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Biomedical subjects

I M Spitz

Publications and source records attributed to I M Spitz.

At least 55 records · Page 3Linked to original sources
PubMed1987

Termination of early gestation with the anti-progestin steroid RU 486: medium versus low dose.

RU 486 is a synthetic steroid which has antiprogesterone and antiglucocorticoid activity. In order to determine the optimal dosage of this drug to terminate early pregnancy, we treated 106 healthy women with normal pregnancies by real time ultrasound examination whose gestational duration was less than 49 days from onset of last menses with either a medium or low dose treatment regimen. A total of 66 patients received the medium dose regimen (100 mg/day X 7 days). Another 10 patients received ergonovine (0.2 mg/day X 6 doses) on Day 4 of the same RU 486 treatment regimen. In the first group, 48 (73%) aborted successfully and, of the second group, 6 (60%) aborted. Eighty percent of the subjects in this group of 76 patients reported side effects of nausea and vomiting, heavy bleeding, severe menstrual cramps or headache. All these side effects were successfully treated with analgesic and antiemetic medication. The remaining 30 subjects were treated with a low dose regimen (50 mg/day X 7 days). Of these 30, 15 (50%) aborted; this incidence was significantly less (p less than 0.05). Following the medium dose treatment regimen, the AM cortisol levels were significantly elevated on treatment Days 4 and 8, as compared to baseline (p less than 0.001), although the mean levels were still within the normal range. With the low dose, there was a non-significant rise in AM cortisol values. Thus the rise in cortisol was significantly greater in the former group than the latter (p less than 0.05). With the medium dose regimen, the women who aborted had significantly lower (p less than 0.05) pretreatment mean B-HCG and progesterone levels than the group that failed to abort. Mean serum levels of RU 486 were not significantly different between the group who aborted and those who did not. RU 486 is a promising agent for termination of early pregnancy.

Abortion, Induced↗
PubMed1987

Effects of the antiprogesterone RU 486 in normal women. I. Single-dose administration in the midluteal phase.

The response to a single oral dose of the antiprogesterone RU 486 was studied in the midluteal phase in 26 normal women. Each subject received a dose between 50 and 800 mg RU 486 on days 6 to 8 after the luteinizing hormone surge and blood samples were taken over the following 48 hours. Another group of five patients received a single oral dose of 200 mg RU 486 and blood sampling was extended for 14 days. Menses were induced in all women but one within 3 days after RU 486 administration. Two distinct patient populations emerged. In nine of the subjects, there was a single bleeding episode and the treatment cycle was significantly shorter (p less than 0.05) than the following cycle. In 16 of these 25 patients a second bleeding episode occurred 19.0 +/- 0.8 days after the luteinizing hormone surge. The total treatment cycle was significantly prolonged (p less than 0.05) when compared with the following cycle. In the group with a single bleeding episode, there was a significant decline in follicle-stimulating hormone, estradiol, and progesterone over the 48-hour sampling period, but there was no change in these values in the group with two bleeding episodes. These two groups could not be separated on the basis of RU 486 dose or serum levels. After the four higher doses, there was a dose-dependent rise in serum prolactin. There were no alterations in mean cortisol values with the three lower doses, but there was a significant increase at 24 and 48 hours after the higher doses. Serum levels of RU 486 were maximal between 1 and 4 hours and the half-life of serum RU 486 was determined to be 24 hours.

Administration, Oral↗
PubMed1987

Effects of the antiprogesterone RU 486 in normal women. II. Administration in the late follicular phase.

RU 486, a synthetic steroid with antiprogesterone receptor activity, was used to investigate the importance of progesterone on gonadotropin secretory dynamics in the midcycle of the normal menstrual cycle. Six normally cycling women were followed for three consecutive cycles. During each cycle, blood samples were obtained beginning on day 10 and continued until menses. After a control cycle, 100 mg RU 486 was given orally between days 10 and 17. The patients were followed for a posttreatment cycle with no medication. When RU 486 was given before the midcycle, the luteinizing hormone surge was delayed by 15.0 +/- 2.1 days after ingestion of the last pill, resulting in cycles of 40.6 +/- 2.6 compared with 28.0 +/- 2.3 days (p less than 0.01). During RU 486 administration and at the time a normal luteinizing hormone surge was anticipated, an attenuated luteinizing hormone/follicle-stimulating hormone surge was noted that was not followed by a rise in progesterone. After the attenuated surge a normal luteinizing hormone/follicle-stimulating hormone level occurred, with a normal rise in progesterone. Estradiol levels during RU 486 administration decreased during treatment, indicating a possible direct action of RU 486 on the ovary.

