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Hypothalamic and Pituitary Function, Study notes of Clinical chemistry

Far Eastern University (FEU)Clinical chemistry

The anatomy and embryology of the hypothalamic-hypophyseal unit, which is responsible for regulating the endocrine system. It covers the different types of cells in the anterior pituitary and their functions, as well as the feedback mechanisms that regulate hormone secretion. The document also explains the relationship between a thermostat and a home heating unit as an example of an open-loop negative feedback system. Additionally, it discusses the regulation of temperature, blood pressure, and blood sugar.

Typology: Study notes

2020/2021

Available from 05/09/2023

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J. ANASTACIO│SECTION 14
Hypothalamic & Pituitary Function
Hypothalamic & Pituitary Function
INTRODUCTION
→ MASTER GLAND (pituitary)
→” To spit mucus” (Greek & Latin term)
→
Hypophysis (undergrowth)- due to its position under the
hypothalamus
→Was later proven to be signaled by the brain to secrete
hormones w/c regulate other endocrine glands
→ ABSENCE OF PITUITARY
• Cessation of growth
• Failure of G.T.A. (gonadal, thyroidal, & adrenal)
functions
→TRANSPONDER (transmitter & responder)
• Translates neural input into a hormonal product
• Main na nagrreceive ng signal then magttransmit ng
signal
• EXAMPLE: PG receives signal from the hypothalamus
then hormones will be secreted
→MEDIAN EMINENCE
• Inferior portion of the hypothalamus
• Together w/ pituitary stalk is critical event in the
formation of hypothalamic-hypophyseal unit
→ DIAPHRAGMA SELLA
• Reflection of dura
• Separates the superior portion of the pituitary from the
hypothalamus
• Penetrated by the infundibulum or pituitary stalk
→INFUNDIBULUM
• Connects the anterior pituitary (adenohypophysis) to
the M.E & hypothalamus
• Contains neural & vascular structures that terminate in
the hypophysis
→POSTERIOR PITUITARY
• Neurohypophysis
• Connected to the supraoptic & paraventricular
hypothalamic nuclei (where vasopressin & oxytocin are
produced) by 2 distinct neurosecretory tracts:
“supraopticohypophyseal & tuberohypophyseal”
→HYPOTHALAMIC-HYPOPHYSIAL PORTAL SYSTEM
• Contained in the infundibulum
• Where the adenohypophysis receives 80-90% of blood
supply & hypothalamic factors
• Primary plexus is in the M.E & is composed of capillaries
lacking a blood-brain barrier (fenestrated capillaries)
• Where hypothalamic nuclei that modulate pituitary
fxn terminate their axons
→LACTOTROPHS- Prolactin-secreting cells
→SOMATOTROPHS- Growth Hormone-secreting cells
→THYROTROPHS- Thyroid Stimulating Hormone-secreting cells
→CORTICOTROPHS- AdrenoCorticoTropin Hormone-secreting
cells
→GONADOTROPS-Luteinizing Hormone & Follicle Stimulating
Hormone-secreting cells
→Pulsatile secretions
→Feedback loops
→Environmental or External modification of
performance
→Diurnal rhythms
→OPTIC CHIASM is near the pituitary gland so if there’s a
pituitary tumor, the px will experience symptoms such as
disturbance in vision because the optic chiasm is being
pressed against it.
→HYPOTHALAMUS small region; links nervous system to
endocrine through the adenohypophysis (Anterior pituitary).
Then the adenohypophysis will secrete hormones that will
go to different endocrine glands.
OUTLINE
INTRODUCTION
HYPOTHALAMIC HORMONES
ANTERIOR PITUITARY HORMONES
POSTERIOR PITUITARY HORMONES
HORMONE SECRETION ABNORMALITIES
HYPOPITUITARISM
Hypothalamus
synthesizes
oxytocin,
arginine
vasopressin
(AVP), adh, etc
stimulates
release
Hormones
Release
hormones to
Luh Punta Si GandHang Tita Tomorrow Sa Hauz Coz Ang
Cute Tignan ng Hauz Gusto Lang pala Humingi Free
Sample ng Hotdog
Hormones released
by hypothalamus
are releasing
hormones
ANTERIOR PITUITARY CELL TYPES
FUNCTIONS
Patrick Fed Eli Doritos
Vasopressin &
oxytocin are
produced in the
hypothalamus
(Adenohypophysis)
(Neurohypophysis)
(Infundibulum)
LOCATION: base of the brain & above
the pituitary; connected to PPG
through infundibulum
pf3
pf4
pf5
pf8
pf9

