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Biomedical subjects

M H Samuels

Publications and source records attributed to M H Samuels.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effects of metoclopramide on fasting-induced TSH suppression.

Short-term caloric deprivation leads to suppression of TSH secretion in healthy subjects, but the mechanism of this effect is unknown. Since dopamine inhibits TSH secretion at physiologic levels, increased endogenous dopamine activity may cause the TSH suppression observed during fasting. To test this hypothesis, 11 healthy subjects underwent four studies: (1) Baseline-subjects were allowed ad libitum food. (2) MCP-subjects were allowed ad libitum food and received iv metoclopramide (MCP) at 30 micrograms/kg/h over 48 h. (3) Fasting-subjects received no caloric intake for 56 h. (4) Fasting+MCP-subjects fasted for 56 h, and received iv MCP during the final 48 h of the study. Serum TSH levels were measured every 15 min during the final 24 h of each study, and a TRH stimulation test was performed at the conclusion of each study: 56 h of fasting decreased 24 h mean TSH levels and TSH pulse amplitude by 40%, with blunting of the TSH response to TRH. MCP infusions increased 24 h mean TSH levels and TSH pulse amplitude 26-34%, with no differences between the fasting and nonfasting studies. MCP infusions did not normalize TSH levels, TSH responses to TRH, or serum T3 levels during fasting. These data suggest that endogenous dopaminergic activity does not play a major role in fasting-induced TSH suppression in healthy subjects.

Adolescent↗
PubMed1996

Differential effects of short-term fasting on pulsatile thyrotropin, gonadotropin, and alpha-subunit secretion in healthy men--a clinical research center study.

In healthy subjects, short term fasting suppresses the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal (HPG) axes, with decreased serum levels of TSH and LH. However, effects of fasting on pulsatile release of TSH, LH, FSH, and alpha-subunit are less clear. Eleven healthy young men each underwent two 2-day studies: a baseline study during normal caloric intake and a fasting study during 56 h of caloric deprivation. During the final 24 h of each study, blood samples were drawn every 15 min for measurement of serum TSH, LH, FSH, and alpha-subunit pulses. Fifty-six hours of fasting caused a 50% suppression of mean TSH levels and TSH pulse amplitude, without altering TSH pulse frequency. Nocturnal TSH pulse amplitude decreased by 60%, with abolition of the usual nocturnal TSH surge. Fasting suppressed mean LH levels and LH pulse amplitude by 30%, without affecting LH pulse frequency. In contrast, mean FSH levels only decreased by 13%, without changes in FSH pulse parameters, whereas mean alpha-subunit levels and pulse amplitude decreased by 20%. These data show that short term fasting has a greater suppressive effect on the hypothalamic-pituitary-thyroid axis than on the HPG axis. Within the HPG axis, FSH is more resistant to fasting-induced suppression than LH, implying discordant regulation of the two gonadotropins during nutritional deprivation. alpha-Subunit suppression during fasting appears to parallel that seen for LH.

Adult↗
PubMed1995

Pattern of recovery of the hypothalamic-pituitary-thyroid axis following radioactive iodine therapy in patients with Graves' disease.

PURPOSE: To characterize the time course of recovery of the hypothalamic-pituitary-thyroid (HPT) axis by determining the frequency, onset, duration, and clinical attributes of the central hypothyroid phase following 131I therapy for Graves' disease and to examine whether the central hypothyroid phase is due to direct pituitary thyrotroph suppression or to hypothalamic thyrotropin-releasing hormone (TRH) deficiency. PATIENTS AND METHODS: Twenty-one hyperthyroid patients with Graves' disease evaluated at a university endocrine clinic and treated with radioactive iodine were prospectively studied. Serial thyroid function levels (serum thyroxine [T4], free thyroxine [free T4], triiodothyronine [T3], and thyroid-stimulating hormone [TSH]) were measured and TRH stimulation tests were performed at 2 to 4 week intervals for all subjects following 131I treatment. None of the patients was treated with thionamides after receiving 131I therapy. RESULTS: Nineteen (90%) of the patients with Graves' disease experienced a transient central hypothyroid phase defined as the presence of a suppressed or inappropriately normal TSH level despite a low free T4 level following 131I treatment. This phase occurred a mean of 62.8 +/- 5.1 days following 131I treatment, persisted for an average of 24.7 +/- 2.4 days, and was not predictive of eventual treatment outcome. All patients had concordantly low T4 and T3 levels during this period and exhibited a blunted TSH response to TRH compared to 29 euthyroid control subjects, suggesting primary feedback suppression at the level of the pituitary thyrotrophs. The suppressed thyrotrophs required a minimum of 2 weeks to recover once patients became hypothyroid. The length of preexisting hyperthyroidism, basal free T4 elevation, and administered dose of 131I failed to predict the duration of the central hypothyroid phase, although a higher dose of 131I was associated with an earlier onset of central hypothyroidism (r = -.51, P < 0.05). CONCLUSIONS: Clinicians should be aware of the delay in the recovery of the HPT axis that occurs in the majority of patients with Graves' disease treated with 131I and is manifested by a transient central hypothyroid phase. The blunted TSH response to TRH stimulation during this period suggests that suppression occurs primarily at the level of the pituitary thyrotrophs. The use of sensitive TSH measurements alone to monitor these patients during this period is not helpful and may be misleading.

