Hormone profile of hypothyroidism in an area of the Central African Republic with endemic goiter]

In the Ouham region of Centro African Republic, one of the present Authors (B.P.) described a severe goiter endemia due to marked iodine deficiency and high daily intake of manioc as staple food. In the present study serum TSH, T3 and T4 of 233 subjects were determined; 150 of them lived in rural villages (Group 1) and 83 lived in Bocaranga, chief town of the province (Group 2). The blood samples done contemporaneously to the epidemiological survey, were strictly randomized in the population examined. The subjects of each group were divided in 4 sub-groups: A) with TSH, T3 and T4 in normal range; B) with elevated TSH; C) with elevated TSH and sub-normal T4; D) with elevated TSH and sub-normal T3 and T4. An apparently euthyroid pattern of TSH, T3 and T4 was evident in only 60 subjects (19.3% from group 1; 37.35% from group 2); the remaining 173 (80.67% from group 1; 62.65% from group 2) were hypothyroid (subclinical in the sub-group B; mild in the sub-group C; overt in the sub-group D). The mean hormonal values of the apparently euthyroid subjects (sub-group A) in the villages and in the chief town, were significantly different (p less than 0.05) from the control values of our laboratory. More significant differences were clearly evident between the control values and the mean values of sub-groups B, C and D in each of the two groups (1 villages; 2 chief town).(ABSTRACT TRUNCATED AT 250 WORDS)     

Screening of geriatric patients for thyroid dysfunction with thyrotropin-releasing-hormone test, sensitive thyrotropin and free thyroxine estimation

Hospitalized geriatric patients (N = 354) from an iodine-deficient area were screened with sensitive thyrotropin (TSH), free and total thyroxine (FT4, T4) and total triiodothyronine (T3) to determine the occurrence rate of clinical and subclinical thyroid dysfunction. The diagnostic value of the tests was compared to each other and to that of the thyrotropin-releasing-hormone test (TRH-test) in order to find the optimal first line screening test in geriatric patients. Clinical hyperthyroidism was found in 13, subclinical hyperthyroidism in 10, overt hypothyroidism in 6 and subclinical hypothyroidism in 8 cases. 20.6% of the patients were euthyroid but had subnormal TSH response to TRH, as a sign of possible thyroid autonomy. The low occurrence rate of clinical thyroid disorders (4.8%) does not justify the screening of geriatric patients in general, but the high probability of thyroid autonomy makes reasonable the investigation of every geriatric patient before iodine administration. Suppressed basal TSH and high FT4 were found to be both sensitive and specific in diagnosing clinical hyperthyroidism, but the predictive value was insufficient; elevated T4 and T3 are specific, but not sensitive. Basal TSH is sensitive, specific and has a good predictive value in diagnosing euthyroidism, whereas normal T4, FT4 or T3 are not specific enough for euthyroidism. Basal TSH is better as a first line test of thyroid function than FT4. A normal basal TSH confirms euthyroidism by itself. Other tests (TRH test, T4, FT4, T3) are necessary to elucidate the clinical importance of a subnormal or suppressed basal TSH.     

Interaction of Copper with Iron, Iodine, and Thyroid Hormone Status in Goitrous Patients

In many developing countries, men and women are at high risk of goiter and iron deficiency. The aim of the recent study is to assess the interaction of (Cu), with iron (Fe), iodine/iodide (I), and thyroid hormones in goitrous patients. Sixty goitrous male (GMPs) and 72 female patients (GFPs) were evaluated for the Cu, Fe, I, and thyroid hormones status in biological samples (serum and urine), and compared to non-goitrous subjects of both genders (M?=?106, F?=?120). The biological samples were analyzed for Cu and Fe concentration using atomic absorption spectrometer, while I was measured by the potentiometric method, prior to microwave-assisted acid digestion (MD). Quality control for the method was established with certified samples. Significantly higher mean values of Cu in serum, and urine samples of GMPs and GFPs, while lower value of Fe and I were observed as compared to control subjects (p?<?0.015), respectively. The mean values of free triiodothyronine (FT3) and free thyroxin (FT4) were found to be lower in goitrous patients of both genders than in the age-matched healthy controls (p?<?0.006 and 0.002), respectively, in contrast high mean values of thyroid-stimulating hormone (TSH) were detected in patients (p?<?0.009), as compared to non-goitrous subjects. It was observed that the deficiencies of Fe, I, and thyroid hormone in goitrous patients could be influenced by efficiency of Cu.     

