Hypothalamic & pituitary disorders Flashcards
Master Gland of the endocrine system
- secretes hormones that stimulate other endocrine organs
Pituitary Gland
Hormones in the anterior lobe (adenohypophysis)
- somatotrophs - GH
- lactotrophs (mammotrophs)- Prolactin
- corticotrophs- ACTH, POMC, Endorphins, Lipotropin
- thyrotrophs- TSH
- gonadotrophs- FSH & LDH
Hormones in the Posterior lobe (nuerohypophysis)
- oxytocin
- ADH
which hormones are Acidophilic cells
A-SP
- somatotrophs - GH
- lactotrophs (mammotrophs)- Prolactin
which hormones are Basophilic cells
B-FLAT
- corticotrophs- ACTH, POMC, Endorphins, Lipotropin
- thyrotrophs- TSH
- gonadotrophs- FSH & LDH
Posterior lobe is made up of what cells ?
Consists of modified glial cells and axonal processes
embryological origin of the anterior lobe?
makes up 80 % of the gland and by epithelial cells
- ectodermal derivative formed from Rathke’s pouch ( which is an upward diverticulum from the primitive buccal cavity)
- no direct neural connection but has indirect connection through capillary portal circulation by which it receives the blood
embryological origin of the posterior lobe?
downgrowth from the primitive neural tissue
- has direct neural connection superiorly with hypothalamus
what separates the posterior and anterior lobes?
VESTIGIAL INTERMEDIATE LOBE
-containing a few cyst cavities lined by cuboidal/columnar epithelium (considered part of the anterior pituitary)
where does the pituitary drain into?
venous drainage from pituitary follows the cavernous sinus both inferior petrosal sinuses
-IPSS is an infrequently used invasive procedure confirming the presence of a hormonally active pituitary microadenoma
why can pituitary enlargement alter vision or cause palsies?
By impinging near the optic chiasm and cranial nerves 3, 4, 5, 6
increase in dopamine will cause?
inhibition of prolactin secretion
what is the most powerful stimuli for prolactin release
- SUCKLING
- TRH
______ increases sensitivity of lactotrophs to TRH
estrogen
what is the MOA of Kallmann Syndrome
due to failure in the differentiation or migration of neurons that arise embryologically in the olfactory mucosa to take up residence in the hypothalamus, as GnRH neurons.
what are the 3 manifestations of Kallmann Syndrome
- congenital hypogonadotropic hypogonadism
- hypo- or anosmia and dec.in gonadal function
- de.c in GnRH hormone = dec. levels of sex steriods ( FSH &LH) —> sexual imaturity and asbsence of secondary characteristics
OXYTOCIN:
site of synthesis
Target organ
physiological effects
paraventricular nuclei
- uterus
- mammary glands
- urterine contractions
- milk-let down and excretion
ADH:
site of synthesis
Target organ
physiological effects
Supraoptic nuclei
CD- renal tubules
inc. water retention (concentrates the urine)
clinical manifestations of pituitary disease:
-Hyperpituitarism
- hypopituitarism
- local mass effects:
- visual field defects:
- Inc. intracranial pressure
Hyperpituitarism
pituitary adenoma, hyperplasia, carcinoma
Hypopituitarism
ischemic injury, surgery or radiation, inflammatory rxns, and nonfunctiona; pituitary adenomas (1/3; dec. secretions)
local mass effects :
sellar expansion , Bony erosion & disruption
visual field defects
bitemporal heminaopsia
ALWAYS : hypothalamic etiology
hypopituitarism + posterior pituitary dysfunction
HYPOpituitarism etiology
-pituitary adenomas and metastatic tumors ( compressing anterior pituitary or stalk (2/3 adenomas are functional))
-hemorrhage; pituitary apoplexy —-> undergoing ischemic necrosis
-infarction; ischemic necrosis of pituitary (sheehan syndrome)
hypothalamic lesions
mass lesions: craniopharyngioma and metastatic tumors
infiltration (sarcoidosis)/ infections (TB)
hypopituitarism: Iatrogenic hypopituitarism
Radiation damage to the hypothalamic- pituitary axis or neurosurgical procedures
hypopituitarism: infiiltrative diseases
- bacterial and viral infections
- langerhans cell histiocytosis
-hemochromatosis - Lymphocytic Hypophysitis
langerhans cell histiocytosis:
involvement of hypothalamic - pituitary axis causes endocrine abnormalities ( panhypopituitarism in 5-20%)
- increased prolactin and galactorrhea (central diabetes insipidus)
- Lymphocytic Hypophysitis:
rare autoimmune condition in Women, infiltrate by T/ B cells
Hypopituitarism patholgy;
- hormone deficiencies
- panhypopituitarism ; all 6 anterior pituitary hormones deficient
- increased mortality esp. due to cardiorespiratory effects
- ADH loss => Diabetes insipidus
what is the correct order of hormone deficiencies for hypopituitarism:
GH, LH/FSH, TSH, ACTH, PR
most common adenoma
prolactinoma
most common deficiency in hyperpituitarism?
