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Biomedical subjects

K Poppe

Publications and source records attributed to K Poppe.

10 recordsLinked to original sources

Thyroid disorders in infertile women.

Thyroid hormones have profound effects on reproduction and pregnancy. There is a known association of hyper- and hypothyroidism with menstrual disturbances and decreased fecundity. Women with reproductive failure also have an increased prevalence of organ specific autoimmunity compared to fertile women. The present study aims to answer the following questions: 1) is there an increased prevalence of thyroid antibodies in infertile women? 2) are thyroid antibodies associated with a particular cause of infertility? and 3) do these antibodies influence outcome of the in vitro fertilization procedure? The answers to the two first questions were evaluated with a case-control study looking at the occurrence of thyroid autoimmunity and thyroid function tests among women of infertile couples (n=438), presenting for the first time at the department of reproductive medicine. For comparison, a control population of parous women (n=100), matched for age, was included. In 45% of the infertile couples a female cause of infertility was identified: endometriosis (11%), tubal disease (30%) and ovarian dysfunction (59%). Male infertility was diagnosed in 38% and idiopathic infertility in 17% of the couples. Mean serum TSH levels were significantly higher in patients with infertility compared with control patients: 1.6 +/- 2.6 versus 1.2 +/- 0.7 mIU/L. The proportion of positive TPO-Abs was higher in all women of infertile couples, compared with controls (14% versus 8%), but the difference was not significant. Considering only the female causes of infertility a significant higher proportion of women had positive TPO-Abs compared with controls (18% versus 8%), and in particular a high prevalence of thyroid autoimmunity was found in women suffering from endometriosis (29%). Both hypo- and hyperthyroidism were more frequent when TPO-Abs were positive, compared to women without thyroid autoimmunity. The results of the present study indicate that endometriosis, increases the relative risk for associated thyroid autoimmunity to 2.3, and therefore screening for thyroid auto-antibodies could be systematically proposed in these women.

Adult↗

Citrate infusion test in the diagnosis of hypocalcemia due to a mutation in the calcium-sensing receptor gene.

The calcium-sensing receptor (Ca-R) is a G-protein-coupled surface receptor that plays a crucial role in calcium homeostasis via parathyroid hormone secretion. Mutations of this receptor can cause a gain in, or loss of, function, leading to hypo- or hypercalcemia, respectively. We report here a family with hypocalcemia in whom a heterozygous missense mutation in exon 4 was demonstrated, predicting a proline to leucine substitution (P221L) in the extracellular part of the Ca-R. Clinical symptoms were limited to fatigue. When serum calcium was further lowered via a citrate infusion, a significant increase in circulating iPTH was observed, although with lower peak values than in normal controls, suggesting a gain in function of the Ca-R. Treatment with calcium supplements and calcitriol led to prohibitive hypercalciuria without normalizing serum calcium. The aims of this case report are: (1) to present a mutation in the Ca-R with a gain in function at a codon where previously loss of function was described, and (2) to suggest that measuring circulating iPTH during a citrate infusion in the presence of familial hypocalcemia is an additional test to diagnose this particular form of hypoparathyroidism.

Journal Article↗

Thyroid and infertility.

Infertility is defined as the inability to conceive after one year of regular intercourse without contraception. The prevalence of infertility is estimated between 12 and 14% and remains stable in recent years. It thus represents a common condition, with important medical, economic and psychological implications. According to a standard protocol infertility evaluation usually identifies different causes, including, male infertility (30%), female infertility (35%), the combination of both (20%), and finally unexplained or "idiopathic" infertility (15%). Female causes of infertility comprise endometriosis, tubal damage and ovulatory dysfunction (OD). Thyroid dysfunction is a condition known to reduce the likelihood of pregnancy and to adversely affect pregnancy outcome. Data on the relationship between thyroid disorders and infertility remain scarce and the association with a particular cause of infertility has not thoroughly been analyzed. In a case-control study we have shown that the relative risk of positive TPO-Abs in infertility due to a female cause and in particular related to endometriosis is significantly increased. Thyroid dysfunction itself is a condition interfering with normal ovarian function and was more frequent in women with positive anti-TPO Abs. We therefore propose that a systematic screening of TSH, free T4 and TPO-Ab could be considered in all women with a female cause of infertility. Prospective follow-up of a cohort of infertile women undergoing assisted reproduction shows a significant increased risk of miscarriage in women with positive anti-TPO Abs compared to women without thyroid auto-immunity after clinical pregnancy is established by the ART procedure. The frequent association of the presence of anti-TPO-Abs and miscarriage is hypothetical explained by the fact that organ specific autoimmune diseases may be secondary to some basic cellular abnormality that directly affects pregnancy outcome. Alternatively, women with thyroid autoimmunity, may experience greater changes in free thyroxine levels during ART and subsequent pregnancy interfering with genital tract physiology and fetal development. Determining the presence of thyroid antibodies before ART procedure is thus useful in identifying women at risk for subsequent clinical miscarriage.

