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Biomedical subjects

H S Jacobs

Publications and source records attributed to H S Jacobs.

At least 55 records · Page 3Linked to original sources
PubMed1996

The outcome of hypophysectomy for prolactinomas in the era of dopamine agonist therapy.

OBJECTIVE: Dopamine agonists are the primary therapeutic modality for the majority of patients with prolactinomas, with pituitary surgery reserved for those patients intolerant of or resistant to these agents. Most published surgical series, however, contain patients treated by surgery as the primary therapeutic modality. Previous exposure to dopamine agonists or the selection of patients with prolactinomas resistant to conventional therapy may potentially compromise the surgical success rate. The purpose of this study was to evaluate the efficacy and safety of pituitary surgery for prolactinomas in a tertiary referral centre where the majority of patients were operated on after treatment with dopamine agonists. DESIGN: A retrospective review of the outcome of pituitary surgery for prolactinomas performed at a tertiary neurosurgical centre by a single neurosurgeon. PATIENTS: Twenty-three patients underwent excision of a macro and 11 excision of a micro-prolactinoma. MEASUREMENTS: Pituitary tumour diameter was determined by CT or MRI imaging. Pre and post-operative measurements were made of serum PRL concentration (off dopamine agonist therapy), free T4, free T3, LH and testosterone (males). Post-operative restoration of a menstrual cycle was taken to indicate resolution of hypogonadism in female patients. RESULTS: The majority (73.9%) of the patients with macro and all with micro-prolactinomas had received dopamine agonists preoperatively. Of the 23 patients with macroprolactinomas, in whom the median preoperative PRL concentration was 13255 mU/l, 17 (73.9%) had radiological evidence of suprasellar extension and 5 (21.7%) cavernous sinus invasion. Only 4 (17.4%) of the patients with macroprolactinomas had a normal serum PRL post-operatively, although there was an improvement in visual fields in 66% of those with preoperative defects. The median preoperative PRL concentration was 4309 mU/l in the patients with microprolactinomas, significantly lower than in the macroprolactinoma group (P = 0.02). Despite a significant fall in serum PRL postoperatively (median PRL 860 mU/l, P = 0.0001), only 45.5% of patients had a normal serum PRL concentration after surgery. CONCLUSIONS: The cure rate following pituitary surgery for prolactinomas in a tertiary referral centre was low when compared with previous series in which surgery was used as the primary therapeutic modality. We suggest this may result both from dopamine agonist pretreatment and the referral of prolactinomas resistant to conventional therapy. The outcome is probably a more realistic reflection of the results of pituitary surgery for prolactinomas as currently practised in the majority of neuroendocrine centres.

Adolescent↗
PubMed1996

Treatment of anovulatory infertility: the problem of multiple pregnancy.

The aim of the study was to assess patient, treatment and cycle characteristics in relation to the risk of multiple conception following ovulation induction in order to reduce the prevalence of this complication of treatment. We performed a retrospective analysis of 208 pregnancy cycles achieved in the Middlesex Hospital outpatient fertility unit. These pregnancies were achieved in 175 anovulatory women who conceived after gonadotrophin or pulsatile GnRH therapy. The multiple conception rate was 13.4%. After spontaneous reductions and abortions the multiple delivery rate was 9.6%. Clinical features associated with an increased risk of multiple pregnancies were the presence of polycystic ovary syndrome and secondary infertility. Comparison between different protocols of ovulation induction revealed no relationship with the risk of multiple conceptions. Although total number of follicles was increased in the multiple conception cycles, the distribution of follicles according to their diameter on the day of human chorionic gonadotrophin (HCG) administration was similar in multiple and singleton conception cycles. Thus, the risk of multiple conception could not be attributed to an increased number of follicles of any particular size but directly related to the total number of the cohort follicles ( > or = 14 mm) and leading follicles > or = 17 mm), rising from 7% with one follicle to 33% with six or more follicles. As we could not find a specific pattern of follicular development that could be associated with multiple conception, we conclude that the difference in the ovarian response leading to multiple conception is quantitative rather than qualitative. The data presented enable the assessment of the risk of multiple conception in any given cycle.

