KL 28.11.13.Vortrag Endocrinology and the heart

Endocrinology and the heart
Mirjam Christ-Crain, Endocrinology, Diabetes & Metabolism
Kardiolunch 28.11.2013
Endokrine Organe
- Pituitary and the heart
- Thyroid and the heart
- Adrenals and the heart
- Gonads and the heart
- Pituitary and the heart
- Thyroid and the heart
- Adrenals and the heart
- Gonads and the heart
Pituitary: Prolactinoma
• - 20% d. Urs v. sek. Amenorrhoe
- beim Mann Hypogonadismus
(Erektile Dysfunktion & Libido)
• - Galaktorrhoe (F 50%, M 20%)
Pituitary: Prolactinoma
First-line treatment: Dopamin Agonists
(Cabergoline, 0.5-1.5mg/wk)
2 Mte
PRL (mU/L) 153’657
12 Mte
15’794
195
Pituitary: Prolactinoma
Parkinson (3mg/d):
Valvular heart disease with high dose cabergolin treatment,
dose-dependent effect
Prolactinoma (0.5-1.5/Wk):
increased risk for valvulopathy only in minority of studies
Insufficient evidence for a consensus statement
Recommended approach:
Patients eduction about potential risk of cabergoline
Treatment with lowest possible dose and shortest duration
Echocardiographic monitoring (every 2 years) in patients with
long-term use in higher than usual doses (i.e. >2mg/week)
Pituitary: Cushing’s disease
Metabol. Sy (70%)
- art. Hypertonie
- Dyslipidämie
- Diabetes mell. Typ II
Adipositas (90%)
- rotes Vollmondgesicht
- stammbetont
(„Bierbauch auf Stelzen“)
Hautveränd. (65%)
- Striae rubrae
- Faciale Plethora
- Ekchymosen, Suffusionen
Muskel/Skelett (60%)
- Osteoporose
- Lumbalgien
- Allg. Schwäche
5j. Mortalität
>50%, v.a. kardiovaskulär
bedingt
Cushing’s disease – cardiovascular risk
Pituitary: Acromegaly
Mortalität bei Akromegalie –
Multizenter Kohortenstudie, n=1362 (UK)
Cause of death
HR
95% CI
p
Cardiovascular disease
1.76
1.47 - 2.07
< 0.001
Cerebrovascular disease
2.06
1.50 - 2.76
< 0.001
Respiratory disease
1.85
1.34 - 2.49
< 0.001
Malignant disease
1.16
0.92 - 1.44
0.1
Overall (all cause mortality)
1.6
1.44 - 1.77
< 0.001
Orme et al., J Clin Endocrinol Metab 1998, 83: 2730
Pituitary: Acromegaly
Cardiovascular risks:
- Hypertension in 20-50%
- Cardiomyopathy: frequently present at diagnosis
(characterized by diastolic dysfuntion and arrhythmias)
- 2/3 of patients with LVH in echocardiography
Patients with severe cardiomyopathy may progress to
heart failure, manifest heart failure in 3-10% of patients.
Successful treatment halts progress of cardiac
dysfunction and reduces cv mortality.
Guidelines: Echocardiography at baseline
- Pituitary and the heart
- Thyroid and the heart
- Adrenals and the heart
- Gonads and the heart
Target Tissues of
Thyroid Hormone Action
TRH
TSH
T3
T4
T3
Thyroid Hormone Action
on the heart
Klein et al, NEJM 2001
Thyroid: Hypothyroidism
Hypothyroidism and the heart
Hemodynamics:
- increased systemic vascular resistance
- normal or decreased heart rate
- decreased contractility
- decreased cardiac output (30-40% lower than normal)
Cardiac structure and function:
- Increased cardiac work and compensatory hypertrophy
Rhythm:
- Sinus bradycardia, prolonged PR and QT intervals.
Cardiovascular risk:
- Accelerated atherosclerosis, coronary artery disease
Auswirkungen der Hypothyreose auf
Risikofaktoren der Atherosklerose?
Diastolic Hypertension
Lipid profile
Hypercoagulable state
Homocysteinemia (?)
HsC-reactive protein (?)
TSH
Subklinische Hypothyreose
• "subklinisch" = periphere Werte (T4, T3, im
Normbereich, TSH erhöht (>4.5mU/L))
I AM
SIGNIFICANT!
SCREAMED THE
DUST SPECK.
