The prognostic significance of thyroid function in mania

Free thyroxine index (FT4I) and thyroxine (T4) levels were measured in 31 manic patients shortly after admission to a psychiatric hospital. Over one-third had elevated thyroid hormone levels, and this was largely due to increases in FT4I. Increased FT4I levels were associated with greater sleep disturbance and with being male, and were negatively associated with having had hospital admissions in the past six months. More interestingly, however, low FT4I levels prospectively predicted more hospital admissions in the 12 months from index admission, and this was not due to past admissions predicting future admissions. This adds to the growing literature on important relationships between thyroid hormones and treatment outcome in patients with affective disorders.     

Euthyroid hyperthyroxinemia and rapid cycling affective disorder: case report

A 32-year-old woman with rapid cycling bipolar illness had numerous clinical problems throughout 19 affective episodes and six hospital admissions within 34 months. Persistent hyperthyroxinemia, always associated with manic episodes, led to a diagnostic work-up that ruled out a primary thyroid dysfunction and pointed to oral contraceptives, appetite suppressants, and psychiatric illness as likely causes of elevated T4 values. The contention that an underlying thyroid hypofunction is the basis of rapid cycling is questioned. The extent to which a bipolar disorder increases T4 levels and the role of euthyroid hyperthyroxinemia in the pathogenesis of rapid cycling are discussed.     

Review: thyroid function in psychiatric illness

The development of highly sensitive immunometric assays for thyroid-stimulating hormone (TSH) has provided increased understanding of thyroid hormone regulation but, paradoxically, has contributed to a kaleidoscopic complexity of thyroid function test variability in hospitalized patients with nonthyroidal illness (NTI). In primary hypothyroidism, an elevated TSH is the most sensitive chemical index available, although early cases may show a hyperresponse of TSH to thyrotropin-releasing hormone (TRH) stimulation when the TSH is still within the normal range. The ability of the new TSH assays to discriminate between normal and low levels now allows the diagnosis of thyrotoxicosis to be confirmed by a suppressed TSH in the presence of elevated serum thyroxine (T4) and/or triiodothyronine (T3). The TRH stimulation test is virtually obsolete for the diagnosis of thyrotoxicosis but remains of much interest in the investigation of psychiatric syndromes. Approximately 25% of patients with depression have a blunted TSH response (a rise of less than 5 microU/mL) that differs from thyrotoxicosis, wherein the TSH response is suppressed under 1 microU/mL. The cause of the blunted TSH is uncertain but is not due to hyperthyroidism. In contrast, close to 15% may have a TSH hyperresponse to TRH and/or elevated antithyroid antibodies. Thyroid hormone treatment may benefit the depression in some of these cases. In the sick thyroid state of nonthyroidal illness, a low T3 level is the initial manifestation. In more severe cases, the T4 also falls, the free T4 level in this situation is variable, both normal and low levels being reported from different laboratories. A diagnosis of hypothyroidism requiring treatment with thyroid hormone therapy is unlikely unless there is a concomitant lowfree T4 and elevated TSH in a patient who is not in the process of recovery. In acute psychiatric admissions, there is a high frequency of hyperthyroxinemia. The TSH in these cases is generally either normal or high, suggesting central activation of the hypothalamic-pituitary-thyroid axis. In most instances, the thyroid function tests normalize within 2 weeks, and treatment directed toward the thyroid gland is not indicated. Suppressed TSH levels, usually associated with a normal free T4, has also been described in such patients. Finally, various medications utilized in psychiatric practice have diverse effects on thyroid function and can cause diagnostic difficulty. These include lithium, phenytoin sodium, and carbamazepine, and their effects are reviewed.     

Hormones, electrolytes, and cerebrospinal fluid proteins in manic-melancholic patients

The concentrations of insulin and thyroid hormones, tryptophan, electrolytes, urea, plasma proteins in the cerebrospinal fluid, and glucose in blood and cerebrospinal fluid in manic-melancholic patients were studied. As control groups served patients suffering from other psychiatric disorders as well as neurological and orthopedic patients. Apart from the blood values of thyroid hormones, the results showed no differences between the various diagnostic groups, neither in the abnormal states nor when recovered. For blood thyroxine and free thyroxine index, a statistically significant differences was seen in unipolar (melancholic) patients, namely a decrease concomitant with the clinical improvement. A tendency in the opposite direction of the thyroxine values was found in bipolar (melancholic) patients. In the manic group a marked decrease in the thyroxine values was obtained in the lithium-treated patients.     

