Thyrotropin-releasing Hormone Test Research Articles

A Rare Form of Hypothyroidism

Secondary hypothyroidism is extremely rare. In the majority of cases, there is a genetic (gene mutations) or structural (mass effect or infiltration) basis for central hypothyroidism, and there is simultaneous deficiency of other adenohypophysial hormones. Isolated deficiency of thyrotropin is even rarer. This report features the case of a woman who had isolated thyrotropin deficiency, with the remainder of the anterior pituitary hormones being normal. The various causes of central hypothyroidism and the role of the thyrotropin-releasing hormone test are briefly described.

Different neuroendocrine profiles of remitted and nonremitted schizophrenic patients

Background: Thyrotropin-releasing hormone (TRH) test and Dexamethasone Suppression Test (DST) are two neuroendocrine tests that have been extensively used in an attempt to predict treatment response and outcome in schizophrenia. The objectives of this study were to investigate (1) the relationship between TRH test and DST and various psychiatric symptoms and (2) the potential value of these tests in prediction of short-term outcome in schizophrenic patients. Methods: TRH test and DST were administered to 58 patients with schizophrenia. All patients were evaluated with a battery of rating scales before neuroendocrine test procedures and at regular intervals for 1 year. Patients were divided into two groups as remitted (RP; n=30) and nonremitted patients (NRP; n=28). Baseline results of these two groups were compared with each other and 30 healthy controls. Results: Basal levels of total T 3 (T 3T) and free T 3 (T 3F) were higher in RP group than controls. Basal prolactin (PRL) level was higher in RP group, but not in NRP, compared to controls. Basal growth hormone (GH) and thyroid-stimulating hormone (TSH) levels of NRP were significantly higher than those of RP. DST nonsuppression was observed at a significantly higher rate in RP than NRP and control group. Blunted TSH response rate in RP group was higher significantly compared to other two groups. Conclusions: The data implicate that higher basal TSH and GH levels may be associated with a poorer treatment response, whereas higher total and free T 3 levels, a blunted TSH response to TRH and nonsuppression on the DST may indicate a better response in schizophrenics.

Postoperative persistent thyrotrophin releasing hormone-induced growth hormone release predicts recurrence in patients with acromegaly.

To assess the predictive value of postoperative thyrotrophin releasing hormone (TRH)-induced GH responsiveness in relation to (late) postoperative outcome in patients in remission after surgery for acromegaly. and methods One hundred and twenty-nine patients underwent surgery for acromegaly in our institution between 1977 and 1996. TRH tests and oral glucose tolerance tests (GTT) were performed and serum IGF-I concentrations were measured pre- and postoperatively and during follow-up. Criteria for postoperative remission were a mean serum GH concentration < 5 mU/l and/or serum GH after an oral glucose tolerance test < 1 mU/l immunofluorometric assay (IFMA) or < 2.5 mU/l (radioimmunosassay), together with a normal serum IGF-I concentration. Preoperatively, the TRH-induced GH response was highly variable, with gradual overlap between 'nonresponders' and 'responders'. Arbitrarily defined as a doubling of serum GH concentration, 45.6% of patients were 'responders' to TRH. GH response after TRH injection was significantly correlated to the TRH-induced prolactin response but not to preoperative GH concentration or adenoma size. After surgery, remission was achieved in 83 of the 129 patients. Postoperative remission was significantly correlated to mean preoperative serum GH concentration and preoperative glucose-suppressed serum GH but not to tumour class. Seventy-one patients with early postoperative remission were followed without adjuvant treatment for a mean of 9.4 +/- 0.7 years (range 0-23 years). Forty-one of these patients were TRH responsive as defined by at least doubling of the serum GH concentration preoperatively. Of the 71 patients, 12 developed recurrence of disease, as defined by insufficient GH suppression during oral GTT, and elevated IGF-I and mean serum GH concentration. Irrespective of the preoperative response to TRH, the initial postoperative TRH test was predictive of developing disease recurrence with a sensitivity of 75% and a specificity of 100% when an absolute GH increase of 3.75 mU/l was chosen to define paradoxical responsiveness. A stimulated GH 1.6 times basal was predictive of recurrence with a sensitivity of 83% and a specificity of 73%, and 2.1 times basal was predictive with a sensitivity of 75% and a specificity of 80%. None of the 32 patients with postoperative normalization of the preoperatively present TRH-induced GH response, defined as a postoperative GH increase < 3.75 mU/l, developed recurrence of disease, while all nine patients with a GH increase above this level developed recurrence of acromegaly. To our knowledge this is the first report which addresses the value of early postoperative TRH-induced GH responsiveness in predicting late surgical outcome using receiver-operating characteristic (ROC) curves to redefine a postoperative paradoxical response instead of arbitrarily chosen criteria. An absolute postoperative GH response of more than 3.75 mU/l was associated with recurrence in all nine patients, while all 32 patients with normalization of previously paradoxical response are still in remission. Our findings from this study demonstrate that the TRH test is a valuable tool in the early identification of patients at risk of developing postoperative recurrence of acromegaly.

