IPOPARATIROIDISMO POST-CHIRURGICO

Roma, 7-9 novembre 2014

IPOPARATIROIDISMO POST-CHIRURGICO

IPOPARATIROIDISMO NELL’ADULTO:

COME OTTIMIZZARE LA GESTIONE

Responsabile Scientifico: Professor Luca Persani 8.45-9.00 Introduzione - Luca Persani

SESSIONE I: TIROIDE

Moderatori: Luca Chiovato, Mario Salvi, Laura Fugazzola 9.00-9.15 Ipotiroidismo - Luigi Bartalena 9.15-9.25 Dibattito

9.25-9.40 Ipertiroidismo - Guia Vannucchi 9.40-9.50 Dibattito

9.50-10.05 Tireopatia in gravidanza - Donatella Cortelazzi 10.05-10.15 Dibattito

10.15-10.30 Nodulo tiroideo - Massimiliano Andrioli 10.30-10.40 Dibattito

10.40-11.00 Coffee Break SESSIONE II: IPOFISI

Moderatori: Marco Losa, Maura Arosio, Renato Cozzi, Anna Spada 11.00-11.15 Malattia di Cushing - Carla Scaroni 11.15-11.25 Dibattito

11.25-11.40 Acromegalia - M.Letizia Fatti 11.40-11.50 Dibattito

11.50-12.05 Prolattinoma - Andrea Lania 12.05-12.15 Dibattito

12.15-12.30 Ipopituitarismo - Gianluca Aimaretti 12.30-12.40 Dibattito

12.40-13.30 Lunch SESSIONE III: PARATIROIDI E MEN

Moderatori: Giovanna Mantovani, Leone Ferrari, Luca Persani 13.30-13.45 Ipoparatiroidismo - Stefania Bonadonna 13.45-13.55 Dibattito

13.55-14.10 Iperparatiroidismo - Sabrina Corbetta 14.10-14.20 Dibattito

14.20-14.35 Men 1 - Uberta Verga 14.35-14.45 Dibattito SESSIONE IV: METABOLISMO

Moderatori: Livio Luzi, Cecilia Invitti, Olga Disoteo, Antonio Pontiroli 14.45-15.00 Ipoglicemie ricorrenti - Massimo Scacchi 15.00-15.10 Dibattito

15.10-15.25 Diabete Mellito caso 1 - Antonio Conti 15.25-15.35 Dibattito

15.35-15.50 Diabete Mellito caso 2 - Emanuela Orsi 15.50-16.00 Dibattito

SESSIONE V: GONADI E SURRENE

Moderatori: Paola Loli, Francesco Cavagnini, Bruno Ambrosi, Manuela Simoni 16.00-16.15 Ipogonadismo dell’adulto - Daniele Santi 16.15-16.25 Dibattito

16.25-16.40 PCOS - Alessandra Gambineri 16.40-16.50 Dibattito

16.50-17.05 Incidentaloma surrenalico - Iacopo Chiodini 17.05-17.15 Dibattito

17.15-17.45 Questionario

Al termine dei lavori è prevista la compilazione del questionario ECM

WORKSHOP INTERATTIVO:

fatti e controversie in endocrinologia

venerdi 29 Novembre 2013 Centro di Ricerca e Cura dell’Invecchiamento Via Mosè Bianchi, 90 - Milano

MODALITÀ DI ISCRIZIONE

La partecipazione al Convegno è gratuita. L’iscrizione è obbligatoria e va effettuata collegandosi al sito INTERNET: www.auxologico.it sezione CORSI & CONVEGNI.

L’Evento è accreditato ECM al sistema Age.Na.S, per la categoria dei Medici (Endocrinologia, Malattie Metaboliche e Diabetologia, Medicina Interna, Medicina Generale).

INFORMAZIONI Segreteria Organizzativa

Istituto Auxologico Italiano - Tel: +39 02 619112458, 0323 514272 Fax: +39 02 700509124 - e-mail: [email protected] Ufficio Stampa: [email protected]

RELATORI E MODERATORI

Gianluca Aimaretti - Università A. Avogadro del Piemonte Orientale Bruno Ambrosi - Gruppo Ospedaliero San Donato Massimiliano Andrioli - IRCCS Istituto Auxologico Italiano Milano

Maura Arosio - Università degli Studi di Milano, Ospedale S. Giuseppe, Multimedica, Milano Luigi Bartalena - Università dell’Insubria, Ospedale di Circolo, Varese

Stefania Bonadonna - IRCCS Istituto Auxologico Italiano Milano Francesco Cavagnini - IRCCS Istituto Auxologico Italiano Milano

Iacopo Chiodini - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano Luca Chiovato - Università degli Studi di Pavia, Fondazione Maugeri, Pavia Antonio Conti - IRCCS Istituto Auxologico Italiano Milano

Simona Corbetta - Università degli Studi di Milano, gruppo Ospedaliero San Donato Donatella Cortelazzi - IRCCS Istituto Auxologico Italiano Milano

Renato Cozzi - Ospedale Niguarda Cà Granda Milano Olga Disoteo - Ospedale Niguarda Cà Granda Milano M.Letizia Fatti - IRCCS Istituto Auxologico Italiano Milano Leone Ferrari - Ospedali Riuniti di Bergamo

Laura Fugazzola - Università degli Studi di Milano, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano

Alessandra Gambineri - Università di Bologna, Policlinico S. Orsola Malpighi - Bologna Cecilia Invitti - IRCCS Istituto Auxologico Italiano Milano

Andrea Lania - Università degli Studi di Milano, Istituto Clinico Humanitas Rozzano Milano Paola Loli - Ospedale Niguarda Cà Granda Milano

Marco Losa - IRCCS Ospedale San Raffaele, Università Vita-Salute - Milano Livio Luzi - Università degli Studi di Milano, gruppo Ospedaliero San Donato Giovanna Mantovani - Università degli Studi di Milano, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano

Emanuela Orsi - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano Luca Persani - Università degli Studi di Milano, Istituto Auxologico Italiano, Milano Antonio Pontiroli - Università degli Studi di Milano, Ospedale San Paolo Mario Salvi - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano Daniele Santi - Università degli Studi di Modena e Reggio Emilia

Massimo Scacchi - Università degli Studi di Milano, IRCCS Istituto Auxologico Italiano Carla Scaroni - Dipartimento di Medicina, DIMED, Azienda Ospedaliera - Università di Padova Manuela Simoni - Università degli Studi di Modena e Reggio Emilia

Anna Spada - Università degli Studi di Milano, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano

Guia Maria Vannucchi - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano Uberta Verga - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano

OBIETTIVO FORMATIVO: (18) Contenuti tecnico-professionali (conoscenze e competenze) specifici di ciascuna professione, di ciascuna specializzazione e di ciascuna attività ultraspecialistica.

con il Patrocinio di

con il contributo non condizionato di

Società Italiana Endocrinologia

i

Stefania Bonadonna

U.O. malattie del Metabolismo Minerale Osseo e Reumatologia

Roma, 7-9 novembre 2014

IPOPARATIROIDISMO POST- CHIRURGICO

•  INCIDENZA

•  FATTORI PREDITTIVI

•  TRATTAMENTO ACUTO e CRONICO

•  NB.