新生儿缺氧缺血性脑病甲状腺功能变化及替代治疗

目的 探讨新生儿缺氧缺血性脑病（ＨＩＥ）甲状腺功能的变化以及甲状腺素替代治疗对预后的影响。方法 应用放射免疫方法对ＨＩＥ患儿３日龄、７日龄及应用甲状腺素替代治疗的１４日龄患儿血清甲状腺激素水平进行动态观察,并将７日龄时血清甲状腺激素水平低下者随机分为２组,对照组继续ＨＩＥ常规治疗,治疗组在此基础上加用甲状腺片治疗,通过观察体温、进乳量的改善、体重的变化以及应用新生儿行为神经测查法（ＮＢＮＡ）进行评估。结果 ３日龄时中、重度ＨＩＥ患儿血清Ｔ３显著低下,各组间有显著性差异,７日龄时重度组Ｔ３仍显著下降,应用甲状腺素替代治疗组与常规治疗组相比ＮＢＮＡ评分、预后判定及进乳量的改善上均有显著性差异。结论 中、重度新生儿ＨＩＥ伴随甲状腺功能降低,且与疾病严重程度呈正相关,恢复期（７日龄）甲状腺功能不恢复者应用甲状腺片替代治     

Thyroid Function Screening in Acute Geropsychiatric Admissions

Thyroid function abnormalities have been associated with psychiatric illness. Even though it is a common practice to assess thyroid function in geropsychiatric patients, a literature search for the past 10 years did not reveal any published studies of assessments of thyroid function abnormalities in acute geropsychiatric populations. A retrospective chart review of 197 acute geropsychiatric inpatients and 14 comparison group patients showed that 40 geropsychiatric patients and 2 comparison group patients had abnormal thyroid function tests (TFTs). The most common abnormality was elevated triiodothyronine uptake (T₃U), which was noted in 19 female and 13 male geropsychiatric patients. The difference in the prevalence of TFT abnormalities between the geropsychiatric patients and the comparison group subjects was not statistically signiflcant. Both T₃U and free thyroxine index (FTI) were significantly higher in the female geropsychiatric patients than in the female comparison group patients. The abnormalities in T₃U and FTI in this study group may be related to an increased prevalence of unidentified systemic illness or to the presence of chronically poor nutrition.     

Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism

PURPOSE: The aim of the study was to evaluate serum thyroid hormone balance in children receiving long-term therapy with carbamazepine (CBZ), valproate (VPA), and phenobarbital (PB). METHODS: We determined serum levels of triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), thyroxine-binding globulin (TBG), and thyroid-stimulating hormone (TSH) in 148 healthy children and 141 children with epilepsy who had been receiving CBZ (61 patients), VPA (51 patients), or PB (29 patients) for 12-161 months. In view of TSH values, three categories of subclinical hypothyroidism were considered: I, TSH greater than the control-group mean + 2 SD (4.37 mIU/L in our study) and <6 mIU/L; II, TSH between 6 and 12 mIU/L; and III, TSH >12 mIU/L. RESULTS: In all treated groups, mean T4 and FT4 levels were lower than in the control group, whereas the CBZ- and VPA-treated children additionally showed reduced mean T3 and TBG levels and increased mean TSH levels. In the group receiving CBZ, 8.2% had TSH values higher than the normal-range maximum, by comparison with only 3.6% of healthy children. The increase in TSH levels was particularly marked in VPA-treated children, accounting for 26% of patients with subclinical hypothyroidism. CONCLUSIONS: Our results, in contrast to previous reports, suggest that CBZ and particularly VPA may induce subclinical hypothyroidism. This suggests a need for careful monitoring of TSH levels in children receiving CBZ or VPA.     

No effect of long-term valproate therapy on thyroid and parathyroid functions in children

In this study, we studied serum calcium, phosphorus, alkaline phosphatase, thyroid hormones (total thyroxine, free thyroxine, thyroid-stimulating hormone), parathyroid hormone, and osteocalcine levels in children with epilepsy who had been receiving long-term valproate (VPA) therapy in order to determine whether there was any effect of VPA therapy on these hormones. The study included 31 patients with epilepsy receiving VPA and 22 healthy age-matched controls. The age ranged from 15 months to 16 years and 18 months to 17 years in the study and control group, respectively. The duration of VPA use was between 12 months and 5 years (1.93 +/- 1.90 years). When comparing the results, we did not find any significant difference in any of the parameters, including serum calcium, phosphorus, alkaline phosphatase, osteocalcine, and thyroid and parathyroid hormone levels, between the study and control group. We suggest that VPA can safely be used with regard to thyroid and parathyroid dysfunction in childhood epilepsy.     

