Neural regulation of pituitary function can serve as a basis for understanding endocrine and reproduction dysfunction in epilepsy. Because the pituitary gland is the final common pathway for central neural modulation of the endocrine system, hypothalamic control of pituitary function is important. The syndrome of functional hypothalamic amenorrhea is an example of stress-induced alteration in endocrine function and may serve as a model to suggest the impact of limbic system activation on reproduction and the endocrine milieu.

Adult↗

PubMed1991

Prevalence of simple adnexal cysts in postmenopausal women.

This prospective study was performed with ultrasound (US) to determine the prevalence of unilocular, nonseptated adnexal cysts ("simple cysts") in healthy postmenopausal women and the relationship between cyst occurrence and both hormone replacement and length of time since onset of menopause. Transabdominal and transvaginal US were performed on 149 volunteers aged 50 years or older. Patients were classified according to hormone regimens (no hormones, unopposed estrogen, continuous daily estrogen and progesterone, and sequential estrogen and progesterone) and time since onset of menopause (less than 5 years, 5-10 years, and greater than 10 years). Simple adnexal cysts were found in 22 women with the aid of transvaginal and/or transabdominal US, yielding a relative frequency of 14.8% +/- 5.7% and a prevalence of 14,800 patients with cysts per 100,000 patients. No statistical relationship was found between cyst frequency and type of hormone replacement or length of time since onset of menopause.

Aged↗

PubMed1991

Endometrial thickness after menopause: effect of hormone replacement.

Ultrasound (US) images of the pelvis were evaluated in 112 asymptomatic postmenopausal women to investigate the normal range of endometrial thickness (double-layer measurement) and the effect of hormone replacement on these measurements. Twenty-one patients (19%) had endometrial thickness greater than 0.8 cm. One patient, with an endometrial thickness of 2.5 cm, had endometrial carcinoma. Consideration of the known actions of estrogen and progestogen on the endometrium led the authors to believe that the clinical significance of an endometrium measuring more than 0.8 cm depends on the patient's hormonal status. Among asymptomatic postmenopausal women with an endometrial thickness between 0.8 and 1.5 cm, those receiving unopposed estrogen or continuous estrogen and progestogen need to undergo dilatation and curettage (D&C) or biopsy and those receiving no hormones or receiving sequential estrogen and progestogen should be encouraged to undergo D&C or biopsy. If a patient in one of the latter two groups is unwilling to undergo an invasive procedure, then US examination at 3-month intervals is acceptable. Any patient with endometrial thickness of at least 1.5 cm should undergo histologic diagnosis, regardless of symptoms or hormone status.

Biopsy↗

PubMed1991

Sublingual administration of testosterone-hydroxypropyl-beta-cyclodextrin inclusion complex simulates episodic androgen release in hypogonadal men.

In search of a more physiological testosterone (T) replacement therapy for hypogonadal states, we evaluated an inclusion complex of T with 2-hydroxypropyl-beta-cyclodextrin (HPBCD). HPBCD enhances T solubility and absorption, but HPBCD is not absorbed. Five hypogonadal men (mean age, 32.4 +/- 2.3 yr) with serum T levels below the normal range were treated in two separate experimental phases with either a 2.5- or 5.0-mg tablet of sublingual (SL) T-HPBCD three times daily for 7 days. Acute pharmacodynamic changes were monitored at baseline and 10, 20, and 40 min and 1, 1.5, 2, 3, 4, and 8 h after administration of the first dose. At the 5-mg dose, a maximal concentration (Cmax) of T (85.4 +/- 11.0 nmol/L) was achieved in 20 min (63 +/- 24-fold increase), followed by a rapid decline to below the normal range (less than 12 nmol/L) at 2 h, with an estimated half-life of decline of 1.87 +/- 0.19 h. The dihydrotestosterone (DHT) Cmax (4.1 +/- 0.5 nmol/L) occurred at 32 +/- 5 min (8.9 +/- 1.3-fold increase) and declined to below the normal range (less than 1.2 nmol/L) after 3 h. The integrated 8 h value for the ratio of T/DHT was 10.0 +/- 1.1, which fell within the normal range. The increment in androstenedione paralleled that in T, and the Cmax (6.8 +/- 0.9 nmol/L) was reached in 24 +/- 4 min (2.3 +/- 0.6-fold increase). Compared to baseline, the Cmax was significantly greater for T (P less than 0.005), DHT (P less than 0.0005), and androstenedione (P less than 0.005). Both estradiol (E2) and estrone (E1) remained in the normal range (less than 200 pmol/L), although the Cmax for E1 was significantly greater than baseline (P less than 0.05). Serum LH levels were suppressed (19.0 +/- 2.6%) at 2 h (P less than 0.05), without a significant change in FSH. During 7 days of treatment, there was no cumulative increase in basal T, DHT, and E2 levels or further decline in LH or FSH levels. There was no change in sex hormone-binding globulin levels. Similar results were observed with the 2.5-mg dose, suggesting that the capacity of SL absorption may be limited to a certain dose of T-HPBCD. The fluctuations in T after SL administration of T-HPBCD resemble endogenous episodic secretion. We conclude that T, complexed with HPBCD, is rapidly absorbed by the SL route and quickly metabolized without sustained elevations of DHT or E2.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1990

