Popaand Fielding (1930) · Target organ breast Liver+ tissues Adrenal cortex Ovary, testicle...
Transcript of Popaand Fielding (1930) · Target organ breast Liver+ tissues Adrenal cortex Ovary, testicle...
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� Popa and Fielding (1930): portalcirculation of the pituitary gland
� 1977 – Medical Nobel Prize: Schallyand Guillemin: hypothalamus has control over the pituitary
• Normal endocrine function requires intact hypothalamus
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� DIMENSIONS1 cm in diameter0.5 to 1 gm in weight
� LOCATION� LOCATIONSella turcicaA bony cavity
� DIVISIONSAnterior lobePosterior lobePars intermedia
Turkish saddle
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• The anterior pituitary is non-neural tissue which unlike the posterior pituitary has no direct nervous connection with the connection with the hypothalamus.
• The tropic hormones secreted by the neurosecretory cells of the hypothalamus reach the target cells of the anterior pituitary by the hypothalamic-pituitary portal system
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�The primary function of the Pituitary Gland is the hormonproduction
�It is considered as the “Master �It is considered as the “Master Gland” because it regulates
› Growth
› Development
› Reproduction
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Hypothalamic Hypothalamic -- pituitary axispituitary axis
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The pituitary hormonesHormone PRL GH ACTH LH, FSH TSH
Horm. Prod. cell
Lactotr somatotr corticotr gonadotr thyreotr
Type of the horm.
PP PP PP GP GP
Secr. stim TSH, estra GHRH, GHRP, ghrelin
CRH, vasopr, cytokins
GnRH, activin, estra
TRH
Secr.inhib. dopamin SS GC, IGF1 Gonadal horm, inhibin
T3,T4, DA,SS, GC
Target organ breast Liver+ tissues Adrenal cortex
Ovary, testicle Thyroid gland
Main effect lactation Stimulation of IGF1, growth
Corticoster. Secr. stimulation
Gonad hormon secr., growth of folliculi, germ cell maturation
T4 synthesis and secr. Stim.
Normal basal plasma cc
5-15 ;5-12ng/ml
Pulsatile secr(non inf)
20-60 pg/ml M: LH: 1-9 IU/l, FSH: 1-8 IU/l FM: dep. Upon cycle
0.3-4.0 mIU/l
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� Producing in pulses� Act on membrane
receptors� The signal is mediated
by second messengersStimulate the emission� Stimulate the emissionof the stored pituitaryhormones
� Stimulate the synthesisof pituitary hormones
� They cause hypertrophyand hyperplasia of targetcells
� Regulate their ownreceptor
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� Severe dysmorphic signs
� Recognition after birth or in childhood
� Sometimes recognition is in adolescence orin young adulthood ( delay of puberty,
hypogonadizmus)hypogonadizmus)
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� 80% sporadic, 20% genetic defect
� Prev: male: 1:10000; female: 1:50000
� Central hypogonadism
� Boys no puberty or� Boys no puberty orpartial, genital hypoplasia
� Girls: no puberty, primary amenorrhoea
� Anosmia ( targetedsmelling tests)
� Brain MRI ( bulbusolfactorius and rhinoencephalon defect)
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� AR
� Prevalence 1:160000
� Retinitis pigmentosa, blindness� Retinitis pigmentosa, blindness
� Hypogonadotropic hypogonadismbecfause of GnRH deficiency
� Obesity
� Developmental defects of
fingers
� Diabetes insipidus
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� Dystrophia adiposogenitalis
� Role of Leptin, or leptin receptor
� Disruption of hunger-
� Etiology is heterogenous
� It can be associatedwith organicdiseases, causing
� Disruption of hunger-satiety centrum and GnRH neurons
� Symptoms: delayed puberty, hypogonadism, overweight
diseases, causingdamage to thehypothalamus(tumour, inflammation)
� It can occur withoutany organic damageas well
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� Prev 1:25000 – 1:50000� Symptoms in newborn
and early childhood(muscle hypotension, difficulty feeding)
� Later hyperphagia, weight gain, dysmorphicdisordersweight gain, dysmorphicdisorders
� Decreased pigmentation� Overweight� Mental retardation� Behavioral defect, sleep
disturbances� Short stature� Central hypogonadism� High plasma ghrelinlevel
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� Etiology is heterogenous� tumour, cyst, vascular defect, bleeding,
inflammation, granulomatous diseases, trauma, irradiation
� Hypopituitarism + disorders of other� Hypopituitarism + disorders of otherhypothalamic structures ( sleep, eating, thermoregulation etc)
� Compression symptoms (headache, hydrocephalus, epilepsia)
� Hypopituitarism, but increasing PRL ( inhibitoryeffect of dopamin falls out)
� Early and often occurs posterior lobe deficiency( diabetes insipidus)
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With neurologic symptoms, such as visualimpairment or headache
As an incidental finding on MRI performedfor some other reason
With hormonal abnormalities
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� Pituitary adenoma – from the third decade; 10% of all intracranial neoplasms