Thyroid function tests in viral chronic hepatitis

One hundred and twenty five patients with virus B or C chronic active hepatitis and postnecrotic cirrhosis and different degrees of liver dysfunction were studied. 1) To determine a thyroid hormonal profile; 2) to evaluate the prognostic value of these tests in relation to the progression of the disease and mortality; 3) compare these findings with Child-Pugh classification. The patients were divided in four groups: a) 31 with chronic active hepatitis; b) 41 with postnecrotic cirrhosis Child A; c) 35 with postnecrotic cirrhosis Child B and d) 18 with postnecrotic cirrhosis Child C. The protocol comprised serum measurements of albumin and bilirrubin, estimates of prothrombin time and clinical evaluation of ascites and encephalopathy, measurement of total serum triiodothyronine, thyroxine, thyroid-stimulating hormone, free thyroxine, reverse triiosothyronine, calculated rT3/T3 index (IrT3) and thyrotropin-releasing hormone test. Total serum triiodothyromnine showed the most significant difference among the groups, gradually lower as the disease became more advanced (CAH: 149.2 +/- 42.3 ng/dL; PNC-A: 137.4 +/- 37.2 ng/dL; PNC-B: 88.0 +/- 28.4 ng/dL and PNC-C: 41.8 +/- 21.9 ng/dL). Low levels of T4 (4.5 +/- 2.0 micrograms/dL) and FT4 (0.7 +/- 0.4 ng/dL) and elevated levels of thyroid-stimulating hormone (7.2 +/- 11.5 microIU/mL), reverse triiosothyronine (60.8 +/- 52.1 ng/dL) and calculated rT3/T3 index (2.2 +/- 2.6) were more frequent in patients with postnecrotic cirrhosis Child C. Thyrotropin-releasing hormone test was normal in the majority of the patients. The present study shows a positive relationship between the low serum levels of T3 and elevated serum levels of rT3 and IrT3/T3 with the degree of hepatic dysfunction according to the Child-Pugh classification.

Thyroid hormones in epileptic children receiving carbamazepine and valproic acid

Carbamazepine and valproic acid are effective antiepileptic drugs for treating many types of epilepsy. Although they are well tolerated, many effects on endocrine function have been reported. Changes in serum thyroid hormones levels in 37 children with epilepsy during carbamazepine and valproic acid therapy were analyzed, and the thyroid hormone concentration after thyrotropin-releasing hormone test was evaluated. Serum thyroxine and free thyroxine levels were significantly lower in patients treated with carbamazepine and carbamazepine plus valproic acid than in the control subjects; serum thyroxine and free thyroxine concentrations were unaffected by valproic acid monotherapy. Serum triiodothyronine and free triiodothyronine concentrations were similar in the three groups of patients studied. Thyroid-stimulating hormone serum levels were normal in all patients, and the thyrotropin responses to the thyrotropin-releasing hormone were similar to control group. Our data suggest that children treated with carbamazepine may have subclinical signs of hypothyroidism, and these changes are more evident if carbamazepine is given in association with valproic acid, while no alteration in thyroid hormones can be found with valproic acid monotherapy. Thyroid-stimulating hormone and thyrotropin-releasing hormone levels do not seem to be affected by these drugs, suggesting that hypothalamic function is not affected in these children.

