The clinical impact of the thyrotropin-releasing hormone test

Because of its ability to cause the release of thyrotropin (TSH), prolactin (PRL), and, under particular circumstances, also of other adenohypopyseal hormones, from the pituitary, thyrotropin-releasing hormone (TRH) has been widely used as a diagnostic tool for about 30 years. The recent introduction of an ultrasensitive TSH assay, able to clearly distinguish suppressed from unsuppressed TSH levels, has rendered the use of the TRH test obsolete in the diagnosis of classic hyperthyroidism. On the contrary, the TRH test is still extremely useful in hyperthyroid patients with inappropriate secretion of thyrotropin, allowing the distinction between TSH-secreting pituitary tumors (usually unresponsive) and the pituitary variant of resistance to thyroid hormone (PRTH) syndrome (always responsive). In hypothyroidism, the TRH test is still of value in patients with preclinical primary hypothyroidism, as they show exaggerated TSH response, and in those with central hypothyroidism, allowing the differentiation between pituitary (secondary) and hypothalamic (tertiary) hypothyroidism. The availability of high-resolution imaging techniques such as magnetic resonance has rendered the use of the TRH test obsolete, to distinguish microprolactionomas from functional hyperprolactinemia. The TRH test still has great clinical value in the follow-up of patients with pituitary tumors (in particular somatotropinomas and clinically nonfunctioning pituitary adenomas) showing abnormal responses of anterior pituitary hormones other than TSH.     

Comparison between TRH-stimulated TSH and basal TSH measurement by a commercial immunoradiometric assay in the management of thyroid disease

In order to assess the current diagnostic role of the TRH test following the introduction of more sensitive "second generation" TSH assays, we studied a series of 259 outpatients, 237 women and 22 men, mean age 44.7 years (range 12-82), 91 of whom (35%) with untreated simple goiter, 133 (51%) with simple nodular goiter on steady state I-thyroxine treatment, 18 (7%) with overt or subclinical hyperthyroidism and 17 (7%) with overt or subclinical hypothyroidism, compared to a control group of 26 euthyroid healthy subjects. Serum TSH was measured by a commercial immunoradiometric assay (clinical sensitivity 0.1 microU/ml). TSH response to TRH was evaluated 30 minutes after giving 200 micrograms TRH i.v. bolus, the results being analyzed both as absolute increase (delta-TSH=stimulated TSH minus basal TSH) and as relative increase (R-TSH stimulated TSH/basal TSH). Using cut-off values of 0.3-3.2 microU/ml, basal TSH measurement was able to detect hypothyroidism (specificity = 100%) and to exclude hyperthyroidism (sensivity = 96.9%), but failed to accurately prove hyperthyroidism (specificity = 93.4%) and, above all, to exclude hypothyroidism (sensitivity = 35.3%) in our ambulatory patients. The delta-TSH values showed a basal TSH dependent linear increase (r = + 0.87, p < 0.001) both including only patients (n = 139) with basal TSH level in the euthyroidism range and including all patients (n = 223) having TSH responsive to TRH. All the patients with detectable basal TSH level displayed detectable TSH response to TRH, as did 19 (= 23.5%) of 81 patients with undetectable (< 0.1 microU/ml) basal value. In particular: a) for subnormal but detectable basal TSH ranging between 0.1 and 0.2 microU/ml, TSH was always hyporesponsive (delta-TSH < or = 2.5 microU/ml), while between 0.2 and 0.3 microU/ml TSH was hyporesponsive in 72.2% and normoresponsive (delta-TSH > 2.5 and < or = 11.9 microU/ml) in the remaining 27.8%; b) for basal TSH values within the normal range (0.3-3.2 microU/ml). TSH was hyporesponsive in 13.7%, normoresponsive in 74.8% and hyperresponsive in 11.5%; c) for high basal TSH values TSH was always hyperresponsive. The analysis of R TSH showed relatively constant values in the range of euthyroidism and hypothyroidism (m +/- SD: 7.4 +/- 2.3 and 7.7 +/- 3.1, respectively), and a marked differentiation of hyperthyroid patients whose R-TSH values were significantly lower (4.2 +/- 3.4) but had a wide individual variability. Linear regression analysis of basal or stimulated TSH and circulating thyroid hormones showed a close negative relationship, being highly significant between delta-TSH and T4 (r = 0.57, p < 0.001) and delta-TSH and FT4 (r = 0.46, p < 0.001). In conclusion, after the introduction of current second generation TSH immunoradiometric assay, the diagnostic role of the TRH test is greatly limited but not to be excluded: it can provide additional information to that obtained with simple basal TSH measurement in the diagnosis of subclinical hypothyroidism and in the precise evaluation of the degree of TSH suppression in patients with a subnormal basal TSH, either for endogenous thyrotoxicosis or I.-thyroxine treatment.     