Adult↗
PubMed1996

The evaluation and management of subclinical pituitary disease.

The advent of sophisticated and sensitive radiologic techniques has undoubtedly improved the evaluation of patients with established endocrine disease. An inevitable consequence of the increased sensitivity and widespread availability of modern imaging is, however, the discovery of apparently asymptomatic mass lesions in endocrine tissues. The clinician is then required to determine the appropriate degree of often uncomfortable and costly investigation in a patient with no overt disease. This article attempts to provide guidelines for the management of the 'pituitary incidentaloma', a pituitary mass lesion evident on a computed tomography or magnetic resonance imaging scan performed for a reason other than the evaluation of the pituitary gland.

Acromegaly↗
PubMed1996

The neuroradiology of Kallmann's syndrome: a genotypic and phenotypic analysis.

A detailed neurological investigation of patients with Kallmann's syndrome (KS) has been performed in an attempt to relate phenotypic characterization with genotype. Twenty-seven subjects with KS were studied (including 12 males with X-linked disease and 3 females). Six male and 2 female normosmics with isolated GnRH deficiency, 1 male with KS variant, and 1 obligate female carrier were also imaged. Evidence for X-linked disease was derived both from analysis of pedigree and by mutation analysis at the KAL locus. The female carrier and all 8 normosmics had normal olfactory bulbs and sulci, as did 3 male KS. The study, therefore, confirms the value of magnetic resonance imaging in the diagnosis of KS, but suggests that the technique is not sufficiently sensitive to differentiate KS from the normosmic form of GnRH deficiency in all cases. Phenotypic characterization of KS was more effectively achieved by accurate estimation of olfactory status. Three new mutations at the KAL locus were identified, 2 single exon deletions and 1 point mutation. In 2 pedigrees with clear X-linked inheritance, no coding sequence mutations were detected; it may be that these harbor mutations of pKAL, the recently characterized 5'-promoter region. No clear relationship could be established between specific phenotypic anomalies and particular KAL mutations. Involuntary, mirror movements of the upper limbs were present in 10 of 12 cases of X-linked KS, but in none of the other subjects. Although this phenomenon has been ascribed to an abnormality of the corpus callosum, in the present study magnetic resonance imaging demonstrated no quantitative or qualitative morphological anomalies of this structure.

Base Sequence↗
PubMed1996

Hypogonadotropic patients with ultrasonographically detected polycystic ovaries: endocrine response to pulsatile gonadotropin-releasing hormone.

To characterize the endocrine response during induction of ovulation in patients with hypogonadotropic hypogonadism and ultrasound findings of polycystic ovary, we performed a retrospective analysis of 22 treatment cycles with pulsatile gonadotropin-releasing hormone (GnRH) in such patients and of 17 treatment cycles in similar patients with ultrasonographically normal ovaries. Of the 21 patients studies, 11 had an ultrasound finding of polycystic ovaries and ten had ovaries that appeared normal. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol levels, number of follicles of diameter > 12 mm (by ultrasound), and ovulation and conception rates were measured. Patients with hypogonadotropic hypogonadism and ultrasound-diagnosed polycystic ovary had pretreatment endocrine status similar to those with normal ovaries, but had much higher baseline ovarian volume. Ovulation induction with pulsatile GnRH induced much higher serum LH concentrations in the former group despite similar FSH levels. This difference preceded any change in estradiol levels. The former group consistently recruited significantly more follicles during pulsatile GnRH treatment. However, ovulation and conception rates were (non-significantly) higher in the latter group. In conclusion, this study characterized a subgroup of hypogonadotropic patients with ovarian morphology, volume and response to ovulation induction similar to in patients with polycystic ovary syndrome. When treated with pulsatile GnRH, those with polycystic ovary significantly hypersecreted LH before their estradiol level changed significantly. The primary lesion in polycystic ovary syndrome seems to be in the ovary, with pituitary hypersecretion of LH secondary to disturbed ovarian feedback signalling.

Estradiol↗
PubMed1996

Polycystic ovary syndrome: the present position.

