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Biomedical subjects

L K Nieman

Publications and source records attributed to L K Nieman.

At least 19 recordsLinked to original sources
PubMed2006

Therapeutic doses of glucocorticoids: implications for oral medicine.

Glucocorticoids can cause adverse systemic side-effects ranging from iatrogenic Cushing's syndrome during treatment, to hypothalamic-pituitary-adrenal axis suppression and clinically significant adrenal insufficiency when the agents are discontinued. While the oral route of administration is most often implicated, it is now becoming more apparent that inhaled and topical administration also can cause these effects. Given the high therapeutic value of glucocorticoids, the ability to prescribe these agents while maintaining a low risk-to-benefit ratio for patients is critical. The aim of this review is to provide oral healthcare practitioners with a practical guide to commonly used glucocorticoids, their adverse effects, and perioperative use.

Administration, Inhalation↗
PubMed2003

Is there a therapeutic role for octreotide in patients with ectopic Cushing's syndrome?

Cushing's syndrome (CS) due to ectopic ACTH secretion (EAS) has a high morbidity and mortality, because of the underlying tumor and the sequelae of severe hypercortisolemia. Therefore, rapid treatment of ectopic CS is mandatory. Scintigraphy shows that up to 80% of ectopic ACTH-producing tumors have somatostatin receptors. While this suggests that somatostatin analogs may reduce ACTH production and treat patients with EAS, the therapeutic role of these agents is still evolving. Here we demonstrate the spectrum of responses to octreotide therapy in 3 patients with EAS. Diagnostic imaging with the 111In-pentetreotide scan did not predict the therapeutic response to octreotide. Two patients with positive somatostatin receptor scintigraphy failed to respond to octreotide, while one with a negative scan reached eucortisolemia on a maintenance dose of 75 microg octreotide twice daily or octreotide LAR 30 mg per month. We conclude that octreotide is not a first line agent to control hypercortisolemia but may be a useful agent when other inhibitors of steroidogenesis fail or parenteral administration is required. Before therapy an octreotide challenge test may predict therapeutic response. Cortisol levels should be monitored regularly on somatostatin analog therapy, because of its unpredictable long-term pharmacodynamic profile.

Adrenocorticotropic Hormone↗
PubMed2003

Diagnosis and complications of Cushing's syndrome: a consensus statement.

In October 2002, a workshop was held in Ancona, Italy, to reach a Consensus on the management of Cushing's syndrome. The workshop was organized by the University of Ancona and sponsored by the Pituitary Society, the European Neuroendocrine Association, and the Italian Society of Endocrinology. Invited international participants included almost 50 leading endocrinologists with specific expertise in the management of Cushing's syndrome. The consensus statement on diagnostic criteria and the diagnosis and treatment of complications of this syndrome reached at the workshop is hereby summarized.

Cardiovascular Diseases↗
PubMed2003

Dynamic evaluation of adrenal hypofunction.

The diagnosis of adrenal hypofunction is suggested by clinical features and confirmed by biochemical testing. The characteristic features of acute primary adrenal insufficiency include orthostatic hypotension, fever, and hypoglycemia. By contrast, patients with chronic primary adrenal insufficiency have a longer history of malaise, as well as fatigue, anorexia, diarrhea, weight loss, joint and back pain, and darkening of the skin. While the clinical presentation of secondary adrenal insufficiency is similar to that of primary adrenal insufficiency, there is no hyperpigmentation, and hypotension and orthostasis are less pronounced. As a result, patients often present with vague, non-specific symptoms and the diagnosis may not be entertained. There is considerable debate regarding the best dynamic test for the diagnosis of adrenal hypofunction. Optimally, a screening test would be economic, convenient and safe. It would have high sensitivity and specificity based on consensus criteria for interpretation. Unfortunately, to date no test meets all of these criteria. Measurement of basal cortisol is an inexpensive and convenient screening test that can include (< 3 microg/dl; 83 nmol/l) or exclude (> 19 microg/dl; 524 nmol/l) adrenal insufficiency. However, most patients will have intermediate values and will require dynamic testing. This review discusses the use of metyrapone, insulin, CRH and synthetic ACTH 1-24 as provocative agents for cortisol secretion. Although the insulin and metyrapone stimulation tests have the advantage of testing the entire hypothalamic-pituitary-adrenal axis, they are cumbersome and carry more risk than the other tests. The 250 microg ACTH test works well to identify primary adrenal hypofunction, but can only detect secondary adrenal hypofunction when there is sufficient time for the glands to atrophy because of reduced endogenous ACTH stimulation. The 1 microg ACTH test has been advocated in the setting of possible secondary adrenal insufficiency, but its widespread use has been mitigated by the lack of a commercial preparation of this small dose and controversy regarding diagnostic criteria. Ultimately, the choice of test should be individualized for each patient, with knowledge of the available reference assays and the vagaries of each test.

