1. ARTERIAL HYPERTENSION:
Hormone Treatments
Thierry Hertoghe, MD

2. Aging =>  Systolic BP
Systolic BP (mmHg)
Fig. : Effect of age on systolic blood-pressure.
Clean group. The Ns for each decade from were 82, 151, 184, 119, 103 and 35.

3. Nondipping Hypertension
= lack of nocturnal fall of the blood pressure (nondipping)
closely associated
target organ damage
worsened cardiovascular outcome
than in patients with essential hypertension with dipping pattern
Cumu-lative Survival
Dippers
24-hour hypertensives
Nondippers

4. White coat hyper-tension Cardio-vascular events
Masked Hypertension
= association of
normal office blood pressure (BP)
high ambulatory or home BP
=> associated
 target organ damage
 adverse cardiovascular events
as in patients with true hypertension
True
hyper-tension
Maskedhyper-tension
Normal BP
White coat hyper-tension
Cardio-vascular events
(Relative Risk)
Piantanida E, Gallo D, Veronesi G, Pariani N, Masiello E, Premoli P, Sassi L, Lai A, Tanda ML, Ferrario M, Bartalena L. Masked hypertension in newly diagnosed hypothyroidism: a pilot study. J Endocrinol Invest Oct;39(10):

5. Nr 1 Treatment for Arterial hypertension: Thyroid

6. ARTERIAL HYPERTENSION: Mechanism in hypothyroidism
Myxoedema
Healthy artery
Accumulation of mucopolysacchardies
hardening of the arteries
pinched AT e.g. 15/10

7. Overt & subclinical hypothyroidism => Stiffer arteries
Brachial-ankle pulse wave velocity
76 postmenopausal patients
With arterial hypertension
40 + euthyroidism
+12%: m/sec
52 + subclinical hypothyroidism)
+7%: m/sec
Elastic artery
Stiff arteries
24 + clinical hypothyroidism
12.85 m/sec
in the patients with SCHT (14.35 (12.5; 15.5) m/sec) and in those with CHT (13.75 (13.05; 15.25) m/sec) was also statistically significantly higher than in the control group (12.85 (12; 13.9) m/sec) (p < 0.05).
Riabtseva OIu, Orlova IaA, Blankova ZN, Chazova TE, Ageev FT. The vascular wall in postmenopausal women with hypothyroidism and hypertension. Ter Arkh. 2013;85(10):64-9.
AIM:
To study a relationship between thyroid function and the stiffness of great arteries in postmenopausal women with arterial hypertension (AH).
SUBJECTS AND METHODS:
The trial enrolled 76 postmenopausal patients with clinical hypothyroidism (CHT) (n = 24) or subclinical hypothyroidism (SCHT) (n = 52) and AH; a control group consisted of 40 postmenopausal women with euthyroidism. Body mass index (BMI), waist and hip circumferences, blood pressure (BP), thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine, total cholesterol, triglycerides were determines; volumetric sphygmography was performed. Brachial-ankle pulse wave velocity (baPWV) was measured; cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) were determined.
RESULTS:
The patients with CHT or SCHT and the controls were matched for age, BMI, BP, and heart rate. TSH levels in patients with SCHT (6.23 (5.27; 8.22) microU/ml) and in those with CHT (11.8 (9.09; 22.7) microU/ml) were statistically significantly higher than in the control group (2.25 (1.5; 2.72) microU/ml) (p < 0.05). Brachial-ankle pulse wave velocity in the patients with SCHT (14.35 (12.5; 15.5) m/sec) and in those with CHT (13.75 (13.05; 15.25) m/sec) was also statistically significantly higher than in the control group (12.85 (12; 13.9) m/sec) (p < 0.05). Comparison of ABI and CAVI revealed no significant differences between the groups. Univariate analysis of the findings showed a significant impact on higher arterial stiffness in the SCHT and the CHT groups. Total cholesterol levels were significantly higher in the SCHT group than in the control one.
CONCLUSION:
The patients with AH and hypothyroidism versus their peers with AH and without thyroid function had significant rises in blood cholesterol levels and arterial stiffness. The rise in lipid levels was significantly marked only in the patients with SCHT; and baPWV equally increased in both the SCHT and the CHT groups.
Riabtseva OIu, Orlova IaA, Blankova ZN, Chazova TE, Ageev FT. The vascular wall in postmenopausal women with hypothyroidism and hypertension. Ter Arkh. 2013;85(10):64-9.

8. Hypothyroidism =>  systolic & diastolic BP
100
recently diagnosed hypothyroid patients
 Healthy euthyroid subjects
Sign.  systolic & diastolic BP
Sign.  mean 24-h systolic BP
Sign.  24-h pulse pressure
Kotsis V, Alevizaki M, Stabouli S, Pitiriga V, Rizos Z, Sion M, Zakopoulos N. Hypertension and hypothyroidism: results from an ambulatory blood pressure monitoring study. J Hypertens May;25(5):993-9.
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodestrial University, Athens, Greece.
Abstract
OBJECTIVE:
To examine differences between hypothyroid patients and healthy volunteers in 24-h ambulatory blood pressure parameters.
METHODS:
The study population consisted of 100 individuals who were recently diagnosed for hypothyroidism. These patients had never been treated before with antihypertensive treatment or received drugs for hypothyroidism. All participants underwent 24-h ambulatory blood pressure monitoring. The control group consisted of 100 healthy volunteers matched one to one for gender and age with the hypothyroid participants.
RESULTS:
Clinic systolic and diastolic blood pressures were significantly higher in patients with hypothyroidism compared with volunteers. The mean 24-h systolic blood pressure and 24-h pulse pressure were significantly higher in patients with hypothyroidism compared with volunteers. The 24-h systolic blood pressure variability was also significantly higher in patients with hypothyroidism. Fasting serum cholesterol tended to be higher in patients with hypothyroidism compared with volunteers but the difference was not statistically significant, while fasting serum triglycerides were significantly higher. Body mass index was also significantly higher in patients with hypothyroidism.
CONCLUSIONS:
These findings indicate that hypothyroidism may be an important predictor of higher mean 24-h systolic blood pressure, 24-h pulse pressure and 24-h systolic blood pressure variability, parameters of ambulatory blood pressure monitoring that have been previously associated with higher cardiovascular target organ damage.
Kotsis V, Alevizaki M, Stabouli S, Pitiriga V, Rizos Z, Sion M, Zakopoulos N. Hypertension and hypothyroidism: results from an ambulatory blood pressure monitoring study. J Hypertens May;25(5):993-9.

9. Hypothyroidism =>  Blood pressure
ARTERIAL HYPERTENSION in thyroid deficiency :
esp. DIASTOLIC
(Tseng, 1989; Menof, 1950

10.  Serum TSH levels within the ref. range =>  disease risk
=33,3% highest
TSH levels of the population
 Serum TSH levels within the ref. range =>  disease risk
Atherosclero-sis (arterial stiffness) (Dagre 2005)
Hypertension (Gumeniak 2005)
cholesterol in auto-immun. thyr.(Michalo-poulou 1998)
 CRP, homocysteine (Gursoy2006)
Aggravation of coronary heart disease (Auer 2003) 
Progressive
 thyroid deficit & disease
Subjects
« above »  
2.5%
Serum TSH
(miU/mL)
Systolic/diastol.
hyper-tension (Iqbal
2006), Glucose, TG (Waterhouse 2007)
Normal
95%
TSH ref. range
Narrowing of arteries (Yun 2007)
 coronary disease death in women
(Asvold 2008)
Highest quartile
insulin sensitive
T4 levels
Subjects in « normal » range
Middle high quartile
Health
levels
TSH >2.1
Metabolic syndrome feature:  insulin resistance in euthyroid subjects with serum T4 within the lowest tertile (vs upper tertile)
TSH >2
(Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab Feb;92(2): )
Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab Feb;92(2):491-6.
Department of Endocrinology, University Medical Center Groningen and University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands.
Abstract
CONTEXT:
Thyroid disease and the metabolic syndrome are both associated with cardiovascular disease.
OBJECTIVE:
The aim of this study was to explore the hypothesis that thyroid function, in euthyroid subjects, is associated with components of the metabolic syndrome, including serum lipid concentrations and insulin resistance.
METHODS:
A total of 2703 adult inhabitants of a middle-sized city in The Netherlands participated in this cross-sectional study. Subjects who were not euthyroid were excluded, as were subjects taking thyroid medication, medication for diabetes, and subjects for whom medication data were not available (n = 1122). Homeostasis model assessment for insulin resistance (HOMA-IR) (mU*mmol/liter2) was calculated as fasting insulin (mU/liter) times fasting glucose (mmol/liter) divided by The metabolic syndrome was defined according to National Cholesterol Education Program's Adult Treatment Panel III criteria.
RESULTS:
After adjustment for age and sex, free T4 (FT4) was significantly associated with total cholesterol [standardized beta (beta) = ; P = 0.014], low-density lipoprotein cholesterol (beta = ; P = 0.004), high-density lipoprotein cholesterol (beta = 0.100; P < 0.001), and triglycerides (beta = ; P < 0.001). Both FT4 and TSH were significantly associated with HOMA-IR (beta = ; P < and beta = 0.055; P = 0.024, respectively). Median HOMA-IR increased from 1.42 in the highest tertile of FT4 to 1.66 in the lowest tertile of FT4. FT4 was significantly related to four of five components of the metabolic syndrome (abdominal obesity, triglycerides, high-density lipoprotein cholesterol, and blood pressure), independent of insulin resistance.
CONCLUSIONS:
We have demonstrated an association between FT4 levels within the normal reference range and lipids, in accordance with the earlier observed association between (sub)clinical hypothyroidism and hyperlipidemia. Moreover, low normal FT4 levels were significantly associated with increased insulin resistance. These findings are consistent with an increased cardiovascular risk in subjects with low normal thyroid function.
TSH >1.53
TSH >1.3.
Average TSH of a population: miU/mL
Healthy thyroid?
TSH > 0.4
Subjects
« below »  
Progressive  thyroid excess & disease
Also: sign.  triglycerides,
 total & LDL cholesterol
(inverse associations w/T4)
2.5%
Lowest quartile
= 25% highest
TSH levels
Aggravation of thyroid deficiency
= 25% lowest
TSH levels

