Anti-goat antibodies as a rare cause of high gonadotropin levels during menopausal transition

Abstract

Objective: To understand the origin of extremely high gonadotropin levels in a perimenopausal woman.

Methods: A 52-year-old woman with a 2?months of amenorrhea followed spontaneous menstrual cycles recovery was referred to our outpatient clinic with elevated follicle-stimulating hormone (FSH, 483 mUI/ml), luteinizing hormone (LH, 475 mUI/ml) and prolactin (PRL, 173?ng/ml). She was known to take levosulpiride. The gonadotropin levels did not fit with the clinical features.

Results: A gonadotroph tumor was ruled out. Further analysis confirmed constantly high FSH, LH and PRL levels. The measurements were repeated using different analytical platforms with different results. After serial dilutions, nonlinearity was present suggesting an immunoassay interference. After post-polyethylene glycol recovery, hormone levels appeared in the normal range. Anti-goat antibodies were recognized in the serum of the patient.

Conclusions: This case report shows a case of falsely abnormal high gonadotropin and PRL levels in a woman during menopause transition. In the clinical practice the evaluation of gonadotropin profile is not recommended at this age, but the abnormal levels stimulated further evaluation. An interference in the assay due to anti-goat antibodies resulted in abnormally high level of FSH and LH. A strict collaboration between clinicians and the laboratory is needed, when laboratory findings do not correspond to clinical findings.     

Lack of nocturnal serum thyrotropin (TSH) surge in patients with chronic renal failure undergoing regular maintenance hemofiltration: a case of central hypothyroidism

Thyrotropin (TSH) secretion was evaluated in a group of patients with chronic renal failure (CRF) undergoing regular maintenance hemofiltration and in normal controls. The study group included 68 patients (39 males and 29 females, age range 39-73 years, mean: 53 years). In all patients blood was drawn at 08:30-09:00 h; in 20 patients the nocturnal (24:00-02:00 h) serum TSH peak was also evaluated; 12 patients underwent stimulation test with synthetic TSH-releasing hormone (TRH). TSH was measured by an ultrasensitive immunoradiometric assay. CRF patients showed a significant decrease in serum total and free thyroxine and triiodothyronine concentrations, which in a substantial proportion of subjects were below the lower normal limit. Serum reverse triiodothyronine and thyroxine-binding globulin values did not differ in the two groups. Despite this trend of thyroid hormones to decrease, no patient had supranormal TSH values as in primary hypothyroidism. While the mean morning TSH concentrations of CRF patients did not differ from those of controls, the mean nocturnal values were significantly reduced in CRF (1.0 +/- 0.2 vs 3.2 +/- 0.4 mU/l, p less than 0.0005) and the nocturnal serum TSH surge was not observed in 18 of the 20 patients (90%) in whom it was evaluated. The mean serum TSH peak value after TSH-releasing hormone (TRH) administration was also reduced in CRF patients, and the TSH response to TRH was blunted in 3 out of 12 patients (25%). The results of this study demonstrate a major impairment of TSH secretion in CRF, which baseline TSH measurements in the morning and the evaluation of the TSH response to TRH may not reveal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dependence of adaptation of the human vertical angular vestibulo-ocular reflex on gravity

We determined the spatial dependence of adaptive gain changes of the vertical angular vestibulo-ocular reflex (aVOR) on gravity in five human subjects. The gain was decreased for 1 h by sinusoidal oscillation in pitch about a spatial vertical axis in a subject-stationary surround with the head oriented left-side down. Gains were tested by sinusoidal oscillation about a spatial vertical axis while subjects were tilted in 15° increments from left- to right-side down positions through the upright. Changes in gain of the vertical component of the induced eye movements were expressed as a percentage of the preadapted values for the final analysis. Vertical aVOR gain changes were maximal in the position in which the gain had been adapted and declined progressively as subjects were moved from this position. Gain changes were plotted as a function of head orientation and fit with a sine function. The bias level of the fitted sines, i.e., the gravity-independent gain change, was –29±10% (SD). The gains varied around this bias as a function of head position by ±18±6%, which were the gravity-dependent gain changes. The gravity-dependent gain changes induced by only 1 h of adaptation persisted, gradually declining over several days. We conclude that there is a component of the vertical aVOR gain change in humans that is dependent on the head orientation in which the gain was adapted, and that this dependence can persist for substantial periods.     