Role of protein degradation in the growth of livers after a nutritional shift

Four patients with idiopathic pituitary dwarfism were shown to have growth hormone (GH), adrenocorticotropin (ACTH), and luteinizing hormone (LH) deficiencies. Basal levels of thyrotropin (TSH) were within normal range in three patients and slightly elevated in one. Exaggerated and delayed responses were obtained after TSH-releasing hormone (TRH) stimulation. Serum thyroxine (T4) values were low (2.3 +/- 0.4 mug/100 ml), while triiodothyronine (T3) levels were in the normal range (1.22 +/- 0.25 ng/ml), both rising substantially after exogenous TSH and consecutive TRH administration. Their hypothyroid state was, therefore, probably due to TRH deficiency. To examine the dose of L-T4 necessary to produce inhibition of the TSH response to TRH, 50 mug/m2/day of L-T4 was administered to these patients. At the end of 4 weeks of replacement, serum T4 rose to 5.2 +/- 0.5 mug/100 ml, whereas T3 was unchanged from the previous levels, after which TSH responses to TRH were completely suppressed in all patients. As a control group, six patients with primary hypothyroidism received gradually increasing doses of L-T4 for 4-week periods, and TSH response to TRH was tested at the end of each dosage of L-T4, until complete inhibition of TSH release was obtained. The primary hypothyroid patients required approximately 150 mug/m2/day of L-T4 for suppression of TSH response to TRH. At this dosage, serum T4 and T3 levels were 8.5 +/- 0.9 mug/100 ml and 2.34 +/- 0.5 ng/ml respectively, which were significantly higher than those levels in the pituitary dwarfs (P less than 0.001 for T4 and P less than 0.01 for T3). These observations indicate that the set point of TSH release in feedback inhibition by throxine is low in idiopathic hypopituitarism with TRH deficiency, and TRH seems to control the pituitary sensitivity to feedback regulation of thyroid hormones.     

Thyrotropin assay by chemiluminescence in the diagnosis of dysthyroidism with low thyrotropin and normal thyroid hormones levels

The performances of a new "3rd generation" chemoluminescence TSH assay (TSH ICMA) with a functional sensitivity of 0.005 mU/l were compared with those of an "ultrasensitive" TSH immunoradiometric assay (TSH IRMA) in a series of patients characterised by a TSH IRMA less than 0.20 mU/l and normal free thyroxin (T4 L) and triiodothyronine (T3 L) concentrations. The 95% cut-off value for hyperthyroidism was 0.03 for TSH ICMA and 0.05 for TSH IRMA. In a first group of 41 subjects undergoing Tc99m thyroid scan, images of multifocal increased uptake or toxic adenoma were associated with a lower TSH ICMA than in patients with a normal isotope scan. TSH ICMA was also lower than TSH IRMA (p < 0.01). At the cut-off value of 0.03 mU/l, the specificity of TSH ICMA was higher than that of TSH IRMA, but the sensitivity were identical. In a second group of 36 patients with severe non-thyroid diseases, TSH ICMA was lower than the cut-off value for hyperthyroidism in 30% of cases, while TSH IRMA was lower than the cut-off value in 40% of cases. A satisfactory concordance was observed between the two methods. In conclusion, the two TSH assays, IRMA and ICMA, provide globally comparable information in subjects with a low TSH and normal T4 L and T3 L. However, the better specificity of TSH ICMA and a smaller overlap with the frank hyperthyroid zone in patients with non-thyroid disease argue in favour of the use of this new assay method.     

