TUMORI IPOFISARI GH-SECERNENTI

Presentazione sul tema: "TUMORI IPOFISARI GH-SECERNENTI"— Transcript della presentazione:

1 TUMORI IPOFISARI GH-SECERNENTI

2 ECCESSO DI GH: NON SOLO ACROMEGALIA…

3 Dalla biologia molecolare…
…alla clinica.

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5 CLONALITA’ DEI TUMORI IPOFISARI
- Un tumore può avere una origine MONOCLONALE, che implica il suo sviluppo a partire da una singola cellula geneticamente alterata. - Un tumore può avere una origine POLICLONALE, ossia può originare da un gruppo di cellule stimolate da fattori che ne promuovono la crescita. Policlonale Monoclonale Tumori ipofisi

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9 Voice deepening Headache Snoring , lip, tongue Joint pain

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11 Arachnodactyly (long fingers) Arachnodactyly (long fingers)
                                                                                                                           Arachnodactyly (long fingers) Marfan's syndrome and homocystinuria are the two  conditions to consider. Of these two, Marfan's syndrome is the most common case you will encounter in the  examination. Mention you like to search other physical signs such  as tall habitus, arm span longer than height, high-arched  palate and kyphosclerosis. Ask to examine the eyes for  lens subluxation. The patients may have aphakia due to  lens extraction or dislocation. Return to the top                                             Arachnodactyly (long fingers) Marfan's syndrome and homocystinuria are the two  conditions to consider. Of these two, Marfan's syndrome is the most common case you will encounter in the  examination. Mention you like to search other physical signs such  as tall habitus, arm span longer than height, high-arched  palate and kyphosclerosis. Ask to examine the eyes for  lens subluxation. The patients may have aphakia due to  lens extraction or dislocation. Return to the top                                                                                                                            Polydactyly (extract digit) There are many conditions associated with polydactyly. However, only Laurence-Moon's and Biedl-Bardet's Syndromes are likely to appear in the examination.  The extract digits may not be immediately apparent unless you count  them. In some patients, the digits may have been amputated in childhood  leaving behind only scar(s). Mention that you would like to examine the fundi for any evidence of  pigmentary retinopathy. The examination may be difficult due to a lack  of cooperation as these patients may have associated mental handicap. Return to the top                                    Polydactyly (extract digit) There are many conditions associated with polydactyly. However, only Laurence-Moon's and Biedl-Bardet's Syndromes are likely to appear in the examination.  The extract digits may not be immediately apparent unless you count  them. In some patients, the digits may have been amputated in childhood  leaving behind only scar(s). Mention that you would like to examine the fundi for any evidence of  pigmentary retinopathy. The examination may be difficult due to a lack  of cooperation as these patients may have associated mental handicap. Return to the top                                                                                                                                  Large hands The hands are large and the fingers are broad. The skin on the dorsum  of the hands is thickened (demonstrated by gently pinching the skin). The most likely case is acromegaly. Mention that you like to examine the visual field of the patient for any  evidence of bitemporal hemianopia. Also look for any optic atrophy  which is classically described as bow-tie atrophy. Return to the top                                      Large hands The hands are large and the fingers are broad. The skin on the dorsum  of the hands is thickened (demonstrated by gently pinching the skin). The most likely case is acromegaly. Mention that you like to examine the visual field of the patient for any  evidence of bitemporal hemianopia. Also look for any optic atrophy  which is classically described as bow-tie atrophy. Return to the top                                                                                                                                              Rheumatoid arthritis The hands show symmetrical arthropathy, consisting of: swelling of the phalangeal joints except the distal phalangeal  joints (the swelling is caused by synovial swelling) Z-deformity of the thumb Boutonniere deformity swan neck deformity ulnar deviation of metacarpophalangeal joint volar subluxation of the palm The palmar sides show palmar erythema and wasting of  the muscles. The muscle power may be weak due to compression of the nerve or rupture of the tendon. The function of the hands  such as writing and unbuttoning are usually good despite the gross deformity. Check for the following signs: rheumatoid nodules at the elbows scars at the wrist from operation for carpal  tunnel syndrome associated ocular signs: such as dry eyes  and scleromalacia perforans Return to the top                                              Rheumatoid arthritis The hands show symmetrical arthropathy, consisting of: swelling of the phalangeal joints except the distal phalangeal  joints (the swelling is caused by synovial swelling) Z-deformity of the thumb Boutonniere deformity swan neck deformity ulnar deviation of metacarpophalangeal joint volar subluxation of the palm The palmar sides show palmar erythema and wasting of  the muscles. The muscle power may be weak due to compression of the nerve or rupture of the tendon. The function of the hands  such as writing and unbuttoning are usually good despite the gross deformity. Check for the following signs: rheumatoid nodules at the elbows scars at the wrist from operation for carpal  tunnel syndrome associated ocular signs: such as dry eyes  and scleromalacia perforans Return to the top                                                                                                                 Psoriatic arthropathy The nails show pitting and onycholysis (lifting of the nail from the nail bed). There are swellings of the joints involving the  distal interphalangeal joint (contrast this with rheumatoid arthritis  in which the distal phalangeal joints are not involved). Sometimes the joint involvement may resemble that of rheumatoid arthritis.  Rarely do you get arthritis mutilans (telescoping of phalanges).  The function of the hands is usually good unless the joints are  severely inflamed. Check for the following signs: look for psoriatic plaques (which may not be apparent  on the hands as in the picture here, they have well-defined  edges with whitish scales) at the elbow, knees and behind  the ears mention you would like to examine the eyes on the slit-lamp  for anterior uveitis or signs of past inflammation such as  pigments on the lens or posterior synechiae. Return to the top                                             Psoriatic arthropathy The nails show pitting and onycholysis (lifting of the nail from the nail bed). There are swellings of the joints involving the  distal interphalangeal joint (contrast this with rheumatoid arthritis  in which the distal phalangeal joints are not involved). Sometimes the joint involvement may resemble that of rheumatoid arthritis.  Rarely do you get arthritis mutilans (telescoping of phalanges).  The function of the hands is usually good unless the joints are  severely inflamed. Check for the following signs: look for psoriatic plaques (which may not be apparent  on the hands as in the picture here, they have well-defined  edges with whitish scales) at the elbow, knees and behind  the ears mention you would like to examine the eyes on the slit-lamp  for anterior uveitis or signs of past inflammation such as  pigments on the lens or posterior synechiae. Return to the top

