Biomedical subjects

L K Nieman

Publications and source records attributed to L K Nieman.

At least 37 records · Page 2Linked to original sources

PubMed1998

Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome.

BACKGROUND: The symptoms of women with premenstrual syndrome improve in response to suppression of ovarian function, although these women have no evidence of ovarian dysfunction. We undertook a study to determine the role of estrogen and progesterone in this syndrome. METHODS: We first studied the effect of ovarian suppression with leuprolide, an agonist analogue of gonadotropin-releasing hormone, or placebo on symptoms in 20 women with the premenstrual syndrome. Ten women whose symptoms improved during leuprolide treatment were given estradiol and progesterone in a double-blind, crossover design, each for four weeks, during continued leuprolide administration. Women without premenstrual syndrome (normal women) participated in a similar protocol. Outcomes were assessed on the basis of daily self-reports by the patients and biweekly rater-administered symptom-rating scales. RESULTS: The 10 women with premenstrual syndrome who were given leuprolide had a significant decrease in symptoms as compared with base-line values and with values for the 10 women who were given placebo. The 10 women with premenstrual syndrome who were given leuprolide plus estradiol or progesterone had a significant recurrence of symptoms, but no changes in mood occurred in 15 normal women who received the same regimen or in 5 women with premenstrual syndrome who were given placebo hormone during continued leuprolide administration. CONCLUSIONS: In women with premenstrual syndrome, the occurrence of symptoms represents an abnormal response to normal hormonal changes.

Adult↗

PubMed1998

Bilateral sampling of the internal jugular vein to distinguish between mechanisms of adrenocorticotropic hormone-dependent Cushing syndrome.

BACKGROUND: Bilateral sampling of the petrosal sinuses to distinguish Cushing disease from the ectopic adrenocorticotropic hormone (ACTH) syndrome is accurate but technically demanding and risky. Bilateral sampling of the internal jugular vein is simpler and safer. OBJECTIVE: To compare bilateral internal jugular vein sampling with bilateral inferior petrosal sinus sampling for distinguishing patients with Cushing disease from those with the ectopic ACTH syndrome. SETTING: Tertiary referral hospital. PATIENTS: 20 patients with surgically proven Cushing disease and 1 patient with proven ectopic ACTH syndrome. INTERVENTION: All patients underwent petrosal sinus sampling and jugular vein sampling before and after administration of corticotropin-releasing hormone (CRH) on separate days. MEASUREMENTS: Ratios of central ACTH to peripheral ACTH in petrosal sinus samples and jugular vein samples were calculated before and after administration of CRH. RESULTS: Ratios of central to peripheral ACTH were diagnostic for Cushing disease (> 2 before administration of CRH and > 3 after administration of CRH) in jugular vein samples from 16 of 20 patients with surgically proven Cushing disease (sensitivity, 80% [95% CI, 56% to 96%]). Ten of these 16 patients (63%) had diagnostic results only after CRH was administered. The average ratio of central to peripheral ACTH in jugular vein samples was 2.7 before CRH and 7.7 after CRH. Ratios of central to peripheral ACTH were diagnostic in petrosal sinus samples from 19 of 20 patients with surgically proven Cushing disease (sensitivity, 95% [CI, 75% to 99%]). Samples from all 19 patients had diagnostic ratios before and after administration of CRH. The average ratio of central to peripheral ACTH in petrosal sinus samples was 17.7 before CRH and 90.0 after CRH. In the patient with the ectopic ACTH syndrome, ratios of central to peripheral ACTH were negative in jugular vein samples and petrosal sinus samples before and after CRH (< 2 and < 3, respectively). CONCLUSIONS: Jugular vein sampling correctly identified ACTH-secreting pituitary adenomas in 80% of patients with proven Cushing disease. Administration of CRH was essential for diagnostic results in 63% of the patients. Jugular vein sampling is less invasive than petrosal sinus sampling. Negative results on jugular vein sampling should be confirmed by petrosal sinus sampling.