Studies on the TRH test on the patients with Graves' disease during the treatment with antithyroid drug (author's transl)

A study was performed to observe serum TSH response following TRH injection (TRH test) in 79 cases of Graves' disease (male 23, female 56, aged 16-70 years old), before and during treatment by antithyroid drug, in a total of 244 occasions. Treatment was mostly the daily administration of methyl-mercaptoimidazole (MMI), and in one case of propylthiouracil (PTU). TRH test was conducted by i.v. administration of 500 mug synthetic TRH, and subsequent 6 blood drawing until 2 hours. Serum TSH was measured by radioimmunoassay in each serum, and serum T4, T3, RT3U and cholestrol were measured in the serum before TRH injection. In some cases, the results of TRH test were compared with those of T3 131I thyroidal uptake suppression test, using the 131I uptake values at 20 min. and 24 hours. Results were obtained as follows: 1) Some cases showed positive TRH test at the early stage of treatment when the patients were in eumetabolic states, while many patients showed no TSH response in spite of their long maintenance at eumetabolic states. 2) When both serum T4 and T3 were high, all cases showed no response of TSH. When serum T4 alone was high, all cases except one case showed no response;whereas when serum T3 alone was high, 5 cases showed normal response. When both serum T4 and T3 were below normal, 2 cases showed no response. When serum T4 was low, all cases showed response; whereas when serum T3 alone was low, 6 cases showed no response. Thus, there was no positive correlation between TSH reactivity and serum concentrations of thyroid hormones. 3) No correlation was observed between TSH reactivity and the period after the onset of hyperthyroidism. 4) In 57 cases of Graves' disease, who were under treatment and in eumetabolic states, a comparison was made between TSH reactivity and the results of T3 suppression test. In T3 suppressed group, 19 showed response, and 3 showed no response; whereas in T3 non-suppressed group, 18 showed response and 17 showed no response. In the group of T3 non-suppression as well as in the group of T3 non-suppression plus TRH no response, there was a significant elevation of serum T3 compared with the control group. 5) TRH test does not appear to be an appropriate test as a predictive method to know the permanent remission of Graves' disease.     

Thyrotropin-secreting pituitary adenoma

Thyrotropin (TSH)-secreting pituitary adenoma (TSPA) is a rare cause of hyperthyroidism and detailed reports of this entity in Taiwan are uncommon. We report a patient with TSPA with symptoms of hyperthyroidism and describe the presentation, endocrine and histologic findings, and treatment. The patient, a 42-year-old man, presented with a 2-year history of weight loss, palpitation, anxiety, and bad temper. He had increased basal serum thyroxine (T4, 18.3 micrograms/dL) and triiodothyronine (T3, 250 ng/dL) concentrations. The TSH concentration was normal (4.6 microIU/mL) and showed impaired response to stimulation by TSH-releasing hormone. Tests for antithyroid antibodies were negative. Thyroid scintigraphy showed mild thyroid enlargement. The thyroid uptake of radioactive iodine (131I) was high at 2 hours (34%) and 24 hours (63%) after 131I administration. Other serum hormone concentrations were within normal limits. Magnetic resonance imaging of the brain showed a microadenoma in the pituitary region. Octreotide and bromocriptine tests showed 78.4% and 58.3% inhibition of TSH, respectively. The patient underwent trans-sphenoidal pituitary tumor excision, and the symptoms of hyperthyroidism subsided after surgery. Six months after the operation, there was no evidence of recurrence of the tumor or symptoms of hyperthyroidism. Hormonal supplements were also not necessary. In conclusion, TSPA is a rare cause of hyperthyroidism. However, in patients with symptoms of hyperthyroidism and increased basal serum T1 and T3 concentrations, but normal or even elevated serum TSH concentrations, TSPA should be considered in the differential diagnosis.     

