Background/Aim: The relationship between the hypothalamic-pituitary-thyroid (HPT) axis and the serotonergic (5-hydroxytryptamine, 5-HT) system is not clear. The aim of the study was to determine platelet biochemical markers (5-HT concentration and monoamine oxidase B, MAO-B, activity) in hypothyroid patients. Methods: The study included 25 medication-free female hypothyroid patients in postoperative follow-up after total thyroidectomy due to papillary thyroid carcinoma, who had not been treated with synthetic thyroxine (T4) for 4 weeks, and 44 age-matched euthyroid healthy women. The platelet 5-HT concentration, platelet MAO-B activity, total T4 and thyroid-stimulating hormone (TSH) levels were determined using spectrofluorimetric methods, radioimmunoassay and fluoroimmunoassay, respectively. Results: Hypothyroid patients had significantly higher TSH, significantly lower T4 levels and platelet 5-HT concentrations, and unchanged platelet MAO-B activity than healthy subjects. A positive correlation was found between the 5-HT concentration and platelet MAO-B activity, and between the platelet MAO-B activity and T4 in control subjects. Conclusions: Reduced platelet 5-HT concentrations in hypothyroid patients suggests a complex interaction between the 5-HT system and HPT axis activity, which could be related to the frequent occurrence of depressive symptoms in hypothyroid patients. The determination of platelet 5-HT concentrations should be considered a diagnostic tool for the evaluation of depressive symptoms in hypothyroid patients during the hormone withdrawal procedure.

1.
Ahmed OM, El-Gareib AW, El-bakry AM, El-Tawab SMA, Ahmed RG: Thyroid hormones states and brain development interactions. Int J Dev Neurosci 2008;26:147–209.
2.
Bauer M, Heinz A, Whybrow PC: Thyroid hormones, serotonin and mood: of synergy and significance in the adult brain. Mol Psychiatr 2002;7:140–156.
3.
Sandrini M, Vitale G, Vergoni AV, Ottani A, Bertolini A: Effect of acute and chronic treatment with triiodothyronine on serotonin levels and serotonergic receptor subtypes in the rat brain. Life Sci 1996;58:1551–1559.
4.
Strawn JR, Ekhator NN, D’Souza BB, Geraciotti TD, Geraciotti JR: Pituitary-thyroid state correlates with central dopaminergic and serotonergic activity in healthy humans. Neuropsychobiology 2004;49:84–87.
5.
Newman M, Agid O, Gur E, Lerer B: Pharmacological mechanisms of T3 augmentation of antidepressant action. International J Neuropsychopharmacol 2003;3:187–191.
6.
Viquerie N, Langin D: Effects of thyroid hormone and gene expression. Curr Opin Clin Nutr Metab Care 2003;6:377–381.
7.
Singhal RL, Rastogi RB, Hrdina PD: Brain biogenic amines and altered thyroid function. Life Sci 1975;17:1617–1626.
8.
Ito JM, Valcana T, Timiras PS: Effect of hypo- and hyperthyroidism on regional monamine metabolism in the adult rat brain. Neuroendocrinology 1977;24:55–64.
9.
Savard P, Merand Y, DiPaolo T, Dupont A: Effect of neonatal hypothyroidism on the serotonin system of the rat brain. Brain Res 1984;292:99–108.
10.
Henley WN, Chen X, Klettner C, Bellush LL, Notestine MA: Hypothyroidism increases serotonin turnover and sympathetic activity in the adult rat. Can J Physiol Pharmacol 1991;69:205–210.
11.
Vanderpump MP, Tunbridge WM: Epidemiology and prevention of clinical and subclinical hypothyroidism. Thyroid 2002;12:839–847.
12.
Forman-Hoffman V, Philibert RA: Lower TSH and higher T4 levels are associated with current depressive syndrome in young adults. Acta Psychiatr Scand 2006;114:132–139.
13.
Łojko D, Rybakowski JK: L-Thyroxine augmentation of serotonergic antidepressants in female patients with refractory depression. J Affect Disord 2007;103:253–256.