Adrenal Cortex Function Tests↗
PubMed2002

High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis.

BACKGROUND: Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population. METHODS AND RESULTS: A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjögren's syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively). CONCLUSIONS: Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population.

Adolescent↗
PubMed2001

Use of a parenteral propylene glycol-containing etomidate preparation for the long-term management of ectopic Cushing's syndrome.

Chronic severe hypercortisolism is associated with life-threatening infections, diabetes and a high surgical mortality rate. Oral medical therapy can inhibit steroidogenesis and reduce the risk of these complications. However, apart from a few reports using an ethyl alcohol formulation of the iv anesthetic etomidate, there is no well-tested parenteral steroidogenesis inhibitor. We used the propylene glycol preparation of etomidate available in the United States to control hypercortisolism in a 39-yr-old man with ectopic ACTH secretion who was unable to take oral medications. Etomidate was administered over a period of 5.5 months. We titrated the dose of etomidate daily using serum cortisol levels, to avoid steroid over replacement and allow for a response to ongoing stress. A reduced dose during a period of acute renal failure achieved adequate control of hypercortisolemia. Suppression of steroidogenesis persisted for at least 14 d and perhaps as long as 6 wk after cessation of the medication. Except for transient myoclonus, the patient tolerated this preparation well. Parenteral propylene glycol containing etomidate can be used safely for a prolonged period to reduce hypercortisolemia in patients unable to take oral medications.

Acute Kidney Injury↗
PubMed2001

Glucocorticoid excess during adolescence leads to a major persistent deficit in bone mass and an increase in central body fat.

Endogenous Cushing's syndrome (CS) in children causes growth retardation, decreased bone mass, and increased total body fat. No prospective controlled studies have been performed in children to determine the long-term sequelae of CS on peak bone mass and body composition. A 15-year-old girl with Cushing disease (CD), and her healthy identical co-twin, were followed for 6 years after the CD was cured. At the 6-year follow-up both twins had areal bone mineral density (BMD) and body composition determined by dual-energy X-ray absorptiometry (DXA) and three-dimensional quantitative computed tomography (3DQCT). Z scores for height, weight, and body mass index (BMI) were -2.3, -0.8 and 0.2, and 1.2, 0.2, and -0.6, in the twin with CD and her co-twin, respectively. In the twin with CD, areal BMD and bone mineral apparent density (BMAD) at different sites varied from 0.7 to 3 SD below her co-twin. Volumetric lumbar spine bone density Z score was -0.75 and 1.0, and total body, abdominal visceral, and subcutaneous fat (%) was 42, 10, and 41 versus 26, 4, and 17 in the twin with CD and her co-twin, respectively. The relationship between total body fat and L2-L4 BMAD was inverse in the twin with CD (p < 0.05), which by contrast in her co-twin was opposite and direct (p < 0.001). In the twin with CD, despite cure, there was a persistent deficit in bone mass and increase in total and visceral body fat. These observations suggest that hypercortisolism (exogenous or endogenous) during adolescence may have persistent adverse effects on bone and fat mass.

Adolescent↗
PubMed2000

Do glucocorticoids cause spinal epidural lipomatosis? When endocrinology and spinal surgery meet.

Here, we report pathogenetic aspects of spinal epidural lipomatosis (SEL) based on a literature review. SEL is a rare entity but can cause significant morbidity. Its symptoms can be identical to those of more common disorders such as vertebral and disc disease, and cord lesions (for example, transverse myelitis, multiple sclerosis and syringomyelia). Therefore, it often goes undiagnosed. In addition, SEL occurs in patients on glucocorticoid therapy, which can lead to myopathy, thereby mimicking the motor symptoms of SEL. Glucocorticoids seem to play a major role in the development of SEL, although idiopathic SEL has also been reported. The latter occurs almost exclusively in obese individuals who may have concurrent hypercortisolism. Once clinically suspected, SEL is best diagnosed by magnetic resonance imaging (MRI). Treatment of SEL is directed at reducing body weight in patients with idiopathic SEL, and at decreasing glucocorticoid excess in patients with endogenous or exogenous hypercortisolism. In severe cases, decompressive laminectomy might become necessary to alleviate the neurological symptoms caused by spinal cord compression.

