CURS

3
 AGENDA
•  Insuficienta hipofizara

•  Hormonii hipofizei posterioare

•  Diabetul insipid
•  SIADH
 Hipopituitarism
= scaderea/disparitia unuia sau mai multor h.hipofizari

Lent/insidious
Acut
Primar = distructia hipofizei anterioare
Secundar = deficit hipotalamic
Mostenit
Dobandit
Izolat = doar 1 hormon
Multiplu

SECVENTA PIERDERII: GH, LH+FSH, TSH, ACTH, PRL

 CAUZE DOBANDITE
•  INVAZIE
TUMORI HIPOFIZA = Adenoame, carcinom, craniofaringiom
•  INFARCT Sd Sheehan = êê TA ??? NASTERI LABORIOASE
Apoplezie hipofizara = infarctarea spontana a unei tumori hipofizare
•  APOPLEXIE Sarcoidoza = DI + alterarea hipotalmusului
Tumori SNC: meningiom, chordom, gliom optic, epidermoid,metastaze
Traumatism sever adulti + COPII
Infiltrare autoimuna, in sarcina, 50% + alte boli autoimune
= spasm al arterelor hipofizare èischemiaèinfractizare
Hemocromatoza = tipic hipogonadism =DEPOZITE DE FIER
Chirurgie
•  INFILTRARE Malformatii vasculare: anevrism paraselar

Histiocitoza = DI + hipofizita anterioara
radioterapie: 60% 45 -50 Gy;
? Sarcina/postpartum SENSIBIITATE HIPOFIZARA LA ISCHEMIE
•  TRAUMATIC
100% radioterapie conventionala
LICHEFIERE TUMORALA SPONTANA
•  AUTOIMUN 25% gamma knife
•  IATROGEN IMUNOTERAPIE: NIVOLUMAB/ PEMBROLIZUMAB/ IPILIMUMAB

•  INFECTIOS
 CAUZA EREDITARE = DE LA NASTERE!!!
MUTATII Deficit hormonal
GENETIC
Kalmann Sd FSH,LH
Prader Willi sd FSH,LH
Lawrence Moon Biedl FSH,LH
RECEPTOR
GHRH receptor GH
CRH receptor ACTH
GhRH receptor FSH,LH
TRH receptor TSH
Leptin receptor LH, FSH
STRUCTURAL
Aplazie hipofizara Oricare
Hipoplazie hipofizara Oricare
Encephalocel Oricare
TRANSCRIPTION FACTOR DEFECT Oricare
MUTATIE HORMONULUI oricare
 Simptome
•  GH
ê stare generala de bine/ energie generala/letargie/fatigabilitate
masa musculara
masa osoasa
alterare crestere (copii)
•  LH/FSH
hipogonadism ????CONTEXT
SARCINA
F: amenoree, anovulatie, hipoeE = alterare lubrefiere, dispareunie
M: alterare libido, DE

•  TSH ALAPTARE





FARA GUSA, fara afectiune tiroidiana
TRAUMATISM
insuficienta tiroidiana = tablou mai usor de hipotiroidism

•  ACTH .....
oboseala, letargie, greata, voma, scadere ponderala
febra, hipotensiune, FARA deshdratare si hipoNA
scadere pilozitate axillo pubian
êCORTIZOL + ANDROGENI SR
fara hiperpgmentare
fara boala SR

•  PRL
absenta lactatiei ......... PRIMUL SEMN in postpartum
 Semne = lent, insiduos
•  Modificari de greutate
•  Piele fina, subtire, palida
•  Riduri fine ale fetei
•  Scadere par axilar + pubian (femei)
•  Atrofie OGE (femei)
•  Depigmentare mucoase
•  Hipotensiune posturala
•  Alterare reflexe profunde
•  Scadere forta musculara
 EXCEPTIE = APOPLEXIA HIPOFOZARA ACUTA
•  FAZA 1 = lichefierea tumorii
= cefalee severa
= alterare vizuala
= oftalmoplegie
= meningism
= alterare constienta