Identification of a silent pituitary somatotropic adenoma based on a paradoxic response of growth hormone on a thyrotropin-releasing hormone or gonadotropin-releasing hormone provocation test

Preoperative endocrinologic identification and surgical removal of a silent somatotropic adenoma among patients with either amenorrhea or galactorrhea, or both, are beneficial for the restoration of menstruation and ovulation. Paradoxic rises of serum growth hormone in either a thyrotropin-releasing hormone or a gonadotropin-releasing hormone provocation test and high serum growth hormone levels were noted in the 3 patients with a silent somatotropic adenoma. (Am J Obstet Gynecol 2001;184:286-8.)

A toxic testicle

A 29-year-old man was seen in May, 1998, with a history of weight loss, diarrhoea, tremor, palpitations, and sweatiness. He had fine tremor, tachycardia, diffuse goitre, prominent eyes, and periorbital oedema. Thyroid function tests at another hospital showed thyroid stimulating hormone (TSH) less than 0·1 (0·5–4·5) mU/L. Free thyroxine (FT4) was not measured. He was started on 20 mg carbimazole daily. Repeat biochemical tests before treatment had shown FT4 18·2 (normal 10·0–24·0) pmol/L, and TSH 1·1 (0·3–4·6) mU/L. Thyroid autoantibodies were weakly positive (microsomal 1/400, thyroglobulin 1/1600). Free triiodothyronine (FT3) was low at 3·4 (4·2–7·1) pmol/L. Full blood count, biochemical profile, erythrocyte sedimentation rate, 24 h urine catecholamines, and 5-hydroxyindolacetic acid concentrations were all normal. There was no resolution of symptoms on carbimazole, and treatment was stopped. He remained symptomatic with ocular discomfort. Ophthalmological examination and magnetic resonance imaging (MRI) of the orbits did not show proptosis. Repeat thyroid function tests over the next 6 months were normal, and mild transient thyroiditis was diagnosed. He was re-referred 6 months later with thyroid function tests done at another hospital showing TSH 0·3 (0·5–4·5) mU/L, and FT4 28 (9·0–20·0) pmol/L. He had similar symptoms to his previous attendance. Thyroid function tests at this hospital showed FT4 of 30·0 pmol/L, FT3 of 9·4 pmol/L, and TSH of 0·9 mU/L, confirmed by equilibrium dialysis. Luteinising hormone was 0·5 (2–12) IU/L, follicle stimulating hormone <0·1 (1–8) IU/L, and testosterone was 30·1 (11–36) nmol/L. Prolactin was 345 (83–414) mU/L. MRI of the pituitary was normal, although a thyrotropin releasing hormone (TRH) test was not done. Repeat thyroid function tests showed thyrotoxicosis, with a suppressed TSH <0·1 mU/L. Carbimazole therapy was restarted. The patient required 60 mg daily to achieve biochemical improvement, and in view of his clinical state, treatment with radioiodine was planned. He attended shortly before this could be given, however, complaining of a hard lump on his testicle. He was referred urgently for orchidectomy. Beta-human chorionic gonadotropin ( HCG) was raised at 6360 (<2) U/L. Histological examination showed a mixed germ cell tumour, with seminoma, embryonal cancer and teratoma, with the seminomatous component staining positively for HCG (figure). Postoperatively, his thyroid state improved, with FT4 12·6 pmol/L, FT3 3·2 pmol/L, and TSH 8·7 mU/L. Carbimazole was stopped with no sign CASE REPORT