Epidural Space↗
PubMed2000

Nighttime salivary cortisol measurement as a simple, noninvasive, outpatient screening test for Cushing's syndrome in children and adolescents.

OBJECTIVE: There is currently no optimal test to screen for endogenous Cushing's syndrome (CS) in children. Traditional 24-hour urine or midnight serum cortisol values may be difficult to obtain or elevated by venipuncture stress. We hypothesized that salivary cortisol measurement is a reliable way to screen for CS in children. STUDY DESIGN: Sixty-seven children (5-17 years) were studied: 24 obese volunteers, 29 non-obese volunteers, and 14 children with CS. Saliva was obtained at 7:30 AM, bedtime, and midnight for measurement of free cortisol by radioimmunoassay. RESULTS: Salivary cortisol was detectable in all morning and evening samples from patients with CS but was frequently undetectable in healthy children at bedtime (66%) and at midnight (90%). With cut points that excluded healthy children, a midnight salivary cortisol value of 7.5 nmol/L (0.27 microg/dL) identified 13 of 14 patients with CS, whereas a bedtime value >27.6 nmol/L (1 microg/dL) detected CS in 5 of 6 patients. The diagnostic accuracies of midnight salivary cortisol and urinary free cortisol per square meter were the same (93%). CONCLUSION: Salivary cortisol measurement at bedtime or midnight rules out CS in nearly all cases. Nighttime salivary cortisol sampling is thus a simple, accurate way to screen for hypercortisolism in children.

Adolescent↗
PubMed2000

A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women.

Previous studies in women have shown that the antiprogestin mifepristone delays or inhibits folliculogenesis. The purpose of this study was to explore whether a new analogue, CDB-2914, has similar effects on folliculogenesis, ovulation, or on subsequent luteal phase endometrial maturation. Forty-four normally cycling, healthy women recorded urine LH and vaginal bleeding during pre-treatment, treatment, and post-treatment cycles. At a lead follicle diameter of 14-16 mm, a single oral dose (10, 50, 100 mg) of CDB-2914 or placebo was given, and daily ultrasound, oestradiol and progesterone were obtained until follicular collapse; an endometrial biopsy was obtained 5-7 days later. Single doses of CDB-2914 were well tolerated. Mid-follicular CDB-2914 suppressed lead follicle growth, causing a dose-dependent delay in folliculogenesis and suppression of plasma oestradiol. At higher doses, a new lead follicle was often recruited. Although luteinized unruptured follicles were observed at the 100 mg dose, all women had follicular collapse. There was a significant delay in endometrial maturation after CDB-2914 at all doses. The treatment cycle was lengthened by 1-2 weeks in 30% at 100, 27% at 50 and 9% at 10 mg. CDB-2914 altered ovarian and endometrial physiology without major effects on menstrual cyclicity and may have therapeutic utility.

Adolescent↗
PubMed2000

Assessing the effects of thyroid suppression on benign solitary thyroid nodules. A model for using quantitative research synthesis.

Systematic review of the available information with a modified, largely quantitative method of research synthesis disclosed that an initial trial of thyroid hormone suppression therapy leads to clinically significant (> or = 50%) reduction of nodule size or arrest of nodule growth in a subset of patients with benign solitary thyroid nodules. In fact, in addition to objective improvements due to decreasing nodule size, L-T4 suppression therapy may benefit patients by reducing perinodular thyroid volume. Consequently, both pressure symptoms and cosmetic complaints may improve (9, 68). Additional studies for the assessment of the risks versus benefits of supraphysiologic doses of L-T4, the optimal level of thyroid suppression and the dose needed to achieve this magnitude of reduction, the optimal length of the initial trial, and the conditions for the continuation of L-T4 thyroid suppression therapy, as well as the identification of markers for patients most likely to respond to this therapy, are warranted. Finally, quantitative assessment of available evidence as described here may be applicable to the review of other controversial issues as well.

Adult↗
PubMed2000

Adrenocorticotropin-independent macronodular adrenal hyperplasia: an uncommon cause of primary adrenal hypercortisolism.