Partial preview of the text

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INTRODUCTION

→ MASTER GLAND (pituitary) → ” To spit mucus” (Greek & Latin term) → Hypophysis (undergrowth)- due to its position under the hypothalamus → Was later proven to be signaled by the brain to secrete hormones w/c regulate other endocrine glands → ABSENCE OF PITUITARY

  • Cessation of growth
  • Failure of G.T.A. (gonadal, thyroidal, & adrenal) functions → TRANSPONDER (transmitter & responder)
  • Translates neural input into a hormonal product
  • Main na nagrreceive ng signal then magttransmit ng signal
  • EXAMPLE: PG receives signal from the hypothalamus then hormones will be secreted → MEDIAN EMINENCE
  • Inferior portion of the hypothalamus
  • Together w/ pituitary stalk is critical event in the formation of hypothalamic-hypophyseal unit → DIAPHRAGMA SELLA
  • Reflection of dura
  • Separates the superior portion of the pituitary from the hypothalamus
  • Penetrated by the infundibulum or pituitary stalk → INFUNDIBULUM
  • Connects the anterior pituitary (adenohypophysis) to the M.E & hypothalamus
  • Contains neural & vascular structures that terminate in the hypophysis → POSTERIOR PITUITARY
  • Neurohypophysis
  • Connected to the supraoptic & paraventricular hypothalamic nuclei (where vasopressin & oxytocin are produced) by 2 distinct neurosecretory tracts: “supraopticohypophyseal & tuberohypophyseal” → HYPOTHALAMIC-HYPOPHYSIAL PORTAL SYSTEM
  • Contained in the infundibulum
  • Where the adenohypophysis receives 80-90% of blood supply & hypothalamic factors
  • Primary plexus is in the M.E & is composed of capillaries lacking a blood-brain barrier (fenestrated capillaries)
  • Where hypothalamic nuclei that modulate pituitary fxn terminate their axons → LACTOTROPHS- P rolactin-secreting cells → SOMATOTROPHS- G rowth H ormone-secreting cells → THYROTROPHS- T hyroid S timulating H ormone-secreting cells → CORTICOTROPHS - A dreno C ortico T ropin H ormone-secreting cells → GONADOTROPS-L uteinizing H ormone & F ollicle S timulating H ormone-secreting cells

→ P ulsatile secretions

→ F eedback loops

→ E nvironmental or E xternal modification of

performance

→ D iurnal rhythms

→ OPTIC CHIASM is near the pituitary gland so if there’s a pituitary tumor, the px will experience symptoms such as disturbance in vision because the optic chiasm is being pressed against it. → HYPOTHALAMUS small region; links nervous system to endocrine through the adenohypophysis (Anterior pituitary).

Then the adenohypophysis will secrete hormones that will

go to different endocrine glands.

OUTLINE

INTRODUCTION

HYPOTHALAMIC HORMONES

ANTERIOR PITUITARY HORMONES

POSTERIOR PITUITARY HORMONES

HORMONE SECRETION ABNORMALITIES

HYPOPITUITARISM

Hypothalamus synthesizes oxytocin, arginine vasopressin (AVP), adh, etc Hypothalamus stimulates release Hormones Release hormones to L uh P unta S i G and H ang T ita T omorrow S a H auz C oz A ng C ute T ignan ng H auz G usto L ang pala H umingi F ree S ample ng H otdog Hormones released by hypothalamus are releasing hormones

ANTERIOR PITUITARY CELL TYPES

FUNCTIONS P atrick F ed E li D oritos Vasopressin & oxytocin are produced in the hypothalamus (Adenohypophysis) (Neurohypophysis) (Infundibulum) LOCATION: base of the brain & above the pituitary; connected to PPG through infundibulum

EMBRYOLOGY & ANATOMY

FUNCTIONAL ASPECTS OF THE

HYPOTHALAMIC-HYPOPHYSEAL UNIT

→ AFFERENT PATHWAYS (INPUTS) TO THE HYPOTHALAMUS

  • Integrated in various specialized nuclei, processed, and then resolved into specific patterned responses →Hypothalamus has many efferent neural connections (outputs) to higher brain centers like the limbic system, the autonomic nervous system, and the pituitary → HYPOTHALAMIC RESPONSE PATTERNS
  • Similar for each specific pituitary hormone & characterized by open-loop negative feedback mechanisms, pulsatility, and cyclicity. → RELATIONSHIP BETWEEN A THERMOSTAT AND A HOME HEATING UNIT
  • Thermostat is set to a given temperature
  • As the temperature in the home falls below the point, the thermostat sends an electrical impulse to the furnace and turns the furnace on
  • Heat is restored to the room and, when the temperature in the room exceeds the predetermined set point, the thermostat turns off the furnace
  • Because the thermostat set point can be adjusted, the furnace–thermostat functional relationship is termed an “open-loop negative feedback system”
  • Means they are subject to external modulation and generally influenced or modified by higher neural input or other hormones → HYPOTHALAMIC-PITUITARY-THYROIDAL AXIS