11. Subclinical hypothyroidism:diastolic BP &  diastolic non-dipping BP
49 patients with subclinical hypothyroidism & without hypertension
 50 healthy controls
Sign.  diastolic, daytime & nighttime diastolic BP’s
(p = 0.001)
Sign.  nighttime systolic blood pressure (p= 0.01)
49% of subclincally hypothyroid patients => diastolic non-dipping => Sign.  frequency of diastolic non-dipping (24 of the 49 patients vsq 26% (13/50) of healthy controls, p = 0.01) => subclinical hypothyroidism => indep. assoc. w/ diastolic non-dipping (RR: 1.18 % CI , p = 0.024). .
Polat Canbolat I, Belen E, Bayyigit A, Helvaci A, Kilickesmez K. Evaluation of Daily Blood Pressure Alteration in Subclinical Hypothyroidism. Acta Cardiol Sin Sep;33(5):
Author information 1
Department of Cardiology, Istanbul Bilim University. 2
Department of Cardiology. 3
Department of Internal Medicine, Okmeydani Training and Research Hospital. 4
Department of Cardiology, Biruni University. 5
Department of Cardiology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey.
Abstract
BACKGROUND:
Subclinical hypothyroidism is the most common thyroid dysfunction in the general population. The relationship between overt thyroid dysfunction and hypertension is generally understood. Besides high blood pressure, non-dipper hypertension is known to increase cardiovascular risk. Our aim is to investigate daily blood pressure changes and the frequency of non-dipping patterns in patients with subclinical hypothyroidism.
METHODS:
49 patients without hypertension with subclinical hypothyroidism were compared with 50 healthy sex- and age-matched controls using ambulatory blood pressure monitoring.
RESULTS:
Thyroid-stimulating hormone (TSH) levels were significantly higher in the subclinic hypothyroidism group, and there was no difference between free triiodothyronine (FT3) and free thyroxine (FT4) levels which could be predicted as a result of the study design. Levels of mean diastolic, daytime diastolic, nighttime diastolic and nighttime systolic blood pressure were significantly higher in the subclinic hypothyroidism group (p = for mean, daytime and nighttime diastolic and p = 0.01 for nighttime systolic). Diastolic non-dipping occurred more frequently in the subclinic hypothyroidism group [subclinical hypothyroidism group 24 patients (49%), control group 13 patients (26%), p = 0.01]. On multivariate analysis, subclinical hypothyroidism was independently associated with diastolic non-dipping (95% confidence interval , odds ratio 1.182, p = 0.024).
CONCLUSIONS:
Our study found that both the frequency of diastolic non-dipping pattern and diastolic blood pressure increase with subclinical hypothyroidism. Therfore, it would appear that searching for non-dipping pattern can add valuable information for patients with subclinical hypothyroidism.
Polat Canbolat I, Belen E, Bayyigit A, Helvaci A, Kilickesmez K. Evaluation of Daily Blood Pressure Alteration in Subclinical Hypothyroidism. Acta Cardiol Sin Sep;33(5):

12. Clinical & Subclinical Hypothyroidism => 3
Clinical & Subclinical Hypothyroidism => 3.3x  risk of Masked Hypertension
64 hypothyroid patients
38 subclinical
26 overt
 50 euthyroid subjects
sign. 3.3x risk of masked hypertension
in (overt & subclinical) hypothyroid patients
Vs euthyroid subjects (3.29, ; p = 0.02)
Piantanida E, Gallo D, Veronesi G, Pariani N, Masiello E, Premoli P, Sassi L, Lai A, Tanda ML, Ferrario M, Bartalena L. Masked hypertension in newly diagnosed hypothyroidism: a pilot study. J Endocrinol Invest Oct;39(10):
Endocrine Unit, Department of Clinical and Experimental Medicine, ASST dei Sette Laghi, Ospedale di Circolo, University of Insubria, Viale Borri, 57, 21100, Varese, Italy. 2
Endocrine Unit, Department of Clinical and Experimental Medicine, ASST dei Sette Laghi, Ospedale di Circolo, University of Insubria, Viale Borri, 57, 21100, Varese, Italy.
Abstract
PURPOSE:
Masked hypertension (MH) is the association of normal office blood pressure (BP) with high ambulatory or home BP. This condition is associated with increased cardiovascular target organ damage, as true hypertension. Because the relation with hypothyroidism is controversial, we investigated it in a pilot longitudinal and controlled study.
METHODS:
We consecutively enrolled 64 newly diagnosed hypothyroid patients, 38 subclinical (s-HYPO), and 26 overt (o-HYPO). The control group consisted of 50 euthyroid subjects seen at outpatient clinics. All participants underwent office and 24-h ambulatory BP measurement.
RESULTS:
BP monitoring revealed a higher prevalence of MH both in s-HYPO (26.3 %) and in o-HYPO (15.4 %) than in euthyroid subjects (10 %, p = 0.05); true hypertension also was more frequent in o-HYPO (11.5 %) and s-HYPO (10.5 %) than in controls (8 %, p = 0.03). The odds ratio for hypertension versus normotension confirmed a significantly increased risk of MH in hypothyroid patients versus euthyroid subjects (3.29, ; p = 0.02). In a subgroup of patients reevaluated after restoration of euthyroidism, an improvement of BP profile was observed, especially in s-HYPO subgroup, with a decreased prevalence of MH (from 25 to 10.7 %) and true hypertension (from 10.7 to 3.4 %).
CONCLUSIONS:
Hypothyroidism may be an important predictor of higher BP values, with an increased risk of MH. Because MH is a cardiovascular risk and can be reversed by thyroid hormone replacement, its presence should represent an indication for thyroid hormone replacement therapy also in patients with s-HYPO.
Piantanida E, Gallo D, Veronesi G, Pariani N, Masiello E, Premoli P, Sassi L, Lai A, Tanda ML, Ferrario M, Bartalena L. Masked hypertension in newly diagnosed hypothyroidism: a pilot study. J Endocrinol Invest Oct;39(10):

13. Arterial hypertension: the association with lower thyroid hormone levels
Piantanida E, Gallo D, Veronesi G, Pariani N, Masiello E, Premoli P, Sassi L, Lai A, Tanda ML, Ferrario M, Bartalena L. Masked hypertension in newly diagnosed hypothyroidism: a pilot study. J Endocrinol Invest Oct;39(10):
Inal S, Karakoç MA, Kan E, Ebinç FA, Törüner FB, Aslan M. The effect of overt and subclinical hypothyroidism on the development of non-dipper blood pressure. Endokrynol Pol. 2012;63(2):97-103
Duan Y, Wang X, Peng W, Feng Y, Tang W, Wu X, Mao X, Bo R, Li W, Chen J, Qin Y, Liu C, Liu C. Gender-specific associations between subclinical hypothyroidism and blood pressure in Chinese adults. Endocrine (2009 Oct 14: Epub ahead of print)
Kileĭnikov DV, Makusheva MV, Volkov VS. Pathogenesis of arterial hypertension in patients with primary hypothyroidism] Klin Med (Mosk). 2009;87(5):30-2
Velkoska Nakova V, Krstevska B, Bosevski M, Dimitrovski Ch, Serafimoski V. Dyslipidaemia and hypertension in patients with subclinical hypothyroidism. Prilozi Dec;30(2):93-102
Guasti L, Marino F, Cosentino M, Cimpanelli M, Rasini E, Piantanida E, Vanoli P, De Palma D, Crespi C, Klersy C, Maroni L, Loraschi A, Colombo C, Simoni C, Bartalena L, Lecchini S, Grandi AM, Venco A. Pain perception, blood pressure levels, and peripheral benzodiazepine receptors in patients followed for differentiated thyroid carcinoma: a longitudinal study in hypothyroidism and during hormone treatment. Clin J Pain Jul-Aug;23(6):518-23
Kotsis V, Alevizaki M, Stabouli S, Pitiriga V, Rizos Z, Sion M, Zakopoulos N. Hypertension and hypothyroidism: results from an ambulatory blood pressure monitoring study. J Hypertens May;25(5):993-9
Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine Jun;24(1):1-13
Streeten DH, Anderson GH Jr, Howland T, Chiang R, Smulyan H. Effects of thyroid function on blood pressure. Recognition of hypothyroid hypertension. Hypertension Jan;11(1):78-83
Fommei E, Iervasi G. The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans. J Clin Endocrinol Metab May;87(5):
Saito I, Ito K, Saruta T. Hypothyroidism as a cause of hypertension. Hypertension Jan-Feb;5(1):112-5