Roma, 7-9 novembre 2014

IPOPARATIROIDISMO POST- CHIRURGICO

•  INCIDENZA

•  FATTORI PREDITTIVI

•  TRATTAMENTO ACUTO e CRONICO

•  NB.

Roma, 7-9 novembre 2014

CAUSE  DI  IPOPARATIROIDISMO  

Organiche Funzionali Disgenetiche

!  Post-chirurgico

!  Autoimmune isolato

!  Sindrome poliendocrina autoimmune tipo I

!  Post-terapia radiometabolica

!  Post-terapia radiante esterna

!  Disordini infiltrativi:

-  Emocromatosi -  Malattia di Wilson

-  Malattie granulomatose -  Metastasi

!  Ridotta secrezione di PTH -  Ipomagnesiemia

-  Mutazioni iperattivanti il CaSR -  Anticorpi stimolanti il CaSR -  Iperparatiroidismo materno -  Mutazioni del gene del PTH

!  Resistenza degli organi bersaglio

-  Ipomagnesiemia

-  Pseudoipoparatiroidismo (tipo 1A, 1B, 1C, 2)

!  Sindrome di DiGeorge

!  Autosomico recessivo

!  Legato al cromosoma X

!  Associato a sordità e displasia renale

!  Associato a ritardo mentale e dismorfismo

!  Neuromiopatie mitocondriali

!  Deficit dell’idrossi-acil-CoA-

deidrogenasi

Roma, 7-9 novembre 2014

IPOCALCEMIA POST- CHIRURGICA

Temporary Postthyroidectomy Hypocalcemia

Stephen A. Falk, MD; Eric A. Birken, MD; Daniel T. Baran, MD Arch Otolaryngol Head Neck Surg. 1988;114(2):168-174.

6.9%

Hypocalcaemia following thyroidectomy for thyrotoxicosis.

See AC, Soo KC.

Br J Surg. 1997 Jan;84(1):95-7.

46%

Roma, 7-9 novembre 2014

IPOPARATIROIDIAMO POST-CHIRURGICO

Complications of thyroid surgery: how to avoid them, how to manage them, and observations on their possible effect on the whole patient.

Reeve T, Thompson NW.

World J Surg. 2000 Aug;24(8):971-5. Review.

1.6%

Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany.

Thomusch O, Machens A, Sekulla C, Ukkat J, Lippert H, Gastinger I, Dralle H.

World J Surg. 2000 Nov;24(11):1335-41.

50%

Roma, 7-9 novembre 2014

Roma, 7-9 novembre 2014

PARATIROIDI

Di norma sono in numero di quattro.

Misurano in media 8x3x2 mm Hanno un peso medio di 40 mg.

Il colorito è generalmente giallo ocra o camoscio.

La sede delle paratiroidi superiori è abbastanza costante sulla faccia posteriore dei lobi tiroidei all’altezza

dell’articolazione cricotiroidea ed in prossimità del punto d’ingresso del ricorrente in laringe

Le paratiroidi inferiori sono poste più lateralmente, tra la faccia posteriore ed il margine laterale del lobo tiroideo, in stretta connessione con l’arteria tiroidea inferiore.

La vascolarizzazione delle PARATIROIDI INFERIORI dipende dall’arteria tiroidea inferiore

Le PARATIROIDI SUPERIORI sono vascolarizzate -  dall’arteria tiroidea inferiore nell’80% dei casi, -  dalla branca posteriore dell’arteria tiroidea

superiore nei restanti casi.

Il drenaggio venoso è assicurato dalla rete di scarico

capsulare tiroidea, dal peduncolo venoso del corpo

tiroideo o da entrambi.

Roma, 7-9 novembre 2014

RISCHIO DI

IPOCALCEMIA POST-CHIRURGICA

5476 pazienti sottoposti a tiroidectomia totale

Thomusch O. et al Surgery 2003, 133:180-5

Aumentata vascolarizzazione del parenchima rispetto al gozzo ed al carcinoma

Roma, 7-9 novembre 2014

FATTORI DI RISCHIO PER

IPOPARATIROIDISMO POSTCHIRURGICO

•  Il numero di paratiroidi che rimangono in situ dopo la tiroidectomia totale è di importanza cruciale nel mantenere l’omeostasi calcica nell’immediato post-operatorio

•  Paratiroidectomia accidentale o necessaria per un corretto svuotamento del comparto centrale (paratiroidi asportate insieme ai linfonodi) o nello svuotamento laterocervicale (difficoltoso scarico venoso paratiroideo – possibile lesione vascolare con infarcimento emorragico delle ghiandole)

Sitges-Serra A. et al., Br J Surg. 2010 Nov;97(11):1687-95

442 pazienti (343 con gozzo, 99 con carcinoma)

Roma, 7-9 novembre 2014

COMPLICANZE DEGLI

INTERVENTI DI TIROIDECTOMIA

LRN 22%

Emorragie LSN 8%

3%

Altro 1%

Infezioni 2%

Ipocalcemia 64%

Rosato et al., World J Surg, 28:271, 2004

14.934  pazien-  –  follow-­‐up  a  5  anni  

Roma, 7-9 novembre 2014

IPOCALCEMIA

POST- CHIRURGICA

techniques and the total number of complications. The scientific rigor regarding the choice of cases and information gathering has been assumed also by the eventual evaluation of a specific technical committee accepted by all the units participating in the study.

Results

The 14,934 cases evaluated were split into two major groups: (1) 13,023 (87%) patients who had benign pathology 1953 (15%) in whom it was diffuse and 11,700 (85%) in whom it was nodular, and (2) 1911 (13%) patients with a malignant pathology. The latter pa- thologies were differentiated in 1731 (91%) cases, medullary in 95 (5%), and undifferentiated in 85 (4%).

Altogether there were 11.799 (78%) women and 3131 (22%) men for a female/male ratio of 3.8:1.0. The mean age was 49 years.

The following interventions were performed: 9599 (64.3%) total thyroidectomies (TTs), 3130 (20.9%) total lobectomies (TLs), 1448 (9.7%) subtotal thyroidectomies with a monolateral remnant (MRSTs), and 757 (5.1%) subtotal thyroidectomies with bilateral remnants (BRSTs) (Fig. 1).