PURPOSE: To describe the imaging findings in the adrenal glands of 12 patients with adrenocorticotropin (ACTH)-independent macronodular adrenocortical hyperplasia (AIMAH). MATERIALS AND METHODS: Computed tomographic (CT) and magnetic resonance (MR) imaging findings in the adrenal glands were reviewed retrospectively in 12 patients (three men, nine women) with ACTH-independent Cushing syndrome and with bilateral nonpigmented multinodular adrenal hyperplasia. The results of pituitary MR imaging, adrenal scintigraphy, and petrosal sampling were available in nine, five, and six patients, respectively. Eleven patients underwent bilateral and one patient underwent unilateral adrenalectomy. RESULTS: Eleven patients had enlarged multinodular adrenal glands: Nodules were 0.1-5.5 cm. The combined weight of both adrenal specimens for the 11 bilateral adrenalectomy specimens was 28-297 g, with a mean weight of 122 g. Glands were hypointense compared with the liver on T1-weighted images and were hyperintense on T2-weighted images. Pituitary MR imaging findings were negative in nine of nine patients. Iodomethylnorcholesterol scintigraphy showed bilateral uptake in four of five patients. Petrosal sinus sampling revealed no petrosal-to-peripheral ACTH gradients before corticotropin-releasing hormone (CRH) stimulation in six of six patients, but three patients had gradients after CRH stimulation. After undergoing bilateral or unilateral adrenalectomy, all patients were cured. CONCLUSION: AIMAH is a rare cause of ACTH-independent Cushing syndrome, with characteristic CT findings of massively enlarged multinodular adrenal glands. Bilateral adrenalectomy is indicated on the basis of clinical and CT findings.

Adrenal Glands↗
PubMed2000

Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin.

Because high circulating levels of glucocorticoids impair immunity and predispose to infections, we evaluated whether indices of cortisol (F) production could predict infections in patients with Cushing syndrome (CS) caused by ectopic production of ACTH (EA). Charts of 54 consecutive patients with untreated EA, without underlying diagnosis of small cell carcinoma of the lung, were reviewed, and types of infections, white blood cell (WBC) count, fever, as well as the glucocorticoid indices [0800 h F, daily urine F excretion (UFC), and daily urine 17-hydroxysteroid/g creatinine excretion (17OHS)], were recorded. Thirty-five patients had no or clinically mild infection; the remaining 19 patients had severe, systemic infection (n = 13) and/or sepsis (n = 6), including either bacterial or opportunistic pathogens or both (73.7%, 42.1%, and 13.8%, respectively). The latter group of patients had significantly higher indices of hypercortisolism (F, UFC, and 17OHS) than those with mild or no infections, but these indices did not correlate with temperature or WBC count. Thresholds for identifying severe infection were selected for maximal positive predictive value and were: F, 43.1 microg/dL; UFC, 2000 microg/day; and 17OHS, 35 mg/g creatinine. The most accurate discriminator for severe infection was 17OHS, based on a positive predictive value of 64.7%. Our data strongly suggests that the likelihood for a bacterial or opportunistic infection in CS patients, even without underlying small cell carcinoma of the lung, is greatest in patients with extreme hypercortisolism. The predictive value of total WBC count or the presence of an elevated temperature is not sufficient to identify patients with severe, life-threatening infection.

Adolescent↗
PubMed1999

Paradoxical response to dexamethasone in the diagnosis of primary pigmented nodular adrenocortical disease.

BACKGROUND: Primary pigmented nodular adrenocortical disease causes the Cushing syndrome in children and young adults and is most frequently associated with the Carney complex. OBJECTIVE: To evaluate diagnostic tests for primary pigmented nodular adrenocortical disease. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: 21 patients with primary pigmented nodular adrenocortical disease. The control groups consisted of 9 patients with macronodular adrenocortical disease and 15 patients with primary unilateral adrenocortical disease (single adenomas). MEASUREMENTS: Clinical characteristics, radiologic imaging, and a 6-day Liddle test with determination of urinary free cortisol and 17-hydroxycorticosteroid excretion. RESULTS: Adrenal imaging and other tests were of limited value for the diagnosis of primary pigmented nodular adrenocortical disease. The Liddle test, however, distinguished patients with this disorder from those with other primary adrenocortical lesions. An increase of 50% or more in urinary free cortisol levels on day 6 of the Liddle test identified 9 of 13 patients (69.2% [95% CI, 46.6% to 91.8%]) with primary pigmented nodular adrenocortical disease, excluded all patients with macronodular adrenocortical disease, and was present in only 3 of the 15 patients with single adrenocortical adenomas (20% [CI, 0% to 40.2%]). An increase in urinary free cortisol excretion of 100% or more on day 6 of the Liddle test identified only patients with primary pigmented nodular adrenocortical disease. CONCLUSIONS: Patients with primary pigmented nodular adrenocortical disease responded to dexamethasone with a paradoxical increase in glucocorticoid excretion during the Liddle test. This feature distinguishes such patients from those who have the Cushing syndrome caused by other primary adrenal disorders and may lead to timely detection of the Carney complex (a potentially fatal disorder) in asymptomatic patients.

