[M6 GROUP 1] Hypothalamic and Pituitary Function Flashcards
PITUITARY is aka
master gland
aka “master gland”
PITUITARY
PITUITARY is derived from both ___ and ___ which means to “____”
Latin,
Greek,
spit mucus
It secrete hormones that regulate the other endocrine glands
PITUITARY
PITUITARY also referred as “___”, from Greek meaning “____”
hypophysis,
undergrowth
hypophysis means
undergrowth
Reflection of dura
Diaphragma sella
It separates superior portion of the pituitary from the hypothalamus
Diaphragma sella
Diaphragma sella is Penetrated by ____
infundibulum
Connects adenohypophysis to the median eminence and
hypothalamus
Infundibulum
Infundibulum connects ____ to the median ___ and
_____
adenohypophysis;
eminence;
hypothalamus
WHAT ARE THE 4 FEATURES THAT DISTINGUISH THE FUNCTION OF PITUITARY
- Feedback loops
- Pulsatile secretions
- Diurnal rhythms
- Environmental or external modification of its performance
What are the three distinct parts of the pituitary:
Anterior pituitary
Intermediate lobe
Posterior pituitary
Anterior pituitary is aka
adenohypophysis
Anterior pituitary or adenohypophysis receives ____ of the ____ and ____ via the _____
80-90%;
blood supply;
hypothalamic factors;
hypothalamic–hypophyseal portal system
Receives 80-90% of the blood supply and hypothalamic factors via
the hypothalamic–hypophyseal portal system
Anterior pituitary or adenohypophysis
Intermediate lobe is aka
pars intermedalis
Poorly developed in humans and has little functional capacity
Intermediate lobe or pars intermedalis
Posterior pituitary is aka
neurohypophysis
Posterior pituitary or neurohypophysis is Responsible for storage and release of ___ and ___
oxytocin
vasopressin
Responsible for storage and release of oxytocin and vasopressin
Posterior pituitary or neurohypophysis
Posterior pituitary or neurohypophysis is Connected to the ___ and ____ hypothalamic nuclei
supraoptic;
paraventricular
Connected to the supraoptic and paraventricular hypothalamic nuclei
Posterior pituitary or neurohypophysis
What are the different Anterior Pituitary Cell Types
Lactotrophs
Somatotrophs
Thyrotrophs
Corticotrophs
Gonadotrophs
Follicle-stimulating hormone
prolactin-secreting cells
Lactotrophs
growth hormone [GH]-secreting cells
Somatotrophs
(thyroid-stimulating hormone [TSH]-secreting cells
Thyrotrophs
adrenocorticotropin hormone [ACTH]-secreting cells
Corticotrophs
luteinizing hormone
Gonadotrophs
[FSH]-secreting cells
Follicle-stimulating hormone
WHAT ARE THE FUNCTIONAL ASPECTS OF THE HYPOTHALAMIC-HYPOPHYSEAL UNIT
Endocrine Feedback Loop
Pulsatility
Cyclic nature of Hormone Secretion
An example of Endocrine Feedback Loop
Hypothalamic-Pituitary-Thyroidal Axis
Can be partially inhibited by adrenal steroids and cytokines
Hypothalamic-Pituitary-Thyroidal Axis
Hypothalamic-Pituitary-Thyroidal Axis Can be partially inhibited by ____ and ___
adrenal steroids
cytokines
TRH means
Thyrotropin-releasing hormone
Thyrotropin-releasing hormone is produced by
hypothalamus
It is a Hypophysiotropic hormone
Thyrotropin-releasing hormone (TRH)
Directs the thyrotrophs
Thyrotropin-releasing hormone (TRH)
TSH-producing cells
thyrotrophs
Thyrotropin-releasing hormone (TRH) secretes?