The thyrotropin releasing hormone stimulation test in alcoholism

The mechanism for a blunted thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) in alcoholics is not known. We performed a combined TRH and gonadoliberin stimulation test on three well-defined groups of nondepressed alcoholic men. Group A comprised patients with acute withdrawal symptoms (n = 28), group B patients abstinent for 5-8 weeks (n = 29) and group C patients who had been abstinent for > 2 years (n = 16). Twenty-two healthy male volunteers were used for comparison. A blunted TSH response to TRH (delta TSH < 5 microU/l) occurred only in groups A (39%) and B (17%). In group A delta TSH showed a significant negative correlation with the severity of withdrawal symptoms and a significant positive correlation with serum magnesium levels. In group B, patients with a family history of alcoholism had significantly lower delta TSH levels than those without such a family history. Groups did not differ with respect to basal and delta prolactin, and TSH responses were not significantly associated with vitamin deficiency, cortisol levels or free thyroid hormone levels. We conclude that TRH stimulation test blunting appears to be related to factors operating in the withdrawal state and improves with continued abstinence. A possible role of genetic factors and serum magnesium needs to be further explored.     

One-year outcome analysis of functional endoscopic sinus surgery for chronic sinusitis

We studied, by means of TSH nocturnal secretion and TRH test, 42 children (4.2-19.9 years) with hypothalamic pituitary disorders and 24 healthy euthyroid children (5.7-15.4 years) as control group. Patients were divided according to their serum values of FT4 in group 1 (n = 27) with FT4 >/=10.3 pmol/l and group 2 (n = 15) with FT4 <10.3 pmol/l. TSH was measured by immunoradiometric assay. TSH nadir, TSH peak and TSH surge were calculated. Both groups differed significantly from control group in TSH surge values: group 1 (p < 0. 05), group 2 (p < 0.01). TRH test was abnormal in 11/27 patients of group 1 and 10/15 patients of group 2. In group 1, 7 patients had normal tests, 2 had abnormalities in both tests, 9 had only TSH nocturnal surge altered and 9 showed only TRH alterations. All patients of group 2 presented thyroid axis abnormalities. In conclusion, in patients with hypothalamic pituitary disorders with low FT4, no further investigation is required to demonstrate thyroid axis alterations, however in patients with normal FT4, nocturnal TSH secretion and TRH test may be required to evidence thyroid abnormalities.     

A rare case of a thyrotropin-secreting pituitary tumor which responded to methimazole

A 52-year-old Japanese male complained of palpitations and excessive sweating. He showed evidence of hyperthyroidism, but without suppression of the serum thyroid-stimulating hormone (TSH). On admission, the serum level of the alpha-subunit of TSH was elevated, but tests for thyroid autoantibodies were negative. The TSH response to thyrotropin-releasing hormone (TRH) was blunted. Imaging studies revealed a pituitary tumor 2 cm in diameter. Administration of methimazole lowered the serum levels of thyroid hormones, and elevated the serum level of TSH. These findings led to the diagnosis of a thyrotropin-secreting pituitary tumor. Immunohistochemical analysis and electron microscopic findings verified the diagnosis.     

Transient hypothyroidism after iodine-131 therapy for Grave's disease

We studied 355 patients with Grave's disease to characterize transient hypothyroidism and its prognostic value following 131I therapy. METHODS: The patients received therapeutic 131I treatment as follows: 333 received a dose < 10 mCi (6.6 +/- 1.9 mCi) and 22 received a dose > 10 mCi (12.8 +/- 2.9 mCi). Diagnosis of transient hypothyroidism was based on low T4, regardless of TSH within the first year after 131I followed by recovery of T4 and normal TSH. RESULTS: After administration of < 10 mCi 131I, 40 patients developed transient hypothyroidism during the first year; transient hypothyroidism was symptomatic in 15. There was no transient hypothyroidism after high doses (> 10 mCi) of 131I. Iodine-131 uptake > 70% at 2 hr before treatment was a risk factor for developing transient hypothyroidism (Odds ratio 2.8, 95% confidence interval 0.9-9.4). At diagnosis of transient hypothyroidism, basal TSH levels were high (51%), normal (35%) or low (14%); therefore, the transient hypothyroidism was not centralized. If hypothyroidism developed during the first 6 mo after basal TSH > 45 mU/liter ruled out transient hypothyroidism. CONCLUSION: The development of transient hypothyroidism and its hormonal pattern did not influence long-term thyroid function. Since no prognostic factors reliably predicted transient hypothyroidism before 131I or at the time of diagnosis, if hypothyroidism appears within the first months after 131I, the reevaluation of thyroid function later is warranted to avoid unnecessary chronic replacement therapy.     

