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Biomedical subjects

L Nieman

Publications and source records attributed to L Nieman.

At least 19 recordsLinked to original sources
PubMed2003

Pseudo-isolated FSH deficiency caused by an inhibin B-secreting granulosa cell tumour: case report.

Isolated FSH deficiency due to a mutation in the FSHbeta subunit is characterized by an extremely low serum FSH concentration. We report a patient who presented with an FSH of 0.8 mIU/ml and infertility associated with anovulation. Endocrinological assessment and immunohistochemistry revealed that a granulosa cell tumour was secreting inhibin B and suppressing FSH; however, LH and estradiol were within their normal ranges. Upon removal of the tumour, inhibin B decreased and FSH levels rose to normal values. The patient subsequently conceived and delivered successfully. Based on this case and on those previously described in the literature, we suggest that inhibin B levels should be evaluated in anovulatory patients having a clinical presentation consistent with functional hypothalamic amenorrhoea and very low to normal values of FSH.

Adult↗
PubMed2000

Estrogen replacement in perimenopause-related depression: a preliminary report.

OBJECTIVES: We examined the efficacy of estrogen in the treatment of depression in perimenopausal women with and without hot flushes. STUDY DESIGN: Women with perimenopause-related depression were randomized in a double-blind parallel design to receive either 17beta-estradiol or placebo for 3 weeks. Subsequently, women receiving estradiol during the first 3 weeks continued receiving estradiol for an additional 3 weeks, whereas women who had received placebo crossed over to estradiol for 3 weeks. Outcome measures included standardized mood rating scales and a visual analog scale self-report instrument. RESULTS: Of 34 female subjects, 16 received estradiol first and 18 received placebo first. After 3 weeks of estradiol, standardized mood rating scale scores and visual analog scale symptom scores (eg, sadness, anhedonia, and social isolation) were significantly decreased compared with baseline scores (P <.01) and were significantly lower than scores in women receiving placebo (P <.01), who showed no significant improvement. Neither the presence of hot flushes nor the duration of treatment (3 weeks vs 6 weeks) influenced outcome. A full or partial therapeutic response was seen in 80% of subjects receiving estradiol and 22% of those receiving placebo. CONCLUSION: In this preliminary study estradiol replacement effectively treats perimenopausal depression independent of its salutary effects on vasomotor symptoms.

Cross-Over Studies↗
PubMed2000

Effects of gonadal steroids in women with a history of postpartum depression.

OBJECTIVE: Endocrine factors are purported to play a role in the etiology of postpartum depression, but direct evidence for this role is lacking. The authors investigated the possible role of changes in gonadal steroid levels in postpartum depression by simulating two hormonal conditions related to pregnancy and parturition in euthymic women with and without a history of postpartum depression. METHOD: The supraphysiologic gonadal steroid levels of pregnancy and withdrawal from these high levels to a hypogonadal state were simulated by inducing hypogonadism in euthymic women-eight with and eight without a history of postpartum depression-with the gonadotropin-releasing hormone agonist leuprolide acetate, adding back supraphysiologic doses of estradiol and progesterone for 8 weeks, and then withdrawing both steroids under double-blind conditions. Outcome measures were daily symptom self-ratings and standardized subjective and objective cross-sectional mood rating scales. RESULTS: Five of the eight women with a history of postpartum depression (62.5%) and none of the eight women in the comparison group developed significant mood symptoms during the withdrawal period. Analysis of variance with repeated measures of daily and cross-sectional ratings of mood showed significant phase-by-group effects. These effects reflected significant increases in depressive symptoms in women with a history of postpartum depression but not in the comparison group after hormone withdrawal (and during the end of the hormone replacement phase), compared with baseline. CONCLUSIONS: The data provide direct evidence in support of the involvement of the reproductive hormones estrogen and progesterone in the development of postpartum depression in a subgroup of women. Further, they suggest that women with a history of postpartum depression are differentially sensitive to mood-destabilizing effects of gonadal steroids.

Adult↗
PubMed1999

Leptin secretion in Cushing's syndrome: preservation of diurnal rhythm and absent response to corticotropin-releasing hormone.