Adult↗
PubMed1995

Glycoprotein-secreting pituitary adenomas.

In the past, pituitary tumours that produce one or more of the glycoproteins (TSH, LH, FSH and alpha subunit) were thought to be rare. However, using modern immunocytochemical and molecular biology techniques, these tumours are being recognized with increasing frequency. Many of these tumours produce glycoprotein alpha and beta subunits in addition to intact glycoproteins. Hormone production is often low compared with tumour size, and serum hormone levels may not be elevated in these patients. Tumours that produce the gonadotrophins (LH or FSH) or alpha subunit account for the majority of clinically non-functioning pituitary adenomas. They do not cause a specific clinical syndrome, and usually present with symptoms of a large mass lesion and/or hypopituitarism. Optimal treatment of these tumours is often difficult. The initial approach is usually transsphenoidal surgery, followed by radiation therapy if there are symptoms due to residual tumour. Medical therapy of gonadotrophin and alpha subunit tumours may include the use of dopamine agonists or somatostatin analogues, although neither has been shown to consistently decrease tumour size. Preliminary trials with experimental GnRH antagonists suggest that these agents may be useful as adjuvant therapy of gonadotrophin tumours. Tumours that produce TSH are rare. Patients present with hyperthyroidism, which is often misdiagnosed as Graves' disease, as well as with symptoms of a pituitary mass lesion. Almost all TSH tumours secrete excess amounts of free alpha subunit. Optimal treatment of these tumours includes transsphenoidal surgery, followed by radiation therapy for residual tumour. The somatostatin analogue octreotide is effective in reducing excess TSH secretion from these tumours, and causes a reduction in tumour volume in a significant minority of patients.

Adenoma↗
PubMed1995

Amyloid goiter in cystic fibrosis.

Chronic infectious or inflammatory diseases lead to amyloid infiltration and dysfunction of many organs, including the kidney, liver, heart, and gastrointestinal tract. Subclinical amyloid infiltration of the thyroid gland has been described in over 80% of such patients. However, symptomatic involvement of the thyroid gland by amyloid is rare. We describe a euthyroid patient with cystic fibrosis and widespread amyloidosis who presented with a rapidly enlarging goiter and symptoms of local compression that compromised his pulmonary status. Fine needle aspiration of the goiter was nondiagnostic. At surgery he proved to have replacement of the thyroid gland by amyloid. A review of the literature reveals only five previous cases of amyloid goiter in patients with cystic fibrosis. However, as more patients survive into adulthood, amyloid goiter may become a more common complication of cystic fibrosis. In contrast to other patients with reactive amyloidosis and goiter, patients with cystic fibrosis may require thyroid surgery to relieve airway compression that can compromise pulmonary function.

Adult↗
PubMed1995

Copulsatile release of thyrotropin and prolactin in normal and hypothyroid subjects.