Thyroid Stimulating Hormone (TSH)
stimulates several steps in the thyroid that are critical in the production and release of thyroid hormone (thyroxine)
Thyroid Stimulating Hormone
The one that suppress TRH and TSH production
Thyroxine
feedback of thyroxine at the level of the
pituitary
Short feedback loop
Short feedback loop is the feedback of thyroxine at the level of the
___
pituitary
feedback at the level of the hypothalamus
Long feedback loop
Feedback between the pituitary and
hypothalamus (when present)
Ultrashort feedback loop
Regulated by neural modulation
Pulsatility
Pulsatility is Regulated by ____
neural modulation
→ Specific for each hypothalamic-pituitary-end-organ unit
Pulsatility
Median interpulse interval for LH
Pulsatility
Pulsatility:
Normal Male: ___
55 minutes
Pulsatility:
Average LH peak duration: _____
40 minutes
Regulatory hypothalamic hormone
Gonadotropin-Releasing Hormone (GnRH)
Its pulse frequency has profound effects on LH secretion profiles
Gonadotropin-Releasing Hormone (GnRH)
Gonadotropin-Releasing Hormone (GnRH)
Increased: reduces ___
gonadotrope secretory response
Gonadotropin-Releasing Hormone (GnRH)
Decreased: increases the ____
amplitude of the subsequent LH pulse
Regulated by nervous system through external signals
Cyclic nature of Hormone Secretion
It means “time giver”
“Zeitgeber”
Process of entertaining or synchronizing theses external cues
into the function of internal biologic clocks
“Zeitgeber”
“Zeitgeber”
Cyclic nature of Hormone Secretion
Cyclic nature of Hormone Secretion is Typified by ___ or ___ secretion
ACTH;
TSH
Cyclic nature of Hormone Secretion:
Typified by ACTH or TSH secretion
o Lowest: _____
o Peak: _____
11:00 pm and 3:00 am
6:00 am to 9:00 am
Nocturnal Levels of TSH is ____ the ____ levels
twice
daytime
Nocturnal Levels of TSH is Increased due to increased ___
pulse amplitude
Actions of Hypothalamic hormones:
● TRH stimulates secretion of ___ and ____
● GnRH stimulates ____ and ___
● Somatostatin (SS) inhibits ___ and ___ release
● Vasopressin (ADH) stimulate ___ secretion
TSH ; prolactin
LH ; FSH
GH ; TSH
ACTH
What are the Actions of Hypothalamic hormones:
● TRH stimulates secretion of TSH and prolactin
● GnRH stimulates LH and FSH
● Somatostatin (SS) inhibits GH and TSH release
● Vasopressin (ADH) stimulate ACTH secretion
What are the different Hypophysiotropic hormones
TRH
GnRH
CRH
GHRH
Somatostatin
Dopamine
HYPOPHYSIOTROPIC HORMONES:
What is the structure of TRH
3 amino acids
HYPOPHYSIOTROPIC HORMONES:
What is the action of TRH
Release TSH and prolactin
HYPOPHYSIOTROPIC HORMONES:
What is the structure of GnRH
10 amino acids
HYPOPHYSIOTROPIC HORMONES:
What is the action of GnRH
Releases LH and FSH
HYPOPHYSIOTROPIC HORMONES:
What is the structure of CRH
41 a.a
HYPOPHYSIOTROPIC HORMONES:
What is the action of CRH
releases ACTH
HYPOPHYSIOTROPIC HORMONES:
What is the structure of GHRH
44 a.a
HYPOPHYSIOTROPIC HORMONES:
What is the action of GHRH
releases growth hormone
HYPOPHYSIOTROPIC HORMONES:
What is the structure of somatostatin
14 and 28 a.a
HYPOPHYSIOTROPIC HORMONES:
What is the action of somatostatin
Inhibits GH and TSH release (additional effects on gut and pancreatic function
HYPOPHYSIOTROPIC HORMONES:
What is the structure of dopamine
1 a.a
HYPOPHYSIOTROPIC HORMONES:
What is the action of dopamine
inhibits prolactin release
prolactin inhibitory factor
dopamine
ANTERIOR PITUITARY HORMONES is characterized as (2)
Direct effectors
Tropic
classification of anterior pituitary hormone that act directly on peripheral tissues
Direct effectors
Example of Direct effectors
GH
Example of Direct effectors
GH
classification of anterior pituitary hormone that is specific for another endocrine gland
Tropic
WHAT ARE THE DIFF TROPIC HORMONES
LH
FSH
TSH
ACTH
Tropic hormone that directs testosterone production from men and women
