Measurement of serum TSH in the investigation of patients presenting with thyroid enlargement.
In otherwise euthyroid patients presenting with thyroid enlargement, reduction in serum thyrotrophin (TSH) concentrations measured in a sensitive assay may be a marker of thyroid autonomy and may therefore indicate a benign underlying pathology. We investigated prospectively a cohort of 467 subjects presenting consecutively to our thyroid clinic with nodular or diffuse enlargement of the thyroid. Subjects were divided into those with normal (0.4-5.5 mU/l), low but detectable (0.1-0.39 mU/l) or undetectable (< 0.1 mU/l) serum TSH concentrations. The final pathological diagnosis was defined by fine-needle aspiration cytology and clinical follow-up of at least 2 years or by fine-needle aspiration cytology and histology following surgical treatment. Serum TSH concentrations below normal were found in 75 patients (16.1%), those with low serum TSH results having higher mean free T4 concentrations, were older and were more likely to be female. In those with undetectable serum TSH, no patient had a diagnosis of thyroid neoplasia and in those with low but detectable TSH, thyroid neoplasms were diagnosed in two patients (3.4%). In those with normal serum TSH, 12.0% had a final diagnosis of thyroid neoplasm (p = 0.013). Overall, thyroid malignancy was found in one patient (1.3%) of those with a serum TSH measurement below the normal range and 6.9% of those with normal serum TSH (p < 0.06). Reduction in serum TSH at presentation may identify a group which requires less intensive investigation and follow-up than those without biochemical evidence of thyroid autonomy. (+info)
Growth hormone-releasing peptide-2 infusion synchronizes growth hormone, thyrotrophin and prolactin release in prolonged critical illness.
OBJECTIVE: During prolonged critical illness, nocturnal pulsatile secretion of GH, TSH and prolactin (PRL) is uniformly reduced but remains responsive to the continuous infusion of GH secretagogues and TRH. Whether such (pertinent) secretagogues would synchronize pituitary secretion of GH, TSH and/or PRL is not known. DESIGN AND METHODS: We explored temporal coupling among GH, TSH and PRL release by calculating cross-correlation among GH, TSH and PRL serum concentration profiles in 86 time series obtained from prolonged critically ill patients by nocturnal blood sampling every 20 min for 9 h during 21-h infusions of either placebo (n=22), GHRH (1 microg/kg/h; n=10), GH-releasing peptide-2 (GHRP-2; 1 microg/kg/h; n=28), TRH (1 microg/kg/h; n=8) or combinations of these agonists (n=8). RESULTS: The normal synchrony among GH, TSH and PRL was absent during placebo delivery. Infusion of GHRP-2, but not GHRH or TRH, markedly synchronized serum profiles of GH, TSH and PRL (all P< or =0.007). After addition of GHRH and TRH to the infusion of GHRP-2, only the synchrony between GH and PRL was maintained (P=0.003 for GHRH + GHRP-2 and P=0.006 for TRH + GHRH + GHRP-2), and was more marked than with GHRP-2 infusion alone (P=0.0006 by ANOVA). CONCLUSIONS: The nocturnal GH, TSH and PRL secretory patterns during prolonged critical illness are herewith further characterized to include loss of synchrony among GH, TSH and PRL release. The synchronizing effect of an exogenous GHRP-2 drive, but not of GHRH or TRH, suggests that the presumed endogenous GHRP-like ligand may participate in the orchestration of coordinated anterior pituitary hormone release. (+info)
Insulin and TSH promote growth in size of PC Cl3 rat thyroid cells, possibly via a pathway different from DNA synthesis: comparison with FRTL-5 cells.
In the rat thyroid cell lines PC Cl3, FRTL- 5 and WRT, proliferation is mainly regulated by insulin or IGF, and TSH. However, the mechanism regulating cell mass doubling prior to division is still unknown. Our laboratory has shown that in dog thyroid cells insulin promotes growth in size while TSH in the presence of insulin triggers DNA replication. In the absence of insulin, TSH has no effect on cell growth. In this report we investigated insulin action on both cell mass and DNA synthesis and its modulation by TSH and insulin in PC Cl3 and FRTL-5 cells. In PC Cl3 cells, insulin activated not only DNA synthesis but also protein synthesis and accumulation. Although TSH potentiated the stimulation of DNA synthesis induced by insulin, enhancement of protein synthesis by both agents was additive. All TSH effects were reproduced by forskolin. Similar effects were also obtained in FRTL-5 cells. This suggests that insulin and TSH, via cAMP, modulate both growth in size and DNA replication in these cell lines. Lovastatin, which blocks 3-hydroxy-3-methylglutaryl coenzyme A reductase, decreased the induction of DNA synthesis, but not of protein synthesis induced by insulin or TSH in PC Cl3 cells. In FRTL-5 cells, lovastatin reduced protein and DNA synthesis stimulated by insulin but not TSH-induced protein synthesis. Taking these data together, we propose that insulin and/or TSH both modulate cell mass doubling and DNA synthesis in these cell lines, presumably via different pathways, and that there are at least two pathways which regulate growth in size in FRTL-5 thyroid cells: one triggered by insulin, which is lovastatin sensitive, and the other activated by TSH, which is not sensitive to lovastatin. (+info)
Development of a thyroid function strategy for general practice.
A study was carried out to investigate a thyroid stimulating hormone (TSH) frontline strategy that could potentially result in a more straightforward interpretation of thyroid function tests, a reduction in the number of inappropriate referrals to medical outpatients, an improvement in the 'turnaround time' of results, and a reduction in the number of unnecessary tests carried out, thereby reducing costs. (+info)
Polarized targeting of epithelial cell proteins in thyrocytes and MDCK cells.