In healthy subjects, thyroid-stimulating hormone (TSH) and prolactin (PRL) are secreted in a pulsatile fashion. However, the factors that control the generation of these pulses are unknown. Since thyrotropin-releasing hormone (TRH) and dopamine (DA) affect levels of both hormones, pulsatile TRH or DA input to the pituitary gland may lead to pulsatile secretion of both TSH and PRL. In this case, TSH and PRL should exhibit significant nonrandom pulse concordance rates. To test this hypothesis, we studied 11 healthy subjects (5 women in the early follicular phase and 6 men) and 11 subjects with primary hypothyroidism (5 untreated and 6 euthyroid on 1-thyroxine therapy). To further test the specific hypothesis that pulsatile TRH entrains pulsatile TSH and PRL secretion, we restudied the 6 treated hypothyroid subjects on the final day of a 9-day constant infusion of TRH. In each study, blood samples were drawn every 15 min for 24 h, and TSH and PRL levels were measured by immunoradiometric assays. Hormone pulses were located by Cluster analysis. Nonrandom TSH and PRL pulse coincidence rates were assessed by a statistically based computer algorithm, which compares observed pulse concordance rates to those expected by chance. In the healthy men and women and the treated hypothyroid subjects, TSH and PRL were copulsatile in a significantly nonrandom fashion. Of TSH pulses 36-45% occurred within 15 min of PRL pulses, while 37-67% of PRL pulses occurred within 15 min of TSH pulses. Similar pulse concordance rates were seen in treated hypothyroid subjects receiving constant TRH infusions. Thus, there appears to be a central factor or factors that stimulate the copulsatile release of TSH and PRL. However, TRH does not appear to play a role in this phenomenon, and the underlying pulse generator(s) for both hormones remains to be elucidated.

Adult↗
PubMed1994

Effects of hydrocortisone on pulsatile pituitary glycoprotein secretion.

During states of stress, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal function can be suppressed. One putative mediator of this stress response may be glucocorticoids, which have widespread effects on thyroid and gonadal function. To characterize dynamic pituitary glycoprotein secretion during glucocorticoid administration, 24-h TSH, LH, FSH, and alpha-subunit pulses were measured in 10 healthy young subjects on 3 occasions: 1) at baseline, 2) during infusions of 100 mg hydrocortisone (HC) over 24 h, and 3) during infusions of 300 mg HC over 24 h. These HC infusions led to serum cortisol levels similar to the endogenous cortisol levels seen in moderate and severe stress. Both HC infusions had profound rapid effects on TSH levels, decreasing TSH pulse amplitude by 60% and abolishing the nocturnal TSH surge. However, TSH pulse frequency was unaltered. In contrast, HC infusions did not change mean or pulsatile LH, FSH, or alpha-subunit secretion. These results suggest that stress levels of cortisol acutely suppress TSH secretion at the pituitary level, with little effect on the TSH pulse generator. On the other hand, the effects of stress and/or hypercortisolism on the gonadal axis may require higher cortisol levels, more prolonged exposure, or other mediators of the stress response.

Adult↗
PubMed1994

Effects of naloxone infusions on pulsatile thyrotropin secretion.

Endogenous opioids are known to modulate the secretion of some anterior pituitary hormones, but they are not thought to have significant effects on TSH secretion. However, dynamic TSH secretion has not been characterized during naloxone infusions. Therefore, we measured TSH levels every 15 min over 24 h in nine healthy young men at baseline and during infusions of naloxone at 2 mg/h. A TRH test was performed after each study. TSH pulses were located by Cluster analysis. Naloxone infusions decreased 24-h mean TSH levels by 28%, from 1.68 +/- 0.20 to 1.21 +/- 0.19 mU/L. Mean daytime TSH levels did not change, but nocturnal TSH levels were decreased by 39%, from 2.21 +/- 0.30 to 1.35 +/- 0.21 mU/L. There were no changes in TSH pulse frequency, but naloxone infusions decreased 24-h TSH pulse amplitude by 32%, from 2.02 +/- 0.26 to 1.37 +/- 0.21 mU/L. Daytime TSH pulse amplitude was relatively unaffected (1.27 +/- 0.15 vs. 1.16 +/- 0.21 mU/L), whereas nocturnal TSH pulse amplitude was decreased by 42%, from 2.72 +/- 0.40 to 1.57 +/- 0.23 mU/L. TSH responses to acute TRH administration were decreased after naloxone infusions (12.38 +/- 1.93 vs. 9.17 +/- 1.36 mU/L). Serum T3 levels fell by 21% during naloxone infusions, from 1.9 +/- 0.1 to 1.5 +/- 0.1 nmol/L, whereas other thyroid hormone levels and cortisol levels were unchanged. These findings suggest that endogenous opioids have significant stimulatory effects on TSH secretion, predominantly during the nocturnal TSH surge.

