Thyroid function at the third trimester of pregnancy in a Northern French population.

OBJECTIVES: During pregnancy, the production rate of thyroid hormone increases when iodine intake is sufficient. However, the appropriateness of the free thyroxin (FT4) immunoassay is questionable. We have therefore evaluated prospectively the thyroid function in pregnancy and the relevance of the FT4 immunoassay. PATIENTS AND METHODS: The thyroid function of 114 pregnant, healthy Parisian women with mild iodine deficiency was studied at the third trimester of pregnancy, 55 of whom served as their own control three months after delivery, and the results were compared to North American reference values. RESULTS: All French pregnant women showed an increase in thyroxin binding globulin (TBG) serum levels. FT4 levels decreased by about 30% at the third trimester of pregnancy, as compared to 10-15% in the American population. Moreover, the increase in total thyroxin (TT4) secretion represented only 27%, as compared to 50% in the American population. Linear regression model analysis showed a positive correlation between levels of TT4 and TBG, TT4 and FT4, as well as FT4 and free thyroxin index (FTI). CONCLUSION: The hypothyroxinemia at the third trimester of pregnancy was more prominent in the Parisian population and insufficient iodine intake could be responsible for the deficient increase in TT4. It is therefore concluded that the inability of the thyroid to establish the required equilibrium could be corrected by systematic iodine supplementation before pregnancy. Finally, the strong correlation between FT4 and FTI suggests that the quality of FT4 test immunoassay is appropriate for estimating FT4 serum levels during pregnancy.

Update on the diagnosis and therapy of distant metastases of differentiated thyroid carcinoma.

Differentiated thyroid cancer, when adequately treated, has an overall good prognosis. However, 10-15% of patients develop distant metastases. The presence of metastases is an important prognostic factor that negatively affects survival. For (131)I-avid distant metastases, (131)I therapy is a very effective treatment modality that induces complete remission in about a third of patients. These figures may be even higher in case of early diagnosis, when tumor burden is still limited. Additional measures may include surgery and/or external beam radiation therapy. Cytotoxic chemotherapy is largely ineffective in patients with progressive, poorly differentiated cancer. These patients should be candidates for trials with new molecularly targeted therapeutic agents. In this paper, a review of diagnostic modalities, prognostic factors and therapeutic options for patients with distant metastases is proposed. In particular, the prognostic value of the early discovery of metastatic disease will be underlined.

A new LH receptor splice mutation responsible for male hypogonadism with subnormal sperm production in the propositus, and infertility with regular cycles in an affected sister.

BACKGROUND: Inactivating LH receptor (LHR) mutations have been described so far in men as well as in women. Phenotypes in men have been variable with in nearly all cases impairment of sex differentiation or azoospermia. We report a milder reproductive phenotype both in a male patient and his sister. METHODS AND RESULTS: We describe a family that carries a homozygous mutation G-->A at position -1 at the intron 10-exon 11 boundary of the LHR gene. The male patient presented with delayed puberty, micropenis and oligospermia. Two of his sisters were homozygous for the same mutation and were infertile. Surprisingly, one of them was found to have had regular ovarian cycles for years and showed normal LH values (6.5 and 10.6 mIU/ml for LH and FSH, respectively). In vitro analysis showed that this altered splicing resulted in an LHR from which eight amino acids are deleted from the extracellular domain (Delta Tyr(317)-Ser(324)). In vitro expression has shown that the receptor was expressed and capable of LH-induced signaling, albeit with reduced potency (P < 0.001). CONCLUSIONS: LHR mutations may represent an underestimated cause of infertility in women, in addition to being responsible for male hypogonadism with reduced spermatogenesis.