GH defeciency
hypo-pituitary effects of ACTH
ex. addison disease
dec. ACTH -> dec. Corstisol
- orthostatic hypotension
- tachycardia
- weakness & lethargy
- adrenal crisis
- mental status changes
- nausea
- vomitting
- abdominal pain
-shock
hypo-pituitary effects of TSH
dec. TSH –> dec. thyroxine
- fatigure
- cold intolerance
- depression
-bradycardia
-constipation
- dry skin
- puffy face
- slow reflexes
hypo-pituitary effects of LH / FSH
dec. LH/FSH –> dec. sex steroids
premenopausal women
- irregular/absent periods
- hot flashes
- vaginal atrophy
- infertility
Men
- erectile dysfn / infertility
- dec. libido
- weight gain
hypo-pituitary effects of GnRH
GnRH–> dec. GH
children
-short
-failure to thrive
adults
- dec. muscle mass / bone density
- inc. fat
hypo-pituitary effects of prolactin
-agalactorrhea
- amenorrhea
- cold intolerance
hypo-pituitary effects of ADH
polyuria
polydipsia
-lethargy
-hypernatremia
-dehydration
what is a Pituitary Apoplexy
Is sudden hemorrhage into the pituitary gland usually associated with a preexisting adenoma.
Pituitary Apoplexy side effects
- Neurosurgical emergency
- Sudden onset excruciating headache, diplopia due to pressure on the oculomotor nerves or ophthalmoplegia
due to involvement of the third (oculomotor), fourth (trochlear), or sixth (abducens) - hypopituitarism.
- In severe cases, it can cause cardiovascular collapse, loss of consciousness, and sudden death ( cortisol
deficiency)
Sheehan’s syndrome sequence of events
pregnancy–> inc . pituitary growth –> hyperplasia (inc . LDH) –> eosinophilic pink stain–> Hypotension in Peripartal period & Low pressure hypophyseal portal system – No increase in blood flow—-> Pituitary ischemic necrosis
*Postpartum necrosis of Anterior pituitary - Panhypopituitarism *
why is the post. pituitary much less susceptible to ischemic injury?
Posterior pituitary receives blood directly from arterial branches
Sheehan’s syndrome pregnant patient will mostly have normal levels of what hormones?
oxytocin and ADH (post pituitary, less likely for ischemic injury)
Sheehan’s syndrome RX?
hormone replacement therapy.
MOA of Empty Sella syndrome
Congenital defect of Sella
* Herniation of arachnoid and CSF
compresses and destroys pituitary
* Pituitary shrinks
* Sella turcica fills up with CSF
Symptoms of empty sella syndrome?