The normal inverse relationship between leptin and cortisol is lost in chronic hypercortisolism. We studied this apparent dysregulation in patients with Cushing's syndrome to investigate 1) the effect of chronic hypercortisolemia on the circadian rhythm of leptin secretion, 2) the response of leptin after administration of CRH, and 3) the short term effect of curative surgery on leptin. The preoperative morning leptin concentration was 54.2 +/- 8.1 ng/mL, and the nighttime value was 68.6 +/- 9.8 ng/mL, reflecting a mean rise of 32.8 +/- 7.6%, similar to the nocturnal increase observed in normal subjects. By contrast, cortisol's diurnal variation (21.8 +/- 1.7 vs. 16.9 +/- 1.1 mg/dL) was blunted. In women, but not men, body mass index correlated with leptin (P = 0.001). Preoperative ACTH and cortisol (both P < 0.0001), but not leptin levels increased after CRH. Ten days after surgery, basal cortisol values were subnormal (1.1 +/- 0.6 mg/dL), but leptin levels remained unchanged and did not increase after CRH. Body mass index and insulin also remained unchanged. Insulin, but not age, urinary free cortisol, or plasma cortisol correlated with leptin (P < 0.05). In summary, patients with Cushing's syndrome have moderately elevated leptin levels that maintain an intact circadian rhythm but do not respond to acute or subacute alterations of cortisol.

Adenoma↗
PubMed1999

Extrapituitary parasellar microadenoma in Cushing's disease.

Negative sellar exploration (despite the results of endocrine evaluation indicating Cushing's disease), the high incidence of failure of total hypophysectomy, and remission of Cushing's syndrome after unsuccessful hypophysectomy and sellar irradiation suggest that the etiology of refractory Cushing's disease, in some patients, lies near the sella but not in the pituitary gland. We present 5 patients, out of 626 who received surgery for Cushing's disease, in whom an ACTH-secreting extrapituitary parasellar adenoma was identified: 2 after unsuccessful total hypophysectomy for the treatment of refractory Cushing's disease, 2 after unsuccessful hemihypophysectomy (the first, 2 yr before treatment at the NIH for Nelson's syndrome; and the second, with recurrent Cushing's disease 5 yr after negative transsphenoidal exploration), and 1 with a preoperative diagnosis of an intraclival microadenoma, which was cured by resection of the tumor. In all cases, an extrapituitary parasellar microadenoma was confirmed unequivocally as the cause of the disease, by negative pathology of the resected pituitary gland (patients 1, 2, 3, and 5), and/or the remission of the disease after selective resection of the extrasellar adenoma (patients 3, 4, and 5). Three of 5 patients had a partial empty sella. These patients support the thesis that ACTH-secreting tumors can arise exclusively from remnants of Rathke's pouch, rather than from the adenohypophysis (anterior lobe or pars tuberalis of the pituitary gland) and can be a cause of Cushing's disease. In the sixth presented case, an extrapituitary tumor was suspected at surgery after negative pituitary exploration, but serial sections of the hemihypophysectomy specimen revealed a microscopic focus of tumor at the margin of the resected gland. This case demonstrates the importance of negative pituitary histology to establish the presence of an extrapituitary parasellar tumor as an exclusive source of ACTH, and it supports the value of clinical outcome to establish the diagnosis with selective adenomectomy of an extrapituitary parasellar tumor. In patients with negative pituitary magnetic resonance imaging, especially in the presence of a partial empty sella, the diagnostic and surgical approach in Cushing's disease should consider the identification and resection of extrapituitary parasellar adenoma, which can avoid total hypophysectomy, as was possible in 3 of our 5 patients.

Adenoma↗
PubMed1999

Levothyroxine replacement therapy in central hypothyroidism: a practice report.

Because of lack of well-documented laboratory criteria, we assessed the usefulness of measuring free thyroxine (FT4) levels for monitoring levothyroxine replacement therapy in patients with central hypothyroidism. This consisted of a retrospective review from 1991-1997 of patient profiles extracted into a Macintosh 4th Dimension data base from the medical information system at a tertiary care biomedical research facility. Information was also retrieved from medical records of 135 ambulatory patients treated by 42 endocrinology practitioners, and 52 ambulatory patients treated by 20 endocrinology practitioners for central and primary hypothyroidism, respectively. Patient profiles were reviewed for most recent thyroid function test results and levothyroxine dosing information. Of 112 (83%) patients with central hypothyroidism who had FT4 levels within the laboratory's reference interval, only 2 had a dosage change. The FT4 concentration was concordant with physician-assessed thyroid status in 65 (82%) of 79 patients (95% CI 72-90, p<0.02) for whom clinical assessment was available in medical records. Thyrotropin, total thyroxine, and triiodothyronine levels were not significantly associated with clinical status (p>0.12) in patients with central hypothyroidism. Despite similar demographic and levothyroxine dosing profiles, patients with central hypothyroidism had significantly lower serum FT4 and thyrotropin concentrations than those with primary hypothyroidism. The appropriateness of levothyroxine replacement therapy in most patients with central hypothyroidism is reflected by a normal FT4 concentration measured with a valid assay. Whether midnormal or upper normal values are necessary for optimal therapy, and whether the therapeutic goal should be different in children than in adults, require prospective studies with independent, objective assessment of thyroid status.

