Unconjugated bisphenol A cord blood levels in boys with descended or undescended testes.

BACKGROUND: Human toxicity of bisphenol A (BPA), a weak estrogenic environmental endocrine disrupting compound, widely used in plastics, baby bottles, cans and dental sealants, is under investigation. Fetal or perinatal exposure in rodents is associated with programmed adult reproductive diseases. Human epidemiological studies remain scarce, especially concerning testicular development. We have investigated the relationship between fetal exposure to BPA and cryptorchidism. METHODS: Using a radioimmunoassay performed after extraction, validated by high-performance liquid chromatography and mass spectrometry, active levels of unconjugated BPA (uBPA) in cord blood (CB) were measured in 152 boys born after 34 weeks gestation, with cryptorchid or descended testes. RESULTS: Active uBPA was detectable in all CB samples, with values in the control group (n = 106) of 0.14-4.76 ng/ml, median: 0.9 ng/ml; mean ± SD: 1.12 ng/ml ± 0.86 ng/ml, which did not differ from cryptorchid boys (n = 46, 1.26 ± 1.13 ng/ml, P = 0.38). uBPA in controls correlated with CB inhibin B (P < 0.01) and total testosterone (P < 0.05), and with maternal milk polychlorinated bisphenyl 138 (P < 0.03). uBPA did not correlate with clinical maternal or fetal parameters or with other steroid or polypeptide CB hormones assessed. CONCLUSIONS: The presence of uBPA in all CB samples suggests placental transfer and fetal exposure. Similar uBPA levels in the control and cryptorchid groups make the participation of fetal exposure to uBPA in the physiopathology of undescended testes unlikely. However, the observed nanomolar uBPA concentrations support assessment of epidemiological relationships between CB uBPA and other human diseases.

Prospective study on the prevalence and associated risk factors of cryptorchidism in 6246 newborn boys from Nice area, France.

To assess the incidence and risk factors of cryptorchidism in Nice area. A 3-year prospective study was conducted at two maternity wards involving neonatal screening of boys born ≥34weeks of amenorrhoea. Methodology was strict with examination at birth, 3 and 12months by the same paediatrician. Two strictly matched controls were included for each case. Information on child and parents (medical history, pregnancy, lifestyle) was recorded using medical chart and self-administered questionnaires. A total of 102 of 6246 boys were born with cryptorchidism (prevalence 1.6%, 95 included). Half of them were still cryptorchid at three and 12months with, however, 10% of secondary re-ascent (recurrent cryptorchidism) at 12months, justifying long-term follow-up. Cryptorchidism at birth was associated with instrumental delivery, inguinal hernia and urogenital malformations, particularly micropenis and paternal history of cryptorchidism. Our results suggest that maternal exposure to anti-rust or phthalates could be a risk factor, whereas eating fruits daily seemed somewhat protective. Prevalence of cryptorchidism in our area is on the lower bracket compared with other countries, and is associated with both familial and environmental risk factors.

[Iodine status and thyroid function of 330 pregnant women from Nice area assessed during the second part of pregnancy]. / Statut iodé et fonction thyroïdienne chez 330 femmes de la région niçoise évaluées en deuxième partie de grossesse.

BACKGROUND: Iodine deficiency (ID) is still common in Western Europe and its prevention remains a challenge, particularly during pregnancy. METHODS: We studied 330 pregnant women in the third trimester of pregnancy for ioduria (UIE) and thyroid tests (TSH, fT4). We collected information on personal history of thyroid disease and treatment with thyroid hormones or iodinated pregnancy tablets. RESULTS AND DISCUSSION: Median UIE was 64 microg/l, reflecting inadequate iodine intake in our population. According to the UIE threshold used for diagnosis (100 to 150 microg/l), ID was present in 74.3% to 85.8% of women; 5.4% had excessive iodine intake, including one taking iodine fortified tablets. Only 8.8% had adequate intake, suggesting that current strategies to eradicate ID are inefficient in our country. Among the 22 women taking iodine supplements, only three had adequate UIE and four had UIE below the detection level, which could suggest either poor compliance or insufficient supplementation. Median fT4 was 12.3pmol/l (8-20.1) and TSH 1.93mUI/l (0.24-6.57). We used different thresholds proposed in the literature to diagnose: hypothyroxinemia: 41.2% were less than 12pmol/l, 10% less than 10.3pmol/l and 1.8% less than 9pmol/l (lower limit of our reference range); subclinical hypothyroidism: 26.3% had TSH greater than 2.5 or 3.9% greater than 4mUI/L, 1.2 to 13% had combined low fT4 (<9pmol/l or <12pmol/) and higher TSH (>2.5mUI/l). There was no correlation between UIE and thyroid tests, nor maternal predicting factors for ID. CONCLUSION: ID is common in our population. The wide range of hypothyroxinemia and subclinical hypothyroidism prevalence should also trigger reflection of diagnostic thresholds and therapeutic intervention.