Abortion, Spontaneous↗

Detailed deletion mapping in sporadic breast cancer at chromosomal region 17p13 distal to the TP53 gene: association with clinicopathological parameters.

Chromosome 17p is among the most frequently deleted regions in a variety of human malignancies including breast cancer. This study has further refined the localization of a putative tumour suppressor gene (TSG) at 17p13 distal to the TP53 gene in breast carcinomas. It was found that 73% (37 of 51) of the breast tumours exhibited loss of heterozygosity (LOH) at one or more loci at 17p13. The allelic loss patterns of these tumours suggest the presence of at least seven commonly deleted regions on 17p13. The three most frequently deleted regions were mapped at chromosomal location 17p13.3-17p13.2 between the markers D17S831 and D17S1845 (56% LOH), at 17p13.1 between D17S1810 and D17S1832 (53% LOH), and at 17p13.1 between D17S938 and TP53 (55% LOH). A significant correlation was found between loss at 17p13 and tumour grade, size, proliferative activity, and oestrogen receptor (ER) status. Losses at 17p13 were seen more frequently in large and poorly differentiated tumours with high proliferative activity. These data support and extend previous reports on the presence of a putative TSG(s) at chromosomal region 17p13 distal to the TP53 gene and show that different subsets of LOH are associated with more aggressive tumour behaviour.

Adult↗

Non-secreting atypical parathyroid adenoma.

Parathyroid tumors can be divided in adenomas and carcinomas, usually detected by hypercalcemia. We report a case of parathyroid adenoma in a young man, who complained of a pressure in the left neck region. Physical examination revealed a firm mass in the neck, without lymphnodes. Although Ca (9.7 mg/dl), phosphorus (3.3 mg/dl) and intact-PTH (49 pg/ml) were normal, imaging techniques (computed tomography scan and sestamibi substraction scan) suggested that the mass could arise from the parathyroid gland. Histology and immune staining for chromogranin and parathyroid hormone confirmed the parathyroid nature of the mass. Histological criteria defined the lesion as an atypical parathyroid adenoma. We review the pathology, diagnosis and treatment of parathyroid adenomas in its non-secreting atypical form.

Adenoma↗

Slow-release lanreotide in the treatment of acromegaly: a study in 66 patients.

OBJECTIVE: Slow-release (SR) lanreotide is a long-acting somatostatin analog that has been developed in order to overcome the inconvenience of multiple daily subcutaneous injections of octreotide, required for metabolic control in acromegaly. Lanreotide SR has been found to be well tolerated and effective in reducing GH and IGF-I levels but clinical data are still limited compared with those with subcutaneous octreotide treatment. DESIGN: Sixty-six unselected patients with active acromegaly were therefore evaluated in a multi-center, prospective, open label study. Lanreotide SR was given at a dose of 30mg intramuscular every 7-14 days. METHODS: At baseline and after 2, 4, 8, 12, 24, 36 and 48 weeks patients underwent a clinical examination with assessment of acromegaly related symptoms, and blood was sampled for serum GH, IGF-I, prolactin, glycosylated hemoglobin, fasting glucose, hematology, kidney function and liver function tests. Biliary ultrasonography and pituitary magnetic resonance imaging were performed at baseline and after one year. RESULTS: Treatment resulted in a significant improvement in the symptom score from 2.69+/-0.27 to 1.06+/-0.17 (P<0.0001). Serum IGF-I levels fell from 699+/-38microg/l at baseline to 399+/-26microg/l (P<0.0001, n=60) after one month, after which levels remained stable: 480+/-37microg/l after 6 months (n=54) and 363+/-32microg/l after one year (n=46). GH levels dropped from 13.8+/-3.2microg/l to 4.3+/-0.7microg/l after one month (P<0.0001, n=60) and remained stable thereafter: 3.9+/-0.4microg/l (n=54) after 6 months and 3.5+/-1.1microg/l after one year (n=46). Twenty-nine out of 66 patients (44%) attained a normal age-corrected IGF-I level and 30 patients (45%) attained a GH level below 2.5microg/l. Pituitary adenoma shrinkage of at least 25% was found in 5 of 14 patients (36%) after one year. Side effects were mainly transient gastrointestinal symptoms and pain at the injection site, resulting in drug discontinuation in only 6 patients (9%). Two patients developed new gall stones. No difference was found between subcutaneous octreotide and lanreotide SR in efficacy and almost all patients preferred the easier dose administration of lanreotide SR. CONCLUSIONS: Long-term treatment of acromegaly with SR-lanreotide is effective in controlling GH and IGF-I levels and symptoms and is well tolerated in the majority of patients. Compared with subcutaneous octreotide, lanreotide SR considerably improves patient's acceptance of therapy while having the same overall efficacy.

