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Showing papers in "The Journal of Clinical Endocrinology and Metabolism in 1973"


Journal ArticleDOI
TL;DR: The purpose of the present study was to investigate the mechanisms by which estrogen production arises in the human female following the menopause, and the results suggest an increase in conversion of A to E1 with age.
Abstract: The purpose of the present study was to investigate the mechanisms by which estrogen production arises in the human female following the menopause. The possibilities considered were a) glandular secretion of estrone (E1) or estradiol (E2), b) the peripheral aromatization of circulating androstenedione (A), or c) the aromatization of other plasma precursors of estrone or estradiol. Studies were carried out in 6 postmenopausal women in which the following were measured: the plasma production rate of A (PRPA), the fraction of plasma androstenedione which was converted to estrone as measured in urine, and in blood, , and the total estrone production rate as measured by the urinary method (PRE1). The mean PRPA, 1.75 mg/24 hr, was about one-half of that observed in premenopausal women and arose principally from the adrenal glands. The mean transfer constant, value was 0.027, which is about twice the value obtained in premenopausal women, suggesting an increase in conversion of A to E1 with age. The results sugg...

875 citations


Journal ArticleDOI
TL;DR: It is concluded that GIP is a potent insulinotropic hormone and probably takes part in physiological potentiation of insulin secretion in response to hyperglycemia during absorption of nutrients from the intestine.
Abstract: The effect of very highly purified gastric inhibitory polypeptide (GIP) on insulin secretion in man was tested in normal volunteers. Administration of physiological doses of GIP together with glucose by IV infusion resulted in potentiation of the rise in IRI in the blood and improvement in glucose tolerance. It is concluded that GIP is a potent insulinotropic hormone and probably takes part in physiological potentiation of insulin secretion in response to hyperglycemia during absorption of nutrients from the intestine.

807 citations


Journal ArticleDOI
TL;DR: A sensitive homologous radioimmunoassay for human prolactin (hPRL) is developed and measures concentrations of hPRL as low as 1 ng/ml of human plasma in a group of randomly selected male and female individuals.
Abstract: We have developed a sensitive homologous radioimmunoassay for human prolactin (hPRL). Prolactin isolated from human pituitary glands was used for generating antibodies in rabbits, for iodination, and for standards. The assay is highly specific for hPRL and measures concentrations of hPRL as low as 1 ng/ml of human plasma. In this assay, the plasma concentrations of hPRL in a group of randomly selected male and female individuals averaged 13 ± 4 (SD) and 14 ± 4 ng/ml, respectively. In contrast, hPRL in the pooled plasma of pregnant women assayed 80 ng/ml; a post-partum plasma measured 215 ng/ml. Of 6 patients with acromegaly, 5 possessed hPRL levels above 34 ng/ml, the average being 40 ± 9 ng/ml. Administration of TSH releasing hormone increased plasma hPRL concentrations by 4-fold in both a male and a female subject, while LH releasing hormone depressed them slightly. The concentration of hPRL in pituitary glands removed at autopsy was 1.5 μg/mg for a male and 1.3 μg/mg for a female. These values approxim...

669 citations


Journal ArticleDOI
TL;DR: Plasma testosterone (T) was measured by a sensitive radioimmunoassay method in 143 normal newborns and infants, finding that in male infants there was an increase of T concentration from birth to the 2-3th months of life, followed by a gradual decrease.
Abstract: Plasma testosterone (T) was measured by a sensitive radioimmunoassay method in 143 normal newborns and infants. In cord blood T levels are significantly higher in male than in female newborns. In male infants there was an increase of T concentration from birth to the 2-3th months of life, followed by a gradual decrease. After the 7th month values observed reached those of prepubertal boys. In females the pattern was very different. T levels dropped rapidly from birth to the second week of life reaching values similar to those of prepubertal girls.

