Association of primary hypothyroidism with preconcious puberty. Presentation of clinical case and the effect of acute inhibition of thyrotropin on the gonadal activity

An 8 2/12 year-old girl with acquired primary hypothyroidism and precociuos puberty is described. Thyroid hormone treatment resulted in the regression of the sexual development, but moderate asymptomatic papilledema appeared as a result of therapy. Serial vaginal smears and measurements of urinary estrogen excretion during acute thyrotropin (TSH) inhibition with 75 mug/day of triiodthyronine (T3), showed a rapid drop in ovaric estrogen production up to prepubertal stage at 17 days of T3 administration. Moreover, a group of children with untreated hypothyroidism was followed through the first 3 to 12 months of thyroid therapy and none developed signs of increased intracranial pressure. These findings as well as the possible pathophysiology involved in this association are discussed.     

Increased serum vascular endothelial growth factor levels and intrathyroidal vascular area in patients with Graves' disease and Hashimoto's thyroiditis

Vascular endothelial growth factor (VEGF) is one of the angiogenic factors. We examined both thyroid volume and intrathyroidal vascular area by color flow Doppler ultrasonography in patients with Graves' disease (GD), Hashimoto's thyroiditis (HT), and subacute thyroiditis. The serum concentrations of thyroid hormones, TSH, TSH receptor antibodies, and VEGF were also examined. There was a significant increase in serum VEGF levels in patients with untreated GD and goitrous HT compared with those in healthy subjects. The serum VEGF levels in untreated patients with subacute thyroiditis were significantly higher than those in patients with untreated GD or HT. There was a significant correlation between serum VEGF levels and the ratio of intrathyroidal vascular area and thyroid area in untreated patients with GD who had a goiter larger than or equal to 40 cm3. There was also a significant correlation between serum VEGF and TSH levels in patients with HT who were hypothyroid and had a goiter. Serum VEGF levels decreased significantly in these patients after treatment; this was accompanied by a significant decrease in intrathyroidal vascular area and thyroid volume. Our study demonstrates that VEGF appears to play an important role in intrathyroidal angiogenesis in patients with GD and goitrous HT.     

Synthesis and biological evaluation of 1,2,5-oxadiazole N-oxide derivatives as hypoxia-selective cytotoxins

A role of psychic stress in precipitating hyperthyroid Graves' disease has been suggested, but the evidence in support of this pathogenetic mechanism is conflicting. In this study we investigated the possible occurrence of Graves' disease in patients with panic disorder, a psychiatric condition characterized by recurrent endogenous stress. The study group included 87 consecutive patients suffering from panic disorder since 1 to 30 years: 17 males (mean age 31.3, range 26-43 years) and 70 females (mean age 37.6, range 15-73 years). Two hundred and sixty-two normal subjects with no present or past history of psychiatric disorder served as controls. Patients were submitted to a full evaluation of the thyroid that included physical examination, assays for free thyroid hormones, TSH, thyroglobulin (TgAb), thyroperoxidase (TPOAb) and TSH receptor (TRAb) antibodies, and thyroid echography. The prevalence of circulating TgAb and/or TPOAb in patients with panic disorder did not differ from that in the control group. Twelve patients with panic disorder (13.7%) had circulating TgAb and/or TPOAb, but none had TRAb. Three out of 12 patients with thyroid antibodies, indicating a genetic susceptibility to autoimmune thyroid disease, had a family history of clinical thyroid autoimmunity, and 4 of them had a hypoechogenic pattern of the thyroid at ultrasound suggesting autoimmune thyroiditis. None of the patients with panic disorder had a previous history of hyperthyroidism. On examination, clinical hyperthyroidism or endocrine ophthalmopathy were not found in any of them. A small goiter was appreciated by palpation in 16 patients (18.3%). Free thyroid hormones and TSH were within the normal range in all patients but one: a 55-year old lady with normal serum free thyroid hormones and undetectable TSH. During an 18-month follow-up she did not develop hyperthyroidism and her TSH spontaneously returned in the normal range. Considering the individual duration of panic disorder, evidence for previous or present Graves' hyperthyroidism was not found for a total of 478 patient-years of exposure to recurrent endogenous stress in the whole study group, and for a total of 39 patient-years in patients with a genetic susceptibility to autoimmune thyroid disease. In conclusion, we found that recurrent endogenous stress did not precipitate Graves' hyperthyroidism in a series of 87 patients with panic disorder, encompassing a total of 478 patient-years of exposure to stress. Failure to activate the hypothalamic-pituitary-adrenal axis by endogenous stress due to panic disorder as opposed to exogenous stress due to life-events might explain why panic disorder does not precipitate Graves' hyperthyroidism.     