FEEDBACK MECHANISM

  • Response of endocrine hormone to stimulation or inhibition → NEGATIVE FEEDBACK MECHANISM
    • An increase in certain hormone leads to a decrease of another hormone - A decrease in certain hormone leads to an increase of another hormone - Most hormones follow negative feedback - Reduces change → POSITIVE FEEDBACK MECHANISM
  • An increase in certain hormone leads to increase of another hormone
  • A decrease in certain hormone leads to a decrease of another hormone
  • Amplifies change

OPEN LOOP NEGATIVE FEEDBACK MECHANISM

  1. If the Hypothalamus detect low thyroid hormones, it will release TRH and the target organ is pituitary
  2. So kapag nastimulate na si pituitary gland, it will release TSH and the target organ is the thyroid gland
  3. If mastimulate si thyroid gland, magssynthesize siya ng T3 and T4 na need ng body
  4. If sobrang dami nang nasynthesize na T3 and T4, T3 and T4 will send a feedback sa brain na marami na sila so stop na ang production and yun ang negative feedback
  5. If mastop ang production ng TRH, mawawala ang TSH production, mawawalan ng signal si thyroid para makapgsynthesize ng T3 and T4 kaya bababa na ang production ng T3 and T4 to prevent excessive production of thyroid hormones → SUMMARY If low level ang Thyroid hormone, tataas ang TRH and TSH kasi massense ni brain na walang TH kasi ang tendency ng body ay gumawa ng maraming TH. Pero if nasobrahan, magssend siya ng signal para mapababa ang level ng TRH then TSH level will decrease eventually. → TEMPERATURE REGULATION
  • If malamig, we shiver kasi blood vessels constrict para maconserve ang heat
  • If malamig naman, blood vessels dilate and we sweat para marelease ang heat → BLOOD PRESSURE REGULATION
  • The receptors receive signals para pabagalin or pabilisin ang tibok ng puso para maregulate ang blood pressure → BLOOD SUGAR REGULATION
  • Magbbreakdown ng glycogen if mababa ang glucose
  • If mataas naman, magssecrete ng insulin para mapababa ang sugar

ANTERIOR PITUITARY INTERMEDIATE LOBE

→ Adenohypophysis → Largest portion →Prolactin, tsh, gh, fsh, lh, & acth are synthesized here →Orig. fr: Rathke’s pouch

  • Evagination of buccal ectoderm that extends progressively upward & is enveloped by the sphenoid bone. → Pars intermedialis →Poorly developed →Confuses radiologists - Form nonfunctional, benign, cystic enlargements of the pituitary. POSTERIOR PITUITARY → Neurohypophysis →Arises fr: Diencephalon →Extension of the axon of hypothalamus →Stores and releases oxytocin and vasopressin (antidiuretic hormone) →Oxytocin & adh are made in the hypothalamus kasi

OTHER EXAMPLES

ULTRASHORT

FEDDBACK

LOOP

SHORT FEEDBACK

LOOP

LONG FEEDBACK LOOP

EXAMPLE

(parallelism)

EXAMPLE

(Endocrine feedback loop)