14. in« normal » free T3 range 1.8 pg/mL = 2.8 pmol/L T3 LOWER LIMIT
 serum Free T3 levels with the reference range associated with cardiovascular disease
Subjects
« above »  
2.5%
5.7 pmol/L
3.7 pg/mL= 5.7 pmol/L T3 UPPER LIMIT
Blood Free T3 level
(pg/mL)
3.1
95%
Subjects
in« normal » free T3 range
2.8
2.4
2.3
 Adverse cardiovascular events (Rays J 2003)
 Severity of coronary artery athero-sclerosis (Auer J 2003)
1.8 pg/mL = 2.8 pmol/L T3 LOWER LIMIT
 left ventricular dysfunction & hyper-trophy (Zoccali C 2006)
Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab Feb;92(2):491-6.
Department of Endocrinology, University Medical Center Groningen and University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands.
Abstract
CONTEXT:
Thyroid disease and the metabolic syndrome are both associated with cardiovascular disease.
OBJECTIVE:
The aim of this study was to explore the hypothesis that thyroid function, in euthyroid subjects, is associated with components of the metabolic syndrome, including serum lipid concentrations and insulin resistance.
METHODS:
A total of 2703 adult inhabitants of a middle-sized city in The Netherlands participated in this cross-sectional study. Subjects who were not euthyroid were excluded, as were subjects taking thyroid medication, medication for diabetes, and subjects for whom medication data were not available (n = 1122). Homeostasis model assessment for insulin resistance (HOMA-IR) (mU*mmol/liter2) was calculated as fasting insulin (mU/liter) times fasting glucose (mmol/liter) divided by The metabolic syndrome was defined according to National Cholesterol Education Program's Adult Treatment Panel III criteria.
RESULTS:
After adjustment for age and sex, free T4 (FT4) was significantly associated with total cholesterol [standardized beta (beta) = ; P = 0.014], low-density lipoprotein cholesterol (beta = ; P = 0.004), high-density lipoprotein cholesterol (beta = 0.100; P < 0.001), and triglycerides (beta = ; P < 0.001). Both FT4 and TSH were significantly associated with HOMA-IR (beta = ; P < and beta = 0.055; P = 0.024, respectively). Median HOMA-IR increased from 1.42 in the highest tertile of FT4 to 1.66 in the lowest tertile of FT4. FT4 was significantly related to four of five components of the metabolic syndrome (abdominal obesity, triglycerides, high-density lipoprotein cholesterol, and blood pressure), independent of insulin resistance.
CONCLUSIONS:
We have demonstrated an association between FT4 levels within the normal reference range and lipids, in accordance with the earlier observed association between (sub)clinical hypothyroidism and hyperlipidemia. Moreover, low normal FT4 levels were significantly associated with increased insulin resistance. These findings are consistent with an increased cardiovascular risk in subjects with low normal thyroid function.
Slow coronary flow (Evrengul
H 2006)
Levels of progressive
 in risk of
disease
Subjects
« below »  
2.5%
ng/dL pmol/L

15. Thyroid treatment may
 High Blood Pressure

16. Rheumatism : Hormone treatment
Arterial hypertension
The nr 1 hormone therapy is with thyroid,
esp. desiccated thyroid (more prolonged action)
Calcitonin + ?
PTH + ?
GH, IGF-1 ±
The actual most reliable: dessiccated (Erfa, Armlour,..)
Thyroid ++
E2 + P+T ++
T++
In case of hypothyroidism
Compounded:
Often -40% action

17. Rheumatism : Hormone treatment
Arterial hypertension
For Thyroid therapy: desiccated thyroid
Calcitonin + ?
PTH + ?
GH, IGF-1 ±
Thyroid ++
E2 + P+T ++
T++
Tip 1: Privilege desiccated thyroid because of its softer, more progressivev& more stable effects) 
T3 alone (ups & downs of activity) or
Synhtetic T3-T4 combinations (peak activity at the end of the morning),
where activity peaks levels could =>  BP

18. Euthyroid Hypothyroid
Normalization of
Diastolic HT
Diastolic HT

19. Hypothyroidism =>  Blood pressure
ARTERIAL HYPERTENSION in thyroid deficiency :
esp. DIASTOLIC (Tseng, 1989; Menof, 1950)
=> OFTEN NORMALIZED BY THYROID TREATMENT (Fuller, 1966)
=> PREVENTION : quite efficient !?
(Barnes B, in hypothyroidism, 1976, Ed Harper & Row, p )

20. Thyroid therapy =>  Systolic Hypertension
15 hypothyroid patients with systolic hypertension
53 % (8) not improved
THYROID TREATMENT
PRIOR
Thyroid THerapy
PATIENTS w/ SYSTOLIC HYPER-TENSION
(mm Hg) 15
NOT IMPROVED 8
47 % (7) improved
Hyper-tensed hypo-thyroid patients
53 % hyper-tensed patients 7
IMPROVED (1)
7 %
40 % (6) cured
7% (1) improved
40 %
CURED (6) normotensed
Fuller H, Jr, Spittell JA, Jr, McConahey WM, Schirger A. Myxedema and hypertension. Postgrad Med. 1966;40:425–8
There is no absolute means of predicting that hypertension associated with myxedema will resolve following treatment of the myxedema. However, the younger the patient, the shorter the duration of hypertension, and the higher the blood cholesterol concentration, the more likely it is that the patient will become normotensive. Myxedema and Hypertension. Available from: [accessed Jun ].
figure : Under thyroid treatment an improvement in systolic blood pressure was noticed in 7 on 15 hypothyroid patients w/ systolic arterial hypertension. 6 of the 7 improved patients were considered as cured. (Fuller H et al, Postgrad Med, 1966, 40 : 425-8)
Fuller H, Jr, Spittell JA, Jr, McConahey WM, Schirger A.
Myxedema and hypertension. Postgrad Med. 1966;40:425–8.

21. DIASTOLIC HYPERTENSION & THYROID TREATMENT
Thyroid therapy =>  Diastolic Hypertension
DIASTOLIC HYPERTENSION & THYROID TREATMENT
hypothyroid patients with diastolic hypertension
12.5 % (11) not improved
Thyroid THerapy
THYROID TREATMENT
PRIOR
87.5 % (77) improved 88
PATIENTS w/ DIASTOLIC HYPERTENSION
(mm Hg)
77 = 87.5 %
hypertensed hypothyroid patients
NOT IMPROVED 11= 12.5 %
29 % (22) cured
71% (55) improved
71 %
IMPROVED (55)
hypertensed patients
CURED (22) normotensed
29 %
Figure: The younger the patient, the shorter the duration of hypertension, & the higher the blood cholesterol concentration, the more likely it is that the hypothyroid systolic & diastolic hypertensed patient will become normotensive
figure : evolution under thyroid treatments of the diastolic blood pressure in 88 hypothyroid patients with diastolic arterial hypertension % (77) patients improved; amongst which 29 % (22) were considered as cured.
(Fuller H et al, Postgrad Med, 1966, 40 : 425-8)
Fuller H, Jr, Spittell JA, Jr, McConahey WM, Schirger A.
Myxedema and hypertension. Postgrad Med. 1966;40:425–8.