Adolescent↗

PubMed1998

Systemic action of human growth hormone following adenovirus-mediated gene transfer to rat submandibular glands.

We have previously suggested that although salivary glands function in an exocrine manner they might none the less offer a useful way to deliver therapeutic proteins systemically. As a direct functional test of this hypothesis, we constructed a recombinant adenovirus (AdCMVhGH) encoding human growth hormone (hGH) and then studied the biological action of hGH produced following transfer of the hGH gene to rat submandibular glands. At 48 h following infusion of AdCMVhGH into these glands via cannulation of the main excretory duct, serum levels of hGH were approximately 16 ng/ml and rat insulin-like growth factor-1 was elevated approximately 25%. Moreover, serum chemistry profiles of rats subjected to in vivo gene transfer displayed alterations in the BUN:creatinine ratio and triglyceride levels presumably reflecting the anabolic actions of the hGH. These results provide the first demonstration of systemic biological action from a transgene product secreted in an endocrine fashion from the salivary glands.

Adenoviridae↗

PubMed1998

The dexamethasone-suppressed corticotropin-releasing hormone stimulation test differentiates mild Cushing's disease from normal physiology.

The dexamethasone-suppressed CRH test (Dex-CRH test) differentiates patients with Cushing's syndrome (CS) from those with pseudo-Cushing states, who have decreased ACTH responses to CRH because of negative feedback exerted by chronic hypercortisolism. Normal subjects, however, have not been studied with the Dex-CRH test, raising concern that this test might not separate patients with CS from patients with normal adrenal function. To determine whether the criterion that separates CS from pseudo-Cushing states also would differentiate patients with Cushing's disease (CD) from individuals with eucortisolism, we studied 20 healthy volunteers during low-dose (2 mg/day) dexamethasone suppression, and then during the Dex-CRH test (CRH stimulation test performed 2 h after completion of low-dose dexamethasone suppression), and contrasted their results with those of 20 patients with surgically proven mild CD [urine free cortisol (UFC) < 1000 nmol/day). Basal UFC was significantly greater in patients with CD (P < 0.001) but within the normal range (55-250 nmol/day) in 4 patients. During low-dose dexamethasone suppression, a UFC less than 100 nmol/day (36 micrograms/day) was found in all but 1 volunteer subject, and a urine 17-hydroxycorticosteroid excretion less than 14.6 mumol/day (5.3 mg/day) was found in all but 2 subjects. During the Dex-CRH test, plasma cortisol less than 38 nmol/L was found in all 20 normal volunteers until 30 min after CRH administration. By contrast, the 15-min CRH-stimulated plasma cortisol exceeded 38 nmol/L in all patients with CD (P < 0.001). Plasma dexamethasone measured just before CRH administration was similar in normal volunteers (13.0 +/- 6.1 mumol/L) and patients with CD (16.4 +/- 6.4 mumol/L). We conclude that cortisol measurements obtained during the Dex-CRH test are suppressed in normal volunteers below those found in mild CD. These results suggest that the Dex-CRH test may be useful in the evaluation of CS in patients without significant hypercortisoluria. However, its value in patients with episodic hormonogenesis has not been tested.

17-Hydroxycorticosteroids↗

PubMed1998

A single midnight serum cortisol measurement distinguishes Cushing's syndrome from pseudo-Cushing states.

Cushing's syndrome (CS) may be difficult to distinguish from pseudo-Cushing states (PCS) based on physical findings or urinary glucocorticoid excretion. As the lack of diurnal variation in serum cortisol is characteristic of CS, we studied whether diurnal cortisol determinations could discriminate CS from PCS. Two hundred and sixty-three patients were evaluated: 240 had CS, and 23 had PCS. Urine was collected for 24 h for measurement of cortisol and 17-hydroxycorticosteroids (17OHCS). Blood was drawn at 2300, 2330, 0000, 0030, and 0100 h and at 0600, 0630, 0700, 0730, and 0800 h the next morning for serum cortisol determination. The main outcome measure was the sensitivity of these parameters for the diagnosis of CS at 100% specificity. A midnight cortisol value greater than 7.5 microg/dL correctly identified 225 of 234 patients with CS and all PCS patients. This sensitivity (96%) was superior to that obtained for any other measure, including urinary cortisol (45%), 17OHCS (22%), any other individual cortisol time point (10-92%), the morning (23%) or the evening (93%) cortisol mean, and the ratio (11%) of morning to evening values. We conclude that at 100% specificity, a single serum cortisol value above 7.5 microg/dL at midnight discriminates CS from PCS with higher sensitivity than 24-h urinary cortisol or 17OHCS, or other individual or combined measures of serum cortisol.

