Thyroid axis function after in-patient treatment of acute psychosis with antipsychotics: a naturalistic study.

BACKGROUND: Endocrine function in psychiatric patients may be affected by mental disorder itself as well as by antipsychotic medications.The aim of this naturalistic observational study was to determine if treatment of acute psychotic episode with antipsychotic medication affects thyroid axis hormone concentrations and if such changes are associated with symptomatic improvement. METHODS: Eighty six adult acute psychotic patients, consecutively admitted to a mental hospital, were recruited for the study. All patients were physically healthy and without thyroid disease. During the hospitalization period all study patients received treatment with antipsychotic medication according to clinical need. Severity of the psychotic episode was evaluated using the Brief Psychiatric Rating Scale (BPRS) and venous blood samples were drawn for analysis of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) concentrations on the day of admission and on the day of discharge from the hospital. RESULTS: Antipsychotic drug treatment was associated with decrease of mean FT3 (p < 0.001) and FT4 (p = 0.002) concentrations; and with increase of mean TSH (p = 0.016) concentrations. Changes in thyroid hormone concentrations were mostly predicted by baseline hormone concentrations. Individual changes were not limited to decrease in high hormone concentrations; in patients who had low FT3 or FT4 concentrations, treatment resulted in increase in concentrations. Such an increase was established in one-quarter of patients for FT3 concentrations and in one-third of patients for FT4 concentrations. Fall in FT4 concentrations negatively correlated with the improvement in the BPRS score (r = -0.235, p = 0.023). CONCLUSIONS: The study indicates that antipsychotic treatment resulted in a decrease in mean FT3 concentrations and in an increase in mean TSH concentrations after recovery from acute psychosis. Symptomatic improvement was less evident in patients who experienced a decrease in FT4 concentrations. TRIAL REGISTRATION: EudraCT No.2007-001541-18.

Fatigue in patients with coronary artery disease: association with thyroid axis hormones and cortisol.

OBJECTIVE: In people with coronary artery disease, the association between endocrine measures and fatigue is not well understood. We evaluated possible associations of fatigue and exercise capacity with function of adrenal axis and thyroid axis. METHODS: Sixty-five men and 18 women (mean age 55 years) attending a rehabilitation program were examined using the Multidimensional Fatigue Inventory, Dutch Exertion Fatigue Scale, and the Hospital Anxiety and Depression Scale. Exercise capacity was measured using a bicycle ergometer procedure. Serum concentrations of free triiodothyronine (T3), free thyroxine (T4), morning cortisol, afternoon cortisol, and change in cortisol concentrations (ΔCortisol) were measured. RESULTS: In univariate regression analysis, lower free T4 concentrations were associated with general and exertion fatigue, lower free T3 concentrations were associated with general and physical fatigue, and lower ΔCortisol was associated with mental fatigue. After adjusting for age, sex, body mass index, hypertension, previous myocardial infarction, heart failure, diabetes, New York Heart Association functional class, depressive symptoms, and anxiety symptoms, lower free T3 concentrations remained associated with physical fatigue (ß = -.224, p = .03); lower free T4 concentrations, with exertion fatigue (ß = -.219, p = .03); and lower morning cortisol and lower ΔCortisol concentrations, with mental fatigue (ß = -.193 [p = .03] and ß = -.180 [p =.04], respectively). Exercise capacity was not associated with endocrine factors. CONCLUSIONS: In coronary artery disease patients, increased thyroid hormone concentrations are associated with decreased physical fatigue and decreased exertion fatigue, and increased cortisol concentrations with decreased mental fatigue. Exercise capacity is not associated with endocrine factors.

Concentrations of thyroid axis hormones in psychotic patients on hospital admission: the effects of prior drug use.