Three year follow-up of borderline congenital hypothyroidism

The purpose of this study was to determine whether children with borderline hypothyroidism in the neonatal period had persistent hypothyroidism after 3 years of levothyroxine replacement therapy. Fourteen term infants with slightly abnormal newborn screening results (thyroxine < 10th percentile, thyroid stimulating hormone [TSH] <40 μU/mL) were identified. The subsequent serum confirmatory TSH results of 12 subjects were modestly elevated (5.3 to 18.8 μU/mL, normal 0.6 to 4.6), whereas 2 subjects who had borderline confirmatory TSH (4.6 and 4.7 μU/mL) had abnormal TSH responses to thyrotropin releasing hormone testing. After 3 years of therapy, levothyroxine was discontinued in 13 patients, and repeat thyroid function tests were obtained 1 month later. Levothyroxine was not discontinued in one patient because he had an elevated random TSH (10 μU/mL) while receiving therapy. At 3 years of age, 13 patients had persistently abnormal thyroid function tests (TSH >4.6 μU/mL or a thyroid releasing hormone test result consistent with primary hypothyroidism), and levothyroxine was reinitiated. Only one patient had normal thyroid function studies. Although prospective studies are still lacking, we recommend levothyroxine replacement in newborns with borderline hypothyroidism.

Expression of Thyrotropin-Releasing Hormone Messenger RNA in Human Pituitary Adenomas With Follicle-Stimulating Hormone Immunoreactivity

To assess the correlation between thyrotropin-releasing hormone (TRH) messenger RNA (mRNA) and the immunoreactive type of human pituitary adenomas. Twenty-eight patients (14 to 73 years old) who had pituitary adenomas (18 nonfunctioning adenomas, 8 growth hormone-secreting adenomas, and 2 prolactinomas) underwent surgical treatment. Pituitaries removed at autopsy from four patients without evidence of pituitary disease were used as controls. Fragments of pituitary adenomas were processed for TRH mRNA by in situ hybridization (radioactive and nonradioactive) and for TRH peptide and anterior pituitary hormones (b-thyrotropin, b-follicle-stimulating hormone [FSH], bluteinizing hormone [LH], prolactin, and growth hormone) by immunohistochemistry with use of the avidinbiotin technique. Quantitative immunohistochemical studies were performed by using image analysis software. The signal was considered positive when more than 5% of the cells were stained. Cells expressing TRH mRNA were detected in 22 of 28 pituitary adenomas--15 of 18 nonfunctioning pituitary adenomas, 5 of 8 growth hormone-secreting adenomas, and both prolactinomas. TRH peptide was revealed in only 10 adenomas, all expressing TRH mRNA as well. All but one nonfunctioning adenoma expressing TRH mRNA in more than 5% of the cells were b-FSH immunoreactive (15 of 16 cases; P<0.005, c 2 test), whereas only 6 of 16 nonfunctioning adenomas exhibited both b-thyrotropin and TRH mRNA and only 5 of 16 were positive for both b-LH and TRH mRNA. These results confirm previous data demonstrating the presence of TRH mRNA and TRH peptide in human pituitary tumor cells. We further showed that the presence of TRH mRNA is significantly correlated with FSH immunoreactive gonadotropinomas. The release of FSH after an intravenous TRH test only in gonadotropinomas, together with local production of TRH, suggests a role for TRH in pathogenesis.

Assessment of hypothalamic-pituitary function by hormonal pulsatility, gonadotropin-releasing hormone and thyrotropin-releasing hormone testing in women with euprolactinemic secondary amenorrhea.

