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Hypertension. 1988;11:78-83
doi: 10.1161/01.HYP.11.1.78
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SUMMARY Hypothyroid ism has been known to be associated, at times, with diastolic hyperten-
sion. We have found in 40 thyrotoxic patients that the induction of hypothyroid ism by radioiodine
therapy significantly increased diastolic blood pressure, raising it above 90 mm Hg in 16 (40%) of the
patients. Restoration of euthyroidism with thyroxine administration significantly reduced the systolic
and diastolic blood pressures in these patients, with a fall in diastolic pressure below 90 mm Hg in nine
of 16 patients. The prevalence of hypothyroid ism was determined by measurements of serum thyrox-
ine and thyrotropin concentrations in 688 consecutive hypertensive patients, referred for evaluation
and therapy of their hypertension. Hypothyroidism was found in 25 (3.6%) of the patients. Restora-
tion of normal serum thyroxine and thyrotropin levels with thyroid hormone replacement therapy
lowered diastolic blood pressure to levels below 90 mm Hg in 32% of these patients who could be
followed up after withdrawal of all antihypertensive drug therapy when euthyroidism had been
restored (i.e., 1.2% of the 688 patients). It is concluded that diastolic hypertension resulting from
hypothyroidism is a relatively common disorder, present in 1.2% of our referred hypertensive
patients, that should be sought and treated. (Hypertension 11: 78-83, 1988)
78
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HYPOTHYROIDISM CAUSING HYPERTENSION/S/reefen et al. 79
BP was measured in the sitting posture, at each office all except seven of the patients (five of whom also had
visit, before treatment with iodine-131 (80 /iCi/g of had diastolic hypertension when thyrotoxic), while the
estimated thyroid weight); 3 to 6 months later when BP in the entire group averaged 130.6 1.9/80.8
euthyroidism had been restored; during the subsequent 1.9 mm Hg. The changes in diastolic BP from the
development of hypothyroidism, which commonly thyrotoxic to the hypothyroid and euthyroid states
follows radioiodine treatment; and after the restoration were highly significant by analysis of variance
of euthyroidism by replacement therapy with sufficient (/><0.0001). The changes in systolic BP were not
L-thyroxine or desiccated thyroid to restore serum thy- significant. No clinical or laboratory differences were
roxine (T4) and thyrotropin or thyroid stimulating hor- found between the patients whose diastolic BP rose
mone (TSH) concentrations to normal. Measurements above 90 mm Hg during hypothyroidism and those
of serum T4 and TSH levels were made by radioimmu- whose diastolic BP remained below 90 mm Hg. How-
noassay at each visit. ever, there were significant correlations between the
In 688 consecutive, untreated patients referred for diastolic BPs during hyperthyroidism and hypothy-
study and management of their hypertension, we mea- roidism ( r = +0.576, p < 0 . 0 0 1 ) , during hyperthy-
sured BP in the recumbent and standing postures with roidism and euthyroidism (r = +0.476, p < 0 . 0 0 5 ) ,
an aneroid sphygmomanometer; serum T4, TSH, and and during hypothyroidism and euthyroidism (r =
electrolyte concentrations, as well as plasma renin ac- + 0.653, p<0.00l).
tivity (PRA),10 after furosemide, 40 mg i.v., and A computer printout of the serum T4 and TSH con-
standing for 2 hours; BP response to the angiotensin II centrations jn the 688 untreated hypertensive patients
antagonist saralasin; and plasma aldosterone concen- is shown in Figure 2. It is evident that serum T4 was
tration after an intravenous infusion of 2 L of 0.9% elevated ( > 12 /ig/dl) in 26 (3.8%) of the patients,
NaCl given over 3.5 hours." 112 The patients varied in while hypothyroidism (serum T 4 < 5 fig/d\ or serum
age from 15 to 70 years, were evenly divided between T S H > 7 /ilU/ml, or both) was present in 25 (3.6%) of
female and male (55:45) patients, and had a mean the patients. Only three of these patients had clinical
body weight of 79.6 kg. Only in three of the five features suggesting hypothyroidism.
patients whose serum TSH exceeded 30 /ilU/ml was Figure 3 shows the results of various functional
the diagnosis of hypothyroidism suspected on clinical measurements in the 25 hypertensive patients who
grounds. Female patients predominated (75:25) were found to have hypothyroidism. Plasma renin ac-
among those patients who were found to be hypothy- tivity, stimulated by furosemide diuresis and orthosta-
roid. Mean body weight in the hypothyroid patients sis, was subnormal (below 1.7 ng/ml/hr) in 13 of 25
was 81.5 2 . 9 kg, and mean age was 49.8 2.5 (52%) patients. Plasma aldosterone fell into the normal
years. Patients who were found to be hypothyroid were range (1.7-8.5 ng/dl) in all but one of the 22 patients in
given L-thyroxine in addition to their usual antihyper- whom it was measured after the 2-L saline infusion.