22. L-Thyroxine => cures nocturnal non-dipping BP in subclinical, not overt, hypothyroidism
 9 healthy controls
80 patients
with
subclinical
or clinical hypothyroidism
Loss of nocturnal dipping BP
THYROXINE TREATMENT
7 patients
with subclinical hypothyroidism
30 patients
with clinical hypothyroidism
 Nighttime dipping BP
(p= to 0.007)
Nath M, Gupta B, Rai M, Singh SK. Reversal of nocturnal non-dipping of blood pressure after Levothyroxine therapy in patients with subclinical hypothyroidism. Diabetes Metab Syndr Dec;11 Suppl 2:S997-S1000.
Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi , India. 2
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi , India. 3
Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi , India. Electronic address:
Abstract
AIMS:
To study the loss of diurnal variation in blood pressure in normotensive patients with Subclinical/overt hypothyroidism and effect of Levothyroxine (L-T4) treatment.
MATERIALS AND METHODS:
In this interventional study 80 patients between years with newly detected OH and SCH (74 women and 6 men) and 9 euthyroid subjects (all men) with blood pressure <140/90 were recruited. All patients underwent 24h ambulatory blood pressure monitoring (ABPM) using ABPM machine before and after treatment with L-T4. Diurnal index (DI), Percent time elevation (PTE), Hyperbaric impact (HBI) were studied pre and post L-T4 treatment.
RESULTS:
Of the 89 subjects (22 SCH, 58 OH and 9 controls), 7 of the SCH and 30 of OH subjects reported back in follow up after L-T4 supplementation for evaluation. DI, HBI and PTE when compared at baseline between different groups (SCH- OH, SCH- control, OH- control) were insignificant. After L-T4 supplementation DI, HBI and PTE varied significantly with p value 0.007, and respectively between SCH- OH only. Post L-T4 analysis in SCH group was statistically insignificant (p-value 0.102) but a trend toward improvement in DI was noted (baseline and post treatment DI mean 7.00 and respectively).
CONCLUSION:
Loss of nocturnal dipping was found in patients with OH and SCH which was restored after L-T4 therapy only in patients with SCH and not with OH.
TREATMENT:
of SCH patients with high cardiovascular risk may be beneficial in this setting and can be a new indication for LT4 therapy in SCH.
Polat Canbolat I, Belen E, Bayyigit A, Helvaci A, Kilickesmez K. Evaluation of Daily Blood Pressure Alteration in Subclinical Hypothyroidism. Acta Cardiol Sin Sep;33(5):
Author information 1
Department of Cardiology, Istanbul Bilim University.
Department of Cardiology.
Department of Internal Medicine, Okmeydani Training and Research Hospital. 4
Department of Cardiology, Biruni University. 5
Department of Cardiology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey.
BACKGROUND:
Subclinical hypothyroidism is the most common thyroid dysfunction in the general population. The relationship between overt thyroid dysfunction and hypertension is generally understood. Besides high blood pressure, non-dipper hypertension is known to increase cardiovascular risk. Our aim is to investigate daily blood pressure changes and the frequency of non-dipping patterns in patients with subclinical hypothyroidism.
METHODS:
49 patients without hypertension with subclinical hypothyroidism were compared with 50 healthy sex- and age-matched controls using ambulatory blood pressure monitoring.
Thyroid-stimulating hormone (TSH) levels were significantly higher in the subclinic hypothyroidism group, and there was no difference between free triiodothyronine (FT3) and free thyroxine (FT4) levels which could be predicted as a result of the study design. Levels of mean diastolic, daytime diastolic, nighttime diastolic and nighttime systolic blood pressure were significantly higher in the subclinic hypothyroidism group (p = for mean, daytime and nighttime diastolic and p = 0.01 for nighttime systolic). Diastolic non-dipping occurred more frequently in the subclinic hypothyroidism group [subclinical hypothyroidism group 24 patients (49%), control group 13 patients (26%), p = 0.01]. On multivariate analysis, subclinical hypothyroidism was independently associated with diastolic non-dipping (95% confidence interval , odds ratio 1.182, p = 0.024).
CONCLUSIONS:
Our study found that both the frequency of diastolic non-dipping pattern and diastolic blood pressure increase with subclinical hypothyroidism. Therfore, it would appear that searching for non-dipping pattern can add valuable information for patients with subclinical hypothyroidism.
No sign. effect on nocturnal dipping BP
Nath M, Gupta B, Rai M, Singh SK. Reversal of nocturnal non-dipping of blood pressure after Levothyroxine therapy in patients with subclinical hypothyroidism. Diabetes Metab Syndr Dec;11 Suppl 2:S997-S1000.

23. Clinical & Subclinical Hypothyroidism => 3
Clinical & Subclinical Hypothyroidism => 3.3x  risk of Masked Hypertension
64 hypothyroid patients
38 subclinical
26 overt
 50 euthyroid subjects
sign. 3.3x risk of masked hypertension
in (overt & subclinical) hypothyroid patients
Vs euthyroid subjects (3.29, ; p = 0.02)
Thyroid therapy => After restoration of euthyroidism:
=> BP profile improvement, esp. in patients with subclinical hypothyroidism
2.3x (-58%)  prevalence of masked hypertension (from 25 to 10.7 %)
2.9x (-68%)  prevalence of true hypertension (from 10.7 to 3.4 %)
Piantanida E, Gallo D, Veronesi G, Pariani N, Masiello E, Premoli P, Sassi L, Lai A, Tanda ML, Ferrario M, Bartalena L. Masked hypertension in newly diagnosed hypothyroidism: a pilot study. J Endocrinol Invest Oct;39(10):
Endocrine Unit, Department of Clinical and Experimental Medicine, ASST dei Sette Laghi, Ospedale di Circolo, University of Insubria, Viale Borri, 57, 21100, Varese, Italy. 2
Endocrine Unit, Department of Clinical and Experimental Medicine, ASST dei Sette Laghi, Ospedale di Circolo, University of Insubria, Viale Borri, 57, 21100, Varese, Italy.
Abstract
PURPOSE:
Masked hypertension (MH) is the association of normal office blood pressure (BP) with high ambulatory or home BP. This condition is associated with increased cardiovascular target organ damage, as true hypertension. Because the relation with hypothyroidism is controversial, we investigated it in a pilot longitudinal and controlled study.
METHODS:
We consecutively enrolled 64 newly diagnosed hypothyroid patients, 38 subclinical (s-HYPO), and 26 overt (o-HYPO). The control group consisted of 50 euthyroid subjects seen at outpatient clinics. All participants underwent office and 24-h ambulatory BP measurement.
RESULTS:
BP monitoring revealed a higher prevalence of MH both in s-HYPO (26.3 %) and in o-HYPO (15.4 %) than in euthyroid subjects (10 %, p = 0.05); true hypertension also was more frequent in o-HYPO (11.5 %) and s-HYPO (10.5 %) than in controls (8 %, p = 0.03). The odds ratio for hypertension versus normotension confirmed a significantly increased risk of MH in hypothyroid patients versus euthyroid subjects (3.29, ; p = 0.02). In a subgroup of patients reevaluated after restoration of euthyroidism, an improvement of BP profile was observed, especially in s-HYPO subgroup, with a decreased prevalence of MH (from 25 to 10.7 %) and true hypertension (from 10.7 to 3.4 %).
CONCLUSIONS:
Hypothyroidism may be an important predictor of higher BP values, with an increased risk of MH. Because MH is a cardiovascular risk and can be reversed by thyroid hormone replacement, its presence should represent an indication for thyroid hormone replacement therapy also in patients with s-HYPO.
Piantanida E, Gallo D, Veronesi G, Pariani N, Masiello E, Premoli P, Sassi L, Lai A, Tanda ML, Ferrario M, Bartalena L. Masked hypertension in newly diagnosed hypothyroidism: a pilot study. J Endocrinol Invest Oct;39(10):

24. Arterial hypertension: the improvement with thyroid treatment
Nath M, Gupta B, Rai M, Singh SK. Reversal of nocturnal non-dipping of blood pressure after Levothyroxine therapy in patients with subclinical hypothyroidism. Diabetes Metab Syndr Dec;11 Suppl 2:S997-S1000.
Piantanida E, Gallo D, Veronesi G, Pariani N, Masiello E, Premoli P, Sassi L, Lai A, Tanda ML, Ferrario M, Bartalena L. Masked hypertension in newly diagnosed hypothyroidism: a pilot study. J Endocrinol Invest Oct;39(10):
Fuller H Jr, Spittell JA Jr, McConahey WM, Schirger A. Myxedema and hypertension. Postgrad Med Oct;40(4):425-8
Gasiorowski W, Plazinska MT. Arterial hypertension associated with hyper and hypothyroidism. Pol Tyg Lek Nov 2-9;47(44-45):

25. Nr 2 Treatment for Arterial hypertension: Transdermal Estrogen + Progesterone Therapies

26. Female hormone replacement may
 High Blood Pressure

27. ARTERIAL HYPERTENSION: Mechanism in Estrogen Deficiency
 Estrogens
=>  relaxation of arterial smooth muscle cells
=> lack of vasodilatation
Estrogens
= vasodilators
e.g. Blood pressure of 160/80 mmHg

28. Arterial hypertension: the association with lower estrogen levels
Harrison-Bernard LM, Schulman IH, Raij L. Postovariectomy hypertension is linked to increased renal AT1 receptor and salt sensitivity. Hypertension Dec;42(6):
Clark JT, Chakraborty-Chatterjee M, Hamblin M, Wyss JM, Fentie IH. Estrogen depletion differentially affects blood pressure depending on age in Long-Evans rats. Endocrine Nov;25(2):173-86
Peng N, Clark JT, Wei CC, Wyss JM. Estrogen depletion increases blood pressure and hypothalamic norepinephrine in middle-aged spontaneously hypertensive rats. Hypertension May;41(5):1164-7

29. Rheumatism : Hormone treatment
Arterial hypertension
Estrogen => transdermal is the first choice
(Bio-identical, prolonged action)
The actual most reliable: (O)Estrogel
In case of ovarian deficiency
Calcitonin + ?
PTH + ?
GH, IGF-1 ±
Thyroid ++
E2 + P+T ++
T++
Compounded: Cheaper, but
Often need to 2x the dose for same action

30. Rheumatism : Hormone treatment
Arterial hypertension
Estrogen therapy in women is should be assoc. w/ Progesterone => oral, vaginal or transdermal
(Bio-identical, prolonged action)
Calcitonin + ?
PTH + ?
GH, IGF-1 ±
Thyroid ++
E2 + P+T ++
T++
The actual most reliable oral/vaginal
Prometrium-Utrogestan
Compounded:
10% liposomal cream
In case of ovarian deficiency
Progesterone
liposomal gel