[Environmental endocrine disruptors and breast cancer: new risk factors?]. / Perturbateurs endocriniens environnementaux et cancer du sein : de nouveaux facteurs de risque ?

Human epidemiological studies and experimental animal data strongly suggest that xenobiotics with estrogenic activity may participate in to the increasing incidence of breast cancer, the most frequent cancer all around the world. Several reports have since 15 years reported positive correlations between blood or peritumoral adipose tissue levels of persistent organic compounds including organochloride pesticides and breast cancer risk. Moreover, fetal or perinatal exposition to low doses of such endocrine disruptors induce premalignant or malignant transformation of adult mammary gland in rodents. However, this environmental endocrine disrupter hypothesis still needs to be demonstrated. Further human studies are needed which will consider the exposition window, the association of several xenoestrogens, the molecular mechanisms involved and the possible individual genetic susceptibility in order to identify pertinent biomarkers and to define acceptable environmental concentration levels for agricultural or industrial chemical new products to be used.

[Environmental pollutants in maternal milk and cryptorchidism]. / Polluants environnementaux dans le lait maternel et cryptorchidie.

OBJECTIVE: Numerous maternal lipophilic compounds are eliminated into milk during lactation, their concentrations reflecting fetal in utero exposure. Some of them are endocrine disruptors. Their role in the occurrence of genital malformation, dysfunction or cancer has been suggested. We wanted to study the exposure of our population and its potential association with cryptorchidism, as few clinical studies are available. PATIENTS AND METHODS: Over three years, we screened for cryptorchidism all boys born alive at or above 34 weeks of gestational age, in two maternity wards (CHU Nice, CHG Grasse). Cryptorchid boys were matched with two controls. Nursing mothers provided a colostrum sample that was screened for 15 compounds known for their antiandrogenic and/or anti estrogenic properties, including dichloro-diphenyl-trichloro-ethylene (DDE), polychlorinated biphenyls (PCBs), dibutylphthalate (DBP) (& metabolite monobutylphthalate-mBP) and hexachlorobenzene (HCB). RESULTS: Out of 6246 boys, 102 were cryptorchid (1.6%). All available colostrums (56 for cryptorchid and 69 for controls) were contaminated. Median concentrations of DDE, PCBs, HCB and phthalates were higher though not significantly in cryptorchid versus controls. Cryptorchid boys were more likely to be classified in the most contaminated groups for DDE and SigmaPCBs, with a trend for mBP. Odds ratio (OR) for cryptorchidism was increased for the highest score of SigmaPCB, with a trend only for DDE versus the lowest score of those components. Our results are similar to those of a Scandinavian study with comparable design. DISCUSSION AND CONCLUSIONS: Our results show the universal contamination of milk with endocrine disruptors in our area, and support the association between congenital cryptorchidism and fetal exposure to PCBs and possibly DDE, alone or in association with other chemicals.

Unilateral testicular tumour associated to congenital adrenal hyperplasia: Failure of specific tumoral molecular markers to discriminate between adrenal rest and leydigioma.