Among all the patients, 14,057 (94%) were operated on for the first time, and there were 877 (6%) reoperations. Regarding tech- niques, 5% of the surgeons stated that they did not take the para- thyroid glands into consideration to avoid damaging them, whereas 95% of them sought the parathyroids out or isolated them to pro- tect them. A total of 56% of surgeons individuated the recurrent laryngeal nerve (RLN), 40% uncovered it anatomically, and 4% did not search for it. All the surgeons noted that they took special care not to injure the external branch of the superior laryngeal nerve.

Considering the interventions overall, the rate of complications was 17.4%. If we do not consider transient complications, however, the overall definitive complication rate was 7.1%.

Symptomatic hypocalcemia, which was seen in 10.0% (8.3% tran- sient, 1.7% definitive) of the entire population, accounted for 63%

of all complications. The data indicated that 0.4% of the hypocal- cemia occurred after lobectomy, with 0.07% of these cases defini- tive (a single case); 14.0% after TTs, with 2.2% of the cases perma- nent; and 5.0% after MRSTs and BRSTs, with definitive cases in 0.6% and 0.8%, respectively (Fig. 2). The incidence of definitive permanent hypocalcemia after surgical interventions for thyroid cancer was significantly higher (3.3%) (Fig. 3).

Laryngeal recurrent nerve (LRN) lesions occurred in 3.4% of all patients with operated thyroids and represented 22.2% of all com-

plications. Recurrent monoplegia had a frequency of 2.0%, the de- finitive lesion had a frequency of 1.0%, and diplegia had an inci- dence of 0.4%. After TT there was a total incidence of recurrent lesions of 4.3% (2.4% transient, 1.3% definitive); the incidence of bilateral lesions was 0.6% (half of these patients, or 0.3%, under- went a tracheotomy.

After TL the overall incidence of LRN lesions was 2.0% (1.4%

transient, 0.6% definitive). After MRST and BRST the total inci- dences of the recurrent lesions were, respectively, 3.0% and 2.0%

(1.4% and 1.1% transient, 1.0% and 0.6% definitive, and 0.6% and 0.1% bilateral lesions, respectively).

In the BRST group all bilateral lesions required tracheotomy, but none in the MRST group did so (Fig. 4). Among all the patients with thyroid cancer, the incidence of the LRN lesion was 5.7%.

Significantly different were the percentages for the different types of cancer. Monoplegia was seen in 1.4% of those with differenti- ated tumors (DTs), 5.4% of those with medullary tumors (MTs), and 16.5% of those with anaplastic tumors (ATs). Among those with a DT, diplegia was seen in 0.5%, and tracheotomy was done in 0.2%. In those with an MT diplegia was seen in 3.2%, and in those with an AT it was seen in 3.5% (Fig. 5).

Lesions of the external branch of the superior laryngeal nerve were suspected in 3.7% of the cases because of the typical symptoms (vocal fatigue, difficulty singing note intonation, limitations to the high voice tones). It was documented in only 0.4% cases.

Hemorrhage occurred in 1.2% of all operated thyroids and ac- counted for 8.0% of the total complications. It occurred in these percentages: 1.6% in the TT patients; 0.4% in the TL patients;

2.1% in the BRST patients; 0.5% in the MRST patients (Fig. 6). It was intraoperative in 15% of the cases and postoperative in the

Fig. 1. Gender and operating techniques distribution. T.T: total thyroid- ectomy; T.L.: total lobectomy; M.R.S.T.: subtotal thyroidectomy with monolateral remnant; B.R.S.T.: subtotal thyroidectomy with bilateral rem- nants.

Fig. 2. Postoperative hypocalcemia.

Fig. 3. Hypocalcemia after thyroid cancer surgery.

272 World J. Surg. Vol. 28, No. 3, March 2004

Rosato et al., World J Surg, 28:271, 2004

TIROIDECTOMIA

TOTALE LOBECTOMIA

TOTALE TIROIDECTMIA SUBTOTALE

SVUOTAMENTO MONOLATERALE TIROIDECTMIA SUBTOTALE SVUOTAMENTO BILATERALE

Roma, 7-9 novembre 2014

IPOCALCEMIA

POST-CHIRURGIA PER NEOPLASIA

techniques and the total number of complications. The scientific rigor regarding the choice of cases and information gathering has been assumed also by the eventual evaluation of a specific technical committee accepted by all the units participating in the study.

Results

The 14,934 cases evaluated were split into two major groups: (1) 13,023 (87%) patients who had benign pathology 1953 (15%) in whom it was diffuse and 11,700 (85%) in whom it was nodular, and (2) 1911 (13%) patients with a malignant pathology. The latter pa- thologies were differentiated in 1731 (91%) cases, medullary in 95 (5%), and undifferentiated in 85 (4%).

Altogether there were 11.799 (78%) women and 3131 (22%) men for a female/male ratio of 3.8:1.0. The mean age was 49 years.

The following interventions were performed: 9599 (64.3%) total thyroidectomies (TTs), 3130 (20.9%) total lobectomies (TLs), 1448 (9.7%) subtotal thyroidectomies with a monolateral remnant (MRSTs), and 757 (5.1%) subtotal thyroidectomies with bilateral remnants (BRSTs) (Fig. 1).

Among all the patients, 14,057 (94%) were operated on for the first time, and there were 877 (6%) reoperations. Regarding tech- niques, 5% of the surgeons stated that they did not take the para- thyroid glands into consideration to avoid damaging them, whereas 95% of them sought the parathyroids out or isolated them to pro- tect them. A total of 56% of surgeons individuated the recurrent laryngeal nerve (RLN), 40% uncovered it anatomically, and 4% did not search for it. All the surgeons noted that they took special care not to injure the external branch of the superior laryngeal nerve.

Considering the interventions overall, the rate of complications was 17.4%. If we do not consider transient complications, however, the overall definitive complication rate was 7.1%.

Symptomatic hypocalcemia, which was seen in 10.0% (8.3% tran- sient, 1.7% definitive) of the entire population, accounted for 63%

of all complications. The data indicated that 0.4% of the hypocal- cemia occurred after lobectomy, with 0.07% of these cases defini- tive (a single case); 14.0% after TTs, with 2.2% of the cases perma- nent; and 5.0% after MRSTs and BRSTs, with definitive cases in 0.6% and 0.8%, respectively (Fig. 2). The incidence of definitive permanent hypocalcemia after surgical interventions for thyroid cancer was significantly higher (3.3%) (Fig. 3).