Dopamine and nonmodulating hypertension.

Sodium loading reduces aldosterone responses to angiotensin II (AII) when compared to the sodium restricted state. Recent investigations suggest that dopamine inhibits the aldosterone secretion and may contribute to the alteration in aldosterone response to AII with sodium intake, since administration of the dopamine antagonist, metoclopramide, enhances the aldosterone responses to AII on a high but not a low salt diet. Nonmodulating hypertension is characterized, in part, by a decreased aldosterone response to AII, raising the possibility that an increased dopaminergic inhibition of aldosterone secretion underlies the adrenal defect in nonmodulating hypertension. To assess this possibility, 69 patients with hypertension were characterized in relationship to their modulation status on a low sodium intake. Dopamine levels were significantly higher (P less than .05) in nonmodulators. To assess the physiologic relevance of these findings, the aldosterone response to AII infusion was assessed before and during administration of the dopamine antagonist, metoclopramide, in 13 patients. The adrenal response to AII did not change after metoclopramide in either hypertensive subgroup. Thus, it is unlikely that the adrenal defect is due to the increase in dopamine levels observed in nonmodulators. In the next study, the impact of dietary sodium intake on urinary dopamine levels was compared in normotensive and hypertensive subjects characterized as modulators and nonmodulators. Both modulators and normotensive subjects demonstrated an increase in urinary dopamine excretion in response to a high sodium intake--a feature that was not observed in the nonmodulators. Thus, the sodium retaining tendency of nonmodulators may reflect, at least in part, a reduction in intrarenal dopamine production in response to a sodium load.

Adrenal Glands↗

PubMed1990

Neuroendocrine sources of chromogranin-A in normal man: clues from selective stimulation of endocrine glands.

Chromogranin-A (CgA), as measured in the circulation by RIA, has emerged as a useful probe of exocytotic sympathoadrenal activity in man as well as of the presence and extent of neuroendocrine neoplasia. Here we studied, using a sensitive RIA, the distribution of CgA immunoreactivity in normal human neuroendocrine tissues. Furthermore, to investigate whether these normal tissue sources measurably contribute to plasma CgA, we measured plasma CgA, catecholamine, and other polypeptide hormone responses to selective stimuli of secretion at several sites within the neuroendocrine system. Immunoreactive CgA was ubiquitous in human neuroendocrine tissues, in rank order of concentration (micrograms per g wet wt): adrenal medulla greater than pituitary greater than pancreas greater than stomach greater than small intestine (jejunoileum) greater than brain (frontal cortex) greater than parathyroid greater than thyroid. Quantitatively, neuroendocrine tissues other than the adrenal medulla possessed only 0.04-25% of the immunoreactivity found in the adrenal medulla. Insulin-induced hypoglycemia, a potent stimulus of adrenomedullary secretion, resulted in 1.7- and 14-fold rises in plasma CgA and epinephrine, respectively. However, insulin-induced hypoglycemia failed to perturb plasma CgA in three bilaterally adrenalectomized patients, suggesting that the adrenal medulla is the source of plasma CgA elevation during hypoglycemia in normal subjects. Cell type-selective secretagogue stimulation of normal endocrine secretory cells other than the adrenal medulla (pituitary, pancreas, gut, thyroid, and parathyroid) induced measurable increments in the concentrations of the resident peptide hormones, but left plasma CgA unperturbed. Nonselective stimulation of a wide variety of endocrine secretory cells with pentagastrin elevated plasma CgA 1.4-fold. However, restriction of pentagastrin's targets by coinfusion of calcium abolished the effect on plasma CgA. Hence, within the normal human neuroendocrine system, only selective stimulation of the adrenal medulla is likely to elevate plasma CgA under physiological or pharmacological circumstances. This is consistent with our finding of the adrenal medulla as the quantitatively major normal neuroendocrine tissue source of CgA immunoreactivity.