Testicular adrenal rest tumours are frequently associated with congenital adrenal hyperplasia (CAH). These ACTH-dependent tumours cannot be easily distinguished histologically from Leydig-cell tumours. We report the case of a 30-year-old man who was explored for infertility, azoospermia and unilateral testicular tumour. High levels of 17-OH progesterone and ACTH, low cortisol and undetectable gonadotropins levels, associated to bilateral adrenal hyperplasia, led to the diagnosis of CAH by 21-OH deficiency with a composite heterozygoty. The testicular tumour was first considered as adrenal rest. However, histological analysis of this unilateral painful tumour showed a steroid-hormone-secreting cell proliferation with atypical and frequent mitosis. To discriminate between a benign adrenal rest tumour and a possible malignant leydigioma, tumoral expression of specific gene products was analyzed by RT-PCR. No 11-beta-hydroxylase nor ACTH receptor mRNAs could be found in the tumour, which did not behave like usual adrenal rest cells. For this unilateral testicular tumour, the lack of adrenal-specific markers associated with a high rate of mitosis and pleiomorphism supported a leydigian origin with malignant potential. However, lack of tumoral LH-R mRNA expression and a tumour-free 3-year follow-up led us to retain the diagnosis of adrenal rest tumour with loss of adrenal gene expression and progressive autonomous behaviour.

[Malignant struma ovarii: false positive PET image for suspected metastasis due to sarcoidosis]. / Goitre ovarien malin: faux positif du TEP-scan lié à une sarcoïdose.

Struma ovarii is an ovarian teratoma mainly composed of thyroid tissue, which can become malignant with possible peritoneal dissemination or even distant metastases. Therapeutic management follows protocols used for thyroid cancer. We report the first use of (18)F-fluorodeoxyglucose positron emission tomography (PET) in the follow-up of malignant struma ovarii with persistently elevated serum thyroglobulin level and negative diagnostic iodine 131 whole body scan after thyroidectomy and four courses of 131 iodine. Hilar and mediastinal lymph node uptake was detected but histological verification concluded that there was a false-positive localization corresponding to sarcoidosis lesions without malignant aspect.

Thyrotropin-secreting pituitary tumors: diagnostic criteria, thyroid hormone sensitivity, and treatment outcome in 25 patients followed at the National Institutes of Health.

We report a large series of 25 patients with TSH-secreting tumors (23 macroadenomas) followed at the NIH. Hyperthyroid symptoms were severe in 14 patients, mild in 8, and absent in 3. Patients were divided into 2 groups according to whether their thyroid had been treated (n = 11) or not (n = 14). In untreated patients, the classical diagnostic criteria (unresponsive TRH test, high alpha-subunit, and high alpha-subunit/TSH ratio) were present, respectively, in 10, 8, and 12 cases (sensitivity, 71%, 75%, and 83%; specificity, 96%, 90%, and 65%). In treated patients, the respective sensitivities of the TRH test, alpha-subunit, and alpha-subunit/TSH ratio were 64%, 90%, and 90%, and their specificities were 100%, 82%, and 73%. Studies of thyroid hormone action revealed no evidence of acquired resistance to thyroid hormone in TSH-secreting tumors. Apparent cure was achieved in 35% of cases by surgery alone and in 22% more by combined therapies. Three deaths occurred, including 1 from metastatic thyrotroph carcinoma. Six patients had residual tumor, with symptoms of hyperthyroidism controlled with octreotide in 5. The size and invasiveness of the tumor, duration of symptoms, and intensity of hyperthyroidism were the main prognostic factors. Thus, early diagnosis and treatment are the keys to a good outcome.

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.

A "hot spot" in the Pit-1 gene responsible for combined pituitary hormone deficiency: clinical and molecular correlates.

Pit-1 is a member of the POU family of transcription factors regulating mammalian development. Pit-1 is thought to be the major cell-specific activator of both the somatotrophs and lactotrophs in the anterior pituitary. When bound to DNA, Pit-1 activates GH and PRL gene expression. Pit-1 is also important for hormonal regulation of the PRL and TSH-beta genes by TRH and cAMP. We studied two unrelated patients with GH, PRL, and TSH deficiencies. Both patients have the same point mutation in the POU homeodomain of the Pit-1 gene (R271W). Patient 1 was studied as an adult and had combined deficiencies of GH, PRL, and TSH. Patient 2, who was studied in infancy, also had GH and PRL deficiencies, but had low thyroid hormone levels with a measurable basal level of TSH and a delayed response of TSH to TRH. Consequently, the current description of Pit-1 gene mutations leading to complete GH, PRL, and TSH deficiencies needs to be expanded to GH and PRL deficiencies associated with a compromise of the thyrotroph's ability to synthesize TSH.