This article discusses two areas that have seen progress in our understanding and management of women with polycystic ovary syndrome. The first relates to factors responsible for clinical expression of the disorder, the second to the management of infertility by surgical methods. These two areas have been chosen partly because of their intrinsic importance and partly because they indicate the breadth of work being pursued by investigators and clinicians in this field.

Cardiovascular Diseases↗
PubMed1995

Effect of laparoscopic ovarian electrocautery on ovarian response and outcome of treatment with gonadotropins in clomiphene citrate-resistant patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of ovarian electrocautery on the ovarian response to gonadotropic stimulation and pregnancy rate (PR) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS) and high basal serum LH levels. DESIGN: Retrospective study. SETTING: Outpatient infertility clinic in a tertiary referral center. SUBJECTS: Twenty-two women with PCOS, high basal serum LH concentrations, and CC resistance who underwent laparoscopic ovarian electrocautery. Treatment with gonadotropin was scheduled after failure to ovulate spontaneously or conceive after electrocautery. Data from gonadotropin-stimulated cycles were compared with data from treatment cycles in the same patients before ovarian electrocautery. MAIN OUTCOME MEASURES: Number of ampules, duration of induction phase, daily effective dose, PR, and pregnancy outcome. RESULTS: Markedly reduced basal serum LH concentrations and normal menstrual cyclicity in 41% of patients were recorded after laparoscopic ovarian electrocautery. Comparison of gonadotropin-stimulated cycles before and after electrocautery revealed significantly higher rates of ovulation and pregnancy after electrocautery as well as significant reduction in the number of ampules, daily effective dose, and duration of the induction phase with hMG and in daily effective dose with FSH. CONCLUSIONS: Our results indicate an increased ovarian sensitivity to gonadotropins after laparoscopic ovarian electrocautery. A preference for laparoscopic ovarian electrocautery over medical treatment in all or selected groups of CC-resistant PCOS patients is suggested.

Adult↗
PubMed1995

In-vitro cervical mucus-sperm penetration tests and outcome of infertility treatments in couples with repeatedly negative post-coital tests.

The results of in-vitro cervical mucus-sperm penetration tests and cross-hostility tests in 178 couples with repeatedly negative post-coital tests were recorded. Using a protocol of three cycles with intra-uterine inseminations (IUI) followed by three cycles with ovulation induction + IUI, the association between the cause of infertility, results of the in-vitro tests and the outcome of infertility treatment was investigated. We found that repeatedly negative post-coital tests are a good indicator of a cervical mucus-sperm penetration problem. The cross-hostility test clearly differentiates the abnormal factor in this interaction, and a good performance of the donors' spermatozoa in the cervical mucus correlates with increased pregnancy rate. In male factor infertility, failure of the husbands' spermatozoa to penetrate cervical mucus was not indicative of a deficient fertilization potential in vivo. In these patients a serious attempt should therefore be made to reverse the infertility by treatment with IUI or ovulation induction + IUI before attempting assisted reproduction. Women with polycystic ovaries and repeatedly negative post-coital tests should be investigated for sperm receptivity of the cervical mucus. Low receptivity of the cervical mucus may imply that endometrial receptivity and oocyte quality are also low. Ovulation induction and not IUI alone should therefore be used as the preferred mode of treatment to improve pregnancy rate.

Cervix Mucus↗
PubMed1995

Transient diabetes insipidus in pregnancy--a consequence of enhanced placental clearance of arginine vasopressin.

We report a patient who presented with transient diabetes insipidus in pregnancy on a background of previous postoperative diabetes insipidus following surgical excision of a prolactinoma. The patient illustrates how the complex changes in water homeostasis occurring during normal pregnancy may unmask latent diabetes insipidus. The major factors operating appear to be a physiological reduction in the thresholds for thirst and arginine vasopressin secretion coupled with a substantial increase in placental clearance of arginine vasopressin. Reversal of these changes after delivery results in normalization of the disordered water homeostasis, with consequent resolution of the diabetes insipidus.

Adult↗
PubMed1995

Ovarian stromal blood flow in women with polycystic ovaries--a possible new marker for diagnosis?

