Effect of 131 iodine therapy on the course of Graves' ophthalmopathy: a quantitative analysis of extraocular muscle volumes using orbital magnetic resonance imaging.

There remains uncertainty as to the effect of radioactive iodine (131I) therapy on the associated ophthalmopathy (GO). Twenty newly diagnosed patients with Graves' hyperthyroidism treated with 131I (median dose, 15.5 mCi) were followed with ophthalmologic evaluations (OE) and magnetic resonance imaging (MRI) at baseline, 2, and 6 months, and with OE alone at 3 years. For MRI, the superior, inferior, and medial rectus muscle volumes and total muscle volumes (TMV) were measured. Replacement levothyroxine was initiated as low thyroxine (T4) levels were noted. At baseline, 10 patients (50%) showed evidence of mild GO by OE and/or MRI. There was a significant difference in TMV between the 20 patients with Graves' hyperthyroidism and 10 controls (mean +/- standard error [SE]; 2,652 +/- 118 vs. 2,046 +/- 96 mm3; P = 0.002) and between the 10 patients with and 10 without GO (3,006 +/- 96 vs. 2,298 +/- 61 mm3; P = 0.001). TMV correlated with the Hertel score (r = 0.56, P = 0.01). TMV showed no significant change at 2 or 6 months posttreatment. The inferior rectus volume increased slightly at 2 months posttreatment (P = 0.03) but remained stable at 6 months. Furthermore, no significant changes occurred in Hertel scores or in clinical assessments up to 3 years posttreatment and none showed worsening or new development of GO. In conclusion, our results show no significant risk for radioiodine-induced initiation or progression of mild GO.

Androgen excess disorders in women.

Edited by Ricardo Azziz, John E. Nestler and Didier Dewailly. Philadelphia, Lippencott-Raven, 1997, $152.00/ pound116.00 (xxv +831 pages), ISBN 0-397-51721-1.

Absence of serologic evidence for hepatitis C virus infection in patients with Hashimoto's thyroiditis.

BACKGROUND/AIMS: This paper explores the reported association between Hashimoto's thyroiditis and hepatitis C virus (HCV) infections. MATERIALS AND METHODS: The results of serologic testing for anti-HCV antibody levels were documented in 28 patients (19 female, 9 male) with Hashimoto's thyroiditis and 23 age and gender matched controls with non-Hashimoto's thyroid disorders. RESULTS: The anti-HCV results were negative in both groups. CONCLUSIONS: These findings suggest that despite a reported high prevalence of Hashimoto's thyroiditis in patients with chronic HCV infections, the reverse is not true and hence routine anti-HCV screening cannot be advocated for patients with Hashimoto's thyroiditis.

Noninvasive diagnosis of resistant ovary syndrome by ultrasonography.

OBJECTIVE: To compare transvaginal ultrasonographic features of the ovaries and endometrium of patients with premature ovarian failure to normally cycling women on oral contraceptives (OCs), menopausal women with an equivalent duration of amenorrhea to the premature ovarian failure group, and patients with Turner's syndrome. DESIGN: Transvaginal ultrasonography in groups of women with premature ovarian failure, OC, and menopause. SETTING: All subjects were studied in an academic tertiary care center. PATIENTS/PARTICIPANTS: Seventeen women with premature ovarian failure, 20 volunteers on OC, 20 with menopause, and 4 patients with Turner's syndrome were studied. INTERVENTION: None, except for OCs in the OC group only. MAIN OUTCOME MEASURES: Frequency of ovarian, ovarian follicle, and endometrial visualization and their respective measurement in the three groups. RESULTS: At least one ovary was visualized in 84% of the premature ovarian failure patients as compared with 95% of the OC and menopause groups and 25% of the Turner patients. Mean ovarian volume was smaller in the premature ovarian failure group as compared with the OC group but equal to that of the menopause group. In the premature ovarian failure group, 41% had follicles in their ovaries as compared with 95% in the OC group, 5% in the menopause group, and none in the Turner group. The number of follicles per ovary was significantly lower in the premature ovarian failure as compared with the OC group, whereas only one subject had a single follicle in the menopause group. Premature ovarian failure subjects with follicles had larger ovaries than those without follicles. Endometrial thickness was not different among the groups. CONCLUSION: Ultrasonography may serve to identify a substantial subset (approximately 40%) of premature ovarian failure patients with ovarian follicles and potential for fertility consistent with the diagnosis of resistant ovary syndrome.

Chronic hyperglycemia in experimental diabetes mellitus of short duration does not contribute to muscle capillary basement membrane thickening.

The effect of chronic hyperglycemia on the relationship of nonenzymatic glycation and capillary basement membrane thickness in muscle was studied in streptozotocin-induced diabetic rats early in the course of diabetes mellitus. Diabetic animals were placed on either standard (24%) or restricted (8%) protein diet. The animals on 8% protein diet had elevated glycated hemoglobin levels (p less than 0.01) and increased levels of nonenzymatic glycation of basement membrane (p less than 0.01) as compared to insulin-treated diabetic (euglycemic), age-matched control, and streptozotocin-injected nondiabetic animals also on 8% protein diet. In contrast, diabetic animals on restricted (8%) protein diet and those on standard (24%) protein diet showed no statistical differences between them with regards to the above parameters. Moreover, there were no statistical differences among diabetic and control animals on either 8 or 24% protein diet with respect to muscle capillary membrane thickness. Even though the peripheral muscle biopsy study of capillary basement membrane is less invasive than kidney biopsy, the results of this study suggest that neither nonenzymatic glycation nor basement membrane thickness can be utilized as predictors of renal dysfunction during early onset of diabetes mellitus.