Molecular analysis of p21 and p27 genes in human pituitary adenomas

OBJECTIVES: To determine the prevalence of thyroid dysfunction in institutionalised elderly people in Cape Town and to assess the usefulness of an abnormal thyroid-stimulating hormone (TSH) concentration as a screening test in this group. DESIGN: Cross-sectional survey. SETTING: Four old-age homes in Cape Town. SUBJECTS: Old-age home residents aged 60 years and over. OUTCOME MEASURES: Serum concentrations of TSH, free thyroxine and free tri-iodothyronine. RESULTS: Serum TSH estimations were performed on 658 participants, and were abnormal in 103 (15.6%)-41 (6.2%) being elevated (> 5.0 microU/ml) and 62 (9.4%) being low (> 0.4 microU/ml). There were 3 newly diagnosed cases of hyperthyroidism and 7 of hypothyroidism. Subclinical disease was diagnosed in 40 subjects. The overall prevalence of thyroid dysfunction in this population was 11.2%. In 22 (3.4%) this had previously been recognised, while in 50 (7.8%) the dysfunction was newly diagnosed by the current survey. The positive predictive value of a TSH concentration > 20 microU/ml in predicting hypothyroidism is 67%, while it will predict 100% of cases of subclinical hypothyroidism. A TSH concentration < 0.1 microU/ml will predict 23% of cases of hyperthyroidism, but 81% of cases of subclinical disease. CONCLUSIONS: The prevalence of thyroid dysfunction in institutionalised elderly people in Cape Town is similar to that reported for elderly people in other centres. Thyroid dysfunction had not previously been recognised in approximately two-thirds of the subjects in this study. The serum TSH concentration is a reliable screening test for thyroid dysfunction in the elderly, but is less useful if used to identify biochemical thyroid disease. An elevated TSH concentration is a better predictor of thyroid dysfunction in the elderly than a depressed TSH concentration.     

Analysis of pulsatile secretion of thyrotropin and growth hormone in the hypothyroid rat

To characterize the role of TRH in the generation of TSH pulsatility as well as the effect of hypothyroidism on episodic GH secretion, blood was constantly withdrawn (30-60 microliters/min) from rats treated with 0.02% methimazole in the drinking water for 8-10 days. This treatment significantly reduced circulating levels of both T3 and T4 and elevated plasma TSH; however, since thyroid hormone titers were still detectable (T3, 39.6 +/- 5.3 vs. 89.8 +/- 5.3 ng/dl in euthyroid animals), methimazole-treated rats were referred to as being mildly hypothyroid. TSH was found to be secreted in secretory bursts, consisting of one to several peaks in these rats. Pulsar analysis of TSH secretory profiles revealed a mean pulse frequency of 2.8 pulses/h, a mean pulse amplitude of 10 ng/pulse, and a mean pulse duration of 0.2 h. Euthyroid rats exhibited similar fluctuations of circulating TSH levels; however, due to the variability of the TSH RIA in the range of euthyroid TSH titers, no significant pulsatility was detected by Pulsar. Mean plasma TSH levels in eu- and hypothyroid rats were 2.3 +/- 0.3 and 14.6 +/- 1.8 ng/ml, respectively. To confirm that the TRH antiserum (TRH-AS) used in the present study for passive immunization had sufficient binding capacity to absorb endogenous TRH release, euthyroid rats were pretreated with either normal rabbit serum or TRH-AS, followed by the injection of clonidine (100 micrograms/kg BW, iv). This alpha 2-adrenergic agonist caused a significant (P < 0.01) 12.7-fold rise in plasma TSH levels in normal rabbit serum-treated animals, which was completely abolished by TRH-AS pretreatment, indicating that clonidine stimulates TSH secretion via activation of hypothalamic TRH release. When TRH-AS was slowly infused into hypothyroid rats that were sampled frequently for the detection of TSH pulsatility, it caused a significant (60.3%; P < 0.01) decrease in mean TSH levels, with TSH titers approaching euthyroid concentrations 1 h after the infusion of TRH-AS. The antiserum treatment also caused the disappearance of statistically significant (Pulsar) TSH secretory pulses. Mild hypothyroidism shifted the GH secretory profiles from a low frequency, high amplitude in euthyroid animals to a high frequency, low amplitude pattern in hypothyroid rats. Mean GH levels in hypothyroid rats were 76% lower than those in euthyroid controls. These findings show that TSH is secreted in a pulsatile fashion in the hypothyroid rat and that TRH is predominantly responsible for the generation of TSH pulsatility.(ABSTRACT TRUNCATED AT 400 WORDS)     

