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Cited by 172Thyroid Disorders and TreatmentsBlood Pressure and Hypertension StudiesHormonal Regulation and Hypertension

The Role of Thyroid Hormone in Blood Pressure Homeostasis: Evidence from Short-Term Hypothyroidism in Humans

Open access
Fommei, Enza, Iervasi, Giorgio·2002·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.87.5.1996
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Abstract

Arterial hypertension is known to be frequently associated with thyroid dysfunction, with a particularly high prevalence in chronic hypothyroidism. However, to our knowledge no comprehensive study addressed causal mechanisms possibly involved in this association. We here report the physiological relationships between blood pressure and neuro-humoral modifications induced by acute hypothyroidism in normotensive subjects. Twelve normotensive patients with previous total thyroidectomy were studied. Ambulatory 24-h blood pressure monitoring was performed, and free T3, free T4, TSH, PRA, aldosterone, cortisol, adrenaline, and noradrenaline were assayed 6 wk after oral l-T4 withdrawal (phase 1) and 2 months after resumption of treatment (phase 2). During the hypothyroid state (TSH, 68.1 ± 27.7 μIU/ml; mean ± sd), daytime arterial systolic levels slightly, but significantly, increased (125.5 ± 9.7 vs. 120.4 ± 10.8 mm Hg; P < 0.05), and daytime diastolic levels (84.6 ± 7.9 vs. 76.4 ± 6.8 mm Hg; P < 0.001), noradrenaline (2954 ± 1578 vs. 1574 ± 962 pmol/liter; P < 0.001), and adrenaline (228.4 ± 160 vs. 111.3 ± 46.1 pmol/liter; P < 0.05) also increased. PRA remained unchanged (0.49 ± 0.37 vs. 0.35 ± 0.21 ng/ml·h; P = NS), whereas both aldosterone (310.3 ± 151 vs. 156.9 ± 67.5 pmol/liter; P < 0.005) and cortisol (409.2 ± 239 vs. 250.9 ± 113 pmol/liter; P < 0.02) significantly increased. By using univariate logistic regression daytime arterial diastolic values, noradrenaline and aldosterone were found to be significantly related to the hypothyroid state (P < 0.02, P < 0.036, and P < 0.024, respectively). In conclusion, our data show that thyroid hormones participate in the control of systemic arterial blood pressure homeostasis in normotensive subjects. The observed sympathetic and adrenal activation in hypothyroidism, which is reversible with thyroid hormone treatment, may also contribute to the development of arterial hypertension in human hypothyroidism.

AI snapshot

Written from the paper’s full text.

TL;DR

In 12 normotensive patients after total thyroidectomy, short-term L-T4 withdrawal-induced hypothyroidism raised daytime systolic and diastolic blood pressure and increased noradrenaline, adrenaline, aldosterone, and cortisol, while PRA did not change. These changes reversed with L-T4 replacement, suggesting thyroid hormone contributes to blood pressure homeostasis and that sympatho-adrenal activation may contribute to hypothyroid hypertension.

Key findings

  • During hypothyroidism (TSH 68.1 ± 27.7 IU/ml), daytime systolic BP increased from 120.4 ± 10.8 to 125.5 ± 9.7 mm Hg (P < 0.05) and daytime diastolic BP increased from 76.4 ± 6.8 to 84.6 ± 7.9 mm Hg (P < 0.001); nighttime BP changes were not significant.
  • Noradrenaline rose from 1574 ± 977 to 2954 ± 1578 pmol/liter (P = 0.001), adrenaline from 111.3 ± 46.1 to 228.6 ± 159.6 pmol/liter (P = 0.05), aldosterone from 156.8 ± 67.4 to 310.3 ± 151.3 pmol/liter (P < 0.005), and cortisol from 251.0 ± 113 to 409.11 ± 239 pmol/liter (P < 0.02).
  • PRA remained unchanged (0.35 ± 0.21 vs. 0.49 ± 0.38 ng/ml·h; NS).
  • In univariate logistic regression, daytime diastolic BP, noradrenaline, and aldosterone were significantly related to the hypothyroid state (P < 0.02, P < 0.036, and P < 0.024, respectively). The paper also reports that BP increased into the hypertensive range in one third of patients when hypothyroidism was induced.