Blood flow changes in the ovarian stroma of women embarking on in-vitro fertilization treatment were assessed on day 2 or 3 of the menstrual cycle using colour and pulsed Doppler ultrasound. Women were divided into three groups: group 1, 63 women with regular, ovulatory menstrual cycles and normal ovaries on ultrasound scan; group 2, 13 women similar to group 1 but with polycystic ovaries (PCO) on ultrasound scan; and group 3, 12 women with biochemical evidence of previous anovulatory cycles and/or oligomenorrhoea and/or elevated serum luteinizing hormone concentrations (> 10 IU/l) in the early follicular phase together with PCO on ultrasound scan. A subjective assessment of the intensity and quantity of coloured areas in the ovarian stroma appeared to be greater in both groups 2 and 3 compared with group 1. Mean (SEM) ovarian stromal peak systolic blood flow velocity (Vmax) was 16.88 (1.79) and 16.89 (2.36) cm/s in groups 2 and 3 respectively. These velocities were significantly greater than the mean (SEM) ovarian stromal Vmax of group 1; 8.74 (0.68) cm/s (P < 0.001). Mean (SEM) ovarian stromal time averaged maximum velocity (TAMX) was 10.55 (0.91) and 10.89 (1.80) cm/s in groups 2 and 3 respectively, both significantly greater than mean ovarian stromal TAMX of group 1, (P < 0.001). There was no significant difference in pulsatility index (PI) between the three groups. There thus appears to be significantly greater ovarian stromal blood flow velocity in women with polycystic ovaries as detected by colour and pulsed Doppler ultrasound. Increased ovarian stromal blood velocity may be a new parameter to assist in the ultrasound diagnosis of PCO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients.

The criteria for the diagnosis of the polycystic ovary syndrome (PCOS) have still not been agreed universally. A population of 1741 women with PCOS were studied, all of whom had polycystic ovaries seen by ultrasound scan. The frequency distributions of the serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and prolactin and the body mass index, ovarian volume, uterine cross-sectional area and endometrial thickness were determined and compared with the symptoms and signs of PCOS. Obesity was associated with hirsutism and an elevated serum testosterone concentration and was also correlated with increased rates of infertility and cycle disturbance. The rates of infertility and cycle disturbance also increased with serum LH concentrations > 10 IU/l. A rising serum concentration of testosterone [mean and 95th percentiles 2.6 (1.1-4.8) nmol/l] was associated with an increased risk of hirsutism, infertility and cycle disturbance. The ovarian volume was correlated with serum concentrations of testosterone, LH and the body mass index, which was also correlated with the uterine area. This descriptive data from the largest reported series of women with PCOS enables the development of a management-orientated approach to the syndrome. Women who are overweight can expect an improvement in their symptoms if they lose weight. An elevated concentration of LH (> 10 IU/l) is associated with infertility and treatment should be chosen accordingly. If the serum testosterone concentration is > 4.8 nmol/l, other causes of hyperandrogenism should be excluded.

Adolescent↗
PubMed1995

Polycystic ovary syndrome: aetiology and management.

Although much clearer ideas concerning therapeutic approaches to patients with polycystic ovary syndrome are developing, the etiology of this enigmatic but common syndrome continues to be a fruitful source of discussion and debate. There is renewed interest in laparoscopic surgical methods of treatment.

Female↗
PubMed1995

Osteopenia as a feature of the androgen insensitivity syndrome.

OBJECTIVE: The syndrome of androgen insensitivity, a paradigm of a hormone resistance syndrome, manifests as failure of masculinization despite normal or high concentrations of serum testosterone. The defect in these 46 XY patients resides in the androgen receptor gene, with consequent defective androgen action and abnormal sexual differentiation. We sought to evaluate whether the adverse sequelae of androgen resistance may extend to skeletal tissue by measuring bone mineral density in six patients with androgen insensitivity. DESIGN: A cross-sectional retrospective study. MEASUREMENTS: Bone mineral density was measured by means of a Dexa (Hologic QDR 1000 scanner). The diagnosis of androgen insensitivity was confirmed in each patient by karyotype and assay of sex hormones. RESULTS: The five adult patients with androgen insensitivity had been exposed to both defective androgen action and variable periods of oestrogen deficiency. The latter resulted from the low circulating oestrogen concentrations (for premenopausal females) before gonadectomy and inadequate oestrogen replacement after gonadectomy. All five adults with androgen insensitivity had osteopenia in both the lumbar spine (T-score -1.52 to -3.85) and femoral neck (T-score -1.34 to -4.91). CONCLUSIONS: Osteopenia in patients with androgen insensitivity may relate to defective androgen action, oestrogen deficiency or a combination of the two. These observations have implications for the management of patients with androgen insensitivity and may provide insight into the effects of androgens on the female as well as the male skeleton.

