HYPOTHALAMUS & PITUITARY

Modifiers of growth hormone secretion • Tumors are the common cause for the
STIMULATE SECRETION INHIBIT SECRETION irregular and excess GH secretion
Sleep Glucose loading • The procedure of choice for treatment
Exercise Beta agonists (epinephrine) of acromegaly is Transsphenoidal
Physiologic stress Alpha blockers (phentolamine) adenomectomy.
Amino acids (arginine) Emotional/psychogenic stress • After surgery, external beam of focused
Hypoglycemia Nutritional deficiencies irradiation is frequently used. Since the
Sex steroids Insulin deficiency Goal in acromegaly treatment is to
Alpha-agonists (eg. Thyroxine deficiency reduce GH secretion, tx using SS
Norepinephrine) analogs, dopaminergic agonists, and GH
Beta-blockers (propranolol)
receptor antagonists maybe employed.
GH regulation of secretion
GH excess: gigantism
• Stimulated by GHRH (growth hormone releasing hormone) &
“hunger hormone” or ghrelin (produced by the stomach) • Occurs before closure of epiphyseal
bones
• Inhibited by GHIH (growth hormone inhibiting hormone); also
called somatostatin [SS] • Person grows abnormally tall often
reaching 8-9 ft with normal body
• GHIH is also produced in GIT & pancreatic secretions
proportions
GH testing
GH deficiency: Pituitary dwarfism
• Measurement of IGF-1 [previously called somatomedins] &
• in adults, as a result of structural or
IGFBP-3
functional abnormalities of pituitary
• Oral glucose loading
• In children, this could be due to genetic or
• Insulin-induced hypoglycemia
tumor such as craniopharyngiomas.
• Combined infusions of GHRH coupled with oral L-DOPA
• dwarfism
GH pathology
• Other causes of dwarfism
• GH excess : Could be acromegaly or
o Not all short stature have GH
gigantism
deficiency but on genetic defects:
• Acromegaly occurs after epiphyseal
o More common type is recessive mutation of GHRH
plates close
gene
• Characterized by overgrowth of bony
o Other causes: loss of GH gene & GH insensitivity
areas like feet, hands, feet, face
GH deficiency: Adult symptoms
• Women most often affected
• Social withdrawal
Usually a result of pituitary tumor . Acromegaly
• Fatigue
develops slowly that patient complains may
• Loss of motivation
center on local effects of tumors like headache
• Osteoroporosis
or visual complaints
Other signs/symptoms • Alterations of body composition
Popular GH deficient test
• Combination infusions of GHRH and L-arginine
• L-arginine coupled with oral L-DOPA
• Interpretation: GH level rise above 3-5 ng/mL (normal)
GH deficiency: treatment
• GH replacement [ costly]
PROLACTIN
• a protein
Structurally similar to GH & human placental lactogen. Produced by
prolactin cells or Lactotropes
Pro: for; lact: milk
• Females: Stimulates and maintains milk production following
childbirth
• Males: involved in testicular function
• Considered as stress hormone
• Classified as direct effector hormone
• Unique among anterior pituitary hormones
Prolactin regulation
• Stimulated by
Organomegaly, epecially thyrogemaly, is common .but hyperthyroidism is • TRH
rare unless the tumor cosecretes TSH. Co secretion of prolactin is • Estrogen [ decrease level allows
observed in 40% of cases prolactin to induce lactation]
• Diffuse overgrowth of ends • stressors [exercise, seizures]
of long bones/spine can • Stimulation of breast
result to debilitating form of
• Prolactin regulation
arthritis
• PIF once believed to be an inhibitor
• Sleep apnea is common
• Dopamine is now the PIF
• Teeth gaps are observed
MEDICATIONS CAUSING HYPERPROLACTINEMIA
• Acromegaly if not treated
• Phenothiazines
can result to early death.
• Butyrophenones
• It is a progressive disease
• Metoclopramide
that affects the whole body.
 HYPOTHALAMUS & PITUITARY

• Reserpine • It is split from a prohormone: pro-opiomelanocortin (POMC)