31. Transdermal Estradiol therapy…=>
Blood Pressure

32. ARTERIAL HYPERTENSION transdermal E2
=>  systolic & diastolic BP & cardiac rhythm
(Del Rio, 1994)
100 µg transdermal E2 patches
=> sign.  BP
- diastolic
- systolic
(Pang SC et al, Fertil Steril, 1993, 59: 76-82)

33. Arterial hypertension: the improvement with estrogen treatment
Harrison-Bernard LM, Schulman IH, Raij L. Postovariectomy hypertension is linked to increased renal AT1 receptor and salt sensitivity. Hypertension Dec;42(6):
Clark JT, Chakraborty-Chatterjee M, Hamblin M, Wyss JM, Fentie IH. Estrogen depletion differentially affects blood pressure depending on age in Long-Evans rats. Endocrine Nov;25(2):173-86
Peng N, Clark JT, Wei CC, Wyss JM. Estrogen depletion increases blood pressure and hypothalamic norepinephrine in middle-aged spontaneously hypertensive rats. Hypertension May;41(5):1164-7

34. Arterial hypertension: the improvement with estrogen & progesterone treatment
Junge W, El-Samalouti V, Gerlinger C, Schaefers M. Effects of menopausal hormone therapy on hemostatic parameters, blood pressure, and body weight: open-label comparison of randomized treatment with estradiol plus drospirenone versus estradiol plus norethisterone acetate. Eur J Obstet Gynecol Reprod Biol Dec;147(2):
Ichikawa A, Sumino H, Ogawa T, Ichikawa S, Nitta K. Effects of long-term transdermal hormone replacement therapy on the renin-angiotensin- aldosterone system, plasma bradykinin levels and blood pressure in normotensive postmenopausal women. Geriatr Gerontol Int Dec;8(4):259-64
Kaya C, Cengiz SD, Cengiz B, Akgun G. Long-term effects of low-dose 17beta-estradiol plus dydrogesterone on 24-h ambulatory blood pressure in healthy postmenopausal women: a 1-year, randomized, prospective study. Gynecol Endocrinol Oct;23 Suppl 1:62-7
Preston RA, Norris PM, Alonso AB, Ni P, Hanes V, Karara AH. Randomized, placebo-controlled trial of the effects of drospirenone-estradiol on blood pressure and potassium balance in hypertensive postmenopausal women receiving hydrochlorothiazide. Menopause May-Jun;14(3 Pt 1):408-14
Gerhard M, Walsh BW, Tawakol A, Haley EA, Creager SJ, Seely EW, Ganz P, Creager MA. Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women. Circulation Sep 22;98(12):
Kornhauser C, Malacara JM, Garay ME, Perez-Luque EL. The effect of hormone replacement therapy on blood pressure and cardiovascular risk factors in menopausal women with moderate hypertension. J Hum Hypertens Jul;11(7):405-11

35. Nr 3 Treatment for Arterial hypertension: Testosterone

36. Arteries = Tubes of mainly smooth muscle cells
Testosterone
= Hormone of muscle cells,
including smooth muscle cells

37. Men with mild hypertension =>  serum total testosterone
            
Men with mild hypertension =>  serum total testosterone
49 men older than 40 years
24 hypertensive patients BP > 140/90mmHg, criteria for mild hypertension
25 healthy subjects: normal systemic BP
Ishikura F, Asanuma T, Beppu S. Low testosterone levels in patients with mild hypertension recovered after antidepressant therapy in a male climacterium clinic. Hypertens Res Feb;31(2): Division of Functional Diagnostic Science, School of Allied Health Science,Faculty of Medicine, Graduate School of Osaka University, Suita, middle-aged men who have begun frequently complaining of erectiledysfunction and nonspecific symptoms similar to those of postmenopausal women,visited a male climacterium clinic in Japan. Some patients, who were alreadytaking antihypertensive medication, discontinued or reduced their dosages ofantihypertensive medication after anti-depressant therapy. Forty-nine males over the age of 40 years were studied to evaluate the relationships between bloodpressure, mental stress, and testosterone levels. The systemic blood pressure(sBP) of 24 patients was higher than the criteria for mild hypertension: 140/90mmHg (HT group) at first visit. The sBP of the other 25 patients was normal (Ngroup). The international index of erectile function (IIEF5) score (normal >21), self-rating depression scale (SDS) score (normal <40), and plasma testosteronelevels were also evaluated before and after anti-depressant therapy withoutandrogen replacement therapy. There were no significant differences between thegroups in IIEF5 or SDS scores. The plasma testosterone levels in the HT group at first visit were significantly lower than those in the N group (230+/-77 vs.343+/-92 ng/dL, p<0.001). After treatment, the IIEF5 scores were unchanged,whereas SDS scores were lower in both groups. Mean systemic blood pressure (mBP) in the HT group significantly decreased from 112+/-7 to 94+/-7 mmHg aftertreatment, concomitant with the disappearance of nonspecific complaints and theincrease of testosterone levels. In the N group, however, neither mBP nortestosterone levels changed. Psychotherapy can ameliorate mild systemichypertension in climacteric men with low testosterone levels. Mental stress mightsuppress the hypothalamic-pituitary-gonadal axis to decrease testosterone levels.
Signif. -33%  serum testosterone in the hypertensive men at first visit than those in the N group (230 vs.343 ng/dL, p<0.001).
Ishikura F, Asanuma T, Beppu S. Low testosterone levels in patients with mild hypertension recovered after antidepressant therapy in a male climacterium clinic. Hypertens Res Feb;31(2):243-8.

38.             
Low testosterone levels in men +mild hypertension partially recovered after antidepressant therapy
SUBJECTS: 49 males > 40 years The systemic blood pressure(sBP)
24 hypertensive patients BP > 140/90mmHg, criteria for mild hypertension: (HT group) at first visit.
the other 25 patients: normal systemic BP (N group).
FINDINGS:
Signi. -33%  serum testosterone in the hypertensive men at first visit than those in the N group (230 vs.343 ng/dL, p<0.001).
After antidepressant therapy
Unchanged IIEF5 scores, SDS scores = lower in both groups.
Sign. -16%  mean systemic blood pressure in the hypertensive (from 112 to 94 mmHg)
concomitant with the disappearance of nonspecific complaints & the increase of testosterone levels.
In the N group, neither mBP nor testosterone levels changed.
=> Psychotherapy can ameliorate mild systemichypertension in climacteric men with low testosterone levels. Mental stress might suppress the hypothalamic-pituitary-gonadal axis to decrease testosterone levels.
Ishikura F, Asanuma T, Beppu S. Low testosterone levels in patients with mild hypertension recovered after antidepressant therapy in a male climacterium clinic. Hypertens Res Feb;31(2): Division of Functional Diagnostic Science, School of Allied Health Science,Faculty of Medicine, Graduate School of Osaka University, Suita, middle-aged men who have begun frequently complaining of erectiledysfunction and nonspecific symptoms similar to those of postmenopausal women,visited a male climacterium clinic in Japan. Some patients, who were alreadytaking antihypertensive medication, discontinued or reduced their dosages ofantihypertensive medication after anti-depressant therapy. Forty-nine males over the age of 40 years were studied to evaluate the relationships between bloodpressure, mental stress, and testosterone levels. The systemic blood pressure(sBP) of 24 patients was higher than the criteria for mild hypertension: 140/90mmHg (HT group) at first visit. The sBP of the other 25 patients was normal (Ngroup). The international index of erectile function (IIEF5) score (normal >21), self-rating depression scale (SDS) score (normal <40), and plasma testosteronelevels were also evaluated before and after anti-depressant therapy withoutandrogen replacement therapy. There were no significant differences between thegroups in IIEF5 or SDS scores. The plasma testosterone levels in the HT group at first visit were significantly lower than those in the N group (230+/-77 vs.343+/-92 ng/dL, p<0.001). After treatment, the IIEF5 scores were unchanged,whereas SDS scores were lower in both groups. Mean systemic blood pressure (mBP) in the HT group significantly decreased from 112+/-7 to 94+/-7 mmHg aftertreatment, concomitant with the disappearance of nonspecific complaints and theincrease of testosterone levels. In the N group, however, neither mBP nortestosterone levels changed. Psychotherapy can ameliorate mild systemichypertension in climacteric men with low testosterone levels. Mental stress mightsuppress the hypothalamic-pituitary-gonadal axis to decrease testosterone levels.
Ishikura F, Asanuma T, Beppu S. Low testosterone levels in patients with mild hypertension recovered after antidepressant therapy in a male climacterium clinic. Hypertens Res Feb;31(2):243-8.