Adult↗
PubMed1998

Effects of fasting on neuroendocrine function and follicle development in lean women.

A 72-h fast in normal weight women during the follicular phase results in transient alterations in neuroendocrine function, but follicle development and follicular phase length remain unaltered. In this study we evaluated neuroendocrine and ovulatory function in lean women (body fat, < or = 20%) undergoing a similar 72-h fast. Compared to fed controls, fasted lean women experienced significant weight loss, blunting of the diurnal variation of cortisol, suppression of the nocturnal TSH rise, and a decrease in T3 levels after a 72-h fast. In contrast to similarly fasted, normal weight women, lean women have significantly higher evening cortisol levels and do not exhibit a normal nocturnal TSH rise after the fast. Lean fasted women exhibited a 19% decrease in the number of LH pulses over 24 h compared to fed women (12.9 +/- 1.3 vs. 16.0 +/- 1.9; P < 0.05). Fasting did not result in significant differences in mean LH, LH amplitude, LH area under the curve, and mean FSH levels in these lean women. Of the seven fasted cycles, two were anovulatory. In the five women studied in fed and fasted cycles, one had interrupted lead follicle development with anovulation, and four had significant lengthening of the follicular phase compared to those during their fed cycles (14.4 +/- 1.2 vs. 13.2 +/- 1.0 days; P = 0.01). The clinical observations made in this small sample of lean women showing more profound changes in neuroendocrine function, anovulation, and lengthened follicular phase after fasting suggest that lean women may be more vulnerable to fasting stress than normal weight women.

Absorptiometry, Photon↗
PubMed1998

Decreased brain glucose utilization in patients with Cushing's disease.

UNLABELLED: Glucocorticoid hormones affect glucose use in different tissues, and the results of several experimental studies have suggested that glucocorticoids have a central action on cerebral metabolism. PET, using the radiotracer 18F-fluorodeoxyglucose (FDG), permits the measurement of cerebral glucose metabolism. METHODS: To investigate whether cerebral glucose metabolism would be altered in patients with increased plasma glucocorticoid levels, we analyzed the FDG PET studies that were done on 13 patients with Cushing's disease and compared the results with those obtained in 13 age-matched normal control subjects. A second FDG PET scan was performed on 4 patients after surgical removal of the pituitary adenoma. RESULTS: Patients with Cushing's disease had a significant reduction in cerebral glucose metabolism compared with normal controls. In the patients on whom a second PET scan was performed, there was a trend toward increased glucose metabolism on the second scan when comparing pre- and postsurgery values for each patient. CONCLUSION: We suggest that the decreased cerebral glucose metabolism we observed in Cushing's disease is attributable to increased glucocorticoid levels, and we speculate that abnormal cerebral glucose metabolism might contribute to the cognitive and psychiatric abnormalities that are frequently observed in patients with Cushing's disease.

Brain↗
PubMed1997

The impact of nonacademic variables on performance at two medical schools.

Recent research shows that nonacademic variables must be taken into account when analyzing the indicators of medical student success. However, most previous studies have been limited to a single institution or population. This study investigated the relationship between nonacademic variables and performance at two very different medical schools. The Noncognitive Questionnaire was administered to 104 students at School A (predominantly white and historically oriented toward women) and 102 at School B (predominantly black). Correlation and multiple regression analyses were conducted to determine the relationship among nonacademic variables, undergraduate academic variables (Medical College Admission Test, undergraduate grade point average, and college quality), basic science grades, and US Medical Licensure Exam Step I (USMLE 1) scores. At School A, leadership/decisiveness, expected difficulty, and motivation predicted higher USMLE I scores and higher basic science grades each semester. At School B, expected difficulty was correlated with higher first semester grades only. For School A women, initiative/commitment was positively associated with both higher grades and higher USMLE scores. For black students of School B, expected difficulty was positively associated with higher grades. Identifying school-specific nonacademic variables of performance is critical to developing improved student support services.