Administration, Oral↗
PubMed1987

Late luteal phase administration of RU486 for three successive cycles does not disrupt bleeding patterns or ovulation.

RU486, a 19-nor steroid, binds with high affinity to the receptors for progesterone and glucocorticoids, blocking the actions of these hormones on their target tissues. We conducted studies to determine whether RU486 administered at the end of the luteal phase would disturb the menstrual rhythm, ovulation, or hormonal parameters in the treatment and post-treatment cycles. The first study was done in six surgically sterilized women during two consecutive cycles. RU486 [17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-(1-propynyl)estra-4,9-dien-3-one; 100 mg/day] was given for 4 consecutive days, commencing on days 23-27 of the first cycle. Menstrual bleeding occurred by the second day of RU486 administration in all women and was indistinguishable from their usual bleeding pattern. The onset of this bleeding was advanced by RU486 administration, since it entailed shortening of the luteal phase with prolongation of the following follicular phase. Serum LH, FSH, estradiol, and progesterone levels were normal in five of the six women in both the treatment and posttreatment cycles. The second study was conducted in 10 women who were not exposed to the risk of pregnancy. RU486 (100 mg/day) was given for 4 consecutive days, commencing 4 days before their expected menses for 3 successive cycles, preceded and followed by 2 placebo-treated cycles. Bleeding patterns were indistinguishable during the RU486 and placebo cycles. Late luteal phase administration of RU486 consistently produced menstrual bleeding within 1-3 days of drug administration. Daily early morning urinary LH excretion in 6 women and estrone glucuronide and pregnanediol glucuronide excretion in 5 women during both placebo and RU486 cycles were consistent with luteinization, suggesting ovulation and appropriate corpus luteum function. We conclude that RU486 has no major effect on menstrual cycle events if given at the time of the natural progesterone withdrawal that occurs before menses in nonpregnant women.

Adult↗
PubMed1986

Persistent müllerian structures in infertile male.

Müllerian duct derivatives were identified in an infertile adult male patient who had long-standing azoospermia and was operated on for inguinal hernia. Persistent müllerian duct syndrome is reviewed, with special emphasis on the pathophysiologic and surgical considerations involved in the treatment of this abnormality.

Adult↗
PubMed1986

Pregnancy termination with a high and medium dosage regimen of RU 486.

Sixty healthy pregnant women who wished to terminate their pregnancy and who were no more than 49 days pregnant were treated with one of three different dose regimens of a synthetic progesterone receptor blocker, RU 486. Serum cortisol was measured to determine the antiglucocorticoid effects of this compound. The high dose but shorter treatment regimen (400 mg/day RU 486 X 4 days or 200 mg/day X 4 days) was associated with a high (greater than 80%) rate of side effects, especially nausea, vomiting, weakness and heavy bleeding and a low rate of success (10%). A group of 50 subjects received the medium dose but longer treatment regimen (100 mg/day X 7 days). This group had less side effects (40-60%) and a 72.3% success rate of complete abortion. The AM cortisol values were significantly elevated in all treatment groups but higher in those receiving the high dose. These values returned to normal one week following cessation of treatment. Medium dose but longer duration (100 mg/day X 7 days) of RU 486 treatment is associated with a higher success rate and less side effects than higher dose therapy administered over a shorter period. There were no predictive indices to determine which subjects would respond successfully. The reason for the failure of the drug in 30% of the subjects on the medium dose is not known at this time.

Abortifacient Agents↗
PubMed1986

Evolution of hypothyroidism in familial goitre due to deiodinase deficiency: report of a family and review of the literature.

