Suppressed Serum Thyrotropin Research Articles

A Case of Graves' Disease Coexistent with Pulmonary Sarcoidosis

Sarcoidosis is a multisystemic granulomatous disease with an of unknown etiology, involving bilateral hilar lymphadenopathy, pulmonary, skin and eye lesions. However, involvement of the endocrine system in sarcoidosis is quite rare, and the coexistence of both diseases is extremely unusual. We describe a 60-year-old woman presenting with sarcoidosis and Graves' disease. She was admitted for evaluation of dry cough, dyspnea, palpitation and general weakness. Both thyroid glands were enlarged diffusely. The thyroid function tests showed suppressed serum thyrotropin and an increased thyroid hormone level. The levels of the TSH receptor antibody, anti-thyroglobulin antibody and anti-microsomal antibody were higher than normal. The radionuclide scan(131 I) showed increased iodine uptake. The chest X-ray revealed pulmonary hilar enlargement and high resolution CT showed both hilar lymph nodes enlargement and tiny parenchymal nodules. The transbronchial lung biopsy showed a noncaseating granuloma without necrosis. We report this case of pulmonary sarcoidosis plus Graves' disease with a review of the relevant literatures. (Tuberc Respir Dis 2007; 62: 417-420)

The association between subclinical hyperthyroidism and blood pressure in a population-based study

Although evidence for an increased risk of hypertension in both overt hyperthyroidism and overt hypothyroidism is consistent, the relation between subclinical hyperthyroidism and blood pressure has not yet received sufficient attention. The Study of Health in Pomerania is a population-based survey in Germany that was conducted in a previously iodine-deficient region. A study population of 4087 subjects (2050 women) without overt hyperthyroidism or increased serum thyrotropin levels was available for the present study. Serum thyrotropin levels < 0.25 mIU/l and < 0.1 mIU/l were considered decreased and suppressed, respectively. Multivariable analyses revealed lower adjusted mean values for systolic blood pressure in subjects with decreased [132.9 mmHg, 95% confidence interval (CI) = 131.1 mmHg; 134.8 mmHg] versus normal serum thyrotropin levels (135.0 mmHg, 95% CI = 134.4 mmHg; 135.6 mmHg, P = 0.04). The adjusted mean values for diastolic blood pressure and pulse pressure did not differ significantly between both groups. Analyses that were performed after all subjects receiving antihypertensive medications had been excluded did not reveal any statistically significant associations between decreased serum thyrotropin levels and the endpoints investigated. There was also no association of suppressed serum thyrotropin levels with blood pressure or hypertension. It is concluded that subclinical hyperthyroidism, as demonstrated by decreased as well as suppressed serum thyrotropin levels and serum free thyroid hormone levels within the reference range, is not associated with hypertension.

Surgery is the Procedure of Choice for the Treatment of Patients with Toxic Adenoma in an Endemic Goitre Area

Purpose : Toxic adenoma is one of the main causes of hyperthyroidism. We investigated the efficacy of surgery in the treatment of toxic adenoma.Methods : Serum thyroid stimulating hormone (TSH) measurement, ultrasound and scintigraphy of the thyroid were made for diagnostic purpose. The safety of surgery was evaluated by postoperative clinical course of patients. The efficacy of surgery was determined by the function of the remaining thyroid tissue.Results : The incidence of hyperthyroidism was 53% in surgically treated patients with nodular goitre in our iodine deficient region. The cause of thyrotoxicosis was toxic adenoma in 15 patients (14%). Suppressed serum TSH levels indicated the hyperthyroidism in all of 15 patients. Solitary solid adenoma was found by ultrasonographic examination, and solitary autonomous hot nodule by thyroid scintigraphy. Surgical treatment consisted of unilateral total lobectomy. It was the primary treatment in 13 patients. Two patients had surgery as secondary treatment after unsuccessful primary radioactive iodine application. The early postoperative clinical course of all patients was uneventful. Thirteen patients who had surgery as primary treatment had normal thyroid function postoperatively contrary to other two patients who became hypothyroid after having unsuccessful radioiodine therapy, and surgery as the secondary treatment. Conclusions : The incidence of hyperthyroidism and toxic adenoma is high in our surgically treated patients with nodular goitre. The diagnosis of toxic adenoma is not difficult by serum TSH measurements, and ultrasound and nuclear imaging of the thyroid. Surgery is effective and safe, and the treatment of choice for patients with toxic adenoma in order to control radically the hyperthyroidism and to achieve the goal of providing the euthyroid status.