• Tricyclic antidepressants • stimulates growth & secretion of adrenal cortex
• Alpha methyldopa Regulation of ACTH
• Antipsychotics • Follows a circadian rhythm
Physiologic effect of prolactin is lactation • Released by corticotropin
Consequence of excess prolactin is hypogonadism release hormone (CRH) & ADH
PROLACTIN PATHOLOGY • Regulated by hypothalamic-
causes of prolactin increase pituitary
• Tumors [prolactinomas] • Affected by both internal &
o the most common type of functional pituitary external factors: fever,
tumor hypoglycemia, stressors
o Prolactin is more than 150 ng/mL Gonadotropins (glyocoproteins)
• Produced by Gonadotropes
• they are: Luteinizing hormone
(LH) and Follicle-stimulating
Hormone (FSH)
• Gonadotropins regulate
functions of gonads
FSH function
• Females: stimulates growth & development of ovarian
follicles, promotes secretion of estrogen by ovaries.
• Males: required for sperm production
LH function
• In females:
o Works with FSH to cause egg-containing follicles to
mature
o Triggers ovulation and promotes synthesis of
• Idiopathic Galactorrhea ovarian hormones
o Seen in women who have been pregnant several • In males:
times and has no pathologic implication o LH stimulates the interstitial cells of the testes to
• Hyperprolactinemia tests produce testosterone
o TSH and Free T4 or total thyroxine and T3 resin Gonadotropin regulation
uptake • Gonadotropins are virtually absent in pre-pubertal age
o If tumor is suspected, tests of other pituitary
function (basal cortisol, LH, FSH, & gender specific
gonadal steroid ( either estradiol or testosterone)
• Management of prolactinemia
o Dopamine agonists are most common treatment to
shrink tumor. Ex are: Bromocriptine mesylate or
cabergoline
o Side effect of Bromocriptine mesylate: orthostatic
hypotension, dizziness and nausea
o Cabergoline has fewer adverse effects
o Neurosurgery is not a primary mode of
prolactinemia management.
o External beam radiotherapy is reserved for high
surgical risk patients with locally aggressive
macroadenomas who are unable to tolerate
dopamine agonists
Thyroid Stimulating Hormone [TSH] glycoprotein.
TSH
• Also called thyrotropin
• stimulates normal secretion of thyroid hormone & growth of
thyroid gland
Regulation of TSH
• Released from thyrotropic cells or
Thyrotropes after TRF stimulation
• regulation by hypothalamus –
pituitary
• Inhibited by GHIH or somatostatin
[SS]
Adrenocorticotropic hormone [ACTH]
a peptide
• ACTH
• Also called corticotropin MELANOCYTE STIMULATING HORMONE [ MSH]
• Secreted by corticotropic cells or a peptide.
Corticotropes • Precursor is proopiomelanocortin(POMC)
• also known as melanotropins or intermedins
 HYPOTHALAMUS & PITUITARY

• MSH stimulate the production and release of melanin (a Pulsatility

process referred to as melanogenesis) • All anterior pituitary hormones are secreted in a pulsatile
by melanocytes in skin and hair fashion.
• MSH actions in the brain have effects on appetite and sexual • The pulse frequency of secretion is regulated by neural
arousal modulation and is specific for each hypothalamic-pituitary-
• May play a role in fat metabolism. end-organ unit.
High MSH seen in:
• pregnancy
• Cushing's disease due to excess ACTH (MSH and ACTH share
the same precursor)
• acanthosis nigricans in the axilla
Hyperpigmentation occurs in
• Hands
• Nipple
• buccal mucosa
• new scars become hyperpigmented, whereas older ones do
not darken.
• Different levels of MSH are not the major cause of racial
variation in skin colour. However, in many red-headed people,
and other people who do not tan well, there are variations in Pulsatility: Three Levels of Integration
their hormone receptors, causing them not respond to MSH • Hypothalamic stimulation–from CNS
in the blood. • Pituitary stimulation–from hypothalamic trophic Hs
Endorphins • Endocrine gland stimulation–from pituitary trophic Hs
• A peptide Three Levels of Integration
• any of a group of hormones secreted within the brain and
nervous system
• They activate the body's opiate receptors, causing an
analgesic effect.
o Inhibit pain perception.
o Effects mimicked by heroin and other opiate drugs.
ANTERIOR PITUITARY HORMONE CONTROL

cyclicity
• The nervous system regulates the cyclic nature of hormone
through external signals
Zeitgeber (time giver)
• It is the process of entraining or synchronizing external cues
into the function of internal biologic clocks.
• Hormones are secreted in different amounts depending of the
time of the day [circadian or diurnal pattern]
• Best examples of cyclicity
o ACTH nadir of secretion is 11:00PM-3:00AM, peak
on awakening or around 6:00-9:00AM
o TSH: 2x higher during the night
o The circadian rhythm of ACTH and the nocturnal
Negative Feedback Controls: Long and Short Loop Reflexes increase of TSH is a result of increased pulse
amplitude.
HYPOPITUITARISM
• PANHYPOPITUITARISM means all pituitary hormones are low
or zero resulting to complete loss of pituitary function
• MONOTROPIC HORMONE DEFICIENCY means a loss of only
one pituitary hormone
Causes of hypopituitarism
• Pituitary tumors
• Parapituitary/hypothalamic tumors
• Trauma
• Radiation therapy/surgery
• Infarction
• Infection
• Infiltrative disease
• Immunologic
• Familial
• Idiopathic
 HYPOTHALAMUS & PITUITARY