Recurrent goiter, hyperthyroidism, galactorrhea and amenorrhea due to a thyrotropin and prolactin-producing pituitary tumor

A 22-year-old woman with recurrent goiter, hyperthyroidism, galactorrhea, and amenorrhea due to a pituitary tumor is described. She had been treated surgically twice for recurrent goiter with tracheal compression. Despite clinical signs of hyperthyroidism and slightly elevated plasma thyroid hormone levels (T4: 11 mug/dl; T3: 189 ng/dl), without thyroid hormone replacement therapy the basal TSH level was elevated up to 23 muU/ml and could not be suppressed by exogenous thyroid hormones: even when the serum thyroid hormone levels were raised into the thyrotoxic range (T4: 16.2 mug/dl T3: 392 ng/dl), the basal TSH fluctuated between 12 and 29 muU/ml. The basal PRL level was elevated up to 6000 muU/ml. The administration of TRH (200 mug iv) led only to small increments of TSH and PRL levels. Bromocriptin (5 mg p.o.) or l-dopa (0.5 g p.o.) suppressed TSH and PRL values significantly. After transsphenoidal hypophysectomy, TSH and PRL were below normal and the patient development panhypopituitarism. The adenoma showed two cell types which could be identified as lactotrophs and thyrotrophs by electronmicroscopy and immunofluorescence. From these data we conclude that the patient had a pituitary tumor with an overproduction of thyrotropin and prolactin.     

High dosage thyroxine treatment in therapy and prevention refractory patients with affective psychoses

Natural killer (NK) cell activity of peripheral blood lymphocytes (PBL) against k562 human tumor cell targets was studied in patients with Graves' disease and Hashimoto's thyroiditis. NK activity was measured in a standard 4-hour 51chromium (Cr) release assay. Cytotoxicity was expressed as lytic units (LU)/10(6) PBL. Significantly decreased NK cell activity was demonstrated in both groups of patients, with mean (+/- SE) lytic units of 10.3 (+/- 9.1) and 13.3 (+/- 10.3) for patients with Graves' disease and Hashimoto's thyroiditis, respectively, compared with 36.0 (+/- 26.3) for age- and sex-matched normal subjects. When patients with Graves' disease were analyzed according to their thyroid status; NK activity was significantly depressed in (1) hyperthyroid patients before treatment; (2) hyperthyroid patients receiving antithyroid therapy; and (3) euthyroid patients receiving antithyroid therapy, compared with normal subjects. Graves' disease patients who were hypothyroid after radioactive iodine therapy or thyroidectomy had normal NK activity. No significant differences between hyperthyroid and euthyroid patients or between hypothyroid patients and normal subjects were demonstrated. NK activity in patients with Graves' disease did not correlate with serum levels of thyroxine, the presence or severity of ophthalmopathy, or titers of serum thyroid antibodies. In patients with Hashimoto's thyroiditis there was no correlation between NK activity and goiter size, titers of antithyroid antibodies, or thyroid status. These findings suggest that depression of NK activity in both disorders is secondary to abnormalities of thyroid hormone secretion, although an effect of the underlying autoimmune reactions has not been excluded.     

Neonatal transient hypothyroidism: aetiological study. Italian Collaborative Study on Transient Hypothyroidism

AIMS: To define the aetiology of neonatal transient hypothyroidism (NTH) and recommend preventive measures. METHODS: Maternal and perinatal clinical data on the use of antiseptics, drugs, and contrast agents containing iodine were collected from 40 subjects. Thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), thyroglobulin (TG), TSH receptor antibodies, thyroid peroxidase antibodies and urinary iodine were measured in random neonatal samples. In the mothers with known or suspected thyroid disorders, TSH, FT4, TSH receptor antibodies and thyroid peroxidase antibodies were also measured. RESULTS: The NTH aetiology was identified in 85% of cases. More than 50% of the babies with transient hypothyroidism had been exposed to iodine; maternal transfer of antibodies had occurred in a third of them. CONCLUSIONS: It is suggested that the practice of using iodine containing disinfectants should be withdrawn, and chlorhexidine substituted instead; that pregnant women should be advised of the adverse effects of using iodine products; and that thyroid function should be monitored whenever iodine is used.     