Adolescent↗
PubMed1995

Osteoporosis in Turner's syndrome and other forms of primary amenorrhoea.

OBJECTIVE: Osteopenia in Turner's syndrome is well recognized. This study is aimed to elucidate whether this is an intrinsic feature of the disorder, or is a non-specific feature resulting from oestrogen deficiency. DESIGN: Comparison of bone mineral density and fracture rate in Turner's patients and in 46,XX women with equivalent oestrogen deprivation from other causes. SUBJECTS: One hundred and twenty women in the reproductive age range (16-45 years): 40 with Turner's syndrome, 40 with other forms of primary amenorrhoea, and 40 healthy controls matched to patients for duration of oestrogen usage. MEASUREMENTS: Measurement of bone mineral density in the lumbar spine (and femoral neck in some subjects) by dual-energy X-ray absorptiometry, and reported history of fracture. RESULTS: Vertebral bone mineral density was similar in women with Turner's syndrome (mean 0.84, SD 0.11 g/cm2) and those with other causes of primary amenorrhoea (mean 0.81, SD 0.11 g/cm2; P = 0.26). Both groups had severe osteopenia compared with healthy controls (mean 1.06, SD 0.09 g/cm2, P < 0.0005, confirmed after correction for height and weight). Fractures had been sustained by 45% (10/22) of Turner's patients for whom information was available, a high frequency compared with controls (P = 0.014); half of these were at 'osteoporotic' sites of fracture (wrist, vertebra, femoral neck). CONCLUSION: Osteopenia in Turner's syndrome is not an intrinsic feature specific to this disorder, but results from extreme oestrogen deprivation. Early treatment with oestrogen is therefore recommended.

Adolescent↗
PubMed1995

Menstrual disturbance and hypersecretion of progesterone in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVE: While menstrual disturbance is often quoted as a feature of congenital adrenal hyperplasia (CAH), little is known about the mechanism of this symptom. We set out to determine the relationship between menstrual pattern and biochemical characteristics of women with CAH due to 21-hydroxylase deficiency. PATIENTS AND DESIGN: All 21 female patients with classic CAH attending the adult endocrinology clinics at The Middlesex Hospital were reviewed. Their ages at menarche and menstrual pattern were recorded and blood samples were taken in the follicular phase of the menstrual cycle when on their usual maintenance therapy. MEASUREMENTS: Measurements of serum LH, FSH, progesterone, 17 alpha-hydroxyprogesterone, testosterone, androstenedione and plasma renin activity were recorded. Urinary steroid profiles were obtained by gas chromatography and mass spectrometry. Molecular genetic analysis of the 21-hydroxylase gene was performed on leucocyte DNA. RESULTS: In the 18 patients who had spontaneous menarche the degree of menstrual disturbance and progesterone excess was related to the effectiveness of adrenal suppressive therapy. Three out of 21 patients, however, failed to experience menarche on standard medical therapy. These patients with primary amenorrhoea were characterized by reduced endometrial thickening, by non-suppressible serum progesterone concentrations despite suppression of 17 alpha-hydroxyprogesterone levels and by the presence of progesterone metabolites in urinary steroid profiles. Molecular genetic analysis did not differentiate between patients with raised progesterone concentrations and those without. CONCLUSION: A subgroup of women with congenital adrenal hyperplasia have the triad of non-suppressible serum progesterone of adrenal origin, primary amenorrhoea and infertility due to failure of endometrial thickening. The characteristic urinary steroid profile best distinguishes this subgroup of women from others with congenital adrenal hyperplasia and menstrual disturbance due to inadequate adrenal suppression.

17-alpha-Hydroxyprogesterone↗