Normal Thyroxine Research Articles

Thyroid-Stimulating Hormone and Prolactin Levels in Breast Cancer

Serum thyroid-stimulating hormone (TSH) and prolactin (PRL) levels were measured before and after intravenous administration of protirelin to 148 patients with breast carcinoma. There was a high prevalence (36%) of elevated basal TSH; however, most of the patients were euthyroid and had normal serum thyroxine and T3 resin uptake. The PRL level was elevated in 22% of the cases. Both the mean PRL and the mean TSH levels for the breast cancer patients were significantly elevated above the respective means in a control group. We could find no correlation between serum TSH and PRL levels, suggesting that the purported association between a decreased thyroid state and breast cancer is probably not mediated through an increased PRL level. The mean survival and mean disease-free interval were shorter for patients with either elevated TSH or elevated PRL levels, but in neither case was the difference statistically significant.

Diagnosis of Sheehan's syndrome using a sequential pituitary stimulation test

Systematic pituitary evaluation was performed in four patients suspected of having Sheehan's syndrome. A sequential pituitary stimulation test, consisting of insulin-induced hypoglycemia followed by stimulation of gonadotropin-(GnRH) and thyroid-releasing hormone (TRH), a metyrapone test, and adrenocorticotropic hormone (ACTH) stimulation test, was performed. All four patients failed to develop a normal increase in serum growth hormone, cortisol, and prolactin (PRL) following insulin-induced hypoglycemia. All patients demonstrated a blunted PRL, follicle-stimulating hormone, and luteinizing hormone response to the combination of GnRH and TRH. Although thyroid stimulating hormone (TSH) response was impaired in all patients, two patients had normal T3 resin uptake and thyroxine, demonstrating minimal TSH reserve maintaining normal baseline free thyroxine index. Metyrapone administration was followed by no increase in 11-deoxycortisol or 17-ketogenic steroids, thereby adding no additional information to the hypoglycemia stimulation. ACTH infusion revealed normal adrenal cortisol response. In conclusion, in patients with suspected postpartum hypopituitarism, a complete pituitary function investigation can be done in a short time by using the described pituitary sequential stimulation test.

Response to thyrotrophin-releasing hormone in atrial dysrhythmias.

Seventy-eight clinically euthyroid patients with atrial dysrhythmias, either established or paroxysmal, and sixty-three patients in sinus rhythm with coronary disease were screened for hyperthyroidism using thyroid function tests including the thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH). All had normal levels of serum thyroxine (T4) apart from three with dysrhythmias who were found to have hyperthyroidism. Twenty per cent of patients with atrial dysrhythmias and 10% of those in sinus rhythm had exaggerated TSH response to TRH. Thirty-six per cent of patients with an exaggerated response of TSH to TRH had significant titres of thyroid auto-antibodies compared with 15% with positive antibodies in those with normal TSH response to TRH. Auto-immune thyroid disease may be more closely related to heart disease than has previously been recognized. Rapid atrial dysrhythmias may occur in the presence of a normal serum thyroxine, high levels of TSH and positive thyroid antibodies.

Thyroid function after surgical treatment of thyrotoxicosis. A report of 100 cases treated with propranolol before operation.

We assessed thyroid function for 12 months after subtotal thyroidectomy in 100 tyrotoxic patients treated with propranolol alone before and immediately after operation. The operation proved safe, with low morbidity. Suppression of the hypothalamic-pituitary-thyroid axis, present in the majority one month after operation, was evidenced by normal or low levels of serum total tri-iodothyronine and thyroxine, but absent or subnormal serum thyrotropin response to thyrotropin-releasing hormone. Eighty patients were euthyroid at 12 months. Three patterns of thyroid function were observed in this group between the first and 12th months: normal serum total tri-iodothyronine, thyroxine and thyrotropin levels at all stages (20 patients); normal serum total tri-iodothyronine and thyroxine, but raised thyrotropin levels on one or more occasions (40 patients); and temporary hypothyroidism (20 patients). Of the remaining 20 patients, permanent hypothyroidism developed in 14, and six relapsed. Postoperative thyroid function was related to the estimated weight of the thyroid remnant.

SPORADIC NON‐TOXIC GOITRE: AN INVESTIGATION OF THE HYPOTHALAMIC–PITUITARY–THYROID AXIS

Thyrotrophin releasing hormone (TRH) tests have been carried out on sixty-two patients with sporadic non-toxic nodular goitre. 61% gave a subnormal thyroid stimulating hormone (TSH) response but had normal plasma thyroxine (T4) and triiodothyronine (T3) levels. T3 administration suppressed 131I uptake by the thyroid adequately in 74% of these and there was normal stimulation of thyroid uptake by exogenous TSH. Prolactin (PRL) rose normally after TRH in all the TRH non-responders. Normal TSH response to TRH was restored by partial thyroidectomy and in some cases by propyl thiouracil administration. Possible reasons for these findings are discussed. It is concluded that these cases were truly euthyroid.