14.
Sjöberg S, Eriksson M, Nordin C: L-Thyroxine treatment and neurotransmitter levels in the cerebrospinal fluid of hypothyroid patients: a pilot study. Eur J Endocrinol 1998;139:493–497.
15.
Cleare AJ, McGregor A, Keane VO: Neuroendocrine evidence for an association between hypothyroidism, reduced central 5-HT activity and depression. Clin Endocrinol 1995;43:713–719.
16.
Kulikov A, Moreau X, Jeanningros R: Effects of experimental hypothyroidism on 5-HT1A, 5-HT2A receptors, 5-HT uptake sites and tryptophan hydroxylase activity in mature rat brain. Neuroendocrinology 1999;69:453–459.
17.
Nemeroff CB: Recent advances in the neurobiology of depression. Psychopharmacol Bull 2002;36:6–23.
18.
Moorley JE: Neuroendocrine control of thyrotropin secretion. Endocr Rev 1981;2:396–436.
19.
Howland RH: Thyroid dysfunction in refractory depression: implications for pathophysiology and treatment. J Clin Psychiatry 1993;54:47–54.
20.
Nemeroff CB: Clinical significance of psychoneuroendocrinology in psychiatry: focus on the thyroid and adrenal. J Clin Psychiatry 1989;50:13–20.
21.
Prange AJ, Wilson IC, Lara PP, Alltop LB, Breese GR: Effects of thyrotropin-releasing hormone in depression. Lancet 1972;ii:999–1002.
22.
Bianchi M, Moser C, Lazzarini C, Vecchiato E, Crespi F: Forced swimming test and fluxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes. Exp Brain Res 2002;143:191–197.
23.
Muck-Šeler D, Jakovljević M, Pivac N: Platelet 5-HT concentrations and suicidal behaviour in recurrent major depression. J Affect Disord 1996;39:73–80.
24.
Muck-Seler D, Pivac N, Sagud M, Mustapic M, Jakovljevic M: The effects of serotonin uptake inhibitors on platelet serotonin: from basic to clinical research; in Shirley AC (ed): Trends in Serotonin Uptake Inhibitors Research. New York, Nova Science, 2005, pp 29–53.
25.
Muck-Seler D, Pivac N, Jakovljević M: Sex differences, season of birth and platelet 5-HT levels in schizophrenic patients. J Neural Transm 1999;106:337–347.
26.
Pivac N, Muck-Seler D, Mustapic M, Sagud M, Darko Marcinko D, Deželjin M, Jakovljevic M: Peripheral biological markers and treatment response in schizophrenia; in French DP (ed): Schizophrenic Psychology: New Research. New York, Nova Science, 2006, pp. 319–370.
27.
Blardi P, Palazzuoli A, de Lalla A, Auteri A: Variations of peripheral markers of serotoninergic system in selected vascular patients. Nutr Metab Cardiovasc Dis 2006;16:210–214.
28.
Fogel WA, Lewinski A, Jochem J: Histamine in food: is there anything to worry about ? Biochem Soc Trans 2007;35:349–352.
29.
Fetkovska N: Platelet activation by low-density lipoprotein and serotonin: the effects of calcium antagonists. J Cardiovasc Pharmacol 1992;19:S25–S28.
30.
Oreland L, Hallman J, Damberg M: Platelet MAO and personality-function and dysfunction. Curr Med Chem 2004;11:2007–2016.
31.
Fagervall I, Ross SB: A and B forms of monoamine oxidase within the monoaminergic neurons of the rat brain. J Neurochem 1986;47:569–576.
32.
Licata G, Davi G, Scaglione R, Dichiara MA, Catalano I, Strano A: Platelet function in hypo- and hyperthyroidism. Boll Soc Ital Biol Sper 1989;65:847–852.
33.
Ford HC, Carter JM: Moderate, chronic hypothyroidism does not lead to more small-sized platelets in the circulation. Thromb Haemost 1988;60:524.