Changes in serum T4, T3 and TSH concentrations in newborns and infants with congenital goiter from the Mazovia region.

Thyroid function was investigated in a group of 61 newborns with congenital goiter before starting the therapy with thyroid hormones. The group included 19 girls and 42 boys, of which 27 were of age not exceeding one week (group I), 19 were between the first and the second week (group II), and 15 were between the second week and the third month of life (group III). The concentrations of the thyroid hormones were determined by radioimmunoassay. The values obtained have been compared with the local reference range obtained for the newborns of the Mazovia region. The values remaining outside the reference range were found in 47.5% of the newborns studied. The elevated values of TSH were observed mainly in group I newborns (12 from 27); among group II newborns there was only one with the elevated values, and none among the newborns of group III. thyroxine (T4) values were lowered in 14 among 27 newborns of group I, and in 2 among 19 newborns of group II; all T4 values were normal in group III. The percentage of the elevated values of triiodothyronine (T3) was higher in older newborns (group III). The elevated level of T3 accompanied by the lowered level of T4 with the normal or moderately elevated level of TSH is characteristic for the adaptation to the deficiency of iodine. There is preferential secretion of T3 aimed at maintaining euthyreosis. The elevated levels of T3 found in 30% of newborns with untreated goiter suggest an intrauterine deficit of iodine as a cause of the goiter appearance.(ABSTRACT TRUNCATED AT 250 WORDS)     

10 years of successful treatment with dextrothyroxine in a girl with TSH-induced hyperthyroidism.

14 years ago, a 5.7-year-old healthy girl was treated with desiccated thyroid for a goiter and elevated TSH levels. The goiter disappeared and TSH levels were normalized. However, hyperthyroidism appeared. Without therapy, the goiter reappeared and hyperthyroidism aggravated. Based on hormone values, TSH-induced hyperthyroidism was diagnosed. After exclusion of neoplastic TSH secretion, treatment with dextrothyroxine (DT4) was initiated at age of 10 years and continued during the last 10 years (except for short periods). The girl became euthyroid, has no goiter and normal TSH values. Since thyrotrophs and peripheral tissues are probably normally sensitive to T4, we postulate that her hypothalamopituitary-thyroid control is operating on a higher set point level for T4.     

Autosomal recessive inheritance of congenital goiter in Afrikander cattle

Congenital goiter was reported in a number of herds of Afrikander cattle in the 1950's. Some affected animals were assembled and maintained as a closed herd. Although considerable biochemical research into the nature of the disease has been conducted, no definitive report has described the mode of inheritance of the defect. This paper presents the results of breeding studies that indicate the defect is inherited as an autosomal recessive. Southern blot analysis of the thyroglobulin gene confirms this finding. In addition, serum levels of TSH (thyroid stimulating hormone, thyrotropin), T3 (3,4,3'-tri-iodothyronine), T4 (thyroxine), rT3 (3,3',5'-tri-iodothyronine), and DIT (diiodotyrosine) of goitrous animals are compared with normal animals.     

Influence of D-thyroxine on plasma thyroid hormone levels and TSH secretion.

Triiodothyronine (T3), thyroxine (T4), basal TSH and TSH after stimulation with TRH were determined in healthy subjects and patients treated with D-thyroxine (DT4). After a dosage of 6 mg DT4 the D/L T4 plasma concentration rose about 4-fold 4 hours after application and was only moderately elevated 14 hours later. To achieve constantly elevated T4 levels 3 mg DT4 were applied in the further experiment every 12 hours. The D/L T4 plasma concentration rose 2.5-4-fold and there was a small but significant increase of the D/L T3 plasma concentration. 74 hours after onset of treatment basal TSH was below detectable limits and the increase of TSH 30 min after injection of 200 mug TRH (TRH test) was only about 15% compared to zero time. The time course of TSH suppression was investigated after treatment with DT4 and LT4 (single dosage of 3 mg). TRH-tests were performed before, 10, 26, 50 and 74 hours after the first dosage of D or LT4. There was no difference in the time course of basal TSH and TSH stimulated by TRH. In 10 patients on DT4 long-term therapy, basal and stimulated TSH were found to be below the detectable limits of 0.4 mug/ml. Our results show that (1) plasma half-life of DT4 is less than 1 day, (2) TSH suppression after D and LT4 treatment is very similar, and (3) in patients on long-term DT4 treatment, TSH plasma concentration is below detectable limits even after stimulation with TRH.     

