Does TSH Reliably Detect Hypothyroid Patients?

OBJECTIVES: To evaluate the reliability of normal Thyroid Stimulating Hormone (TSH) as a thyroid function test and assess the effect of Adrenocorticotropic Hormone (ACTH) on serum TSH concentration. DESIGN AND METHODS: Patients presenting to the National Institutes of Health Department of Endocrinology outpatient clinic with symptoms consistent with hypothyroidism were identified. Thyroid hormone concentrations were measured by liquid chromatography/tandem mass spectrometry and immunoassay. Patients with normal TSH concentrations were assessed for both clinical and biochemical hypothyroidism.We evaluated the effect of ACTH stimulation (performed on patients for assessment of adrenal function) on TSH concentration. RESULTS: Patients with symptoms consistent with hypothyroidism but with normal TSH values in the range of 1-4 IU/mL and normal free T4 (FT4) values by immunoassay measurements were confirmed to be biochemically hypothyroid following measurements of thyroid hormones by mass spectrometry. We present case studies of two patients, a 76-year-old male and a 58-year-old female. Improvement in the male patient's hypothyroid symptoms, including afternoon fatigue, constipation, alopecia, dry skin and high cholesterol, was documented after initiating thyroid hormone replacement.ACTH stimulation resulted in an average decrease of 17% in TSH between time 0 and 60 minutes post stimulation. CONCLUSION: Although measurement of TSH is a convenient screen for thyroid function, it is influenced by many factors which may affect its overall reliability. We believe thyroid function should be assessed by more than a single test. We recommend measurement of thyroid hormone concentrations by mass spectrometry if the patient's clinical presentation is discordant with their TSH levels.

Assessment of genetic variability of resistance to gastrointestinal nematode parasites in Creole goats in the humid tropics.

Goat production is widespread in the tropics. Goats are very susceptible to gastrointestinal nematode infection, but there is less evidence of their genetic resistance. Genetic resistance of Creole goats to gastrointestinal nematodes has been studied at Guadeloupe in the French West Indies since 1995. The objective of this research was to investigate genetic variation for resistance to gastrointestinal nematode infection, in order to introduce this trait into breeding schemes. Genetic variability was assessed within a Creole experimental flock. Forty-nine sire groups were characterized at weaning and 55 during fattening after weaning. Kids were naturally infected, mainly by Haemonchus contortus and Trichostrongylus colubriformis. Fecal egg counts were determined once at weaning and every 6 and 7 wk after drenching during fattening. Blood samples were collected every 7 wk during fattening for determination of packed cell volume. Live weights were recorded at weaning and at the beginning and middle of every infection period during fattening. Genetic parameters were estimated using the REML for multivariate animal models. The heritability estimate for transformed fecal egg count was 0.37+/-0.06 at weaning. During fattening, it increased from 0.14+/-0.05 at 4 mo to 0.33+/-0.06 at 10 mo. Heritabilities of packed cell volume ranged from 0.10 to 0.33. At weaning, maternal heritability of fecal egg count reached 0.26 and direct heritability 0.20. After 6 mo of age, maternal effects were found to be unimportant for fecal egg count and packed cell volume. Live weights presented significant genetic variability. Genetic relationships between fecal egg counts and live weight in infected pastures were never significant. Genetic correlations between packed cell volume and live weight decreased from 0.47 to 0.10 from weaning to 10 mo of age. These results demonstrated the feasibility of breeding for improved resistance to nematodes in Creole kids.

Genetic susceptibility and transmission factors in scrapie: detailed analysis of an epidemic in a closed flock of Romanov.

Information from a scrapie epidemic in a closed INRA Romanov flock is presented. Performances, pedigree, histopathological diagnoses and PrP genotypes were recorded from the beginning of the outbreak (in 1993). Between 1st of April, 1993 and 1st of May, 1997, 1015 animals were exposed to scrapie, and 304 died from this disease. A major influence of the polymorphisms at codons 136, 154 and 171 is shown, A136H154Q171 allele carriers proving to be nearly as resistant as A136R154R171 carriers. A possible relationship between gastrointestinal parasitism and scrapie is discussed. There is evidence of maternal transmission, with a risk ratio for artificially fed lambs of 67 percent of the risk of lambs fed by their mother. Our results strongly suggest that resistant animals were not healthy carriers or at least were less infectious when comparing risk for lambs born to healthy dams either of resistant (risk = 0.431) or of susceptible (risk = 1.000) genotype.

