[A case of post-partum remission of acquired dyserythropoiesis, a rare cause of anemia in disseminated lupus erythematosus]. / Une observation de rémission post-partum d'une dysérythropoïèse acquise, une cause rare d'anémie au cours du lupus érythémateux disséminé.

INTRODUCTION: Amongst the various causes of anemia in systemic lupus erythematosus, isolated and acquired erythrocyte dysplasia is rare and most often part of global dysmyelopoiesis. EXEGESIS: The authors report a case of acquired erythrocyte dysplastic syndrome that occurred in a 34-year-old woman in whom previous diagnosis had evidenced systemic lupus erythematosus of rather benign course. Other causes of dysmyelopoiesis were ruled out. Myeloid stem cell cultures showed selective inhibition of erythroid cells growing, with no particular effect of the patient's serum. While a corticosteroid treatment with prednisone (1 mg/kg/d) did not show any efficacy upon anemia, the patient's pregnancy was followed by prolonged correction of hemoglobin, making possible the tapering of prednisone down to 10 mg/d. CONCLUSION: Acquired erythrocyte dysplastic syndrome remains a rare cause of anemia in systemic lupus erythematosus. This case report suggests an immunological phenomenon, but the mechanisms underlying both the appearance and long-lasting remission after pregnancy remain unexplained.

Dialysis arthropathy: outcome after renal transplantation.

PURPOSE: Patients treated by long-term maintenance hemodialysis frequently develop a form of chronic arthropathy that is strongly associated with beta 2-microglobulin amyloid deposition and related, at least in part, to beta 2-microglobulin retention. Successful renal transplantation is followed by a rapid fall in serum beta 2-microglobulin levels and might allow dissolution of amyloid deposits. The purpose of this work was to investigate the effects of renal transplantation on dialysis arthropathy. PATIENTS AND METHODS: Fourteen renal transplant recipients were selected on the basis of previous hemodialysis treatment for at least 10 years (mean 16) and a history of chronic joint pain prior to transplantation. They all received 10 to 17.5 mg/d of prednisone. Posttransplant rheumatologic manifestations were studied prospectively and compared to pretransplant rheumatologic manifestations recorded in medical charts and reported during patient interviews. Pretransplant and posttransplant articular roentgenograms were separately analyzed by three observers who were blinded to timing of the films. Beta 2-microglobulin amyloid was identified by Congo red staining and immunohistology. RESULTS: After a mean posttransplant interval of 54 months (range 12 to 121), the articular condition was improved in 10 patients, unchanged in 1, and worsened in 3, according to patients' assessments. The number of painful joints decreased significantly (P < 0.05) as compared to the pretransplant period. However, the number and size of subchondral bone erosions remained unchanged, destructive arthropathies generally worsened, and articular beta 2-microglobulin amyloid deposits were identified in 2 patients, 2 and 10 years after renal transplantation, respectively. CONCLUSION: Renal transplantation appeared to arrest progression of beta 2-microglobulin amyloid in dialysis patients, but it neither led to dissolution of deposits nor prevented progression of destructive arthropathies. Most articular symptoms were improved, probably as a result of corticosteroid therapy.

Diurnal rhythm of testosterone induced by human chorionic gonadotrophin (hCG) therapy in isolated hypogonadotrophic hypogonadism: a comparison between subcutaneous and intramuscular hCG administration.

When human chorionic gonadotrophin (hCG) is used to stimulate testosterone synthesis and release in males with hypogonadotrophic hypogonadism, it is administered two or three times weekly by intramuscular injection. We have compared the pharmacokinetics of a twice weekly standard dose of hCG (5000 U) given for the first week by intramuscular injection and in the second week by self-administered subcutaneous injection. The patients studied had Kallmann's syndrome, isolated idiopathic hypogonadotrophic hypogonadism or post-traumatic isolated hypogonadotrophic hypogonadism. Salivary testosterone was collected twice daily at 08.00 h and 20.00 h, and serum testosterone was collected after 0, 24 h, 72 h, 120 h and 168 h each week. The cumulated serum and salivary testosterone levels were comparable on both intramuscular and subcutaneous hCG. In normal males there is diurnal variation in testosterone, with peak serum levels in the morning falling to a nadir in the evening. The exact nature and controlling factors of this circadian rhythm have not been established. In four of the subjects, the twice weekly hCG injections, either subcutaneous or intramuscular, produced a regular testosterone diurnal rhythm. The other four patients had fluctuations in testosterone but with no strict diurnal pattern. This study provides evidence that the luteinizing hormone-like action of hCG is necessary to prime the circadian rhythm but only a single bolus of hCG is sufficient to induce the rhythm in the absence of endogenous gonadotrophin production. In conclusion, self-administered subcutaneous hCG is safe and produces comparable levels of serum and salivary testosterone to that administered by the intramuscular route. Moreover, it was very well accepted by the patients and was preferred to conventional treatments. Human hCG in some patients with hypogonadotrophic hypogonadism produces normal physiological changes in daily testosterone levels.