39.  serum LH, Testosterone
Hypertensive men:
 serum LH, Testosterone
Men + Arterial Hypertension :
-  plasma testosterone (free & total) : - 30 %
(13 patients w/AHT  w/controls)
(Hughes GS et al, Atherosclerosis, 1990, 84 (2-3): )
-  plasma LH & testosterone
(Tuev AV et al, Res Med Zh, 1992, 3: 10-3)
-  plasma testo (free & total)
(Phillips GB et al, J Hypertens, 1993, 11(7): )
!! Antihypertensive drugs
(beta-blockers, reserpine, prazosine, …)
 plasma testosterone (Zanozdra NS et al, Klin Med Mosk, 1990, 68 (7): 89-92; Gumbatov, Kardiologiia, 1992, 32(3): 37-40) 

40. Testosterone treatment may
 High Blood Pressure

41. Rheumatism : Hormone treatment
Arterial hypertension
Testosterone therapy
start preferably with transdermal liposomal cream of testosterone
Softer
more stable testosterone levels
Compounded testosterone liposomal gel
10 % (men)
0.5% (womern)
Testosterone
liposomal gel

42. Testosterone’s =>arteries: Mechanism
= vasodilator

43. ARTERIAL HYPERTENSION: Mechanism in Testosterone Deficiency
=>  parasympathetic nervous activity =>  relaxation of arterial smooth muscle cells
=> lack of vasodilatation
Testosterone
= vasodilator
e.g. Blood pressure of 160/80 mmHg

44. Nr 4 Treatment for Arterial hypertension: Growth hormone (& IGF-1) Therapies

45. => Arterial hypertension
GH deficiency
=> Arterial hypertension

46. ARTERIAL HYPERTENSION: Mechanism in Growth Hormone Deficiency
=>  Distensibility of the arteries
Growth hormone
=>  Tissue elasticity
e.g. blood pressure of 160/90 mmHg

47. (Landin-Wilhelmsen 1994) =>  systolic &  diastolic AT
 serum IGF-1
=>  systolic &  diastolic AT
(Landin-Wilhelmsen 1994)
Note : GH-therapy in young adults
=> NO effect on blood pressure
(Bengtssen BA et al, J Clin Endocrinol Metab, 1993, 76: ; Beshyah SA et al, J Intern Med, 1995, 237 (1): 35-42)

48.  sympathetic nervous system activity
Pathologic alterations that may contribute to or are associated w/ elevated BP in aging
 Arterial stiffness
 sympathetic nervous system activity
 Baroreceptor sensitivity
   &   adrenergic responsiveness
 Endothelial cell-derived relaxing factor fn
 Sodium sensitivity
 Plasma renin activity
 insulin resistance
(Supiano MA, 1996, Hypertension in Geriatric Medicine, 3th edition, Eds Springer-Verlag, NY)

49. GH & IGF-1 treatments may
 High Blood Pressure

50. Arterial hypertension
GH THERAPY
! Avoid inducing with GH =>vthyroid excess
TIP 1: Start at lower dose then carefully increase to moderately high dose
= > REMAIN slightly SUBOPTIMAL until the BP is normalized:l
0.1 – 0.25 mg/day of GH
Emergency & severe heart weakness
0.3 mg/day GH daily permanently
mg/day of hydrocortisone
or mg/day of methylprednisolone
TIP 2: GH works better than IGF-1
to reduce the blood pressure
thanks to its
greater elasticity-enhancing effects
greater weight-reducing effects. 50

51. 
Subcutaneous IGF-1 injections mg/day at bedtime (may start at high dose)
Slow Progress: First improvement during the 2-4 months, up to months for full improvement

52. 6 months of GH treatment
=>  diastolic blood pressure & total peripheral resistance in GH deficient adults
Figure: double-blind placebo-controlled cross-over study
Caidahl K, Eden S, Bengtsson BA. Cardiovascular and renal effects of growth hormone.
Clin Endocrinol (Oxf) Mar;40(3):

53. 6 months of GH treatment on diastolic blood pressure & total peripheral resistance in GH deficient adults
Figure: double-blind placebo-controlled cross-over study
Caidahl K, Eden S, Bengtsson BA. Cardiovascular and renal effects of growth hormone.
Clin Endocrinol (Oxf) Mar;40(3):

54. Nr 5 Treatment for Arterial hypertension at night: Melatonin

55. Arterial hypertension
=> Associated with Melatonin deficiency

56. Arterial Hypertension:
 Melatonin
ARTERIAL HYPERTENSION =>
 serum melatonin (Birau N, 1980)
Pinealectomy =>  blood pressure (rats) (Holmes W,ProceedingsB.P.S., 1975,Dec.:306)

57. Arterial hypertension: the association with lower melatonin levels
Cui HW, Zhang ZX, Gao MT, Liu Y, Su AH, Wang MY. Circadian rhythm of melatonin and blood pressure changes in patients with essential hypertension. Zhonghua Xin Xue Guan Bing Za Zhi Jan;36(1):20-3
Zeman M, Dulková K, Bada V, Herichová I. Plasma melatonin concentrations in hypertensive patients with the dipping and non-dipping blood pressure profile. Life Sci Mar 4;76(16):
Cagnacci A, Arangino S, Angiolucci M, Melis GB, Tarquini R, Renzi A, Volpe A. Different circulatory response to melatonin in postmenopausal women without and with hormone replacement therapy. J Pineal Res Oct;29(3):152-8
Rapoport SI, Shatalova AM, Malinovskaia NK, Vettenberg L. Melatonin production in hypertensive patients. Klin Med (Mosk). 2000;78(6):21-4
Rapoport SI, Shatalova AM, Oraevskii VN, Malinovskaia NK, Vetterberg L. Melatonin production in hypertonic patients during magnetic storms. Ter Arkh. 2001;73(12):29-33
Tetsuo M, Polinsky RJ, Markey SP, Kopin IJ. Urinary 6-hydroxymelatonin excretion in patients with orthostatic hypotension. J Clin Endocrinol Metab Sep;53(3):607-10
8):36-41

58.             
 ratio of nighttime/daytime urine 6-SMT levels => positively corr. with  blood pressure during nighttime (P < 0.05) in all groups
Non-dipping hypertensive patients:
Sign.  nighttime urine 6-SMT levels
Sign.  ratio of nighttime/daytime urine 6-SMT levels
vs control & dipping hypertensive groups (all P <0.01).
Moreover, ratio of nighttime/daytime urine 6-SMT levels are positively correlated blood pressure reduction during nighttime (P < 0.05) in all groups
Cui HW, Zhang ZX, Gao MT, Liu Y, Su AH, Wang MY. [Circadian rhythm of melatonin and blood pressure changes in patients withessential hypertension] Zhonghua Xin Xue Guan Bing Za Zhi Jan;36(1):20-3.Department of Emergency, Hospital of Weifang Medical University, Weifang , China. To observe the association between melatonin (MLT) secretion and bloodpressure changes during 24 hours in hypertensive patients (HPT) with (dipping) orwithout (non-dipping) night time blood pressure reduction. METHODS: The 24-hourblood pressure and urine 6-SMT (6-sulfatoxymelatonin, metabolism product of MLTin urine) in the daytime and nighttime were measured in normal control subjects(n = 20), non-dipping HPT group (n = 32) and dipping HPT group (n = 36). RESULTS:As expected, blood pressure reduction during the night was significantly lower innon-dipping HPT group compared to control and dipping HPT groups. Nighttime 6-SMTwas significantly higher than daytime 6-SMT in all groups and nighttime urine6-SMT levels and ratio of nighttime/daytime urine 6-SMT levels were significantlylower in non-dipping HPT group compared to control and dipping HPT groups (all P < 0.01). Moreover, ratio of nighttime/daytime urine 6-SMT levels are positivelycorrelated blood pressure reduction during nighttime (P < 0.05) in all groups.CONCLUSIONS: Circadian rhythm of MLT secretion is maintained but nighttime MLTsecretion was significantly reduced and related to disorders of circadian rhythm of blood pressure in non-dipping HPT group.
Cui HW, Zhang ZX, Gao MT, Liu Y, Su AH, Wang MY. [Circadian rhythm of melatonin and blood pressure changes in patients withessential hypertension] Zhonghua Xin Xue Guan Bing Za Zhi Jan;36(1):20-3.

59. ARTERIAL HYPERTENSION: Mechanism in Melatonin Deficiency
 Melatoninat night
=>  parasympathetic nervous activity =>  relaxation of arterial smooth muscle cells
=> lack of vasodilatation at night
Melatonin
= vasodilator
e.g. Blood pressure of 180/100 mmHg

60. Melatonin treatment may
 High Blood Pressure

61. Arterial hypertension
Arterial hypertension
Sublingual
Doses:
Sublingual Melatonin: mg/day
or Oral: mg/day
At bedtime
Oral
TIP: contrary to many other hormone treatments in arterial hypertension, melatonin doses may be higher (supraphysiological) such as 2-5 mg, particularly in patients with nondipping BP at night

62. MELATONIN =>  blood pressure
Melatonin therapy =>  blood pressure in
Arterial Hypertensive men (humans) &
pinealectomized rats (Holmes SW, Pr. BPS, 1975, 306)
Mechanism :
- relaxes smooth muscle tone of the aorta
-  its response to vasoconstriction stimulants (of alpha-1 & 2 adrenergic receptors) (Weekley LB, J Pineal Res, 1991, 11: 28-34)
-  serotonin liberation in corpus striatum & hypothalamus
(Chuan JI, Pharmacology, 1993, 47: 94-7)
-  (inhibits) orthosympathic system &  (stimulates) the parasympathic nervous system
-  bradycardia + arterial hypotension
-  corticosterone secretion (Zeman M, Comp Biochem Physiol Comp Physiol, 1993, 105: 323-8)

63. Melatonin =>  Hypertension
Arterial tension (mm/Hg)
Controls
Placebo
Melatonin
systolic
diastolic
Figure: Melatonin treatment reduces essential hypertension
(Birau N et al, IRSC medical Science, 1981, 9 :906)

