DIMENSIONS 1 cm in diameter 0.5 to 1 gm in weight. LOCATION Sella turcica A bony cavity. DIVISIONS Anterior lobe Posterior lobe Pars intermedia
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2 DIMENSIONS 1 cm in diameter 0.5 to 1 gm in weight LOCATION Sella turcica A bony cavity DIVISIONS Anterior lobe Posterior lobe Pars intermedia
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4 body temperature autonomic nervous system emotional and food behavior endocrine (via the pituitary) circadian rhythm.
5 The primary function of the Pituitary Gland is the hormonproduction It is considered as the Master Gland because it regulates Growth Development Reproduction
6 Hypothalamic - pituitary axis
7 The pituitary hormones Hormone PRL GH ACTH LH, FSH TSH Horm. Prod. cell Type of the horm. Lactotr somatotr corticotr gonadotr thyreotr PP PP PP GP GP Secr. stim TSH, estra GHRH, GHRP, ghrelin CRH, vasopr, cytokins GnRH, activin, estra Secr.inhib. dopamin SS GC, IGF1 Gonadal horm, inhibin TRH T3,T4, DA,SS, GC Target organ breast Liver+ tissues Adrenal cortex Ovary, testicle Thyroid gland Main effect lactation Stimulation of IGF1, growth Normal basal plasma cc 5-15 ;5-12ng/ml Pulsatile secr(non inf) Corticoster. Secr. stimulation Gonad hormon secr., growth of folliculi, germ cell maturation pg/ml M: LH: 1-9 IU/l, FSH: 1-8 IU/l FM: dep. Upon cycle T4 synthesis and secr. Stim miu/l
8 Producing in pulses Act on membrane receptors The signal is mediated by second messengers Stimulate the emission of the stored pituitary hormones Stimulate the synthesis of pituitary hormones They cause hypertrophy and hyperplasia of target cells Regulate their own receptor
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11 Severe dysmorphic signs Recognition after birth or in childhood Sometimes recognition is in adolescence or in young adulthood ( delay of puberty, hypogonadizmus) Soumeya N Fedala et al.:congenital midline Abnormalities: About two cases International Journal of Clinical Case Reports, 2013, Vol. 3, No. 9
12 Etiology is heterogenous tumour, cyst, vascular defect, bleeding, inflammation, granulomatous diseases, trauma, irradiation Hypopituitarism + disorders of other hypothalamic structures ( sleep, eating, thermoregulation etc) Compression symptoms (headache, hydrocephalus, epilepsia) Hypopituitarism, but increasing PRL ( inhibitory effect of dopamin falls out) Early and often occurs posterior lobe deficiency ( diabetes insipidus)
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14 With neurologic symptoms, such as visual impairment or headache As an incidental finding on MRI performed for some other reason With hormonal abnormalities
15 Pituitary adenoma from the third decade; 10% of all intracranial neoplasms Other: physiologic enlargement of the pituitary, bening and malignant tumors
16 By size and the cell of origin < 1 cm: microadenomas > 1 cm: macroadenomas The tumors can arise from any of cell of the anterior pituitary May result in increased secretion of hormone produced by the cell Decreased secretion of other hormones due to compression
17 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
18 Hormone deficiencies Most common gonadotropins : hypogonadism Hormone overproduction
19 Hormonal evaluation Radiologic evaluation Clinical evaluation
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21 May include of both basal hormone measurement and dynamic stimulation testing All pituitary masses should have screening basal hormone measurements, including: - Prolactin - TSH, ft4 - ACTH, AM cortisol, midnight salivary cortisol - LH, FSH, estradiol or testosterone - Insulin-like growth factor 1 (IGF1)
22 Dinamic stimulation/suppression testing may be useful in select cases to further evaluate pituitary reserve 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
23 All patients with macroadenomas should undergo formal visual field testing
24 Observation Pharmacotherapy Surgery Radiation therapy
25 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 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
26 Most useful in prolactinomas, alone or with other intervention May be used in certain other functioning tumors as adjunctive therapy along with surgical and/or radiotherapy
27 Transnasal, transsphenoideal approach used for 95% of pituitary tumors