Achievement↗
PubMed1996

Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor.

Brain tumor-associated cerebral edema arises because tumor capillaries lack normal blood-brain barrier function; vascular permeability factor (VPF, also known as vascular endothelial growth factor, VEGF) is a likely mediator of this phenomenon. Clinically, dexamethasone reduces brain tumor-associated vascular permeability through poorly understood mechanisms. Our goals were to determine if suppression of permeability by dexamethasone might involve inhibition of VPF action or expression, and if dexamethasone effects in this setting are mediated by the glucocorticoid receptor (GR). In two rat models of permeability (peripheral vascular permeability induced by intradermal injection of 9L glioma cell-conditioned medium or purified VPF, and intracerebral vascular permeability induced by implanted 9L glioma), dexamethasone suppressed permeability in a dose-dependent manner. Since 80% of the permeability-inducing activity in 9L-conditioned medium was removed by anti-VPF antibodies, we examined dexamethasone effects of VPF expression in 9L cells. Dexamethasone inhibited FCS- and PDGF-dependent induction of VPF expression. At all levels (intradermal, intracranial, and cell culture), dexamethasone effects were reversed by the GR antagonist mifepristone (RU486). Dexamethasone may decrease brain tumor-associated vascular permeability by two GR-dependent mechanisms: reduction of the response of the vasculature to tumor-derived permeability factors (including VPF), and reduction of VPF expression by tumor cells.

Animals↗
PubMed1995

Role of surgery in management of adrenocorticotropic hormone-producing islet cell tumors of the pancreas.

BACKGROUND: Ectopic adrenocorticotropic hormone-producing islet cell tumors of the pancreas (ACTH-ICT) are a rare cause of Cushing's syndrome with a severe and rapidly progressive clinical course. METHODS: Charts were reviewed on all patients evaluated and treated for proven Cushing's syndrome caused by ACTH-ICT (n = 12), specifically for the role of surgery in the management of this disease. RESULTS: Ten (83%) of twelve patients with ACTH-ICT had liver metastases at the time of diagnosis (eight of eight with Zollinger-Ellison syndrome, two of four without Zollinger-Ellison syndrome). Surgical management of the primary tumor included three patients who underwent distal pancreatectomy combined with hepatic resection and one patient who underwent laparoscopic enucleation of a tumor from the pancreatic tail. Eight of twelve patients underwent bilateral adrenalectomy to control symptoms of Cushing's syndrome, including three patients who underwent concurrent distal pancreatectomy and hepatic resection. Six of twelve patients died of the disease within 2 1/2 years of diagnosis, four are alive with progressive hepatic metastases, and one has biochemical evidence of disease. CONCLUSIONS: ACTH-ICT of the pancreas is an aggressive tumor, particularly when there is coproduction of gastrin. The benefit of aggressive surgical resection of primary or metastatic ACTH-ICT has not been established. However, palliative bilateral adrenalectomy is justified, because no patients had biochemical cures after aggressive surgical resection in this series.

ACTH Syndrome, Ectopic↗
PubMed1995

Short-term fasting affects luteinizing hormone secretory dynamics but not reproductive function in normal-weight sedentary women.