Laryngeal recurrent nerve (LRN) lesions occurred in 3.4% of all patients with operated thyroids and represented 22.2% of all com-

plications. Recurrent monoplegia had a frequency of 2.0%, the de- finitive lesion had a frequency of 1.0%, and diplegia had an inci- dence of 0.4%. After TT there was a total incidence of recurrent lesions of 4.3% (2.4% transient, 1.3% definitive); the incidence of bilateral lesions was 0.6% (half of these patients, or 0.3%, under- went a tracheotomy.

After TL the overall incidence of LRN lesions was 2.0% (1.4%

transient, 0.6% definitive). After MRST and BRST the total inci- dences of the recurrent lesions were, respectively, 3.0% and 2.0%

(1.4% and 1.1% transient, 1.0% and 0.6% definitive, and 0.6% and 0.1% bilateral lesions, respectively).

In the BRST group all bilateral lesions required tracheotomy, but none in the MRST group did so (Fig. 4). Among all the patients with thyroid cancer, the incidence of the LRN lesion was 5.7%.

Significantly different were the percentages for the different types of cancer. Monoplegia was seen in 1.4% of those with differenti- ated tumors (DTs), 5.4% of those with medullary tumors (MTs), and 16.5% of those with anaplastic tumors (ATs). Among those with a DT, diplegia was seen in 0.5%, and tracheotomy was done in 0.2%. In those with an MT diplegia was seen in 3.2%, and in those with an AT it was seen in 3.5% (Fig. 5).

Lesions of the external branch of the superior laryngeal nerve were suspected in 3.7% of the cases because of the typical symptoms (vocal fatigue, difficulty singing note intonation, limitations to the high voice tones). It was documented in only 0.4% cases.

Hemorrhage occurred in 1.2% of all operated thyroids and ac- counted for 8.0% of the total complications. It occurred in these percentages: 1.6% in the TT patients; 0.4% in the TL patients;

2.1% in the BRST patients; 0.5% in the MRST patients (Fig. 6). It was intraoperative in 15% of the cases and postoperative in the

Fig. 1. Gender and operating techniques distribution. T.T: total thyroid- ectomy; T.L.: total lobectomy; M.R.S.T.: subtotal thyroidectomy with monolateral remnant; B.R.S.T.: subtotal thyroidectomy with bilateral rem- nants.

Fig. 2. Postoperative hypocalcemia.

Fig. 3. Hypocalcemia after thyroid cancer surgery.

272 World J. Surg. Vol. 28, No. 3, March 2004

Rosato et al., World J Surg, 28:271, 2004

Roma, 7-9 novembre 2014

0%

10%

20%

30%

40%

50%

60%

70%

80%

5 gg 3 mesi 2 anni

Graves GMN K

INCIDENZA DI

IPOPARATIROIDISMO POST-CHIRURGICO

CASISTICA UO ORL REGGIO EMILIA 1989-2009 – 3.700 PAZIENTI

Michele Zini - Andrea Frasoldati – V erter Barbieri 2010

Roma, 7-9 novembre 2014

IPOPARATIROIDISMO POST-CHIRURGICO

•  INCIDENZA

•  FATTORI PREDITTIVI

•  TRATTAMENTO ACUTO e CRONICO

•  NB.

Roma, 7-9 novembre 2014

Roma, 7-9 novembre 2014

FATTORI PREDITTIVI PER

IPOPARATIROIDISMO POST-CHIRURGICO

•  Un valore di PTH inferiore ai 10 pg/ml nelle prime 24h dopo tiroidectomia totale è predittivo di ipocalcemia in oltre il 90% dei pazienti.

Sitges-Serra A. et al., Br J Surg. 2010 Nov;97(11):1687-95

442 patienti (343 con gozzo, 99 con carcinoma)

Roma, 7-9 novembre 2014

LIVELLI DI PTH:

PREDITTIVI DI IPOPARATIROIDISMO

gruppo 1:

•  dosaggio di PTH a 4 ore

•  trattamento con calcitriolo + calcio se PTH < 10 pg/ml

gruppo 2:

•  Controllo storico senza PTH precoce e trattamento in base alla calcemia

Youngwirth L et al., Surgery. 2010 Oct;148(4):841-4

OUTCOMES: gruppo 1 gruppo 2:

ipocalcemia sintomatica: 7 % 17 %

accessi al PS: 1.8 % 8.0 %

(271 pazienti consecutivi sottoposti a tiroidectomia totale)

Roma, 7-9 novembre 2014

PREVENZIONE  

IPOPARATIROIDISMO  POST-­‐CHIRURGICO  

Meta-analisi di 4 studi (706 pazienti) 346 calcitriolo 288 calcio orale 72 controlli

Ipocalcemia sintomatica in 4% 19% 31%

Conclusione: il trattamento profilattico con Vitamina D e calcio è efficace nel ridurre l’incidenza di sintomi di ipocalcemia transitoria.

Sanabria A et al., International Journal of Surgery 9 (2011)46-51

postoperative paresthesia. Roh¹⁰ showed statistical differences in serum calcium but not in parathyroid hormone on postoperative days 1, 2 and 7. Patients treated with vitamin D or metabolites and oral calcium developed milder symptoms of hypocalcemia in comparison with patients in the control group. There is no infor- mation about the rate of permanent hypoparathyroidism.

The RCTs selected included 706 patients: 346 in the vitamin D or metabolites group, 288 in the oral calcium group and 72 in the control group (Table 3). The rate of hypocalcemia symptoms was 13/346 (4%, 1e23%) patients in the vitamin D or metabolites group, 28/288 (19%, 7e35%) in the oral calcium group and 22/72 (31%, 24e41%) in the control group. The OR value for the comparison between calcitriol þ calcium as compared to no treatment was 0.32 (95% CI, 0.13e0.79). Statistical heterogeneity was not identified (P ¼ 0.45) (Fig. 2). The number needed to treat was six (95% CI, 4e12). The OR value was 0.31 (95% CI, 0.14e0.70) for the compar- ison between the vitamin D or metabolites and exclusive calcium treatment groups. Statistical heterogeneity was not identified (P ¼ 0.40) (Fig. 3). The number needed to treat was six (95% CI, 4e19). The funnel plot for the comparison between vitamin D or metabolites and oral calcium did not show asymmetry. The Begg test showed a P-value of 0.56.

As malignancy and hyperthyroidism rates could be a source of heterogeneity between studies, we used these variables to make a meta-regression. A meta-regression is a statistical method which assesses the effect of a covariable on the final result of the meta- analysis. The results of this regression did not show a statistically significant difference (p > 0.05), but its statistical power is low in reviews with few trials. For the case of intraoperative management of parathyroid glands, the heterogeneity of the data did not allow any adjustment.

