Background: The effects of thyroid deprivation on the autonomic modulation to the heart remain controversial. Methods: In this study in patients followed for thyroid carcinoma, we investigated (1) heart rate variability parameters and the baroreflex gain and (2) intracellular catecholamine levels in circulating lymphocytes during short-term hypothyroidism (phase 1) and after reinstitution of TSH-suppressive thyroid hormone replacement (phase 2). Results: The RR interval value (p < 0.01) and systolic blood pressure (p < 0.05) were higher in phase 1 than in phase 2. The low-frequency/high-frequency (LF/HF) ratio was significantly lower in the hypothyroid state (p < 0.05), with a higher HF component (p < 0.05). After adjusting for mean RR interval in the regression model, the difference between the power of RR interval oscillations calculated in the two states was greater for the LF band (p = 0.005) and it was borderline significant for the HF band (p = 0.052). The baroreflex gain αLF index was similar in the two phases. The stimulus-induced cellular production of norepinephrine and epinephrine in peripheral blood mononuclear cells was significantly higher in phase 2. Conclusion: The neurally-mediated influences on the sinus node and the study of intracellular catecholamine production suggest a reduced sympathoexcitation in hypothyroidism compared with the treatment phase. The early increase in blood pressure observed after thyroid hormone withdrawal is not due to impaired sensitivity of the baroreflex arc.

Keywords:
Hypothyroidism, Spectral analysis, Baroreflex sensitivity, Intracellular catecholamines
1.
Klein I: Thyroid hormone and the cardiovascular system. Am J Med 1990;88:631–637.
2.
Polikar R, Burger A, Scherrer U, Nicod P: The thyroid and the heart. Circulation 1993;87:1435–1441.
3.
Coulombe P, Dussault J II, Walker P: Catecholamine metabolism in thyroid disease. II. Norepinephrine secretion rate in hyperthyroidism and hypothyroidism. J Clin Endocrinol Metab 1977;44:1185–1189.
4.
Polikar R, Kennedy B, Ziegler M, O’Connor DT, Smith J, Nicod P: Plasma norepinephrine kinetics, dopamine-β-hydroxylase, and chromogranin-A in hypothyroid patients before and following replacement therapy. J Clin Endocrinol Metab 1990;70:277–281.
5.
Pijl H, de Meijer PHEM, Langius J, Coenegracht CIGM, van den Berk AHM, Chandie Shaw K, Boom H, Schoemaker RC, Cohen AF, Burggraaf J, Meinders AE: Food choice in hyperthyroidism: potential influence of the autonomic nervous system and brain serotonin precursor availability. J Clin Endocrinol Metab 2001;86:5848–5853.
6.
Cosentino M, Zaffaroni M, Giorelli M, Marino F, Ferrari M, Bombelli R, Rasini E, Trojano M, Lecchini S, Livrea M, Frigo G: Adrenergic modulation of the immune response. Trends Pharmacol Sci 2004;25:350–351.
7.
Musso NR, Brenci S, Setti M, Indiveri F, Lotti G: Catecholamine content and in vitro catecholamine synthesis in peripheral human lymphocytes. J Clin Endocrinol Metab 1996;81:3553–3557.
8.
Cosentino M, Marino F, Bombelli R, Ferrari M, Rasini E, Lecchini S, Frigo GM: Stimulation with phytohaemagglutinin induces the synthesis of catecholamines in human peripheral blood mononuclear cells: role of protein kinase C and contribution of intracellular calcium. J Neuroimmunol 2002;125:125–133.
9.
Ferrari M, Cosentino M, Marino F, Bombelli R, Rasini E, Lecchini S, Frigo GM: Dopaminergic D1-like receptor-dependent inhibition of tyrosine hydroxylase mRNA expression and catecholamine production in human lymphocytes. Biochem Pharmacol 2004;67:865–873.
10.
Marino F, Cosentino M, Bombelli R, Ferrari M, Lecchini S, Frigo GM: Endogenous catecholamine synthesis, metabolism, storage and uptake in human peripheral blood mononuclear cells. Expl Hematol 1999;27:489–495.
11.
Christensen NJ, Bratholm P, Knudsen JH: Lymphocyte norepinephrine and epinephrine as indices of long-term changes in sympathoadrenal activity in human subjects. J Gravit Physiol 1997;4:P115–P116.
12.
Christensen NJ, Knudsen JH: Peripheral catecholaminergic function evaluated by norepinephrine measurements in plasma, extracellular fluid, and lymphocytes, from nerve recordings and cellular responses. Adv Pharmacol 1998;42:540–544.
13.
Cacciatori V, Gemma ML, Bellavere F, Castello R, De Gregori ME, Zoppini G, Thomaseth K, Moghetti P, Muggeo M: Power spectral analysis of heart rate in hypothyroidism. Eur J Endocrinol 2000;143:327–333.
14.
Inukai T, Takanashi K, Kobayashi H, Fujiwara Y, Tayama K, Aso Y, Takemura Y: Power spectral analysis of variations in heart rate in patients with hyperthyroidism or hypothyroidism. Horm Metab Res 1998;30:531–535.
15.
Xing H, Shen Y, Chen H, Wang Y, Shen W: Heart rate variability and its response to thyroxine replacement therapy in patients with hypothyroidism. Chin Med J 2001;114:906–908.
16.
Baselli G, Cerutti S: Identification techniques applied to processing of signals from cardiovascular system. Med Inform (Lond) 1985;10:223–235.
17.
Akaike H: A new look at the statistical model identification. IEEE Trans Autom Control 1974;19: 716–723.
18.
Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology: Heart rate variability. Standards of measurements, physiological interpretation, and clinical use. Circulation 1996;93:1043–1065.
19.