•  FAZA 2 = insuficienta hipofizara acuta
= Deficit sever de ACTH= hipotensiune, deshidratare, coma, moarte
•  FAZA 3 = insuficienta hipofizara cronica
= DI = prima saptamana
= hipogonadism = prima luna
= hipotiroidism = 2-3 luni
= hipocorticism = 4-6 luni

Sugerata •  Semne +
simptome
clinic sugestive

•  Dozari bazale
POZITIV •  CENTRAL + PERIFERIC

•  Teste
CONFIRMARE stimulatorii

•  Context
•  Evaluare
PATOGENIE imagistica
•  Teste aditionale
 Teste de laborator
ORICE INSUFICIENTA BANUITA SE CONFIRMA CU TEST SE STIMULARE

Hipofiza Periferie Stimulare Raspuns normal

GHê IGF 1ê Hipoglicemie : GH > 5 ng/dL
INSULINA 0.1-0.15 UI/kgc
ACTHê Cortisolê Hipoglicemie : Cortisol > 18 mg/mL
INSULINA 0.1-0.15 UI/kgc
Metyrapone PO Cortisol < 7 mg/mL
30mg/kgc ACTH > 75 pg/mL
TSHê FT3, FT4ê TRH 200-500 mcg IV TSH > 2.5- fold, TSH > 5-6 IU/L
LH/FSHê E2ê GhRH 100 mcg IV LH > 2-3 –fold LH > 10 IU/L
TTê FSH > 1.5-2-fold FSH > 1 IU/L
PRL ê TRH 200 mcg IV PRL > 2.5-fold

DIFERENTIATA INSUFICIENTA ORGANICA (R -) de cea functionala (R +)

 Modificari asociate

•  Hipoglicemie (ACTH, TSH, GH)

•  Hiponatremie (TSH)
•  Anemie (GH, TSH)
•  Dislipidemie (TSH, GH)
•  Scadere Densitate minerala osoasa (LH/FSH, GH)
 Imagistic
•  RMN hipofiza – in dinamica

•  Camp vizual

•  Context anamnestic
Sugerata
clinic •  Semne + simptome sugestive

• Dozari bazale
POZITIV • CENTRAL + PERIFERIC

• Teste
CONFIRMARE stimulatorii

•  Context
•  Evaluare
imagistic
PATOGENIE a
•  Teste
aditional
e
TRATAMENT
TRATAMENT = SUBSTITUTIE
in ordinea SEVERITATII deficitelor

1.  Linia corticotropa

2. Linia tireotropa
3.Linia gonadotropa
4.? Linia somatotropa

u Linia retrohipofizara
 Linia CORTICOTROPA
o  Substitutie cu glucocorticoizi
Conditii bazale per os
o  Hydrocortison – fiziologic 15-20 mg/zi
o  Alternativa – nonfiziologic - Prednison 5-7.5 mg/zi
o  DOZA : 3x1/3

FARA Minerlocorticoid (sistem RAA dependent!!!!!)
STRES = cresterea de x3 .... x10 dozelor
? Boala cronica
? chirurgie, traumatism
? sarcina, nastere,
? infectii acute,
? Deshidratare: diaree, varsaturi, transpiratii importante

URMARIRE !!! NU avem analize pt urmarire
- greutate, TA, stare generala, calitate viata
 LINIA TIREOTROPA
o  Substitutie cu h.tiroidieni
•  Preparate de T4
1.6 mcg/kg/zi 75 – 150 mcg/zi
•  preparate T4 + T3
cazuri selectate
!!! Contraindicat la varstnici/ gravide/tahiaritmii

o  Intotdeauna linia ACTH se trateaza prima = T3+T4 accelereaza
metabolismul glucocorticoizilor