4. Discussion

Postoperative hypocalcemia is a common problem after thyroidectomy, due to its high frequency and the decrease in quality of life for patients who suffer from severe symptoms.^1,2 Furthermore, postoperative hypocalcemia has increased the length of stay and discouraged the widespread use of thyroidec- tomy as an outpatient procedure.^3,5,6

Some authors have tried to assess the utility of serum calcium and parathyroid hormone measurements in the postoperative period as a way to predict which patients will develop hypocalcemia.

Selecting the most recent articles published on MEDLINE was expected to elucidate the efficacy of this approach. Toniato et al.⁷ assessed pre- and postoperative measurement of PTH and found a specificity and positive predictive value of 96% and 93%, respec- tively. However, sensitivity was low. Cavicchi et al.²¹found a sensi- tivity of 100% with a specificity ranging from 46 to 85%. Erbil et al.²² found a 16-fold increase in the risk of hypocalcemia with PTH levels under 10 pg/ml. If we assume a specificity of 95% similar to the other studies, the expected sensitivity is approximately 80%. These results show that even in the best hands and with the availability of modern serum tests, it is not easy to predict with certainty which patients are going to develop postoperative hypocalcemia.

Other authors suggested the use of routine prophylactic vitamin D or metabolites þ calcium or exclusive calcium as an alternative strategy to decrease the rate of hypocalcemia, based on the prin- ciple that offering prophylaxis to all patients will help all suscep- tible patients, even those that are not detected by serum tests. This approach would avoid the routine measurement of serum calcium and in cases of symptomatic hypocalcemia; the crisis will be less severe and easy to treat in comparison with patients who do not receive any prophylaxis.^8e12 On the other hand, based on the philosophy of patient-centered outcomes, levels of calcium or PTH do not necessarily represent the most important final clinical outcome for the patients: the symptoms of hypocalcemia. Only four studies assessed the effectiveness of this therapy under the demanding conditions of an RCT. However, although individually the trials showed a statistically significant difference, the sample size of each one was too small to allow reliable conclusions and does not offer a precise estimate. Our meta-analysis with more than 700 patients showed a decrease of almost 70% in the rate of

Table 3

Patients and outcomes data.

AUTHOR VITAMIN D

GROUP

Hypocalcemia symptoms (%)

ORAL CALCIUM GROUP

Hypocalcemia symptoms (%)

NO INTERVENTION GROUP

Hypocalcemia symptoms (%)

PATIENTS TOTAL

Hypocalcemia TOTAL (%)

Roh 45 3 (6.6) 45 11 (24.4) 90 14 (15.5)

Bellantone 26 6 (23.0) 26 9 (34.6) 27 11 (40.7) 79 26 (36.7)

Pisaniello 60 1 (1.6) 60 4 (6.6) 120 5 (4.2)

Tartaglia 104^a 3 (2.8) 202 15 (7.4) 417 94 (22.5)

111^b 0 (0)

215 3 (1.4)

a Vitamin D group 0.5mg.

b Vitamin D group 1m^g.

Table 2

Risk of bias evaluation.

Bellantone Pisaniello Tartaglia Roh

Sequence generation Yes Yes No Yes

Allocation concealment UNCLEAR UNCLEAR UNCLEAR UNCLEAR

Blind evaluation UNCLEAR Yes UNCLEAR UNCLEAR

Incomplete outcome data No No No No

Intention-to-treat analyses Yes Yes Yes Yes

Statistical methods description Yes Yes Yes Yes Intervention criteria description Yes Yes Yes Yes

Odds ratio

.1 1 10

Study Odds ratio % Weight

(95% CI)

0.44 (0.13,1.44)

Bellantone 56.3

0.22 (0.06,0.86)

Roh 43.7

0.32 (0.13,0.79) Overall (95% CI)

Fig. 2. Forrest plot for comparison between vitamin D or metabolites þ calcium vs. no treatment.

A. Sanabria et al. / International Journal of Surgery 9 (2011) 46e51 49

symptomatic postoperative hypocalcemia between the group treated with vitamin D or metabolites þ calcium as compared to no prophylaxis or exclusive calcium groups. These results showed that vitamin D or metabolites þ calcium is the most effective strategy.

However, the confidence intervals are too wide to consider the results obtained to be precise estimates.

The studies showed a significant range of variability in patients’

characteristics. The rate of hyperthyroidism varied from 0 to 13%. In the Tartaglia study¹⁵where the rate of hyperthyroidism was higher, the OR of the individual study was lower, which supports the idea that in cases of high risk, a larger protective effect is expected. Also, the malignancy rate varied from 8 to 83% and the same phenomenon occurs for the case of Roh study¹⁰where the malignancy rate was higher. The same argument could be used to support the inclusion of patients with radical neck dissection as occurred in the Roh study¹⁰ (19%). Recent data from an RCT made by Roh in patients who underwent total thyroidectomy and central neck dissection confirmed these assumptions.²³Even more, the randomized design of the studies compensates for different types of surgery (as neck dissection and methods to identify or manage the parathyroid glands) and variations in the definitions of hypocalcemia. The main principle of randomization is balancing between groups, known and unknown variables that could affect the final outcome. As the rate of permanent hypoparathyroidism was similar between studies it is not expected that variability in the intraoperative management of the parathyroid glands could have an important effect on the results of the study. However, some elements related to methodological quality such as the blind evaluation of results and allocation concealment are weak in this analysis. This diminished the quality of the trials, but this may be an effect of inadequate reporting because the trials did not include all of the elements suggested by the CONSORT statement.²⁴ It is important to note that a lack of blind evaluation and adequate allocation concealment may have biased the results of these studies. One factor to consider is the method of clinical detection of symptoms and the definition of clinically rele- vant hypocalcemia. Up to date, only one instrument has been specifically designed and statistically validated to assess the symp- toms of postoperative hypoparathyroidism, but this scale is not widely applied in trials assessing complications of thyroidectomy.²⁵ Therefore, the detection of the symptom could be biased. However, we consider that a careful collection of data in a previously designed format could compensate the risk of bias derived from this lack of homogeneity in the definition of hypocalcemia.

One probable advantage not included in this analysis is the avoidance of routine serum calcium measurements. If the

prophylaxis is administered, symptoms of hypocalcemia are the markers of an adequate level of serum calcium. Furthermore, some patients present low serum calcium levels but never suffer symp- toms, which could potentially lead to the administration of calcium or to extended hospital stays unnecessarily. Another advantage is the ability to offer thyroidectomy as an outpatient procedure, because the risk of hypocalcemia decreases to very low levels that allow more confident ambulatory control.

Although some concerns exist about the possibility of developing a temporary state of hypercalcemia, these data could not be obtained from the primary trials. Furthermore, the potential adverse vents derived from the treatment in all patients, such as gastric symptoms or constipation, were not adequately assessed in the studies and could represent an increase in costs not considered in the analysis.