Serum thyroxine change and clinical recovery in psychiatric inpatients

Serum free thyroxine (FT4), total thyroxine (TT4), and Brief Psychiatric Rating Scale (BPRS) measurements were obtained following hospital admission and at 2-week intervals during hospitalization in 80 male psychiatric inpatients with a variety of major psychotic and affective disorders. A strong correlation between the range values for BPRS sum and for FT4 (p less than 0.005) and TT4 (p less than 0.001) levels indicated that change in overall symptom severity was linked to change in thyroxine levels during clinical recovery. We found the relationship not to be a simple one, but to require definition of criteria for three patient subgroups for each hormone, taking into account the initial absolute thyroxine level, as well as the direction and magnitude of hormonal change during recovery. The hormonally defined "good recovery" subgroup included patients with high initial thyroxine levels that then fell substantially, patients with low initial thyroxine levels that then rose substantially, and patients with initial thyroxine levels in the middle range that subsequently changed substantially. The hormonally defined "poor recovery" subgroup included those patients not meeting these criteria. The degree of clinical improvement in the hormonally defined good recovery group was significantly greater by almost twofold than the poor recovery group both for FT4 (p less than 0.04) and TT4 (p less than 0.02). These findings suggest that a "normalizing" principle underlies the relationship between clinical recovery and thyroxine levels and that both FT4 and TT4 levels within the normal range appear to have clinical significance in either reflecting or contributing to the course of a variety of psychiatric disorders and possibly having a role in pathogenesis.     

Thyroid status in senile dementia of the Alzheimer type (SDAT)

Thyroid function was investigated in a group of 21 patients with severe senile dementia of the Alzheimer type (SDAT) and in a group of 17 age and sex matched normal controls. Free thyroid hormone levels (triiodothyronine (T3) and thyroxine (T4) were measured, as were also the thyrotrophin (TSH), prolactin (PRL) and growth hormone (GH) responses to thyrotrophin releasing hormone (TRH)). When compared to controls, patients demonstrated a significantly lower free T3 value (but not free T4), a blunted TSH response to TRH, slightly elevated basal PRL and GH values and a small GH response to TRH. However, all differences were small in biological terms and were within the laboratory's normal range. This emphasizes the relative normality of neuroendocrine function, particularly thyroid status, in SDAT.     

Carbamazepine, serum thyroid hormones and myocardial function in epileptic patients.

Serum thyroid hormone and thyrotropin levels were assayed and the myocardial function was evaluated by measuring systolic time intervals both in 30 patients with epilepsy on long-term carbamazepine monotherapy and in 19 healthy volunteers. Serum thyroxine, free thyroxine and triiodothyronine levels were significantly lower (p < 0.001) in the patient group than in the control group and systolic time intervals were similar in both groups.     

Brief Communication: NO EFFECT OF LONG-TERM VALPROATE THERAPY ON THYROID AND PARATHYROID FUNCTIONS IN CHILDREN

In this study, we studied serum calcium, phosphorus, alkaline phosphatase, thyroid hormones (total thyroxine, free thyroxine, thyroid-stimulating hormone), parathyroid hormone, and osteocalcine levels in children with epilepsy who had been receiving long-term valproate (VPA) therapy in order to determine whether there was any effect of VPA therapy on these hormones. The study included 31 patients with epilepsy receiving VPA and 22 healthy age-matched controls. The age ranged from 15 months to 16 years and 18 months to 17 years in the study and control group, respectively. The duration of VPA use was between 12 months and 5 years (1.93 &#45 1.90 years). When comparing the results, we did not find any significant difference in any of the parameters, including serum calcium, phosphorus, alkaline phosphatase, osteocalcine, and thyroid and parathyroid hormone levels, between the study and control group. We suggest that VPA can safely be used with regard to thyroid and parathyroid dysfunction in childhood epilepsy.     

Correlation between serum myoglobin and thyroid status in myasthenia gravis

In 52 patients with myasthenia gravis serum myoglobin showed a significant inverse correlation to circulating thyroxine and triiodothyronine levels. The highest myoglobin concentration (240 ng/ml) was found in a myasthenia gravis patient with hypothyroidism. Slightly elevated myoglobin (54-60 ng/ml) was measured in four euthyroid myasthenic patients. The data suggest that a concomitant hypothyroid state must be excluded whenever high myoglobin levels are found in myasthenia gravis.     

Sleep apnea and hypothyroidism presenting as depression in two patients

Two patients are described who presented with depression and were later found to have both obstructive sleep apnea and hypothyroidism. Both patients had normal thyroxine (T4) levels but elevated thyroid-stimulating hormone (TSH) levels. Thyroid replacement led to resolution of both apnea and depression. The possibility of hypothyroidism as a cause of sleep apnea and depression is discussed.     

Psychological depressive symptoms in grade II hypothyroidism in a nursing home

In an effort to explore the relationship between Grade II hypothyroidism and depressive symptoms, 16 nursing home residents with normal free thyroxine index and elevated basal thyrotropin (thyroid-stimulating hormone; TSH) levels were matched for age, sex, nursing level of care, and certain medications with a control group who had normal basal TSH levels. The Geriatric Depression Scale (GDS) was administered to all participants. Basal TSH elevation was not associated with increased psychological depressive symptoms on the GDS.     