Subclinical hypothyroidism and risk for CHD
Rodondi et al., JAMA 2010
Subclinical hypothyroidism and risk for CHD
Rodondi et al., JAMA 2010
Algorithm for subclinical Hypothyroidism
TSH> 4.5mU/L
Repeat TSH and FT4
TSH >10mU/L
TSH 4.5-10mU/L
Pregnant or
considering pregnancy?
No
Yes
Symptoms,
TPO, Struma?
No
Monitor
6-12mtl
Treatment with
Levothyroxine
Yes
Consider
Treatment
Treatment with
Levothyroxine
Thyroid: Hyperthyroidism
Tox. Adenom
M. Basedow
Hyperthyroidism and the heart
Hemodynamics:
- decreased systemic vascular resistance
- Increased heart rate
- Increased plasma volume
→ Increased cardiac output (50-300% higher than normal)
Cardiac structure and function:
- LV diastolic dysfunction
Rhythm:
- Sinus tachycardia, atrial fibrillation in 10-15%
Cardiovascular risk:
- 2 meta-analyses (7 cohort studies): 1.7 fold elevated risk
for CV mortality
Subklinische Hyperthyreose
• "subklinisch" = periphere Werte (T4, T3, im
Normbereich, TSH erniedrigt (<0.45 mU/L))
I AM
SIGNIFICANT!
SCREAMED THE
DUST SPECK.
Subclinical hyperthyroidism
– risk factor for atrial fibrillation
Incidence for VHF:
subclinical HT:13%
overt HT:14%
euthyroidism: 2%
Personen >60j. mit TSH <0.1 ohne vorbestehendes VHF 
Risiko 3x in den nächsten 10 Jahren ein VHF zu entwickeln
3x
Auer: Am Heart J 2001; Sawin: NEJM 94
TSH-Suppression & Mortality
Parle JV, Lancet 2001
Subclinical hyperthyroidism and risk for CHD
Collet et al, JAMA 2012
Algorithm for subclinical hyperthyroidism
TSH<0.45mU/L
Repeat TSH and FT4
TSH < 0.1mU/L
Determine Aetiology (Szinti, TRAK)
Treatment
TSH 0.1-0.45mU/L
Heart Disease, esp. VHF
Osteoporosis,
Symptoms, Age >60?
No
Monitor 3-12mtl
Yes
Determine Aetiology,
Treatment
Thyroid: Amiodorone treatment
Täglicher Jodbedarf
Jodzufuhr mit 200 –
600 mg Amiodarone
150-200 µg
75 – 225 mg
T ½ in Tagen
Amiodaron
52.6 ± 23.7
Therapeutic strategies
Wirksamkeit der Thionamide reduziert, höhere Dosis nötig (Typ I)
Typ II: Glucocorticoide 40mg/Tag 1-3 Monate, anschliessend Dosis ↓
Radiojodtherapie wg. hoher intrathyreoidaler Jodkonzentration
nicht möglich
Thyreodiektomie bei schwerer, therapierefraktärer Hyperthyreose
Operation am 17.11. , anschliessend keine SD-Medikamente A
Thyroid
and congestive
heart failure
Euthyroid
Sick Syndrom
Schwere
Krankheit
TSH
fT4
Normalbereich
T3
DD: Hyperthyreose
→ T3 bestimmen
Schweregrad der Krankheit
Erholungsphase
Verlauf von Schilddrüsenhormonen am Bsp
eines Patienten mit akuter Krankheit
Datum
TSH mU/l fT4 pmol/l T3 nmol/l
11.06.2013 0.502
15.8
-
04.07.2013 0.023 ↓
27.6 ↑
1.1 ↓
10.07.2013 1.030
17.5
4.0
Verlauf CRP
10.07.2007
48.4 +
mg/l
02.07.2013
364.6 +
mg/l
01.07.2013
503.2 +
mg/l
30.06.2013
313.6 +
mg/l
30.06.2013
302.1 +
mg/l
29.06.2013
130.6 +
mg/l
28.06.2013
55.4 +
mg/l
11.06.2013
46.7 +
mg/l
Low T3 Syndrom as risk factor for cardiovascular mortality in
patients with cardiac diseases
Iervasi, G. et al. Circulation 2003;107:708-713
T3 replacement for postoperative non-thyroidal illness?
Kaptein et al. J Clin Endocrinol Metab 2010
T3 replacement for patients with heart failure?