Adrenal Medulla↗

PubMed1990

Effects of the antiprogesterone RU486 in the early follicular phase of the menstrual cycle.

To investigate the role of progesterone (P) in the early follicular phase, the antiprogesterone effect of RU486 was examined in five normally cycling women monitored by daily hormonal levels during three consecutive cycles (control, treatment, and recovery). In addition, luteinizing hormone (LH) pulse characteristics were assessed by frequent blood sampling (10 minutes for 10 hours) on day 3 of the control and the corresponding day of treatment cycles. Administration of RU486 (3 mg/kg, orally) for the first 3 days of the menstrual cycle did not significantly alter the length of the follicular phase (13.4 +/- 1.7 to 15.2 +/- 1.3 days), the LH surge, or the luteal phase length (12.2 +/- 0.5 to 12.6 +/- 0.7 days). The intermenstrual length of the treatment cycle (29.8 +/- 1.9 days) did not differ from the control (27.6 +/- 1.8 days) or recovery cycles (29.6 +/- 2.5 days). Integrated secretion of P and estradiol (E2) did not vary during the luteal phase of the control, treatment, or recovery cycles. During RU486 treatment, LH pulse frequency, pulse amplitude, and mean LH were not altered. Whereas mean E2 levels were significantly decreased from 150.5 +/- 15.1 to 110.1 +/- 7.0 pmol/L, follicle-stimulating hormone, P, adrenocorticotropin hormone, and cortisol were not significantly altered. Thus, in spite of the transient decrement in E2 secretion during RU486 treatment, the integrity of the ovulatory menstrual cycle was maintained. We conclude that administration of the antiprogesterone RU486 at the dose used during the first 3 days of the follicular phase does not perturb menstrual cyclicity.

Adrenocorticotropic Hormone↗

PubMed1989

Menopause and estrogen replacement therapy.

As America ages the menopausal woman is emerging as a principal focus in the health care system. Research efforts continue to define the mechanism for vasomotor instability, osteoporosis, and new and improved methods of estrogen administration. Though attenuation of symptoms of hot flushes, urogenital atrophy, and prevention of osteoporosis can be accomplished by judicious estrogen replacement therapy, the attendant risk of endometrial cancer can be minimized by concurrent administration of progestogen. Gallbladder disease must be considered as an additional risk. Surveillance for early detection of breast cancer is an integral part of care for the climacteric woman. Of greatest concern and potentially greatest impact is the evolution of data endorsing estrogen replacement as a preventive measure against cardiovascular disease. With the goal of maximizing the quality of the last third of each woman's life, individual assessment of signs and symptoms of the climacteric and, if indicated, prescription for a tailored hormone replacement schedule remain the mainstay of care.

Climacteric↗

PubMedDate not supplied

Diabetic ketoacidosis associated with pheochromocytoma.

A 29-year-old woman was found to have diabetic ketoacidosis associated with classic findings of pheochromocytoma, an association previously undescribed. The patient also had a significant insulin requirement that resolved after tumor excision. Pheochromocytoma with associated hyperglycemia and glycosuria has been reported since 1912, but ketoacidosis has been thought not to occur with pheochromocytoma. The findings in this case are described, and glucose metabolism in pheochromocytoma is reviewed.

Adrenal Gland Neoplasms↗