The pituitary-thyroid axis in patients with pituitary disorders

The pituitary-thyroid axis of 12 patients, exposed to transsphenoidal pituitary microsurgery because of nonfunctioning adenomas (6), prolactinomas (3) and craniopharyngioma (1), or to major pituitary injury (1 apoplexy, 1 accidental injury), was controlled more than 6 months following the incidents. The patients did not receive thyroid replacement therapy and were evaluated by measurement of the serum concentration of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), T3-resin uptake test and thyrotropin (TSH, IRMA method) before and after 200 micrograms thyrotropin releasing hormone (TRH) iv. The examination also included measurement of prolactin (PRL) and cortisol (C) in serum. Apart from 1 patient with pituitary apoplexy all had normal basal TSH levels and 9 showed a significant TSH response to TRH. Compared to 40 normal control subjects the 12 patients had significantly decreased levels of T4, T3 and rT3 (expressed in free indices), while the TSH levels showed no change. Five of the patients, studied before and following surgery, had all decreased and subnormal FT4I (free T4 index) after surgery, but unchanged FT3I and TSH. The levels of FT4I were positively correlated to both those of FT3I and FrT3I, but not to TSH. The TSH and thyroid hormone values showed no relationship to the levels of PRL or C of the patients exposed to surgery. It is concluded that the risk of hypothyroidism in patients exposed to pituitary microsurgery is not appearing from the TSH response to TRH, but from the thyroid hormone levels.     

Variation of the thyrotropin-releasing-hormone (TRH) stimulated thyrotropin (TSH) response in comparison with the tyhroid-gland-suppression test and the triiodothyronine (T3) and thyroxine (T4) blood levels in the so-called euthyroid endocrine ophthalmopathy]

21 patients with active signs of euthyroid Graves' disease were given 400 mug thyrotropin-releasing hormone (TRH) i.v. All subjects with unresponsiveness to TRH had a nonsuppressible thyroidal 131I-uptake. On the basis of serum total T3 14 patients were hyperthyroid, 2 more had an elevated value of free T3. 4 patients with normal total T3 and nonsuppressible 131I-uptake were unresponsive to TRH, in 2 of them the free T3 fraction was elevated, however. 4 subjects with nonsuppressible 131I-uptake had a TRH stimulated TSH response. 2 of these subjects had hyperthyroid values of free and total T3 in serum and responded to TRH with an exaggerate TSH increment. The variations of TRH responsiveness may demonstrate a different threshold of the pituitary and the peripheral T3 receptors.     

Normalization of thyroid stimulating hormone levels in acromegalic patients after selective adenomectomy

Changes in TSH secretion in six acromegalic patients were studied before and after transsphenoidal adenomectomy (Hardy's method) and compared to normal subjects and six patients with prolactinoma. Basal serum GH levels ranging from 5 to over 250 ng/ml before adenomectomy decreased to below 5 ng/ml after the operation, and the abnormal responses of GH to TRH observed initially in three of the six patients almost disappeared in the post-adenomectomy period. The response of serum TSH to TRH in acromegalic patients improved in each of the six patients after the operation. The TRH-stimulated TSH secretion in patients with prolactinoma of a size and grade similar to those in acromegalic patients was not so extremely low as that in the acromegalic subjects. As indicators of thyroid function, serum triiodothyronine (T3), thyroxine (T4), T3-uptake levels and free T4 indices did not change significantly after adenomectomy as compared with those before the operation in five of the six patients tested. Serum T3, T4 and T3-uptake levels and free T4 indices before adenomectomy were normal or subnormal in each patient except for a high serum T4 level and free T4 index before the operation in only one patient. Thus, it is difficult to conclude that the function of thyrotrophs was decreased by pressure upon the intact pituitary gland by the tumor, or that the thyroid gland also became hypertrophic secondary to the elevated GH, resulting in a large quantity of thyroid hormone being secreted, which caused a suppression of TSH secretion by negative feedback.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pituitary-thyroid axis reactivity to hyper- and hypothyroidism in the perinatal period: ontogeny of regulation of regulation and long-term programming of responses.