Malliani A, Pagani M, Lombardi F, Cerutti S: Cardiovascular neural regulation explored in the frequency domain. Circulation 1991;84:482–492.
20.
Guasti L, Zanotta D, Mainardi LT, Petrozzino MR, Grimoldi P, Garganico D, Diolisi A, Gaudio G, Klersy C, Grandi AM, Simoni C, Cerutti S: Hypertension-related hypoalgesia, autonomic function and spontaneous baroreflex sensitivity. Auton Neurosci 2002;99:127–133.
21.
Guasti L, Simoni C, Mainardi L, Crespi C, Cimpanelli M, Klersy C, Gaudio G, Grandi AM, Cerutti S, Venco A: Global link between heart rate and blood pressure oscillations at rest and during mental arousal in normotensive and hypertensive subjects. Auton Neurosci 2005;120:80–87.
22.
Faes L, Porta A, Cucino R, Cerutti S, Antolini R, Nollo G: Causal transfer function analysis to describe closet loop interactions between cardiovascular and cardiorespiratory variability signals. Biol Cybern 2004;90:390–399.
23.
Pagani M, Somers V, Furlan R, Dell’Orto S, Conway J, Baselli G, Cerutti S, Sleight P, Malliani A: Changes in autonomic regulation induced by physical training in mild hypertension. Hypertension 1988;12:600–610.
24.
Porta A, Furlan R, Rimoldi O, Pagani M, Malliani A, Van de Borne BP: Quantifying the strength of the linear causal coupling in closed-loop interacting cardiovascular variability signals. Biol Cybern 2002;86:241–251.
25.
Robbe HWJ, Mulder LJM, Ruddel H, Langewitz WA, Veldman JBP, Mulder G: Assessment of baroreceptor reflex sensitivity by means of spectral analysis. Hypertension 1987;10:538–543.
26.
Cosentino M, Bombelli R, Ferrari M, Marino F, Rasini E, Maestroni GJ, Conti A, Boveri M, Lecchini S, Frigo G: HPLC-ED measurement of endogenous catecholamines in human immune cells and hematopoietic cell lines. Life Sci 2000;68:283–295.
27.
Barczynski M, Thor P: Reversible autonomic dysfunction in hyperthyroid patients gastric myoelectrical activity and empting. Clin Auton Res 2001;11:243–249.
28.
Burggraaf J, Tulen JHM, Lalezari S, Schoemaker RC, De Meyer PHEM, Meinders AE, Cohen AF, Pijl H: Sympathovagal imbalance in hyperthyroidism. Am J Physiol 2001;281:E190–E195.
29.
Cacciatori V, Bellavere F, Pezzarossa A, Dellera A, Gemma ML, Thomaseth K, Castello R, Moghetti P, Muggeo M: Power spectral analysis of heart rate in hyperthyroidism. J Clin Endocrinol Metab 1996;81:2828–2835.
30.
Girard A, Hugues FC, Le Jeunne C, Elghozi JL: Short-term variability of blood pressure and heart rate in hyperthyroidism. Clin Auton Res 1998;8:181–186.
31.
Pitzalis MV, Mastropasqua F, Massari F, Ciampolillo A, Passantino A, Ognissanti M, Mannarini A, Zanna D, Giorgino R, Rizzon P: Assessment of cardiac vagal activity in patients with hyperthyroidism. Int J Cardiol 1998;64:145–151.
32.
Foley CM, McAllister RM, Hasser EM: Thyroid status influences baroreflex function and autonomic contributions to arterial pressure and heart rate. Am J Physiol 2001;280:H2061–H2068.
33.
Lipman RD, Salisbury JK, Taylor JA: Spontaneous indices are inconsistent with arterial baroreflex gain. Hypertension 2003;42:481–487.
34.
Nollo G, Porta A, Faes Del Greco L, Disertori M, Ravelli F: Causal linear parametric model for baroreflex gain assessment in patients with recent myocardial infarction. Am J Physiol 2001;280:H1830–H1839.
35.
Coppola AR, Ladenson PW: Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab 2003;88:2438–2444.
36.
Fommei E, Iervasi G: The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans. J Clin Endocrinol Metab 2002;87:1996–2000.
37.
Mattila J, Bunag RD: Pressor and sympathetic responses to dorsal raphe nucleus infusions of TRH in rats. Am J Physiol 1990;258:R1464–R1471.
38.
Morley JE, Tuck ML, Mayes DM, Rosenblatt S, Hershman JM: Thyrotropin-releasing hormone increases plasma norepinephrine in man. Horm Res 1981;14:18–23.
39.
Vagn Nielsen H, Hasselstrom K, Feldt-Rasmussen U, Mehlsen J, Siersbæk-Nielsen K, Friis T, Haunso S, Trap-Jensen J: Increased sympathetic tone in forearm subcutaneous tissue in primary hypothyroidism. Clin Physiol 1987;7:297–302.
40.
Nedvidkova J, Haluzik M, Bartak V, Dostalova I, Vlcek P, Racek P, Taus M, Behanova M, Svacina S, Alesci P, Pacak K: Changes of noradrenergic activity and lipolysis in the subcutaneous abdominal adipose tissue of hypo- and hyperthyroid patients: an in vivo microdialysis study. Ann NY Acad Sci 2004;1018:541–549.
41.
Cosentino M, Marino F, Bombelli R, Ferrari M, Lecchini S, Frigo GM: Unravelling dopamine (and catecholamine) physiopharmacology in lymphocytes: open questions. Trends Immunol 2003, 24:581–582.
42.
Valcavi R, Menozzi C, Roti E, Zini M, Lolli G, Roti S, Guiducci U, Portioli I: Sinus node function in hyperthyroid patients. J Clin Endocrinol Metab 1992;75:239–242.
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