Alteration of stimulated TSH and prolactin response in children treated with growth hormone

The plasma TSH and prolactin responses to thyrotropin releasing hormone (TRH) were measured in 5 children with isolated growth hormone deficiency prior to, during and after the administration of human growth hormone (hGH). TSH and prolactin secretory patterns were not uniformly concordant. TSH responses to TRH infusion were suppressed in 4 subjects after 5 days or 1 month of hGH administration despite normal serum thyroxin concentrations. Prolactin responses were suppressed in all 5 subjects after 5 days of hGH administration. After 8 months of hGH therapy both TSH and prolactin responses returned toward pre-hGH values. Our finding that suppression of the TRH-induced TSH and prolactin secretory responses are reversible during hGH administration supports the concept of altered neuroregulation in this form of hypothalamic disorder.

Thyroid hormone concentrations and inhibition of thyroid stimulating hormone secretion in euthyroid subjects with autonomous thyroid nodules

Abstract. Sixty‐four euthyroid patients with autonomous thyroid nodules and normal thyroxine (T4) concentrations and tri‐iodothyronine resin uptake have been studied. The serum tri‐iodothyronine (T3) concentration of the patients was 2.24 (±0.67) ng/ml, significantly higher than in a group of fifty‐seven euthyroid control subjects (1.58 ± 0.30 ng/ml). When no extranodular tissue was visible on the basal thyroid scan, the T3 was 2.31 (±0.63) ng/ml, significantly higher than in patients with some extranodular uptake on the basal scan (1.91 ± 0.42 ng/ml). There was no significant difference in the serum T4 concentrations of the patients (7.37 ± 2.10 μg/100 ml) compared to the control group (6.88 ± 1.89 μg/100 ml). The T4 concentrations were not correlated with total or partial inhibition of the extranodular tissue. The thyroid hormone concentrations were not directly correlated to the size of the nodule assessed by scan imaging. The thyroid stimulating hormone (TSH) concentration of the patients (1.52 ± 0.38 μU/ml) was significantly lower than in normals (2.49 ± 0.96 μU/ml). No significant difference was found in the TSH concentrations of patients with partial or total inhibition of extranodular tissue irrespective of the T3 concentration. A thyrotrophin releasing hormone stimulation test in twelve patients did not increase the serum TSH, irrespectively of the T3 concentration.These data show the high frequency of elevated serum T3 concentrations despite normal serum T4 concentration in euthyroid patients with autonomous thyroid nodules. They confirm that inhibition of TSH secretion can occur when thyroid hormone concentrations are in the normal range.

Enhanced Peripheral Conversion of Thyroxine to Triiodothyronine During hGH Therapy in GH Deficient Children

Eight patients with idiopathic hypopituitarism were studied to evaluate changes in hypothalamic-pituitary-thyroid function during the course of their therapy with hGH. Before treatment, 5 patients were in an euthyroid state with normal serum thyroxine (T4) levels and normal TSH response to TSH-releasing hormone (TRH) (group I), while 3 patients was associated with hypothalamic hypothyroidism (group II). Overall observation period was 6–14 months. Following 1–2 months of hGH therapy, serum T4-I concentrations decreased below the initial level both in group I and II (84 ± 23% and 60 ± 20% of the initial value, respectively, P < 0.05). However, patients of group I showed a prompt rise in serum triiodothyronine (T3) level, resulting in marked elevation of T3/T4 ratio and acceleration of growth, whereas in group II serum T3 remained unchanged at the previous level without promotion of growth rate (180 ± 40% vs. 105 ± 13%, P < 0.001). After L-T4 replacement for the latter, gradual increase in serum T3 with conc...

