Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two thyroid axis findings are often reported in depressed patients: autoimmune thyroiditis and abnormal thyrotropin (thyroid stimulating hormone, TSH) responses to thyrotropin-releasing hormone (TRH). The TSH response to TRH can be exaggerated, suggesting subclinical hypothyroidism; it can alternatively be blunted, for reasons poorly understood. We selected 28 women who had been found to have major depression for TRH testing. Fifteen patients had autoimmune thyroiditis and 13 had diffuse nontoxic goiter. The endocrinological diagnoses were verified by fine-needle aspiration biopsy and cytological assessment. Patients with overt hypothyroidism and hyperthyroidism were excluded from the study. There were no differences between the two groups in total triiodthyronine and thyroxine plasma levels or severity of depression. In the autoimmune group, basal TSH and Dmax TSH tended to be higher (p < 0.1); peak TSH was significantly higher (p < 0.05), suggesting that the prevalence of subclinical hypothyroidism was also higher. Blunted TSH responses were found about as often in one group as the other.
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PMID:Thyrotropin response to TRH stimulation in depressed patients with autoimmune thyroiditis. 782 17

The adjunctive use of triiodothyronine (T3) with tricyclic antidepressants is generally believed to augment the efficacy of the tricyclic medications in unipolar, bipolar, and treatment-resistant depression. In the small subset of depressed patients with evidence for overt or subclinical hypothyroidism, the efficacy of supplementary T3 is logically presumed to derive from the amelioration of the hypothyroidism. It is, however, uncertain why adjunctive T3 therapy is often effective in the initially euthyroid depressed patient and if such therapy induces subclinical hyperthyroidism. To determine the metabolic state induced by low-dose T3 treatment, rats were administered nonpulsatile, submaintenance doses of T3 to achieve marked but incomplete suppression of the serum thyroxine (T4) (to 25%-50% of control levels) and serum thyrotropin (TSH) concentrations over a 10-week interval. No statistically significant change in the serum T3 was observed. At sacrifice, multiple parameters of peripheral metabolic status (growth rate, heart rate, organ weights, and tissue alpha-glycerophosphate dehydrogenase activities) in cerebrum, liver, kidney, spleen, and testes were consistent with euthyroidism. Thus, in a centrally regulated T3-predominant environment such as accompanies treatment with submaintenance doses of T3, originally euthyroid animals appear to remain in a euthyroid metabolic state.
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PMID:Metabolic implications of low-dose triiodothyronine administration in rats: relevance to the adjunctive use of triiodothyronine in the treatment of depression. 789 63

In order to evaluate the function of the hypothalamic-pituitary-thyroid (HPT)-axis in unipolar depression, the authors measured basal 0800h plasma levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) by means of the new, ultrasensitive assays (TSH-IRMA) in 69 healthy controls, 62 minor, 101 simple major, and 57 melancholic depressed subjects. Basal HPT-axis hormone levels of almost all (96.8%) unipolar depressed patients fell within the normal, euthyroid range. None of the major depressed subjects showed subclinical hypothyroidism. It was found that 8.8% of the melancholic subjects exhibited some degree of subclinical hyperthyroidism. Basal TSH-IRMA values were significantly lower in melancholic patients than in healthy controls, minor and simple major depressed patients, and in major vs. minor depressed subjects. FT4 circulating levels were significantly higher in melancholic patients than in all other subjects. Basal TSH-IRMA and FT4 levels were significantly correlated with severity of illness. In depression, there was a significant and negative correlation between basal TSH-IRMA values and FT4 concentrations. No significant gender- or age-related differences in TSH-IRMA or thyroid hormones were detected in depression. It is argued that--in depression research--the assays of basal TSH-IRMA should replace thyrotropin releasing hormone tests.
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PMID:An evaluation of basal hypothalamic-pituitary-thyroid axis function in depression: results of a large-scaled and controlled study. 812 50