In conclusion, the use of prophylaxis for hypocalcemia comprising vitamin D or metabolites þ calcium or exclusive calcium is effective to decrease the incidence of symptoms of temporary hypocalcemia.

Funding

Universidad de La Sabana.

Conflict of interest

The authors do not have any conflict of interest.

Ethical approval

This is a systematic review and do not include patients. The approval was made by the School of Medicine, Universidad de La Sabana.

References

1. Falk SA, Birken EA, Baran DT. Temporary postthyroidectomy hypocalcemia.

Arch Otolaryngol Head Neck Surg1988;114:168e74.

2. Rao RS, Jog VB, Baluja CA, Damle SR. Risk of hypoparathyroidism after surgery for carcinoma of the thyroid. Head Neck 1990;12:321e5.

3. Chia SH, Weisman RA, Tieu D, Kelly C, Dillmann WH, Orloff LA. Prospective study of perioperative factors predicting hypocalcemia after thyroid and parathyroid surgery. Arch Otolaryngol Head Neck Surg 2006;132:41e5.

4. Pisaniello D, Parmeggiani D, Piatto A, Avenia N, d’Ajello M, Monacelli M, et al.

Which therapy to prevent post-thyroidectomy hypocalcemia? G Chir 2005;26:357e61.

5. Mishra AK, Agarwal A. Same-day discharge after total thyroidectomy: the value of 6-hour serum parathyroid hormone and calcium levels. Head Neck 2005;27:1112e3.

6. Payne RJ, Hier MP, Tamilia M, Mac NE, Young J, Black MJ. Same-day discharge after total thyroidectomy: the value of 6-hour serum parathyroid hormone and calcium levels. Head Neck 2005;27:1e7.

7. Toniato A, Boschin IM, Piotto A, Pelizzo M, Sartori P. Thyroidectomy and parathyroid hormone: tracing hypocalcemia-prone patients. Am J Surg 2008;196:285e8.

8. Moore Jr FD. Oral calcium supplements to enhance early hospital discharge after bilateral surgical treatment of the thyroid gland or exploration of the parathyroid glands. J Am Coll Surg 1994;178:11e6.

9. Bellantone R, Lombardi CP, Raffaelli M, Boscherini M, Alesina PF, De Crea C, et al. Is routine supplementation therapy (calcium and vitamin D) useful after total thyroidectomy? Surgery 2002;132:1109e12.

10. Roh JL, Park CI. Routine oral calcium and vitamin D supplements for prevention of hypocalcemia after total thyroidectomy. Am J Surg 2006;192:675e8.

11. Testa A, Fant V, De Rosa A, Fiore GF, Grieco V, Castaldi P, et al. Calcitriol plus hydrochlorothiazide prevents transient post-thyroidectomy hypocalcemia.

Horm Metab Res2006;38:821e6.

12. Uruno T, Miyauchi A, Shimizu K, Tomoda C, Takamura Y, Ito Y, et al. A prophylactic infusion of calcium solution reduces the risk of symptomatic hypocalcemia in patients after total thyroidectomy. World J Surg 2006;30:304e8.

13. Cheah WK, Arici C, Ituarte PH, Siperstein AE, Duh QY, Clark OH. Complications of neck dissection for thyroid cancer. World J Surg 2002;26:1013e6.

14. Higgins J, Green S. Cochrane Handbook for systematic reviews of interventions Version 5.0.0. Chichester, UK: John Wiley & Sons; 2008.

15. Tartaglia F, Giuliani A, Sgueglia M, Biancari F, Juvonen T, Campana FP.

Randomized study on oral administration of calcitriol to prevent symptomatic hypocalcemia after total thyroidectomy. Am J Surg 2005;190:424e9.

16. Bove A, Bongarzoni G, Dragani G, Serafini F, Di Iorio A, Palone G, et al. Should female patients undergoing parathyroid-sparing total thyroidectomy receive routine prophylaxis for transient hypocalcemia? Am Surg 2004;70:533e6.

Odds ratio

.1 1 10

Study Odds ratio % Weight

(95% CI)

0.18 (0.05,0.62)

Tartaglia 42.0

0.24 (0.03,2.19)

Pisaniello 13.4

0.57 (0.17,1.92)

Bellantone 44.6

0.31 (0.14,0.70) Overall (95% CI)

Fig. 3. Forrest plot for comparison between vitamin D or metabolites þ calcium vs.

exclusive calcium.

A. Sanabria et al. / International Journal of Surgery 9 (2011) 46e51 50

Roma, 7-9 novembre 2014

1°gg

2° gg

3° gg

4° gg

5°gg 6°gg 7°gg

0 10 20 30 40 50

numero pazienti

Nadir ipocalcemico - Timing

Casistica UO ORL Reggio Emilia 1989-2009 – 3.700 pazienti

Michele Zini - Andrea Frasoldati – V erter Barbieri 2010

Roma, 7-9 novembre 2014

IPOPARATIROIDISMO POST-CHIRURGICO

•  Ipoparatiroidismo alla dimissione:

–  In tutti i pazienti che vengono dimessi con terapia con calcitriolo e/o calcio

•  Ipoparatiroidismo transitorio

–  In tutti i pazienti in cui sussista il fabbisogno di vitamina D e/o calcio per un periodo inferiore ai 6 mesi

•  Ipoparatiroidismo permanente

–  In tutti i pazienti in cui persista di fabbisogno di vitamina D

e/o calcio a distanza di 6 mesi

Roma, 7-9 novembre 2014

INCIDENZA

IPOPARATIROIDISMO POSTCHIRURGICO

CASISTICA UO ORL REGGIO EMILIA 1989-2009 – 3.700 PAZIENTI

Michele Zini - Andrea Frasoldati – V erter Barbieri 2010

Roma, 7-9 novembre 2014

INCIDENZA DELL’IPOPARATIROIDISMO POSTCHIRURGICO

Ipoparatiroidismo postchirurgico (tiroidectomia totale):

transitorio: 30 %

permanente: fino a 8.6 %

Youngwirth L et al., Journal of Surgical Research 163, 69–71 (2010)

Roma, 7-9 novembre 2014

PROBABILITÀ DI RECUPERO

DELLA FUNZIONE PARATIROIDEA

F i g . 2 . P r o b a b i l i t y o f recovery of parathyroid function in patients with p r o t r a c t e d h y p o p a r a - thyroidism, determined by serum calcium and PTH concentrations at 1 month after total thyroidectomy.