The aim of this study was to determine the concentrations of thyroid axis hormones in psychotic patients on hospital admission and to search for the associations between the concentrations of these hormones and prior drug use as well as mental symptoms. MATERIAL AND METHODS. Psychiatric diagnoses, psychotropic drug use, and the severity of psychoses were evaluated using the standard methods on admission. Venous blood from patients and healthy controls was drawn for the analysis of free thyroxin (FT(4)), free triiodothyronine (FT(3)), thyroid-stimulating hormone (TSH), and sex hormone-binding globulin (SHBG) concentrations. RESULTS. Eighty-one psychotic patients, free of a thyroid disorder, were enrolled into the study. Compared with the controls, they displayed the higher FT(4) concentrations in the general group (P=0.003) and the higher SHBG concentrations only in men (P=0.013). The FT(4) concentration was higher in the patients who were not taking an antipsychotic drug on admission (P=0.039). No significant correlation was found between the severity of psychosis and concentrations of thyroid axis hormones. However, the FT(3) concentration in the general group and TSH concentration in women correlated with the factor of the Brief Psychiatric Rating Scale expressing elevated mood. CONCLUSIONS. Our study confirms the higher FT(4) concentrations in a significant proportion of acute psychotic patients. The concentrations of thyroid axis hormones were found to be associated with prior antipsychotic treatment on hospital admission.

Psychiatric manifestations of Graves' hyperthyroidism: pathophysiology and treatment options.

Graves' disease is an autoimmune disorder that is the most common cause of hyperthyroidism. Other symptoms associated with the disease are goitre, ophthalmopathy, and psychiatric manifestations such as mood and anxiety disorders and, sometimes, cognitive dysfunction. Graves' hyperthyroidism may result in these latter manifestations via the induction of hyperactivity of the adrenergic nervous system. This review addresses the psychiatric presentations, and their pathophysiology and treatment, in patients with hyperthyroidism, based on literature identified by a PubMed/MEDLINE database search. Although the focus is on mental symptoms associated with Graves' disease, it is not always clear from the literature whether patients had Graves' disease: in some studies, the patients were thought to have Graves' disease based on clinical findings such as diffuse goitre or ophthalmopathy or on measurements of thyroid antibodies in serum; however, in other studies, no distinction was made between Graves' hyperthyroidism and hyperthyroidism from other causes. Antithyroid drugs combined with beta-adrenoceptor antagonists are the treatments of choice for hyperthyroidism, as well as for the psychiatric disorders and mental symptoms caused by hyperthyroidism. A substantial proportion of patients have an altered mental state even after successful treatment of hyperthyroidism, suggesting that mechanisms other than hyperthyroidism, including the Graves' autoimmune process per se and ophthalmopathy, may also be involved. When psychiatric disorders remain after restoration of euthyroidism and after treatment with beta-adrenoceptor antagonists, specific treatment for the psychiatric symptoms, especially psychotropic drugs, may be needed.

Depression and thyroid axis function in coronary artery disease: impact of cardiac impairment and gender.

BACKGROUND: Increased rates of depression are reported in coronary artery disease (CAD). In heart disease, depression increases disability, reduces quality of life, and increases mortality. HYPOTHESIS: The study was undertaken to examine the relationship between depression and thyroid axis function in patients with CAD. METHODS: In all, 73 patients with CAD, consecutively admitted to a cardiac rehabilitation hospital, were assessed for depression using the Hospital Anxiety and Depression scale (HADS). Blood was drawn for assessment of thyroid axis hormones and the N-amino terminal fragment of the pro-B-type natriuretic peptide (NT-pro BNP). RESULTS: The patients with CAD with depressive symptoms had a higher prevalence of cardiac failure (p = 0.04), higher NT-pro BNP concentrations (p = 0.02), and lower free triiodothyronine (T3) concentrations (p = 0.04) than patients with CAD but without depressive symptoms. They also showed a strong trend (p = 0.058) toward a higher incidence of the low T3 syndrome. Higher NT-pro BNP concentrations were related to lower total T3 concentrations (r = -0.294, p = 0.011) and to higher reverse T3 concentrations (r = 0.353, p = 0.002). In men, higher scores of depression were related to lower total T3 concentration (r = -0.289, p = 0.034) and to higher NT-pro BNP concentration (r = 0.380, p = 0.005). CONCLUSION: These findings suggest that symptoms of depression in patients with CAD are associated with changes in thyroid axis function and with cardiac impairment, especially in men.