CSH rhinorrhea, headache,
hypopituitarism
* Pituitary absent - empty sella on
imaging
which is the 1º ite in the body where ADH is stored & released?
post. pit. lobe
Hypofunction of hypothalamus and posterior pituitary – Reduced ADH ( Vasopressin secretion) leads to?
diabetes insipidus
different stimuli where ADH is released from axon terminals in the neurohypophysis include:
- increased plasma osmotic pressure (Dehydration)
- left atrial distention
- exercise
pathology of Central Diabetes Insipidus:
ADH deficiency
reduced aquaporins
reduced water moving from tubules to blood
pathology of Nephrogenic Diabetes Insipidus:
kidney not responding to ADH
Etiology of Central Diabetes Insipidus:
➢Pituitary disorders
- Transection of pituitary stalk (post-traumatic) or suprasellar tumors compressing
pituitary stalk .
- Infiltrative disease to posterior pituitary (ex: metastasis, sarcoidosis)
➢Hypothalamic disease (eg. Histiocytosis X)
Etiology of Nephrogenic Diabetes Insipidus:
-Drugs - Lithium, demeclocycline)
- PKD
- Genetic disease – ADH receptor / Aquaporin
effects of Central Diabetes Insipidus:
inc. serum osmo- thirsty (polydipsia)
lots of urine excreted - polyuria , reduced urine osmo.
effects of psychogenic Diabetes Insipidus:
- inc. water intake
- reduced ADH secretion
- inc. urine output (polyuria)
after 2-3hrs of water deprivation give ADH what will happen to urine osmolality for Central diabetes insipidus?
inc. urine osmo.
Central diabetes insipidus RX?
DDAVP
after 2-3hrs of water deprivation give ADH what will happen to urine osmolality for Nephrogenic diabetes insipidus?
NO CHANGE in urine osmo
Nephrogenic diabetes insipidus treatment?
Thiazide
what is SYNDROME OF INAPPROPRIATE SECRETION (SIADH)
Excessive production of ADH → oliguria, resorption of excessive amounts of free water, hyponatremia and cerebral edema
What are some causes of SIADH
-Paraneoplastic syndrome- ectopic ADH by malignant neoplasms (particularly small cell carcinomas of the lung)/ Pneumonia
- Head trauma- local injury to the hypothalamus or neurohypophysis ,stroke, hemorrhage
- Drugs = Carbamazepine, SSRI, NSAID
MOA for SIADH
Increased ADH–> Increased Aquaporins–> (Increased water retained in blood) Reduced plasma osmolality –> Oliguria & Increased urine osmolality –> inc. Na+ excretion in urine >40mEq/L –>Hyponatremia
induced neuronal swelling and cerebral edema
Summary of electrolyte abnormalities in SIADH:
-Urine Osm is greater than Plasma Osm
-Dilutional hyponatremia
-Increased urinary sodium excretion(>40mEq/L)
Clinical Feautures of electrolyte abnormalities in SIADH:
- Hyponatremia:
Mild- nausea and forgetfulness
Severe - Seizures and coma - Euvolemia
Moist mucous membranes, No edema, No JVD
what is the diagnosis:
Head trauma + dec. serum Na+, + inc. urinary osmolality
SIADH
what is the diagnosis:
frequent urination
thirst
hypernatremia
sig. inc. in urine conc. w/ desmopressin
Diabetes insipidus (central)
MEN- 1 are the 3P’s:
Pituitary
PTH
pancreas
Non Functional tumors – mass effect:
- Optic chiasm compression – bitemporal hemianopsia
- Headache
- Hypopituitarism- compression of anterior pituitary or stalk (>75% causes Panhypopituitarism)
Pituitary Adenoma causes ?