tensive drugs in increasing doses until serum T4 and Intravenous infusion of saralasin, at 0.05 to 20 /Ltg/kg/
TSH concentrations were restored to normal. When min, lowered the diastolic BP more than normally
this had been accomplished, their hypotensive medica- (i.e., by > 8 mm Hg) in three, raised it to some extent
tions were tapered and stopped to determine whether in 17 patients, and raised diastolic BP by more than 8
the BP would remain in the normal range during treat- mm Hg in six of these 17 patients. Cardiac index,
ment with thyroid replacement only. measured in two patients, was high-normal in one and
All of these studies were approved in advance by the low-normal in the other patient, while systemic vascu-
Institutional Review Board for the Protection of Hu- lar resistance was elevated in both patients studied.
man Subjects at the SUNY Health Science Center Follow-up was incomplete in five of the hypothy-
(Syracuse, NY, USA). roid patients because of death (one), loss to follow-up
(two), and departure of the patient from this area
Results (two). Figure 4 shows BP responses to the restoration
Figure 1 shows the results of the systolic and diastol- of euthyroidism in the remaining 20 hypothyroid pa-
ic BP measurements in the 40 patients with hyperthy- tients. In eight, diastolic BP fell below 90 mm Hg
roidism. Before radioiodine therapy, eight of the pa- when they became euthyroid and remained below 90
tients had systolic hypertension and five had diastolic mm Hg when all antihypertensive medications had
pressures above 90 mm Hg; the mean SEM values been stopped for at least 6 months. In the other 12
for the 40 patients were 138.2 3.2/77.7 2.0 mm patients diastolic BP remained above 90 mm Hg when
Hg. When they had become euthyroid after I3II treat- euthyroidism had been restored unless antihyperten-
ment, mean systolic BP fell to 132.6 3.7 mm Hg sive drugs were administered. Four of the patients in
while diastolic pressure rose to 81.2 1.9 mm Hg. this group had severe renal insufficiency, with one of
The subsequent fall in serum T4 concentration to hypo- the four requiring chronic hemodialysis. Female pa-
thyroid levels was associated with a change in mean tients predominated both in those whose BP fell to
BP to 141.4 4.6/88.4 2 . 4 mm Hg. When they normal levels on thyroxine therapy alone (6 female, 2
were hypothyroid, 16 of the 40 patients had diastolic male patients) and in those who continued to require
BPs above 90 mm Hg. Restoration of euthyroidism (T4 other antihypertensive therapy after they had become
and TSH both within normal limits) by replacement euthyroid (9 female, 3 male patients); both groups
therapy, reduced the diastolic BP below 90 mm Hg in reflected the preponderance of women among hypo-
40 131
BEFORE I THERAPY AFTER 1 THERAPY
HYPO- EUTHYROID ON
20 HYPERTHYROID EUTHYROID[ r H Y R O I D REPLACEMENT R
32 24 16 8 0 4
thyroid patients in general. There was a significant age The serum T4 and TSH measurements in the 688
difference (p< 0.025) between these two groups of hypertensive patients revealed the presence of unrec-
patients: the mean age of those whose hypertension ognized hypothyroidism in 3.6%. Although serum T4
was corrected by thyroxine alone was 41.3 6 . 0 concentration was normal in several of these patients,
(SEM) years (range, 21-67 years), while in the second the elevation of serum TSH levels was assumed to
group mean age was 57.1 3.2 years (range, 28-68 indicate the presence of primary hypothyroidism, in
years). accordance with current views.13 Among the hypothy-
roid patients, there was a higher prevalence (52%) of
Discussion low renin hypertension (associated with subnormal
It is evident from this study that diastolic BP rose stimulated PRA levels and an agonistic BP response to
significantly during the change from hyperthyroidism saralasin14) than in euthyroid hypertensive patients of
to hypothyroidism and fell significantly when euthy- whom 30% had low PRA levels." The suppressed
roidism was restored in the 40 originally thyrotoxic level of PRA did not result from autonomously and
patients. These observations confirm the similar find- unsuppressibly elevated plasma aldosterone concen-
ings described by Davis and Davis4 in some of the trations, except in one patient, who did not have evi-
elderly thyrotoxic patients whose clinical responses to dence of an adrenal adenoma by computed tomograph-
radioactive iodine therapy they reported. No less than ic scanning. The hemodynamic measurements in two
40% of our patients had diastolic BPs over 90 mm Hg of these patients disclosed elevation of the systemic
when they were hypothyroid, and in most of these the vascular resistance, as is found in most patients with
blood pressure fell below 90 mm Hg after adequate sustained hypertension.