To evaluate the integrated hypothalamic-pituitary function of euprolactinemic secondary amenorrhea, blood samples of 23 patients were taken every 15 min for 4 hours in examination of pulsatile LH, FSH, PRL secretions and then 2 hours GnRH, TRH tests were performed. Nine normal cycling women (group I) served as the controls. Thirteen amenorrheic women (group II) revealed responsive bleeding to progestin injection and the other 10 women (group III) were nonresponsive. The LH frequency, amplitude, and LH response to GnRH of groups II and I were comparable, whereas delta PRL after TRH in group II (60.8 +/- 18.9 ng/ml) exhibited a significantly (P < 0.05) exaggerated response, as compared with that of group I (43.6 +/- 11.4 ng/ml). The LH frequency (1.3 +/- 0.4/4h) and amplitude (1.7 +/- 0.4 mIU/mL) of group III were significantly lower (P < 0.01) than those in group I (2.4 +/- 0.5 and 2.5 +/- 0.5, respectively), but their delta LH and delta FSH responses to GnRH showed no differences from those of controls. The frequency, amplitude of PRL and delta PRL response to TRH in group III were no significant difference with those of group I. These results suggest that masked PRL hypersecretion and loss of the regulatory pulsatility of gonadotropin release may be responsible in part for the causes resulting to euprolactinemic secondary amenorrhea. The analysis of these hormonal environments is useful for the understanding of clinical perspectives, pathophysiology and management.

The clinical impact of the thyrotropin-releasing hormone test.

Because of its ability to cause the release of thyrotropin (TSH), prolactin (PRL), and, under particular circumstances, also of other adenohypopyseal hormones, from the pituitary, thyrotropin-releasing hormone (TRH) has been widely used as a diagnostic tool for about 30 years. The recent introduction of an ultrasensitive TSH assay, able to clearly distinguish suppressed from unsuppressed TSH levels, has rendered the use of the TRH test obsolete in the diagnosis of classic hyperthyroidism. On the contrary, the TRH test is still extremely useful in hyperthyroid patients with inappropriate secretion of thyrotropin, allowing the distinction between TSH-secreting pituitary tumors (usually unresponsive) and the pituitary variant of resistance to thyroid hormone (PRTH) syndrome (always responsive). In hypothyroidism, the TRH test is still of value in patients with preclinical primary hypothyroidism, as they show exaggerated TSH response, and in those with central hypothyroidism, allowing the differentiation between pituitary (secondary) and hypothalamic (tertiary) hypothyroidism. The availability of high-resolution imaging techniques such as magnetic resonance has rendered the use of the TRH test obsolete, to distinguish microprolactionomas from functional hyperprolactinemia. The TRH test still has great clinical value in the follow-up of patients with pituitary tumors (in particular somatotropinomas and clinically nonfunctioning pituitary adenomas) showing abnormal responses of anterior pituitary hormones other than TSH.

Low response of the thyroid gland to endogenous thyrotropin increased by thyrotropin-releasing hormone in patients with euthyroid Graves' disease.

Euthyroid Graves' disease is defined as Graves' ophthalmopathy without hyperthyroidism, and the thyroid-stimulating antibody (TSAb) has been known to be a good marker for diagnosis. However, the question of why TSAb does not cause hyperthyroidism arises. To settle this, we examined thyroid responsiveness to endogenous thyrotropin (TSH) increased by thyrotropin-releasing hormone (TRH) in 23 patients with euthyroid Graves' disease. Nineteen patients (83%) had positive TSAb and 21 (91%) had at least one of the autoantibodies to the thyroid gland. Only one patient (4%) had positive thyroid-stimulation blocking antibody (TSBAb). Basal levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyrotropin (TSH) in patients were not different from those in age- and sex-matched normal controls (n = 25). Response of TSH to TRH was normal; however, an increase of FT3, either absolute or as a multiple of baseline, in the TRH test in these patients (0.46+/-0.23 pg/mL, P < 0.001; 1.14+/-0.09 fold, p < 0.001) was significantly lower than that in controls (0.86+/-0.19 pg/ml; 1.26+/-0.07 fold). There was no correlation between the deltaFT3/deltaTSH ratio and TSAb activity. It is concluded that thyroid responsiveness in euthyroid Graves' disease is lower than in normal controls and this explains the euthyroid function in the patients even in the presence of TSAb.