Adolescent↗

PubMed1998

Plasma levels of corticotropin-releasing hormone in the inferior petrosal sinuses of healthy volunteers, patients with Cushing's syndrome, and patients with pseudo-Cushing states.

The objective of this study was to determine whether measurements of human CRH in the inferior petrosal sinuses could distinguish patients with Cushing's syndrome from those with pseudo-Cushing states or normal physiology. Twenty-five patients with Cushing's disease, 17 patients with the syndrome of ectopic ACTH, 7 patients with Cushing's syndrome of adrenal origin, 6 patients with pseudo-Cushing states, and 11 volunteers believed to have normal hypothalamic-pituitary-adrenal axes were studied. Basal plasma human CRH and ACTH were measured at two time points in the petrosal sinuses and in a peripheral vein. Most subjects were studied after the administration of intravenous diazepam or midazolam and fentanyl, but because of the known inhibitory effects of such sedation on CRH secretion, 2 normal volunteers and 3 patients with pseudo-Cushing states were studied without sedation. Human CRH levels were near or below the detection limit of the assay in all subjects. Although the normal volunteers and patients with pseudo-Cushing states who were studied without sedation had significantly greater inferior petrosal sinus ACTH levels than those who received sedation, there were no differences in measured human CRH levels for any of the groups. We conclude that inferior petrosal sinus human CRH levels are not easily measured in the inferior petrosal sinuses and cannot be used to determine whether individual patients may have hypersecretion of CRH causing their ACTH secretion.

Adrenocorticotropic Hormone↗

PubMed1998

Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing's disease and no demonstrable pituitary tumor on magnetic resonance imaging.

OBJECT: Pituitary surgery has been reported to produce remission of Cushing's disease with preservation of pituitary function in only 60 to 70% of patients. The inability to identify an adenoma accounts for most failed sellar explorations. Most negative surgical explorations occur in patients in whom magnetic resonance (MR) imaging of the pituitary demonstrates normal findings, which happens in at least 35 to 45% of patients with Cushing's disease. METHODS: To examine the usefulness of intraoperative ultrasonography (IOUS) for identifying an adenoma in patients with no demonstrable tumor (negative findings) on pituitary MR imaging. we prospectively assessed the results of IOUS in 68 patients with a negative (59 patients) or equivocal (nine patients) MR image from a consecutive series of 107 patients with Cushing's disease (64%). We compared surgical findings and outcomes in these 68 patients with a group of 68 patients with Cushing's disease and negative findings on MR imaging in whom IOUS was not available. Intraoperative ultrasonography localized a tumor in 47 (69%) of 68 patients with negative findings on MR imaging. Surprisingly, the size of the adenomas that were detected with IOUS compared with the size of those not detected did not differ (6.8+/-3.4 mm compared with 6.1+/-2.8 mm [mean+/-standard deviation], respectively [p=0.51). In four patients, no adenoma was found at surgery or in the pathological specimen ("true negative"). In eight patients, nine abnormalities detected by IOUS that were suspected adenomas were negative on exploration ("false positive"). Thus, IOUS has a sensitivity of 73% and a positive predictive value of 84% for detecting pituitary adenomas in patients with Cushing's disease and negative findings on MR imaging. Compared with the 68 patients who did not undergo IOUS. remission after surgery was improved (61 patients [90%] compared with 57 patients [84%]), the number of tumors found on exploration was increased (61 tumors compared with 51 tumors, p=0.02), and the number of hemihypophysectomies was decreased (five compared with 15; p=0.02) with IOUS. When the groups were compared after excluding patients with prior pituitary surgery, tumors were found in 91% versus 72% (p=0.008), and remission occurred in 95% versus 87% of patients, respectively, in the groups that had or did not have IOUS. CONCLUSIONS: The IOUS is a sensitive imaging modality when used in patients with Cushing's disease in whom findings on pituitary MR imaging are negative. The improved ability to detect and localize these tumors by using IOUS positively affects surgical outcome.