To evaluate the role of perinatal thyroid status in the development of pituitary-thyroid axis regulation, we administered triiodothyronine to newborn rats for the first five days postpartum to achieve hyperthyroidism, or propylthiouracil perinatally to rat dams and pups from gestational day 17 through postnatal day 5 to achieve hypothyroidism. Plasma T4, T3, and TSH levels were determined from birth through 50 days postpartum. Administration of exogenous T3 produced the expected immediate suppression of plasma T4 and TSH, with recovery toward normal values beginning within days of discontinuing the T3 regimen. Plasma T3 values were markedly elevated during the period in which T3 was being given, but subsequently became subnormal, with deficits persisting into young adulthood. With the PTU regimen, plasma T4 and T3 levels were markedly suppressed through postnatal day 10, rose over the ensuing two weeks, but nevertheless showed significant deficits into adulthood. TSH levels in the immediate neonatal period were subnormal in the PTU group, despite the marked lowering of circulating thyroid hormones; TSH then rose dramatically to levels four times normal, subsiding to control values by the end of the first month. These results suggest that a critical period exists in which regulation of pituitary-thyroid axis function is programmed. During this phase, TSH secretion can be suppressed by excess thyroid hormones, but cannot be increased by hormone deficiencies. Perhaps more importantly, perinatal thyroid status "programs" its own future reactivity, so that early hypothyroidism results in reduced T4 and T3 levels in adulthood, despite normal levels of TSH.     

Goiter prevalence,serum selenium,and urine iodine status in a previously iodine-deficient area in Turkey

This study was planned to investigate goiter prevalence and serum selenium and urine iodine status among school-age children in the Ankara region of Turkey. Nine hundred five (905) children were investigated; 847 of them were included in the study. Thyroid ultrasound was performed on children who were suspected of being goitrous at physical examination. Serum TSH, thyroxine, triiodotyronine, thyroid antibody, and urine iodine concentrations (UIC) are also measured. Ultrasound measurements revealed a goiter in 107 (12.6%) of the 847 children. Goiter prevalence was significantly lower among iodized-salt users compared to the noniodized salt using group. UIC and serum selenium levels in the goitrous group were significantly lower compared to the nongoitrous group. Despite legally enforced table salt iodization, the region shows the characteristics of mild iodine deficiency. In addition to lower UIC, goitrous children have lower serum selenium levels compared to the nongoitrous ones. Thus, selenium deficiency plays an important role in goiter endemics in Turkey. It can be postulated that table salt iodization might not be enough for the preventive measures of goiter, but informing people about the correct ways of iodized salt consumption, enforcing the iodization of industrial salts, and, as important as these measures, taking selenium deficiency into consideration are essential for preventing goiters in endemic areas.     

Seasonal changes in circadian rhythms of body temperatures in humans living in a dry tropical climate

Seven volunteers (3 females and 4 males; 3 Caucasians and 4 Africans) participated in two 24 h sessions during the cool dry (CD) and the hot dry (HD) seasons of the sahelian tropical climate. Body temperatures were taken on portable cassette recorders for 24 h. Rectal (Tre) and mean skin (Tsk) temperatures decreased in the HD compared to the CD conditions, meeting one of the criteria for adaptation to heat. No ethnic differences in thermal responses were found. Males and females differed in their body temperature rhythms and in their reactions to heat. Body temperatures were higher in females than in males. Males reacted to heat with a decrease in Tre, without change in the Tre-Tsk gradient. Females showed a decrease in both Tre and Tsk, more marked for Tsk, with an increase in the Tre-Tsk gradient. It was concluded that males showed seasonal acclimatization to heat via a decrease in metabolism confirmed by a decrease in plasma levels of thyroid stimulating hormone (TSH) in the HD condition. Females showed a mixed metabolic and thermolytic type of acclimatization, with an absence of variation in plasma TSH levels. In conclusion, the steady rise in temperature between the CD and HD conditions was sufficient to trigger an acclimatization to heat similar in Caucasian and African subjects, although exposure to the external climate differed widely.     