Inhibitory action of oral thyrotropin-releasing hormone on the glucoregulatory response of the oral glucose tolerance test.

Thyrotropin-releasing hormone (TRH) has been found in the gastrointestinal tract, where it mainly exerts an inhibitory action. We used oral TRH, a stable and powerful formulation, to explore the glucoregulatory response of oral glucose tolerance test (OGTT) on obese patients with impaired glucose tolerance (IGT). Seven obese patients with IGT and eight controls were investigated. Three tests were performed on three separate days. On day 1, An oral TRH test: a 40 mg TRH tablet, was given. Blood samples for blood glucose (BG), proinsulin (PI), insulin (INS), C-peptide (CP), thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) were collected every 30 minutes for 3 hours. On day 2, an OGTT with 75 g glucose was performed. On day 3, an oral TRH test was administered 30 minutes before the OGTT, and blood was collected every 30 minutes for 3 hours. Oral-TRH had no effect on basal BG and on pancreatic hormone secretion. Oral TRH, coupled with OGTT in both controls and obese patients, led to a significant inhibition of BG (p < 0.01), of CP (p < 0.001), and of INS (p < 0.001) during the first hour of administration, and afterward, there was only a very slight increase, compared with levels after only OGTT treatment. After OGTT, PI peaked at 90 minutes (9.4+/-3 ng/mL) in controls and at 60 minutes (12.7+/-2.5 ng/mL) in obese patients. TRH application prior to OGTT inhibited PI secretion for 90 minutes in controls, whereas in obese patients PI levels were decreased, not inhibited, during the OGTT. The mechanism of the inhibitory TRH action on OGTT-induced increase of BG and pancreatic hormone secretion is not clear. It could be due to inhibition of gastric motility, and on a paracrine effect that enhances secretion of somatostatin that then suppresses INS, CP, and possibly PI levels. The partial escape of PI from the TRH blockade in obese patients with IGT might indicate a diminished functioning capability of beta-cells and that TRH cannot affect the INS processing within the beta-cells in these patients.

Thyroid function in early pregnancy I: Thyroid-stimulating hormone response to thyrotropin-releasing hormone

Maternal thyroid function in pregnancy is influenced by many factors. This study was undertaken to clarify the mechanism of thyroid regulation in the first trimester of normal pregnancy. We performed the thyrotropin-releasing hormone (TRH) test in eight women in the first trimester (week 6-9) of pregnancy and ten normal women in early follicular phase. Basal plasma levels of free triiodothyronine and free thyroxine were within the normal range in both groups, whereas thyroid-stimulating hormone (TSH) was at the lower limit of the normal range in pregnant women. TRH stimulation evoked a TSH response with a peak of 14.1 ± 1.2 mIU/ml at 30 min. In control subjects TSH increased in response to TRH with a peak of 7.4 ± 1.1 mIU/ml at 30 min. Statistical analysis with Student's t test revealed significantly higher TSH levels (p < 0.01) in pregnant women.The most striking finding was the enhanced responsiveness of TSH to TRH stimulation while the thyroid hormones, free triiodothyronine (fT3) and free thyroxine (fT4), remained in the normal range. This response was similar to that observed in central hypothyroidism. These results suggest that the reduction in maternal pituitary TSH levels is due to human chorionic gonadotropin (hCG) inhibition of TRH secretion.