SPECTRUM OF THYROID FUNCTION IN PATIENTS REMAINING IN REMISSION AFTER ANTITHYROID DRUG THERAPY FOR THYROTOXICOSIS

Thyroid function was assessed in 110 patients who were in remission for a period of 7.6±0.6 years (mean ±S.E.) (range 0.25-25 years) after the withdrawal of antithyroid drug therapy for thyrotoxicosis. On the basis of clinical examination and on the results of thyroid-function tests, the following group of patients were identified: (I) euthyroid with normal plasma-total thyroxine (T4) and triiodothyronine (T3) concentrations, but an absent or subnormal response of plasma-thyrotrophin (T.S.H.) to thyrotrophin-releasing hormone (T.R.H.) (16%); (II) euthyroid with normal concentrations of plasma total T4 and T3 and a normal plasma-T.S.H. response to T.R.H. (59%); (III) euthyroid with normal concentrations of circulating thyroid hormones and a normal basal plasma-T.S.H., but an exaggerated plasma-T.S.H. response to T.R.H. (13%); (IV) euthyroid with normal plasma total T4 and T3 concentrations, but a raised basal plasma-T.S.H. concentration and an exaggerated plasma-T.S.H. response to T.R.H. (6%); (v) hypothyroid (6%). Although the need for short-term follow-up to identify those patients treated with antithyroid drugs who will relapse is well recognised, 16% of all patients in remission for longer than 4 years (10.8±0.7 years) in the present study showed some degree of thyroid failure. Evidence of hypothyroidism was associated with an increased frequency of thyroid microsomal antibodies. If the morbidity of the late development of hypothyroidism is to be avoided, patients who have been treated with antithyroid drugs should have long-term follow-up, as do patients treated surgically or with radioiodine.

Thyroid Function in Malignant Lymphoma

Thyroid function was studied in 36 patients with various stages of malignant lymphoma. Stage IVB patients exhibited characteristic changes in thyroid biochemistry in the form of lowered triiodothyronine (T3) and elevated free thyroxine (FT4), but normal thyroxine. Moreover, the concentration of thyroxine-binding prealbumin and albumin was lowered, whereas thyroxine-binding globulin was normal. Thyroid-stimulating hormone was slightly elevated but showed a normal increase after administration of thyrotrophin-releasing hormone. Patients with less extensive disease differed only slightly from the controls. The results agree with previous studies of patients suffering from other chronic diseases. The mechanisms underlying the hormonal changes have been only partially elucidated. When investigating patients with disseminated malignant disease for thyroid disease, the above mentioned changes in thyroid biochemistry must be borne in mind. Single analyses of FT4 and T3 may give rise to a false assumption of hyper- or hypothyroid states in patients who are in fact euthyroid.

Pharmacological influences on T 4 to T 3 conversion in rat liver

Five groups of 8 rats were treated with normal diet, diphenylhydantoin, dexamethasone, thyroxine (T 4) and phenobarbital respectively for 14 days. After this period plasma triiodothyronine (T 3), T 4 and reverse T 3 (rT 3) concentrations as well as the T 4 to T 3 converting activity in the liver homogenates were determined. Plasma T 3 was low after dexamethasone, T 4 and phenobarbital. Plasma T 4 was low after dexamethasone and elevated after T 4. rT 3 plasma concentrations were at the lower limit of detection in all groups. The converting activity in the liver homogenate was significantly increased after diphenylhydantoin and very much depressed after dexamethasone. These results support the concept that different drugs may influence the peripheral thyroid hormone metabolism, especially the T 4 to T 3 conversion. However other pathways might be affected also because plasma T 3 levels did not always reflect the converting activity in the liver.

Functioning thyroid masses in childhood and adolescence: Clinical, surgical, and pathologic correlations

Six girls, aged 5 to 15 years, presented with thyroid masses in otherwise nonpalpable thyroid glands and with normal serum thyroxine levels. Scintiscanning before and after TSH stimulation confirmed the presence of autonomous nodules in the four adolescents, of whom two had elevated T3 levels. Surgical exploration revealed adenomatous thyroid hyperplasia in three of the girls and papillary adenocarcinoma in the fourth. Scans in the other two girls revealed absence of the left lobe. One of them proved to have agenesis of the left lobe with enlargement of the right lobe because of lymphocytic thyroiditis. The other girl had an ectopic thyroid with chronic inflammation. A thorough diagnostic evaluation of single or multiple functioning thyroid masses in children and adolescents is essential in establishing the correct diagnosis. The possibility that carcinoma can occur in autonomous nodules as well as in hemiagenesis and ectopic thyroid tissue is discussed. An approach to the management of functioning thyroid masses in the pediatric age group is proposed.

Pituitary-thyroid regulation in euthyroid patients with Graves' disease previously treated with antithyroid drugs.