Self-administered subcutaneous human menopausal gonadotrophin for the stimulation of testicular growth and the initiation of spermatogenesis in hypogonadotrophic hypogonadism.

OBJECTIVE: We determined whether or not self-administered subcutaneous human menopausal gonadotrophin (hMG) therapy is safe and effective in the stimulation of testicular growth and initiation of spermatogenesis in men with hypogonadotrophic hypogonadism where human chorionic gonadotrophin alone had failed. DESIGN: Human menopausal gonadotrophin was self-administered subcutaneously in two dosage regimens to patients requiring (a) fertility (Group I), 37.5 IU twice daily (total weekly dose 525 IU) (n = 7) and (b) increased testicular size (Group II) 37.5 IU once daily (total weekly dose 265.5 IU) (n = 2). Patients were assessed on a monthly basis. PATIENTS: Nine patients with hypogonadotrophic hypogonadism were studied. Six patients had idiopathic isolated hypogonadotrophic hypogonadism, one Kallman's syndrome, one idiopathic isolated hypogonadotrophic hypogonadism secondary to trauma and one with panhypopituitarism secondary to radiotherapy for a hypothalamic pituitary tumour. Five of these patients had a history of unilateral or bilateral cryptorchidism. MEASUREMENTS: Semen analysis and serum testosterone. Testicular size was assessed by use of a Prader orchidometer. RESULTS: Six of seven patients (four with a history of cryptorchidism) requesting fertility attained sperm counts of > 10 million/ml. Three pregnancies have been achieved so far. One failure occurred in a patient with a previous history of cryptorchidism. In Group I patients (a) with an initial testicular volume of 4 ml or less (n = 4), mean size increased from 3.25 +/- 0.9 (SD) ml to 12.2 +/- 3.8 ml, (b) an initial testicular volume of > 4 ml mean size (n = 3) increased from 9.2 +/- 3.9 ml to 10.3 +/- 4 ml. In Group II (n = 2) testis size increased from a mean of 3.0 +/- 1.4 ml to 9.0 +/- 1.4 ml over a 6-months treatment period. CONCLUSION: Self-administered subcutaneous human menopausal gonadotrophin is a safe and effective mode of therapy in increasing testicular size and inducing spermatogenesis in males with hypogonadotrophic hypogonadism.

Comparison of methods for the determination of unbound triiodothyronine in pregnancy.

OBJECTIVE: To study the changes in unbound T3 concentration in the first trimester of pregnancy. DESIGN: We measured serum unbound T3 concentration before and after termination of pregnancy. PATIENTS: Twenty-six clinically euthyroid women. MEASUREMENTS: We used one non-analogue assay (Sclavo) and three analogue assays (Amersham, Becton Dickinson and Diagnostic Products Corporation). RESULTS: Regression analysis did not show any significant agreement between the analogue and non-analogue assays. After termination of pregnancy, unbound T3 concentration as measured by Sclavo and Amersham assays did not change whereas unbound T3 concentration increased and decreased as measured by Becton Dickinson and Diagnostic Products assays respectively. Changes were not directly related to albumin or thyroid binding globulin. CONCLUSION: We believe unbound T3 concentrations as measured by the analogue assays used in this study are due to a balance of errors and cannot be used to determine true physiological changes in pregnancy.

Human chorionic gonadotropin may not be responsible for thyroid-stimulating activity in normal pregnancy serum.