� Other: physiologic enlargement of the pituitary, bening and malignant tumors
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� By size and the cell of origin
� < 1 cm: microadenomas
� > 1 cm: macroadenomas� > 1 cm: macroadenomas
� The tumors can arise from any of cell ofthe anterior pituitary
� May result in increased secretion of hormone produced by the cell
� Decreased secretion of other hormones
due to compression
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� Gonadotroph adenomas - clinically nonfunctioning sellar masses
� Tryreotroph adenomas - can present clinically nonfunctioning, or may cause hyperthyreoidism
� Corticotroph adenomas – Cushing’s disease
� Lactotrophs – hyperprolactinaemia, which leads to hypogonadism in women and men
� Somatotrophs – acromegaly
� Sometimes mixed
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� Neurologic symptoms – visual defects (suprasellar extension, leading to compression of the optic chiasm)
� Headaches
� Diplopia – oculomotor nerve compression – lateral extension
� Pituitary apoplexia – sudden haemorrhage into the adenoma –headache + diplopia
� Cerebrospinal fluid rhinorrhoea
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� Hormone deficiencies – thorough questions
� Most common – gonadotropins : hypogonadism
� Hormone overproduction
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�Hormonal evaluation
�Radiologic evaluation
�Clinical evaluation
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� Preferred imaging study for the pituitary
� Better visualization of soft tissues and � Better visualization of soft tissues and vascular structures than CT
� No exposure to ionizing radiation
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� May include of both basal hormone measurement and dynamic stimulation testing
� All pituitary masses should have screening basal hormone measurements, including:
- Prolactin- Prolactin
- TSH, fT4
- ACTH, AM cortisol, midnight salivary cortisol
- LH, FSH, estradiol or testosterone
- Insulin-like growth factor 1 (IGF1)
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Dinamic stimulation/suppression testing may be useful in select cases to further evaluate pituitaryreserve and/or for pituitary hyperfunction:
- DXM suppression testing- DXM suppression testing- Oral glucose GH suppression test- GHRH, L-Dopa, arginine- CRH stimulation- Metyrapone- TRH stimulation- GnRH stimulation- Insulin-induced hypoglicaemia
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� All patients with macroadenomas should undergo formal visual field testing
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�Observation
�Pharmacotherapy�Pharmacotherapy
�Surgery
�Radiation therapy
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� If less than 20 mm and no neurologic and hormonal abnormalities:
Monitor for adenoma size, visual changes and hormonal hypersecretion in 6 and 12 months, then annually for a few yearshypersecretion in 6 and 12 months, then annually for a few years
� Lesions less than 10 mm and proven to
have no hormonal hypersecretion:Lesions 2 to 4 mm no further testing required
Lesions 5 to 9 mm: MRI can be done once or twice over the subsequent two years; if the lesion is stable in this period, the frequency can be decreased
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� Most useful in prolactinomas, alone or with other interventionother intervention
� May be used in certain other functioning tumors as adjunctive therapy along with surgical and/or radiotherapy
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� Transnasal, transsphenoidealapproach
� used for 95% of pituitary tumors
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Risks of surgery:
- 4.6% post op neurologic complication:
- Infarction/haemorrhage- Infarction/haemorrhage
- 2-10.5% diabetes insipidus
- 8.8% fuid and electrolyte
- 2% cerebrospinal fluid rhinorrhoea
- 2% meningitis
- 3.2% cranial nerve 3-4 or 6 palsies
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�Surgery is the first line treatment of symptomatic pituitary adenomas
�Useful when medical or radiotherapy failsfails
�Surgery provides prompt relief from excess hormone secretion and mass effect
�Indicated in pituitary apoplexy with compressive symptoms
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� Reserved for patients with larger tumorsand/or persistent hormonal hyperfunctiondespite surgical intervention
- Conventional radiotherapy (Slow response, 5-10 yrs. for full effect)
- Gamma knife radiotherapy ( narrowlyfocused area, long term data not yetavailable)
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Prolactin
� Predominant central control mechanism is inhibitory (dopamin)
� This regulatory pathway accounts for PRL � This regulatory pathway accounts for PRL hypersecretion after pituitary stalk section
� TRH and VIP induces PRL release
� Glucocorticoids and thyroid hormone weaklysuppress PRL secretion
� PRL levels rise after exercise, meals, sexualintercourse, minor surgical procedures, generalanaesthesia, myocard. infarction and other formsof acute stress.