Concomitant association of thyroid sarcoidosis and Graves' disease

OBJECTIVE: Graves' disease (GD) with sarcoid involvement of the thyroid gland has rarely been reported. METHOD: We report a case of GD with thyroid sarcoidosis in a 28-year-old woman. Thyroid function was assessed by triiodothyronine (T(3)), thyroxine (T(4)), thyroid-stimulating hormone (TSH) and TSH receptor antibodies (TSH-R Ab). Thyroid scintigraphy, ultrasound and fine-needle aspiration biopsy were performed. The patient underwent surgery. RESULT: The patient had a nodular goiter. Serum T(3), T(4) and TSH-R Ab levels were elevated with suppressed TSH level. Scintigraphy showed diffuse activity as seen in GD, and ultrasound revealed that parenchyma was heterogenous. Sarcoidosis was discovered on routine chest X-ray. Although no sarcoid involvement was found on specimen, the thyroid gland showed non-caseating granulomas on histology. CONCLUSION: Since sarcoid involvement of the thyroid gland can cause hypofunction, we report the uncommon infiltration of sarcoidosis with hyperthyroidism.     

Cytologic characterization of postiodization residual goiter in schoolchildren by fine needle biopsy

OBJECTIVE: To determine the relevance and utility of fine needle biopsy (FNB) for providing a tissue-level diagnosis during a community-based survey of postiodization residual goiter in schoolchildren in India. STUDY DESIGN: A total of 14,762 schoolchildren (56.0% girls and 44.0% boys), aged 6-18 years, with a countrywide representation, were clinically screened for the presence of goiter. FNB was performed under field conditions by means of a nonaspiration technique from both lobes of goitrous glands. The cytologic diagnosis and findings were correlated with age, sex, goiter grade and biochemical parameters of serum T4, TSH, thyroid microsomal (TMA) and thyroglobulin (TGA) antibodies. RESULTS: The overall prevalence of goiter was 23.0%, with a greater frequency in girls (27.1%) than boys (17.8%). FNB was successful in 75.6% of subjects without any significant complications. The cytologic diagnoses in 1,312 successful cases were colloid goiter (92.8%), Hashimoto's thyroiditis (4.6%), focal lymphocytic thyroiditis (1.7%) and hyperplastic goiter (0.9%). Autoimmune thyroiditis (AIT), which accounted for only 6.3% cases, showed a strikingly different age-specific prevalence between girls and boys. Serologic markers of TMA and TGA at various titers were observed to lack requisite sensitivity and specificity for establishing an accurate diagnosis of AIT. CONCLUSION: The nonaspiration technique of FNB is capable of yielding valuable diagnostic information during an epidemiologic survey of goiter. The technique can be easily performed under field conditions on children without significant complications. FNB is preferable to serologic markers for accurate diagnosis of AIT. A relatively low frequency of AIT, as observed in the present study, raises the possibility of a significant role of environmental goitrogens as the underlying pathogenetic factor in postiodization residual goiter in Indian schoolchildren.     