Although hCG can activate thyroid cells in culture there is considerable doubt as to whether it is responsible for the changes in thyroid function which occur during normal pregnancy. Thyroid-stimulating activity (TSA), measured using iodide uptake into FRTL-5 cells, was demonstrated in 32/51 (63%) first and 15/29 (52%) third trimester sera. Free T3 was increased (P less than 0.001) and TSH decreased (P less than 0.01) in first trimester. In the early pregnancy group there was a positive correlation between hCG and TSA (r = 0.594, P less than 0.001) and a negative correlation between hCG and TSH (r = -0.329, P less than 0.02). In third trimester hCG concentration was often below that required to produce TSA in vitro and TSA could not be neutralized by antibodies to hCG. There was no correlation between hCG and TSH or thyroid hormones in the third trimester. In 26 women TSA decreased in parallel with serum hCG concentration after termination of pregnancy (P less than 0.001). Free T3 also decreased (P less than 0.01) and TSH increased (P less than 0.05) after termination. TSA persisted in many patients even after hCG was either very low or undetectable. Purified hCG stimulated iodide uptake in a concentration-dependent manner. Stimulation of iodide uptake by TSH was inhibited by the simultaneous presence of low concentrations of hCG while activity was restored with high concentrations. hCG may contribute to the thyroid changes in early pregnancy. However the poor correlation between TSA and thyroid tests suggests that other factors may be involved. The partial agonist activity of hCG may account for some of the inconsistencies observed but TSA in serum from late pregnancy or after termination of pregnancy is almost certainly due to another hormone or growth factor.

Thyrotoxicosis and hyperemesis gravidarum associated with a serum activity which stimulates human thyroid cells in vitro.

OBJECTIVE: To investigate in-vitro thyroid stimulatory activity in the serum of patients with hyperemesis gravidarum and thyrotoxicosis. DESIGN: Serum from hyperthyroid patients was incubated with cultures of human thyroid cells. Attempts were made to neutralize stimulatory activity with antisera to hCG. PATIENTS: Five patients presenting in early pregnancy with hyperemesis and thyrotoxicosis. MEASUREMENTS: Serum concentrations of thyroid hormones (total and free), TSH and hCG. Accumulation of extracellular cAMP in response to serum. RESULTS: All five patients had biochemical hyperthyroidism with no evidence of an underlying autoimmune disease. The mean cAMP accumulation over 4 hours with sera from 12 non-pregnant controls was 130.6 (121.8-142.8), from 12 pregnant controls 132.4 (118.1-143.8), compared with values of 144.7, 159.1, 166.2, 178.9 and 320.5 for the thyrotoxic patients. The stimulatory activity could not be neutralized by addition of anti-hCG or by depleting the sera of hCG. CONCLUSIONS: Thyrotoxicosis may present with hyperemesis in early pregnancy. Clinical and biochemical features may be masked by the pregnancy or by the intercurrent illness. The hypothesis that hCG is a thyroid stimulator in patients with hyperemesis gravidarum is not supported by the immuno-neutralization data in this study.

Endocervical carcinoma and precursor lesions: c-myc expression and the demonstration of field changes.

The monoclonal antibody Myc 1-6E10 was used in an immunocytochemical technique to examine the expression of the c-myc oncogene in normal endocervices and those with glandular intraepithelial neoplasia and invasive malignancy. Eleven of 14 normal endocervical biopsy specimens did not express the gene, while three showed nuclear, or light basal cytoplasmic localisation of the gene product, or both. All but one of 14 cases of low and high grade glandular intraepithelial neoplasia, and all 17 cases of invasive adenocarcinoma, showed a pan-cellular pattern of immunostaining. Of considerable additional interest was the demonstration of field changes in morphologically normal glandular epithelium in those biopsy specimens with concurrent cervical glandular intraepithelial neoplasia or adenocarcinoma. This was manifest as increased concentrations of myc proteins compared with normal tissues. These results further support the role of the c-myc gene in oncogenesis, and in the light of field changes, suggest possible difficulties in the clinical management of this group of patients.

The role of hCG in regulation of the thyroid gland in normal and abnormal pregnancy.

There is strong evidence that at least some forms of hCG can interact with and stimulate the thyroid both in vitro and in vivo. Changes in thyroid tests are sufficiently common in normal pregnancy for us to regard them as physiologic. The evidence that hCG is the agent responsible for these changes remains largely circumstantial but is now supported by an increasing body of evidence from laboratory studies. Trophoblastic tumors secrete variant forms of hCG that can stimulate the thyroid, but we do not know if they have any role in the extreme examples of thyroid stimulation encountered in normal pregnancy. Preparations of hCG from pregnancy urine bind to thyroid membranes from a wide variety of species, but they do not activate adenylate cyclase in all assay systems. The enzyme in human thyroid cells or membranes is, at best, only weakly stimulated by hCG. There are ample in vitro data that hCG can stimulate the thyroid, but studies using human thyroid cells have yielded conflicting results. The most direct evidence comes from the study of thyroid tests in normal pregnancy. In early pregnancy, when hCG concentrations are highest, free thyroid hormones are increased and serum TSH concentration is decreased. An inverse correlation exists between serum hCG and TSH concentrations, but hCG generally correlates poorly with individual thyroid tests. An activity in pregnancy serum related to hCG is able to stimulate FRTL-5 cells and may account for the changes in thyroid function observed in pregnancy. Structural considerations, along with data from biologic assays and sensitive thyroid function tests, suggest that hCG has significant thyroid-stimulating activity. This information suggests that the thyroid may be under dual control from both hCG and TSH in early pregnancy.