Bioassay of thyrotropin receptor antibodies with Chinese hamster ovary cells transfected with recombinant human thyrotropin receptor: clinical utility in children and adolescents with Graves disease

OBJECTIVE: The objective of this study was to compare the clinical utility of a new bioassay for thyrotropin (TSH) receptor antibodies (Abs) with the conventional radioreceptor assay and with measurement of thyroid peroxidase Abs in the diagnosis of Graves disease in childhood. STUDY DESIGN: Serum samples obtained from 22 children and adolescents with Graves disease (19 hyperthyroid, 3 in remission), 13 children and adolescents with chronic lymphocytic thyroiditis, and 17 normal children in a control group were evaluated. RESULTS: TSH receptor Abs were detected by bioassay in 10 (91%) of 11 patients with active Graves disease but in 0 of 2 patients in remission, 0 of 13 normal members of the control group, and 0 of 11 patients with chronic lymphocytic thyroiditis including 1 with thyrotoxicosis. The sensitivity and specificity of TSH receptor Abs detected by radioreceptor assay studied in the same 11 patients and in an additional 11 patients was similar to bioassay. In contrast, thyroid peroxidase Abs were detected in only 12 (71%) of 17 patients with Graves disease but in 11 of 11 patients with chronic lymphocytic thyroiditis and in 0 of 17 members of the control group. CONCLUSION: Bioassay of TSH receptor Abs is both sensitive and specific for the diagnosis of active Graves disease in the young. When cost and simplicity are considered, however, bioassay offers no advantage over radioreceptor assay for initial diagnostic screening. Rather, bioassay for TSH receptor Abs may be useful in thyrotoxic patients who are negative initially in the radioreceptor assay or in treated patients whose clinical picture is discordant with results in the radioreceptor assay.     

Failure of triiodothyronine to inhibit TSH-mediated thyroid hormone release in man

We studied the effect of short-term triiodothyronine administration on thyroid gland responsivity to exogenous thyrotropin in four euthyroid human subjects. Thyroidal iodine release and serum thyroxine during daily im injections of bovine TSH were not significantly inhibited, despite a four-fold elevation in serum T3 concentrations. This negative finding contrasts with earlier positive reports of a regulatory "short-loop" effect of elevated circulating T3 on the thyroid gland. This difference may be due either to the use in previous murine or in vitro studies of non-physiologic, high doses of exogenous T3, or failure to control the withdrawal of the trophic effect of endogenous TSH in man on the subsequent glandular response.     

Changes in thyroid hormones by treatment with aspirin and prednisolone in subacute thyroiditis with hyperthyroidism

Thyroid functions were studied in 11 patients with subacute thyroiditis accompanied by signs and symptoms of hyperthyroidism, and were compared with 13 patients with untreated thyrotoxicosis in which serum T4 was elevated to the identical level. Serum T3 was also elevated in subacute thyroiditis but to a significantly lower extent than in thyrotoxicosis. Therefore the ratio of T4/T3 was significantly higher in subacute thyroiditis than in thyrotoxicosis. Although duration of thyroid swelling was shorter in the group treated by prednisolone than by aspirin, the accelerated ESR, thyroid tenderness and fever subsided almost similarly in the two groups. Serum T4 and T3 levels declined more rapidly in treatment with prednisolone compared with aspirin. In patients treated by aspirin initial increase in T3 level occurred transiently with simultaneous decrease in the T4/T3 ratio. These changes suggest the increase in peripheral conversion of T4 to T3. Even in severe cases of subacute thyroiditis associated with hyperthyroidism, aspirin treatment is an effective therapy and there is no recurrence following withdrawal of the medication.     

Inhibition in the senso-motor cortex of cats

The clinical course from birth and serial measurements of serum T3, T4 and TSH in an infant with untreated neonatal thyrotoxicosis are reported. The thyroid hormone levels fell exponentially with time at rates very much slower than those previously reported for the maternally-transmitted thyroid stimulating antibody generally thought to cause the disorder. Steady physiological levels of thyroid hormones were achieved after 110 days (serum T3 = 3.4 NMOL/L, T4 = 118 nmol/l). TSH first rose to a measurable level after about 90 days.     