Methods

  • Twelve normotensive patients (9 women, 3 men; mean age 50.7 ± 8.4 yr) with previous total thyroidectomy and radioiodine ablation for stage I differentiated thyroid cancer were studied in two phases: 6 wk after L-T4 withdrawal (hypothyroid phase 1) and 2 months after resumption of oral L-T4 replacement (phase 2).
  • At both time points, 24-h ambulatory BP monitoring was performed with a SPACE-LABS 90207 device, and plasma free T3, free T4, TSH, PRA, aldosterone, cortisol, adrenaline, and noradrenaline were assayed.
  • Continuous variables were compared by paired t test or Wilcoxon test; relationships were assessed by linear regression and univariate logistic regression, with P < 0.05 considered significant.

Limitations

  • Stated: the authors caution that results from this unique short-term human model may not transfer directly to long-term thyroid function abnormalities.
  • Stated: changes in catecholamines, aldosterone, and cortisol are difficult to interpret per se because hypothyroidism may alter intravascular volume, hormone clearance, salt sensitivity, vasopressin, and atrial natriuretic peptide.
  • Evident from the text: the sample is small (n = 12) and highly selected (normotensive patients with treated thyroid cancer and no other disease or pharmacological treatment), and the study lacks a separate control group, so generalizability is limited.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1210/jcem.87.5.8464

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

8 of 29 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Interpretationcitation

    In the presence of reduced PRA, ALDO secretion could be sustained by ACTH.

    “In the presence of a reduced PRA, ALDO secretion could be sustained by the pituitary hormone ACTH; according to this finding, recent studies have reported a reactive increase in ACTH secretion in response to adrenal cortex dysfunction induced by acute hypothyroidism in experimental animals (33,34).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [33] Tohei, 1997, Adrenal and gonadal function in hypothyroid adult male rats., J Endocrinol source
    • cites [34] Tohei, 1998, Hypersecretion of corticotrophin-releasing hormone and arginine vasopressin in hypothyroid male rats as estimated with push-pull perfusion., J Endocrinol source
  • Premisecitation

    In the hyperthyroid state, an increase in renin release secondary to the hormone-dependent decrease in systemic vascular resistance may stimulate the angiotensin-aldosterone axis and sodium reabsorption.

    “in the hyperthyroid state the increase in renin release secondary to the hormone-dependent decrease in systemic vascular resistance may stimulate the angiotensin-aldosterone axis and consequently sodium reabsorption (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [13] Klein, 2001, Thyroid hormone and the cardiovascular system., N Engl J Med source
    • cites [14] Levey, 1971, Catecholamine sensitivity, thyroid hormone and the heart: a reevaluation., Am J Med source

      The Physiologic and Pharmacologic Studies section describes hyperthyroidism’s hyperdynamic circulation and thyroid hormone’s effects on the heart, but does not address the proposed renal mechanism. Searches for renin release, systemic vascular resistance, aldosterone, and sodium reabsorption found no passage supporting that chain; page numbers were unavailable in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [15] Polikar, 1993, The thyroid and the heart: a reevaluation., Circulation source
  • Interpretationreasoning

    Sympatho-adrenal stimulation could contribute to sustain BP levels during acute hypothyroidism as a possible mechanism counteracting the decrease in myocardial inotropism and cardiac output.

    “Sympatho-adrenal stimulation could thus contribute to sustain BP levels during acute hypothyroidism as a possible mechanism counteracting the decrease in myocardial inotropism and cardiac output (4,14,15).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [4] Klein, 1990, Thyroid hormone and the cardiovascular system., Am J Med source
    • cites [14] Levey, 1971, Catecholamine sensitivity, thyroid hormone and the heart: a reevaluation., Am J Med source

      The Physiologic and Pharmacologic Studies section (page unavailable) reports reduced intrinsic contractility in hypothyroid cat heart muscle but unaltered responsiveness to catecholamines and sympathetic nerve stimulation. This supports the possibility of an adrenergic response despite reduced contractility, but the paper does not say that sympatho-adrenal stimulation sustains blood pressure or offsets reduced cardiac output during acute hypothyroidism. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [15] Polikar, 1993, The thyroid and the heart: a reevaluation., Circulation source
  • Premisecitation

    Observational studies have shown a high prevalence of hypertension, particularly in chronic hypothyroidism.

    “Observational studies in the literature have pointed out a high prevalence of hypertension, particularly in chronic hypothyroidism (1)(2)(3)(4)(5)”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [1] Endo, 1979, Re-evaluation of a possible high incidence of hypertension in hypothyroid patients., Am Heart J source
    • cites [2] Saito, 1983, Hypothyroidism as a cause of hypertension., Hypertension source

      The Summary (pp. 112–115) reports a higher prevalence of hypertension in hypothyroid than euthyroid patients with chronic thyroiditis (14.8% versus 5.5%). The Discussion emphasizes the finding in patients over 50, but the paper does not establish that hypertension is particularly prevalent in chronic, as opposed to other, hypothyroidism. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [3] Klein, 1989, Thyroid hormone and high blood pressure. In: Laragh JH, Brenner BM, Kaplan NM, eds. Endocrine mechanisms in hypertension., New York: Raven Press; vol

      Not checked in the free run.