Benign tumor of anterior pituitary cells
* May be associated with MEN syndrome
* Majority are hyperfunctioning (2/3rds)
✓ Functional tumors present with features based on hormone produced
Classification- based on size:
(<1cm)
Microadenoma– incidentaloma, 14% prevalence at autopsy
Classification- based on size:
(>1cm)
Macroadenoma– cause visual defects
Classification – Based on cell type:
PRL/GH/ACTH/TSH/ FSH LH
what distinguishes Adenomas from non-neoplastic tissue
Cellular monomorphism (all eosinophilic) and absence of reticulin network
Prolactinoma (Lactotroph adenoma) Hormonal symptoms:
- Gonadotrophin inhibition
✓Females- infertility & menstrual disorders ( amenorrhea) diagnosed early
✓Males-decreased libido & Gynaecomastia, headache ( late diagnosis - macroadenoma) - Induction of lactation ( galactorrhea-milky nipple discharge)
- Osteoporosis & fractures – low estrogen
Prolactinoma Treatment:
Inhibited by Dopamine agonists – Bromocriptine, cabergoline
what is stalk effect
mass in the suprasellar compartment may disturb the normal
inhibitory influence of hypothalamus on prolactin secretion
Somatotroph Adenomas ( Growth hormone secreting adenoma)
- 2nd most common functional adenoma
- elevated growth hormone (GH) and elevated somatomedin C (insulin-like growth
factor 1[IGF-1]).
what is GH – direct tissue effect
Increased insulin resistance
Increased fat utilization
increased protein synthesis
IGF-1 – growth & proliferation is for
Bone, cartilage, soft tissue
what is Gigantism (children)
- rare!
– increased linear bone growth (epiphyses not fused)
Tall stature with long extremities, large hands & feet, thickened calvarium, prognathism, excess sweating and oily skin
what is Acromegaly (adults)
-(Acro- extremity)
- enlarged bones of hands, feet and jaw
fingers thickened- sausage shaped
- Growth of visceral organs - Thyroid, heart, liver, adrenals
enlarged tongue
- Organ dysfunction – cardiac failure
GH adenomas Lab Dx for GH
➢GH increased
GH secretion pulsatile + short half life ( 20 min)
- Increases muscle mass
- Anti-insulin effect – Gluconeogenesis, resistance
(Diabetogenic)
GH adenomas Lab Dx for IGF-1
- IGF-1(Somatomedin C) increased
- enhances chondrogenesis + soft tissue and linear growth
of bones. - half life 20 hrs, secreted by liver in response to GH
- Levels of IGF-1 correlate with adenoma size
What is the test for acromegaly?
- Serum IGF-1:-Raised
- If raised, perform OGTT:-
* Healthy person: Glucose will provide negative feedback and decrease GH
* Acromegaly: Glucose does NOT suppress the GH
Lack of suppression of GH levels with IV bolus of
glucose confirms __________
GH hyper secretion
Diagnose the following:
“hat does not fit”
more common
mean age= 4th decade
delay onset
M=W affected
Acromegaly
describe Laron syndrome
- defect in growth hormone receptor (GHR).
-GROWTH HORMONE INSENSITIVITY
Laron Syndrome occurs in what ppl?
occurs mainly in people of Mediterranean origin and is responsible for dwarfism in African pygmies.
describe physical characteristics for growth hormone insensitivity (laron syndrome)
- short stature due to extreme resistance to GH
- Tend to be obese
why does growth hormone insensitivity (Laron syndrome) have high serum GH levels, but low concentrations of IGF-I.
bcuz there is no GH receptor on hepatocytes , which secretes IGF-1
__________________ indirectly reflects GH receptor status
Low GH binding protein
what is Corticotroph adenomas MOA?
- Produce ACTH, causing hypercortisolism (Cushing disease) + hyperpigmentation (MSH- same precursor as ACTH)
what is Nelson Syndrome
mostly microadenomas ( may grow into large aggressive tumors if both adrenals are removed for treating Cushing syndrome in a patient with pre-existing pituitary adenoma
what is the DX:
* benign tumour commonly in suprasellar region
* arising from remnants of Rathke’s pouch.
* more common in children and young adults.
* Though benign, compresses as well as invades the adjacent structures extensively
- Caudally into sella turcica to destroy the pituitary gland
- Anteriorly optic chiasm (causing visual field defects)
- Superiorly into hypothalamus (increasing intracranial pressure)
craniopharyngioma
describe the GROSS morphology of craniopharyngioma
cystic, reddish-grey mass with dark “motor oil” fluid composed of cholesterol and hemorrhage