Persistent hyperCKemia: fourteen patients studied in retrospect

Fourteen patients with persistently raised serum creatine kinase activity (hyperCKemia) were studied in retrospect. Clinical and laboratory findings did not point to any established neuromuscular disorder. In 8, manual occupation with local muscle strain apparently caused the hyperCKemia despite a low total work load. One patient had subclinical hypothyroidism with a normal serum thyroxine and and elevated thyroid-stimulating hormone level. CK normalized with L-thyroxine therapy. In 2, including one manual worker, myoadenylate deaminase was deficient. The hyperCKemia remained unexplained in 4 patients.     

Renal,thyroid and parathyroid function during lithium treatment: laboratory tests in 207 people treated for 1–30 years

A total of 207 patients (diagnoses revised according to DSM-HI-R) attended our outpatient clinic and were treated with lithium for 1–30 years. They were subjected to conventional renal, thyroid and parathyroid function tests. With increasing treatment duration, the renal tests showed only moderate deviations from expected reference values. No patient developed renal insufficiency. Oversubstitution (thyrotropin ≤0.1 mU/l) was suspected in 25% of the patients on thyroxine. Cross-sectionally unrecognized hypothyroidism was found in 6% of the patients. Elevated ionized serum calcium was found in 25% and elevated serum intact parathyroid hormone in 23% of the patients.     

THE VIBRATION PERCEPTION THRESHOLD IN GASTRECTOMIZED PATIENTS WITH LOW SERUM B12

In 42 gastrectomized patients with low serum B12 the vibration perception threshold (VPT) was significantly elevated as compared with a control group. Forty patients were followed up after 6-12 months of intensive vitamin B12 therapy. Within an adequately treated group (25 patients) remission of symptoms and signs of peripheral neuropathy was observed, including a statistically significant reduction of the VPT measured on the medial malleolus and big toe. Such a reduction was not observed in the adequately treated group of patients with myclopathy. Findings in the inadequately treated group were less definite, both as regards remission of clinical findings and VPT. In four untreated patients the neurological symptoms and signs progressed during the follow-up period. On the basis of these findings intensive and long-lasting treatment with vitamin B12 is recommended for gastrectomized patients showing signs of neuropathy.     

Thyroid Function with Antiepileptic Drugs

Serum thyroid hormone balance was assessed in 108 patients receiving chronic antiepileptic drug (AED) therapy. Forty-five patients were receiving carbamazepine (CBZ), 26 phenytoin (PHT), 16 CBZ-PHT, 11 valproate (VPA), and 10 CBZ-VPA. Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in patient groups receiving CBZ and/or PHT. Serum T4 concentrations were below the normal range in 24 (53.3%) CBZ patients, 11 (42.3%) PHT patients, 12 (75%) CBZ-PHT patients, and in all 10 patients (100%) receiving CBZ-VPA. Furthermore, serum levels of FT4 were below the normal range in 13 (28.9%) CBZ patients, 6 PHT (23.1%) patients, 5 (31.3%) CBZ-PHT patients, and 5 (50%) CBZ-VPA patients. Despite the decreased serum T4 and FT4 levels in these patients, serum basal and stimulated thyrotropin (TSH) concentrations were normal, except for the slightly increased basal TSH in the CBZ-VPA group. In the VPA group, the findings were different from those in other patients: T4 serum levels were unchanged and FT4, T3, and basal TSH levels increased, but stimulated TSH levels did not differ from those of the control group. The decrease in serum thyroid hormone levels during CBZ and/or PHT medication probably is caused by an accelerated hepatic plasma clearance of these hormones due to induction of hepatic microsomal enzyme systems by these AEDs. VPA, an AED with no liver enzyme-inducing properties, does not cause similar changes. The feedback mechanism is not activated, possibly because of a hypothalamic interference by CBZ and PHT.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in serum thyroxine (T4) and serum thyroid stimulating hormone (TSH) during prolonged lithium treatment

We determined serum T4 and serum TSH serially in a cohort of patients given lithium treatment for up to 6 years; the total lithium exposure time was 409 years and the average serum lithium concentration 0.69 mmol/l. T4 showed a small and not significant fall at 6 months and returned to the pre-lithium level at 12 months. Hereafter, T4 rose gradually and after 6 years of lithium treatment T4 was 53% higher than the pre-lithium value. TSH was significantly increased at 6 and 12 months and then returned to the pre-lithium level. Eight patients required thyroxine treatment for lithium-induced hypothyroidism, i.e. 2 per 100 years of lithium exposure time. Single deviant values of T4 and TSH could be seen, followed by normal values. We suggest that TSH is determined at intervals during lithium treatment. It may be prudent to subject lithium-treated patients with abnormal thyroid values to re-examination and to abstain from starting thyroxine treatment on the basis of a single deviant value.