307 citations


Journal ArticleDOI
TL;DR: Double antibody radioimmunoassays developed to measure gonadotropinreleasing hormone (Gn-RH) produced inhibition curves which were parallel to those obtained with the synthetic Gn-RH standard.
Abstract: Double antibody radioimmunoassays have been developed to measure gonadotropinreleasing hormone (Gn-RH). Thyrotropin-releasing hormone, melanocyte-stimulating hormone inhibiting factor, various Gn-RH analogs and the components of serum per se did not appear to influence the assay. Serum containing endogenous or endogenous plus exogenous Gn-RH, crude hypothalamic extracts, and various Gn-RH analogues all produced inhibition curves which were parallel to those obtained with the synthetic Gn-RH standard. Exogenous Gn-RH could be quantitatively recovered from 200 μl of serum obtained from sheep in different reproductive states. Sensitivity of the radioimmunoassay ranged from 1 to 3.8 pg per assay tube with the more sensitive antibody. Using this same radioimmunoassay system the coefficient of variation for 12 samples in the same assay was 5.9% while the coefficient of variation for 2 samples in 6 different radioimmunoassays was 14.7%. The level of Gn-RH in serum of normal rams was 71 ± 1.4 (se) pg/ml as compar...

282 citations


Journal ArticleDOI
TL;DR: It was concluded that any sampling period longer than 5 min gives an erroneous depiction of events and this was exemplified in the case of ACTH secretion.
Abstract: Plasma concentrations of ACTH (by radioimmunoassay) and cortisol (by competitive protein binding) were measured in a normal man at 5-min intervals from 0100 to 0900 hr. During this time there were 18 episodes of ACTH secretion and 13 episodes of cortisol secretion. On occasion, 2 or more episodes of ACTH secretion in close temporal relationship were reflected in a single sustained elevation of cortisol concentration. Estimates were obtained of the amounts of ACTH produced per episode which ranged from 0.5 μg to 4.5 μg at an average rate over the whole study of 0.29 μg per min. The plasma concentrations achieved in most instances were more than sufficient to produce maximal adrenal secretion of cortisol. Cortisol secretion began about 10 min after initiation of ACTH secretion. Cortisol secretion ranged from 0.1 mg to 2.9 mg per episode at an average rate over the whole study of 105 (μg/min. It is concluded that any sampling period longer than 5 min gives an erroneous depiction of events and this was exempl...

266 citations


Journal ArticleDOI
TL;DR: It is concluded that the nocturnal rise is dependent on the occurrence of sleep, not on the inherent rhythm related to time of day.
Abstract: Four normal young adults underwent partial or complete inversion of their sleepwaking cycles to determine the relationship of the nocturnal release of human prolactin to sleep. Prolactin release shifted immediately and completely with shifts of sleep onset of 3, 6 and 12 hr. Thus, the nocturnal rise is dependent on the occurrence of sleep and is not based on an inherent rhythm related to time of day.

249 citations


Journal ArticleDOI
TL;DR: PRL responses in each of 3 age groups of females, 20-39, 40-59 and 60-79 years old, were nearly double the responses observed in males of the same age groups, but individual variability was greater in the older subjects of both sexes.
Abstract: Synthetic thyrotropin releasing hormone (TRH) was administered intravenously to normal human subjects and the serum prolactin (PRL) response was measured. The effects of dose and of age and sex of the recipients on the PRL response were evaluated. The maximum increase in scrum PRL above the baseline level (max APRL) was used as the index of response. The max APRL increased linearly as a function of the log of the TRH dose between 6.25 and 100 μg of TRH, but did not increase further in response to 400 and 800 μg of TRH. Mean PRL responses did not vary with age in subjects of the same sex, but individual variability was greater in the older subjects of both sexes. PRL responses in each of 3 age groups of females, 20-39, 40-59 and 60-79 years old, were nearly double the responses observed in males of the same age groups (58.9 ± 4.7 ng/ml in all females vs 28.7 ± 2.4 ng/ml in all males, mean ± sem). In order to avoid diagnostic error in evaluating PRL response to TRH, criteria must be employed that are specif...

247 citations


Journal ArticleDOI
TL;DR: A sensitive radioreceptor assay (RRA) capable of detecting 0.2 ng of human growth hormone (hGH) has been developed using plasma membrane fragments derived from the liver of pregnant rabbits and 125I-hGH.
Abstract: A sensitive radioreceptor assay (RRA) capable of detecting 0.2 ng of human growth hormone (hGH) has been developed using plasma membrane fragments derived from the liver of pregnant rabbits and 125I-hGH. Human, monkey, bovine and ovine GH all inhibit the binding of 125I-hGH, while the inhibition by hPL or human prolactin (hPRL) was minimal.