Adenoma↗

PubMed1997

Inferior petrosal sinus AVP in patients with Cushing's syndrome.

OBJECTIVE: In both normal volunteers and patients with Cushing's disease, one dominant inferior petrosal sinus (IPS) contains higher concentrations of AVP and ACTH than the contralateral (non-dominant) IPS, but ovine corticotrophin-releasing hormone (oCRH)-stimulated AVP in the petrosal sinuses is greater in Cushing's disease than in normal volunteers. To distinguish whether greater oCRH-releasable AVP might be specifically related to the presence of a pituitary corticotrophinoma, or be due to hypercortisolism per se, we compared IPS AVP in patients with Cushing's disease with those of patients with other causes of Cushing's syndrome. PATIENTS: Twenty-three patients with Cushing's disease, 16 patients with the syndrome of ectopic ACTH and seven patients with Cushing's syndrome of adrenal origin. MEASUREMENTS: AVP and ACTH, measured both before and 3, 5 and 10 minutes after oCRH in the petrosal sinuses, and in a peripheral vein. RESULTS: In all three groups, AVP concentrations were lateralized such that most of the AVP was found in one, dominant IPS. oCRH significantly increased IPS ACTH only in patients with Cushing's disease (p < 0.001), whereas it significantly increased dominant IPS AVP levels in all three patient groups (P < 0.01). However, neither dominant nor non-dominant IPS AVP (basal or oCRH-stimulated) were significantly different among patients with Cushing's disease, ectopic ACTH or Cushing's syndrome of adrenal origin. Basal and oCRH-stimulated IPS AVP were negatively correlated with urine free cortisol. CONCLUSIONS: Inferior petrosal sinus AVP levels are similar in all forms of Cushing's syndrome, and thus the higher inferior petrosal sinus AVP levels in patients with Cushing's disease compared with normal volunteers are unlikely to be related specifically to the presence of the pituitary corticotrophinoma. While AVP may play a role in pituitary corticotroph tumourigenesis or may be secreted by some pituitary corticotroph tumours, the observation that CRH-stimulated inferior petrosal sinus AVP levels are higher in Cushing's disease than in normal volunteers appears most likely to be related to the low endogenous CRH levels induced by hypercortisolism, rather than a consequence of Cushing's disease itself. We hypothesize that low endogenous CRH leads to increased sensitivity of central nervous system CRH receptors to exogenous CRH, and thus to greater ovine CRH-stimulated AVP.

ACTH Syndrome, Ectopic↗

PubMed1997

Selective excision of adenomas originating in or extending into the pituitary stalk with preservation of pituitary function.