MRI-demonstrable regression of a pituitary mass in a case of primary hypothyroidism after a week of acute thyroid hormone therapy

Although magnetic resonance imaging (MRI) characteristics of pituitary gland hyperplasia in primary hypothyroidism have been previously described, the time span necessary for the regression of the hyperplasia in response to acute thyroid hormone (TH) therapy has not been defined. A 26-yr-old woman underwent 131I ablation 11 yr before admission. Intermittent poor compliance to levothyroxine (LT4) therapy led to inappropriately high serum thyroid-stimulating hormone (TSH) for her triiodothyronine (T3) and thyroxine (T4) levels. The patient was investigated to rule out TSH-secreting pituitary adenoma or resistance to TH. On admission, the patient's clinical features and thyroid function tests, as well as thyrotropin-releasing hormone (TRH) and acute T3 suppression tests, were in favor of profound primary hypothyroidism. MRI revealed symmetrical enlargement of the pituitary gland with distinct morphological characteristics of a macroadenoma. The patient began high-dose TH therapy and was rescanned six days later. The follow-up scan revealed a dramatic shrinkage of the pituitary gland. Four weeks later, serum T4 and TSH were within the normal range, and repeat MRI scan of the pituitary at that time showed a normal gland. This case is the first to document dramatic shrinkage of pituitary hyperplasia in long-standing primary hypothyroidism within one week of acute TH therapy. MRI alone is unable to reliably differentiate between a TSH-secreting pituitary adenoma and hypothyroidism-induced pituitary hyperplasia. Dynamic endocrine testing as well as repeat pituitary MRI after a brief TH trial may provide a firm diagnosis in similar cases.     

Exogenous sphingosine 1-phosphate induces neurite retraction possibly through a cell surface receptor in PC12 cells

Alterations in thyroid function tests are very common in patients with NTI. Multiple, complex, and incompletely understood mechanisms are involved in these abnormalities. Knowledge of these abnormalities is necessary to avoid errors in the diagnosis of thyroid disease. Measurement of serum TSH, free T4, and free T3 levels by direct equilibrium dialysis/RIA methods probably yield most useful (accurate) information in the setting of NTI. Patients with low free T4 by these methods and normal or low TSH have secondary hypothyroidism. This may be due to NTI per se, drugs administered for treatment of NTI, or associated pituitary or hypothalamic disease; the latter consideration may require evaluation of cortisol reserve, PRL, and/or gonadotropins. A serum TSH level above 20-25 microU/mL probably reflects primary hypothyroidism; accompanying findings of goiter, low free T4, and positive antithyroid antibodies help establish the diagnosis. An elevated serum concentration of rT3 argues against hypothyroidism. Studies have demonstrated no discernible benefit of treatment of NTI patients with T4. Some studies have shown a few benefits of treatment with T3 in selected cases, but much more needs to be learned. There is no evidence of harm by treatment of NTI patients with up to replacement doses of T3. As some NTI patients may indeed be hypothyroid, the term ESS should be replaced with NTIS.     

Antibodies against thyroid gland peroxidase and thyroglobulin in various thyroid diseases

Autoantibodies to thyroperoxidase (anti-TPOAb) and thyroglobulin (anti-TgAb) were measured in 564 patients with various thyroid disorders and in 59 healthy subjects using chemiluminometric immunoassay. The frequency of elevated titers was 8.6% in healthy subjects, 76.2% in patients with untreated hyperthyroidism and diffuse goiter, 80.7% in patients with relapse of hyperthyroidism. 83.4% of patient with hyperfunction changed spontaneously to hypothyroidism and 71.5% of patients with hypothyroidism and goiter had antibodies above the normal range. Unexpectedly low prevalence of autoantibodies were detected in patients with primary myxoedema without goiter (48.2%) and in patients with endocrine ophthalmopathy and euthyroidism (33.2%). In the subgroup of patients with hyperthyroidism under methimazole treatment we found an incidence of positivity of 56% and the mean of positive values was lower compared with the untreated ones. In 42.8% of patients with hyperthyroidism and diffuse goiter treated successfully by methimazole, surgery or radioiodine elevated concentrations of antibodies could be detected, however they were in remission for more than five years. 197 (82.4%) of the patients with positive antibody titers showed higher concentrations to peroxidase compared with thyroglobulin. 57.9% of serum samples positive for anti-TPOAb were negative for anti-TgAb, whereas 9.4% of samples positive for anti-TgAb were anti-TPOAb negative. The diagnosis of thyroid autoimmunity could generally be based on measurement of anti-TPOAb with additional measurement of anti-TgAb in special cases.     