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Prolactinoma� Disruption of dopamine - pituitary stalk
compression � Primary hypothyroidism (increases TRH)� Acromegaly� Acromegaly� Estrogen increase (pregnancy), lactation� Liver cirrhosis� PCOS� Chest wall burns-neuronal effect like suckling� Chronic renal failure� Drugs (verapamil, H2 blockers, estrogens,
opiates, dopamine receptor antagonists)
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� Most common functional pituitary tumor
� 25-30% of all pituitary adenomas
Annual incidence 3/100.000� Annual incidence 3/100.000
� 10% are lactotroph and somatotroph suchas GH producing
� Presents with amenorrhoea and infertility, osteoporosis
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Laboratory investigation
� Basal fasting morning PRL levels ( norm: < 20 ug/L)
� Falsely elevated values may be caused by aggregated forms of circulating PRL, which are biologically inactive (macroprolactinaemia)
� Hypothyreoidism should be excluded
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� Treat only if symptomatic
(headache, vision changes)
� Dopamin agonist (Bromocriptine)� Dopamin agonist (Bromocriptine)
� Cabergoline / Quinagolid
Not recommended for breastfeeding
� Transsphenoideal surgery if unsuccessful
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� Therapeutic goals include control of hyperPRL, reduction of tumor size, restoration of menses and fertility, improvement of galactorrhoeaimprovement of galactorrhoea
� Dopamine agonists (bromocriptine, cabergoline)
� If causing major visual defect and unresponsive, consider transsphenoideal surgery
� Bromocriptine until preg occurs, then stop
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� Microadenomas can significantly increase insize
� Visual field check 2-3 mos. MRI prn
� If neurologic symtomps occur during preg, usually about 14 wga, restart treatment
� If severe and unresponsive: 2nd trimesterconsider surgery
: 3rd trimester: Wait until pp
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Pierre Marie párizsi neurológus 1886 –acromegaliaacromegalia„akron”=vég„megas”=nagy
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Adults: Acromegaly
Infants: Gigantism
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� On growth
� In children (as the epiphyses are unfused)
• Increased chondrogenesis
• Increased linear growth ( both inconjunction with somatomedins)
� In adults ( where the epiphyses have fused)
Thickening of bones
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Growth Hormone
� GHRH, ghrelin GHRP stimulate GH release
� Somatostatin (hypothalamus preoptic area) inhibits GH secretion
� IGF-1 is the peripheral target hormone for GH� IGF-1 is the peripheral target hormone for GH
� IGF-1 feeds back to inhibit GH, as well as GC excess
� Estrogen induces GH
� Inactivating mutation of the GHRH receptor cause profound dwarfism
� GH secretion is pulsatile, with greatest levels at night
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� A disorder caused by excess production of GH
� Is rare with prevalence of 36-96 per 1 million
The onset is insidious and very slow leading to � The onset is insidious and very slow leading to
delay in diagnosis by mean of 9 years
� Reduced overall survival by an average of 10 years
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Dysmorphic syndrome
Cardiomyopathy
Colon cancer
Hypertension
Sleep apnoe
QoL
Diabetes mellitus
Arthropathy
Colao et al. Endocr Rev 2006Chanon et al. Best Pract Res EndocrinolMetab 2009Giustina et al Nat Rev Endocinol 2013
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� Major function: maintain metabolic homeostasis and mediate the neuroendocrine stress response
� POMC is the precursor for ACTH
� POMC products in blood are secreted in equimolar amounts (but circulating concentrations differ)
� ACTH – adrenal steroid production
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� Weigh gain, muscle weakness, loss of scalp hair, backache, fractures, menstrual irregularity, hirsutism
� Truncal obesity with thin limbs� Truncal obesity with thin limbs
� Rounded plethoric face
� Dorsocervical and supraclavicular fat pad(Buffalo’s hump)
� Hirsutism
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� Skin:› Atrophied, thin cigarette paper-like
› Easy bruisability
› Purplish abdominal striae
› Hyperpigmentation› Hyperpigmentation
› Fungal infection of skin and nails
� Myopathy
� Hypertension
� Diabetes mellitus
� Osteoporosis
� hypogonadism
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Cushing’ s
Normaldiurnalrythm
Serumcortisollevels
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� Urinary free cortisol
� ACTH
� Serum Cortisol (08:00 and 22:00)� Serum Cortisol (08:00 and 22:00)
� Dexamethasone Suppression Test
� MRI pituitary
� Inferior petrosal sinus sampling
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� 1914 - Simmonds
FSH-LH (gonadotropins)� FSH-LH (gonadotropins)
� H-GH
� TSH
� ACTH
� PRL, vasopressin
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� A disorder in which the pituitary gland fails to produce one or more of its hormones partially or completely.
� Inherited or acquired
� Reflects the mass effect of tumours, consequences of inflammation or vascular damage
� Prevalence is 45.5 per 100,000
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� Development/structural
� Tumors
� Trauma (surgical, radiation, head injuries)injuries)
� Infarction
› Sheehan Syndrome
› Pituitary apoplexy
� Autoimmune
� Infiltration and infection
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� Onset: is usually gradual
� The severity depends on the degree � The severity depends on the degree and rapidity of hormones depletion
� The clinical features match those of the target gland
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� Thin and dry skin, decreased pigmentation, hair loss
� Breast atrophy, secunder amenorrhoea
� Decreased libido, impotence
� Mental decline, memory loss, slowness, � Mental decline, memory loss, slowness, depression, somnolence
� Short stature in childhood, susceptibility for hypoglycaemia, body fat accumulation, delayed teething
� After delivery the milk secretion doesn’t start
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� Treat the underlying disease as well!
� Hydrocortison and after that levothyroxin � Hydrocortison and after that levothyroxin supplementation is essential
� Restore fertility is difficult
� GH supplementation in adults is controversial - quality of life improvement