Thyroid storm prior to induction of anaesthesia

A 53- year-old woman without a previous history of thyroid disease was scheduled for mastectomy. On arrival in the operating theatre unpremedicated she appeared restless and tachycardic. Midazolam and fentanyl was administered intravenously. Concomitantly, sinus tachycardia developed and a flush reaction was observed in the skin of the thoracic region and neck. The blood pressure increased to 265/160 mmHg and the patient lost consciousness and became apnoeic. Unconsciousness and apnoea lasted for approximately 25 min and the operation was postponed. Further investigations revealed an elevated serum free thyroxine level and suppressed serum thyrotropin diagnostic of hyperthyroidism. The serum TSH receptor antibody concentration was elevated, indicating that the patient was suffering from Graves' disease. We present a case of a previously unknown hyperthyroid patient, with breast cancer, presenting as a thyroid crisis on induction of anaesthesia. Although being quite a rare occurrence, unsuspected thyroid disease should be borne in mind when an agitated patient enters the operating theatre.

Treatment of thyrotoxicosis

Thyrotoxicosis is the clinical syndrome resulting from excess circulating free thyroxine (free-T4) and/or free tri-iodothyronine (free-T3) (Figure 1). Thyrotoxicosis is common, with a lifetime incidence of about 2% in women and 0.2% in men. The diagnosis is usually confirmed by the finding of a suppressed serum thyroid stimulating hormone (TSH) concentration in the presence of elevated free thyroid hormone levels. Because free-T3 concentration tends to rise before free-T4, ‘T3 toxicosis’ (elevated free-T3, but normal free-T4) is often the earliest phase of any form of thyrotoxicosis.

Low but detectable serum thyroid-stimulating hormone concentrations in ambulant subjects not receiving thyroxine.

In laboratories employing 'front-line' sensitive thyroid-stimulating hormone (TSH) measurement, it is generally accepted that a fully suppressed serum TSH concentration (third-generation assay) alongside normal serum concentrations of free thyroid hormones indicates subclinical hyperthyroidism. However, other explanations are often provided for low but detectable serum TSH concentrations, such as drug effects or non-thyroidal illness. We investigated 25 consecutive ambulant individuals, identified over an 18-month period as having low but not fully suppressed TSH concentrations (third-generation assay; sensitivity 0.003 mIU/L) with additional free thyroxine (T(4)), free tri-iodothyronine (T(3)) and thyroid microsomal antibody estimations and thyroid isotope scanning (technetium). Concentrations of serum hormones (median, inter-quartile range) were: TSH, 0.23, 0.17-0.26 mIU/L (reference range 0.34-5.6 mIU/L); free T(4), 14.6, 10.6- 17.6 pmol/L (reference range 10-25 pmol/L); free T(3), 6.1, 5.7-6.6 pmol/L (reference range 4.5-7.5 pmol/L). Thyroid antibodies were negative in all but one individual. On isotope scanning, nine individuals had hot nodules and ten individuals had multinodular goitres (MNG). Of the six with normal scans, ultrasound scanning showed a definite MNG (n = 1) and early MNG (n = 2). A low but detectable serum TSH concentration, obtained using a third-generation assay, found in an ambulant individual, is frequently a pointer to underlying thyroid disease.