ANTERIOR PITUITARY HORMONES

→Hormones are larger & more complex than those

synthesized in the hypothalamus

→ Tropic

  • Actions specific to another endocrine gland
  • LH, FSH, TSH, & ACTH

→ Direct effectors

  • Act directly on peripheral tissue
  • GH & Prolactin (PRL) HORMO NE

TARGET GLAND STRUCTURE FEEDBACK

HORMONE

LH Gonad (tropic) Dimeric glycoprotein Sex steroids E 2 - Estradiol T- Testosterone FSH Inhibin TSH Thyroid (tropic) Thyroid hormones T3- triiodothyronin e T4- thyroxine ACTH Adrenal (tropic) Single peptide derived from Proopiomelanocor tin (POMC) Cortisol GH Multiple (direct effector) Single peptide Insulin-like growth factor (IGF- 1 ) PRL Breast (direct effector) Unknown MNEMONICS: L eo F ed T im A pple G rapes P ineapple GnRH stimulates secretion of LH, which in turn, stimulates gonadal secretion of sex steroids (Estradiol, Testosterone, & Progesterone). In a classical negative feedback loop, sex steroids inhibit the secretion of gonadotropin-releasing hormone & also appears to have direct negative effect on Gonadotrops. The Sertoli cells produce inhibin which is released to the blood when the sperm count is too high. This inhibits the release of GnRH & FSH which will cause spermatogenesis to slow down. TRH stimulates APG to produce TSH, the TSH then stimulates thyroid to produce TH (T4/T3) until levels in the blood return normal. TH exerts negative feedback control over the hypothalamus & APG, thus, controlling the release of both TRH from hypothalamus & TSH from APG. When ACTH level in blood is low, a group of cells in the hypothalamus release corticotropin-releasing hormone which stimulates pituitary to secrete ACTH into the bloodstream. High levels of ACTH are detected by the adrenal gland receptors which stimulate secretion of cortisol, causing blood levels of cortisol to rise. As cortisol levels rise, they start to slow down the release of CRH from hypothalamus and ACTH from PG. As a result, the ACTH level starts to fall.

LH

→Luteinizing Hormone →Directs testosterone production from Leydig cells in men →Ovulation in women →LH surge in women means ovulation →LH testosterone in men FSH → Follicle-Stimulating Hormone →Responsible for ovarian recruitment and early folliculogenesis in women →Spermatogenesis in men →Responsible for follicle maturation →FSH sperm sa men TSH → Thyroid- Stimulating Hormone →Directs TH production from thyroid gland ACTH → Adrenocorticotropin hormone →Responsible for formation & secretion of cortisol →Regulates adrenal steroidogenesis GH → Growth Hormone → aka Somatotropin →An insulin antagonist →Somatotrophs produce GH → Somatotrophs comprise 1/3 of normal pituitary weight →A single peptide with 2 intramolecular disulfide bridges →Structurally related to prolactin & human placental lactogen →Belongs to the direct effector class of AP hormones →STIMULATED BY

  • Hypothalamic peptide (GHRH) →INHIBITED BY
  • Somatostatin (SS) →Pulse secretion →AVERAGE INTERPULSE INTERVAL
  • 2 - 3 hours →MOST REPRODUCIBLE PEAK
  • Onset of sleep →If the hormonal products from other endocrine glands are replaced (thyroxine, adrenal steroids, & gonadal steroids), growth is not restored until GH is administered. →Have direct effects on substrate metabolism in numerous tissues & stimulates the liver to produce growth factors that are critical in enhancing linear growth →Enhances growth of bone & muscles → AMPHIBOLIC HORMONE
  • Directly influences both anabolic & catabolic processes → ONE MAJOR EFFECT
  • Allows individual to transition from fed state to fasting state w/o shortage of substrates for normal intracellular oxidation →Directly antagonizes effect of insulin on glucose metabolism →Promotes hepatic glucogenesis →STIMULATES LIPOLYSIS
  • Enhanced lipolysis provides oxidative substrate for peripheral tissue like skeletal muscle
  • Conserve glucose for the CNS by stimulating the hepatic delivery of glucose & opposing insulin- mediated glucose disposal →GH DEFICIENCY IN CHILDREN
  • Accompanied by hypolycemia →HYPOGLYCEMIA IN ADULTS
  • Occur if both GH & ACTH are deficient →ANABOLIC EFFECTS OF GH
  • Reflected by enhanced protein synthesis in skeletal muscle & other tissues
  • Translated into a (+) nitrogen balance & phosphate retention →Mediated by factors initially called somatomedins →Structurally homologous to proinsulin →NEW NOMENCLATURE
  • Insulin-growth factor (IGF)
  • EXAMPLE: Somatomedin C (major growth factor induced by GH, now IGF-I) →IGFs have cell surface receptors that are distinct from insulin →Supraphysiologic levels of IGF-II can bleed over on the insulin receptor & cause hypoglycemia →Hyperinsulinemia can partially activate IGF-I receptors →GH stimulates the production of IGF-I from the liver, so IGF-I becomes a biologic amplifier of GH levels.