Screening of candidate oncogenes in human thyrotroph tumors: absence of activating mutations of the G alpha q, G alpha 11, G alpha s, or thyrotropin-releasing hormone receptor genes.

Activating mutations encoding substitutions at positions Arg201 and Gln227 of the alpha-subunit of the stimulatory G protein. G10 have been found in about 40% of pituitary somatotroph tumors. Although the etiology of thyrotroph adenomas is unknown, their autonomous behavior and blunted response to stimulatory hypothalamic hormone superficially resemble those of somatotroph tumors. We hypothesized that a subset of thyrotroph tumors might be caused by dominant somatic mutations that lead to inappropriate activation of the Gq/phospholipase C beta/Ca2+/protein kinase C. pathway normally triggered by occupancy of the TRH receptor (TRHR). We, therefore, screened samples from nine thyrotroph tumors for the presence of activating mutations of the alpha q, alpha 11, and TRHR genes. Fragments of alpha q and alpha 11 complementary DNA encompassing residues (Arg183 and Gln209) that correspond to Arg201 and Gln227 of alpha q were amplified and sequenced. Temperature gradient gel electrophoresis was used to screen for heterozygous mutations in the TRHR coding sequence as well as for known alpha s mutations. No mutations were detected. We conclude that mutations in these regions of the alpha q, alpha 11, alpha s, and TRHR genes occur infrequently, if at all, in human thyrotroph tumors. Alternative mechanisms underlying thyrotroph tumorigenesis, including changes in the expression levels of G protein alpha-subunits or TRHR, dysregulation of downstream components, inappropriate activation of other stimulatory pathways, or loss of inhibitory inputs, remain to be explored.

Prevalence and mechanisms of hearing loss in patients with resistance to thyroid hormone.

Hearing impairment was anecdotally reported in resistance to thyroid hormone (RTH), a condition caused by mutations in the beta-thyroid hormone receptor (beta TR) gene. Because of its ontogenic distribution in the cochlea, the beta TR may have a pivotal role in the development of auditory function. To assess the prevalence and mechanisms of hearing impairment in RTH, 82 RTH-positive (RTH+) patients and 55 unaffected relatives (RTH-) underwent systematic audiological examination, including puretone and speech reception thresholds, and tests studying middle ear (tympanometry and acoustic reflexes), cochlear (otoacoustic emissions), and retrocochlear integrity (brain stem auditory evoked potentials). Significant hearing loss was present in 21% of RTH+ patients vs. none in RTH- patients. More RTH+ patients had abnormal tympanometry (34% vs. 12%) and abnormal acoustic reflexes (39% vs. 19%). Isolated conductive deficit was found in 7 of 17 RTH+ patients with hearing loss, isolated sensorineural deficit in 7 cases, and mixed deficit in 3 cases. Cochlear dysfunction was found in 50% of all RTH+ patients, with or without hearing loss. Retrocochlear function was normal. No morphological cochlear abnormalities were detected on computed tomography of the temporal bone. In conclusion, hearing loss is a significant problem in RTH, with an equal frequency of conductive (probably related to the frequent ear infections) and sensorineural deficits. Abnormal otoacoustic emissions suggest that the mutant beta TR has a specific negative impact on cochlear function.

Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant.

Resistance to thyroid hormone (RTH) is a syndrome in which patients have elevated thyroid hormone (TH) levels and decreased sensitivity to its action. We describe a child with extreme RTH and a severe phenotype. A 22-month-old female presented to the NIH with goiter, growth retardation, short stature, and deafness. Additionally, the patient had hypotonia, mental retardation, visual impairment, and a history of seizures. Brain magnetic resonance imaging showed evidence of demyelination and bilateral ventricular enlargement. The patient had markedly elevated free T3 and free T4 levels of more than 2000 pg/dl (normal, 230-420 pg/dl) and more than 64 pmol/liter (normal, 10.3-20.6 pmol/liter), respectively, and TSH of 6.88 mU/liter (normal, 0.6-6.3 mU/liter). These are the highest TH levels reported for a heterozygous RTH patient. A T3 stimulation test confirmed the diagnosis of RTH in the pituitary and peripheral tissues. Molecular analyses of the patient's genomic DNA by PCR identified a single base deletion in exon 10 of her TRbeta gene that resulted in a frameshift and early stop codon. This, in turn, encoded a truncated receptor that lacked the last 20 amino acids. Cotransfection studies showed that the mutant TR was transcriptionally inactive even in the presence of 10(-6) M T3 and had strong dominant negative activity over the wild-type receptor. It is likely that the severely defective TRbeta mutant contributed to the extreme RTH phenotype and resistance in our patient.