Undetectable PTH: <4 pg/ml low PTH: 4-12 pg/ml

Sitges-Serra A. et al., Br J Surg. 2010

Nov;97(11):1687-95

Roma, 7-9 novembre 2014

IPOPARATIROIDISMO POST-CHIRURGICO

•  INCIDENZA

•  FATTORI PREDITTIVI

•  TRATTAMENTO ACUTO e CRONICO

•  NB.

Roma, 7-9 novembre 2014

IPOPARATIROIDISMO

POST-CHIRURGICO

Roma, 7-9 novembre 2014

(Calcifediolo)

(Calcitriolo)

PTH

IPOPARATIROIDISMO

POST-CHIRURGICO

Roma, 7-9 novembre 2014

PTH

25 (OH)D

1,25 (OH)

D

Assorbimento di calcio dal lume intestinale

Rilascio di calcio dall’osso

calcifediolo calcitriolo

Vit D3 colecalciferolo

fegato

rene

TRATTAMENTO

x

Roma, 7-9 novembre 2014

TRATTAMENTO ACUTO

SE IPOCALCEMIA SEVERA O PAZIENTE SINTOMATICO:

rapido decremento dei valori plasmatici di calcio

-  CRISI IPOCALCEMICA (spesso scatenata da iperventilazione e alcalosi metabolica)

-  Inizia con parestesie periorali e alle estremità

-  CRISI TETANICA

-  Spasmi alla muscolatura del volto e agli arti

-  Adduzione delle braccia al tronco, flessione dell’avambraccio sul braccio -  Mano con atteggiamento a “mano da ostetrico”

-  Spasmo laringeo -  Crisi convulsive

-  Manifestazioni cardiovascolari (iootensione, bradicardia, alterata contrattilità, aritmie)

-  QUADRO TETANICO ATIPICO nelle fasi iniziali -  Astenia cefalea

-  Parestesie

-  Dolore addominale -  Nausea

-  Vomito

IN ETA’ PEDIATRICA -  Tremori

-  Fascicolazioni

-  Crisi convulsive

Roma, 7-9 novembre 2014

TRATTAMENTO ACUTO

Michele Zini 2010

Se ipocalcemia severa o paziente sintomatico:

–  calcio e.v. con controlli quotidiani della calcemia e fosforemia

- inizialmente 2 mg/kg – fiale di calcio gluconato 9.3 mg per ml - poi 15 mg/kg nelle 24 h successive in infusione lenta

–  Calcitriolo 1 mcg/die in 2 somministrazioni

Pazienti in terapia con digitale

Pazienti in terapia anticomiziale

Roma, 7-9 novembre 2014

TRATTAMENTO CRONICO

•  Iniziare terapia se calcemia <7.5 - 8 mg/ml

–  considerare i valori preoperatori

–  tenere conto della distanza dall’intervento –  valutare l’andamento della calcemia

•  Farmaci:

–  calcitriolo 0.25 – 1.5 µg/die

–  calcio 1 – 3 g/die

Roma, 7-9 novembre 2014

Trattamento ipoparatiroidismo postchirurgico

Follow-up:

–  calcemia ogni 3-4 giorni, in dipendenza del grado di ipocalcemia e delle dosi di farmaci impiegate

–  riaffido al Medico di Medicina Generale:

•  prognosi buona con elevata probabilità di progressiva riduzione dell’apporto di calcio e vitamina D

•  proseguire controlli fino a stabilizzazione dei valori

•  controllare calcemia ad ogni follow-up a distanza

Roma, 7-9 novembre 2014

IPOPARATIROIDISMO POST-CHIRURGICO

L’OBIETTIVO E’ QUELLO DI MANTENERE LA CONCENTRAZIONE DI CALCIO SIERICO

NELLA PARTE INFERIORE

DELL’INTERVALLO DI NORMALITA’

8.5 - 9 mg/dl

Roma, 7-9 novembre 2014

IPOPARATIROIDISMO POST-CHIRURGICO

SE SI SVILUPPA IPERCALCIURIA PRIMA DI RAGGIUNGERE LIVELLI SODDISFACENTI

DI IPOCALCEMIA

Può essere associato diuretico tiazidico

es. idroclorotiazide 25-50 mg/die

Roma, 7-9 novembre 2014

IPOPARATIROIDISMO POST- CHIRURGICO

•  INCIDENZA

•  FATTORI PREDITTIVI

•  TRATTAMENTO ACUTO e CRONICO

•  NB.

Roma, 7-9 novembre 2014

HUNGRY BONE SYNDROME

GRAVE IPOCALCEMIA

aumentato assorbimento osseo del calcio del fosfati e del magnesio per persistenza dell’attività osteoblastica

L’improvvisa riduzione del PTH induce

Un arresto del riassorbimento osseo del calcio ad opera degli osteoclasti senza modificazione dell’attività osteoblastica

pre-esistente grave deficit di vitamina D

Può richiedere trattamento con alte dosi di

vitamina D e calcio per settimane o mesi

Roma, 7-9 novembre 2014

TRIADE

-  IPERCALCEMIA

-  ALCALOSI METABOLICA

-  INSUFFICIENZA RENALE DI VARIO GRADO

Associata all’assunzione di alte dosi di calcio ed alcali facilmente assorbibili

Spesso in associazione a tiazidici dati per aumentare il

riassorbimento di calcio a livello del tubulo renale

Roma, 7-9 novembre 2014

GRAVIDANZA

•  Controllo mensile della calcemia

•  Terzo trimestre: placenta acquisisce attività 1alfa idrossilasica PTH-

indipendente, con possibile

formazione di metaboliti attivi della vitamina D

•  Può essere necessario ridurre la posologia della vitamina D o

addirittura sospenderla

Roma, 7-9 novembre 2014

ALLATTAMENTO

•  Attento monitoraggio della calcemia

•  L’ipofisi produce prolattina, che stimola l’attività 1 alfa idrossilasica renale

•  Promuove la sintesi di 1,25(OH)2D3

•  Anche qui può essere

necessario ridurre la dose

di calcitriolo

Roma, 7-9 novembre 2014

CONCLUSIONI

Strategie possibili

dell’ipoparatiroidismo post-chirurgico

•  Strategia “predittiva”

•  PTH precoce

•  Strategia “preventiva”

•  trattamento sistematico a tutti

•  Strategia “reattiva”

•  trattare l’ipocalcemia quando questa è presente Dott. Michele Zini

Arcispedale S. Maria Nuova, Reggio Emilia

Roma, 7-9 novembre 2014

IPOPARATIROIDISMO NELL’ADULTO:

COME OTTIMIZZARE LA GESTIONE

Responsabile Scientifico: Professor Luca Persani 8.45-9.00 Introduzione - Luca Persani