245 citations


Journal ArticleDOI
TL;DR: In this article, the mean androstenedione level during the middle third of the menstrual cycle was significantly higher than during the earlier (p < 0.01) or later portions.
Abstract: Utilizing specific radioimmunoassays serum androstenedione, testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were measured daily in the same aliquots of sera in 6 ovulatory menstrual cycles. In 3 of 6 cycles a progressive increase in serum androstenedione concentration was seen during the follicular phase. The mean androstenedione level during the middle third of the menstrual cycle was significantly higher than during the earlier (p < 0.01) or later (p < 0.001) portions. Serum testosterone levels in the same individual cycles showed random variations. Again the mean T level was significantly higher (p < 0.001) during the middle third as compared to either the beginning or end of the menstrual cycle.

232 citations


Journal ArticleDOI
TL;DR: A favorable response to orbital irradiation was observed even in some patients who had previously responded poorly to systemic corticosteroid therapy, and severe asymmetrical extra-ocular paresis was not relieved following treatment, even though other concomitant manifestations of ophthalmopathy improved.
Abstract: Patients with severe Graves' ophthalmopathy have been treated by selective orbital irradiation using a well-collimated, high-energy, x-ray beam generated by a linear accelerator. Severity of involvement and response to therapy was judged by a numerical scoring procedure and by clinical assessment. Of 23 patients treated, 15 (65%) experienced an excellent or good response, which occurred soon after the start of radiotherapy. No patient was made worse by treatment. A favorable response to orbital irradiation was observed even in some patients who had previously responded poorly to systemic corticosteroid therapy. Severe visual acuity loss or elevated intraocular pressure were not considered to be contraindications to radiation treatment. Severe asymmetrical extra-ocular paresis was not relieved following treatment, even though other concomitant manifestations of ophthalmopathy improved. Anatomic, physiologic and immunologic concepts concerning the pathogenesis of the eye lesions constitute the rati...

Journal ArticleDOI
TL;DR: Estrogen receptor in human breast cancer tissue is markedly labile under the conditions usually employed for assay, but significant increases in assay sensitivity can be achieved with the use of thiol reagents (dithiothreitol) at low temperatures.
Abstract: Estrogen receptor in human breast cancer tissue is markedly labile under the conditions usually employed for assay. Significant increases in assay sensitivity can be achieved with the use of thiol reagents (dithiothreitol) at low temperatures. These modifications may be important in preventing misclassification of a patient's tumor as being potentially autonomous with regard to endocrine therapy.

Journal ArticleDOI
TL;DR: It is concluded that the mechanism of the glucocorticoid suppressive action on TSH secretion after short-term, low doses of glucoc Corticoid administration may be an impaired secretion of endogenous TRF, which results in a supernormal TSH response induced by exogenous TRF.
Abstract: The influences of glucocorticoid administration or increased serum corticoid concentration on TRF-induced TSH release was studied in patients receiving glucocorticoids and in patients with Cushing's syndrome. The TRFinduced TSH release was inhibited in patients who had received glucocorticoids for long periods or in high doses. These patients had received more than 60 mEq of cortisol per day for more than six months. Definite plasma TSH increases by TRF were observed in patients receiving shortterm, low doses or intermittent, low doses administration of glucocorticoid. Little or no rise of plasma TSH occurred following TRF administration to patients with Cushing's syndrome. From these observations it is possible to conclude that the mechanism of the glucocorticoid suppressive action on TSH secretion after short-term, low doses of glucocorticoid administration may be an impaired secretion of endogenous TRF, which results in a supernormal TSH response induced by exogenous TRF. With long-term and high doses ...

Journal ArticleDOI
TL;DR: Synthetic (linear) somatostatin (SRIF, somatotropin-release inhibiting factor) abolished the elevation of serum GH concentration induced in normal human subjects by the administration of L-dopa and arginine.
Abstract: Synthetic (linear) somatostatin (SRIF, somatotropin-release inhibiting factor) abolished the elevation of serum GH concentration induced in normal human subjects by the administration of L-dopa and arginine. Within the dose used (250 μg, iv and 500 μg constant infusion) somatostatin. did not inhibit the rise in circulating PRL normally observed with arginine infusion nor did it modify basal levels of serum GH, TSH, PRL, FSH and LH.