Polarized trafficking signals may be interpreted differently in different cell types. In this study, we have compared the polarized trafficking of different proteins expressed endogenously in primary porcine thyroid epithelial cells to similar proteins expressed in MDCK cells. As in MDCK cells, NH4Cl treatment of filter-grown thyrocytes caused mis-sorted soluble proteins to exhibit enhanced secretion to the apical medium. In independent studies, thrombospondin 1 (a thyroid basolaterally secreted protein) was secreted basolaterally from MDCK cells. Likewise, the 5'-deiodinase (a thyroid basolateral membrane protein) encoded by the DIO1 gene was also distributed basolaterally in transfected MDCK cells. Consistent with previous reports, when the secretion of human growth hormone (an unglycosylated regulated secretory protein) was examined from transfected MDCK cells, the release was nonpolarized. However, transfected thyrocytes secreted growth hormone apically in a manner dependent upon zinc addition. Moreover, two additional regulated secretory proteins expressed in thyrocytes, thyroglobulin (the major endogenous glycoprotein) and parathyroid hormone (an unglycosylated protein expressed transiently), were secreted apically even in the absence of zinc. We hypothesize that while cellular mechanisms for interpreting polarity signals are generally similar between thyrocytes and MDCK cells, thyrocytes allow for specialized packaging of regulated secretory proteins for apical delivery, which does not require glycosylation but may involve availability of certain ions as well as appropriate intracellular compartmentation. (+info)
Biological activities of tyrosine-containing somatostatin analogs on inhibition of secretion of thyrotropin and growth hormone.
The following five tyrosine-containing analogs of somatostatin (GIF) were synthesized by the solid-phase method: Tyr-GIF: [Tyr6]-GIF; [Tyr7]-GIF; [Tyr8]-GIF; [Tyr11]-GIF. These analogs except [Tyr8]-GIF were demonstrated to possess almost the same potency to inhibit thyrotropin release stimulated by thyrotropin-releasing hormone as that of synthesized GIF in vivo. [Tyr8]-GIF had potencies less than 0.5% of GIF. They also had the activity to inhibit Nembutal-induced growth hormone rise. The structure-activity relationship and availability of these analogs for radioimmunoassay were discussed. (+info)
Reverse triiodothyronine, thyroid hormone, and thyrotrophin concentrations in placental cord blood.
Reverse triiodothyronine (rT3), triiodothyronine (T3), thyroxine (T4), thyroxine binding globulin (TBG), and thyrotrophin (TSH) were measured in sera from placental cord blood in an unselected series of 272 deliveries. In this series the concentrations of rT3 (mean 3.33 nmol/l, 95% confidence limits 1.6--7.0 nmol/l), were log normally distributed and did not overlap the adult normal range (0.11--0.44 nmol/l). There were no correlations between the cord blood concentrations of rT3, T3, T4, and TSH. The cord serum rT3 concentration was not influenced by maturity, birth-weight, or neonatal risk factors, whereas these factors did affect the concentrations of T3, T4, AND TBG. There is no arteriovenous rT3 concentration difference across the placenta, therefore the cord rT3 reflects the systemic rT3 concentration in the baby at birth. As rT3 in the neonate largely, if not entirely, derives from thyroxine from the fetal thyroid, measurement of the cord rT3 concentration may be a good immediate screening test for neonatal hypothyroidism. (+info)
Central hypothyroidism associated with retinoid X receptor-selective ligands.
BACKGROUND: The occurrence of symptomatic central hypothyroidism (characterized by low serum thyrotropin and thyroxine concentrations) in a patient with cutaneous T-cell lymphoma during therapy with the retinoid X receptor-selective ligand bexarotene led us to hypothesize that such ligands could reversibly suppress thyrotropin production by a thyroid hormone-independent mechanism and thus cause central hypothyroidism. METHODS: We evaluated thyroid function in 27 patients with cutaneous T-cell lymphoma who were enrolled in trials of high-dose oral bexarotene at one institution. In addition, we evaluated the in vitro effect of triiodothyronine, 9-cis-retinoic acid, and the retinoid X receptor-selective ligand LGD346 on the activity of the thyrotropin beta-subunit gene promoter. RESULTS: The mean serum thyrotropin concentration declined from 2.2 mU per liter at base line to 0.05 mU per liter during treatment with bexarotene (P<0.001), and the mean serum free thyroxine concentration declined from 1.0 ng per deciliter (12.9 pmol per liter) at base line to 0.45 ng per deciliter (5.8 pmol per liter) (P<0.001) during treatment. The degree of suppression of thyrotropin secretion tended to be greater in patients treated with higher doses of bexarotene (>300 mg per square meter of body-surface area per day) and in those with a history of treatment with interferon alfa. Nineteen patients had symptoms or signs of hypothyroidism, particularly fatigue and cold intolerance. The symptoms improved after the initiation of thyroxine therapy, and all patients became euthyroid after treatment with bexarotene was stopped. In vitro, LGD346 suppressed the activity of the thyrotropin beta-subunit gene promoter in thyrotrophs by as much as 50 percent, an effect similar to that of triiodothyronine and 9-cis-retinoic acid. CONCLUSIONS: Hypothyroidism may develop in patients with cutaneous T-cell lymphoma who are treated with high-dose bexarotene, most likely because the retinoid X receptor-selective ligand suppresses thyrotropin secretion. (+info)