INDIRECT EFFECTS

ACTIONS OF GROWTH HORMONE

SEX STEROIDS INHIBIN T3/T TRH TSH T4/T CORTISOL

→IGFs are complexed to specific serum binding proteins that have been shown to affect the actions of IGFs in many ways →IGF-binding protein III (IGFBP-III)

  • Best studied member of the IGFBP family.
  • The levels of IGFBP III are positively correlated with IGF-I levels and, as a result, GH levels.
  • Because of this relationship, IGF-I has been used in the clinical evaluation of both GH deficiency and excess →GH deficiency occurs in both children and adults.
  • IN CHILDREN, it may be familial, or it may be due to tumors, such as craniopharyngiomas.
  • IN ADULTS, it is a result of structural or functional abnormalities of the pituitary, however, a decline in GH production is an inevitable consequence of aging and the significance of this phenomenon is poorly understood. →Although GH deficiency in children is manifest by growth failure, not all patients with short stature have GH deficiency. →There have been several genetic defects identified in the GH axis.
  • MORE COMMON TYPE- Recessive mutation in the GHRH gene that causes a failure of GH secretion.
  • RARER MUTATION- Loss of the GH gene itself, has also been observed.
  • Mutations that cause GH insensitivity have also been reported.
  • These mutations may involve the GH receptor, IGF-I biosynthesis, IGF-I receptors, or defects in GH signal transduction. →Patients with GH insensitivity do not respond normally to exogenously administered GH. →Structural lesions of the pituitary or hypothalamus may also cause GH deficiency and may be associated with other anterior pituitary hormone deficiencies. →An adult GH deficiency syndrome has been described in patients who have complete or even partial failure of the anterior pituitary. →SYMPTOMS (extremely vague)
  • Social withdrawal
  • Fatigue
  • Loss of motivation
  • Diminished feeling of well-being
  • But several studies have documented increased mortality in adults who are GH deficient although this relationship is less clear in adults. →Osteoporosis and alterations in body composition (i.e., reduced lean body mass) are frequent concomitants of adult GH deficiency. →GH replacement therapy has become relatively simple with the advent of recombinant human GH. →Currently, the cost of GH is the major limiting factor for replacement. PRL →Prolactin →A pituitary lactogenic hormone & stress hormone →Its AA structure is like GH → Structurally related to GH and human placental lactogen →DIRECT EFFECTOR HORMONE
  • Has diffused target tissue
  • Lacks a single endocrine end organ →UNIQUE AMONG THE AP HORMONES
  • Major mode of hypothalamic regulation is tonic inhibition rather than intermittent stimulation →Initiation & maintenance of lactation. →Has vital functions in relationship to reproduction →PROLACTIN INHIBITORY FACTOR (PIF)
  • Was considered a polypeptide hormone capable of inhibiting prolactin secretion →Dopamine
  • Only neuroendocrine signal that inhibits prolactin and the elusive PIF →Any compound that affects dopaminergic activity in the median eminence of the hypothalamus will also alter prolactin secretion. →MEDICATIONS THAT CAUSE HYPERPROLACTINEMIA
  • Butyrophenones
  • Phenothiazines
  • Metoclopramide
  • Reserpine
  • Tricyclic Antidepressants
  • Methyldopa
  • Antipsychotics →DISRUPTION OF THE PITUITARY STALK
  • Tumors
  • Trauma
  • Inflammation →TRH directly stimulates prolactin secretion and increases in TRH (as seen in primary hypothyroidism) elevate prolactin levels. →Estrogens directly stimulate lactotropes to synthesize prolactin. →PATHOLOGIC STIMULATION OF THE NEURAL SUCKLING REFLEX
  • Likely explanation of hyperprolactinemia associated with chest wall injuries →HYPERPROLACTINEMIA
  • May also be seen in renal failure and polycystic ovary syndrome →PHYSIOLOGIC STRESSORS THAT ELEVATE PROLACTIN
  • Exercise
  • Seizures → FEEDBACK EFFECTOR is unknown →Primary regulation of prolactin secretions
  • Tonic inhibition (e.g., dopamine)
  • Also regulated by several hormones , including:
  1. Gonadotropin Releasing Hormone (GRH)
  2. Thyrotropin-Releasing Hormone (TRH)
  3. Vasoactive Intestinal Polypeptide (VIR) →STIMULATION OF BREASTS
  • Causes the release of prolactin secreting hormones from the hypothalamus through a spinal reflex act. →CONSEQUENCE OF PROLACTIN EXCESS
  • Hypogonadism
  • By suppression of gonadotropin secretion from the pituitary
  • By inhibition of gonadotropin action at the gonad →The suppression of ovulation seen in lactating postpartum mothers is related to this phenomenon. →Inhibits gonadotropin (FSH & LH) kaya if nagpapabreastfeed, walang menses si mother →Pituitary tumor that directly secretes prolactin →Represents the most common type of functional pituitary tumor →CLINICAL PRESENTATION OF PROLACTINOMA depends on:
  • Age
  • Gender
  • Size of the tumor →Premenopausal women most frequently complain of menstrual irregularity/amenorrhea, infertility, or galactorrhea →MEN OR POSTMENOPAUSAL WOMEN SYMPTOMS:
  • Pituitary mass
  • Headaches
  • Visual complaints
  • Reduced libido
  • Erectile dysfunction →The reason(s) for the varied presentations of a prolactinoma are somewhat obscure but likely relate to the dramatic, noticeable alteration in menses or the abrupt onset of a breast discharge in younger women. →By contrast, the decline in reproductive function in older patients may be overlooked as an inexorable consequence of “aging.” →One recently recognized complication of prolactin- induced hypogonadism is osteoporosis. →There are many physiologic, pharmacologic, and pathologic causes of hyperprolactinemia. →COMMON ERROR
  • Ascribe any elevation to a prolactinoma. →ELEVATIONS IN PROLACTIN THAT INDICATE PROLACTINOMA- (>150 ng/mL) →DEGREE OF ELEVATION- correlated with tumor size →MODEST ELEVATIONS (25–100 ng/mL) may be seen with:
  • Pituitary stalk interruption
  • Use of dopaminergic antagonist medications
  • Primary thyroidal failure
  • Renal failure
  • Polycystic ovary syndrome