Triiodothyronine accelerates and enhances the antipsychotic effect of risperidone in acute schizophrenia.

In acute psychotic schizophrenia patients we investigated if the combination of triiodothyronine (T3) plus risperidone was more effective when compared to risperidone monotherapy. Thirty-two in-patients meeting the DSM-IV-TR diagnostic criteria for schizophrenia and without thyroid disease received risperidone (flexibly adjusted dose for tolerability) and were randomized to additionally receive either T3 (25 µg daily; risperidone plus T3 group) or placebo (risperidone plus placebo group). Treatment lasted until meeting the response to treatment criteria defined as score of ≤ 3 on the Clinical Global Impression Severity and Improvement scales. Acute psychotic episode symptom severity was evaluated using the Brief Psychiatric Rating Scale (BPRS) at treatment initiation and at the final study assessment. Fourteen patients were randomized to receive risperidone plus T3 and eighteen to receive risperidone plus placebo. The time until treatment response was shorter in the risperidone plus T3 group relative to the risperidone plus placebo group (25.5 ± 4.4 days vs 32.2 ± 8.2 days, respectively; p = 0.001). Moreover, there was a greater reduction of BPRS-total score (p = 0.01) in the risperidone plus T3 group relative to the risperidone plus placebo group. Treatment with T3 was associated with shorter time to treatment response (ß = -0.440, p = 0.022) and with greater improvement in BPRS score (ß = 0.240, p = 0.053), independent of patients' gender, age, baseline BPRS score and mean risperidone dose. The study confirms that addition of T3 to risperidone was associated with accelerated and enhanced treatment response in acutely psychotic schizophrenic patients.

Mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease.

OBJECTIVE: To evaluate the prevalence of mood and anxiety disorders in women with treated hyperthyroidism caused by Graves' disease and to compare them with the prevalence of such findings in women without past or present thyroid disease. METHODS: Thirty inpatient women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease and 45 women hospitalized for treatment of gynecologic disorders such as abnormal vaginal bleeding, benign tumors or infertility were evaluated for the prevalence of mood and anxiety diagnoses using a standard Mini-International Neuropsychiatric Interview and for mood and anxiety ratings using the Profile of Mood States (POMS). At the time of assessment, it was discovered that 14 of 30 women with treated hyperthyroidism caused by Graves' disease were still hyperthyroid, while 16 women were euthyroid. RESULTS: Significantly greater prevalence of social anxiety disorder, generalized anxiety disorder, major depression and total mood and anxiety disorders, as well as higher symptom scores on the POMS, was found in hyperthyroid women with Graves' disease in comparison with the control group. A prevalence of total anxiety disorder, as well as history of mania or hypomania and lifetime bipolar disorder, but not lifetime unipolar depression, was more frequent in both the euthyroid and the hyperthyroid subgroups of study women in comparison with the control group. CONCLUSIONS: These results confirm a high prevalence of mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease. Hyperthyroidism plays a major role in psychiatric morbidity in Graves' disease.

Historical sexual abuse and current thyroid axis profiles in women with premenstrual dysphoric disorder.