Role of the 2 adenine (g.11293_11294insAA) insertion polymorphism in the 3' untranslated region of the factor VII (FVII) gene: molecular characterization of a patient with severe FVII deficiency

Polymorphic variants in the gene encoding factor VII (F7) affect the plasma levels of this coagulation protein and modify the clinical phenotype of FVII deficiency in some patients. In this study we report the in vitro functional analysis of a novel polymorphic variant located in the 3' untranslated region of F7: g.11293_11294insAA. To determine whether this variant regulates FVII expression, we initially compared an expression vector containing FVII cDNA with g.11293_11294insAA with the FVII wild-type (WT) construct. The kinetics of mRNA production showed that the insertion decreases the steady-state FVII mRNA levels. To assess whether the insertion influences the phenotype of FVII-deficient patients, we evaluated its effect on the expression of FVII in a patient with severe FVII deficiency (undetectable FVII activity and antigen) carrying two additional homozygous missense variations (p.Arg277Cys and p.Arg353Gln). The two substitutions alone reduced the expression of FVII activity and antigen in vitro, but with the insertion polymorphism in our expression vector the patient's phenotype of undetectable plasma FVII was recapitulated. The insertion polymorphism in the 3' untranslated region of F7 is another modifier of FVII expression that might explain the poor genotype-phenotype correlation in some FVII-deficient patients.     

Multi-walled carbon nanotube-induced inhalation toxicity: Recognizing nano bis-demethoxy curcumin analog as an ameliorating candidate

Human beings and ecosystems are being possibly exposed to CNTs, as there is a rise in global production rate of carbon nanotubes (CNTs). This may affect the health of humans and increases the environmental risk. We have already reported the pulmonary toxicity due to the inhalation of MWCNTs. We claim that a compound with anti-inflammatory and antioxidant activity may ameliorate the CNT-induced toxic effect. With this view, we have investigated the ameliorative effect of intravenously-administered nano bis-demethoxy curcumin analog (NBDMCA) against MWCNTs-induced inhalation toxicity by examining the lung histopathology for inflammatory cell dynamics, pulmonary remodeling and estimating the inflammatory biomarkers in the broncho-alveolar lavage fluid. We observed that NBDMCA could ameliorate the injury as evidenced by the decline in the levels of markers of inflammation, cell damage, and the histopathological changes induced by MWCNTs. We conclude that NBDMCA may be used to reduce the risk of MWCNTs-induced inhalation toxicity.     

Effect of captopril on renal function in patients with essential hypertension

The glomerular filtration rate (creatinine clearance), glomerular permeability (qualitative and quantitative proteinuria), tubular reabsorption (k-λ chains of immunoglobulins and lysozyme) and indexes of tubular cell lysis (alpha-glucosidase and gamma-glutamyltranspeptidase) were measured in the urine of 10 patients with moderate, uncomplicated essential hypertension during placebo therapy and after captopril given at increasing doses of 25, 50, 100 and 200 mg twice daily, the first three doses being given for 3 days and the last one for 4 weeks in all patients and for an additional 6 months in 5 patients. During placebo therapy, proteinuria was absent in eight patients and detectable (glomerular and selective) in two; selective proteinuria appeared in two and a decrease in selectivity was observed in two patients with previous proteinuria after 4 weeks of captopril therapy. No proteinuria was detectable in the five patients followed up for 6 months, not even in the one in whom a decrease in glomerular selectivity had occurred after 4 weeks. The glomerular filtration rate was unchanged as were lysozyme and gamma-glutamyltranspeptidase values, while light chains were always undetectable. Alpha-glucosidase showed some increase; however, increments were transient and always much lower than those observed with known tubular toxic drugs. These data show that under our experimental conditions captopril caused no evident changes in glomerular and tubular function.     

The female pelvic floor through midlife and aging

Female pelvic floor is a complex functional unit involved in multiple functions that extend beyond the sole support of pelvic organs. Pelvic floor dysfunction globally affects micturition, defecation and sexual activity. Evolutionary modifications such ad adaptation to upright standing, walking and the need to deliver fetuses with larger head diameters made the fascial and muscle support of the pelvic floor vulnerable, therefore predisposing women to pelvic organ prolapse and incontinence. Different than in males, the female pelvic floor undergoes a number of adaptive changes related to life and endocrine events. Most of the clinical manifestations of these changes become apparent after menopause and throughout aging in women. This review article summarizes the key aspects of the pathophysiology and the clinics of the modifications of the pelvic floor in women through midlife and beyond. A particular focus is given to the relationship between urinary and bowel dysfunction.