Major determinant of pituitary cell lineage
PROP1
Corticotrop cell devt occurs earliest and is independent of PROP1 determined lineages. What is a prerequisite for POMC expression
T pit protein
Effect of VIP and serotonin pn prolactin secretion
Stimulates PRL
Share a common a subunit expression under developmental control of Gata2
TSH
Gonadotropin expressing cells
Transfeiption factors
Detemines gonadotroph development
SP1 and DAX1
Effect of opiates on PRL
Acutely induce PRL release
Effect of cyproheptadine on PRL
Attenuatea noctirnal prl secretion
Side effects of pituitary irradiation
- hypopituitarism
- second brain tumors
- cerebrovascular doseases
- visual damage
- brain necrosis
To minimize visual damage what is recommended dose od radiation
Less than 200 rads
Second brain tumors reported after pituitary irradiation
Glioma
3 phases of post op diabetes insipidus
- Transient disorder
- Interphase 6-11
- 3rd phase return to DI
Rathke’s pouch is where thne ___ is derived
Anterior and intermiediate lobes of the pituitary
Parasellar masses
Locally invasive
From midline notochord remnants
Mucin rich matrix
Chordomas
Critical neuroectodermal sugnal
Dorsal gradient of pituitary devt
Needed for initial puch invagination
BMP4
Pituitary stem cell progeniyors that express this marker can regenerate in times of stress
Sox 1 and sox 2
Rieger syndrome
Mutation in eye umbilicL cord defect in…
Pitx2
Sequence of hormone loss
Pituitary compression
GFLTA
Radiation
GFLAT
Stimulates PRL secretion
TEVS
TRH
Estrogen
VIP
Serotonin
Inhibits prolactin
DECT dopamine Endothelin 1 Calciyonin TGF B
Anti psychotic drug with minimal effect on PRL levels so you may shift to this to rule out drug induced hyperprolactinemia (short of stopping the meds)
Olanzapine
Hallmarks of pathologic prolactinemia
Galactorrhea
Reporxuctive dysfunxction
Chiari frommel syndrome
Pathologic hyper prolactinemia
Post partim galactorrhe
Amenorrhea
Ureteo ovarian atrophy
Time frim discontinuation of nursing continued milk production is abnormal
6 months
How come 50% of patients with actomegaly have galactorrhea despite normal prolactin levels
Human GH is a potent lactogen
The most frequent cause of galactorrhea
Normoprolactinemic galactorrhea
PRL deficiency with central hypothyroidism
Immunoglubulin superfamily member 1 defficiency syndrome
Side effect CRH stimulation test
Table
Flushing
Side effect metyrapone test
Nausea insomnia adrenal crisis
Effect of norepinephrine to GH secretion
A adrenergic increases release
B adrenergic inhibits
These substances account for GH release during exercise and stress
Endorphins and enkephalins
These STIF teceptor subtypes mediate GH secretion
2 and 5
Effect of ghrelin
Binds growth hormone secretagogue receptor to release GHRH and pituitary GH
70% of GH secretion in its diurnal rhythm occurs when
Slow wave sleep
The signature property of GH
Protein anabolism, reducing urea synthesis and urea secretion
Effect of GH on glucose metabolism
Insulin like effects: enhanced glucose uptake in cells
Whole body: suppresses glu oxidation while enhancing hepatic glu production
Critical factor for corticotroph cell differentiation
Tpit
Where are corticotrophs clustered
Central medial pituitary wedge
Weight of pituitary gland
600 mg
GH uses
Osteoporosis
HIV cachexia
Melanocortin receptor for melanocyte stimulation
MCR1
Mcr2 adrenals
Mcr 3 Nd 4 leptin
MOA metyrapone
Inhibits adrenal 11 B hydroxylase
Most common endocrine deficit encountered with ipilimumab induced hypophysitis
Secondary adrenal insuffiency
Median onset of ipilimumab induced hupophysitis
CTLA4
Isolated in prolactinomas
PTTG
MEN1 gene
Chromosome 11q13
MEN 4 gene
CDKN1B
Mutations seen in patients with gigantism
AIP mutations
Rx DI
Vasopressin
Desmopressin
Chlorpropamide
Indomethacin
Not recomended:
Carbamazepine
Clofibrate
Natriuretic agents for DI
Thiazide
Amiloride
Indapamide
Target bp alpha blockadr
<120/80 seared
>90 sbp standing
Losnsger duration of alpha blockade needed
Cathecholamine cardiomyopathy
Cathecholamine induced vasculitis
When to start alpha blockade
7-10 days pre op
When to start beta blocked
2-3 days pre op
Target HR beta blockade
60-80 bpm
Anaesthesia to use in pheo
Propofol
Etomidate
Barbiturates
Inhibits aldosterone
Heparin
ANP
Dopamine
“HAD”
MC cause of hyperaldosteronism
Bilateral idopathic hyperplasia
When to test hyperaldo
Hypertension and hypokalemia Resi hrn Icidentaloma and htn Onset of HTN at young age <20 Sever htn >150/100 Whenever considering secondary HTN
Positive result for hyperaldosteronism screening
PAC> 15
Renin < 1
20 ratio
High renin high aldo
Renovascular disease
Diff liddle from AME
Give amiloride /traimtene (corrects liddle)
How to diagnose SAME
24 h urine cortisol and cortisone
Increase ratio in the 24h urine
Age risk foctors fot DM
Unite age over 40
Williams 45
prevalence of DM
- 8% IDF
7. 2% Unite
Criteria for diagnosis of atypical pituitary adenomas
Invasion Rapid growth Recurrenc Diameter more than 4 cn Resistance to medical therapy Carcinoma, if extracranial metastasis
WHO 2004 diagnosis attpical adrenocorticotrophic hormone
Aggressive invasive Pleomorphic Increased mitotic activity Ki 67 >3% P53 immunoreactivity
Genes assic wifh familial pituitary tumor syndromes
Men1
Men4
Carney complex
Familial isolated pit adenomas
Used to treat aggresisve pituitrytumors that failed to respond to other therapy or if with evidence of carcinoma
Temozolomide
Interferes with drug efficacy of temozolomide
O MGMT
Radiation Dose for irradiation pituitary mass
Max 5000 rads
180 rad 5-6 weeks
Indications for pituitary ireadiation
P242 Adjuvant to surgical therapy 1) pit adenoma 2) craniopharyngioma 3) nelson syndrome 4) nonadenomatous sellar mass 5) tumor recurrence 6) hormone hypersecretion recurrence
Second brain tumors implicated post pituitary irradiation
Gliomas
Astrocytonas
Acromegaly treatment which emgances insulin sensitivity hence suited for patients with co existing diabetes
Pegvisomant
Marker of responsiveness to pegvisomant
IGF-1
Because action is on peripheral receptor and levels of GH rise as IGF1 negative feedback is lost
Monitoring of patients on pegvisomant
Hepatic transaminases every 6 mos
Monitoring tumor growth