Changes in thyroid hormone levels during growth hormone therapy in initially euthyroid patients: lack of need for thyroxine supplementation

The occurrence of central hypothyroidism in previously euthyroid children during GH therapy has been reported with widely varying incidence. We monitored the acute effects on the hypothalamic-pituitary-thyroid axis in 15 euthyroid children with classic GH deficiency during the first year of GH therapy. All were initially euthyroid, as assessed by normal baseline TSH, T4, free T4, and T3 levels and negative antithyroid antibodies. A thyroid profile (T4, free T4 index, T3, rT3, and TSH) was performed at baseline and 1, 3, 6, 9, and 12-15 months after GH therapy began; a TRH stimulation test was performed at baseline and after 1, 3, and 9 months of therapy. By 1 month, there were significant decreases in T4, free T4 index, and rT3, and significant increases in T3 and the T3/T4 ratio. The changes from baseline values were greatest at 1 month, were almost universal for all thyroid values, and showed a gradual return to baseline from 3-12 months. There were no clinical signs of hypothyroidism and no change in baseline or TRH-stimulated TSH levels or in cholesterol levels, and all patients grew at velocities expected for the treatment schedule. There is little evidence for the development of clinically significant hypothyroidism in the great majority of initially euthyroid patients after GH therapy is begun. T4 supplementation is seldom needed in such patients.     

Relationship of thyroid states and serum thrombomodulin (TM) levels in patients with Graves' disease: TM, a possible new marker of the peripheral activity of thyroid hormones

Thrombomodulin (TM) is a thrombin receptor glycoprotein that functions as an anticoagulant on the surface of endothelial cells. Serum TM is regarded as a new marker of generalized endothelial cell damage. Serum TM concentrations were measured in 75 patients with Graves' disease and 75 age- and sex-matched healthy subjects. Serum TM levels in patients in the hyperthyroid state were significantly increased, while those in patients in the hypothyroid state due to treatment were significantly decreased compared with levels in control subjects. All patients with untreated Graves' disease had markedly elevated TM levels. Serum TM levels correlated closely with thyroid hormone concentration (TM vs. free T4, r = 0.858; P = 0.001). Serial measurement of individual patients revealed that serum TM levels paralleled thyroid hormone concentration, reaching normal control values upon attainment of euthyroidism. On the other hand, there was no significant correlation between serum TM concentration and titer of antithyroglobulin antibodies, titer of antimicrosomal antibodies, serum thyroglobulin level, or goiter size, and serum TM was not directly influenced by TSH receptor antibodies or resting pulse rates. The close correlation between serum TM and thyroid hormone concentration suggests that thyroid hormones might influence the synthesis or metabolism of TM on the surface of endothelial cells in patients with Graves' disease.     

Changes in serum thyrotropin (TSH) in man during halofenate administration

Halofenate, a serum lipid-lowering agent which inhibits binding of thyroid hormone to thyroxine-binding globulin (TBG), was administered daily for 14 days to 8 hypothyroid subjects with elevated TSH concentrations as a result of incomplete thyroxine (T4) therapy. Drug administration resulted in mean increases in serum dialyzable fraction T4 (DFT4) of 52% over pretreatment levels (P less than 0.01) and in dialyzable fraction triiodothyronine (DFT3) of 26% in 7 subjects, (P less than 0.01). During halofenate treatment in these 7 subjects, serum TSH concentrations decreased significantly (mean = 39%, P less than 0.01) when DFT4 and DFT3 were increased by halofenate. In only two subjects was there a convincing temporal relationship between increased serum absolute free T4 (AFT4) and decreased serum TSH concentrations. Contrary to what would be predicted from the "free hormone hypothesis", changes in serum TSH concentration in these hypothyroid patients appeared to relate primarily to changes in the free fraction of circulating T4 and T3 (DFT4, DFT3), rather than to alterations in AFT4 or AFT3. Halofenate did not alter serum TBG binding capacity. An eighth subject did not show increased DFT4 and DFT3 during halofenate treatment despite achievement of therapeutic serum levels of the agent; in this patient, serum TSH levels rose progressively throughout the period of inadequate T4 replacement and halofenate administration. In hypothyroid patients, short-term halofenate use suggests that the pituitary-thyroid hormone feedback circuit can respond to increases in serum DFT4 and DFT3 in the absence of detactable increases in absolute free hormone concentrations.     