Journal ArticleDOI
TL;DR: Round the clock hPRL concentrations exhibit briefly episodic, rather aperiodic, circhoral variation that rarely approaches undetectability or reported t½ values of labeled exogenous PRL.
Abstract: A recently developed, sensitive, specific homologous radioimmunoassay for human prolactin (hPRL) made possible our study of hPRL variation in plasma across sleep-wake cycles and in daytime naps. Samples were drawn at 20-min intervals from 5 normal young adults (4 ♂, 1 ♀), studied over at least three 24-hr periods each, and in 12 daytime naps. Study periods consisted of 1–3 baseline sleep-wake cycles per subject (total 8/5 subjects), 1-2 sleep-wake cycles per subject in which the wake cycle contained a single 2-hr daytime nap period (total 8 sleep-“nap” cycles/5 subjects) and a single daytime nap added onto the end of a 24-hr sleep-wake cycle (total 4/4 subjects). Sleep was polygraphically monitored. Round the clock hPRL concentrations exhibit briefly episodic, rather aperiodic, circhoral variation that rarely approaches undetectability or reported t½ values of labeled exogenous PRL. The briefly episodic pattern does not repeat itself at 24-hr periods or in sleep each night, and is not synchronous with hGH...

Journal ArticleDOI
TL;DR: Apomorphine hydrochloride increased the concentration of growth hormone (GH) in serum above 10 ng/ml in all 12 subjects and decreased serum prolactin (PRL) levels in 4 subjects, compatible with modulation of GH secretion by a dopaminergic mechanism.
Abstract: Apomorphine hydrochloride was administered sc to 12 adult men on 23 occasions. In doses of 0.75–1.0 mg, apomorphine-HCl increased the concentration of growth hormone (GH) in serum above 10 ng/ml in all 12 subjects; peak values occurred at 30–60 min following injection. The increase was antagonized in the 4 subjects pretreated with chlorpromazine. Apomorphine decreased serum prolactin (PRL) levels in 4 subjects but only in a dose of 1.0 or 1.5 mg; the compound failed to decrease chlorpromazineinduced elevated levels of PRL. The drug had no effect on serum LH or FSH. These results are compatible with modulation of GH secretion by a dopaminergic mechanism. Further studies are needed to determine the reliability and potential clinical usefulness of apomorphine as an agent to stimulate GH secretion.

Journal ArticleDOI
TL;DR: A sensitive and reliable radioimmunoassay combined with celite column chromatography for specific determination of plasma testosterone (T) is described and levels of unbound T in the first two weeks of life are still significantly higher in male than in female infants.
Abstract: A sensitive and reliable radioimmunoassay combined with celite column chromatography for specific determination of plasma testosterone (T) is described. The percentage binding was measured by equilibrium dialysis. In 28 normal newborns, total T concentration is significantly higher in male (68.1 ± 59.5) than in female newborn infants (12.0 ± 6.2) while binding of T increases rapidly after birth. Although there is no sex difference in TeBg capacity, levels of unbound T in the first two weeks of life are still significantly higher in male than in female infants. There was no sex difference in 62 normal prepubertal children studied, the total T concentration being 6.62 ± 2.46 and 6.58 ± 2.48 ng/100 ml in boys and girls, respectively; the binding of T and unbound T levels were identical in both. In 17 patients with Turner syndrome, total T concentration (13.6 ± 3.1 ng/100 ml) was significantly higher than in prepubertal children and increased (21.5 ± 2 ng/100 ml) under moderate estrogen therapy while the perc...

Journal ArticleDOI
TL;DR: In this article, the effects of epinephrine on plasma glucagon levels were studied in 8 normal subjects, and the results showed that during infusion of 6 μg/min for 1 hr, the plasma glucose levels rose progressively from a mean (± sem) level of 125 ± 9.1 pg/ml to a mean maximum of 180 ± 18.7 pg/m, p < 0.01.
Abstract: To determine the influence of the adrenergic system on pancreatic alpha-cell function in man, effects of epinephrine on plasma glucagon levels were studied in 8 normal subjects. During infusion of epinephrine (6 μg/min for 1 hr) plasma glucagon rose progressively from a mean (± sem) level of 125 ± 9.1 pg/ml to a mean maximum of 180 ± 18.7 pg/ml, p < 0.01. Despite coexistent hyperglycemia, plasma insulin did not increase appreciably. Thus epinephrine stimulates glucagon secretion in man while inhibiting insulin release. The adrenergic system therefore appears to influence both pancreatic alphaand beta-cell function in man.