64. Melatonin => to decrease BP
            
Melatonin => to decrease BP
Among patients with hypertension
some exhibit a much greater reduction in blood pressure at night (the so-called 'extreme dippers' & 'dippers')
others exhibit only a slight night time reduction in systolic and diastolic pressure ('non-dippers' & 'inverted dippers')
Longitudinal studies of these patients => inverted dippers & non-dippers die at a faster rate than do dippers & extreme dippers.
The chronic administration of melatonin to individuals with hypertension => measurable drop in night time systolic & diastolic blood pressure.
the higher the night time level of endogenous melatonin (estimated from urinary metabolite of melatonin, 6-hydroxymelatonin sulphate) => the greater the reduction in arterial blood pressure at night
Reiter RJ, Tan DX, Korkmaz A. The circadian melatonin rhythm and its modulation: possible impact on
hypertension. J Hypertens Aug;27 Suppl 6:S17-20.
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA.
In experimental rodents, surgical removal of the pineal gland, the major source
of circulating melatonin, causes a gradual and sustained rise in blood pressure.
Conversely, when melatonin is chronically administered to pinealectomized rodents
the increment in blood pressure is ameliorated. In humans as well, the night time
rise in endogenous circulating melatonin levels may be inversely related to the
reduction in night time blood pressure. Among patients with hypertension, some
exhibit a much greater reduction in blood pressure at night (the so-called
'extreme dippers' and 'dippers'), whereas others exhibit only a slight night time
reduction in systolic and diastolic pressure ('non-dippers' and 'inverted
dippers'). Longitudinal studies of these patients show that inverted dippers and
non-dippers die at a faster rate than do dippers and extreme dippers. The chronic
administration of melatonin to individuals with hypertension induces a measurable
drop in night time systolic and diastolic blood pressure. Moreover, the higher
the night time level of endogenous melatonin (estimated from urinary metabolite
of melatonin, 6-hydroxymelatonin sulphate), the greater the reduction in arterial
blood pressure at night. The implication of these findings is that melatonin may
have utility as an antihypertensive agent
Reiter RJ, Tan DX, Korkmaz A. The circadian melatonin rhythm and its modulation: possible impact on hypertension. J Hypertens Aug;27 Suppl 6:S17-20

65. Arterial hypertension: the improvement with melatonin treatment
Rechciński T, Trzos E, Wierzbowska-Drabik K, Krzemińska-Pakuła M, Kurpesa M. Melatonin for nondippers with coronary artery disease: assessment of blood pressure profile and heart rate variability. Hypertens Res Jan;33(1):56-61
Reiter RJ, Tan DX, Korkmaz A. The circadian melatonin rhythm and its modulation: possible impact on hypertension. J Hypertens Aug;27 Suppl 6:S17-20.
Rechciński T, Kurpesa M, Trzos E, Krzeminska-Pakuła M. The influence of melatonin supplementation on circadian pattern of blood pressure in patients with coronary artery disease--preliminary report. Pol Arch Med Wewn Jun;115(6):520-8
Cagnacci A, Arangino S, Angiolucci M, Maschio E, Melis GB. Influences of melatonin administration on the circulation of women. Am J Physiol Feb;274(2 Pt 2):R335-8
Cagnacci A, Arangino S, Angiolucci M, Maschio E, Longu G, Melis GB. Potentially beneficial cardiovascular effects of melatonin administration in women. J Pineal Res Jan;22(1):16-9
Cagnacci A, Arangino S, Angiolucci M, Melis GB, Facchinetti F, Malmusi S, Volpe A. Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. Clin Endocrinol (Oxf) Feb;54(2):261-6
Arangino S, Cagnacci A, Angiolucci M, Vacca AM, Longu G, Volpe A, Melis GB. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol May 1;83(9):1417-9
Burgess HJ, Sletten T, Savic N, Gilbert SS, Dawson D. Effects of bright light and melatonin on sleep propensity, temperature, and cardiac activity at night. J Appl Physiol Sep;91(3):
Nishiyama K, Yasue H, Moriyama Y, Tsunoda R, Ogawa H, Yoshimura M, Kugiyama K. Acute effects of melatonin administration on cardiovascular autonomic regulation in healthy men. Am Heart J May;141(5):E9
Lusardi P, Preti P, Savino S, Piazza E, Zoppi A, Fogari R. Effect of bedtime melatonin ingestion on blood pressure of normotensive subjects. Blood Press Monit Apr;2(2):99-103
Kitajima T, Kanbayashi T, Saitoh Y, Ogawa Y, Sugiyama T, Kaneko Y, Sasaki Y, Aizawa R, Shimisu T. The effects of oral melatonin on the autonomic function in healthy subjects. Psychiatry Clin Neurosci Jun;55(3):
Zaslavskaia RM, Biiasilov NS, Akhmetov Kzh, Teiblium MM. Capozide-50 alone and in combination with melatonin in therapy of hypertension. Klin Med (Mosk). 2000;78(11):39-41
Zaslavskaia RM, Komarov FI, Shakirova AN, Teiblium MM, Akhmetov KZh. Effect of moxonidine monotherapy and in combination with melatonin on hemodynamic parameters in patients with arterial hypertension. Klin Med (Mosk). 2000;78(4):41-4
Zaslavskaia RM, Komarov FI, Goncharov LF, Goncharova ZF, Makarova LA. Comparative study of the effectiveness of Cozaar monotherapy and Cozaar and melatonin combined therapy in aged patients with hypertension. Klin Med (Mosk). 1998;76(12):49-51
Zaslavskaia RM, Shakirova AN, Komarov FI, Teiblium MM, Akhmetov KZh. Effects of melatonin alone and in combination with aceten on chronostructure of diurnal hemodynamic rhythms in patients with hypertension stage II. Ter Arkh. 1999;71(12):21-4
Zaslavskaia RM, Komarov FI, Makarova LA, Shakirova AN, Narmanova OZh, Biiasilov N. Time-dependent effects of antihypertensive agents and chronocorrecting action of melatonin in patients with arterial hypertension. Vestn Ross Akad Med Nauk. 2000;(8):36-41
Arterial hypertension: the improvement with melatonin treatment
Rechciński T, Trzos E, Wierzbowska-Drabik K, Krzemińska-Pakuła M, Kurpesa M. Melatonin for nondippers with coronary artery disease: assessment of blood pressure profile and heart rate variability. Hypertens Res Jan;33(1):56-61
Reiter RJ, Tan DX, Korkmaz A. The circadian melatonin rhythm and its modulation: possible impact on hypertension. J Hypertens Aug;27 Suppl 6:S17-20.
Rechciński T, Kurpesa M, Trzos E, Krzeminska-Pakuła M. The influence of melatonin supplementation on circadian pattern of blood pressure in patients with coronary artery disease--preliminary report. Pol Arch Med Wewn Jun;115(6):520-8
Cagnacci A, Arangino S, Angiolucci M, Maschio E, Melis GB. Influences of melatonin administration on the circulation of women. Am J Physiol Feb;274(2 Pt 2):R335-8
Cagnacci A, Arangino S, Angiolucci M, Maschio E, Longu G, Melis GB. Potentially beneficial cardiovascular effects of melatonin administration in women. J Pineal Res Jan;22(1):16-9
Cagnacci A, Arangino S, Angiolucci M, Melis GB, Facchinetti F, Malmusi S, Volpe A. Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. Clin Endocrinol (Oxf) Feb;54(2):261-6
Arangino S, Cagnacci A, Angiolucci M, Vacca AM, Longu G, Volpe A, Melis GB. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol May 1;83(9):1417-9
Burgess HJ, Sletten T, Savic N, Gilbert SS, Dawson D. Effects of bright light and melatonin on sleep propensity, temperature, and cardiac activity at night. J Appl Physiol Sep;91(3):
Nishiyama K, Yasue H, Moriyama Y, Tsunoda R, Ogawa H, Yoshimura M, Kugiyama K. Acute effects of melatonin administration on cardiovascular autonomic regulation in healthy men. Am Heart J May;141(5):E9
Lusardi P, Preti P, Savino S, Piazza E, Zoppi A, Fogari R. Effect of bedtime melatonin ingestion on blood pressure of normotensive subjects. Blood Press Monit Apr;2(2):99-103
Kitajima T, Kanbayashi T, Saitoh Y, Ogawa Y, Sugiyama T, Kaneko Y, Sasaki Y, Aizawa R, Shimisu T. The effects of oral melatonin on the autonomic function in healthy subjects. Psychiatry Clin Neurosci Jun;55(3):
Zaslavskaia RM, Biiasilov NS, Akhmetov Kzh, Teiblium MM. Capozide-50 alone and in combination with melatonin in therapy of hypertension. Klin Med (Mosk). 2000;78(11):39-41
Zaslavskaia RM, Komarov FI, Shakirova AN, Teiblium MM, Akhmetov KZh. Effect of moxonidine monotherapy and in combination with melatonin on hemodynamic parameters in patients with arterial hypertension. Klin Med (Mosk). 2000;78(4):41-4
Zaslavskaia RM, Komarov FI, Goncharov LF, Goncharova ZF, Makarova LA. Comparative study of the effectiveness of Cozaar monotherapy and Cozaar and melatonin combined therapy in aged patients with hypertension. Klin Med (Mosk). 1998;76(12):49-51
Zaslavskaia RM, Shakirova AN, Komarov FI, Teiblium MM, Akhmetov KZh. Effects of melatonin alone and in combination with aceten on chronostructure of diurnal hemodynamic rhythms in patients with hypertension stage II. Ter Arkh. 1999;71(12):21-4
Zaslavskaia RM, Komarov FI, Makarova LA, Shakirova AN, Narmanova OZh, Biiasilov N. Time-dependent effects of antihypertensive agents and chronocorrecting action of melatonin in patients with arterial hypertension. Vestn Ross Akad Med Nauk. 2000;(