The following paper deals with the current research in hyperthyroidism, with special accent to Graves' disease. Besides severe psychological trauma a breakdown of neurotic defense mechanism on the ground of a special personality structure was thought to be the trigger of the disease. The metabolic changes became the main point of interest. The influence of thyrostatic, surgical and radioactive therapies on psychological symptoms, was investigated. Thereby, the previously anticipated emotional factors became less significant in the aetiology of the disease. A recent study (Paschke 1990) suggests that patient with hyperthyroidism have, even in an euthyrotic state, an increased vulnerability to anxiety provoking situations. At this point it is not clear, due to the retrospective nature of the study, whether the vulnerability exists prior to the unset of the disease or is a result of the metabolic disorder. Both thyroxin and TRH are being successfully used in the treatment of major depression. TRH acts as a neurotransmitter in the autonomic nervous system and can be demonstrated in the peripheral lymphocytes. However, the exact mechanisms of action of thyroxin and TRH are still unknown. Graves' disease is an autoimmune disease, that can be caused by specific HLA antigens. Thereby, a changed subpopulation of lymphocytes can be demonstrated, as well as there disturbed functions. A correlation between high scores for anxiety and depression on one hand and the occurrence of an abnormal T4/T8 ratio on the other hand, have been reported in a small number of cases (Paschke 1990). The psychological symptoms in hyperthyroidism are similar to the symptomatology of neurotic anxiety and the anxious depressive syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Psychosomatic aspects of hyperthyroidism with special reference to Basedow's disease. An overview]. 837 18

Misdiagnosis of hyperthyroidism is explained first of all by errors in symptoms analysis, absence of ophthalmopathy, thyroid enlargement, predominant lesion of one system, atypical onset, various clinical masks (ischemic heart disease, active rheumatic fever with mitral and aortic defects, endogenic depression, obesity, gastrointestinal and hepatic diseases).
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PMID:[Difficulties in diagnosis of thyrotoxicosis in internal medicine]. 869 70

The clinical and biochemical features of postpartum thyroid disease were analysed in 152 antithyroid peroxidase antibody-positive (anti-TPO+ve) women and compared with 239 anti-TPO-ve age-matched control postpartum women. All were assessed monthly for up to 12 months postpartum. Seventy three anti-TPO+ve women developed postpartum thyroiditis (PPT): 19.2% hyperthyroid alone, 49.3% hypothyroid alone, and 31.5% characterized by hyper- followed by hypothyroidism. None of the antibody-negative women developed any thyroid dysfunction. A significant increase in many of eleven symptoms of hypothyroidism and some of eight symptoms of hyperthyroidism compared to control women was observed in all anti-TPO+ve women, independent of thyroid status. This was particularly seen in women who later developed PPT when they were euthyroid, but was also observed in euthyroid anti-TPO+ve women who showed no decline of thyroid function during the postpartum period. Although PPT is usually transient, this condition, and the euthyroid antibody-positive state, may be associated with significant symptomatology, including an increased incidence of minor to moderate depression. Early recognition of this syndrome by antenatal screening of thyroid antibodies may contribute to improved management of women during the postpartum period.
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PMID:The clinical spectrum of postpartum thyroid disease. 875 46