Acromegaly↗

Calcitonin reserve in different stages of atrophic autoimmune thyroiditis.

The objective of this study was to determine the calcitonin (CT) hormone reserve in different severity of atrophic autoimmune thyroiditis (AAT). Forty-eight female patients with AAT were divided into four groups based on basal and peak thyrotropin (TSH) values (after oral thyrotropin-releasing hormone [TRH], free triiodothyronine (FT3) and free thyroxine (FT4) ranging from normal in group 1 to overt hypothyroidism in group 4. All had thyroid antibodies. The control group comprised euthyroid females of comparable age, without thyroid antibodies. Basal CT and CT response to calcium infusion (area under the curve) were investigated as parameters of CT reserve. Basal CT was lower in groups 2 to 4 of patients with AAT (compared to controls), but the difference was not significant. Stimulated CT levels were lower (p < 0.05) in all groups of patients compared to controls, with markedly reduced CT-secretory reserve in group 4. Thyroid antibody concentrations and, basal and postinfusion calcium levels were not significantly different among the various groups. In conclusion CT deficiency (especially stimulated values) occurs in AAT and is more severe in hypothyroid patients than in earlier stages of AAT.

Administration, Oral↗

Using 5-mm bipolar cutting forceps: a new multifunctional instrument.

The most technically challenging step in performance of esophagogastric fundoplication is division of the short gastric vessels that connect the splenic hilum to the gastric fundus. Consistent dependable coagulation and division of these vessels would be a significant advance that would make the procedure more widely available to patients, since it would provide surgeons with a safe technique for providing a reliable loose "wrap." Such an instrument has now become available and is called the "bipolar cutting forceps." One of the authors has recently used the tool (5-mm version) for the laparoscopic completion of five Toupet fundoplications and two gastrojejunostomies. The instrument functioned in both the locked and manual mode and provided effective bipolar coagulation and scalpel division of thick lesser curve and greater omental tissue. No bleeding was noted, and all procedures were completed without conversion to laparotomy. The notion that such a multifunctional instrument will lead to cost reductions is possible but yet unproven.

Electrocoagulation↗

Expression and mutational analysis of Nm23-H1 in liver metastases of colorectal cancer.

It has been proposed that nm23-H1, a candidate suppressor gene for metastasis, plays an important role in metastasis formation of human tumours. In order to investigate its role in the progression of colorectal cancer, we analysed 22 liver metastases of this malignancy with respect to mutational changes, loss of heterozygosity and expression levels of nm23-H1. Although genetic alterations in nm23-H1 have recently been described in those colorectal adenocarcinomas which give rise to distant metastases, we were unable to detect any mutation in the coding sequence of nm23-H1 in the metastatic tissue itself. We further analysed the metastases with respect to allelic deletions at the chromosomal locus of nm23. However, no loss of heterozygosity could be detected in ten informative cases. Moreover, the mRNA expression levels of nm23-H1 in the metastatic tissues were not significantly different from those in normal colon mucosa. Thus, although nm23-H1 might be involved in metastasis suppression of certain tumour types, in colorectal tumour progression its role remains to be determined.

Base Sequence↗

Toxic intrathoracic goiter and mediastinal lymphadenopathy: an unusual presentation of systemic primary AL amyloidosis.

Mediastinal lymphadenopathy and goiter have been associated with primary amyloidosis, although not in the same patient. One previous case report described the association of an amyloid goiter and hyperthyroidism (due to Graves' disease) with primary amyloidosis. Till now no case reports of patients presenting simultaneously with mediastinal lymphadenopathy, intrathoracic amyloid goiter and hyperthyroidism as the first manifestation of systemic primary (idiopathic) amyloidosis have been described. The present case report describes the clinical, biological radiological and histological features in such a male patient.

Aged↗