When the surgeon identifies an adenoma within the gland and selectively excises it, endocrine-active pituitary tumors are usually cured and pituitary function is preserved. Occasionally ectopic adenomas arise primarily in the pituitary stalk or arise superiorly in the midportion of the anterior lobe and extend upward within the stalk. To determine if these tumors can be selectively excised with preservation of pituitary function, the authors examined the outcome of selective adenomectomy in 10 patients with Cushing's disease with an ectopic adenoma originating in, and confined to, the stalk (four microadenomas) or an adenoma extending superiorly through the diaphragma sella and into the stalk (five microadenomas and one macroadenoma) from an operative series of 516 patients with Cushing's disease. To reach the adenoma transsphenoidally in these patients, the diaphragma sella was incised anteroposteriorly in the midline to the anterior edge of the stalk, the suprasellar cistern was entered, and the adenoma was selectively excised using care to limit injury to the infundibulum. After selective adenomectomy, Cushing's disease remitted in all patients. All patients were hypocortisolemic immediately after surgery and required hydrocortisone for up to 21 months. Apart from the adrenal axis, pituitary function was normal in five patients in the immediate postoperative period, including two patients with tumors confined to the stalk and three patients with preoperative hypothyroidism (one patient) and/or hypogonadism (three patients). Three others with transient postoperative hypothyroidism (one patient) or diabetes insipidus (two patients) had normal pituitary function within 7 months of surgery. One patient with hypothyroidism and one with hypogonadism before surgery had panhypopituitarism postoperatively. A patient with a microadenoma located high in the stalk next to the optic chiasm had bitemporal hemianopsia postoperatively. These results demonstrate the feasibility of achieving curative transsphenoidal resection and preservation of pituitary function in cases of pituitary adenomas that are confined to the pituitary stalk or tumors that extend superiorly within the stalk from an intrasellar origin.

Adenoma↗

PubMed1997

Cushing's syndrome.

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Adrenocorticotropic Hormone↗

PubMed1996

Inferior petrosal sinus sampling in healthy subjects reveals a unilateral corticotropin-releasing hormone-induced arginine vasopressin release associated with ipsilateral adrenocorticotropin secretion.

Arginine vasopressin (AVP) acts synergistically with corticotropin-releasing hormone (CRH) to stimulate ACTH release from the anterior pituitary. In a previous study of bilateral simultaneous inferior petrosal sinus (IPS) sampling in healthy human subjects, we observed lateralized ACTH secretion, suggesting lateralized secretion of an ACTH-regulating hypothalamic factor. To investigate this possibility, we measured ACTH, CRH, AVP, and oxytocin (OT) levels in the IPS and the peripheral circulation in nine normal volunteers, before and after 1 microgram/kg i.v. bolus ovine CRH (oCRH). At baseline, ACTH, AVP, and OT exhibited a significant (P < 0.05) two to threefold intersinus gradient (ISG), indicating the existence of a dominant petrosal sinus. Endogenous CRH was undetectable in all samples. Despite similar exogenous oCRH levels in both petrosal sinuses, oCRH caused a significant increase (P < 0.001) in the ACTH ISG (15.8 +/- 5.6, mean +/- SEM), suggesting increased responsiveness of one dominant side of the anterior pituitary. This was associated with an ipsilateral CRH-induced AVP release and a significant increase (P < 0.01) in the AVP ISG (8.6 +/- 2.3), suggesting lateralized AVP secretion by the hypothalamus. Furthermore, the increased AVP ISG after oCRH correlated strongly with the ACTH ISG (r = 0.92, P < 0.01). oCRH administration did not affect OT. These findings suggest that there is a dominant petrosal sinus in healthy volunteers that appears to reflect a dominant side of the adenohypophysis, characterized by increased functional activity and/or responsiveness of the pituitary corticotrophs. This may reflect lateralized hypothalamic and/or suprahypothalamic function resulting in CRH-responsive lateralized secretion of AVP from parvocellular and/or magnocellular axons in the median eminence and the posterior pituitary. Although the functional and teleologic significance of these findings remains to be investigated, our data suggest a novel mechanism for CRH-mediated ACTH release, namely CRH-induced release of AVP which then enhances CRH action on the corticotrophs. Furthermore, our data represent the first direct evidence for the concept of brain lateralization with respect to neuroendocrine secretion.

Adrenocorticotropic Hormone↗

PubMed1996

A comparison of the overnight and the standard metyrapone test for the differential diagnosis of adrenocorticotrophin-dependent Cushing's syndrome.