Raised activity of the LH axis caused by activating mutations of LH receptor gene presents with precocious puberty in boys, analogous to the presentation of LH secreting pituitary adenomas (Faggiano et al., 1983; Ambrosi et al., 1990). LH "hyperactivity' in females appears to have no effect. Hyperactivity of the FSH axis caused by activating mutations of the FSH receptor gene might parallel the presentation of FSH secreting pituitary adenomas with Sertoli cell hypertrophy in men (Heseltine et al., 1989) or reversible premature ovarian failure in women (Moses et al., 1986; Okuda et al., 1989). Indeed the first such case to be described is a male who maintained testicular volume and fertility in the absence of gonadotrophins (Gromoll et al., 1996). Female precocious puberty may require hyperactivity of both gonadotrophin axes because of the "two-cell' arrangement required for ovarian oestrogen production. Mutations of the Gs alpha-subunit gene can mimic this situation in some women with the McCune-Albright syndrome (Malchoff et al., 1994). Lack of LH activity caused by defects in the LH beta molecule causes infertility in men and that resulting from inactivating mutations of the LH receptor gene causes Leydig cell agenesis in men while ovarian development in females is relatively normal. Lack of FSH activity caused by defects in the FSH beta caused infertility in a female, and that caused by inactivating mutations of the FSH receptor gene causes ovarian dysgenesis in women but only variable depression of spermatogenesis in men. Incidentally, this categorization of reproductive disorders may also be applied to the TSH axis. Pituitary adenomas and activating mutations of the TSH receptor gene (Parma et al., 1993) cause hyperthyroidism and TSH beta gene defects (Hayashizaki et al., 1989) and inactivating mutations of the TSH receptor gene (Sunthornthepvarakul et al., 1995) cause hypothyroidism. To complete the analogy with thyroid disorders, it is curious that despite structural similarities with the TSH receptor, neither LH nor FSH receptor autoantibodies have a prominent role in ovarian pathophysiology (Moncayo et al., 1989; Van Weissenbruch et al., 1991; Simoni et al., 1993). Complete gonadotrophin resistance is likely to be very rare, however, so what are we likely to find in partial gonadotrophin resistance? Might the "resistant ovary syndrome' come right in the end, with corresponding minor FSH receptor mutations? Experience with insulin and androgen resistance syndromes suggests that such a scenario is unlikely. Insulin receptor gene mutations are found in extreme Type A insulin resistance but not in moderate forms of insulin resistance (O'Rahilly et al., 1991). Androgen receptor gene mutations are found in nearly all cases of complete androgen insensitivity but rarely in partial forms (Patterson et al., 1994). Mild resistance to hormone action is rarely detectable in relatives who are heterozygous for receptor mutations which are inherited in a recessive pattern. It seems unlikely therefore, that individuals heterozygous for inactivating receptor mutations will manifest symptoms of reproductive disorders and account for common conditions. Thus, while mutation analysis provides new insights into the gender specific role of the gonadotrophins the cause of early gonadal failure in the majority of individuals remains a mystery.
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PMID:Clinical manifestations of genetic defects affecting gonadotrophins and their receptors. 903 30

From an endocrine outpatient clinic and psychiatric outpatient clinic in Kaunas, Lithuania, 41 women with major depression were selected for study. Three groups of depressed women were established: 15 with autoimmune thyroiditis (AIT); 13 with diffuse non-toxic goiter (DNG); 13 with no thyroid disease (NTD). Standard biochemical tests were used to exclude patients with overt hypothyroidism or overt hyperthyroidism. At baseline the three groups were similar in age and almost identical in severity of depression. In part because of exclusion criteria, all baseline biochemical measures were similar. However, a slight elevation of thyroid-stimulating hormone (TSH) in the AIT group was noted and considered to indicate a tendency toward subclinical hypothyroidism. After thyrotropin-releasing hormone (TRH) administration, six AIT women and six DNG women, but no NTD women, showed blunted TSH responses. As a group DNG women showed smaller TRH responses than other women. Four AIT women showed exaggerated TSH responses. In all three groups basal TSH correlated positively with TSH response to TRH. Basal prolactin (PRL) responses to TRH infusion were similar in all three groups. However, the four AIT women with enhanced TSH responses also showed enhanced PRL responses. Indeed, in the AIT group, but only in this group, PRL responses were correlated with both TSH and basal TSH. In all groups of women the PRL response was unrelated to basal PRL.
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PMID:Pituitary responses to thyrotropin releasing hormone stimulation in depressed women with thyroid gland disorders. 904 46