Primary radiotherapy of prolactinomas. Eight- to 15-year follow-up.

Eight women with amenorrhea, galactorrhea, and hyperprolactinemia, of whom six had macroadenomas and two had microadenomas, were treated with conventional (cobalt-60) external radiotherapy, and their progress was monitored for eight to 15 years. Normoprolactinemia was established in five of these patients after two to 13 years (median, nine years). A recurrence was treated surgically in one patient, and stable prolactin values and roentgenographic features have been maintained in two patients. Hypopituitarism has developed in only one patient to date, and no other complications of radiotherapy have been observed. These findings, together with the few previous reports on the long-term effects of radiotherapy on macroprolactinomas, have been compared with the long-term results following surgery or dopamine agonist therapy. The normalization of prolactin values is considerably delayed following radiotherapy compared with the other two therapeutic modalities. However, radiotherapy affords permanent normalization without recurrence in a larger percentage of patients than does surgery and avoids the considerable ongoing cost and inconvenience of daily drug ingestion. The long-term development of hypopituitarism appears to be an acceptably small risk of radiotherapy. Thus, conventional radiotherapy is an attractive treatment option, particularly for macroprolactinomas; adjunctive bromocriptine can be used while awaiting the longer-term benefits of radiotherapy.

Failure to interrupt established pregnancy in humans by D-tryptophan-6-luteinizing hormone-releasing hormone.

Four women 5 to 8 weeks into pregnancy, scheduled for therapeutic abortions, were given an analog of gonadotropin-releasing hormone, D-tryptophan-6-LHRH, in an effort to interrupt pregnancy. The treatment consisted of 100-micrograms injections, given twice daily for 5 to 10 days. No decline in serum beta-hCG or progesterone was noted, and menstrual extraction was needed in all women for pregnancy interruption. These data indicate that D-Trp-6-LHRH is not effective as an abortifacient in established pregnancy.

PIP: Treatment with superactive luteinizing hormone-releasing hormone (LHRH) analogs (LHRH-A) for pregnancy termination was studied to determine its efficacy. 4 women, scheduled for abortion, whose last menstrual periods occurred 46-69 days before day of pregnancy diagnosis participated in the study. They were treated twice daily with 100 mcg of LHRH-A, by injection. Treatment lasted from 5-10 days. Blood samples were obtained before and during treatment and were assayed for levels of progesterone, prolactin, and beta-human chorionic gonadotropin subunit. Patient 1 was treated for 10 days, Patient 2 for 5 days, Patient 3 for 6 days, and Patient 4 for 9 days. None of the patients aborted. There were no clinical signs of pregnancy regression; nonoe of the women cramped, nor did they experience any side effects. In addition, there were no declines in the hormones measured; rather levels of progesterone and chorionic gonadotropin rose, as they would with increasing gestation. (e.g., Patient 1 was 50 days from last menstrual period. Her progesterone level before treatment was 19 ng/ml; her chorionic gonadotropin beta-subunit level before treatment was 398 mIU/ml. After treatment, the progesterone level rose to 41 and the gonadotropin level to 472. All women underwent menstrual extraction within 3 days of treatment termination. THere was no evidence that D-Trp-5-LHRH, at the dosage given, could interrupt pregnancy (as it had in rats). Larger doses would also probably be ineffective since the dose used was larger than that known to induce luteolysis.

Effects of hyperprolactinemia on calciotropic hormones.

Serum 1,25-dihydroxyvitamin D, parathyroid hormone, calcium, phosphorus and alkaline phosphatase levels as well as the renal handling of phosphorus were measured in female patients with hyperprolactinemia. Despite elevated prolactin levels, none of the patients showed an imbalance of the biochemical parameters of mineral homeostasis. Neither surgery nor bromocriptine treatment, both of which brought PRL within the normal limits, had an appreciable effect on the circulating concentrations of mineral and calciotropic hormones. These results do not allow us to assign a definite role to PRL in the control of mineral metabolism in man.

Pharmacology of bromocriptine in health and disease.

Bromocriptine, a lysergic acid derivative with a bromine atom at position 2, has been found to have unique effects on the dopamine receptors in the pituitary and central nervous system and peripherally. It is rapidly and completely absorbed from the gut and is mainly excreted in the bile and faeces. It seems to have a particular specificity for the pituitary prolactinotrophe although it does have other effects in different diseases states. In spite of the fact that it is an ergot derivative, it is remarkably free of ergot vascular side effects in the doses needed for therapeutic benefit. The most common adverse effect are nausea, vomiting and postural symptoms. These can be overcome by starting at low doses and increasing the therapeutic levels. Its major use is in the suppression of prolactin in states where this hormone is elevated irrespective of cause. It has also been used in the treatment of acromegaly and is under investigation for use in other disease states probably linked with prolactin system or dopaminergic receptors.