OBJECTIVE: We wished to develop optimal criteria for interpreting the single-dose overnight metyrapone test and to compare the diagnostic efficiency of the overnight and the standard 6-dose metyrapone tests for the differential diagnosis of ACTH-dependent Cushing's syndrome. DESIGN: Retrospective pilot study based on all patients who completed both metyrapone tests and whose diagnoses were subsequently confirmed surgically. PATIENTS: Sixty-three patients, 57 with pituitary tumours and 6 with ectopic ACTH syndrome, were studied. MEASUREMENTS: The sensitivity and specificity were determined using stimulation of plasma 11-deoxycortisol and suppression of plasma cortisol as endpoints for the overnight test and stimulation of urine 17-hydroxysteroid and plasma 11-deoxycortisol as endpoints for the standard test. The lest response that gave the highest sensitivity for the diagnosis of Cushing's disease, with 100% specificity, was determined for each test endpoint. RESULTS: Both the stimulation of plasma 11-deoxycortisol and the suppression of plasma cortisol were expressed as the ratio of the post-metyrapone value to baseline. A plasma 11-deoxycortisol ratio > than 220 or a plasma cortisol ratio > 0.6 was associated with 100% specificity for diagnosis of Cushing's disease by the overnight test. When these two criteria were combined, the sensitivity was 65%, which was significantly higher than that obtained using either steroid alone: 42% for both plasma 11-deoxycortisol and plasma cortisol. The sensitivity of 65% for the overnight test, at 100% specificity, was nearly identical to that of the standard test in the same patients: 67% for the combined criterion of > 70% stimulation of urine 17-hydroxysteroid or > 480-fold increase of plasma 11-deoxycortisol. When the criteria for both the overnight and standard tests were combined, the sensitivity increased to 84%, which was higher than that obtained using the criteria for either test alone (P < 0.02). CONCLUSION: The single-dose overnight metyrapone test, which can be performed in 24 hours and which avoids the disadvantages associated with timed urine collections, has a nearly identical sensitivity (for a specificity of 100%) as the 6-dose standard metyrapone test for the diagnosis of Cushing's disease. Furthermore, the diagnostic performance of a criterion that combines the results of both tests is significantly better than the best criterion for either test alone.

ACTH Syndrome, Ectopic↗

PubMed1996

Factitious Cushing syndrome.

There have been few reports of factitious Cushing syndrome. To characterize the clinical and laboratory features leading to this unusual diagnosis, we describe 6 patients (5 women, 1 man), ages 31-44, identified retrospectively among 860 patients evaluated for hypercortisolism at the National Institutes of Health Clinical Center. All six patients had multiple surgeries unrelated to Cushing syndrome and a history of depression or anxiety. Four patients had close contact with the medical profession, three a history of drug abuse, and three had undergone previous treatment for Cushing syndrome. The physical features of Cushing syndrome were variable and not helpful in the differential diagnosis with endogenous Cushing syndrome. Four patients had striking variability in urine-free cortisol (UFC) and 17-hydroxysteroid (17-OHCS) values from low to high. Adrenal computed tomography, performed in two patients, showed small adrenal glands (n = 1) or a left-sided mass (n = 1), and adrenal magnetic resonance imaging, performed in one patient, showed atrophic glands. Pituitary magnetic resonance imaging, carried out in four patients, was either normal (n = 1) or exhibited questionable signs of microadenoma (n = 3). Determination of synthetic glucocorticoids by high pressure liquid chromatography (HPLC) was positive in the four patients in whom it was performed. Factitious Cushing syndrome is a difficult diagnosis. To conserve time and resources, high pressure liquid chromatography analysis of urine steroids, the most definitive test for the factitious disorder, should be performed whenever there is clinical suspicion of glucocorticoid abuse.

Adrenal Glands↗

PubMed1996

Inferior petrosal sinus arginine vasopressin concentrations in normal volunteers and patients with Cushing's disease.