LH
LH – directs ___ production from:
✓ Men: ___
✓ Women: ___
testosterone;
Leydig cells;
Ovulation
FSH is responsible for:
✓ Men: ____
✓ Women: ___
Spermatogenesis;
Ovarian recruitment and Ovulation
TROPIC HORMONES that directs thyroid hormone production
TSH
TROPIC HORMONES that regulates adrenal steroidogenesis
ACTH
What are the diff anterior pituitary hormone
LH
FSH
TSH
ACTH
GH
PRL
What is/are the anterior pituitary hormone that targets the gonad (tropic) gland
LH
FSH
anterior pituitary hormone with dimeric glycoprotein structure
LH
FSH
TSH
What is/are the anterior pituitary hormone that targets THYROID (TROPIC) GLAND
TSH
What is/are the anterior pituitary hormone that targets adrenal (tropic) gland
ACTH
What is/are the anterior pituitary hormone that targets Multiple (direct effector) gland
GH
What is/are the anterior pituitary hormone that targets breast (direct effector) gland
Prolactin
anterior pituitary hormone with SINGLE PEPTIDE DERIVED FROM POMC structure
ACTH
anterior pituitary hormone with SINGLE PEPTIDE
GH
PRL
LH
Feedback hormone: ____
Sex steroids
FSH
Feedback hormone: ____
Inhibin
TSH
Feedback hormone: ____
Thyroid hormones
ACTH
Feedback hormone: ____
cortisol
GH
Feedback hormone: ____
IGF-1
PRL
Feedback hormone: ____
Unknown
____ of people harbor clinically silent ___
20%
pituitary adenomas
____ of ___ individuals have ____ observed under ___
10% - 30%;
normal;
pituitary tumors;
MRI examinations
____ of the lesions removed from carefully selected patients who have undergone ____ surgery are ____
91%;
transsphenoidal ;
pituitary tumors
Most common Pituitary tumor
prolactin secreting pituitary tumors
Have an MIB-1 proliferative
index greater than 3%
Atypical Pituitary Tumors
monoclonal antibody used to detect Ki-67
MIB-1
- a marker of cell proliferation
Ki-67
Excessive p53 immunoreactivity
Atypical Pituitary Tumors
Atypical Pituitary Tumors has Excessive ____
p53 immunoreactivity
Increased mitotic activity
Atypical Pituitary Tumors
Macroadenomas
Atypical Pituitary Tumors
Show invasion into surrounding structures like the cavernous sinuses
Atypical Pituitary Tumors
● Seen during puberty and pregnancy
PHYSIOLOGIC ENLARGEMEN (OF PITUITARY TUMORS)
PHYSIOLOGIC ENLARGEMEN (OF PITUITARY TUMORS) IS SEEN DURING ___ AND ___ DUE TO ____
puberty;
pregnancy;
lactotroph hyperplasia
seen in long standing primary thyroidal failure
Thyrotroph and lactotroph hyperplasia
Gonadal failure
Gonadotroph hyperplasia
GROWTH HORMONE IS AKA
Somatotropin
Structurally related to prolactin and human placental lactogen
GROWTH HORMONE
GROWTH HORMONE IS Structurally related to ___ and ___
prolactin;
human placental lactogen
GROWTH HORMONE is produced by the ___ specifically the ___
(____)
pituitary gland;
somatotrophs;
pituitary cells
Produced by the pituitary gland specifically the somatotrophs
(pituitary cells)
GROWTH HORMONE
Release of this hormone is stimulated by the growth hormone-releasing hormone (GHRH)
GROWTH HORMONE
GROWTH HORMONE Release is stimulated by the ____
growth hormone-releasing hormone
(GHRH)
enteric hormone that plays an important role in nutrient sensing, appetite, and in glucose regulation leading to stimulation of GH secretion
Ghrelin
This hormone is secreted in pulses
GH
GH is secreted in ___
pulses
GROWTH HORMONE:
Between pulses, level of GH may be ____ leading to clinical evaluation of ____ based on a ____, ____
undetectable;
GH deficiency;
single;
challenging measurement
Other modifiers of Growth hormone secretion that STIMULATES GH Secretion
Sleep
Exercise
Physiologic stress
Amino acids
Hypoglycemia
Sex steroids
α-Agonists
β-Blockers
Other modifiers of Growth hormone secretion that INHIBITS GH Secretion
Glucose loading
β-Agonists
α-Blockers
Emotional/psychogenic stress
Nutritional deficiencies
Insulin deficiency