Acute food withdrawal reversibly inhibits the hypothalamic-pituitary-gonadal axis in men and in rhesus monkeys, and it produces defects in LH pulsatility in normal-weight women. However, the clinical effect of short-term nutritional deprivation on the reproductive axis of normally cycling women has not been evaluated. Thus we studied the effect of a 3-day fast during the midfollicular phase on menstrual cycle length, gonadotropin secretory patterns, follicular development, and ovulation. After a baseline ovulatory cycle, 12 women within 15% of ideal body weight were randomized to be fed (n = 7) or fasted (n = 10) on cycle days 7 to 9. Five of the women repeated the study and received the alternate diet. Endocrine and metabolic parameters of fasting and reproductive physiology were measured on cycle days 6 to 12. Fasted physiology was demonstrated by characteristic alterations in growth hormone, insulin-like growth factor I, TSH, and T3 levels. During fed cycles, the number of LH pulses remained constant on cycle days 6, 9 and 11, whereas mean LH levels, LH area under the curve, and LH pulse amplitude increased significantly over this time (all P < 0.05). In contrast, fasted cycles were marked by a significant decrease in the number of LH pulses on the last day of the fast (cycle day 9, P < 0.05) and by a lack of increase over time of mean LH values, LH area under the curve, and LH pulse amplitude. Follicle development, as assessed by daily ultrasound examination and estradiol measurements, was similar in all cycles and was followed by ovulation in all women; follicular and luteal phase lengths of fasted and fed cycles were similar. We conclude that the alterations in LH secretory dynamics that occur during a 3-day fast are not sufficient to perturb follicle development and cycle lengths in normal-weight sedentary women. The resilience of the reproductive axis in these healthy women contrasts with the sensitivity of the hypothalamic-pituitary-gonadal axis to acute nutritional withdrawal in men and in monkeys. We speculate that differences in the set point for sensing fuel availability or in the status of energy balance before the initiation of food deprivation may account for these species-specific and sex-specific variabilities.

Adult↗
PubMed1991

Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases.

Based on our review of 35 cases and the literature, we found the spectrum of pulmonary neuroendocrine (NE) tumors to be too broad to fit into the traditional three-category classification scheme of typical carcinoid (TC), atypical carcinoid (AC), and small-cell lung carcinoma (SCLC). We found that a spectrum of high- and low-grade tumors exist between TC and SCLC and that in the past many of these tumors have been called AC. We chose to adhere to Arrigoni's definition of AC, as his original criteria characterized a low-grade tumor. For the higher grade non-small-cell tumors (NSCLC), we propose a fourth category of large-cell neuroendocrine carcinoma (LCNEC), which is characterized by: (a) light microscopic NE appearance; (b) cells of large size, polygonal shape, low nuclear-cytoplasmic ratio (N:C), coarse nuclear chromatin, and frequent nucleoli; (c) high mitotic rate [greater than 10/10 high-power fields (HPF)] and frequent necrosis; and (d) NE features by immunohistochemistry (IHC) or electron microscopy (EM). Thus, after deciding that a pulmonary NE tumor is high grade, the major diagnostic issue is separation of LCNEC from SCLC. This distinction is based not only on cell size, but on a variety of morphologic features. We studied 20 TC, six AC, five LCNEC, and four SCLC and characterized the clinical, light microscopic, EM, IHC, and flow cytometric features of each type of tumor. We did not find any advantage to IHC, EM, or flow cytometry over light microscopy in the subclassification or prediction of prognosis; however, these methods were useful in characterizing these four types of pulmonary NE tumors and in demonstrating their NE properties. LCNEC must be distinguished from a fifth category pulmonary NE tumor: NSCLC with NE features in which NE differentiation is not evident by light microscopy and must be demonstrated by EM or IHC. Although the prognosis of LCNEC appears to be intermediate between AC and SCLC, larger numbers of patients will be needed to demonstrate significant differences in survival.

Adrenocorticotropic Hormone↗
PubMed1991

Corticotropin-releasing hormone testing in pituitary disease.

The availability of CRH for clinical use and the data so far generated by clinical investigators interested in its application to the problem of Cushing's syndrome have resulted in a new approach to the differential diagnosis of Cushing's syndrome (Fig. 2). Once the diagnosis of Cushing's syndrome is made with certainty, an initial separation into ACTH-dependent versus ACTH-independent categories is made on the basis of the plasma ACTH response to CRH. Plasma ACTH levels in excess of 10 pg/mL imply an ACTH-dependent process. Patients with an ACTH-dependent process are then divided into eutopic versus ectopic sources on the basis of the central to peripheral gradient of ACTH measured in the inferior petrosal sinuses simultaneously 3 to 5 minutes after the administration of CRH, 1 microgram/kg. The average post-CRH gradient in patients with eutopic ACTH-dependent Cushing's syndrome is 50. The lower bound is 3.3. Ectopic sources have a gradient of less than 2. Patients with ACTH-independent Cushing's syndrome can be confidently evaluated with imaging techniques, such as CT or MRI, looking for adrenal neoplasm or the "normal to small" glands characteristic of micronodular adrenal dysplasia.

Adrenal Gland Neoplasms↗