Follow up dozare FT4 = la limita superioara a normei
Semne clinice disparitie
 Linia gonadotropa
o  Tratament de baza
premenopauza: E2 + P
Femei tinere COC
De durata 21 zile 10 zile
Estradiol 1-2 mg + Progesteron 100 mg
estradiol conjugat 0.3-1.25 mg + Progesteron 100 mg
estradiol valerat 1-2 mg + Progesteron 100 mg

o  Fertilitate
rFSH = stimulare crestere foliculara...
hCG = inducere ovulatie

 !!!!
•  Perioada de adminsitrare limitata
–  Postpubertate – varsta medie a climaxului (51de ani)

•  DOZa fixa de substitutie

•  Evaluare – strict a posibilelor EA

–  Hiperplazie endometriala
–  Proliferare mamara
–  lipidograma
 Contraindicatii
•  Cancer ovar
•  Cancer san
•  Cancer endometrial
•  Sangerare vaginala neevaluata
•  Insuficienta hepatica
•  Hiperplazie endometriala neevaluata
•  Tromboembolism pulmonar, TVP, BTA
•  Hipertensiune netratata
•  LES
•  Profirie cutanata
•  Hipersensibilitate la preparate
 LINIE GONADOTROPA
o  Tratament de baza
Substitutie androgenica
Testosteron gel zilnic 20 mg/zi
Testosteron cipionat IM 100-200 mg/2 saptamani
Testosteron undecanoat IM 1000 mg/3 luni

Preparate orale sunt evitate – efecte hepatice

FERTILITATE = SPERMATOGENEZA
Beta hCG
!! FARA PREPAARTE DE TESTOSTERON inhiba spermatogeneza)
 !!!!
•  Perioada de adminsitrare limitata
–  Postpubertate – senescenta

•  DOZa fixa de substitutie

•  Evaluare – strict a posibilelor EA

–  Hiperplazie prostatica
–  Apnee de somn
–  Hemoconcentratie
–  Lipidograma
 Contraindicatii
•  Cancer prostata
•  Cancer de san
•  Boala vasculara netratata
•  Insuficienta hepatica severa
•  Policitemia
•  Apneea de somn
 LINIA SOMATOTROPA
•  Amelioreaza calitatea vietii
•  Efect antiaterogenic
•  Scadere greutatea
•  Creste masa nongrasa
•  Scade masa grasa
•  Creste DMO
•  Creste capacitatea de efort

•  !!! EA: edeme artralgii, mialgii, sd de tuel carpian, HIC

benigna, hperglicemie, acromegalie iatrogena
•  NU s-a dovedit ca faciliteaza cresterea cancerelor/
cancerogeneza de novo
 Indicatii
•  < 30 de ani = 0.4-0.5 mg/zi
•  30-60 de ani = 0.2-0.3 mg/zi
•  > 60 de ani = 0.1- 0.2 mg/zi

Tinta = normalizare IGF1

 postpartum

•  KL, F 36 ani (15.05.1980)

•  Data prezentare 12.2016

•  FATIGABILITATE EUTHYROX 112.5 mcg/zi

•  LIBIDOU DIMINUAT

•  DORINTA DE O NOUA SARCINA

 App

-  Nastere 2010
-  Sd HELLP luna a 7 a de sarcina
-  Nastere op cezariana
-  Spitalizare prelungita de circa 2 luni

-  Reluarea ciclurilor menstruale la 3 luni postpartum

-  OBOSEALA postpartum
•  OBOSEALA

•  03.2012 dg de Boala Tiroidiana Autoimuna

•  Ac aTPO = 318 UI/L [<35]
•  TSH = 11.5 mUI/L [0.27-4.2]
•  FT4 = 11.4 pmol/L [10.6-22.7]
•  TRATAMENT cu h.Tiroidieni 25 mcg/zi

•  01.2014 50 mcg/zi
•  TSH = 3.8 mUI/L [0.27-4.2]
•  FT4 = 13.9 pmol/L [10.6-22.7]
•  12.2016
•  Clinic
•  Paloare
•  Epilare spontana pubiana

•  TSH = 4.49 mUI/L [0.550-4.78]

•  FT4 = 14.4 pmol/L [10.6-22.7]
•  Ecografie tiroidiana LTD = 9.6/14.0/27.3 mm, vol=
1.91 ml
•  LTS = 7.1/8.4/20.0 mm, vol = 0.62 ml
 CE FACEM?