Gerdes et al. Circulation 2010
- Pituitary and the heart
- Thyroid and the heart
- Adrenals and the heart
- Gonads and the heart
Primärer Hyperaldo - Klinik
• Na+-Retention:
Art. Hypertonie, leichte Hypernatriämie
• K+-Exkretion:
Hypokaliämie - Muskelkrämpfe /-schwäche, kardiale
Arrhythmien
• Metabolische Alkalose
• Hypomagnesiämie
„indirekte Aldosteron-Wirkung“
Aldosteron - Wirkung
- Aldosteron
Aldosteron-Rezeptoren:
• distales Nephron
• Kolon, Hippocampus
• Herz, Gefässe
→ ↑Wachstumsfaktoren im
Gewebe
→ Entzündung,
Mikroangiopathie, Fibrose
„direkte Aldosteron-Wirkung“
Adrenals: Hyperaldosteronism
«direkte und indirekte» Wirkung
Primärer Hyperaldo vs.
essentielle Hypertonie
• Case-control Studie, 65 APA, 59 IHA
• matched für Alter, Geschlecht, BD, HF, Raucher, Gluc, Chol
7.5 ±4.2
1035 ±481
300
28 ±24
321 ±166
35
• Patienten mit Primärem Hyperaldosteronismus sind im Vergleich zu
Patienten mit EHT einem erhöhten kardiovaskulären Risiko
ausgesetzt.
Milliez X, Jour Am Coll Card, 2005
Adrenals: Pheochromocytoma
Adrenals: Pheochromocytoma
Adrenals: Pheochromocytoma
- Hypertension in >50% of patients, sustained or paroxysmal
- Higher variability of BP compared to patients
with essential hypertension
- Higher incidence of target organ damage
Adrenals: Pheochromocytoma
- Pituitary and the heart
- Thyroid and the heart
- Adrenals and the heart
- Gonads and the heart
Gonads: Male Andropause
Verschreibungen in USA↑↑:
2012: 2 Mia Dollar Gewinn für Pharmafirmen, Ziel: bis 2017 Betrag verdoppeln.
CH: >40j: Messungen von Testosteron in
letzten 3 Jahren verdoppelt
2012: Testosteronprodukte für 6 Mio
verkauft, Absatz 32% zugenommen
Gonads: Male Andropause
Konzentration,
Stimmung 
Muskelmasse 
Fett 
Libido 
Erekt Dysfkt
Knochen Dichte 
Gonads: Male Andropause
Cardiovascular effects of Testosteron?
- Prospective observational studies: modest association
between low Testosterone and incident cardiovascular event
Ruige et al, JCEM 2013
Gonads: Male Andropause
Cardiovascular effects: Evidence from treatment studies
- Recent Metaanalysis: difference according to
source of funding, increased risk if NOT funded by industry
- No RCT’s with primary endpoint cardiovascular risk
- Overall: no statistically significant difference
(low number of events)
- Events: Arrhythmia, hypertension, MI, edema, CABG,
thrombosis, Heart failure….
Gonads: Male Andropause
Cardiovascular effects: Evidence from treatment studies
- Biggest study (N=209): stopped early because of
higher incidence of cv events in Testosteron group
- 2 studies evaluating effect of T on atherosclerosis ongoing
- Pending clarification of benefits and risks:
cautious approach in elderly men required
Basaria et al, NEJM 2010
Gonads: Male Andropause
- National cohort study of men with T<11 nmol/L who underwent coronary
angiography between 2005-11
- Of 8700 men with low T, 1300 started T therapy after angiography
- rate of events (MI, stroke, death) 25% in T group vs 19% in no Testogroup
Vigen et al, JAMA 2013
Conclusions
- Pituitary:
- Prolactinoma: if high dose Cabaser: valvulopathy (?)
- Cushing: increased cv risk
- Acromegaly: increased cv risk, echocardiography
at baseline (and follow-up?)
- Thyroid:
- Hypothyroidism: diverse effects on heart (hemodynamics, cv risk,
rhythm, cardiac structure & function)
- subclinical HT: increased cv risk (?)
- Hyperthyroidism: effects on hemodynamics, cv risk, rhythm,
cardiac structure & function
- subclinical HT: VHF, cv risk (?)
- Amiodarone induced hyper / hypothyroidism
- Euthyroid sick syndrome
- Adrenals:
- Hyperaldosteronism: Hypertension, increased cv risk
- Pheochromocytoma: Hypertension, arrhythmia, ischemia
- Hypogonadism elderly men:
- unclear evidence about benefit and risk of T treatment