To understand why some patients with hyperthyroidism due to Graves' disease remain euthyroid after a course of antithyroid drug therapy, pituitary-thyroid regulation was studied in 20 such patients who had remained well for six months or longer after the withdrawal of antithyroid drugs. Only patients who were clinically euthyroid and had normal serum thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) concentrations were studied. Serum TSH responses to thyrotropin-releasing hormone (TRH) and thyroid suppression were determined in all patients. Seven patients had normal responses to both tests. Six patients had a subnormal response to TRH and abnormal suppression. Five patients had a subnormal response to TRH and normal suppression, and two patients had a normal TSH response to TRH and abnormal suppression. There were no differences in the mean serum T4, T3 or TSH concentrations between any of the groups. The mean duration of time after antithyroid drug withdrawal was 19 months in the patients in whom both tests were abnormal, whereas it was 58 months in those in whom both tests were normal and 45 months in those with a subnormal TSH response to TRH and a normal suppression test. Thus, in 13 of the 20 patients studied, various degrees of abnormality of pituitary-thyroid regulation were demonstrable. These results suggest that, in most patients with Graves' disease who remain clinically and biochemically euthyroid after a course of antithyroid drug therapy, the disease persists in a mild or subclinical form.

Dissociation between TSH and prolactin dynamics in treated thyrotoxicosis.

TSH and prolactin secretory patterns in thyroid disease have generally been reported as concordant. We studied TSH and prolactin responses to TRH infusion (500 mug) in euthyroid individuals previously treated for thyrotoxicosis with 131I or antithyroid drugs. The 131I-treated group (seven men, twenty women) had been clinically and biochemically euthyroid (normal serum thyroxine and triiodothyronine levels) for 6 months to 4-5 years (kappa +/- SD = 17-1 +/- 4-1 months). Based on maximal TSH increment (deltaTSH), three patient groups were identified: Group 1 [normal deltaTSH, n = 6]: delta prolactin was normal in two, blunted in one and exaggerated in three. Group 2 (exaggerated TSH response, n = 8): delta prolactin was normal in two, blunted in one and exaggerated in five. Group 3 (TSH nonresponders, n = 13): delta prolactin was normal in five, blunted in three, and exaggerated in five. Eleven patients (three men, eight women) were studied after 6 months antithyroid-drug treatment. All were clinically and biochemically euthyroid. All but one showed a blunted TRH-TSH response. All three men showed an exaggerated delta prolactin as did four of eight women. Three women showed a blunted delta prolactin and in one, delta prolactin was normal. Thus, TRH-induced TSH and prolactin response patterns in treated thyrotoxicosis are not uniformly concordant, and, while a blunted or absent TSH response commonly persists long after euthyroidism has been restored, this is most frequently accompanied by a normal or exaggerated prolactin response.

Fresh and cultured thyroid gland: survival and function after implantation.

Isogeneic or allogeneic thyroid glands were implanted into thyroidectomized recipeint rats. These grafts, either fresh or cultured, were placed in hamstring muscle pocket or under the renal capsule. Survival and function of the grafts were evaluated by: restoration of normal levels of serum thyroxine, weight gain, kidney transamidinase (a thyroxine-induced enzyme), and histological appearance of re-excised implants. A isografts, fresh and cultured, functioned well as ectopic thyroid glands, though restoration of normal serum thyroxine levels was more rapid for the fresh implants. Fresh allografts functioned transiently but then failed due to rejection. No function was detected for cultured allografts, and rejection was seen histologically. The rat thyroid allograft therefore differs from the rat parathyroid allograft, which often can function for several months despite histological evidence of rejection. Maintenance in tissue culture prior to implantation does not appear to alter the longterm immunogenicity of either organ.

Serum thyrotrophin concentration: an unreliable test for detection of early hypothyroidism after thyroidectomy.

Three groups of patients who had undergone subtotal thyroidectomy for Graves's disease, toxic multinodular goitre, or euthyroid multinodular goitre 12 to 15 years before and in whom a normal serum thyroxine (T-4) level was found were each divided into two subgroups on the basis of a normal or a raised serum thyrotrophin concentration. There was no difference in mean serum T-4 concentration between patients with normal and those with raised serum thyrotrophin concentrations, and the values were similar to the mean T-4 values of the normal population. The mean serum triiodothyronine values of all groups were higher than normal, but the mean values of the groups with a normal and a raised serum thyrotrophin were similar. After thyroidectomy a mildly raised serum thyrotrophin does not in itself indicate the presence of hypothyroidism.

