Pilot study on the assessment of the setpoint of the hypothalamus-pituitary-thyroid axis in healthy volunteers.

OBJECTIVE: To determine the log-linear relationship between TSH and free thyroxine in healthy subjects, and the variation in baseline TSH/free thyroxine (FT(4)) combination in each individual. SUBJECTS AND METHODS: Twenty-one healthy volunteers (nine males and 12 females; mean age 60 years, range 51-74) were randomized to receive at 2300 h with 2-week intervals a single dose of placebo, 125 microg T(4) and 250 microg T(4) (arm 1, n=10), or placebo, 25 microg triiodothyronine (T(3)) and 50 microg T(3) (arm 2, n=11). Blood samples were taken in the morning (0800-1100 h) before and following the administration of the drug for the assessment of TSH, FT(4) and T(3). RESULTS: Intra- and inter-individual variation and the individuality index of the four baseline serum samples were respectively 21.6%, 41.9% and 0.52 for TSH; 9.9%, 16.5% and 0.60 for FT(4); and 9.3%, 16.0% and 0.58 for T(3). Substantial differences existed in the location of individual working points within the reference range. T(4) administration increased FT(4) (but not T(3)) and decreased TSH, resulting in a log-linear relationship (log TSH=1.50-0.059xFT(4), P<0.05) for the whole group. T(3) administration increased T(3) and decreased TSH (but not FT(4)), resulting in a log-linear relationship (log TSH=0.790-0.245xT(3), P<0.001) for the whole group. Log-linear relationships were not always significant when assessed for each subject separately. CONCLUSION: Individuality indices of TSH, FT(4) and T(3) are all

Evaluation of endocrine tests. D: the prolonged fasting test for insulinoma.

OBJECTIVE: To establish the diagnostic performance of the prolonged fasting test in patients suspected of insulinoma. METHODS: We included all patients who were referred to our department between August 1995 and August 2006 with a clinical suspicion of insulinoma. Insulinoma was diagnosed by a positive Whipple's triad during the prolonged fast in combination with an insulin/C-peptide ratio below 1. The presence of insulinoma was confirmed by histopathological data, which was considered the golden standard. If the prolonged fast was negative, long-term follow-up was obtained. RESULTS: Ten patients had a positive Whipple's triad during the prolonged fast: eight had a histologically proven insulinoma, and two had factitious hypoglycaemia (insulin/C-peptide ratio >1.0) One additional patient likely had an insulinoma, but the Whipple's triad remained absent at up to 56 hours of fasting. Follow-up (median 53 months (3 to 142) in 76% of patients with a negative fasting test revealed no missed cases of insulinoma. During the prolonged fast the glucose, insulin and C-peptide concentrations overlapped in patients with and without insulinoma. CONCLUSION: In our centre, the prolonged fasting test defined as a positive Whipple's triad in combination with an insulin/C-peptide ratio <1 had a sensitivity of 88.9% and a specificity of 100% for the diagnosis of insulinoma.

Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death.

BACKGROUND: To examine the relationship between maternal TSH and free thyroxine (FT(4)) concentrations in early pregnancy and the risk of miscarriage, fetal or neonatal death. METHOD: Cohort study of 2497 Dutch women. TSH, FT(4), and thyroid peroxidase antibodies concentrations were determined at first booking. Child loss was operationalized as miscarriage, fetal or neonatal death. Women with overt thyroid dysfunction were excluded. RESULTS: Twenty-seven cases of child loss were observed. The mean TSH and FT(4) level in the women with child loss was 1.48 mU/l and 9.82 pmol/l compared with 1.11 mU/l and 9.58 pmol/l in women without child loss. The incidence of child loss increased by 60% (OR=1.60 (95% confidence interval (CI): 1.04-2.47)) for every doubling in TSH concentration. This association remained after adjustment for smoking, age, parity, diabetes mellitus, hypertension, previous preterm deliveries, and previous preterm stillbirth/miscarriage (adjusted odds ratio=1.80 (95% CI: 1.07-3.03)). This was not true for FT(4) concentrations (OR=1.41 (95% CI: 0.21-9.40); P=0.724). CONCLUSION: In a cohort of pregnant women without overt thyroid dysfunction, the risk of child loss increased with higher levels of maternal TSH. Maternal FT(4) concentrations and child loss were not associated.

Ethnic differences in TSH but not in free T4 concentrations or TPO antibodies during pregnancy.

OBJECTIVE: To describe the TSH, free T4 and thyroid peroxidase antibody (TPO-Ab) concentrations during pregnancy among four ethnic groups and to determine reference values for these parameters during normal pregnancy. METHODS: Cross-sectional study of a cohort of 3270 pregnant women living in the city of Amsterdam. Blood samples were drawn at first booking in the first or second trimester. TSH, free T4 and TPO-Ab concentrations were determined. Four ethnic groups were studied: Dutch, Surinam, Turkish and Moroccan. RESULTS: Plasma TSH increased and free T4 decreased from the first to the second trimester of pregnancy for all the ethnic groups. Ethnic differences were observed in TSH concentrations, with Dutch females having the highest TSH levels compared to the other three ethnic groups. The median TSH difference was 0.16 mU/l between the Dutch and Moroccan women, 0.15 mU/l between the Dutch and Surinam women and 0.10 mU/l between the Dutch and Turkish women. These could not be explained by differences in age, parity and current smoking status. No differences were seen in free T4 concentrations between the four ethnic groups. The prevalence of TPO-Ab was comparable across the ethnic groups (about 6% in each); the concentration of TPO-Ab was also comparable among the ethnic groups. The Dutch women had a higher lower-limit (2.5 percentile) of the TSH reference range than the Surinam, Turkish and Moroccan women, ranging from 0.14 mU/l for the Surinam and Moroccan to 0.27 mU/l for the Dutch women. CONCLUSION: The increase in TSH and decrease in free T4 values during pregnancy correspond to previous reported studies. Pregnant Dutch women had consistently higher TSH values than the ethnic group, but corresponding free T4 levels and TPO-Ab did not differ between these ethnic groups.