Genetic variability in resistance of Creole goats to natural infection with trichostrongylids in Guadeloupe.

The objective of this study was to show the existence of genetic variability in resistance of Creole goats to natural infection with intestinal nematodes. Four successive cohorts of male and female kids were reared from weaning during 9 months in intensive pangola pastures (stocking rate 1.4 t/ha, regrowth of 21 days, 300 kg N/ ha/year of fertilization). All cohorts considered, 203 offsprings from 13 bucks and 149 goats were used in the experiment. Animals were treated with an oral dose of ivermectin every seven weeks, from 3 to 11 months of age. They were sampled for fecal egg counts (FEC) and packed cell volume (PCV), 6 weeks after drenching, when 6 and 10 months old. Haemonchus contortus and Trichostrongylus colubriformis were the predominant species. Data of one cohort when 6 months of age and another one when 10 months old were not included in calculations because a self-cure occurred during a rainy season. Estimated means of FEC after square-root transformation were 1054 and 711 respectively for 6-month-old and 10-month-old kids. Phenotypic correlations between FEC and PCV were -0.46 (p < 0.001) and -0.29 (p < 0.01) when 6 and 10 months old, respectively. FEC repeatabilities estimated as variance ratio were 0.47 and 0.06 for within-age measures (data recorded at one week interval) and between age measures (6 vs. 10 months) respectively. No sire effect was significant for PCV. Sire effect on FEC was more significant when 6 months old (p < 0.03) than when 10 months old (p < 0.15). Further studies are now being carried out to confirm this genetic determinism of resistance to natural infection with strongyles in Creole goats.

Worm population characteristics and pathological changes in lambs after a single or trickle infection with Teladorsagia circumcincta.

The regulation of the worm population and of its pathological effects was studied after a single or trickle infection with T. circumcincta. One hundred and twenty lambs, 60 Romanov and 60 Mérinos d'Arles, 3 months old, were distributed in four balanced groups: non-infected (G0), infected with 7000 L3 per animal once and slaughtered after 4 weeks (G14) or 8 weeks (G18), and infected 8 times and slaughtered after 8 weeks (G88). Parasitological, histological, haematological parameters and weight gains were recorded on each animal. Female and artificially nursed lambs had lower worm burdens and egg counts (epg) than males and naturally suckled lambs. No difference in parasitological parameters was seen between the two breeds, but Mérinos lambs infected once, had a higher increase in pepsinogen concentrations than Romanov lambs. In the infected animals, a significant proliferation of mast and eosinophil cells was observed in the abomasum wall. Serum pepsinogen concentrations were significantly higher 3 weeks p.i. and the weight gain was depressed during the first month p.i. The worm population was more numerous and younger in group G14 compared with G18 in which 24% of the worms had been expelled during the second month p.i. The female worms in G18 were longer and had more eggs in utero and higher egg output. After the trickle infection (G88) the take was reduced, female worms were longer with more eggs in vagina (pars ejectrix) and there was a higher variability in the number of eggs (compared with G18 data). The pepsinogen rise was smaller but no specific effect was seen on histological and haematological parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

A FORTRAN subroutine to compute inbreeding and kinship coefficients according to the number of ancestral generations.

This paper presents a FORTRAN IV subroutine to calculate inbreeding and kinship coefficients from pedigree information in a diploid population without self-fertilization. The user can specify the number of ancestral generations to be taken into account. It is thus possible to determine contributions of succeeding ancestral generations to the inbreeding and kinship coefficients under consideration. The subroutine is based on a recursive procedure that generates systematically all paths connecting two individuals. NP and NM, whose kinship coefficient is to be calculated (or between the father NP and the mother NM of the individual whose inbreeding coefficient is to be calculated). These paths obey the following conditions: (i) a given path does not contain the same parent-offspring link more than once; (ii) the vertex of a path is an ancestor common to individuals NP and NM, with a rank lower or equal to the parameter specified in input. Constraints regarding the size of the corpus of genealogical data and the storage method are discussed, as well as the interest of this subroutine compared to the existing ones. An example of application is given.