Thyroid hormone resistance and increased metabolic rate in the RXR-gamma-deficient mouse.

Vitamin A and retinoids affect pituitary-thyroid function through suppression of serum thyroid-stimulating hormone (TSH) levels and TSH-beta subunit gene expression. We have previously shown that retinoid X receptor-selective (RXR-selective) ligands can suppress serum TSH levels in vivo and TSH-beta promoter activity in vitro. The RXR-gamma isotype has limited tissue distribution that includes the thyrotrope cells of the anterior pituitary gland. In this study, we have performed a detailed analysis of the pituitary-thyroid function of mice lacking the gene for the RXR-gamma isotype. These mice had significantly higher serum T4 levels and TSH levels than did wild-type (WT) controls. Treatment of RXR-gamma-deficient and WT mice with T3 suppressed serum TSH and T4 levels in both groups, but RXR-gamma-deficient mice were relatively resistant to exogenous T3. RXR-gamma-deficient mice had significantly higher metabolic rates than did WT controls, suggesting that these animals have a pattern of central resistance to thyroid hormone. RXR-gamma, which is also expressed in skeletal muscle and the hypothalamus, may have a direct effect on muscle metabolism, regulation of food intake, or thyrotropin-releasing hormone levels in the hypothalamus. In conclusion, the RXR-gamma isotype appears to contribute to the regulation of serum TSH and T4 levels and to affect peripheral metabolism through regulation of the hypothalamic-pituitary-thyroid axis or through direct effects on skeletal muscle.

Effect of iodine supplementation on a pediatric population with mild iodine deficiency.

A cross-sectional study in two stages consisted of healthy children to assess the effect of iodine supplementation on a pediatric population with mild iodine deficiency in an ongoing program in the Province of Pontevedra, northwestern Spain. In the first survey (1984), 1565 schoolchildren and in the second survey (1995) 907 schoolchildren were randomly selected from the population. In January 1985, a mandatory consumption of iodized salt in our region was begun. In both surveys we studied prevalence of goiter, urinary iodine excretion, and prevalence of thyroid dysfunction. Similar prevalences of goiter were observed in both surveys, 3.7% versus 3.9%; however, significantly lower prevalence of Ib and II degree goiters were observed in the second survey. The mean iodine excretion was 88.6 +/- 73 microg/L (median 66.3) and 146.4 +/- 99 microg/L (median 115.7), p < 0.01 for the first and second surveys, respectively. Finally, the overall prevalence of thyroid dysfunction was similar in both surveys, 9.2% versus 7.0%; however, significantly lower prevalence of suppressed serum thyrotropin (TSH), considered as a marker of subclinical hyperthyroidism, was observed in the second survey when compared to the first, 0.1% versus 2%, p < 0.01. Our results are in agreement with the recent data from Denmark, where the prevention of subclinical hyperthyroidism occurring in the elderly as a consequence of longstanding mild iodine deficiency is the reason that the Danish finally started iodine supplementation on a national basis. In conclusion, long-term correction of mild iodine deficiency in a pediatric population has beneficial effects on the prevalence of high-degree goiters, and this correction reduces significantly the prevalence of subclinical hyperthyroidism. The present observation constitutes a strong argument for correcting even mild iodine deficiency.

A T2S cross-reactive material (compound W) in hyperthyroid patients with trophoblastic disease.