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13 ACROMEGALY Cushing: The pituitary body & its disorders
             Before disease              Disease onset              12 yrs of disease              17 yrs of disease               Square hand               Phalanges

14 Diagnosi Inizio della malattia

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18 MORTALITA’ NELL’ACROMEGALIA
La mortalità nel paziente acromegalico è circa il doppio rispetto a quella attesa nella popolazione sana. La mortalità è legata soprattutto a: Malattie cardio-vascolari Malattie respiratorie Malattie cerebro-vascolari Malattie neoplastiche

19 TERAPIA DELL’ACROMEGALIA
La terapia degli adenomi ipofisari GH-secernenti può essere chirurgica, radioterapica o medica. Essa è finalizzata a: a) rimuovere la neoplasia o ridurne il volume; b) sopprimere l'ipersecrezione ormonale; c) risolvere o almeno limitare insorgenza e progressione delle complicanze; d) correggere eventuali deficit ipofisari associati mediante adeguato trattamento sostitutivo.

20 TERAPIA CHIRURGICA Rappresenta tuttora il trattamento di prima scelta.
Approccio per via trans-sfenoidale. Guarigione > 80% dei casi se microadenoma (< 1 cm diametro), < 50% se macroadenoma (> 1 cm diametro) Guarigione = GH < 2.5 ng/ml Normalizzazione IGF-1 GH (nadir) < 1 (0.3) ng/ml dopo OGTT Melmed et al., J Clin Endocrinol Metab , 2009

21 TERAPIA RADIANTE - La radioterapia è stata per lungo tempo considerata l’opzione terapeutica di seconda scelta e generalmente proposta nelle situazioni in cui le condizioni del paziente non consentano l’intervento o se il tumore è profondamente infiltrato a livello della regione ipotalamica. - La radioterapia può essere effettuata con metodica convenzionale, frazionata a campi contrapposti o stereotassica. - Il limite principale di quest’opzione terapeutica è rappresentato dall’efficacia assai tardiva (anche 10 anni o più) e dalle possibili complicanze (es. frequente ipopituitarismo). - Oggi è spesso opzione di terza scelta.

22 TERAPIA FARMACOLOGICA
Utilizzata come trattamento di “seconda linea” (dopo chirurgia o in attesa di risultato della radioterapia). Tre classi di farmaci disponibili Analoghi della somatostatina (octreotide, lanreotide) (successo 60/70% pz.) Dopamino-agonisti (successo < 10% pz). Antagonisti recettore GH (pegvisomant). Quest’ultimo indicato per pazienti resistenti agli altri trattamenti (circa 30%).

23 La terapia medica può essere trattamento di scelta in casi in cui le dimensioni e l’estensione sia tale da non rendere possibile un successo chirurgico o in presenza di controindicazioni alla chirurgia legate ad età e/o comorbidità del paziente.