The heart is a major target organ for thyroid hormone action, and marked changes occur in cardiac function in patients with hypothyroidism or hyperthyroidism. Triiodothyronine (T3)-induced changes in cardiac function can result from direct or indirect T3 effects. Direct T3 effects result from T3 action in the heart itself and are mediated by nuclear or extranuclear mechanisms. Extranuclear T3 effects, which occur independently of nuclear T3 receptor binding and increases in protein synthesis, influence primarily the transport of amino acids, sugars, and calcium across the cell membrane. Nuclear T3 effects are mediated by the binding of T3 to specific nuclear receptor proteins, which results in increased transcription of T3-responsive cardiac genes. The T3 receptor is a member of the ligand-activated transcription factor family and is encoded by cellular erythroblastosis A (c-erb A) genes. T3 increases the heart transcription of the myosin heavy chain (MHC) alpha gene and decreases the transcription of the MHC beta gene, leading to an increase of myosin V1 and a decrease in myosin V3 isoenzymes. Myosin V1, which is composed of two MHC alpha, has a higher myosin ATPase activity than myosin V3, which contains two MHC beta. The globular head of myosin V1, with its higher ATPase activity, leads to a more rapid movement of the globular head of myosin along the thin filament, resulting in an increased velocity of contraction. T3 also leads to an increase in the speed of diastolic relaxation, which is caused by the more efficient pumping of the calcium ATPase of the sarcoplasmic reticulum (SR). This T3 effect results from T3-induced increases in the level of the mRNA coding for the SR calcium ATPase protein, leading to an increased number of calcium ATPase pump units in the SR. Overall, T3 leads to an increase in ATP consumption in the heart. In addition, less chemical energy of ATP is used for contractile purposes and more of it goes toward heat production, which causes a decreased efficiency of the contractile process in the hyperthyroid heart. The pathophysiologic basis for myxedema is the opposite of that discussed for the hyperthyroid heart. In addition to decreased direct effects of thyroid hormone in cardiac myocytes, indirect effects occur through decreases in peripheral oxygen consumption and changes in hemodynamic parameters. Myofibrillar swelling with loss of striation and interstitial fibrosis occurs on histologic examination of hypothyroid hearts. In addition, accumulation of mucopolysaccharide substances (Glycosaminoglycans) can be demonstrated. On electron microscopic examination, mitochondria show disruption and lipid inclusion. Cardiac papillary muscle obtained from animals with hypothyroidism shows a depression of the force velocity curve and reduced rate of tension development, indicating significant contractile abnormalities. In patients with hypothyroidism, a true enhanced incidence of hypertension (increased peripheral vascular resistance) has been found. In addition, hypercholesterolemia and impairment of fatty acid mobilization are associated with myxedema and present additional risk factors for the development of atherosclerotic cardiovascular disease.
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PMID:[Cardiovascular effects of thyroid hormones]. 906 69

Alpha interferons have been used widely to treat chronic hepatitis C virus infection. These include recombinant interferons, purified natural leukocyte, and lymphoblastoid interferons. Alpha interferon is administered by subcutaneous or intramuscular injection either daily or three times weekly for a period of 6 to as long as 24 months. A wide array of adverse effects of alpha interferon have been described. Several side effects such as fever, headache fatigue, arthralgias, and myalgias are common, especially with the initial injections. These early side effects of interferon are predictable and are encountered in the majority of patients. These may not require dose modification, but can be problematic for a significant proportion of patients. Other adverse events effects may require dose modification or even discontinuation of therapy in 2% to 10% of patients. Neuropsychiatric side effects such as depression and irritability can be most troublesome; their mechanisms are not well understood. Granulocytes, platelets, and red blood cell counts decrease during treatment, but the decreases are usually mild, although they can be dose limiting if cell counts are low initially. Interferon has important immunomodulatory properties, and treatment can induce autoimmune phenomena, the most frequent being autoimmune thyroiditis with either hypothyroidism or hyperthyroidism, especially in predisposed patients. Other autoimmune disease can be aggravated by interferon therapy. Severe and even life-threatening side effects of interferon occur in 0.1% to 1% of patients; these include thyroid, visual, auditory, renal, and cardiac impairment, and pulmonary interstitial fibrosis. Some of these side effects may be irreversible. Higher doses of interferon (above 5 million units three times weekly) cause higher rates of adverse events than standard doses. Contraindications to alpha interferon have been recognized.
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PMID:Side effects of alpha interferon in chronic hepatitis C. 930 75


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