Three Consecutive Pregnancies in a Patient with Chronic Autoimmune Thyroid Disease Associated with Hypothyroidism and Extremely High Levels of Anti-Thyrotropin Receptor Antibodies.

Background: Thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAb) can be present in chronic autoimmune thyroiditis. Transplacental TRAb transfer can lead to fetal thyroid dysfunction and serious complications. Patient Findings: We report the case of a woman with autoimmune hypothyroidism and extremely high TRAb levels, with blocking and stimulating activities (biological activities characterized with Chinese hamster ovary cells expressing TSHR). At week 22 of her first pregnancy, sonography detected fetal growth retardation and cardiac abnormalities (extreme tachycardia, right ventricular dilatation, pericardial effusion). The mother's TRAb level, assayed later, was 4030 IU/L (n < 10). Delivered via caesarean section gestational week 30, the newborn girl had several malformations, signs of malnutrition, goiter and hyperthyroidism associated with elevated TRAb (1200 IU/L). The newborn died 26 days after delivery. Faced with persistently high TRAb levels and a desire to become pregnant again, the woman was treated with three consecutive 740-MBq activities of iodine-131, which resulted in a decrease in TRAb to 640 IU/L. The patient had two subsequent pregnancies 16 and 72 months after the radioiodine administration. During the close follow-ups, fetal development was normal, and initial TRAb levels during the two pregnancies were 680 and 260 IU/L, respectively, which initially decreased but then increased in late pregnancy. In both cases, labor was induced at 34 weeks. The newborns, mildly hyperthyroid at birth, required carbimazole treatment at days 5 and 2, respectively. The mild hyperthyroidism despite high TRAb levels was likely due to the concomitant presence of stimulating and blocking TRAb. The two girls, now aged 12 and 8 years, are in good health. The mother has no detectable thyroid gland tissue and is euthyroid on levothyroxine (175 µg/d). Her TRAb level gradually decreased to 136 IU/L. Summary and Conclusions: This remarkable case illustrates the severe consequences of untreated fetal hyperthyroidism and the need to assay and follow-up TRAb levels in women of reproductive age with autoimmune thyroiditis.

Clinical evaluation of the use of a multifunctional remotely controlled insulin pump: multicenter observational study.

Current insulin pumps now feature advanced functions for calculating insulin dosages, delivering insulin and analyzing data, however, the perceived usefulness of these functions in clinical settings has not been well studied. We assessed the use and patient perceptions of an insulin delivery system (Accu-Chek® Combo, Roche Diagnostics, Mannheim, Germany) that combines an insulin pump and a handheld multifunctional blood glucose meter with integrated remote control functions. This prospective, observational, multicenter study enrolled 74 type 1 diabetes patients within 13 weeks after starting use of the pump system. At 4 to 24 weeks, investigators collected usage data from the latest 14-day period. Seventy-two patients completed the evaluation, aged 39 ± 15 years, diabetes duration 16 ± 13 years, HbA1c 8.3 ± 1.6%. At follow-up, 62 (86.1%) patients used the remote control for ≥50% of all boluses, 20 (27.8%) used the bolus advisor for ≥50% of all boluses, and 42 (58.3%) viewed at least 1 of the e-logbook reports. More than 95% of users appraised the functions as easy-to-use and useful; median scores from VAS (0 = useless to 100 = indispensable) ranged from 72 to 85. A high percentage of study patients used the system's advanced features, especially the remote control feature for bolusing. Overall, patients assessed the functions as useful and easy to use. Results support the implementation of these smart capabilities in further insulin pump developments.

Treatment of pituitary adenomas by fractionated stereotactic radiotherapy: a prospective study of 110 patients.

PURPOSE: To optimize and reduce the toxicity of pituitary adenoma irradiation by assessing the feasibility and effectiveness of fractionated stereotactic radiotherapy (FSR). METHODS AND MATERIALS: Between 1990 and 1999, 110 consecutive patients, 47 with a functioning adenoma, were treated according to a strategy of either early surgery and FSR (n = 89) or FSR only (n = 21). Of the 110 patients, 75 had persistent macroscopic tumor and 47 persistent hormonal secretions; 15 were treated in the prophylactic setting. The linear accelerator-delivered dose was 50.4 Gy (5 x 1.8 Gy weekly), with a 2-mm safety margin. RESULTS: After a minimal follow-up of 48 months, only 1 patient had developed progression. Of the 110 patients, 27 (36%) had a complete tumor response, 67 (89.3%) had an objective tumor response, 20 (42%) had a hormonal complete response, and 47 (100%) had a hormonal objective tumor response. The proportion of patients without a complete tumor response, objective tumor response, complete hormonal response, and objective hormonal response was 85.1%, 62%, 83%, and 59.3% at 4 years and 49.3%, 9%, 59.3%, and 10.6% at 8 years, respectively. The sole unfavorable predictive factor was preoperative SSE >20 mm for tumor response (p = 0.01) and growth hormone adenoma for the hormonal response (p <0.001). No late complications, except for pituitary deficiency, were reported, with a probability of requiring hormonal replacement of 28.5% and 35% at 4 and 8 years, respectively. Nonfunctioning status was the sole unfavorable factor (p = 0.0016). CONCLUSIONS: Surgery plus FSR is safe and effective. FSR focused to the target volume seems more suitable than standard radiotherapy, and standard fractionation reduces the risk of optic neuropathy sometimes observed after single-dose radiosurgery. Therefore, FSR allows us to consider combined transrhinoseptal surgery and early radiotherapy, with a curative goal without patient selection.

Study of diurnal fluctuations of plasma methoxyamines in healthy volunteers.

OBJECTIVE: We studied the diurnal fluctuations of plasma concentrations of methoxyamines (metanephrine and normetanephrine) and of their parent amines (epinephrine and norepinephrine) in normotensive subjects. DESIGN: Serial blood sampling at 09.00 h, 11.00 h, 12.00 h, 14.00 h, 16.00 h, 18.00 h and 20.00 h in 28 healthy volunteers at rest. Determination of plasma concentrations of free catecholamines and total methoxyamines (free and sulpho-conjugates) was carried out by high-performance liquid chromatography with electrochemical detection. RESULTS: Mean (+/- SD) plasma concentrations of total metanephrine (MN) and normetanephrine (NMN) were 4.31 +/- 1.73 nmol/l (range: 0.96-9.3 nmol/l) and 8.13 +/- 2.54 nmol/l (range: 3.14-17.0 nmol/l), respectively. The NMN/MN ratio ranged between 0.8 and 7.8 (mean +/- SD 2.1 +/- 1.0). Mean plasma concentrations of free epinephrine and norepinephrine were 0.21 +/- 0.12 nmol/l (range: 0.06-1.39 nmol/l) and 1.61 +/- 0.62 nmol/l (range: 0.47-4.01 nmol/l), respectively. Despite marked intraindividual fluctuations, mean methoxyamine and catecholamine levels remained constant over the entire duration of the experiment. CONCLUSIONS: The absence of fluctuations of plasma levels of total methoxyamines suggests that their measurement could be carried out at any time within the diurnal time frame. Further investigations, however, remain necessary to validate these findings in patients with hypertension and/or pheochromocytoma, and to explain the ever important intraindividual variation in plasma concentrations of methoxyamines and of their parent compounds.