SESSIONE I: TIROIDE

Moderatori: Luca Chiovato, Mario Salvi, Laura Fugazzola

9.00-9.15 Ipotiroidismo - Luigi Bartalena 9.15-9.25 Dibattito

9.25-9.40 Ipertiroidismo - Guia Vannucchi 9.40-9.50 Dibattito

9.50-10.05 Tireopatia in gravidanza - Donatella Cortelazzi 10.05-10.15 Dibattito

10.15-10.30 Nodulo tiroideo - Massimiliano Andrioli 10.30-10.40 Dibattito

10.40-11.00 Coffee Break

Moderatori: Marco Losa, Maura Arosio, Renato Cozzi, Anna Spada

11.00-11.15 Malattia di Cushing - Carla Scaroni 11.15-11.25 Dibattito

11.25-11.40 Acromegalia - M.Letizia Fatti 11.40-11.50 Dibattito

11.50-12.05 Prolattinoma - Andrea Lania 12.05-12.15 Dibattito

12.15-12.30 Ipopituitarismo - Gianluca Aimaretti 12.30-12.40 Dibattito

12.40-13.30 Lunch

SESSIONE III: PARATIROIDI E MEN

Moderatori: Giovanna Mantovani, Leone Ferrari, Luca Persani

13.30-13.45 Ipoparatiroidismo - Stefania Bonadonna 13.45-13.55 Dibattito

13.55-14.10 Iperparatiroidismo - Sabrina Corbetta 14.10-14.20 Dibattito

14.20-14.35 Men 1 - Uberta Verga 14.35-14.45 Dibattito

SESSIONE IV: METABOLISMO

Moderatori: Livio Luzi, Cecilia Invitti, Olga Disoteo, Antonio Pontiroli

14.45-15.00 Ipoglicemie ricorrenti - Massimo Scacchi 15.00-15.10 Dibattito

15.10-15.25 Diabete Mellito caso 1 - Antonio Conti 15.25-15.35 Dibattito

15.35-15.50 Diabete Mellito caso 2 - Emanuela Orsi 15.50-16.00 Dibattito

SESSIONE V: GONADI E SURRENE

Moderatori: Paola Loli, Francesco Cavagnini, Bruno Ambrosi, Manuela Simoni

16.00-16.15 Ipogonadismo dell’adulto - Daniele Santi

16.15-16.25 Dibattito

16.25-16.40 PCOS - Alessandra Gambineri 16.40-16.50 Dibattito

16.50-17.05 Incidentaloma surrenalico - Iacopo Chiodini 17.05-17.15 Dibattito

17.15-17.45 Questionario

Al termine dei lavori è prevista la compilazione del questionario ECM

WORKSHOP INTERATTIVO:

fatti e controversie in endocrinologia

venerdi 29 Novembre 2013 Centro di Ricerca e Cura dell’Invecchiamento Via Mosè Bianchi, 90 - Milano

MODALITÀ DI ISCRIZIONE

La partecipazione al Convegno è gratuita. L’iscrizione è obbligatoria e va effettuata collegandosi al sito INTERNET: www.auxologico.it sezione CORSI & CONVEGNI.

L’Evento è accreditato ECM al sistema Age.Na.S, per la categoria dei Medici (Endocrinologia, Malattie Metaboliche e Diabetologia, Medicina Interna, Medicina Generale).

INFORMAZIONI

Segreteria Organizzativa

Istituto Auxologico Italiano - Tel: +39 02 619112458, 0323 514272 Fax: +39 02 700509124 - e-mail: [email protected] Ufficio Stampa: [email protected]

RELATORI E MODERATORI

Gianluca Aimaretti - Università A. Avogadro del Piemonte Orientale Bruno Ambrosi - Gruppo Ospedaliero San Donato

Massimiliano Andrioli - IRCCS Istituto Auxologico Italiano Milano

Maura Arosio - Università degli Studi di Milano, Ospedale S. Giuseppe, Multimedica, Milano Luigi Bartalena - Università dell’Insubria, Ospedale di Circolo, Varese

Stefania Bonadonna - IRCCS Istituto Auxologico Italiano Milano Francesco Cavagnini - IRCCS Istituto Auxologico Italiano Milano

Iacopo Chiodini - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano Luca Chiovato - Università degli Studi di Pavia, Fondazione Maugeri, Pavia

Antonio Conti - IRCCS Istituto Auxologico Italiano Milano

Simona Corbetta - Università degli Studi di Milano, gruppo Ospedaliero San Donato Donatella Cortelazzi - IRCCS Istituto Auxologico Italiano Milano

Renato Cozzi - Ospedale Niguarda Cà Granda Milano Olga Disoteo - Ospedale Niguarda Cà Granda Milano M.Letizia Fatti - IRCCS Istituto Auxologico Italiano Milano Leone Ferrari - Ospedali Riuniti di Bergamo

Laura Fugazzola - Università degli Studi di Milano, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano

Alessandra Gambineri - Università di Bologna, Policlinico S. Orsola Malpighi - Bologna Cecilia Invitti - IRCCS Istituto Auxologico Italiano Milano

Andrea Lania - Università degli Studi di Milano, Istituto Clinico Humanitas Rozzano Milano Paola Loli - Ospedale Niguarda Cà Granda Milano

Marco Losa - IRCCS Ospedale San Raffaele, Università Vita-Salute - Milano Livio Luzi - Università degli Studi di Milano, gruppo Ospedaliero San Donato Giovanna Mantovani - Università degli Studi di Milano, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano

Emanuela Orsi - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano Luca Persani - Università degli Studi di Milano, Istituto Auxologico Italiano, Milano Antonio Pontiroli - Università degli Studi di Milano, Ospedale San Paolo

Mario Salvi - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano Daniele Santi - Università degli Studi di Modena e Reggio Emilia

Massimo Scacchi - Università degli Studi di Milano, IRCCS Istituto Auxologico Italiano Carla Scaroni - Dipartimento di Medicina, DIMED, Azienda Ospedaliera - Università di Padova Manuela Simoni - Università degli Studi di Modena e Reggio Emilia

Anna Spada - Università degli Studi di Milano, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano

Guia Maria Vannucchi - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano Uberta Verga - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano

OBIETTIVO FORMATIVO: (18) Contenuti tecnico-professionali (conoscenze e competenze) specifici di ciascuna professione, di ciascuna specializzazione e di ciascuna attività ultraspecialistica.

con il Patrocinio di

con il contributo non condizionato di

Società Italiana Endocrinologia

i

U.O. malattie del Metabolismo Minerale Osseo e Reumatologia

RINGRAZIAMENTI

•  Prof. Sergio Ortolani

•  Dott.ssa Maria Luisa Bianchi

•  Dott. Roberto Cherubini

•  Dott.ssa Silvia Vai

•  Dott. Michele Zini