False-positive iodine-131 whole-body scans due to cholecystitis and sebaceous cyst.

False-positive whole-body 131I scans are not frequent but have serious consequences in the management of patients with thyroid cancer. They can be classified in four main groups: elimination of iodine in body fluids, infection or inflammation, cysts or transudates and nonthyroid tumors. We report on two patients with false-positive post-therapy 131I scans. The first patient had uptake projected in the right pelvic area which was later proven to be a large gluteal sebaceous cyst. The second patient had uptake in the gallbladder area that did not disappear after 131I treatment; she underwent exploratory laparotomy which revealed extensive chronic cholecystitis. These cases illustrate two new causes of false-positive 131I whole-body scans (sebaceous cyst and cholecystitis), which highlights two mechanisms (elimination in body fluid and inflammation).

Significant effects of mild endogenous hormonal changes in humans: considerations for low-dose testing.

We review the significant and adverse health effects that can occur with relatively small endogenous hormonal changes in pubertal and adult humans. We discuss the effects of hormonal changes that occur within normal physiologic ranges--such as the rising levels of estrogen in peripuberty, which cause growth spurts at low levels and then the fusion of epiphyses at higher levels--and the hormonal variations during the menstrual cycle and their relation to genital phenotypic changes and intercurrent disease evolution. We turn next to adaptive changes in gonadal and other functions during aging, exercise, stress, starvation, and chronic diseases, which can serve as models for the effects of exogenous, hormonally active compounds. Then we review the states of borderline hormonal imbalances such as subclinical (having few or very mild symptoms, if any) hypothyroidism or hyperthyroidism, glucose intolerance, and other endocrine conditions. Finally, we review the deleterious systemic effects of gonadal imbalance. Information stemming from clinical observations leads to the concept of "no threshold" within the endocrine system and thus illustrates the importance of considering low-dose testing for chemicals that interfere with hormonal activity. We also urge attention to more sensitive, less visible end points such as osteoporosis, increased risk for cardiovascular disease, or cognitive changes.

Screening methods for thyroid hormone disruptors.

The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. Participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful; however, this method requires validation and standardization prior to use as a broad-based screen.

Thyroid hormones correlate with symptoms of hyperactivity but not inattention in attention deficit hyperactivity disorder.

The diagnostic validity of dividing attention deficit hyperactivity disorder (ADHD) into two distinct subgroups, one with and one without hyperactivity, is controversial since there have been no physiological differences demonstrated between these two subgroups. In this study, the relationship between thyroid hormones and symptoms of hyperactivity was examined in subjects with resistance to thyroid hormone (RTH) and their unaffected family members. Clinical data were collected on 152 subjects; 75 subjects with RTH and 77 family members without RTH. Each subject was assessed using DSM-III-R criterion based, structured psychiatric interviews, and Total T3 (TT3), Total T4 (TT4) and TSH concentrations were measured. The total number of ADHD symptoms were assigned to either inattention or hyperactivity subgroups using DSM-III-R criteria. The total number of ADHD symptoms were then reassigned to inattention or hyperactivity/impulsivity subgroups using DSM-IV criteria. Pearson R correlation coefficients were calculated separately for the RTH and unaffected family members groups in order to determine the relationships between TSH, TT3 and TT4 concentrations, and the DSM-III-R and DSM-IV symptom categories of ADHD in both groups. TSH concentrations were not significantly correlated with any of the symptom categories in either group. However, in the RTH group, both TT3 and TT4 concentrations were significantly and positively correlated with total symptoms of ADHD (DSM-III-R) as well as symptoms of inattention (DSM-III-R) and symptoms of hyperactivity (DSM-III-R). When DSM-IV criteria were used, which reassigns symptoms of impulsivity from the inattention to the hyperactivity category, only the positive correlation between TT3 and TT4 concentrations and symptoms of hyperactivity/impulsivity (DSM-IV) remained significant. In the group of unaffected family members, the relationship between TT3 concentrations and symptoms of hyperactivity/impulsivity (DSM-IV) was the only significant correlation. The data support the hypothesis that thyroid hormones may provide a physiological basis for the dichotomy between symptoms of inattention and symptoms of hyperactivity, particularly when DSM-IV criteria are applied.