  • Premisecitation

    In animal models, T3 has a positive direct inotropic effect.

    “In animal models T 3 has a positive direct inotropic effect by inducing a predominant synthesis of fast ␣-isoforms of heavy myosin chains and by increasing calcium-adenosine triphosphatase and cAMP levels, together with the number and sensitivity of ␤-adrenergic receptors (6 -10).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [6] Dilmann, 1990, Biochemical basis of thyroid hormone action in the heart., Am J Med source
    • cites [7] Morkin, 1993, Regulation of myosin heavy chain genes in the heart., Circulation source

      In Regulatory Factors (page not provided), the paper describes an inotropic action of thyroid hormone, T3 stimulation of calcium uptake, and thyroid-hormone-induced fast myosin isoforms in rabbits and rats. It also says an isoform switch is unlikely to be the major mechanism of that inotropic action. The cited passages do not establish the claimed increases in cAMP or in the number and sensitivity of β-adrenergic receptors. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [8] Kiss, 1994, Thyroid hormone-induced alterations in phospholamban protein expression. Regulatory effects on sarcoplasmic reticulum Ca2+ transport and myocardial relaxation., Circ Res source
  • Classified as probably not a substantial claim. 3
  • May combine two claims. 7
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The prevalence of hypothyroidism in the general nonselected hypertensive population is 3-4%.

    “the consistent prevalence (3-4%) of hypothyroidism in the general nonselected hypertensive population (1,2,36)”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [1] Endo, 1979, Re-evaluation of a possible high incidence of hypertension in hypothyroid patients., Am Heart J source
    • cites [2] Saito, 1983, Hypothyroidism as a cause of hypertension., Hypertension source

      The Patient Population section describes women with chronic thyroiditis, not a general nonselected hypertensive population. The Age-Matched Comparisons section reports the prevalence of hypertension among hypothyroid patients (14.8%), which reverses the direction of the claimed prevalence. A search for the 3–4% estimate and for unselected hypertensive patients found neither in our copy. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [36] Streeten, Hypertension source

      The Results report hypothyroidism in 25 of 688 hypertensive patients (3.6%), supporting the 3–4% figure for this study's patients. But these were patients referred for hypertension evaluation, and the authors explicitly say their prevalence cannot be taken to represent the entire hypertensive population. The claim's extension to a general, nonselected population is therefore unsupported. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    In the hypothyroid state, mean 24-h systolic BP was less than 140 mm Hg in all patients, and mean diastolic BP was 90 mm Hg or higher in four cases.

    “In the hypothyroid state mean 24 h systolic BP (SBP) was less than 140 mm Hg in all patients; in four cases the mean diastolic BP (DBP) was 90 mm Hg or higher (see Fig. 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In phase 1, nighttime systolic BP was inversely related to morning cortisol levels as well as DBP.

    “Nighttime systolic BP was inversely related to morning CORT levels as well as DBP.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    During hypothyroidism, PRA was at the lower normal limit in nine patients and almost suppressed in the remaining three.

    “During hypothyroidism, PRA was at the lower normal limit in nine patients and was almost suppressed in the remaining three (Ͻ0.20 ng/ml⅐h).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In phase 1 (hypothyroidism), fT3 and TSH correlated with NA levels; the regression was negative for fT3 and positive for TSH.

    “During hypothyroidism, fT 3 and TSH correlated with NA levels; the regressions was negative for fT 3 and positive for TSH, respectively.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    To improve reliability and reduce interassay variability, each serum sample was assayed on several occasions in the same experiment and in different sessions (at least three times).

    “To improve the reliability of measurements and to reduce the effects of interassay variability, we assayed each serum sample on several occasions in the same experiment and in different sessions (at least three times) (24).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Iervasi, 1996, Normalization of peripheral thyroid hormone metabolism induced by successful chronic amiodarone treatment in patients with ventricular arrhythmias., Eur J Clin Invest source

  • May combine two claims.

    Interpretationown data

    Thyroid hormone deprivation promotes an increase in BP as well as activation of the sympathetic/adrenal systems.