In a previous study we observed increased serum levels of a 3,3'-diiodothyronine sulfate (T2S)-like material (compound W) in women who received human chorionic gonadotropin (hCG) treatment. In the present study we assessed serum compound W values in 113 women (total serum sample: 190) with trophoblastic disease, in 7 normal nonpregnant women during the menstrual cycle and 7 women given hCG treatment in the course of in vitro fertilization. Fifty-three women with trophoblastic disease had serum free thyroxine (FT4) concentrations greater than 3.0 ng/dL with suppressed serum thyrotropin (TSH) levels; 61 had FT4 values less than 3.0 ng/dL with a mean TSH of 0.83 mU/L. Mean (+/- SE) compound W concentrations in the high FT4 group were significantly higher than in the low FT4 group (76 +/- 8.1 vs. 21 +/- 1.7 ng T2S equivalent, p < 0.001) There were significant correlations between serum hCG and compound W concentrations (r = 0.472, p < 0.001), serum FT4 and hCG (r = 0.503, p < 0.0001) and serum FT4 and compound W (r = 0.585, p < 0.0001). In nonpregnant women serum compound W levels increased from 7.5 +/- 8 ng/dL at the end of the menstrual period to 15 +/- 1.7 ng/dL 21 days after the last menstrual period. Finally, a single dose of hCG (10,000 USP units, intramuscularly) increased mean (+/- SE) serum compound W levels from 12.8 +/- 2.3 to 64 +/- 9.7 ng/dL and 54 +/- 12 ng/dL at 9 and 16 days, respectively. These results indicate that hCG and perhaps luteinizing hormone (LH) increase serum compound W concentrations in women. The mechanism and significance presently are unclear.

Thyrotoxic Bone Disease in Women: A Potentially Reversible Disorder

To measure changes in spinal and femoral neck bone mineral densities in patients treated for Graves thyrotoxicosis. Cohort study. Tertiary care center. Fifteen women with active Graves thyrotoxicosis. Six patients were premenopausal and nine were postmenopausal. All patients had evidence of thyrotoxicosis as indicated by a raised total serum thyroxine, suppressed serum thyroid-stimulating hormone, and an elevated technetium-99m pertechnetate thyroid scan. A control group of 15 healthy volunteers matched for age, sex, and menopausal status were followed during the same period. Bone mineral density was measured by dual-energy x-ray absorptiometry at baseline and after 12 months of antithyroid therapy when euthyroidism had been achieved. After 12 months of therapy, total serum thyroxine, total serum triiodothyronine, serum alkaline phosphatase, and serum bone Gla-protein activities had returned to normal in all patients (P < 0.001 for all comparison between initial and final biochemical measurements). During this interval, the mean lumbar spine bone mineral increased from an initial value of 1.01 g/cm2 to 1.07 g/cm2, an increase of 6.6% per year (95% CI, 3.6% to 9.6%) (P < 0.001 compared with controls). Increases in femoral neck (1.2%/y; CI, -2.1% to 4.5%; P = 0.2 compared with controls) and femoral trochanter bone mineral (3.2%/y; CI, 2.4% to 8.7%; P = 0.2 compared with controls) were not statistically significant. Using forced-entry multiple regression analysis, the severity of the thyrotoxicosis was independently associated with the percentage increment in lumbar spine bone mineral density after 12 months of antithyroid therapy. Effective treatment of Graves thyrotoxicosis was associated with increases in lumbar spine and femoral neck bone mineral. Although the changes in bone mineral were modest, our data suggest that thyrotoxic bone loss may be a reversible disorder.

Limitations to the Use of a Sensitive Assay for Serum Thyrotropin in the Assessment of Thyroid Status

In the majority of clinical settings, a suppressed serum thyrotropin (s-TSH) level determined by the new sensitive assays is diagnostic of thyrotoxicosis. This has led to its proposed use as a screen for thyroid disease. However, s-TSH may be suppressed in conditions other than thyrotoxicosis. We retrospectively reviewed s-TSH measurements made in a large heterogeneous population to determine in which settings a suppressed value could potentially lead to misdiagnosis. We found that a suppressed s-TSH level was useful in making the diagnosis of autonomous thyroid function and in the assessment of thyroid hormone replacement therapy in patients with primary, but not central, hypothyroidism. Hyperthyroidism caused by either intrinsic thyroid disease or thyroid hormone administration accounted for 83% (111/134) of suppressed values; however, central hypothyroidism, nonthyroidal illness, acute psychiatric illness, or the administration of medication was responsible for this finding in 17% (23/134). While a suppressed s-TSH level is generally excellent in the diagnosis of pituitary suppression by thyroid hormone, in specific clinical settings, a suppressed s-TSH level may be seen in the absence of thyroid hormone excess. The limitations of its use as a first-line screen in those conditions must be recognized.