Thyroxine deficiency
EXAMPLE of amino acids used to STIMULATE GH secretions
Arginine
EXAMPLE of α-Agonists used to STIMULATE GH secretions
norepinephrine
EXAMPLE of β-blockers used to STIMULATE GH secretions
propranolol
EXAMPLE of β-Agonists used to INHIBIT GH secretions
epinephrine
EXAMPLE of α-Blockers used to INHIBIT GH secretions
phentolamine
Amphibolic hormone
GH
GH is ____ hormone
Amphibolic hormone
anabolic effects of the action of GH (Amphibolic hormone)
Reflected by enhanced ____ in
tissues which is translated into ___ and
phosphate retention
protein synthesis;
positive nitrogen balance;
phosphate retention
ACTIONS OF GH:
Major effect is permitting the effective ___ of an individual from ___ to ____ (without experiencing a ___ of _____)
transition ;
fed state ;
fasting state ;
shortage ;
substrates
Major effect is permitting the effective transition of an individual from fed state to fasting state
ACTIONS OF GH
ACTIONS OF GH
Directly ___ the effect of ___ on ___
antagonizes ;
insulin ;
glucose metabolism
Directly antagonizes the effect of insulin on glucose metabolism
ACTIONS OF GH
ACTIONS OF GH:
Promotes ___
hepatic gluconeogenesis
Promotes hepatic gluconeogenesis
ACTIONS OF GH
ACTIONS OF GH:
Stimulates ___
lipolysis
Indirect effects of ___ is mediated by ____ (former name) that is
now known as ____
GH ;
somatomedins ;
Insulin-like Growth Factor (IGF)
What are the Indirect effects of GH
→ Hypoglycemia
→ Hyperinsulinemia
→ Stimulation of IGF-1 production
→ Inhibition of neoplastic cell proliferation
→ Higher rates of colorectal cancer risk
Indirect effects of GH that amplifies GH levels
Stimulation of IGF-1 production
___ and ___ levels are measured through ____. Elevated levels
of these two are consistent with sustained ___
IGF-I ;
IGFBP-3 ;
assays ;
excess of GH
Increased IGF-I is associated with ___
Hepatoma
Low IGF-I is associated with ___ (3)
✓ Poorly controlled diabetes
✓ Malnutrition
✓ Chronic illnesses
Individuals with active acromegaly shows ___ levels of IGFBP-3
ABNORMAL
Abnormal levels of IGFBP-3 is seen in individuals with __
active acromegaly
Definitive testing for determination of autonomous production of GH
Oral glucose loading
Oral glucose loading is Performed after ____
overnight fasting
Performed after overnight fasting
Oral glucose loading
In Oral glucose loading, Px is given ___
100g oral glucose load
GH is measured at time zero, 60, and 120 minutes after glucose ingestion
Oral glucose loading
In Oral glucose loading, GH is then measured at time ___, ___, and ___ ___ after ____
zero ;
60 ;
120 ;
minutes ;
glucose ingestion
Result of Oral glucose loading;
Undetectable GH = ___
Normal
Result of Oral glucose loading;
Detectable GH = ___
Acromegaly
Insulin-like Growth Factor (IGF) TESTING:
Gold standard: ___
: Insulin-induced hypoglycemia
Most widely used for testing GH
Combination infusions of GHRH and L-arginine or infusion of L-arginine coupled with oral L-DOPA
: Most widely used for testing GH
Combination infusions of ____ and ____ or ___ of L-arginine
coupled with oral ____
GHRH ;
L-arginine ;
infusion ;
L-DOPA
What is the GH levels of patient who is not GH deficient
> 3-5 ng/mL
Results from pathologic or autonomous GH excess and pituitary tumor
ACROMEGALY
ACROMEGALY
Results from pathologic or autonomous _________and _________
GH excess
pituitary tumor
tumors causing acromegaly are results of the ectopic production of _________
GHRH (Growth Hormone-Releasing Hormone)
Diseases Associated with Acromegaly
Gigantism
Patient with GH-producing tumors may develops
Gigantism
FEATURES OF GIGANTISM
✓ progressive enlargement of the ____________
✓ growth of ________, including the _______ and bones of the ____
✓ significant gaps between their _____
✓ overgrowth of the _____________ or the ______ can produce a debilitating form of ________.