28 Risks of surgery: - 4.6% post op neurologic complication: - Infarction/haemorrhage % diabetes insipidus - 8.8% fuid and electrolyte - 2% cerebrospinal fluid rhinorrhoea - 2% meningitis - 3.2% cranial nerve 3-4 or 6 palsies
29 Surgery is the first line treatment of symptomatic pituitary adenomas Useful when medical or radiotherapy fails Surgery provides prompt relief from excess hormone secretion and mass effect Indicated in pituitary apoplexy with compressive symptoms
30 Reserved for patients with larger tumors and/or persistent hormonal hyperfunction despite surgical intervention - Conventional radiotherapy (Slow response, 5-10 yrs. for full effect) - Gamma knife radiotherapy ( narrowly focused area, long term data not yet available)
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32 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)
33 Most common functional pituitary tumor 25-30% of all pituitary adenomas Annual incidence 3/ % are lactotroph and somatotroph such as GH producing Presents with amenorrhoea and infertility, osteoporosis
34 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
35 Treat only if symptomatic (headache, vision changes) Dopamin agonist (Bromocriptine) Cabergoline / Quinagolid Not recommended for breastfeeding Transsphenoideal surgery if unsuccessful
36 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 transsphenoideal surgery Bromocriptine until preg occurs, then stop
37 Microadenomas can significantly increase in size 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 trimester consider surgery : 3rd trimester: Wait until pp
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39 Production in pulses (4-11 pulse/die), daily rythm To check GH only once is not enough Stress, eating, physical exercise also influence GH production GH acts on IGF-1 6 separate binding protein 98% - GH producing benign adenoma 1-2%: ectopic GHRH producing tumor: hypophysis hyperplasia, hypophysis carcinoma, iatrogenic GH Isolated familiar somatotropinoma begins in childhood gigantism
40 Adults: Acromegaly Infants: Gigantism
41 On growth In children (as the epiphyses are unfused) Increased chondrogenesis Increased linear growth ( both in conjunction with somatomedins) In adults ( where the epiphyses have fused) Thickening of bones
42 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 cause profound dwarfism GH secretion is pulsatile, with greatest levels at night
43 A disorder caused by excess production of GH Is rare with prevalence of 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
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47 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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49 Corticotroph pituitary adenoma, that secretes ACTH resulting in chronic overproductionof cortisol by the adrenal glands The chronic state of hypercortisolism is associated with significant morbidity that severely impairs quality of life When untreated or insufficiently treated, CD can lead to increased mortality with cardiovascular disease as leading cause of death
50 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
51 Skin: Atrophied, thin cigarette paper-like Easy bruisability Purplish abdominal striae Hyperpigmentation Fungal infection of skin and nails Myopathy Hypertension Diabetes mellitus Osteoporosis hypogonadism
52 Urinary free cortisol ACTH Serum Cortisol (08:00 and 22:00) Dexamethasone Suppression Test MRI pituitary Inferior petrosal sinus sampling
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54 Simmonds FSH-LH (gonadotropins) H-GH TSH ACTH PRL, vasopressin
55 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
56 Development/structural Tumors Trauma (surgical, radiation, head injuries) Infarction Sheehan Syndrome Pituitary apoplexy Autoimmune Infiltration and infection
57 Onset: is usually gradual The severity depends on the degree and rapidity of hormones depletion The clinical features match those of the target gland
58 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 for hypoglycaemia, body fat accumulation, delayed teething After delivery the milk secretion doesn t start
59 Treat the underlying disease as well! Hydrocortison and after that levothyroxin supplementation is essential Restore fertility is difficult GH supplementation in adults is controversial - quality of life improvement
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