A.  CRESTEM DOZA DE SUBSTITUTIE TIROIDIANA?

B.  CAUTAM MAI DEPARTE?

C.  ESTE DOAR UN SD SOMATOSENZITIV?

D.  AVEM O ANEMIE SEVERA -- evaluare

hematologica?
•  VSH = 25 mm/h [<20]
•  Ht = 33 % [35-45]
•  Hb = 10.3 g/dL [11.7-15.5]
•  Er = 3.4 x106/ μL [3.8-5.1]

•  cortizol = 49.17 nmol/L [171-536]

•  DHEAS = 20.2 μg/dL [60.9-337]
•  sodiu = 141 mmol/L [136-145]
•  potasiu = 4.18 mmol/L [3.3-5.1]

1.  Confirmare TEST de STIMULARE
• 

•  cortizol bazal = 2.73 μg/dL

•  250 μg ACTH iv
•  30’ cortizol stimulat = 9.85 μg/dL [>18]
•  60’ cortizol stimulat = 11.23 μg/dL [> 18]

Bronstein SR. JCEM 2016 ENDO PAI Guidelines

Cartaya E. Endocr Pracy. 2015;21:508
•  2. Localizare

•  ACTH = 14.89 pg/mL [7.2-63.3]

•  !!!! ACTH > x2 limita de sus a normei = insuficiente perifericaI

•  CENTRALA

• 
• 

Bronstein SR. JCEM 2016 ENDO PAI Guidelines

 BILANT HIPOFIZAR COMPLET
•  IGF-1 = 32.95 ng/mL [80-277]
•  PRL = 109.1 pmol/L [127-637]
•  FSH = 2.64 UI/L [2.5-10.2]
•  LH = 3.50 UI/L [1.90-12.50]

•  ……….TSH = 4.49 mUI/L [0.550-4.78]

•  ……….FT4 = 13.9 pmol/L [10.6-22.7]

•  Insuficienta centrala pe linie de GH, ACTH si PRL cu

prezervarea linie gonadotrope + tireotrope
 TRATAMENT

1.  Instituire supleere adrenala

–  Hidrocortison 20-25 mg/zi 10-10-5
–  DHEAS 30-60 mg/zi

stare generala

2. Continuare supleere tiroidiana
valoarea FT4 la limita de sus a normei
-  H.tiroidien accelereaza metabolizarea glucocorticoizilor
-  Substitutia estrogenica é CGB

Ajustare
–  + 5-10 mg efort fizic prelungit/stres emotional/
DESHIDRATARE
–  + 5-10 mg sarcina
–  + 10-50 mg infectii, sd febril, interventii minore
–  +100-200 mg nastere, interventii majore, ATI
–  + 300 mg septicemie

Quinkler M, Hahner S. Clin Endocirnol 2012; 76:21
Grossman AB. Endocrine Metab 2010; 95:4855
Lebbe M, Clin Endocrinol 2012; 76: 497
Curs SRE
Debono M. Eur J Endocrinol 2009; 160:179
 FATIGABILITATE
•  CC, Barbat, 19 ani
•  T = 195 cm tatal = 180 cm, mama = 170 cm
•  G = 68 kg
•  Caractere sexuale secundare normale

•  FATIGABILITATE, LENTOARE
•  MODIFICARI DE PERSONALITATE
•  CEFALEE FRECVENTA

•  Medicul de faimile dg de hipotiroidie pe fond de boala autoimuna:

•  TSH = 11.82 μUI/mL [0.35-4.94]

•  Ft4 = 0,83 ng/dL [0.7-1.48]
•  Ac anti TPO = 273.2 UI/mL [<5.61]
•  GH random = 3.73 ng/mL [<3]
% PACIENTI cu EutIroiDIE, HIPOTIROIDIE SubclinicA si
CLINICA CE RAPORTEAZA SIMPTOME

60% eutiroidieni
au ≥ 1 simptom
15% ≥ 4 simptome

R5. Sistemul de scoring clinic NU ESTE UTIL

IN diagnosticul + Grade A, BEL 1
Canaris et al.
 CARE ESTE CEL MAI PROBABIL
DIAGNOSTIC?

A.  Hipotiroidie izolata pe fond de BTA

B.  GIGANTISM cu insuficienta tiroidiana

secundara

C.  Poliendocrinopatie tip II asociere

tiroidiana/hipofizara
 Screening Suprarenalian ACTIV

Cortizol bazal < 0.05 μg/dL [6.02-18.40]
DHEAS < 15 mcg/dL [110.0-507.7]
Na 141 mM/L [132-146]
K 4.8 M/L [3.5-5.1]





 … continuam investigatiile
Cortizol = 0.06 μg/dL [6.02-18.40]
•  Stimulare cu ACTH 250 μg
DHEAS < 15.0 μg/dL
•  Cortizol bazal [110.0-510.0]
< 0.05 μg/dL [6.02-18.40]
Cortizol 30’ 0.62 [>18|

HLG
•  Cortizol 60’ 0.87 [>18]

•  Leucocite = 4.06 [4.8-11.0]

•  Neutrofile = 37.5 % [53-68]
•  ACTH < 5.0 pg/mL
Limfocite = 48% [25-45]
[< 46]




 Bilant hipofizar

PRL 16.41 ng/mL [5.40-15.40]
LH 6.4 UI/L [1.10-8.40]
FSH 7.65 UI/L [1.40-18.10]
TT 6.83 ng/mL [2.65-27.76]





 ?

•  Insuficienta secundara – compresiune

tumorala

•  Insuficienta secundara - nontumorala

•  IGF1 = 55.0 ng/mL [117-323]
BILANT FUNCTIONAL BILANT IMAGISTIC
•  GH = 0.659 ng/mL [0.05-3.0]
•  Glicemie = 71 mg/dL [74-106]
•  FSH = 7.65 μg/dL [1.4-18.1]
•  LH = 6.42 μg/dL [1.10-8.40]
•  per os 100 glucoza
•  TT = 6.83 ng/mL [2.65-8.0]

•  60’
•  PRL = 16.41 ng/mL [5.4-15.4]
•  IGF1 = 56.2 ng/mL [117-323]
•  GH = 0.245 ng/mL [<1]
•  IGF1 = 55.0 ng/mL [117-323]
•  120’
•  GH = 0.659 ng/mL [0.015-3.0]
•  IGF1 = 54.90 ng [117-323]
•  GH = 0.078 ng/mL [<1]
1.  Empty Sella dobandita cu insuficienta pe linie
somatotropa si corticotropa
•  - Proces de sexualizare INTACT
•  - Proces de crestere INTACT

•  2. Boala tiroidiana autoimuna cu hipotirodie

sublinica
 Empty Sella dobandita

•  Traumatism

•  Adenoame hipofizare tratate

•  Autoliza tumorala spontana

•  Sd Sheehan

Cjiloiro S.EJE 2017.177:275

 TRAtament

•  I Supleere adrenala

•  II Supleere tiroidiana
•  CV femei de 76 de ani

•  Oboseala marcata
•  Paloare tegumentara
•  Plus ponderal
•  Disparitia unei HTA vechi
•  Cefalee zilnica