Thyroid function in choriocarcinoma: demonstration of a thyroid stimulating activity in serum using FRTL-5 and human thyroid cells.

Hyperthyroidism is a well recognized complication of gestational trophoblastic tumours (GTT) and may be due to high circulating concentrations of human chorionic gonadotrophin (hCG) or its variants. We have studied 24 clinically euthyroid women with GTT. Eight were biochemically hyperthyroid with low or undetectable serum thyrotrophin (TSH) and had a mean serum hCG of 361.2 x 10(3) IU/l compared to 76.2 x 10(3) IU/l in the other patients (P less than 0.01). Purified hCG stimulated iodide uptake into FRTL-5 cells with 25 x 10(3) IU/l being equivalent in potency to 1 mU/l of thyrotrophin (TSH). Sixteen out of the 24 sera (67%) stimulated iodide uptake when applied to the cells at a 1:10 dilution. Sera from all eight hyperthyroid patients contained thyroid stimulating activity. The mean hCG concentration in the 16 stimulatory sera was 238.2 x 10(3) IU/l compared to 37.1 x 10(3) IU/l in the other eight sera (P less than 0.01). Six men with hCG-secreting testicular tumours were biochemically euthyroid although three of their sera stimulated iodide uptake into FRTL-5 cells. In human thyroid cells the mean cAMP production over 4 h with sera from five healthy controls was 54.2 +/- 1.81 pmol/mg cell protein compared to 67.0 +/- 3.8 pmol/mg protein with sera from five choriocarcinoma patients (P less than 0.02). Serum from patients with gestational trophoblastic tumours contains a thyroid stimulating activity which may be hCG and whose presence correlates with hyperthyroidism.

Nuclear and "cytoplasmic" estrogen and progesterone receptors in squamous cell carcinoma of the cervix.

Biopsies from 131 women with squamous cell carcinoma of the cervix diagnosed between May 1983 and July 1986 were assayed for nuclear and "cytoplasmic" estrogen receptors (NER and CER). Progesterone receptors (PR) were also assayed in 45 of these tumors. About a third of the tumors contained both CER and NER. One or the other fraction contained ER in 76.9% of cases and PR in 66.6%. Although there was a trend for those women whose tumors contained CER or NER to have a better prognosis, this was not significant. There was no evidence that PR status affected the prognosis.

Nucleolar organiser regions in adenocarcinoma in situ and invasive adenocarcinoma of the cervix.

Silver binding nucleolar regions (AgNORs) were evaluated in normal endocervix, adenocarcinoma, and its potential precursor, adenocarcinoma in situ (AIS), in an attempt to increase an understanding of the natural history of cervical adenocarcinoma and to identify a marker for abnormal endocervical (atypical glandular) cells which could aid diagnosis and follow up of endocervical lesions. For every 50 cells the mean AgNOR counts were as follows: normal endocervical cells (n = 15) 79.8 (95% Cl 68-91); AIS (n = 20) 200.7 (95% Cl 182-219); and invasive adenocarcinoma (n = 30) 299 (271-328). There was no overlap between the groups of normal endocervical cells and invasive adenocarcinoma, but there was significant overlap between cases of invasive adenocarcinoma and carcinoma in situ. In six out of 17 cases with AIS, NOR count in adjacent morphologically normal glandular cells ("internal" controls) was increased when compared with the "external" (normal endocervical) control group. This suggests the presence of wider field changes not previously identified using routine histological methods. The findings suggest that AIS is a potential premalignant precursor of invasive adenocarcinoma, but that assessment of NORs is of no practical use in discriminating between the histological types of cervical carcinoma.

Thyroid-stimulatory effects of human chorionic gonadotrophin in early pregnancy. In vivo and in vitro studies.