We studied two sisters who developed large non-toxic goitres in adolescence. Deiodinase deficiency was diagnosed by a rapid thyroid uptake of radioactive iodine (RAI) at 2 hours associated with a marked fall in thyroidal 131I by 24 hours. Serial RAI scans in the second patient documented evolution of the iodine-deficient state. Conservation of intra-thyroidal iodine stores was maintained by avid iodine uptake and failure to release organified 131I. With progressive loss of inorganic iodine, hypothyroidism developed, associated with a rise in serum TSH which further exacerbated the loss of iodine. Treatment with L-thyroxine resulted in an improvement of thyroid function, but normalization was achieved only after small doses of Lugol's iodine were administered. These studies illustrate the variable nature and late onset of an inborn error of thyroid metabolism. This family supports an autosomal recessive mode of inheritance for deiodinase deficiency. We have documented progression from a euthyroid to hypothyroid state resulting from decompensation of iodine conservation mechanisms.

Adult↗
PubMed1985

Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU 486.

A patient with Cushing's syndrome due to ectopic ACTH secretion was treated successfully with the new glucocorticoid antagonist RU 486 [17 beta-hydroxy-11 beta-(4-dimethylamino phenyl) 17 alpha-(1-propynyl)estra-4,9-dien-3-one]. This compound is a 19-nor steroid with substitutions at positions C11 and C17 which antagonizes cortisol action competitively at the receptor level. Oral RU 486 was given in increasing doses of 5, 10, 15, and 20 mg/kg . day for a 9-week period. Treatment efficacy was monitored by assessment of clinical status and by measuring several glucocorticoid-sensitive variables, including fasting blood sugar, blood sugar 120 min after oral glucose administration, and plasma concentrations of TSH, corticosteroid-binding globulin, LH, testosterone-estradiol-binding globulin, and total and free testosterone. With therapy, the somatic features of Cushing's syndrome (buffalo hump, central obesity, and moon facies) ameliorated, mean arterial blood pressure normalized, suicidal depression resolved, and libido returned. All biochemical glucocorticoid-sensitive parameters normalized. No side-effects of drug toxicity were observed. We conclude that RU 486 may provide a safe, well tolerated, and effective medical treatment for hypercortisolism.

Adrenocorticotropic Hormone↗
PubMed1984

TSH secretion in thalassemia.

Thyroid function has been evaluated in 6 prepubertal male and 9 female thalassemic patients. Four of the latter were sexually immature (Group I), with very low estradiol levels and the remainder had more advanced sexual development (Group II). Subjects were challenged with TRH and the response compared to adult controls and a group of 15 males aged 13-18 years with constitutional delayed adolescence. All patient groups and controls had normal levels of T4, T3 and T3 resin uptake. When compared to adult controls or males with constitutional delayed adolescence, the male thalassemic patients had increased basal TSH levels with an exaggerated response to TRH. Long term testosterone enanthate led to a decrease in integrated TSH secretion, showing that androgens may decrease the TSH response to TRH. The more sexually mature females of Group II also had increased basal and stimulated TSH levels; however, the sexually immature females of Group I had basal TSH and TSH responses to TRH equivalent to female controls. In Group I patients there were, moreover, no changes in TSH response during administration of estradiol valearate for 3 months and conjugated estrogens for 8 months. The high basal and stimulated TSH levels in the males and Group II females are most likely due to subclinical primary hypothyroidism. This has been previously described in thalassemia. On the other hand, failure of estrogens to increase the TSH response to TRH in Group I females is evidence of pituitary involvement, which is also well documented in this clinical condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Effect of non aromatizable androgens on LHRH and TRH responses in primary testicular failure.