In patients with Cushing's disease (CD), basal inferior petrosal sinus arginine vasopressin (AVP) concentrations are greater than peripheral levels and are further increased by the administration of CRH. AVP has an interpetrosal sinus gradient similar to that for ACTH, leading to the hypotheses that petrosal sinus AVP might either be derived from the corticotroph adenoma or be important for adenoma formation. To determine whether petrosal sinus AVP is truly increased in patients with CD, we compared inferior petrosal sinus and peripheral venous AVP and ACTH levels in 23 patients with CD and 9 healthy volunteers before and after iv ovine CRH. In both groups, AVP and ACTH showed interpetrosal lateralization, such that greater levels of both hormones were found at each time point in a single dominant petrosal sinus. When both hormones exhibited lateralization (an intersinus gradient > 1.5), ACTH and AVP always lateralized together. In patients with CD, the ACTH interpetrosal sinus lateralization correctly identified the side of the pituitary containing the tumor in 75% of evaluable patients, whereas the AVP interpetrosal sinus lateralization identified 63% (P = NS). Ovine CRH stimulated AVP in both the dominant and nondominant petrosal sinuses in patients with CD. Although basal AVP in the dominant petrosal sinus was not significantly different in patients with CD and normal volunteers (144 +/- 85 vs. 13.0 +/- 4.3 pmol/L; P = 0.058), dominant petrosal sinus AVP was significantly elevated in patients with CD compared to normal volunteers at 3 min (269 +/- 122 vs. 45.1 +/- 30.0 pmol/L; P < 0.05) and 5 min (315 +/- 120 vs 40.2 +/- 23.6 pmol/L; P < 0.05) after ovine CRH administration. Peripheral venous AVP levels were similar in all groups. We conclude that lateralization of AVP secretion occurs in both patients with CD and normal volunteers, but there is greater CRH-stimulated AVP secretion in the inferior petrosal sinuses of patients with CD.

Adrenocorticotropic Hormone↗

PubMed1996

A prospective controlled study of luteal and endometrial abnormalities in an infertile population.

OBJECTIVE: To investigate whether luteal and endometrial abnormalities occur more frequently in an infertile population and thus contribute to infertility. DESIGN: Prospective controlled clinical study. SETTING: Outpatient clinic in an academic research institution. PARTICIPANTS: Thirty-three fertile controls and 31 infertile women without ovulatory disorders, tubal disease, or male factors. INTERVENTIONS: All women underwent an endometrial biopsy 9 days after the LH surge followed by an IM injection of 5,000 IU hCG. Blood samples were drawn immediately before hCG administration for serum P and placental protein 14 (PP14) measurements, at 6 hours after hCG stimulation for serum P concentrations, and on day 5 after hCG administration for serum PP14 levels. MAIN OUTCOME MEASURES: Histologic dating of the endometrium and serum P and PP14 measurements. RESULTS: Abnormal endometrial biopsies occurred more frequently in infertile (43%) than in fertile women (9%). Except for one case, these specimens were not associated with low hCG-stimulated P levels. Serum PP14 measurements varied widely and did not discriminate subjects with abnormal endometrial development. CONCLUSIONS: Disruption of endometrial maturation without a concomitant defect of the corpus luteum occurs more frequently in an infertile population and thus may contribute to infertility.

Adult↗

PubMed1995

Growth hormone receptor messenger ribonucleic acid expression in leiomyoma and surrounding myometrium.