OBJECTIVE: This study investigated whether women with premenstrual dysphoric disorder (PMDD) who also had histories of sexual abuse differed from women with PMDD with no previous sexual abuse and from women without PMDD in hypothalamic-pituitary-thyroid (axis measures). METHODS: Ten sexually abused women with PMDD were compared with 18 nonabused women with PMDD and 22 nonabused women without PMDD for hypothalamic-pituitary-thyroid axis hormone concentrations during the follicular and luteal phases of confirmed ovulatory cycles. RESULTS: Compared with the women without PMDD, only the group of women with PMDD with sexual abuse showed greater variance in both cycle phases in thyroid-stimulating hormone concentrations and greater luteal phase variance in free and total thyroxine (T4) and reverse tri-iodothyronine (T3). In the group of nonabused women with PMDD, there was greater variance in follicular phase thyroxine-binding globulin concentrations compared with the group without PMDD. Women with PMDD with abuse had greater mean concentrations of total T3 and thyroxine-binding globulin, greater total T3/free T4 and free T3/free T4 ratios, and lower ratios of free T3/total T3 and free T4/total T4 than either of the other 2 nonabused groups. Greater total T3 concentrations and histories of major depression independently predicted premenstrual symptoms in all women with PMDD, together accounting for 31% to 38% of the variance in anxiety, anger, and depression ratings. CONCLUSIONS: These results suggest increased conversion of T4 to T3 and increased binding of thyroid hormones in women with PMDD with previous sexual abuse. Abnormal total T3 concentrations may have pathophysiological significance in PMDD.

Mental improvement after replacement therapy with thyroxine plus triiodothyronine: relationship to cause of hypothyroidism.

We treated 26 hypothyroid women - 11 with autoimmune thyroiditis and 15 who had been treated for thyroid cancer - with their usual dose of thyroxine (T4) or with a regimen in which 50 &mgr;g of T4 had been replaced by 12.5 &mgr;g of triiodothyronine (T3). Patients were first randomly assigned to one regimen for 5 wk and then to a second regimen for an additional 5 wk. The substitution of T3 for a portion of T4 caused expected changes in concentrations of thyroid hormones and thyroid-stimulating hormone (TSH). After combined hormone treatment there were clear improvements in both cognition and mood, the latter changes being greater. The patients who had been treated for thyroid cancer showed more mental improvement than the women with autoimmune thyroiditis, perhaps because they were more dependent on exogenous hormone. Some mood improvements correlated positively with changes in TSH while others correlated negatively with changes in free T4.

Thyroid disease and mental disorders: cause and effect or only comorbidity?

PURPOSE OF REVIEW: To discuss the effects of thyroid dysfunction and thyroid autoimmunity on mental symptoms and disorders in patients with thyroid disease with reference to recent epidemiological, clinical, and genetic findings. RECENT FINDINGS: During brain development, iodine deficiency, maternal thyroid dysfunction, and neonatal thyroid malformations together with genetic factors contribute to neurological deficit. Most adults with thyroid dysfunction will develop mental symptoms. In hyperthyroidism, adrenergic hyperactivity is a major cause of psychiatric symptoms, and beta-adrenergic antagonists are effective treatment. Most patients with severe hypothyroidism will also demonstrate mental symptoms; however, causality is not so evident as in hyperthyroidism. Polymorphism in deiodinase genes and in transporter genes appears to make an important contribution to the presentation of mental symptoms as well as to the outcome of treatment of hypothyroidism. A thyroid autoimmunity process may by itself contribute to mental symptoms in vulnerable patients. Data from epidemiological studies provide conflicting evidence as to associations between thyroid disorders and mental symptoms. SUMMARY: In the adult brain, compared with the developing brain, brain-thyroid relationships are less apparent but still important. Adrenergic hyperactivity is a major cause of psychiatric symptoms in hyperthyroidism. Genetic factors contribute to the development and treatment outcome of mental disorder in hypothyroidism.

The thyrotropin-releasing hormone (TRH) hypothesis of homeostatic regulation: implications for TRH-based therapeutics.

The functions of thyrotropin-releasing hormone (TRH) in the central nervous system (CNS) can be conceptualized as performed by four anatomically distinct components that together comprise a general TRH homeostatic system. These components are 1) the hypothalamic-hypophysiotropic neuroendocrine system, 2) the brainstem/midbrain/spinal cord system, 3) the limbic/cortical system, and 4) the chronobiological system. We propose that the main neurobiological function of TRH is to promote homeostasis, accomplished through neuronal mechanisms resident in these four integrated systems. This hypothesis offers a unifying basis for understanding the myriad actions of TRH and TRH-related drugs already demonstrated in animals and humans. It is consistent with the traditional role of TRH as a regulator of metabolic homeostasis. An appreciation of the global function of TRH to modulate and normalize CNS activity, along with an appreciation of the inherent limitations of TRH itself as a therapeutic agent, leads to rational expectations of therapeutic benefit from metabolically stable TRH-mimetic drugs in a remarkably broad spectrum of clinical situations, both as monotherapy and as an adjunct to other therapeutic agents. The actions of TRH are numerous and varied. This has been viewed in the past as a conceptual and practical impediment to the development of TRH analogs. Herein, we alternatively propose that these manifold actions should be considered as a rational and positive impetus to the development of TRH-based drugs with the potential for unique and widespread applicability in human illness.

