dimensions location divisions - semmelweis egyetem · target organ breast liver+ tissues adrenal...

� DIMENSIONS1 cm in diameter0.5 to 1 gm in weight

� LOCATIONSella turcicaA bony cavity

� DIVISIONSAnterior lobePosterior lobePars intermedia

• body temperature

• autonomic nervous system

• emotional and food behavior

• endocrine (via the pituitary)

• circadian rhythm.

�The primary function of the Pituitary Gland is the hormonproduction

�It is considered as the “Master Gland” because it regulates

› Growth

› Development

› Reproduction

Hypothalamic - pituitary axis

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, germcell 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. Uponcycle

0.3-4.0 mIU/l

� Producing in pulses� Act on membrane

receptors� The signal is mediated

by second messengers� Stimulate the emission

of the stored pituitaryhormones

� Stimulate the synthesisof pituitary hormones

� They cause hypertrophyand hyperplasia of targetcells

� Regulate their ownreceptor

� Severe dysmorphic signs

� Recognition after birth or in childhood

� Sometimes recognition is in adolescence orin young adulthood ( delay of puberty,

hypogonadizmus)

Soumeya N Fedala et al.:Congenital midline Abnormalities: About two casesInternational Journal of Clinical Case Reports, 2013, Vol. 3, No. 9

� Etiology is heterogenous� tumour, cyst, vascular defect, bleeding,

inflammation, granulomatous diseases, trauma, irradiation

� 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)

With neurologic symptoms, such as visualimpairment or headache

As an incidental finding on MRI performedfor some other reason

With hormonal abnormalities

� Pituitary adenoma – from the thirddecade; 10% of all intracranialneoplasms

� Other: physiologic enlargement of thepituitary, bening and malignant tumors

� By size and the cell of origin

� < 1 cm: microadenomas

� > 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

� Neurologic symptoms – visual defects(suprasellar extension, leading tocompression of the optic chiasm)

� Headaches

� Diplopia – oculomotor nerve compression– lateral extension

� Pituitary apoplexia – suddenhaemorrhage into the adenoma –headache + diplopia

� Cerebrospinal fluid rhinorrhoea

� Hormone deficiencies

� Most common – gonadotropins : hypogonadism

� Hormone overproduction

�Hormonal evaluation

�Radiologic evaluation

�Clinical evaluation

� May include of both basal hormonemeasurement and dynamic stimulation testing

� All pituitary masses should have screeningbasal hormone measurements, including:

- Prolactin

- TSH, fT4

- ACTH, AM cortisol, midnight salivarycortisol

- LH, FSH, estradiol or testosterone

- Insulin-like growth factor 1 (IGF1)

Dinamic stimulation/suppression testing may be useful in select cases to further evaluate pituitaryreserve and/or for pituitary hyperfunction:

- DXM suppression testing

- Oral glucose GH suppression test

- GHRH, L-Dopa, arginine

- CRH stimulation

- Metyrapone

- TRH stimulation

- GnRH stimulation

- Insulin-induced hypoglycaemia

� All patients with macroadenomas shouldundergo formal visual field testing

�Observation

�Pharmacotherapy

�Surgery

�Radiation therapy

� If less than 20 mm and no neurologic and hormonal abnormalities:

Monitor for adenoma size, visual changes and hormonalhypersecretion 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 thesubsequent two years; if the lesion is stable in this period, thefrequency can be decreased

� Most useful in prolactinomas, alone or withother intervention

� May be used in certain other functioningtumors as adjunctive therapy along withsurgical and/or radiotherapy

� Transnasal, transsphenoidealapproach

� used for 95% of pituitary tumors

Risks of surgery:

- 4.6% post op neurologiccomplication:

- Infarction/haemorrhage

- 2-10.5% diabetes insipidus

- 8.8% fuid and electrolyte

- 2% cerebrospinal fluid rhinorrhoea

- 2% meningitis

- 3.2% cranial nerve 3-4 or6 palsies

�Surgery is the first line treatment of symptomatic pituitary adenomas

�Useful when medical or radiotherapyfails

�Surgery provides prompt relief fromexcess hormone secretion and masseffect

�Indicated in pituitary apoplexy withcompressive symptoms

� 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)

Prolactinoma� Disruption of dopamine - pituitary stalk

compression� Primary hypothyroidism (increases TRH)� 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)

