Thyrotropin-Induced Hyperthyroidism: Use of Alpha and Beta Subunit Levels to Identify Patients with Pituitary Tumors
IONE A. KOURIDESE. Chester RidgwayBruce D. WeintraubS. Thomas BigosMarvin C. GershengornFarahe Maloof
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Abstract:
Six hyperthyroid patients with inappropriately elevated serum thyrotropin (TSH) had serum concentrations of the common alpha subunit of the glycoprotein hormones (alpha) and the beta subunit of TSH (TSH-β) measured by radioimmunoassay. The three patients with a pituitary tumor had markedly elevated serum alpha levels of 105, 16.6, and 19.5 ng/ml and TSH of 34, 1.7, and 5.6 εU/ml, yielding molar alpha to TSH ratios of 31 to 98; TSH-β was not detected (<;0.5 ng/ml). The three patients without a pituitary tumor had serum alpha concentrations of 1.2, 0.5, and 1.0 ng/ml and serum TSH levels of 160, 9.3, and 90 εU/ml, yielding molar alpha to TSH ratios <1; TSH-β was 1.3, 0.5, and 0.5 ng/ml. Subunit and TSH secretion in the patients with a pituitary tumor demonstrated little or no change after thyrotropin releasing hormone (TRH) or thyroid hormone administration. In contrast, serum subunit and TSH levels increased after TRH in the patients withou a pituitary tumor; both basal and peak subuni and TSH levels after TRH decreased after th* administration of thyroid hormone although the] were still inappropriately high in relation to th* elevated serum thyroid hormone levels. In botl the tumor and non-tumor patients, alpha subuni and TSH concentrations decreased after the administration of dexamethasone. Inthe patients with; pituitary tumor, hypophysectomy followed by radiotherapy caused a decrease in serum alpha and TSf concentrations, as well as remission of hyperthyroidism. Thepresence of elevated serum alph; concentrations and undetectable TSH-β in patientswith TSH-induced hyperthyroidism may serve to identify those patients with a pituitary tumor and in certain patients the reduction of serum alph; may better indicate the adequacyof therapy,Keywords:
Pituitary Tumors
Basal (medicine)
Thyroid-stimulating hormone
Alpha (finance)
TRH stimulation test
Subclinical infection
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Abstract. The relationship between serum thyrotropin (TSH) and serum triiodothyronine (T 3 ) before and after injection of different doses of thyrotropin releasing hormone (TRH), given as single injections or as multiple injections with short intervals, was investigated in normal men. A positive correlation between prestimulated serum TSH and serum T 3 levels and between the increase in the serum TSH and the serum T 3 levels after TRH was found when repeated tests were performed in the same individual. There was a dose dependent TSH and T 3 response to TRH. The smallest dose that produced a maximal response of both TSH and T 3 was only 30 μg TRH. After six injections of 30 μg TRH with an interval of 30 minutes the increase in TSH was two times and the increase in T 3 was three times as high as the maximal increase after single injections of TRH. This test with multiple injections of TRH may prove to be of clinical value in the measurement of both pituitary and thyroid function in selected patients. The close positive correlation between the serum TSH and serum T 3 levels in basal conditions, demonstrated in four normal subjects in this study, probably reflects the steady state level determined by the hypothalamus from which the feedback control of TSH secretion operates.
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Twenty-three euthymic alcoholics in medium- and long-term abstinence were studied as were 20 healthy controls. All underwent a Thyrotropin Releasing Hormone/Thyrotropin Stimulating Hormone (TRH/TSH) stimulation test. Ninety per cent of medium-term abstinent and 100 per cent of long-term abstinent alcoholics had a response within the normal range. However, overall, the TSH responses to TRH were significantly less than in controls. Our study suggests that while there is some improvement in TRH/TSH responses in long-term abstinent patients, there is still evidence of hypo function in those over 1 year alcohol-free.
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In order to gain insight into the neuroendocrine mechanism underlying the paradoxical GH response to TRH in acromegalic patients, we have investigated the effect of an infusion of Naloxone (Nal, 1.6 mg/hr for two hours), on a TRH test performed both in responder (n = 9) and non-responder (n = 5) acromegalic patients. The response of GH, PRL and TSH to TRH injection were evaluated. NAL did not exert significant variations in the GH response, even if different patterns of GH response during NAL were observed in the group of TRH-responder patients. Similarly, TRH-induced PRL response was not significantly affected by the infusion of an opiate antagonist. On the contrary, a significant inhibition of the TSH response was observed in the group of TRH-responder patients (delta TSH after TRH 4.76 +/- 1.11 microU/ml, after NAL + TRH 2.81 +/- 0.99 microU/ml, p < 0.05). No significant effects were observed in the TRH non-responder patients (delta TSH after TRH 4.58 +/- 1.44 microU/ml, after NAL + TRH 6.26 +/- 3.27 microU/ml). The differences observed in the two groups of patients could be ascribed to a different endogenous somatostatinergic tone and could furnish a prognostic indication in acromegalic patients.
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Abstract. The relationship between serum thyrotropin (TSH) and serum triiodothyronine (T3) before and after injection of different doses of thyrotropin releasing hormone (TRH), given as single injections or as multiple injections with short intervals, was investigated in normal men. A positive correlation between prestimulated serum TSH and serum T 3 levels and between the increase in the serum TSH and the serum T3 levels after TRH was found when repeated tests were performed in the same individual. There was a dose dependent TSH and T3 response to TRH. The smallest dose that produced a maximal response of both TSH and T3 was only 30 ug TRH. After six injections of 30 ug TRH with an interval of 30 minutes the increase in TSH was two times and the increase in T3 was three times as high as the maximal increase after single injections of TRH. This test with multiple injections of TRH may prove to be of clinical value in the measurement of both pituitary and thyroid function in selected patients. The close positive correlation between the serum TSH and serum T3 levels in basal conditions, demonstrated in four normal subjects in this study, probably reflects the steady state level determined by the hypothalamus from which the feedback control of TSH secretion operates.
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Serum TSH levels were measured by radioimmunoassay before and after giving synthetic thyrotropin releasing hormone (TRH) to normal subjects and to patients with thyroid or pituitary disease. Normal individuals responded to TRH with reproducible dose-related increments in serum TSH. Females tended to show a greater response to a given dose of TRH than did males, but sex dependent differences were usually not significant. Daily testing with TRH blunted the TSH response; alternate day testing showed less blunting in preliminary studies. Hyperthyroid patients had undetectable baseline TSH levels; seven of nine failed to respond to TRH. Patients with primary hypothyroidism had an exaggerated response to TRH. Treatment with dexamethasone suppressed their elevated baseline TSH levels but not the response to TRH. Euthyroid patients with pituitary lesions were tested with TRH and were found to have intact TSH reserve in most cases. In general, pituitary surgery or radiation obliterated the response to TRH. Dose-response curves and data illustrating the above responses are presented.
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