Primary end points in phase III clinical trials of severe head trauma: DRS versus GOS. The American Brain Injury Consortium Study Group

Analysis of patients with persistent hypothyroidism due to Hashimoto's thyroiditis suggested that metabolism of thyroxine (T4), including deiodination to triiodothyronine (T3), was reduced in the elderly. The increase in the serum levels of T4 after oral administration of T4 was augmented in the elderly, whereas increase in the serum T3 level was not. Possibly due to the reduction in the pituitary deiodinase, suppression by T4 administration of serum thyrotropin (TSH) level was the same in elderly as in younger subjects despite a larger increase in the serum levels of T4 in the elderly. Consequently, the amount of T4 required to maintain a normal serum TSH level did not differ between elderly and younger subjects. Other characteristics of elderly patients with Hashimoto's thyroiditis were that goiter size was smaller, that hypothyroidism was more frequent, and that Graves' disease was less frequent.     

Medical treatment of multinodular goiter

Thyroid nodules are among the most common clinical problems in endocrinology. Among several factors responsible for the development of goiter, circulating TSH plays a major role because of its direct growth-promoting effects on the thyroid cells; moreover TSH may enhance the effects of other local growth factors which act in a paracrine mode in the thyroid gland. In addition, autoimmune thyroiditis can clinically appear as thyroid nodules frequently with the functional aspect of a subclinical hypothyroidism. For these reasons a therapeutical approach based on the thyroxine suppression of TSH secretion has become largely used by 1970s and is correctly employed in 75% of the patients with thyroid nodules whose biopsies result benign.     

Levothyroxine suppressive therapy for solitary thyroid nodule

In order to evaluate the efficacy of a TSH suppressive dose of levothyroxine to reduce the volume of a single thyroid nodule we studied 55 euthyroid patient: 45 (group A) were suppressed with LT4 (mean 1.7 +/- 0.9 micrograms/Kg/day) for 21.3 +/- 5.3 months, and 10 patients (group B) served as controls. All the nodules were "cold" at scintiscanning, solid at ultrasonography and benign by fine-needle aspiration cytology. As responders were assumed the nodules shrinked at the end of treatment of 50% in volume. Thyroid function values (TSH, T4, FT4, T3, FT3, thyroid peroxidase and thyroglobulin antibodies), clinical and ultrasonographic findings were evaluated initially and at the end of the study. A significant nodular volume decrease occurred in 8 treated patients (17.8%) while 37 (82.2%) amongst the group suppressed and all controls showed no change (A vs B = NS). In two untreated patients new nodules were noted; no new nodules were discovered in the treated group (A vs B p < 005). No side effects occurred in any treated patient, even if at the end of treatment a significant T4 and FT4 (p < 0.01) increase was observed. No one onset parameter can predict the response to the therapy. These results suggest that only a small group of patients affected by a single thyroid nodule seems to respond to a TSH suppressive therapy.     

Central hyperthyroidism

Central hyperthyroidism is a rare condition in which thyrotoxicosis results from primary overproduction of TSH by the pituitary gland with subsequent thyroid enlargement and hyperfunction. The two known causes of central hyperthyroidism are TSH-producing pituitary tumors (TSHomas) and the syndrome of PRTH. Both of these entities are characterized by clinical thyrotoxicosis, diffuse goiters, elevated circulating levels of free T4 and T3, and a nonsuppressed serum TSH. It is critical to distinguish central hyperthyroidism from the much more common types of primary hyperthyroidism, all of which have undetectable TSH values. TSHomas and PRTH can usually be differentiated from one another by measuring the serum alpha-subunit and the TSH response to intravenous TRH or exogenous thyroid hormone, and by pituitary imaging studies. TSHomas are usually benign adenomas arising from the monoclonal expansion of neoplastic thyrotropes. Causative oncogenes have not yet been convincingly identified. PRTH is a nonneoplastic disorder caused by inherited mutations in the gene for the thyroid hormone receptor beta; it is a poorly understood variant of GRTH. For unclear reasons, in PRTH, the pituitary gland is resistant to the feedback inhibitory effects of circulating thyroid hormones while peripheral tissues respond normally, causing patients to experience the toxic peripheral effects of thyroid hormone excess. TSHomas are best treated by transphenoidal surgical removal. Radiotherapy is indicated for inoperable or incompletely resected tumors. Octreotide administration is a useful adjunct for preoperatively reducing tumor size and for the medical management of surgical treatment failures. PRTH is ideally treated by chronically suppressing TSH secretion with medications such as D-thyroxine, TRIAC, octreotide, or bromocriptine. If such therapy is ineffective or unavailable, thyroid ablation with radioiodine or surgery may be employed with subsequent close monitoring of both thyroid hormone status and pituitary gland size.     