hands and feet
facial bones, mandible, skull.
teeth
ends of long bones, spine, arthritis
Enumerate the clinical features of gigantism
● Overt Diabetes or glucose intolerance
● Hypertension
● Accelerated atherosclerosis
● Proximal muscle weakness, resulting from acquired myopathy
● Sleep apnea is common
● Organomegaly, especially thyromegaly, is common.
● Hyperthyroidism
Symptoms of Acromegaly
● Excessive sweating or heat intolerance
SYMPTOMS OF ACROMEGALY
If left untreated, acromegaly increases risk of the following:
✓ heart disease, resulting from the combination of hypertension
✓ coronary artery disease
✓ diabetes/insulin resistance
✓ risk of developing cancer
DIAGNOSIS
T/F: however, some patients with acromegaly have normal random levels of GH.
True
DIAGNOSIS
● patients with normal, random levels of GH, elevated levels of ____
IGF-I
Definitive test for acromegaly
nonsuppressibility of GH to glucose loading
TREATMENT ACROMEGALY
Transsphenoidal adenomectomy
External beam or focused irradiation
THREE DIFFERENT CLASSES OF GH SUPPRESSION AGENTS
SS analogs
dopaminergic agonists
GH receptor antagonists
Example of SS analogs
octreotide and lanreotide
Example of dopaminergic agonists
cabergoline and bromocriptine
Example of GH receptor antagonist
pegvisomant
GH deficiency occurs in
both children and adults.
GH DEFECIENCY
In ______, it may be familial or due to tumors, such as _____________.
children
craniopharyngiomas
GH DEFECIENCY
In _______, it is a result of structural or functional abnormalities of the _______.
adults
pituitary
GENETIC DEFECT
A (recessive/dominant) mutation in the _____ gene that causes a failure of GH secretion
recessive
GHRH
In genetic defect, there is a loss of ______
GH gene itself
GENETIC DEFECTS
Mutations that cause GH ______
insensitivity
GENETIC DEFECTS
structural lesions of the ______ or _______ may also cause GH deficiency and may be associated with other _____________________________.
pituitary
hypothalamus
anterior pituitary hormone deficiencies
An ___________ has been described in patients who have complete or even partial failure of the anterior pituitary.
adult GH deficiency syndrome
An adult GH deficiency syndrome has been described in patients who have complete or even partial failure of the _________
anterior pituitary.