17-Hydroxycorticosteroids↗
PubMed1999

Construction and in vivo efficacy of a replication-deficient recombinant adenovirus encoding murine growth hormone.

We have constructed a recombinant, replication-deficient, first-generation adenovirus-encoding mouse GH (mGH), AdCMVmGH. This virus directed mGH production from an epithelial cell line in vitro in a dose-dependent manner. When injected into the quadriceps muscle or submandibular ducts of mGH-deficient Snell dwarf mice, AdCMVmGH resulted in the production of significantly elevated serum mGH levels. Furthermore, after i.m. injection, dwarf mice increased in weight by 8% over 4 days and close to 100% by 30 days. When AdCMVmGH was administered to 3- to 4-week-old rats by i.v. injection to assess general metabolic responses, serum mGH, insulin-like growth factor 1, triglycerides and cholesterol levels were significantly elevated. AdCMVmGH should be a valuable experimental tool for the controlled, directed expression of mGH in preclinical mouse model studies.

Adenoviridae↗
PubMed1999

The hypoplastic inferior petrosal sinus: a potential source of false-negative results in petrosal sampling for Cushing's disease.

Our purpose was to describe the hypoplastic or plexiform inferior petrosal sinus as a potential cause of false-negative sampling results in patients with Cushing's disease. Five hundred and one patients with surgically proven Cushing's disease and negative or equivocal magnetic resonance imaging scans of the pituitary gland underwent petrosal sinus sampling. Four patients (0.8%) with surgically proven Cushing's disease had false-negative results of petrosal sinus sampling. Retrograde inferior petrosal sinograms in these patients were reviewed to evaluate the anatomy of the inferior petrosal sinuses for abnormalities that could have contributed to this misdiagnosis. In addition, the retrograde inferior petrosal sinograms of 100 consecutive patients were reviewed to establish the frequency of asymmetric and/or hypoplastic inferior petrosal sinuses. All four patients with false-negative results of petrosal sampling demonstrated a hypoplastic or plexiform inferior petrosal sinus ipsilateral to an ACTH-secreting microadenoma. When the sampling catheter was in the hypoplastic petrosal sinus, retrograde sinograms from the contralateral side demonstrated anomalous drainage patterns on the side of the hypoplastic sinus. Because the negative results of petrosal sinus sampling false-suggested the presence of the ectopic ACTH syndrome, curative transsphenoidal surgery in these four patients was delayed up to 31 months. We conclude that the presence of a unilateral hypoplastic or plexiform inferior petrosal sinus can result in anomalous drainage from the pituitary gland that may lead to false-negative sampling results in patients with Cushing's disease.

Adolescent↗
PubMed1999

Lack of utility of (111)In-pentetreotide scintigraphy in localizing ectopic ACTH producing tumors: follow-up of 18 patients.

Octreotide scintigraphy has been advocated as the principal imaging modality for localizing ectopic ACTH-secreting tumors in Cushing's syndrome. To assess its usefulness we reviewed the course of 18 consecutive patients with ectopic ACTH-producing tumor. Imaging included (111)In-pentetreotide scintigraphy, computed tomography (CT), and/or magnetic resonance imaging (MRI). Tumor was detected initially in 7/18 patients, and in 3/18 during follow-up. No ACTH-secreting tumor was detected by octreotide scintigraphy when CT/ MRI were negative. Seventeen of forty octreotide scintigrams were abnormal. CT and/or MRI confirmed tumors in 10, but demonstrated nonendocrine lesions in association with 6 false positive octreotide scintigrams. Hepatic venous sampling for ACTH refuted one lesion detected by octreotide and CT scans. Twenty-three of forty octreotide scintigrams were normal. Of these, 8 were false negative, as CT and/or MRI detected tumor; 10 agreed with negative CT and MRI, and 5 correctly refuted false positive CT and/or MRI scans. Repeated CT/ MR, but not octreotide scintigraphy, led to tumor resection in 2 patients. We conclude that octreotide scintigraphy does not offer greater sensitivity than CT/MRI and that false positive scans are common. Although octreotide scintigraphy may be helpful in selected cases, it is not a significant advance over conventional imaging for ectopic ACTH-secreting tumors.

ACTH Syndrome, Ectopic↗