Effects of environmental synthetic chemicals on thyroid function.

Synthetic chemicals are released into the environment by design (pesticides) or as a result of industrial activity. It is well known that natural environmental chemicals can cause goiter or thyroid imbalance. However, the effects of synthetic chemicals on thyroid function have received little attention, and there is much controversy over their potential clinical impact, because few studies have been conducted in humans. This article reviews the literature on possible thyroid disruption in wildlife, humans, and experimental animals and focuses on the most studied chemicals: the pesticides DDT, amitrole, and the thiocarbamate family, including ethylenethiourea, and the industrial chemicals polyhalogenated hydrocarbons, phenol derivatives, and phthalates. Wildlife observations in polluted areas clearly demonstrate a significant incidence of goiter and/or thyroid imbalance in several species. Experimental evidence in rodents, fish, and primates confirms the potentiality for thyroid disruption of several chemicals and illustrates the mechanisms involved. In adult humans, however, exposure to background levels of chemicals does not seem to have a significant negative effect on thyroid function, while exposure at higher levels, occupational or accidental, may produce mild thyroid changes. The impact of transgenerational, background exposure in utero on fetal neurodevelopment and later childhood cognitive function is now under scrutiny. There are several studies linking a lack of optimal neurological function in infants and children with high background levels of exposure to polychlorinated biphenyls (PCBs), dioxins, and/or co-contaminants, but it is unclear if the effects are caused by thyroid disruption in utero or direct neurotoxicity.

Graves' disease following thyrotoxic painless thyroiditis. Analysis of antibody activities against the thyrotropin receptor in two cases.

The exact immunologic mechanisms that lead to the emergence and progression of painless ("silent") thyroiditis remain unclear. We report two cases of painless postpartum thyroiditis followed by Graves' disease, where extensive immunologic evaluation supported a possible pathogenetic association. The time course of changes in thyroid function tests, 123I thyroidal uptake values, and thyrotropin receptor antibodies (TSHRAbs) were documented. The existence of stimulating TSHRAbs (TSAbs) activating the cyclic adenosine monophosphate (cAMP) and phosphatidylinositol 4,5-bisphosphate (PIP2) signal cascades and their functional epitopes, as well as two different thyrotropin-binding inhibitory immunoglobulins (TBII) were documented in both patients at the time of diagnosis of Graves' disease. We suggest that susceptible persons may develop an immunologic response that can trigger the appearance of a mixture of species of TSHRAbs, which in turn may lead to the sequential occurrence of painless thyroiditis and Graves' disease. Additionally, the multiple phases of hyperthyroidism and hypothyroidism that can occur in these patients may reflect the existence and changing spectrum of TSHRAbs in their sera.

[Pulmonary tuberculosis and HIV seropositivity at the Principal Hospital of Dakar (Senegal)]. / Tuberculose pulmonaire et séropositivité HIV à l'hôpital principal de Dakar (Sénégal).

In a prospective survey conducted in 1990 in the Principal Hospital of Dakar, pulmonary tuberculosis was 2.3 times more frequent in HIV seropositive patients (12.5%) than in HIV seronegative patients. We studied 22 cases of pulmonary tuberculosis in HIV+ patients and compared them with a control group of HIV- patients admitted for pulmonary tuberculosis. Tuberculosis occurred in 6 out of 22 asymptomatic HIV+ patients, in 15 out of 22 patients with clinical AIDS and in 1 patient with ARC syndrome. Clinical signs were the same as in controls, except for patients with advanced AIDS who developed cardinal signs. TB intra-dermal reactions were more often negative in HIV+ patients, notably those with HDV1, expressing immunodepression. Radiological images were typical in 81% of patients and in 86% of controls. However, concomitant infections were common in both groups, with atypical radiology and hyperleukocytosis. At light microscopy, there was no difference in the frequency of acid and alcohol fast bacilli between the two groups. The mortality rate was increased in HIV+ patients, but this was not due to tuberculosis. Relapses were frequent in both groups, due to poor compliance with treatment.