Symptoms of Adult GH Deficiency Syndrome
✓ __________
✓ _________
✓ _________
✓ _____________________
✓ Frequent concomitants of adult GH deficiency are __________ and alterations in _________
✓ ___________ with the advent of recombinant ________
✓ social withdrawal
✓ fatigue
✓ loss of motivation
✓ diminished feeling of wellbeing
✓ Osteoporosis, body composition
✓ GH replacement therapy, human GH
Considered a stress hormone
Prolactin
Prolactin is considered as a _____
stress hormone
● Has vital functions in relation to reproduction
Prolactin
Prolactin has has vital functions in relation to _______
reproduction
Classified as a direct effector hormone
Prolactin
Prolactin is classified as a ___________
direct effector hormone
the physiologic effect of prolactin is ________
lactation
● tonic inhibition is its major mode of hypothalamic regulation
Prolactin
PROLACTIN
● _________is its major mode of hypothalamic regulation
tonic inhibition
inhibits prolactin
Dopamine
Pituitary tumor directly secreting prolactin
Prolactinoma
Most common type of functional pituitary tumor
Prolactinoma
PROLACTINOMA
Clinical presentation depends on the ________ of the patient and the ________
age and gender
size of the tumor
HYPERPROLACTINEMIA CAUSES
● Medications (dopaminergic antagonist)
● Disruption of the pituitary stalk
● Increased Thyrotropin-releasing Hormone
● Pathologic stimulation of neural sucking reflex
● Primary thyroidal failure
● Renal failure
● Polycystic ovary syndrome
● Pregnancy
● Exercise and seizures
MANAGEMENT OF PROLACTINOMA
Therapeutic goals
- Decreasing tumor mass
- Restoration of normal gonadal function and fertility
- Osteoporosis prevention
- Preservation of normal anterior and posterior pituitary function
MANAGEMENT OF PROLACTINOMA
Therapeutic Options
- Simple observation
- Surgery
- Radiotherapy
- Medical management with dopamine agonists
FACTORS TO CONSIDER FOR PROLACTINOMA MANAGEMENT:
- Tumor size
- Preferences of the patien
TUMOR SIZE
Macroadenomas
Microadenomas
Macroadenomas size
> 10 mm
Microadenomas size
<10 mm
Among the tumor sizes, which is LESS likely to be cured?
Macroadenomas
most commonly used therapy for microprolactinomas
Dopamine agonists
● cause tumor shrinkage in >90% of patients
DOPAMINE RECEPTOR AGONISTS:
DOPAMINE RECEPTOR AGONISTS:
● cause tumor shrinkage in ____ of patients
> 90%
DOPAMINE RECEPTOR AGONISTS:
also shrink ________________
prolactin-secreting macroadenomas
T/F: Dopamine receptor agonist is discontinued during pregnancy unless tumor regrowth is detected
True
Types of Dopamine receptor agonists
- Bromocriptine mesylate
- Cabergoline
Example of Bromocriptine mesylate
Parlodel
Example of Cabergoline
Dostinex
DOPAMINE RECEPTOR AGONISTS
Has an adverse effects
Bromocriptine mesylate
What are the adverse effect of Bromocriptine mesylate
orthostatic hypotension, dizziness,
nausea, GI problems
BROMOCRIPTINE MESYLATE
Remedy for GI adverse effects: __________
intravaginal administration
DOPAMINE RECEPTOR AGONISTS
Fewer adverse effects
Cabergoline (Dostinex)
DOPAMINE RECEPTOR AGONISTS
Administered weekly due to its longer duration of action
Cabergoline (Dostinex)
Cabergoline (Dostinex) is linked to
valvular heart disease development
Cabergoline (Dostinex) is linked to valvular heart disease development - due to its ability to interact with _________________________________________________
5-hydroxytryptamine (5-HT)2B serotonergic receptor
NOT a primary mode of prolactinoma management
NEUROSURGERY
● Indications for neurosurgical intervention:
- Pituitary tumor apoplexy (hemorrhage)
- Acute visual loss due to macroadenoma
- Cystic prolactinoma
- Intolerance to medical therapy
- Tumor resistance to dopaminergic agonists
Surgical cure rates are (directly/inversely) proportional to ______ and degree of ________
INVERSELY
tumor size
prolactin elevation.