34.
Coban E, Yazicioglu G, Ozdogan M: Platelet activation in subjects with subclinical hypothyroidism. Med Sci Monit 2007;13:211–214.
35.
Guimaraes V, DeGroot LJ: Moderate hypothyroidism in preparation for whole body 131I scintiscans and thyroglobulin testing. Thyroid 1996;6:69–73.
36.
Mück-Šeler D, Pivac N, Sagud M, Jakovljević M, Mihaljevic-Peleš A: The effects of paroxetine and tianeptine on peripheral biochemical markers in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2002;26:1235–1243.
37.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–275.
38.
Mueller-Oerlinghausen B, Roggenbach J, Franke L: Serotonergic platelet markers of suicidal behaviour – do they really exist? J Affect Disord 2004;79:13–24.
39.
Pivac N, Kozarić-Kovačić D, Mustapić M, Deželjin M, Nenadić-Šviglin K, Muck-Šeler D: New research on alcohol abuse and alcoholism: peripheral biological markers in alcoholism; in Walcott TA (ed): Drug and Alcohol Abuse Research Focus. New York, Nova Science, 2007, pp 1–62.
40.
Ljubicic D, Stipcevic T, Pivac N, Jakovljevic M, Muck-Seler D: The influence of daylight exposure on platelet 5-HT levels in patients with major depression and schizophrenia. J Photochem Photobiol B 2007;89:63–69.
41.
Rasgon N, McGuire M, Tanavoli S, Fairbanks L, Rapkin A: Neuroendocrine response to an intravenous L-tryptophan challenge in women with premenstrual syndrome. Fertil Steril 2000;73:144–149.
42.
Leibenluft E, Fiero PL, Rubinow DR: Effects of menstrual cycle on dependent variables in mood disorder research. Arch Gen Psychiatry 1994;51:761–781.
43.
Guicheney P, Leger D, Barrat J, Trevoux R, De Lignieres B, Roques P, Garnier JP, Boyers, P, Grenier J, Dreux C, Meyer P: Platelet serotonin content and plasma tryptophan in peri- and post-menopausal women: variations with plasma estrogen levels and depressive symptoms. Eur J Clin Invest 1988;18:297–304.
44.
Muck-Seler D, Pivac N, Mustapic M, CrnceZ, Jakovljevic M, Sagud M: Platelet serotonin and plasma prolactin and cortisol in healthy, depressed and schizophrenic women. Psychiatry Res 2004;127:217–226.
45.
Vaccari A, Biassoni R, Timiras P: Selective effects of neonatal hypothyroidism on monoamine oxidase activities in the rat brain. J Neurochem 1983;40:1019–1025.
46.
Oreland L: Platelet monoamine oxidase, personality and alcoholism: the rise, fall and resurrection. Neurotoxicology 2004;25:79–89.
47.
Nishi K, Mück-Šeler D, Hasegawa S, Watanabe A, Diksic M: Acute effects of moclobemide and deprenyl on 5-HT synthesis rates in the rat brain: an autoradiographic study. Brain Res Bull 2006;70:368–377.
48.
Denicoff KD, Joffe RT, Lakshmanan MC, Robbins J, Rubinow DR: Neuropsychiatric manifestations of altered thyroid state. Am J Psychiatry 1990;147:94–99.
49.
Berrios GE, Leysen A, Samuel C, Dowson J: Psychiatric morbidity following total and partial thyroidectomy. Acta Psychiatr Scand 1985;72:369–373.
50.
Montero-Pedrazuela A, Venero C, Lavado-Autric R, Fernandez-Lamo I, Garcia-Verdugo JM, Bernal J: Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior. Mol Psychiatr 2006;11:361–371.
51.
Tejani-Butt SM, Yang J, Kaviani A: Time course of altered thyroid states on 5-HT1A receptors and 5-HT uptake sites in rat brain: an autoradiographic analysis. Neuroendocrinology 1993;57:1011–1018.
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