OBJECTIVE: Uterine leiomyomas are the most common pelvic tumors, occurring in one of four women, and they represent the single most common indication for hysterectomy. The genesis and growth-promoting factors responsible for their development are poorly understood. We speculate that growth hormone may play a role in the initiation of these tumors; women with acromegaly have a higher incidence of leiomyomas and growth hormone promotes uterine growth in rats, with or without the addition of estradiol. We evaluated the presence of growth hormone receptor messenger ribonucleic acid in the human uterus and leiomyomas to investigate whether growth hormone might act directly rather than by hepatic generation of insulin-like growth factor-I. STUDY DESIGN: Paired samples of leiomyomas and adjacent normal myometrium from nine premenopausal women (32 to 52 years old) were collected at surgery. Three patients received a gonadotropin-releasing hormone agonist for 3 months before the surgical procedure; six did not receive any adjuvant therapy. We used a digoxigenin-labeled oligoprobe sharing no homology to the growth hormone-binding protein or to the prolactin receptor, to investigate whether growth hormone receptor messenger ribonucleic acid was present in tissue sections or amplified complementary deoxyribonucleic acid from leiomyoma and the surrounding myometrium. RESULTS: The ratios of growth hormone receptor/reduced glyceraldehyde-phosphate dehydrogenase in leiomyomas and the surrounding myometrium as assessed by densitometry analysis of polymerase chain reaction products were similar and were not altered by gonadotropin-releasing hormone agonist treatment. In situ hybridization localized the growth hormone receptor messenger ribonucleic acid to the nuclei and cytoplasm of leiomyoma and myometrium. CONCLUSION: The presence of growth hormone receptor messenger ribonucleic acid suggests that the human uterus is a target tissue for growth hormone action. Future investigations are needed to investigate further the role of growth hormone in the development of leiomyomas.

Adult↗

PubMed1995

Role of preoperative iodocholesterol scintiscanning in patients undergoing adrenalectomy for Cushing's syndrome.

BACKGROUND: Iodocholesterol scintiscanning (IS) is a noninvasive, functional diagnostic test. We report our experience with IS as an adjunct for adrenal surgery for Cushing's syndrome. METHODS: Between April 1983 and October 1994, 23 patients with Cushing's syndrome from benign primary adrenal disease underwent IS and computed tomography (CT) and/or magnetic resonance imaging (MRI). Twelve patients had unilateral adrenal involvement with a solitary adenoma (n = 11) or unilateral multinodular disease (n = 1), and 11 patients had bilateral adrenal disease. RESULTS: In patients with Cushing's syndrome caused by unilateral adrenal disease, IS was 100% specific and 100% sensitive, whereas in two cases CT/MRI incorrectly showed bilateral disease. In patients with Cushing's syndrome with bilateral adrenal involvement, IS had one false-negative result with nonvisualization. CT/MRI showed unilateral disease in four cases and no abnormalities in two. All patients in this series were cured of Cushing's syndrome after unilateral adrenalectomy in 11 cases and bilateral adrenalectomy in 12 cases. CONCLUSIONS: IS is a highly sensitive and specific imaging modality and is an essential adjunct to biochemical testing in planning adrenal resections for Cushing's syndrome caused by primary adrenal disease.

Adenoma↗

PubMed1995

Adrenocorticotropic hormone-secreting pheochromocytomas: the exception to the rule.

BACKGROUND: Operative management of pheochromocytomas dictates resection of the involved adrenal and exploration-resection of the contralateral gland if enlarged. We describe an exception to this rule. METHODS: We report the largest series of patients with adrenocorticotropic hormone (ACTH)-secreting pheochromocytomas and review the world literature. RESULTS: Four patients presented with findings of adrenocorticoid and catecholamine excess, as well as elevated levels of plasma ACTH, urinary metanephrines, and urinary free cortisol. Abdominal computed tomography scans revealed bilateral adrenal hyperplasia, and magnetic resonance imaging scans showed a unilateral adrenal mass with a bright T2 signal suggesting a pheochromocytoma. Two patients underwent adrenal venous sampling localizing ACTH secretion to the pheochromocytoma. All underwent unilateral adrenalectomy for a benign tumor without morbidity or death, leaving the contralateral hyperplastic adrenal in situ. After operation all patients experienced normalization of their levels of plasma ACTH, urinary metanephrines, and urinary free cortisol with resolution of symptoms. Combining our series with previously reported cases of ACTH-secreting pheochromocytomas, almost all are benign (20 of 21), in contrast to most ACTH-secreting tumors. CONCLUSIONS: ACTH-secreting pheochromocytomas are the exception to the rule; unilateral adrenalectomy is curative and the contralateral hyperplastic adrenal can be preserved. This approach results in resolution of both syndromes of hormone excess and preserves long-term adrenal function.

17-Hydroxycorticosteroids↗