Medical thoracoscopy in the management of pneumothorax

In a general practice population of 11,300 patients, 223 were known to have diabetes mellitus. Thirteen diabetic patients (5.8%) had a previous diagnosis of thyroid disease. The study excluded 17 patients who received sole diabetes care at a secondary referral centre (of whom 5 had a previous diagnosis of thyroid disease), 8 with a previous diagnosis of thyroid disease receiving community care, and 1 patient who declined screening. New thyroid disease was diagnosed in 11 patients (8 female, 3 male): 5 with primary hypothyroidism, 4 with subclinical hypothyroidism, 1 with hyperthyroidism and 1 with subclinical hyperthyroidism. Thus the prevalence of undiagnosed thyroid disease in diabetic patients receiving community diabetes care was 5.5% (9.5% of female patients), and the prevalence of thyroid disease (previously known and diagnosed as a result of screening) in the entire population of diabetic patients registered in the general practice was 10.8%. These findings suggest that screening for thyroid disease should be considered in patients receiving diabetes care in the community.     

Hypothyroidism and hyperthyroidism in major depression revisited

BACKGROUND: The aim of our study was to evaluate the prevalence of thyroid abnormalities among depressed outpatients and to examine the response to treatment of those subjects with relatively low or high thyroid hormone levels. METHOD: Outpatients (N = 200) 18 to 65 years of age who met DSM-III-R criteria for major depression were screened for the presence of thyroid abnormalities using a number of thyroid indices. Of these patients, 166 were then treated openly with the antidepressant fluoxetine for 12 weeks. We assessed whether patients with relatively low or high thyroid hormone levels had a different response to treatment compared with other patients. The 17-item Hamilton Rating Scale for Depression (HAM-D-17) was administered during the study to assess changes in depressive symptoms. Thyroid function was assessed by measuring T3, T4, free T4 index (FT4I), T3 uptake (T3U), and serum thyroid-stimulating hormone (TSH) levels. RESULTS: No clinical cases of hyperthyroidism or hypothyroidism were detected. Of the patients examined, 5 (2.6%) had slightly elevated TSH levels (range, 4.7-8.2); none of these had T4 or FT4I levels below the normal range. Subnormal levels of T4 or FT4I were found in 1 subject (0.5%). T3 and T3U levels were below the normal range in a larger number of patients (7.6% and 15.0% respectively), but only 1 of these patients had elevated TSH levels. None of the patients had levels of TSH below the normal range, and only 3 subjects (1.5%) had T4 levels above the normal range. No relationship was found between response rate (assessed as either change in HAM-D-17 score or as remission of depressive symptoms with a HAM-D-17 score < or = 7 for 3 consecutive weeks) and each of the thyroid tests, even after adjusting for baseline severity of depression. CONCLUSION: In depressed outpatients, it appears that hypothyroidism and hyperthyroidism are extremely uncommon and that the presence of subtle thyroid function abnormalities does not have an impact on treatment outcome.     

Infantile and juvenile hypothyroidism with the gland in place and low radio-iodide uptake

27 hypothyroid infants of children, with a low iodine uptake in spite of a thyroid gland or thyroid tissue in normal pretracheal place, have been studied. 21 cases are related to primary thyroid involvement leading to vanishing iodine or technetium uptake. In 8 of these cases, clinical onset in late childhood, high frequency of antithyroid antibodies and of familial thyroid dysfunction were similar to those found in childhood's thyroiditis. 8 other cases had a precocious onset (first months in 6, first year in 1, second year in 1) with some pretracheal iodine uptake when first studied and no uptake at further examinations, 1 patient having received no treatment from first to second study, the others being without treatment from more than two months and certain of them receiving injections of TSH. The last 5 cases of this group were those of children born to 2 mothers with treated hypothyroidism, with low iodine uptake in pretracheal place. The role of genetic factors and auto-immunity in theses cases is discussed. The 6 other patients had clinically isolated hypothyroidism secondary to TSH deficiency, eventually associated to clinically inapparent GH or ACTH deficiencies, most of them by hypothalamic defect with normal response to TRH.     