Journal ArticleDOI
TL;DR: Oral administration of 150 mg of 5-hydroxytryptophan resulted in a rise in plasma human growth hormone (HGH), ACTH and cortisol in most of the subjects tested, but not plasma ACTH or cortisol response to 5-HTP.
Abstract: Oral administration of 150 mg of 5-hydroxytryptophan (5-HTP) resulted in a rise in plasma human growth hormone (HGH), ACTH and cortisol in most of the subjects tested. Concomitant administration of glucose with 5-HTP significantly blunted plasma HGH response, but not plasma ACTH or cortisol response to 5-HTP.

Journal ArticleDOI
TL;DR: Evidence is provided that human fetal testicular tissue accumulates testosterone in a pattern suggesting higher androgen production at the time of male genital differentiation.
Abstract: Testosterone and estradiol concentrations were measured by isotope-displacement assays in the gonads and adrenals of 54 human fetuses (33 male, 21 female) delivered by hysterotomy. Results were correlated with crownrump (CR) length which ranged from 5 to 24 cm, corresponding to 10–25 weeks fetal age. Testosterone concentration averaged 1400 pg/mg in the testes but was negligible (<90 pg/mg) in the ovaries and in the adrenals of both sexes. Testosterone was found in appreciable amounts in the testes from the youngest specimens, reached a peak at 7–10 cm CR-length and declined by 13–14 cm CR-length. Little or no estradiol was detected in fetal testes, ovaries and adrenals and there were no sex differences in these levels. These data provide evidence that human fetal testicular tissue accumulates testosterone in a pattern suggesting higher androgen production at the time of male genital differentiation.

Journal ArticleDOI
TL;DR: Plasma AVP levels in animals also rose with dehydration, increased plasma hypertonicity and hypovolemia and fell with hydration, and in patients with diabetes insipidus smoking was followed by up to several hundred-fold increases in plasma AVP.
Abstract: A highly sensitive specific radioimmunoassay (RIA) method for the measurement of arginine vasopressin (AVP) is described. The sensitivity of the assay is 0.1 pg/ml. A simple extraction technique from plasma is described with a consistent recovery of about 65–70%, and without alteration in the immunoreactivity of the extracted hormone. AVP levels, uncorrected for recovery, ranged between 1.3 and 8.5 pg/ml (mean 3.7 pg/ml) in humans after 12–25 hr of water deprivation, and were consistently less than 1.2 pg/ml after water loading. AVP levels were undetectable in 6 patients with diabetes insipidus. Smoking was followed by up to several hundred-fold increases in plasma AVP. Plasma AVP levels in animals also rose with dehydration, increased plasma hypertonicity and hypovolemia and fell with hydration.

Journal ArticleDOI
TL;DR: Comparison of immunostained sections and serial sections stained with various cytologic coloration procedures showed that the cell type reactive with the gonadotropin antisera varied widely in staining, which supports the immunohistologic demonstration that FSH and LH are both found in a single cell population.
Abstract: The human hypophyseal cells containing follicle stimulating hormone (FSH) and luteinizing hormone (LH) were identified immunohistologically by an immunoglobulin-peroxidase bridge procedure. Antisera to FSH and LH reacted selectively with their specific antigens in characterization studies employing radioactive binding analyses and the immunohistologic method after absorption with purified glycoprotein hormones. In serial immunostained sections, the same cells reacted with both gonadotropin antisera. Comparison of immunostained sections and serial sections stained with various cytologic coloration procedures showed that the cell type reactive with the gonadotropin antisera varied widely in staining. All remaining chromophilic cells were recognizable as producing pituitary hormones other than gonadotropins and were unreactive with gonadotropin antisera. The latter histologic finding supports the immunohistologic demonstration that FSH and LH are both found in a single cell population. The gonadotropic cells...