Human chorionic gonadotrophin (hCG) shares structural similarity with pituitary thyrotrophin (TSH) and may act as a thyroid stimulator. We have studied serum hCG levels, thyroid function tests and the ability of serum to stimulate cultured thyroid cells in 40 subjects between 6 and 12 weeks of pregnancy. Serum free tri-iodothyronine was increased and serum TSH reduced in pregnancy samples (both p less than 0.05). hCG was detectable in all pregnancy sera with a mean level of 105.6 X 10(3) U/l. Serum from 24 of the 40 (60%) patients stimulated iodide uptake into cultured FRTL-5 thyroid cells. The potency of sera in stimulating cells correlated with the hCG level (r = 0.710, p less than 0.01). The stimulatory activity in some, but not all, sera could be specifically neutralized with antiserum to hCG. Partially purified hCG stimulated iodide uptake and growth of thyroid cells at concentrations of 50 X 10(3) U/l and above. In these experiments, 25 X 10(3) U/l of hCG produced equivalent stimulation to 1 mU/l of TSH. In 8 patients tested before and after termination of pregnancy, the thyroid-cell-stimulatory activity of serum declined rapidly in parallel with serum hCG. hCG may stimulate the thyroid gland at concentrations which prevail in normal pregnancy. Its potential as a physiological regulator of the thyroid gland is not widely appreciated and requires further study.

Solitary plasmacytoma of the spine. Long-term clinical course.

The data for 19 patients with solitary plasmacytoma of the spine were reviewed with regard to clinical course and prognosis (median follow-up, 96 months). Eight patients presented with spinal cord compression. A monoclonal immunoglobulin was initially detected in seven of 15 evaluable patients. Treatment included radiotherapy (18 of 19) and/or surgery (11 of 19) and chemotherapy (eight of 19). Spinal cord compression was reversed in every patient. The expected survival rate was 85% at 10 years after diagnosis. Local recurrence or dissemination was observed in 13 patients. It occurred within 5 years of diagnosis in 11 patients and was localized (that is, local recurrence or single bone metastasis) in eight patients. It was always associated with the appearance or an increase of the M component. Dissemination frequently had a "metastatic" pattern with no diffuse bone marrow plasmacytosis. The incidence of local recurrence (five patients) and leukemia (four patients) was high. Local recurrence and/or dissemination were significantly more frequent in patients with the M component at diagnosis than in those without it (P less than 0.05; relative risk, R = 4). The effectiveness of surgery and chemotherapy combined with radiotherapy is also discussed.

Saliva oestriol, oestradiol, oestrone and progesterone levels in pregnancy: spontaneous labour at term is preceded by a rise in the saliva oestriol:progesterone ratio.

Saliva steroid levels reflect the unbound unconjugated (free, biologically active) plasma hormone levels. Saliva oestriol (E3), oestradiol (E2), oestrone (E1) and progesterone levels were estimated by radioimmunoassay in saliva samples obtained twice a week from 18 weeks gestation until 38 days before delivery and then daily until the spontaneous onset of labour at term from 20 normal pregnant women. The overall percentage increases in the median concentrations of E3, E2, E1 and progesterone were 718, 370, 80 and 214%, respectively, in the last 20 weeks and 149, 82, 24 and 41%, respectively, in the last 6 weeks of pregnancy. The median E3:progesterone ratio rose slowly from 0.65 at 20 weeks before delivery to 1.0 at 5 weeks before delivery and then rapidly to 1.65 one day before the spontaneous onset of labour. There was an increase in the E3:progesterone ratio from less than 1 to greater than 1 before labour in every subject.

Increased saliva oestriol to progesterone ratio before preterm delivery: a possible predictor for preterm labor?

Saliva oestriol, oestradiol, and progesterone concentrations were measured in 23 women who went into spontaneous preterm labour. The patients fell clinically and biochemically into two groups. The 13 who went into preterm labour with intact membranes had a saliva oestriol to progesterone ratio greater than one in every case and greater than the 95th centile for their length of gestation in 12 cases; by contrast, all those who went into spontaneous preterm labour after prolonged rupture of the membranes had an oestriol to progesterone ratio less than one and below the 50th centile for their period of gestation in the one to four days before delivery. Saliva oestradiol to progesterone ratios were randomly distributed throughout the normal range in both groups. It appears that preterm labour without prior prolonged rupture of the membranes is, like term labour, preceded by an increase in the saliva oestriol to progesterone ratio. It may therefore be possible to use this ratio to predict preterm labour.