Oxidative DNA base damage, antioxidant enzyme activities and selenium status in highly iodine-deficient goitrous children

The objective of this study was to investigate oxidative DNA damage, and the levels of antioxidant enzymes (AOE) and selenium (Se) in relation to iodine deficiency and/or goiter in children. The study was performed in a group of goitrous high school children (15-18 years of age) ( n =14) with severe or moderate iodine deficiency. Thyroid hormones (TSH, FT 4 , TT 4 , FT 3 , TT 3 ), urinary iodine (UI) and plasma Se levels, and erythrocyte glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT) activities were determined and compared with those of a control group consisting of non-goitrous high school children ( n =14) with normal UI levels or mild iodine deficiency. In the goitrous group, concentrations of FT 4 , TT 4 , plasma Se and UI, and activities of GSHPx and SOD were found to be significantly lower. Six typical hydroxyl radical-induced base lesions in genomic DNA of peripheral blood were identified and quantified by gas chromatography/isotope-dilution mass spectrometry (GC/IDMS), and higher levels of DNA base lesions were observed in the goitrous group. The results suggest that highly iodine-deficient goitrous children may be under oxidative stress, which may lead to greater level of oxidative damage to DNA. This study supports the evidence for the reported relationship between iodine deficiency and the increased incidence of thyroid malignancies.     

Pituitary resistance to thyroid hormone--a case report

Pituitary resistance to thyroid hormone is a very rare cause of hyperthyroidism. It is characterized by normal, or elevated TSH concentration with high concentration of T3 and T4. Here, we present a case of a 24-year-old woman who suffered from mild thyrotoxicosis and diffuse goiter for several years. She had elevated fT3 and fT4 with slightly elevated TSH concentration. Pituitary adenoma was excluded as magnetic resonance imaging showed normal pituitary gland, alpha subunit was within normal range and TSH concentration increased after TRH administration. Sonography revealed normoechogenic, slightly enlarged thyroid gland. Previously, she was given thiamazole, but without any significant amelioration. Thus, the diagnosis of the syndrome of pituitary resistance to thyroid hormone was established. The patient was given bromocriptine at a dose of 10 mg per day. After 2 months of treatment she achieved a state of constant euthyrosis and following next few months thyroid volume diminished.     

Evaluation of Iron in Serum and Urine and their Relation with Thyroid Function in Female Goitrous Patients

In many developing countries, women are at high risk of goiter and iron deficiency anemia (IDA). Iron deficiency adversely affects thyroid metabolism and may decrease the efficiency of thyroid hormones in areas of endemic goiter. The aim of the present study was to compare the level of iron (Fe) in biological samples (serum and urine) and serum thyroid hormones, thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxin (FT4) of goitrous female patients (GFPs; n = 69) with those of nongoitrous women as control subjects (n = 117), age range 21–45 years. The biological samples were analyzed for Fe concentration using flame atomic absorption spectrophotometer, prior to microwave-assisted wet acid digestion. The validity and accuracy of the method was checked by the certified sample and with those obtained by conventional wet acid digestion method on the same CRM and real samples. The overall recoveries of Fe in serum and urine were found in the range of 97.2–98.6% of certified values. The results of this study showed that the mean values of Fe in serum and urine samples of GFPs were significantly reduced as compared to control subjects (p = 0.002 and p = 0.015, respectively). The mean values of FT3 and FT4 were found to be lower in GFPs than in the age-matched healthy control women; in contrast, high mean values of TSH were detected in GFPs (p = 0.003). There was a positive correlation between serum Fe concentration and TSH (r = 0.85, p = 0.01), FT3 (r = 0.95, p = 0.003), and FT4 levels (r = 0.98, p = 0.007) in GFPs. It was observed that iron deficiency is prevalent in GFPs, so the need of Fe supplementation will be required to improve the efficacy of thyroid metabolism in goitrous women.     

A case of the syndrome of inappropriate secretion of TSH.

A girl aged 4 years with goiter and accelerated physical and skeletal growth was found to be hyperthyroid on the basis of elevated serum thyroid hormone level, nevertheless both the basal TSH and TSH responsiveness to TRH were maintained within the normal range. Serum TSH was suppressed by exogenous T3 and dexamethasone administration, but not significantly changed after propylthiouracil (PTU) treatment. The diurnal rhythmicity of anterior pituitary hormones was preserved with the high nocturnal peak of TSH and prolactin. Clinically, neither thyrotoxic signs nor evidences of pituitary tumor were observed. Her accelerated growth and elevated thyroid hormone level appeared to be induced by inappropriate secretion of TSH. In view of the literature, this is the first case of the syndrome of inappropriate secretion of TSH excluding the neoplastic origin in Japan.