Adult↗
PubMed1994

Cushing's syndrome and the nodular adrenal gland.

This article examines Cushing's syndrome in four main categories as associated with nodular adrenal glands: adrenal adenoma, adrenal carcinoma, primary pigmented nodular adrenal dysplasia, and macronodular adrenal hyperplasia. A summary of clinical features of these four categories is presented.

Adenoma↗
PubMed1993

Pulsatile TSH secretion during 48-hour continuous TRH infusions.

Thyroid-stimulating hormone (TSH), like other anterior pituitary hormones, is normally secreted in a series of pulses over 24 h. However, the factors that control TSH pulse generation are unknown. We investigated the potential role of thyrotropin-releasing hormone (TRH) in TSH pulse generation by measuring TSH pulses during constant TRH infusions. Two groups of subjects were studied: five healthy subjects and five subjects with treated primary hypothyroidism and normal TSH levels. Each subject underwent four separate studies: (1) TSH levels were measured every 15 min over 24 h (baseline study). (2) TSH levels were measured every 15 min over 48 h during TRH infusions at 0.1 microgram/min (low dose TRH study). (3) TSH levels were measured every 15 min over 48 h during TRH infusion at 0.5 microgram/min (medium dose TRH study). (4) TSH levels were measured every 15 min over 48 h during TRH infusions at 1.0 microgram/min (high dose TRH study). TSH pulses were located by cluster analysis. We found that constant TRH infusions at any of the doses utilized did not alter TSH pulse frequency in normal or treated hypothyroid subjects, although pulse amplitude increased. Normal subjects had lower TSH pulse amplitude than treated hypothyroid subjects at all TRH doses, perhaps due to slightly higher serum T3 levels. This suggests that, at least acutely, pulsatile input of TRH to the pituitary gland does not determine pulsatile TSH release. However, TRH may modulate TSH pulse amplitude.

Adult↗
PubMed1993

Pulsatile secretion of parathyroid hormone in normal young subjects: assessment by deconvolution analysis.

Preliminary reports suggest that PTH is secreted in a pulsatile fashion. However, available studies have not attempted to calculate actual PTH secretion rates in healthy individuals. To accurately characterize PTH secretory dynamics in healthy subjects, we studied seven young women and six young men, all of whom had hip and spine bone densities by dual photon densitometry in the upper tertile for age-matched control subjects. PTH concentrations were measured by immunoradiometric assay in blood sampled every 2 min over 6 h. Ionized calcium levels were obtained during the second and third hours of the study. Plasma PTH profiles were subjected to deconvolution analysis, which resolves measured hormone levels into secretion and clearance components. Cross-correlation analysis was performed to assess direct or inverse correlations between serum PTH and ionized calcium concentrations at various time lags. In these subjects, PTH was secreted in a dual fashion, with significant basal (tonic) secretion and PTH pulses approximately every 20 min. Pulsatile PTH secretion accounted for approximately 25% of the total secreted PTH. There were no differences in PTH secretory parameters between men and women, nor were there any significant correlations between PTH and ionized calcium concentrations. We conclude that in normal subjects, the predominant mode of PTH secretion is tonic, with superimposed PTH pulses of small amplitude but high frequency. The clinical significance of this complex physiological pattern of secretion awaits further study.

Adult↗
PubMed1992

Cocaine impairs gonadotropin secretion in oophorectomized monkeys.

OBJECTIVE: Our objective was to determine whether cocaine alters gonadotropin secretion in oophorectomized monkeys. STUDY DESIGN: Oophorectomized monkeys with elevated gonadotropin levels were chronically cannulated to allow blood sampling every 15 minutes. Monkeys received either saline solution or 2 or 4 mg/kg cocaine hydrochloride as an intravenous bolus. Other oophorectomized monkeys were pretreated with either saline solution or 4 mg/kg cocaine 2 hours before bolus gonadotropin-releasing hormone administration, and plasma luteinizing hormone and follicle-stimulating hormone levels were measured every 15 minutes for 3 hours. Monkeys were also given either saline solution or 4 mg/kg of cocaine with gonadotropin-releasing hormone simultaneously, and plasma gonadotropin levels were measured every 15 minutes for 3 hours. Serum luteinizing hormone and follicle-stimulating hormone levels were measured by radioimmunoassay. RESULTS: Both doses of cocaine resulted in a significant decrease in luteinizing hormone levels compared with controls. Follicle-stimulating hormone levels were significantly decreased only with the 4 mg/kg dose of cocaine. There was no difference in luteinizing hormone and follicle-stimulating hormone responses to gonadotropin-releasing hormone in the cocaine-treated monkeys compared with saline solution-treated monkeys by using repeated-measures analysis of variance. CONCLUSION: These findings demonstrate that acute cocaine administration to oophorectomized primates inhibits basal luteinizing hormone-follicle-stimulating hormone secretion but not gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone release. In the absence of an effect on gonadotropin-releasing hormone-stimulated gonadotropin release, we conclude that the impaired luteinizing hormone-follicle-stimulating hormone secretion after cocaine administration is due in part to a direct effect of cocaine on gonadotropin-releasing hormone neurons or on hypothalamic neurotransmitter modulation of gonadotropin-releasing hormone release.