Journal ArticleDOI
TL;DR: Comparisons of the 9 cases of “typical” APA with the 7 patients with IAH showed other differences, and the diurnal curve of plasma aldosterone in APA showed a decline from early morning to late evening, parallel with falling plasma cortisol, regardless of stimulation of renin by posture, sodium depletion or spironolactone.
Abstract: In 9 of 11 ambulatory patients with hyperaldosteronism due to aldosterone-producing adenoma (APA). plasma aldosterone fell during the morning; but in all 7 cases of idiopathic adrenal hyperplasia (IAH) standing caused an increase in plasma aldosterone. Further comparisons of the 9 cases of “typical” APA with the 7 patients with IAH showed other differences. The diurnal curve of plasma aldosterone in APA showed a decline from early morning to late evening, parallel with falling plasma cortisol, regardless of stimulation of renin by posture, sodium depletion or spironolactone. In APA, plasma aldosterone was increased after ACTH injection and decreased after dexamethasone. In IAH, although aldosterone secretion can be stimulated by ACTH, the ordinary diurnal rhythm of plasma aldosterone does not parallel plasma cortisol, and is not consistently altered by dexamethasone. Plasma aldosterone in IAH is consistently increased by standing, as well as by a low-sodium diet. After spironolactone, both PRC an...

Journal ArticleDOI
TL;DR: An autosomal dominant mode of inheritance with incomplete expressivity is suggested by analysis of the six kindreds studied, although genetic heterogeneity can not be excluded.
Abstract: Hypogonadotropic eunuchoidism is a well recognized form of familial hypogonadism characterized by selective gonadotropin deficiency and sexual infantilism. Often, olfactory dysfunction or cryptorchidism are also present. Six kindreds of patients with hypogonadotropic eunuchoidism were studied in order to ascertain the mode of inheritance in this disorder. Thirtyfive percent of the siblings of affected individuals exhibited either hypogonadism, olfactory dysfunction or cryptorchidism. Olfactory dysfunction and hypogonadism were expressed in both men and women, although more commonly in men. Male to male transmission of anosmia was observed. An autosomal dominant mode of inheritance with incomplete expressivity is suggested by analysis of the six kindreds studied, although genetic heterogeneity can not be excluded. The most common abnormalities detected among the kindred members were olfactory dysfunction (26 patients), hypogonadism (21 patients), and cryptorchidism (6 patients). Hare-lip or cleft palate, a...

Journal ArticleDOI
TL;DR: The data support the concept that although there is a specific seminiferous tubular factor regulating F SH secretion, testicular steroids also modulate FSH secretion.
Abstract: The effect of sex steroids on plasma concentrations of FSH and LH was studied in 18 men. Steroids were administered by constant infusion for 96 hr at twice the estimated daily production rate of normal men to obtain stable levels in peripheral blood. Testosterone, 15 mg daily, increased plasma testosterone and estradiol levels 2-fold and suppressed FSH and LH approximately 40% during the 3rd and 4th days of infusion. Infusion of estradiol, 90 μg daily, caused similar suppression of FSH and LH (approximately 30%), and addition of 17α-hydroxyprogesterone, 4.5 mg daily, to the estradiol, 90 μg daily, had no additive effect. Dihydrotesterone, in pharmacologic dosage (7.5 mg daily) produced no detectible changes in plasma FSH or LH. There was no evidence for a selective effect of any of the steroids on FSH secretion. This study supports our previous concept that although there is a specific seminiferous tubular factor regulating FSH secretion, testicular steroids also modulate FSH secretion.

Journal ArticleDOI
TL;DR: A patient with Cushing's disease who exhibited a “paradoxical response to dexamethasone” was studied in detail over a period of 100 days in an effort to determine the basis of her unusual response to attempted pituitaryadrenal suppression, and it became apparent that her pituitaries overactivity was spontaneously rhythmic.
Abstract: A patient with Cushing's disease who exhibited a “paradoxical response to dexamethasone” was studied in detail over a period of 100 days in an effort to determine the basis of her unusual response to attempted pituitaryadrenal suppression. In the course of the study it became apparent that her pituitary-adrenal overactivity was spontaneously rhythmic, with cycles occurring approximately every 11 days, and that the apparent paradoxical response to dexamethasone had been purely fortuitous. Urinary 17-hydroxycorticosteroids at the peaks of the cycles averaged 125 mg per day and, at the nadirs, 18 mg per day. The cycles were not altered by treatment with dexamethasone, metyrapone, cortisol, or L-dopa. During the interval between spontaneous peaks, adrenal responsiveness to exogenous ACTH and pituitary–adrenal responsiveness to exogenous vasopressin were demonstrable, thus excluding cyclic exhaustion of pituitary or adrenal reserve as an explanation for the periodic hormonogenesis. The patient's hypercortisoli...