� Most common functional pituitary tumor

� 25-30% of all pituitary adenomas

� Annual incidence 3/100.000

� 10% are lactotroph and somatotroph suchas GH producing

� Presents with amenorrhoea and infertility, osteoporosis

Laboratory investigation

� Basal fasting morning PRL levels ( norm: < 20 ug/L)

� Falsely elevated values may be caused byaggregated forms of circulating PRL, which are biologically inactive(macroprolactinaemia)

� Hypothyreoidism should be excluded

� Treat only if symptomatic

(headache, vision changes)

� Dopamin agonist (Bromocriptine)

� Cabergoline / Quinagolid

Not recommended for breastfeeding

� Transsphenoideal surgery if unsuccessful

� Therapeutic goals include control of hyper-PRL, reduction of tumor size, restoration of menses and fertility, improvement of galactorrhoea

� Dopamine agonists (bromocriptine, cabergoline)

� If causing major visual defect and unresponsive, consider transsphenoidealsurgery

� Bromocriptine until preg occurs, then stop

� 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

� Production in pulses (4-11 pulse/die), dailyrythm

� To check GH only once is not enough

� Stress, eating, physical exercise alsoinfluence GH production

� GH acts on IGF-1– 6 separate binding protein

� 98% - GH producing benign adenoma

� 1-2%: ectopic GHRH producing tumor: hypophysis hyperplasia, hypophysiscarcinoma, iatrogenic GH

� Isolated familiar somatotropinoma – beginsin childhood – gigantism

Adults: Acromegaly

Infants: Gigantism

� 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

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, and GC excess inhibit GH (feedback)

� Estrogen induces GH

� Inactivating mutation of the GHRH receptor causeprofound dwarfism

� GH secretion is pulsatile, with greatest levels atnight

� 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

delay in diagnosis by mean of 9 years

� Reduced overall survival by an average of 10 years

� Major function: maintain metabolichomeostasis and mediate theneuroendocrine stress response

� POMC is the precursor for ACTH

� POMC products in blood are secreted in equimolar amounts (but circulatingconcentrations differ)

� ACTH – adrenal steroid production

� Corticotroph pituitary adenoma, that secretesACTH resulting in chronic overproductionofcortisol by the adrenal glands

� The chronic state of hypercortisolism is associated with significant morbidity thatseverely impairs quality of life

� When untreated or insufficiently treated, CD can lead to increased mortality withcardiovascular disease as leading cause of death

� Weigh gain, muscle weakness, loss of scalp hair, backache, fractures, menstrual irregularity

� Truncal obesity with thin limbs

� Rounded plethoric face

� Dorsocervical and supraclavicular fat pad(Buffalo’s hump)

� Hirsutism

� Skin:› Atrophied, thin cigarette paper-like

› Easy bruisability

› Purplish abdominal striae

› Hyperpigmentation

› Fungal infection of skin and nails

� Myopathy

� Hypertension

� Diabetes mellitus

� Osteoporosis

� hypogonadism

� Urinary free cortisol

� ACTH

� Serum Cortisol (08:00 and 22:00)

� Dexamethasone Suppression Test

� MRI pituitary

� Inferior petrosal sinus sampling

� 1914 - Simmonds

� FSH-LH (gonadotropins)

� H-GH

� TSH

� ACTH

� PRL, vasopressin

� 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 orvascular damage

� Prevalence is 45.5 per 100,000

� Development/structural

� Tumors

� Trauma (surgical, radiation, headinjuries)

� Infarction

› Sheehan Syndrome

› Pituitary apoplexy

� Autoimmune

� Infiltration and infection

� Onset: is usually gradual

� The severity depends on the degree and rapidity of hormones depletion

� The clinical features match those of the target gland

� Thin and dry skin, decreased pigmentation, hair loss

� Breast atrophy, secunder amenorrhoea

� Decreased libido, impotence

� Mental decline, memory loss, slowness, depression, somnolence

� Short stature in childhood, susceptibility forhypoglycaemia, body fat accumulation, delayed teething

� After delivery the milk secretion doesn’tstart

� Treat the underlying disease as well!

� Hydrocortison and after that levothyroxinsupplementation is essential

� Restore fertility is difficult

� GH supplementation in adults is controversial- quality of life improvement