Thyroid-stimulating hormone responses after single administration of thyrotropin-releasing hormone and combined administration of four hypothalamic releasing hormones in beagle dogs

Thyrotropin (TSH) responses were determined in eight healthy male beagle dogs after a single administration of thyrotropin-releasing hormone (TRH) and the combined administration of four hypothalamic releasing hormones, i.e., corticotropin-releasing hormone, growth hormone-releasing hormone, gonadotropin-releasing hormone, and TRH. In both tests, TRH was administered in a dose of 10 μg/kg. Basal TSH concentrations ranged form 0.07 to 0.27 μg/1(mean ± SE, 0.14 ± 0.02 μg/1). The administration of TRH, alone or in the combined test, resulted in a prompt and significant increase in TSH with mean (±SE) plasma TSH peaks of 1.26 ± 0.22 μg/1 at 10 min and 0.85 ± 0.17 μg/1 at 30 min, respectively. The area under the curve (0–120 min) was significantly lower in the combined test than in the single TRH test, whereas the increments were not significantly different. It is concluded that measurements of TSH responses to TRH alone and in combination with other releasing hormones can be used for the assessment of pituitary thyrotropic cell function. In the combined test, the TSH response is slightly lower than that in the single test.

Nonfunctioning adenomas of the pituitary

The term “nonfunctioning” pituitary adenomas (NFPA) implies heterogeneity, since it relies on a clinical definition that is mainly related to tumor mass. The first complaint is often of impaired visual function, and despite the secretion of gonadotropins, hypogonadism is frequent. NFPA must be differentiated from prolactinomas, because of the therapeutic implications, but although prolactin (PRL) levels greater than 200 ng/mL indicate prolactinoma, PRL levels of 100 to 150 ng/mL are equivocal. An assessment of gonadotropin response to gonadotropin-releasing hormone (GnRH) is of no use, but the thyrotropin-releasing hormone (TRH) test is invaluable. NFPA are monoclonal in origin, but genetic mutations data have not clarified their etiology, which remains largely unknown. Proliferating cell nuclear antigen expression is increased in recurrent adenomas, as is abnormality and overexpression of the protein kinase C family in aggressive tumors. Mutations of tumor-suppressor genes, such as the p53 and Rb genes, and of the metastasizing suppressor gene nm23, have been found in invasive tumors. Immunohistochemistry data confirm that most NFPA originate from gonadotroph cells; many NFPA are negative for all anterior pituitary hormones tested, although isolated or clustered cells are often positive for glycoprotein hormones or their subunits. Silent gonadotroph and also silent growth hormone (GH) or corticotroph tumors can constitute the anatomical basis for clinical NFPA. The heterogeneity of the immunohistochemistry data is reflected in the receptor complex of these tumors. Dopaminergic receptors have recently been visualized in vivo and there are also receptors for TRH or GnRH, since levels of α or β subunits and intact gonadotropins increase after TRH or GnRH stimulation. As a result, three second-line pharmacological approaches have been tried: dopamine agonists, octreotide, and GnRH superagonists or antagonists, with tumor shrinkage of up to 11% to 20%. However, surgery should be tried first.

Neuroendocrine and sleep variables in major depressed inpatients: role of severity

To evaluate the reliability of the endogenous concept of depressive illness according to the Newcastle Endogenous Depression Diagnostic Index (NEDDI), 155 major depressive inpatients with NEDDI scores ≥ 6 (endogenous) were matched for gender and age (± 5 years) to 155 major depressive inpatients with NEDDI scores ≤6 (nonendogenous). When sleep polygraphic variables, neuroendocrine parameters (dexamethasone suppression and thyrotropin-releasing hormone tests), and various clinical variables (unipolar/bipolar status, psychotic/nonpsychotic subtype, and severity of the depressive episode) were examined, statistically significant differences between endogenous and nonendogenous patients emerged for three variables: the thyroid-stimulating hormone response to the thyrotropin-releasing hormone test, the dexamethasone suppression test response at 16:00 h, and the percentage of time awake during the night. However, when the effects of age and severity of depression were controlled, those differences disappeared.

An update on diagnostic methods in the investigation of diseases of the thyroid.