Reserved for high surgical risk patients with locally aggressive macroadenomas and intolerance to dopamine agonists
RADIOTHERAPY
Radiotherapy is reserved for high surgical risk patients with locally aggressive _________ and intolerance to __________
macroadenomas
dopamine agonists
condition with unknown cause
Idiopathic
- inappropriate lactation
Galactorrhea
Lactation occurring in women with normal prolactin levels
IDIOPATHIC GALACTORRHEA
Seen in women who have been pregnant several times and has no pathologic implication,
IDIOPATHIC GALACTORRHEA
T/F: Idiopathic galactorrhea may be a manifestation of a localized increased sensitivity to prolactin in breast tissue.
True
A diagnosis of exclusion
IDIOPATHIC GALACTORRHEA
Failure of either the pituitary gland or the hypothalamus
Hypopituitarism
● Loss of anterior pituitary function
Hypopituitarism
HYPOPITUITARISM
Loss of ___________
anterior pituitary function
HYPOPITUITARISM
Complete loss of function: ______
panhypopituitarism
HYPOPITUITARISM
Single loss of a pituitary hormone:
monotropic hormone deficiency
HYPOPITUITARISM
Immediate detectable lost hormones:
tropic hormones
Example of tropic hormones lost in Hypopituitarism
ACTH
TSH
LH,
FSH
HYPOPITUITARISM
Delayed unnoticeable lost hormones:
direct effectors (GH and prolactin)
HYPOPITUITARISM LABORATORY DIAGNOSIS
(Primary/Secondary) failure is accompanied by dramatic (decrease/increase) in circulating levels of the corresponding _________
Primary
increases
pituitary tropic hormone
HYPOPITUITARISM LABORATORY DIAGNOSIS
___________ is associated with low or normal levels of ________
Secondary failure
tropic hormones
HYPOPITUITARISM LABORATORY DIAGNOSIS
T/F: Only tropic hormone is measured.
FALSE; Both tropic and target hormone levels should be measured
Most common cause of hypopituitarism
Pituitary tumors
Infections in Hypopituitarism
fungal infections
tuberculosis
syphilis
infiltrative disease in Hypopituitarism
hemochromatosis
sarcoidosis, or
histiocytosis
Immunologic (hypopituitarism)
lymphocytic hypophysitis
Familial (hypopituitarism)
Kallmann’s syndrome; rare
TREATMENT OF PANHYPOPITUITARISM:
● Replacement therapy
● Thyroxine, glucocorticoids, and gender-specific sex steroids
● Pulsatile GnRH infusions:
● Gonadotropin preparations:
TREATMENT OF PANHYPOPITUITARISM:
for patients with Kallmann’s syndrome
Pulsatile GnRH infusions
TREATMENT OF PANHYPOPITUITARISM:
for patients with gonadotropin deficiency
Gonadotropin preparations
POSTERIOR PITUITARY HORMONES a.k.a
NEUROHYPOPHYSIS
Extension of the forebrain
POSTERIOR PITUITARY HORMONES / NEUROHYPOPHYSIS
POSTERIOR PITUITARY HORMONES / NEUROHYPOPHYSIS is extension of the _____
forebrain
Serves as storage for two homologous nonapeptides
POSTERIOR PITUITARY HORMONES / NEUROHYPOPHYSIS
What are the two homologous nonapeptides stored in Posterior pituitary hormones/Neurohhypophysis
ADH & Oxytocin
Both have an autocrine or a paracrine function
ADH & OXYTOCIN
ADH & OXYTOCIN
Both have an ________ or a _______ function
autocrine
paracrine
Originate primarily in the paraventricular nuclei of the hypothalamus
Oxytocin
OXYTOCIN
Originate primarily in the ____________ of the hypothalamus
paraventricular nuclei
Oxytocin plays a major role in
lactation
labor
parturition
OXYTOCIN
Unique because its secretion responds in a ________________
positive feedback mechanism
ACTION OF OXYTOCIN
1) contraction of ___________
2) contraction of the ___________
myoepithelial cells in the breast
uterus
The contraction of myoepithelial cells in the breast causes _________
ejection of milk
The contraction of uterus induces ________
labor
A synthetic oxytocin
Pitocin
● Used in obstetrics to induce labor
Pitocin
Pitocin is used in obstetrics to ______
Induce labor
Recent Studies linked Oxytocin to a variety of biosocial behaviors including _________ and ___________
maternal nurturing
mother-infant bonding.