Role of protein degradation in the growth of livers after a nutritional shift

Four patients with idiopathic pituitary dwarfism were shown to have growth hormone (GH), adrenocorticotropin (ACTH), and luteinizing hormone (LH) deficiencies. Basal levels of thyrotropin (TSH) were within normal range in three patients and slightly elevated in one. Exaggerated and delayed responses were obtained after TSH-releasing hormone (TRH) stimulation. Serum thyroxine (T4) values were low (2.3 +/- 0.4 mug/100 ml), while triiodothyronine (T3) levels were in the normal range (1.22 +/- 0.25 ng/ml), both rising substantially after exogenous TSH and consecutive TRH administration. Their hypothyroid state was, therefore, probably due to TRH deficiency. To examine the dose of L-T4 necessary to produce inhibition of the TSH response to TRH, 50 mug/m2/day of L-T4 was administered to these patients. At the end of 4 weeks of replacement, serum T4 rose to 5.2 +/- 0.5 mug/100 ml, whereas T3 was unchanged from the previous levels, after which TSH responses to TRH were completely suppressed in all patients. As a control group, six patients with primary hypothyroidism received gradually increasing doses of L-T4 for 4-week periods, and TSH response to TRH was tested at the end of each dosage of L-T4, until complete inhibition of TSH release was obtained. The primary hypothyroid patients required approximately 150 mug/m2/day of L-T4 for suppression of TSH response to TRH. At this dosage, serum T4 and T3 levels were 8.5 +/- 0.9 mug/100 ml and 2.34 +/- 0.5 ng/ml respectively, which were significantly higher than those levels in the pituitary dwarfs (P less than 0.001 for T4 and P less than 0.01 for T3). These observations indicate that the set point of TSH release in feedback inhibition by throxine is low in idiopathic hypopituitarism with TRH deficiency, and TRH seems to control the pituitary sensitivity to feedback regulation of thyroid hormones.     

The interaction of cationic liposomes with the skin-associated bacterium Staphylococcus epidermidis: effects of ionic strength and temperature

OBJECTIVE: Treatment with recombinant interferon-alpha (rIFN-alpha) may induce autoimmunity. We have evaluated the effect of rIFN-alpha on pre-existing thyroid disease with special reference to changes in TSH receptor antibody. DESIGN AND PATIENTS: Five patients, who had a history of autoimmune thyroid disease diagnosed between 2 and 16 years earlier (three patients had Graves' disease while two had Hashimoto's thyroiditis), were treated with rIFN-alpha for chronic hepatitis C. Before, during and after rIFN-alpha therapy, we determined thyroid function, antithyroid antibody, thyroid echogenicity and the surface phenotype of the peripheral and intrathyroidal lymphocytes. RESULTS: Four of the patients developed overt hypothyroidism after 4-7 months of rIFN-alpha therapy, and two of them had a preceding history of low-uptake thyrotoxicosis. Recovery of thyroid function was observed in all four patients. Strongly positive blocking type TSH receptor antibody was detected and an increase in the percentage of CD19 positive cells in the intrathyroidal lymphocytes was also observed in three of the patients even though the goitre size increased in two of them. One of the patients became thyrotoxic later when stimulating type TSH receptor antibody became positive. Another patient suffered from reversible hypothyroidism although stimulating type TSH receptor antibody remained strongly positive throughout the clinical course. CONCLUSIONS: Our data thus indicated a high incidence of an unusual type of reversible hypothyroidism with TSH receptor antibodies in patients with chronic hepatitis C and pre-existing autoimmune thyroid disease after recombinant interferon-alpha therapy through a mechanism involving both the humoral and cellular immune systems.     

Dose-response of prolactin and thyrotropin to N3im-methyl-thyrotropin releasing hormone in euthyroid men

The synthetic N3im-methyl analogue of thyrotropin releasing hormone (methyl-TRH) was administered intravenously to 15 euthyroid men, ages 36-62, in graded doses from 6.25 mug to 500 mug in order to establish the range of response of prolactin (PRL), TSH, T3 and T4 to various doses of methyl-TRH. There was a dose-related rise in serum TSH, PRL, T3, and T4 which gave a nearly linear relationship when the integrated area of response was used as an index of response to the various doses of methyl-TRH. All 15 men had a clear elevation in TSH, PRL, T3 and T4 following the lowest dose of methyl-TRH TESTED (6.25 mug). There was considerable variability in the response to methyl-TRH among the individuals. One hundred mug of methyl-TRH gave a maximum TSH response; a 25 mug dose elicited a maximum PRL response.