ENDOCRINE ASPECTS OF THE ROTHMUND-THOMSON SYNDROME

Three siblings (15 6/12 to 17 6/12 yrs.) with the Rothmund-Thomson Syndrome showed the following characteristic features: low birth weight for gestation, severe growth failure (present height: 110–113 cm), mental retardation, alopecia, hypoplastic nails, absent sexual development with cryptorchidism in the males, microdontia and anodontia, aphakia, decreased sweating, and congential poikiloderma, Routine studies were normal. Radiographs revealed delayed bone age in the males, complete epiphyseal fusion in the female, and generalized skeletal abnormalities. Endocrine studies revealed normal glucose responses with hyperinsulinemia to oral glucose, I.V, tolbutamide, and arginine. All had normal serum TSH, thyroxine and serum cortisol levels. Serum growth hormone (hGH) responses were variable but each subject showed at least one value over 10 ng/ml to argine (0.5 gm/kg) or insulin (0.10 u/kg) with insulin insensitivity, Serum hGH response to L-DOPA (0.5 gm p.o.) were all less than 6 ng/ml. Basal serum LH, FSH and testosterone were decreased and LH-RH (100 ug S.C.) did not produce a significant rise in serum LH or FSH in any of the subjects. The patients were treated with testosterone 10 mg/day, hGH 15 units/week or estradiol 50 μg/day respectively, for 6 months, with no clinical benefit. These studies suggest normal pituitary function for TSH, ACTH, and hGH, but the absent LH/FSH response to LH-RH with low basal levels suggest diminished pituitary gonadotropin reserve.

Free serum thyroxine level and basal metabolic rate. Aids to diagnosis in malnutrition and small-for-gestational-age dwarfism.

Measurement of the basal metabolic rate (BMR) and the total and free serum thyroxine values in response to feeding are aids in the diagnosis of growth failure. Infants with small-for-gestational-age dwarfism gained weight poorly in the hospital, had a low BMR before and after spontaneous or induced weight gain, and a normal serum thyroxine value. Infants with linear growth failure due to chronic malnutrition had a normal BMR but a low serum thyroxine value that rose to normal with weight gain; infants with clinical signs of recent weight loss had a low BMR and a low serum thyroxine value, both of which rose to normal with weight gain. Increases of the BMR were sharp and very rapid; they preceded the rise of the serum thyroxine value in some cases.

Thyroid-stimulating hormone levels in idiopathic euthyroid goiter.

Utilizing a double antibody radioimmunoassay for human TSH we compared distribution of serum TSH in 167 normal individuals and 51 patients with idiopathic euthyroid goiter. In addition to being clinically euthyroid both groups had normal total thyroxine, and free thyroid index. Forty-two percent of the goiter group had high TSH and the general distribution of TSH values in the goiterous patients was significantly higher than normal (P less than 0.001). Anlysis of subgroups of the normal and goiter populations indicated that the high TSH could not be attributed to age, sex, use of birth control pills or differences between diffuse and multinodular goiter. TSH levels were significantly higher in patients with goiter less than 1 yr compared to goiter greater than 1 yr (P less than 0.025). In patients with goiter greater than 1 yr the TSH levels remained significantly higher than normal (P less than 0.025). These results support the hypothesis that TSH plays a role in the genesis of idiopathic goiter. The elevation may be present only early in the course of goiter development but is also present in a significant number of patients with long standing goiter.

Nonpuerperal lactation and normal prolactin regulation.

Prolactin secretion was evaluated in 11 consecutive patients referred with nonpuerperal lactation who did not have clinical evidence of pituitary tumors. Six patients had normal fasting prolactin (PRL) levels, 13.8 plus or minus 1.8 ng per ml (Group I), and the other 5 women had elevated basal serum PRL concentrations, 182 plus or minus 72 ng per ml (Group II). All Group II patients had amenorrhea; however, 5 of 6 Group I patients had menstrual periods. The 24-h mean serum PRL concentrations were 12.8 plus or minus 1.2 (SEM), 13.3 plus or minus 0.7, and 165 plus or minus 62 ng per ml for the controls and Group I and II, respectively. A pattern of intermittent PRL discharge during the day characterized each group; however, a normal sleep related increase in serum PRL concentration was absent in the Group II patients. Chlorpromazine produced greater than two-fold increases in serum PRL concentrations in the controls and Group I patients; however, this response was absent in Group II. L-Dopa produced appropriate suppression of serum PRL concentrations in the normals and both patient groups. Normal serum growth hormone, thyroxine, and plasma cortisol characterized each group. Serum estrogen and/or LH and FSH were decreased in 3 of 5 Group II patients; however, the serum concentrations of these hormones were normal in 5 of 6 Group I patients. Short term L-dopa therapy was effective in suppressing lactation in 3 of 5 Group II patients, and it also decreased lactation in the 4 treated Group I patients without significantly altering 24-h mean serum PRL concentrations in the latter group. hypothalamic-pituitary dysfunction was present in certain patients with nonpuerperal lactation who had elevated 24-h mean PRL concentrations and no PRL release following chlorpromazine and sleep. Frequently, however, nonpuerperal lactation is associated with normal prolactin secretion.