replacement therapy. These data certainly substantiate It was of interest to find that in no less than eight
the theoretical possibility that some patients who are patients with unrecognized hypothyroidism, or 1.2%
seen with hypertension might have unrecognized hy- of the 688 patients studied, therapeutic restoration of
pothyroidism and could be restored to normotension euthyroidism was associated with a fall in diastolic BP
with thyroxine replacement therapy alone. below 90 mm Hg. It is possible that the fall in BP
FIGURE 2. Serum thyroxine and thyrotropin (TSH) concentrations in 688 untreated hypertensive patients re-
ferred for refractoriness to therapy. In 25 patients (large dots) hypothyroidism was evident from subnormal serum
thyroxine (in 11) or elevated serum TSH (in 19) concentrations or both.
represented a placebo response, though the lack of an derson, Jr., S. Wagner, unpublished observations,
adequate reduction of BP during treatment given be- 1987) have confirmed the general principle that hyper-
fore the initiation of T4 replacement therapy would tension in older persons frequently persists when the
argue against that possibility. Thus, in these individ- initiating cause has been removed. It is possible, there-
uals, 1.2% of the 688 patients studied, it is reasonable fore, that if hypothyroidism had been discovered and
to attribute their hypertension to the demonstrated hy- treated at an earlier age, more of our patients would
pothyroidism and it was possible to control the hyper- have been responsive to T4 alone.
tension with thyroxine alone, without the variety of Although the prevalence of hypothyroidism in our
antihypertensive drugs that they had been given before hypertensive patients cannot be taken to indicate its
cessation of the therapy for the diagnostic studies. The prevalence in the entire hypertensive population, it is
hypothyroid patients whose diastolic BP fell below 90 likely that a large number of hypertensive patients are
mm Hg on L-thyroxine therapy alone were younger being given a vast array of modern antihypertensive
than those who continued to require other antihyper- drugs instead of the one hormone, T4, which they real-
tensive therapy after becoming euthyroid. Our recent ly need both to correct their hypertension and to over-
observations in patients with primary aldosteronism come their hypothyroidism. Since hypothyroidism is
and renal arterial stenosis (D. H. P. Streeten, G. H. An- mild and usually not clinically recognizable and since
in in r,l
tients.
s
; -
16. Bouhnik J, Galen F-X, Clauser E, Menard J, Corvol P. The tients with thyrotoxicosis and myxoedema. Clin Sci Mol Med
renin-angiotensin system in thyroidectomized rats. Endocri- 1973;45:163-171
nology 1981;108:647-650 21. Schneckloth RE, Kurland GS, Freedberg AS. Effect of vari-
17. Aikawa JK. The nature of myxedema-alterations in serum elec- ation in thyroid function on the pressor response to norepineph-
trolyte concentrations and radiosodium space and in exchange- rine in man. Metabolism 1953;2:546-555
able sodium and potassium content. Ann Intem Med 1956; 22. Fregly MJ. Thyroid activity of spontaneously hypertensive
44:30-39 rats. Proc Soc Exp Biol Med 1975;149:124-132
18. Waters AK. Body water compartments and exchangeable body 23. Fregly MJ, Baker MI, Gennaro JF Jr. Comparison of effects of
sodium in hypothyroidism. J Nucl Med Allied Sci 1978;22:43- thyroidectomy with propylthiouracil treatment on renal hyper-
45 tension in rats. Am J Physiol 1960; 198:4-12
19. Wiswell JG, Hurwitz GE, Coronho V, Bing OHL, Child DL. 24. Fregly MJ. Prevention of salt hypertension by propylthiouracil
Urinary catecholamines and their metabolites in hyperthyroid- treatment in rats. Proc Soc Exp Biol Med 1959;102:299-302
ism and hypothyroidism. J Clin Endocrinol Metab 1963;23: 25. Rioux F, Berkowitz BA. Role of the thyroid gland in the
1102-1106 development and maintenance of spontaneous hypertension in
20. Christensen NJ. Plasma noradrenaline and adrenaline in pa- rats. Circ Res 1977;40:306-312