FUNCTIONS

Antagonize the dopamine D2 receptor causes an elevation in prolactin as a result of interruption of the flow of dopamine from the hypothalamus to the lactotropes, the pituitary prolactin- secreting cells.

GROWTH HORMONE DEFICIENCY

PROLACTINOMA

OTHER CAUSES OF HYPERPROLACTINEMIA

MODIFIERS OF GROWTH HORMONE SECRETION

STIMULATES INHIBITS Sleep Glucose loading Sex steroids (estradiol) β-agonists (epinephrine) Amino acids (arginine) Thyroxine deficiency α- agonists (norepinephrine) α-blockers (phentolamine) β- blockers (propranolol) Exercise Emotional/psychogenic stress Physiologic stress Insulin deficiencies → α- agonists- mimic the action of α-receptors → α- receptors- when activated, has certain effects

  • Norepinephrine stimulates α-receptors
  • β- blockers inhibit the action of β-receptors

POSTERIOR PITUITARY HORMONES

→Extension of forebrain →Represents storage region of vasopressin (ADH) and oxytocin

OXYTOCIN

→Cyclic nonapeptide w/ identical disulfide bridges

(connecting AA residues 1 & 6)

→As a posttranslational modification, C-terminus is

amidated

→PITOCIN

  • Synthetic oxytocin
  • Used in obstetrics to induce labor

→MAJOR ACTION

  • Lactation
  • Major role in labor and parturition (panganganak)
  • Prolactin kasi sa lactation kaya sa oxytocin ay milk

ejection

  • Shown to have effects on pituitary, renal, cardiac, &

immune function

  • Oxytocin functions in the muscle contraction sa

panganganak

→Positive feedback mechanism

VASOPRESSIN

→OTHER NAMES

  • Antidiuretic hormone (ADH)
  • Arginine vasopressin (AVP)
  • Argipressin

→Structurally similar to oxytocin, differs only by 2 AA

→Cyclic nonapeptide w/ identical disulfide bridges

→Vasopressin receptors in the kidney (V 2 ) are concentrated

in the renal collecting tubules & the ascending limb of the

loop of Henle.

→ MAJOR ACTION

  • Regulate renal free water excretion (water balance)
  • Potent pressor agent
    • Effects on blood clotting by promoting factor VII

release from hepatocytes and Von Willebrand Factor

release from endothelium

  • Coupled to adenylate cyclase and when activated,

induces insertion of aquaporin-2, a water channel

protein, into the tubular luminal membrane

→These vasopressin receptors (V1a and V1b) are coupled

to phospholipase C

→Hypothalamic osmoreceptors and vascular

baroreceptors regulate the release of vasopressin from the

posterior pituitary

→The osmoreceptors are extremely sensitive tosmall

changes in plasma osmolality, w/ an average osmotic

threshold for vasopressin release in humans of 284 mOsm/kg

  • As plasma osmolality increases, vasopressin secretion

increases. The consequence is a reduction in renal free

water clearance, a lowering of plasma osmolality, and

a return to homeostasis

  • The vascular baroreceptors (located in the left atrium,

aortic arch, and carotid arteries) initiate vasopressin

release in response to a fall in blood volume or blood

pressure

  • A 5% to 10% fall in arterial blood pressure in normal

humans will trigger vasopressin release; however, in

contrast to an osmotic stimulus, the vasopressin

response to a baroreceptor-induced stimulus is

exponential

  • In fact, baroreceptor-induced vasopressin secretion

will override the normal osmotic suppression of

vasopressin secretion

→DIABETES INSIPIDUS (DI)

  • Characterized by copious production of urine

(polyuria) and intense thirst (polydipsia)

  • Consequence of vasopressin deficiency
  • Total vasopressin deficiency is unusual , PX presents with

a partial deficiency.