We have assessed the gonadotropin, TSH and PRL responses to the non aromatizable androgens, mesterolone and fluoxymestrone, in 27 patients with primary testicular failure. All patients were given a bolus of LHRH (100 micrograms) and TRH (200 micrograms) at zero time. Nine subjects received a further bolus of TRH at 30 mins. The latter were then given mesterolone 150 mg daily for 6 weeks. The remaining subjects received fluoxymesterone 5 mg daily for 4 weeks and 10 mg daily for 2 weeks. On the last day of the androgen administration, the subjects were re-challenged with LHRH and TRH according to the identical protocol. When compared to controls, the patients had normal circulating levels of testosterone, estradiol, PRL and thyroid hormones. However, basal LH, FSH and TSH levels, as well as gonadotropin responses to LHRH and TSH and PRL responses to TRH, were increased. Mesterolone administration produced no changes in steroids, thyroid hormones, gonadotropins nor PRL. There was, however, a reduction in the integrated and incremental TSH secretion after TRH. Fluoxymesterone administration was accompanied by a reduction in thyroid binding globulin (with associated decreases in T3 and increases in T3 resin uptake). The free T4 index was unaltered, which implies that thyroid function was unchanged. In addition, during fluoxymesterone administration, there was a reduction in testosterone, gonadotropins and LH response to LHRH. Basal TSH did not vary, but there was a reduction in the peak and integrated TSH response to TRH. PRL levels were unaltered during fluoxymesterone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Hormonal profile after insulin-induced hypoglycemia in chronic calcific pancreatitis. Pancreatic, pituitary and adrenal responses.

The present investigation defined the pattern of pancreatic, pituitary and adrenal responses after insulin-induced hypoglycemia in chronic calcific pancreatitis (CCP) related to alcohol abuse, and assessed the role of some of these hormones in the counterregulation of blood glucose. We studied 6 Black men with recently diagnosed CCP, all showing radiological evidence of pancreatic calcification and normal glucose tolerance, as well as 7 matched nonobese male controls. After a standard iv insulin tolerance test inducing marked hypoglycemia, patients with CCP showed significantly impaired mean plasma pancreatic glucagon and pancreatic polypeptide responses compared to the controls. Mean basal plasma somatostatin levels tended to be higher in chronic pancreatitis and remained so throughout the test without altering consistently; in the controls somatostatin peaked significantly at 30 min. Concerning extrapancreatic hormonal changes, plasma growth hormone, prolactin and total catecholamines responded normally in CCP, but plasma cortisol rose to significantly higher levels than controls at 60 and 120 min after the injection of insulin. This, coupled with the brisk output of catecholamines, may have prevented the heightened sensitivity to insulin anticipated because of their hypoglucagonemia. We conclude that patients with CCP show impaired pancreatic hormone release after insulin hypoglycemia with the exception of somatostatin; there is also an excessive rise in plasma cortisol, possibly related to the long standing abuse of alcohol in the past.

Adrenal Glands↗
PubMed1984

Hyperthyroidism due to inappropriate TSH secretion with associated hyperprolactinaemia--a case report and review of the literature.

A patient with inappropriate thyrotrophin (TSH) secretion is described. She initially presented with classical hyperthyroidism during pregnancy, responded to propylthiouracil and, subsequently, had a normal delivery. Hyperthyroidism persisted and 7.5 months later a subtotal thyroidectomy was performed. After a further 16 months, mild symptoms of hyperthyroidism recurred. She again responded to propylthiouracil, but developed galactorrhoea. At that stage, it was noted that she had persistently elevated circulating TSH in the presence of elevated T4 and T3 levels. Her symptomatology was mild, although objective indices of thyroid activity, including pulse rate, BMR, sex hormone binding globulin and cholesterol, were indicative of hyperthyroidism. CT scan and tomography of the sella were normal. She had a markedly exaggerated TSH response to thyrotrophin releasing hormone (TRH). Basal TSH and responsiveness to TRH was suppressed by high dose dexamethasone. The TSH response to TRH was partially suppressed by exogenous T3, but there was no effect on basal TSH levels. TSH also decreased slightly with L-dopa and bromocriptine. Circulating TSH rose markedly during methimazole administration. TSH alpha and beta subunits were elevated and appropriate for the high TSH. In addition, both subunits increased following TRH. The patient had basal hyperprolactinaemia with an impaired prolactin (PRL) response to TRH and metoclopramide. PRL suppressed with L-dopa and bromocriptine. The remaining anterior pituitary function was intact. Most of the laboratory findings argue against the presence of a TSH producing pituitary tumour and the most likely cause for inappropriate TSH secretion in this patient is selective resistance of the thyrotroph to thyroid hormones. A mild element of peripheral resistance might also be present. The hyperprolactinaemia could be related to lactotroph resistance to thyroid hormone. The complexities of treatment in this patient are stressed. Therapy was initially attempted with low dose dexamethasone, but this had no effect. T3 treatment produced an exacerbation of her symptomatology and did not influence basal TSH, thyroid hormones, or 131I uptake. Bromocriptine administration for 11 months partially suppressed basal TSH without influencing T3 and there was an increase in T4. Methimazole did decrease her T4 and T3, but TSH and PRL rose to even greater levels. Her hyperthyroidism was eventually controlled with an ablative dose of 131I. Thyroid hormone will be given in an attempt to suppress her TSH.