Subclinical hypothyroidism: deciding when to treat

While screening patients for thyroid disease, physicians often find increased thyrotropin-stimulating hormone (TSH) levels in patients whose free thyroxine (T4) levels are not below normal. This state, termed "subclinical hypothyroidism," is most commonly an early stage of hypothyroidism. Although the condition may resolve or remain unchanged, within a few years in some patients, overt hypothyroidism develops, with low free T4 levels as well as a raised TSH level. The likelihood that this will happen increases with greater TSH elevations and detectable antithyroid antibodies. Because patients with subclinical hypothyroidism sometimes have subtle hypothyroid symptoms and may have mild abnormalities of serum lipoproteins and cardiac function, patients with definite and persistent TSH elevation should be considered for thyroid treatment. Levothyroxine, in a dosage that maintains serum TSH levels within the normal range, is the preferred therapy in these patients.     

Accelerated evolution of cytochrome b in simian primates: adaptive evolution in concert with other mitochondrial proteins?

We have devised a practical, sensitive and specific method for simultaneous measurement of free thyroxine (FT4) and free triiodothyronine (FT3) in undiluted serum by direct equilibrium dialysis radioimmunoassay (RIA). Two hundred microliters serum sample was dialyzed against buffer (pH 7.4) for 20 hours at 37 degrees C and approximately 800 microL of the dialysate was used for measuring FT4 and FT3 simultaneously. The assay was set up in polystyrene tubes coated with anti-T4 antibody and available commercially for FT4 measurement (Quest-Nichols Institute, San Juan Capistrano, CA). The mean +/- SE (range) FT4 concentration (ng/dL) was 1.2 +/- 0.04 (0.7.0 to 2.30) in 54 normal subjects. It was significantly increased (3.6 +/- 0.4 [1.8 to 9.6], n = 20) in hyperthyroidism and clearly decreased (0.40 +/- 0.04 [1.10 to 0.70], n = 26] in hypothyroidism. All nonthyroid illness (NTI) patients had normal FT4 except 3, 2 of whom were on amiodarone and 1 had received heparin. Serum FT4 concentration was minimally elevated in 18 newborn cord blood serum (1.40 +/- 0.08 [0.90 to 2.2], cf. normal p < .05). The mean serum FT3 concentration (pg/dL) was 285 +/- 10 (134 to 454) in 54 normal sera. It was clearly increased in hyperthyroidism (1033 +/- 98 [593 to 2134], n = 20, p < .001). However, serum FT3 varied widely in hypothyroidism (27 to 597, mean 235 +/- 24, NS) as did serum total T3 (19 to 175). Interestingly, however, the mean serum FT3 concentration was normal (273 +/- 28 [62 to 575, NS]) in 25 NTI patients. All of these patients had low serum total T3 (46 +/- 5.0 [10 to 84], ng/dL; normal 84 to 160, p < 0.001), while FT3 was clearly normal in 21 of 25 patients and low in the remaining 4 patients. Similarly, among 18 newborn cord blood sera serum FT3 concentration was normal in 15 and subnormal only in the remaining 3 while all had clearly subnormal total T3 (28 to 74 ng/dL). CONCLUSIONS: (1) A practical, sensitive, and specific assay for simultaneous measurement of FT4 and FT3 is described; (2) FT3 is consistently elevated in hyperthyroidism while FT4 is elevated in most (approximately 85%) cases; (3) FT4 is consistently decreased in hypothyroidism but FT3 varies widely; (4). Serum FT3 concentration is normal in approximately 83% of patients with the low T3 syndrome in NTI and newborn cord blood serum. These data suggest that normal FT3 may explain clinical euthyroidism in many patients with the low T3 syndrome.