Limitations to the use of a sensitive assay for serum thyrotropin in the assessment of thyroid status

In the majority of clinical settings, a suppressed serum thyrotropin (s-TSH) level determined by the new sensitive assays is diagnostic of thyrotoxicosis. This has led to its proposed use as a screen for thyroid disease. However, s-TSH may be suppressed in conditions other than thyrotoxicosis. We retrospectively reviewed s-TSH measurements made in a large heterogeneous population to determine in which settings a suppressed value could potentially lead to misdiagnosis. We found that a suppressed s-TSH level was useful in making the diagnosis of autonomous thyroid function and in the assessment of thyroid hormone replacement therapy in patients with primary, but not central, hypothyroidism. Hyperthyroidism caused by either intrinsic thyroid disease or thyroid hormone administration accounted for 83% (111/134) of suppressed values; however, central hypothyroidism, nonthyroidal illness, acute psychiatric illness, or the administration of medication was responsible for this finding in 17% (23/134). While a suppressed s-TSH level is generally excellent in the diagnosis of pituitary suppression by thyroid hormone, in specific clinical settings, a suppressed s-TSH level may be seen in the absence of thyroid hormone excess. The limitations of its use as a first-line screen in those conditions must be recognized.

Subclinical Hyperthyroidism: Possible Danger of Overzealous Thyroxine Replacement Therapy

Many patients taking customary doses of levothyroxine have slightly elevated serum thyroxine (T4), apparently normal serum triiodothyronine, suppressed serum thyrotropin (thyroid-stimulating hormone; TSH) concentrations, and no clinical symptoms of hyperthyroidism. Recent reports suggest that these patients may have adverse effects from subclinical hyperthyroidism, including abnormally short systolic time intervals, elevations in liver enzymes, and reductions in bone density. Controversy exists about which thyroid function tests should be used to monitor patients taking levothyroxine. A review of currently available data suggests that replacement doses of levothyroxine given to hypothyroid patients should be adjusted so that serum TSH measured by the new sensitive assays is within the normal range. Patients requiring suppressive doses of levothyroxine to shrink goitrous thyroid tissue or to prevent growth of abnormal tissue should be given the minimal dose needed to accomplish the desired clinical or biochemical response.

Maturational effect of triiodothyronine and its analog 3,5-dimethyl-3'-isopropyl-L-thyronine on sucrase activity in the small intestine of the developing rat.

In this study we compared the effect of 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) with that of triiodothyronine (T3) on sucrase activity in the small intestine of the fetal and suckling rat. DIMIT (5 micrograms/100 g BW) was injected into pregnant Sprague--Dawley rats on days 17-20 of gestation and DIMIT (10 and 50 micrograms/100 g BW) and T3 (10 and 50 micrograms/100 g BW) were given subcutaneously to two groups of sucklings on days 4-7 and 11-14. Fetal animals were sacrificed on day 21 of gestation; sucklings on days 8 and 15. Sucrase activity in the proximal, middle, and distal small intestine was assayed. DIMIT and T3 suppressed serum thyroid-stimulating hormone (TSH) in the fetus and suckling. Sucrase activity was increased in all small intestinal segments in the fetal and older suckling groups. In the younger sucklings the effect was seen only in the middle and distal segments. In both fetal and suckling groups the sucrase response was dose related. Thus, DIMIT has a thyromimetic effect on development of sucrase activity. The lack of sucrase reactivity in the proximal segment of the younger (8-day-old) sucklings to the administration of either DIMIT or T3 is interesting but unexplained.