The prevalence of abnormal biochemical thyroid function reported here is substantial and confirms previous reports in smaller populations. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest elevations of TSH corresponded to changes in lipid levels that may affect cardiovascular health. Individual symptoms were not very sensitive, but patients who report multiple thyroid symptoms warrant serum thyroid testing. These results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement.

Short-term hypothyroidism after L-T4 withdrawal is associated with a significant decline in quality of life that is abrogated by rhTSH use.

We measured serum concentrations of somatomedin-C by radioimmunoassay in 57 acromegalic patients and compared them with various indicators of disease activity. The mean fasting somatomedin-C concentration was 6.8 U per milliliter (range, 2.6 to 21.7) for the acromegalics and 0.67 U per milliliter (range, 0.31 to 1.4) for 48 normal, fasting adults. The somatomedin-C concentration correlated significantly with: heel-pad thickness (r = 0.73), fasting glucose (r = 0.74), and one-hour postprandial glucose (r = 0.77). In contrast, "glucose-suppressed" growth hormone correlated weakly (r = 0.34, 0.36, 0.34) with these clinical indexes of severity. Fasting growth hormone levels showed no correlation (r = 0.14). Five active acromegalics had "normal" growth hormone levels after glucose suppression, but they had elevated somatomedin-C. In 15 patients studied one year after treatment, changes in somatomedin-C concentrations paralleled the degree of clinical improvement. Measurement of somatomedin-C appears to provide a reliable means for confirming the diagnosis of acromegaly and of clinical disease activity than measurement of growth hormone concentrations.

We have assessed the effect of fasting for 10 days on plasma concentrations of immunoreactive somatomedin C and urinary urea excretion in seven obese male volunteers. From a mean prefast value of 0.83 U/ml, plasma somatomedin C fell to 0.21 U/ml after 10 days of fasting. A prompt increase was observed with refeeding. The change in somatomedin C during fasting showed a highly significant correlation with the change in urinary urea nitrogen excretion (r = 0.74; P less than 0.001). It also was shown that inhibitors which interfere with quantitation in somatomedin bioassays are not observed in the RIA for somatomedin C. The results of this study suggest that measurement of plasma somatomedin C provides a sensitive indicator of nitrogen loss and may be useful in monitoring the changes in protein metabolism that occur during alterations in nutritional status.

Measuring serum androgen levels in women has been challenging due to limitations in method accuracy, precision sensitivity and specificity at low hormone levels. The clinical significance of changes in sex steroids across the menstrual cycle and lifespan has remained controversial, in part due to these limitations. We used validated liquid chromatography tandem mass spectrometry(LC-MS/MS) assays to determine testosterone (T) and dihydrotestosterone (DHT) along with estradiol (E2) and estrone (E1) levels across the menstrual cycle of 31 healthy premenopausal females and in 19 postmenopausal females. Samples were obtained in ovulatory women in the early follicular phase (EFP), midcycle and mid luteal phase (MLP). Overall, the levels of T, DHT, E2 and E1 in premenopausal women measured by LCMS/MS were lower overall than previously reported with immunoassays. In premenopausal women, serum T, Free T, E2, E1 and SHBG levels peaked at midcycle and remained higher in the MLP, whereas DHT did not change. In postmenopausal women, T, free T, SHBG and DHT were significantly lower than in premenopausal women, concomitant with declines in E2 and E1. These data support the hypothesis that the changes in T and DHT that occur across the cycle may reflect changes in SHBG and estrogen, whereas in menopause, androgen levels decrease. LC-MS/MS may provide more accurate and precise measurement of sex steroid hormones than prior immunoassay methods and can be useful to assess the clinical significance of changes in T, DHT, E2 and E1 levels in females.

GATA2 is expressed in the pituitary during development and in adult gonadotropes and thyrotropes. It is proposed to be important for gonadotrope and thyrotrope cell fate choice and for TSH production. To test this idea, we produced a pituitary-specific knockout of Gata2, designed so that the DNA-binding zinc-finger region is deleted in the presence of a pituitary-specific recombinase transgene. These mice have reduced secretion of gonadotropins basally and in response to castration challenge, although the mice are fertile. GATA2 deficiency also compromises thyrotrope function. Mutants have fewer thyrotrope cells at birth, male Gata2-deficient mice exhibit growth delay from 3-9 wk of age, and adult mutants produce less TSH in response to severe hypothyroidism after radiothyroidectomy. Therefore, Gata2 appears to be dispensable for gonadotrope and thyrotrope cell fate and maintenance, but important for optimal gonadotrope and thyrotrope function. Gata2-deficient mice exhibit elevated levels of Gata3 transcripts in the pituitary gland, suggesting that GATA3 can compensate for GATA2.

In this 12-week trial, the thyroid hormone analogue eprotirome was associated with decreases in levels of atherogenic lipoproteins in patients receiving treatment with statins. (ClinicalTrials.gov number, NCT00593047.)

Subclinical hypothyroidism is defined as an elevated serum TSH level associated with normal total or free T 4 and T 3 values. The overall prevalence has been reported to range from 4 -10% in large general population screening surveys (1-5) and from 7-26% in studies of the elderly (1-3, 6 -11). Because of the frequency with which this condition is encountered, important questions have been raised regarding its clinical relevance and appropriate management. One of the myths that surrounds subclinical hypothyroidism is that the laboratory profile of an elevated serum TSH and normal free thyroid hormone levels really represents "compensated hypothyroidism." The reasoning behind this idea is that, since the circulating levels of thyroid hormones are within the normal range with only the serum TSH being elevated, the affected subject is really euthyroid because the increased TSH is stimulating and driving the thyroid gland to produce normal thyroid hormone levels. Certainly, elevated serum TSH levels do stimulate even a diseased thyroid gland to produce and release more thyroid hormone. However, as long as the serum TSH level remains elevated, the thyroid hormone levels are not truly normal for that individual. The clearance kinetics of thyroid hormones and TSH from the circulation actually make such a conclusion inescapable. Because the half-life of T 4 is 7 d and that of T 3 is 1 d, the serum TSH, which has a half-life of less than 1 h, would certainly be expected to return to normal if thyroid hormone levels were, indeed, normal for that individual. An elevated TSH in an individual patient, thus, means that the circulating thyroid hormone concentrations are insufficient, with a few rare exceptions (TSH-secreting tumors, thyroid hormone resistance syndromes). We, indeed, believe that subclinical hypothyroidism represents mild thyroid failure and is a clinically important disorder that has adverse clinical consequences and that should be treated in most, if not all, cases. We will support this position by reviewing the reported objective data regarding its natural history, its clinical manifestations, and the benefits of treatment. Natural historyMild thyroid failure represents an early stage of thyroid disease that will commonly progress to overt hypothyroid-ism. Progression has, in fact, been reported to occur in approximately 3-18% of affected patients per year (10 -17). One study evaluated the natural history of mild thyroid failure in 154 female patients over a 10-yr period; 57% of patients continued to have mild thyroid failure, 34% of patients progressed to overt hypothyroidism, and 9% of patients reverted to a normal TSH level. How many of the 9% had a transient form of thyroiditis such as silent, subacute, or postpartum thyroiditis is unclear (17). The strongest predictors of progression are the presence of antithyroid antibodies, serum TSH values greater than 20 U/ml, a history of radioiodine ablation for Graves' disease, a history of external radiation therapy for nonthyroid malignancies, and chronic lithiu...