Pituitary tumors • Acts primarily on the mammary gland (“letdown reflex”)and

• Direct effects of tumors or the sequelae of treatment of uterus
tumors are the most common causes of pituitary failure • increases contraction of smooth muscle of the vas deferens
• Tumors compress or replace normal tissue or interrupting the thus may also act to facilitate sperm transport (non-pregnancy
flow of hypothalamic hormones by destroying the pituitary state)
stalk • oxytocin has been shown to have effects on pituitary, renal,
hypoPituitarism causing tumors cardiac and immune function.
• Parasellar tumors [meningiomas and gliomas]
• Metastatic tumors [ breast & lung]
• Hypothalamic tumors [craniopharyngiomas or
dysgerminomas]
Pituitary tumors
• Postpartum ischemic necrosis of the pituitary following a
complicated delivery (Sheehan’s syndrome) typically presents
as profound, unresponsive shock or as failure to lactate in the
puerperium.
Panhypopituitarism causing tumors
• Most common are:
o Large, nonsecretory pituitary tumors
o (Chromophobe adenomas or null cell carcinomas)
o Macroprolactinomas
• Rarer type:
o Hemorrhage or pituitary tumor apoplexy
Panhypopituitarism treatment
• Replacement therapy
POSTERIOR PITUITARY Pitocin
• Synthetic oxytocin which is used in obstetrics to induce labor
AVP-arginine vasopressin- a peptide
• Is also known as antiduretic hormone (ADH-old name)
• Also a cyclic nonapeptide with an identical disulfide bridge
• Differs from oxytocin by only 2 amino acids
Why called vasopressin?
• It causes vasoconstriction, primarily of visceral blood vessels,
raising blood pressure. This response targets ADH receptors
found on vascular smooth muscle
Regulation of AVP Secretion
• Response to changes in blood pressure:
o Blood pressure receptors in heart, aortic arch, and
carotid artery
• Increased blood pressure results in decreased AVP release
o decreased water reabsorption
o decreased blood volume, blood pressure
• Decreased blood pressure results in increased AVP release
o increased water
hypophysis: Posterior Pituitary reabsorption
• Extension of the forebrain o increased blood
• Comprised of the endings of axons from cell bodies in the volume, pressure
hypothalamus (supraoptic and paraventricular)
• Axons pass from the hypothalamus to the posterior pituitary Vasopressin major action is to regulate
via the hypothalamohypophysial tract renal free water excretion
• Posterior pituitary hormones are synthesized in the cell bodies AVP and Water Balance
of neurons in the supraoptic and paraventricular nuclei and is • Action: increases permeability
closely linked to the production of neurophysin of the distal convoluted tubule
Hormones of posterior pituitary and collecting ducts to water
• Hormones are stored in vesicles • Result:
in the posterior pituitary until o increased water
release into the circulation reabsorption from urine
o decreased urine volume
Oxytocin- a peptide
o decreased osmolality of interstitial fluids
• Is synthesized as the precursor o increased blood pressure
hormone: prepro-oxyphysin Regulation of AVP Secretion
• Oxy: rapid; tocia: childbirth • Response to osmolality of interstitial fluid:
• Is a cyclic nonapeptide, with o Osmoreceptors in the brain detect changes in
disulfide bridge connecting osmolality of the interstitial fluid or blood.
amino acid residues 1 & 6. o Increased osmolality results in increased [solutes]
• Secretion is increased during AVP release
labor resulting to contraction of o increased water reabsorption
uterine smooth muscles o decreased osmolality of fluids
 HYPOTHALAMUS & PITUITARY

o Decreased osmolality results in decreased ADH • Manage through: fluid restriction; monitoring of Na levels
release = NEGATIVE FEEDBACK!
o decreased water reabsorption
o increased osmolality of fluids
• AVP release is also inhibited by alcohol, caffeine (diuretics) –
dehydrating effect “dry mouth” or intense thirst morning after
→ INCREASED urine output.
o decreased water reabsorption
o increased urinary volume
o potential for dehydration
• Some drugs can also antagonize ADH release: diuretics used to
treat high bp, edema, or CHF.
• Feedback mechanisms in the control of blood osmotic
pressure—the control of ADH.
Feedback mechanisms in the control of blood osmotic pressure—the
control of ADH.

Treatment of vasopressin excess

• Conivaptan and tolvaptan ( vasopressin V2 receptor
antagonists)

POSTERIOR PITUITARY PATHOLOGY

DIABETES INSIPIDUS (DI)
• Insufficient AVP
o This results to impaired water reabsorption from
DCT, collecting ducts. Diabetes: overflow. Insipidus:
tasteless ; distinguishing from mel: honey. Take note
that total vasopressin is unusual, and the typical
patient presents with a partial deficiency.
• increase urine volume 10 times [polyuria]
• intense thirst [ polydipsia]
Hypothalamic DI
Idiopthic DI
tests
• Water deprivation
• Monitoring of fluid osmolality
ADH hypersecretion
• Can occur in children with meningitis or in adults who have
neurosurgery, hypothalamic injury, or cancer [particularly lung
cancer]
• Can also occur after general anesthesia
SIADH
• Syndrome of inappropriate ADH secretion
• Marked by retention of fluid, headache, disorientation due to
brain edema, weight gain & decreased solute concentration in
the blood