  • The causes of hypothalamic DI:

1) Apparent autoimmunity to vasopressin-

secreting neurons

2) Trauma

3) Diseases affecting pituitary stalk function

4) Various central nervous system or pituitary

tumors

→Up to 30% of px will have idiopathic DI

→DEGREE OF VASOPRESSIN DEFICIENCY

  • Determines if the diagnosis can be apparent or may

need extensive investigation

→INAPPROPRIATELY LOW VASOPRESSIN LEVEL WITH AN

ELEVATED PLASMA OSMOLALITY

  • Would yield a reasonably secure diagnosis of DI

→In less obvious cases, the px may require a water

deprivation test and serial determinations of serum and

urine osmolality are performed to check the patient’s ability

to conserve water

→Under selected circumstances, a therapeutic trial of

vasopressin or a synthetic analog, such as dDAVP, may be

offered and used to assess the patient’s response.

  • Amelioration of both polyuria and polydipsia is a

positive response & a presumptive diagnosis of DI is

made

  • If the px has primary polydipsia (compulsive water

drinking), a profound hypo-osmolar state (water

intoxication) can ensue due to the continued ingestion

of copious amounts of fluids and a reduced renal

excretion of free water

→CONIVAPTAN

  • Vasopressin V2 receptor antagonist
  • Approved for the management of euvolemic

hyponatremia due to vasopressin excess

→Both ADH & Oxytocin are synthesized in the supraoptic and paraventricular nuclei of the hypothalamus →They are transported to the neurohypophysis (PPG) via their axons in the hypothalamoneuro- hypophyseal tract

HORMONE SECRETION ABNORMALITIES

Pituitary tumors Gigantism Acromegaly Dwarfism Kallman’s syndrome Diabetes insipidus

  • ‘Di pa nagclose epiphyseal line
  • There is still room for the bone to grow
  • Hahaba ang bone
  • Proportional
  • mababa AVP
  • Diabetes insipidus (DI), characterized by copious production of urine (polyuria) and intense thirst (polydipsia), is a consequence of vasopressin deficiency.
  • Central (no AVP at all)
  • Nephrogenic (insensitive)
  • Delayed/Absent puberty
  • Impaired sense of smell
  • Hypogonadotropic so no tropic hormones (walang GNRH kaya wala magstimulate kay LH and FSH na magsynthesize)
  • Underdeveloped gonads (no testes or ovaries), so no sexual development
  • Small penis (undescended testes na baka nasa may stomach or abdomen pa)
  • No deepening of voice
  • No breast development basta walang development of secondary characteristics
  • (kala mo man kasi nga yung girls walang development so they look like men)
  • Autopsy studies show that 20% of people harbor clinically silent pituitary adenomas
  • Findings consistent with pituitary tumors are observed in 10-30% of normal individuals undergoing MRI examinations
  • They account for 91% of the lesions removed from px who underwent transsphenoidal surgery
  • MOST COMMON- prolactin-secreting pituitary tumors; followed by nonfunctioning/null cell tumors & tumors that secrete GH, gonadotropins, ACTH, or TSH.
  • Close medical follow-up is recommended if the incidentally discovered lesion is hormonally silent & is less than 1cm in diameter.
  • PHYSIOLOGIC ENLARGEMENT- during puberty & pregnancy (due to lactotroph hyperplasia)
  • THYROTROPH OR GONADOTROPH HYPERPLASIA- can be seen in longstanding primary thyroidal or gonadal failure
  • Excess hormones are secreted especially like macroadenoma; prolactin is affected kaya women have irregular menses
  • Results from pathologic or autonomous GH excess & pituitary tumor (in majority of patients)
  • A hypermetabolic condition which causes the px to complain of excessive sweating or heat tolerance
  • Ectopic production of GHRH
  • Closed epiphyseal lines
  • Horizontal growth
  • Slow development of features
  • RESULTS: Enlargement of hands, feet, facial bones, frontal bossing, mandible, & bones of the skull
  • ADVANCED CASE: gap between the teeth
  • OTHER COMPLAINTS: headache or visual disturbance; symptoms related to loss of anterior pituitary hormones (hypopituitarism)
  • Diffuse overgrowth of the ends of long bones or the spine can cause arthritis
  • Not longitudinal if the condition occurred following puberty
  • Because GH is an insulin antagonist, glucose intolerance or overt diabetes can occur. Hypertension, accelerated atherosclerosis, & proximal muscle weakness will result from acquired myopathy may also be seen late in the illness.
  • Sleep apnea is common
  • Organomegaly especially thyromegaly is common
  • Hyperthyroidism is rare unless the tumor cosecretes TSH
    • IF LEFT UNTREATED: shortens life expectancy due to increased risk of heart disease, resulting from hypertension, coronary artery disease, and diabetes/insulin resistance.
    • Confirming the dx of acromegaly is easy. Some px w/ acromegaly have normal random levels of GH. An elevated level of GH that does not suppress normally with glucose loading equates to an easy diagnosis.
    • In px w/ normal, but inappropriately sustained, random levels of GH, elevated levels of IGF-I are helpful; however, nonsuppressibility of GH to glucose loading is the definitive test
    • Challenging treatment
    • GOAL OF TREATMENT- tumor ablation, with continued function of the remainder of the pituitary. Transphenoidal adenomectomy is the procedure of choice
    • If normal GH levels and kinetics (normal suppressibility to glucose) are restored following surgery, the patient is likely cured. Unfortunately, GH-producing tumors may be too large or may invade into local structures that preclude complete surgical extirpation, and the patient is left with a smaller, but hormonally active, tumor. External beam or focused irradiation is frequently used at this point, but it may take several years before GH levels decline. In the interim, efforts are made to suppress GH. Two different classes of agents, somatostatin analogs and dopaminergic agonists, may be employed for GH suppression, but it is important to note that dopaminergic agonists are only effective if the tumor cosecretes prolatin.
    • PEGVISOMANT- a GH receptor antagonist, has recently been approved as an adjuvant in the medical management of acromegaly.