    “our data indicate that thyroid hormone deprivation promotes an increase in BP as well as activation of the sympathetic/adrenal systems.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The short-term hypothyroid state induced by 6-week L-T4 withdrawal is a valid model for studying the physiological role of thyroid hormone in BP homeostasis.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The prevalence of renovascular hypertension is about 1%.

    “that of renovascular hypertension (ϳ1%), one of the most investigated forms of secondary hypertension (37).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Kaplan, 1998, Renal vascular hypertension, In: Pine Jr JW, ed. Clinical hypertension. Baltimore: Williams & Wilkins;

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Study design and conductreasoning

    The study selected normotensive patients free from any pharmacological treatment to investigate thyroid function and BP physiology in the absence of cardiovascular disease.

    “For this reason we selected a group of normotensive patients, all of them free from any pharmacological treatment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Thyroid hormone can increase angiotensinogen and atrial natriuretic peptide levels and decrease vasopressin levels.

    “thyroid hormone can increase angiotensinogen (16) and atrial natriuretic peptide levels (17,18) and respectively decrease vasopressin levels (19,20).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [16] Dzau, 1982, Hormonal control of angiotensinogen production., Life Sci source
    • cites [17] Zamir, 1993, Thyroid hormone restores atrial stretch-induced secretion of atrial natriuretic peptide in hypophysectomized rats., Horm Metab Res source
    • cites [18] Sergev, 1990, Thyrotropin-releasing hormone increases plasma atrial natriuretic peptide levels in humans., J Endocrinol Invest source
10 of 10

  • The paper relies on this without support.

    There are no prior studies on normotensive subjects showing the effect of short-term thyroid hormone variation on both blood pressure and its regulatory mechanisms.

    “To our knowledge, there are no studies carried out on normotensive subjects showing the effect of a short-term variation in thyroid hormone levels on both blood pressure and some of its important regulatory mechanisms represented by renin, sympathetic, and adrenal systems.”

  • The paper relies on this without support.

    The short-term hypothyroid state induced by 6-week L-T4 withdrawal is a valid model for studying the physiological role of thyroid hormone in BP homeostasis.

    “We addressed this issue by the use of a unique clinical model encompassing a short-term variation from a state of acute hypothyroidism to one of restoration of normal thyroid function in normotensive patients.”
2 of 2

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Several abstract hormone values differ from Table 1

    Minor

    The abstract and Table 1 give different values for the hypothyroid-state adrenaline mean (228.4 versus 228.6), hypothyroid-state PRA SD (0.37 versus 0.38), and treated-state aldosterone mean (156.9 versus 156.8). These differences are not attributable to rounding the tabulated values to the abstract's printed precision.

  • Noradrenaline SD differs between abstract and Table 1

    Minor

    The abstract gives the treated-state noradrenaline SD as 962 pmol/liter, whereas Table 1 gives 977 pmol/liter for the same mean.

  • Daytime DBP logistic-regression P value differs from Table 3

    Minor

    The abstract reports P < 0.02 for daytime diastolic blood pressure, but Table 3 gives P = 0.0287. Both values indicate significance at 0.05, but the tabulated value does not meet the abstract's stated threshold.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Klein, 1989, Thyroid hormone and high blood pressure. In: Laragh JH, Brenner BM, Kaplan NM, eds. Endocrine mechanisms in hypertension., New York: Raven Press; vol, 2, 61

Cited by

Sorted by citations

Related

Authors
Fommei, E., & Iervasi, G.
Affiliations
University of Pisa (IT)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2002-05-01
Volume
87
Issue
5
Pages
1996-2000
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.87.5.1996
OpenAlex
W2050166046
Cited by
172
References
37
Citations by year
2026: 1 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 16 · 2014: 11 · 2013: 9 · 2012: 7
FWCI
3.26
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Keywords
thyroid hormones, hypothyroidism, blood pressure, hypertension, thyroidectomy, levothyroxine withdrawal, norepinephrine, epinephrine, aldosterone, cortisol, renin-angiotensin system, sympathetic nervous system, thyroid-stimulating hormone, ambulatory blood pressure monitoring, normotensive subjects, diastolic blood pressure
MeSH terms
Adrenal Glands, Adult, Aged, Aldosterone, Blood Pressure, Combined Modality Therapy, Cortisone, Female, Homeostasis, Humans, Hypothyroidism, Male, Middle Aged, Regression Analysis, Renin, Sympathetic Nervous System, Thyroid Hormones, Thyroid Neoplasms, Thyroidectomy

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