Journal ArticleDOI
TL;DR: Both the sera from untreated hyperthyroid patients and LATS-IgG also stimulated the accumulation of cyclic AMP in human thyroid slices in vitro.
Abstract: In an attempt to detect a thyroidstimulating substance in the sera of hyperthyroid patients, human and guinea pig thyroid slices were incubated directly in the sera of untreated hyperthyroid patients. The intracellular colloid droplets were enumerated in 25 follicles of the incubated slices. Eighty-two % of LATS-negative sera obtained from untreated hyperthyroid patients did stimulate intracellular colloid droplet formation in normal human thyroid slices. More than 0.1 mU/ml of bovine TSH was required to produce the increase of colloid droplets similar to that produced by LATS-negative sera. A similar increase in colloid droplet formation was also produced by LATS-IgG in human thyroid slices of normal tissue and Graves' disease as well. The sera from normal subjects were without effect in this respect. Both the sera from untreated hyperthyroid patients and LATS-IgG also stimulated the accumulation of cyclic AMP in human thyroid slices in vitro. Although LATS-IgG stimulated colloid droplet formation in gui...

Journal ArticleDOI
TL;DR: To determine the incidence of thyroid dysfunction in patients receiving therapy with lithium carbonate, serial determinations of serum thyrotropin (TSH) and thyroxine (T4) concentrations were made in 255 patients receiving lithium.
Abstract: To determine the incidence of thyroid dysfunction in patients receiving therapy with lithium carbonate, serial determinations of serum thyrotropin (TSH) and thyroxine (T4) concentrations were made in 255 patients receiving lithium. The patients were followed for an average of 8 months and the longest period of lithium treatment was 65 months. The mean peak TSH level in the lithium treated patients was 3 times higher than in the control groups; elevated (>8 μU/ml) TSH levels occurred in 29.8% of the patients (76) at some time during treatment. At the time of final testing, 14.1% (36) of the patients had elevated serum TSH levels. The mean peak and final thyroxine concentrations in the lithium treated patients were only slightly lower than those in the control groups. In 15 patients whose final serum TSH levels were over 20 μU/ml, the mean thyroxine concentration was 2.9 μg/100 ml. A significantly higher incidence of positive anti-thyroglobulin antibody tests was found in these patients. Most were considere...

Journal ArticleDOI
TL;DR: The precision of the method is comparable to the competitive protein binding assay and there is excellent correlation between the estimation of T4 by these two methods (correlation coefficient, 0.97) in all clinical states.
Abstract: A method for the immunoassay of thyroxine (T4) in unextracted human serum is presented. Thyroxine-binding antibody was obtained by immunization of a rabbit with bovine thyroglobulin. Sodium salicylate is used to block the binding of both labeled and unlabeled T4 to serum thyroxine-binding proteins. Bound and free labeled hormone are separated by adsorption to dextran-coated charcoal. The method is sufficiently sensitive to allow duplicate determinations at two dilutions using 20 μ1 of serum. The precision of the method is comparable to the competitive protein binding assay and there is excellent correlation between the estimation of T4 by these two methods (correlation coefficient, 0.97) in all clinical states.

Journal ArticleDOI
TL;DR: Unstable patterns of serum LH, FSH, and T concentration were demonstrated during frequent interval sampling in 4 normal men; no consistent relationship of T levels to the onset of LH rises could be seen.
Abstract: Unstable patterns of serum LH, FSH, and T concentration were demonstrated during frequent interval sampling in 4 normal men. No consistent relationship of T levels to the onset of LH rises could be seen. However, onethird of the LH peaks was followed by a rise in T levels and each T elevation was preceded by an LH peak. The frequency of release and half-times of disappearance for LH and FSH did not change during clomiphene treatment in 2 of these normal subjects (100 mg/day); elevated serum gonadotropins resulted from an increased magnitude of release per pulse. A similar exaggeration of T secretion was seen. Testosterone propionate injection (25 mg) on day 4 of clomiphene treatment further elevated circulating T levels without lowering serum gonadotropins.