HYPOPITUITARISM

→Failure of either the pituitary or hypothalamus

  • Results in the loss of anterior pituitary function → PANHYPOPITUITARISM
  • Complete loss of function →MONOTROPIC HORMONE DEFICIENCY
  • Loss of only a single pituitary hormone →Loss of a tropic hormone (ACTH, TSH, LH, and FSH) is reflected in function cessation of the affected endocrine gland →Diagnosis is relatively straightforward →PRIMARY FAILURE
  • Accompanied by dramatic increases in circulating levels of the corresponding pituitary tropic hormone →SECONDARY FAILURE (hypopituitarism)
  • Associated with low or normal levels of tropic hormone →In primary hypothyroidism, for example, the circulating levels of thyroxine are low and TSH levels may exceed 200 μU/mL (normal, 0.4–5.0). As a result of pituitary failure in hypothyroidism, TSH levels are inappropriately low and typically less than 1.0 μU/mL. →To differentiate between primary and secondary deficiencies
  • Both tropic and target hormone levels should be measured when there is any suspicion of pituitary failure or as part of the routine evaluation of gonadal or adrenal function
  • If one secondary deficiency is documented, it is essential to search for other deficiency states and the cause for pituitary failure
  • For example, failure to recognize secondary hypoadrenalism may have catastrophic consequences if the patient is treated with thyroxine
  • Similarly, initially overlooking a pituitary or hypothalamic lesion could preclude early diagnosis and treatment of a potentially aggressive tumor

CAUSES OF HYPOPITUITARISM

  1. Pituitary tumors
  2. Parapituitary/hypothalamic tumors
  3. Infarction
  4. Infection
  5. Immunologic
  6. Idiopathic
  7. Infiltrative disease
  8. Familial
  9. Radiation therapy/surgery
  10. Trauma

ETIOLOGY OF HYPOPITUITARISM

→ MOST COMMON CAUSES OF PITUITARY FAILURE

  • Direct effects of pituitary tumors
  • Sequelae of treatment of tumors →PITUITARY TUMORS MAY CAUSE PANHYPOPITUITARISM BY:
  • Compressing or replacing normal tissue
  • Interrupting the flow of hypothalamic hormones by destroying the pituitary stalk → MOST COMMONLY ASSOCIATED
  • Large, nonsecretory pituitary tumors (chromophobe adenomas or null cell tumors)

GH

GH

GIGANTISM

DIABETES INSIPIDUS

KALLMANN’S SYNDROME

PITUITARY TUMORS

ACROMEGALY