Oxytocin, also has been shown to have effects on ________________ (5)
pituitary
renal
cardiac
metabolic
immune function
Synthesized by hypothalamic supraoptic nuclei
ADH
ADH is synthesized by
hypothalamic supraoptic nuclei
ADH
Stimulus: (inc/dec) plasma osmolality, (inc/dec) BP and BV
inc
dec
ADH
Its significant role is to regulate ___________, hence has a central role in ________
renal free water excretion
water balance
ACTIONS OF ADH
RECEPTORS
V2 receptors
V1 receptors
increases H20 permeability (aquaporin-2) of cells in
renal collecting tubules and ascending loop of Henle via V2 receptors coupled with adenylate kinase
● V2 receptors
V2 RECPETORS
increases H20 permeability (______) of cells in
_________ and ascending _______ via V2 receptors coupled with __________
aquaporin-2
renal collecting tubules
loop of Henle
adenylate kinase
capable of vasoconstriction via V1 receptors coupled
with Phospholipase C
V1 Receptors
V1 RECEPTORS
capable of _________ via V1 receptors coupled
with ______________
vasoconstriction
Phospholipase C
● Regulates release of vasopressin from posterior pituitary
HYPOTHALAMIC OSMORECEPTORS AND VASCULAR
BARORECEPTORS
HYPOTHALAMIC OSMORECEPTORS AND VASCULAR
BARORECEPTORS
● Regulates release of vasopressin from ________
posterior pituitary
extremely sensitive even to small changes in
plasma osmolality
Osmoreceptors
OSMORECEPTORS
______________ADH average osmotic threshold
284 mOsm/kg
T/F: When plasma osmolality increases ADH secretion also increases
True
When plasma osmolality increases ADH secretion also increases, which in turn (reduces/increases) renal free water clearance, (increasing/lowering) plasma osmolality and returning ________
reduces
lowering
homeostasis
Vascular Baroreceptors locations
left atrium
aortic arch
carotid arteries
initiate ADH release in response to decreased BV
or BP – 5% to 10% fall in arterial BP in normal humans
→ Vascular Baroreceptors
VASCULAR BORORECEPTORS
initiate ADH release in response to (increased/decreased) BV
or BP – ______ fall in arterial BP in normal humans
decreased
5% to 10%
T/F: Baroreceptor-induced ADH secretion will override the normal osmotic suppression of ADH secretion
true
PATHOPHYSIOLOGY OF ADH DEFICIENCY
● Diabetes Insipidus
● Primary polydipsia
characterized by polyuria, and polydipsia
● Diabetes Insipidus
A typical patient presents with a partial ADH deficiency
● Diabetes Insipidus
→ Causes of hypothalamic DI:
o Apparent autoimmunity to ADH-secreting neurons
o Trauma
o Diseases affecting pituitary stalk function
o Various CNS or pituitary tumors
____ of patients will have idiopathic DI
30%
Diagnosis of DI
Secured diagnosis of DI if inappropriately (low/high) ADH level with (decreased/increased) plasma osmolality
low
increased
TESTS FOR DIABETES INSIPIDUS
✓ Water deprivation Test
✓ Therapeutic Trial of ADH or Synthetic Analog
✓ Therapeutic Trial of ADH or Synthetic Analog such as ___________
desmopressin (dDAVP)
compulsive water consumption, water intoxication
Primary polydipsia
TREATMENT FOR ADH EXCESS
- Restricting water intake to small amounts each day for ADH excess
- Conivaptan and tolvaptan, ADH V2 receptor antagonists
TREATMENT FOR ADH EXCESS
a historical cornerstone of treatment
- Restricting water intake to small amounts each day for ADH excess
TREATMENT OF ADH EXCESS
approved for management of euvolemic hyponatremia due to ADH excess
Conivaptan and tolvaptan, ADH V2 receptor antagonists