Adult↗
PubMed1984

Growth and sexual development before and after sex steroid therapy in patients with thalassemia major.

Growth, sexual development, and hypothalamic-pituitary-gonadal function were evaluated in 23 patients with thalassemia major (14 female and nine male) aged 13 to 29 years. Five women (group 1) with hemoglobin levels of less than 7 g/dL, which were maintained by transfusions during childhood, did not spontaneously enter puberty. They had evidence of severe hypothalamic-pituitary dysfunction. Maintaining hemoglobin levels of about 8 g/dL resulted in spontaneous onset of puberty in seven of nine female patients (group 2), but had no such ameliorative effect on the nine male patients. In the latter, peak luteinizing hormone (LH) responses to gonadotropin releasing hormone correlated with bone age. Treatment with testosterone produced inconsistent partial inhibition of LH and follicle-stimulating hormone (FSH) responses to stimulation. After discontinuation of testosterone treatment, a rebound of basal testosterone, LH, and FSH levels was observed, but this was not sustained. These findings are compatible either with dysfunction of hypothalamic maturation or with partial pituitary dysfunction. Four of the group 1 females and six of the males treated with appropriate sex hormones showed satisfactory pubertal progression. Acceleration in linear growth was observed in four of the male patients whose epiphyses were still open. Treatment was well tolerated in all patients.

Adolescent↗
PubMed1983

The dissociation of the exaggerated prolactin and thyrotropin responses in seminiferous tubule failure following the administration of a double-pulse of thyrotropin-releasing hormone.

PRL and TSH secretion has been evaluated in 11 patients with seminiferous tubule failure and 9 controls. When compared to the controls, the patients had increased basal FSH, TSH and PRL levels. However, LH, E2, T and thyroid hormone levels were similar to the controls. Both groups were given two pulses of TRH (200 micrograms) at 30 min intervals. Following the initial pulse of TRH, the patients demonstrated exaggerated TSH and PRL responses. The administration of a second pulse of TRH led to a further increment of TSH secretion in the patients. There was, however, no PRL response to the second TRH pulse in either patients or controls although mean PRL levels remained significantly greater in the patients.

Adult↗
PubMed1983

The role of thyrotrophin releasing hormone in the diagnosis of isolated gonadotrophin deficiency.

We studied the response of PRL and TSH to thyrotrophin-releasing hormone (TRH) in 15 boys with delayed adolescence and 6 male subjects with isolated gonadotrophin deficiency (IGD). TRH tests were repeated in the IGD subjects during and 1 month following hCG treatment. Male IGD subjects showed a significantly decreased basal and TRH induced PRL response compared to male controls and subjects with delayed adolescence. Human chorionic gonadotrophin (HCG) treatment of male IGD subjects restored basal and stimulated PRL levels to the range of normal controls. This was, presumably, an estrogenic effect since non aromatizable androgens did not increase the PRL response; moreover, the antioestrogen, clomiphene, decreased the PRL response when given with HCG. The TSH response to TRH in delayed adolescents was increased as compared to adult male controls and IGD subjects and was similar to adult female controls. HCG treatment of IGD subjects had no effect on basal nor peak TSH levels, although ethinyl oestradiol did increase the TSH response in two IGD subjects. These studies show that the PRL and TSH responses to TRH may differentiate delayed adolescence from IGD. The increased TSH response to TRH in delayed adolescence as compared to adult males, is a manifestation of an enhanced oestrogen effect in these patients. The abnormal PRL dynamics in IGD is a consequence of estrogen deficiency.

Adolescent↗