66. Nr 6 Treatment for Arterial hypertension: DHEA

67. Arterial hypertension
=>  DHEA levels

68. Arterial Hypertension: DHEA Deficiency
 urinary DHEAs in hypertensive patients
(Coleman, Diabetes, 1982, 31: 830-!33)
 urinary DHEA & etiocholanolone glucuronide
(Gansler, Proc Soc Exp Biol Med, 1985, 180: )
 urinary 17-ketosteroids (Rom, Environ Res, 1991, 55 (2):

69. HYPERTENSION:  urinary DHEA
Urinary DHEAs
Figure 1 : poor urinary levels of DHEA sulfate in hypertensive subjects
Healthy subjects
Hypertensive subjects
Figure 2 : low urinary levels of adrenal androgens (incl. DHEA) in hypertensive subjects
Men
Urinary androgens
Women
Hypertensive subjects
Women
Men
Healthy subjects

70. Hypertensive subjects
HYPERTENSION:  urinary DHEA metabolites
Healthy
men
Urinary 17-ketosteroids
Hypertensive subjects
women
women
men
Figure : Low urinary levels of adrenal androgens (incl. DHEA) in hypertensive subjects
Nowaczynski W et al. Can J Biochem. 1968; 46 (9):

71. ARTERIAL HYPERTENSION: Mechanism in DHEA deficiency
=>  parasympathetic nervous activity =>  relaxation of arterial smooth muscle cells
=> lack of vasodilatation
DHEA
= vasodilator
e.g. Blood pressure of 160/80 mmHg

72. DHEA treatment may
 High Blood Pressure

73. DHEA treatment: in adults:
Arterial hypertension
DHEA treatment:
in adults:
Women: mg/day
Men: mg/day
Compounded:
Often -40% action

74. DHEA =>  Arterial Hypertension induced by glucocorticoids
DHEA-therapy
 arterial hypertension only if hypertension is induced by glucocorticoids
No effect of DHEA on genetic AHT or AHT induced with mineralocorticoids
(Turner, Am J Physiol, 1990, 258: E )

75. Nr 7 Treatment for Arterial hypertension: Methylprednisolone in case of Aldosterone excess

76. Glucocorticoids =>  Arterial Hypertension induced by mineralocorticoids (aldosterone)
ARTERIAL HYPERTENSION can be induced in patients with cortisol deficiency by  production of aldosterone, due to  ACTH levels, trying to stimulate the adrenals to make more cortisol
=> Treatment= methylprednisolone, which at low doses of 3-5 mg/day does not increase the BP, but  well aldosterone secretion =>  BP

77. CORTISOL => Blood Pressure
Cortisol therapy
1.  ARTERIAL HYPOTENSION
 cortisol =>  Arterial tension (Wong, 1993)
2.  ARTERIAL HYPERTENSION
Cortisol therapy =>  vasopressin (Raff, 1990)
 AHT of lupus eryt. (Handa, 1994)
!! AHT with excess cortisol/glucocorticoids appears only in predisposed persons (lacking 11-beta-hydroxysteroid - deshydrogenase that inactivates cortisol into much less active cortisone) => accumulation of cortisol (Walker, 1992)

78. Nr 8 Treatment for Arterial hypertension: Oxytocin

79. Arterial hypertension: the assoc. with lower oxytocin (receptor)levels
Light KC, Grewen KM, Amico JA. More frequent partner hugs and higher oxytocin levels are linked to lower blood pressure and heart rate in premenopausal women. Biol Psychol Apr;69(1):5-21
Light KC, Grewen KM, Amico JA, Brownley KA, West SG, Hinderliter AL, Girdler SS. Oxytocinergic activity is linked to lower blood pressure and vascular resistance during stress in postmenopausal women on estrogen replacement. Horm Behav May;47(5):540-8
Light KC, Grewen KM, Amico JA. Higher baseline OT before partner contact was associated with lower BP a more frequent partner hugs and higher oxytocin levels are linked to lower blood pressure and heart rate in premenopausal women. Biol Psychol Apr;69(1):5-21 Amico JA, Corder CN, McDonald RH Jr, Robinson AG. Levels of the oxytocin-associated and vasopressin-associated neurophysins in plasma and their responses in essential hypertension. Clin Endocrinol (Oxf) Mar;20(3):289-97
Grewen KM, Girdler SS, Amico J, Light KC. Effects of partner support on resting oxytocin, cortisol, norepinephrine, and blood pressure before and after warm partner contact. Psychosom Med Jul-Aug;67(4):531-8
Holt-Lunstad J, Birmingham WA, Light KC. Influence of a "warm touch" support enhancement intervention among married couples on ambulatory blood pressure, oxytocin, alpha amylase, and cortisol. Psychosom Med Nov;70(9):976-85
Light KC, Smith TE, Johns JM, Brownley KA, Hofheimer JA, Amico JA. Oxytocin responsivity in mothers of infants: a preliminary study of relationships with blood pressure during laboratory stress and normal ambulatory activity. Health Psychol Nov;19(6):560-7
Light KC, Grewen KM, Amico JA, Boccia M, Brownley KA, Johns JM. Deficits in plasma oxytocin responses and increased negative affect, stress, and bloodpressure in mothers with cocaine exposure during pregnancy. Addict Behav Nov;29(8):
Martins AS, Crescenzi A, Stern JE, Bordin S, Michelini LC. Hypertension and exercise training differentially affect oxytocin and oxytocin receptor expression in the brain. Hypertension Oct;46(4): (Lower oxytocin receptors in hypertension)

80. Arterial hypertension: the improvement with oxytocin therapy
Kitchin AH, Konzett H, Pickford M. Comparison of effects of valyl(3)-oxytocin and syntocinon on the cardiovascular system of man. Br J Pharmacol Chemother Dec;14:567-70
Gutkowska J, Jankowski M, Mukaddam-Daher S, McCann SM. Oxytocin is a cardiovascular hormone. Braz J Med Biol Res Jun;33(6): Uvnäs-Moberg K. Oxytocin may mediate the benefits of positive social interaction and emotions. Psychoneuroendocrinology Nov;23(8):819-35
Uvnas-Moberg K, Petersson M. Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing. Z Psychosom Med Psychother. 2005;51(1):57-80
Petersson M, Lundeberg T, Uvnäs-Moberg K. Short-term increase and long-term decrease of blood pressure in response to oxytocin-potentiating effect of female steroid hormones. J Cardiovasc Pharmacol Jan;33(1):102-8
Maier T, Dai WJ, Csikós T, Jirikowski GF, Unger T, Culman J. Oxytocin pathways mediate the cardiovascular and behavioral responses to substance P in the rat brain. Hypertension Jan;31(1 Pt 2):480-6.
Petty MA, Lang RE, Unger T, Ganten D. The cardiovascular effects of oxytocin in conscious male rats. Eur J Pharmacol Jun 7;112(2):203-10
Petersson M, Uvnäs-Moberg K. Postnatal oxytocin treatment of spontaneously hypertensive male rats decreases blood pressure and body weight in adulthood. Neurosci Lett Aug 1;440(2):166-9
Holst S, Uvnäs-Moberg K, Petersson M. Postnatal oxytocin treatment and postnatal stroking of rats reduce blood pressure in adulthood. Auton Neurosci Aug 30;99(2):85-90
Petersson M, Lundeberg T, Uvnäs-Moberg K. Oxytocin decreases blood pressure in male but not in female spontaneously hypertensive rats. J Auton Nerv Syst Sep 10;66(1-2):15-8
Petersson M, Alster P, Lundeberg T, Uvnäs-Moberg K. Oxytocin causes a long-term decrease of blood pressure in female and male rats. Physiol Behav Nov;60(5):1311-5
Weis FR Jr, Markello R, Mo B, Bochiechio P. Cardiovascular effects of oxytocin. Obstet Gynecol Aug;46(2):211-4 Weis FR Jr, Markello R, Mo B, Bochiechio P. Cardiovascular effects of oxytocin. Obstet Gynecol Aug;46(2):211-4 (Oxytocin given as a bolus of 5 to 10 IU decreases blood pressure and increases heart rate, stroke volume and cardiac output)

81. Conclusion & Any Questions?

82. Conclusion Patients with arterial hypertension
are (multiple) hormone-deficient
need hormone therapies (treats the cause) much more than antihypertensive (treats the consequences)
Antihypertensive drugs remain usefule as a transient role during the 6-15 months necessary to get back a healthy blood pressure
Doses: In most cases relatively low to medium physiological doses of the missing hormones are necessary to reduce/cure arterial hypertension