Iodine deficiency and iodine-deficiency disorders continue to be problems in several parts of Europe, requiring further improvements in the techniques employed in thyroid diagnosis, and particularly in the early diagnosis and risk assessment of autonomously functioning thyroid tissue. For the latter purpose, scintigraphy with technetium-99m pertechnetate under exogenous or endogenous thyroid-stimulating hormone (TSH) suppression provides the best results. Significant methodological improvements in laboratory tests have resulted from the application of new luminescent techniques and gene technology to thyroid function tests. Especially TSH measurement using second- or third-generation assays ensures diagnostic accuracy, so that the thyrotropin-releasing hormone (TRH) test is now almost always unnecessary. The differentiation of blocking and stimulating TSH receptor antibodies is relevant when discrepant results are obtained with respect to thyroid function. Determination of glycosaminoglycans in urine may become a helpful tool in the follow-up of endocrine ophthalmopathy. Some new imaging agents have recently been applied in the scintigraphy of thyroid diseases, such as octreotide, or in thyroid diagnosis, such as fluorodeoxyglucose. Both improve the detectability of metastases of thyroid cancer, especially if the radioiodine scan is negative.

Correlation between vasopressin baseline and TSH-blunting in depressives

A blunted thyrotropin (TSH) response is a predictor of a good response to antidepressant drug treatment in depressives and neuroleptic treatment in paraphrenic patients (Larger et al 1986). The aim of the following study was to elucidate possible relationships between different endocrine systems and to shed light on the pathogenetic hypotheses of TSH-blunting. In order to evaluate especially hypothalamic activity in severe depression we were interested in the vasopressin system as another hormonal system underlying hypothalamic control. Thirty-four patients who met the criteria for major depression according to DSM-III-R were subjected to the thyrotropin-releasing hormone (TRH) test. We also took baseline readings of the cortisol, neurophysinI (hNpI, reflecting vasopressin plasma levels), and neurophysinII (hNpII, reflecting oxytocin plasma levels) levels. Likelihood ratio tests were done with logistic regression models to analyze the phenomenon of TSH-blunting. We observed that the likelihood of a blunted TSH response increases with higher levels of hNpI and low levels of cortisol, but is unrelated to hNpII levels.

Prophylactic application of thyrostatic drugs during excessive iodine exposure in euthyroid patients with thyroid autonomy: a randomized study

In a prospective, randomized study we examined the influence of prophylactic short-term thyrostatic therapy on thyroid iodine metabolism in patients with euthyroid autonomy undergoing elective coronary angiography. From a total of 1177 patients, 51 fulfilled the criteria of euthyroid autonomy before coronary angiography (negative thyrotropin-releasing hormone test, 10-min uptake of at least 1.2%, 99mTc and no elevation of free thyroxine and free triiodothyronine indices) and were randomized into three groups: group 1 (N = 17) received 20mg/day of thiamazole and group 2 (N = 17) received 900 mg/day of sodium perchlorate; thyrostatic therapy was begun on the day before angiography and continued for 14 days; group 3 (N = 17) served as controls without treatment. Parameters of thyroid function-free thyroxine (FT4) index and free triiodothyronine (FT3) index, thyrotropin (TSH) and delta-TSH urine iodine excretion and 99mTc uptake were determined before and 30 days after coronary angiography. At the end of the study the mean FT4 index and FT3 index were elevated significantly in the control group compared with baseline values, but were still within the normal range. In contrast, the mean FT4 index and FT3 index remained unchanged in the treated groups. Four mild cases of hyperthyroidism were observed at the end of the study: two cases in the control group and one case in each of the treated groups. Thyrotropin suppression, urine iodine excretion and 99mTc uptake differed significantly between the treated groups and the control group. In the treated groups TSH suppression, urine iodine excretion and 99mTC uptake remained unchanged 30 days after coronary angiography compared with baseline values. In the control group the degree of TSH suppression and the level of urine iodine excretion increased (about twofold) significantly after coronary angiography, whereas 99mTc uptake decreased significantly (ca. 50%). In conclusion, short-term prophylactic thyrostatic therapy seems to have a protective effect against iodine excess in patients with euthyroid autonomy. However, mild hyperthyroidism could not be prevented in some cases. Probably a combination therapy of thiamazole and perchlorate would be more effective.