Thyroxine vs thyroxine plus triiodothyronine in treatment of hypothyroidism after thyroidectomy for Graves' disease.

It was recently demonstrated that treatment with levorotatory thyroxine (T4) plus triiodothyronine (T3) compared with treatment with T4 alone improves psychologic functioning in hypothyroid patients with thyroid cancer or autoimmune thyroiditis. In the present double-blind crossover study, we again compared the effects of combined thyroid replacement vs monotherapy on psychologic function, endocrine function, cardiovascular function, and body composition. The patients were women who were hypothyroid after thyroidectomy for Graves' disease. The substitution of 10 microg of T3 for 50 microg of T4 caused a statistically significant decrease in free T4 concentration but no significant change in T3 or thyroid-stimulating hormone concentration. Symptoms of hypothyroidism and of hyperthyroidism tended to decrease on a standard symptom scale after combined treatment. With combined hormone replacement, mental state tended to improve on some mood scales but not on cognitive tests. We found alterations in left ventricular diastolic function but no change in body composition after the combined treatment regimen. These preliminary findings in a small group of patients with Graves' disease are consistent with earlier findings that thyroid replacement with T4-T3 combination improves mental functioning.

Combined Use of Thyroid Hormone and ECT.

Neurocognitive deficits, including acute confusion and memory impairment, remain important effects of electroconvulsive therapy (ECT). Laboratory and clinical research demonstrates interactions among neurocognitive functioning, the hypothalmic-pituitary-thyroid axis, depressive mood, and ECT. Preclinical studies have demonstrated that exogenous triiodothyronine (T(3)) administered to animals receiving electroconvulsive shock (ECS) protects against ECS-related amnesia and accelerates the "antidepressant effects" of ECS, possibly due to alterations in catecholamine and/or indoleamine neurotransmission. Clinical data suggest that combined treatment with T(3) and ECT results in increased clinical efficacy of ECT and diminished neurocognitive side effects.

Preliminary study of the relationship between thyroid status and cognitive and neuropsychiatric functioning in euthyroid patients with Alzheimer dementia.

OBJECTIVE: To investigate whether variations within normal ranges of thyroid functioning are related to cognitive and neuropsychiatric functioning in Alzheimer disease (AD). BACKGROUND: Mild alterations of thyroid hormone levels, even in the normal range, are associated with changes in mood and cognitive functioning in older, nondemented adults, and lower concentrations of thyroid hormones have been shown to be associated with an increased risk for cognitive decline. Less is known about the relationship between thyroid hormone levels and cognitive and neuropsychiatric dysfunction in AD. METHOD: Twenty-eight euthyroid patients with AD on donepezil underwent evaluation of thyroid status, including measures of thyroid-stimulating hormone (TSH) and free thyroxine (FT4), and cognitive and neuropsychiatric assessment with the Alzheimer's Disease Assessment Scale, Neuropsychiatric Inventory, and Visual Analog Mood Scales. RESULTS: Correlational analyses indicated statistically significant associations between FT4 concentrations and self-reported feelings of fear and fatigue. Fear and fatigue were negatively correlated with FT4. There were no significant relationships between thyroid hormones and cognition and other depressive and anxiety symptoms. CONCLUSIONS: Results of this preliminary study support a relationship between thyroid status and neuropsychiatric symptoms in euthyroid individuals with AD, with lower concentrations of FT4 associated with fear and fatigue.