Analysis of Variance↗
PubMed1992

Effects of dopamine and somatostatin on pulsatile pituitary glycoprotein secretion.

The hypothalamic factors dopamine (DA) and somatostatin (SRIH) inhibit pituitary glycoprotein secretion, but little is known regarding the effects of these factors on glycoprotein pulses. To address this question, 12 healthy volunteers underwent frequent blood sampling over 12 h at baseline and during 12-h infusions of DA and/or SRIH. TSH, LH, FSH, and alpha-subunit (alpha) levels were measured in all samples, and hormone pulses were located by Cluster analysis. Both DA and SRIH suppressed TSH pulse amplitude by 70%, while SRIH decreased TSH pulse frequency as well. Both infusions decreased LH pulse amplitude by 30-35%, but had no effect on pulse frequency. In contrast, neither infusion significantly altered FSH pulse parameters, although mean FSH levels declined 15%. DA had no effect on pulsatile alpha secretion, while SRIH decreased alpha pulse frequency. Serum thyroid hormone levels declined during both infusions, but there were no major changes in serum sex steroid levels. Thus, the hypothalamic inhibitory factors DA and SRIH had divergent effects on glycoprotein hormone pulses. The major effects on pulse amplitude, rather than frequency, imply that these factors do not play major roles in the generation of glycoprotein pulses, although SRIH may directly affect the TSH and alpha pulse generators.

Adolescent↗
PubMed1992

Central hypothyroidism.

Central hypothyroidism is an uncommon condition characterized by insufficient thyroid gland stimulation by TSH, owing to hypothalamic and/or pituitary dysfunction. It is rarely isolated but more often occurs in conjunction with deficiencies of other pituitary hormones, as well as with neurologic symptoms and signs owing to hypothalamic/pituitary lesions. The diagnosis rests on documentation of clinical and biochemical hypothyroidism with an inappropriately low or nonelevated serum TSH level. Recent studies suggest that the temporal pattern of TSH secretion, as well as TSH structure, is altered in central hypothyroidism, providing a mechanism for the induction of the hypothyroid state in this condition.

Animals↗
PubMed1991

Pulsatile glycoprotein hormone secretion in glycoprotein-producing pituitary tumors.

To study patterns of hormone production and secretion in glycoprotein-producing pituitary tumors, 12 patients with such tumors underwent the following studies. Preoperatively, all patients had serum TSH, LH, FSH, and alpha-subunit levels measured every 15 min for 24 h. Hormone pulses were located by cluster analysis, and pulse parameters were compared to those in healthy young men, healthy young women, healthy postmenopausal women, and subjects with primary hypothyroidism. After surgery, immunocytochemistry for the four glycoproteins was performed on all tumors, and Northern blot analysis was performed in six tumors with probes for the four subunits. By immunocytochemistry, 42% of the tumors were positive for TSH beta, 83% for LH beta, 75% for FSH beta, and 92% for alpha-subunit. Preoperative serum hormone levels varied widely between patients and were not well correlated with the intensity of immunocytochemical staining. Northern blot analysis did not appear to be as sensitive as immunocytochemistry for detection of the glycoproteins. All patients had pulsatile glycoprotein secretion, with pulses of normal frequency but varied amplitude. These results suggest that in patients with glycoprotein tumors, hormone pulses may be an integral part of autonomous secretion, or that hypothalamic control is involved in glycoprotein secretion and, perhaps, in the pathogenesis of these tumors.

Adenoma↗