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Biomedical subjects

L Kahana

Publications and source records attributed to L Kahana.

At least 19 recordsLinked to original sources

Safety and efficacy after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium: results of a 1-year extension study.

Enteric-coated mycophenolate sodium (EC-MPS) is an enteric-coated formulation of mycophenolic acid. A 12-month, multicenter, double-blind, randomized clinical study demonstrated that converting maintenance renal transplant patients from mycophenolate mofetil (MMF) to EC-MPS is safe and does not affect efficacy. In an open-label study extension, 130 patients initially randomized to MMF were converted to EC-MPS (newly exposed); 130 initially randomized to EC-MPS continued on EC-MPS (EC-MPS long-term). A composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, or death occurred in 3 (2.3%) newly exposed and 2 (1.5%) EC-MPS long-term patients during the extension phase. One patient died and one lost his graft. BPAR occurred in 3 (2.3%) newly exposed patients and 1 (0.8%) EC-MPS long-term patient. During the first 12 months of the extension phase, incidence and type of adverse events was similar in both groups and comparable to that seen in the core study. Nine cases of malignancy were reported, mainly nonmelanoma skin cancers. EC-MPS dose adjustments for adverse events were required in <12% of patients. At the end of the 12-month extension, 58 (44.6%) and 64 (49.2%) newly exposed and EC-MPS long-term patients, respectively, had reported at least one gastrointestinal adverse event. Mean serum creatinine remained stable at the 12-month visit of the extension study (137 micromol/L in the newly exposed and 142 micromol/L in the EC-MPS long-term groups). The results of this study demonstrate the long-term safety of EC-MPS and reconfirm the safety of converting MMF maintenance renal transplant patients to EC-MPS.

Adult↗

Safety of inhaled corticosteroids delivered by plastic and metal spacers.

BACKGROUND: Because of its non-electrostatic properties the metal Nebuchamber (NC) valved holding chamber (VHC) delivers a greater mass of aerosol to the mouth than the polypropylene Aerochamber (AC) VHC. Delivery of more aerosol to the lungs may also increase systemic absorption of inhaled corticosteroids (ICS) and hypothalamo-pituitary-adrenal (HPA) suppression. METHODS: Thirty children (mean 4.3 (SD 0.3) years) received 200 micro g budesonide twice daily by NC or AC, both with the mask provided, in a randomised, two month crossover trial. Twenty four hour urinary free cortisol (UFC) was determined as a measure of HPA suppression. RESULTS: UFC decreased from 42.3 (7.8) nmol UFC/nmol creatinine control to 26.2 (2.4) (p = 0.06 v control) after AC, and to 24.5 (2.5) (p = 0.04 v control) after NC (p = 0.4 AC v NC). CONCLUSIONS: Despite a greater total dose delivered to the mouth, NC is not associated with greater HPA suppression when using 400 micro g/day budesonide under real life conditions in young children.

Anti-Inflammatory Agents↗

Chronic burnout, somatic arousal and elevated salivary cortisol levels.

Burnout syndrome, comprised of the symptoms of emotional exhaustion, physical fatigue, and cognitive weariness, is believed to be a result of ineffective coping with enduring stress. This study of 111 nonshift blue-collar workers free of cardiovascular disease (CVD) examined whether chronic burnout is associated with a state of somatic and physiological hyperarousal. Results showed that 37 workers exhibited symptoms of chronic burnout, with symptoms lasting at least 6 months. These workers, compared to those with no burnout symptoms (n = 52) or nonchronic burnout symptoms (n = 22), had higher levels of tension at work, postwork irritability, more sleep disturbances and complaints of waking up exhausted, and higher cortisol levels during the work day. These results suggest that chronic burnout is associated with heightened somatic arousal and elevated salivary cortisol levels. This may be part of the mechanism underlying the emerging association between burnout and risk of CVD.

Adaptation, Psychological↗

Atrial natriuretic peptide and endothelin concentrations in human milk during postpartum lactation.

Milk samples from lactating women (n = 24) were examined for atrial natriuretic peptide (ANP) and endothelin-1 (ET-1) content throughout the first 3 months postpartum. Samples were collected at the beginning (foremilk) and towards the end (hindmilk) of nursing. ANP was detected in the milk samples. A value of 9.4 +/- 1.8 pmol/l (mean +/- SEM) was observed on the third day postpartum. No significant variations in concentrations were observed during the 3 months examined. Foremilk and hindmilk ANP concentrations were also similar. ET-1, as previously reported, is present in the milk of lactating women. According to our observations, the concentration of ET-1 varies during the first 3 postpartum months. The highest concentrations were observed on the third day (10.2 +/- 1.8 pmol/l) of lactation, decreasing to 4.5 +/- 0.8 pmol/l after 1 week (p < 0.05) and to 2.0 +/- 0.3 pmol/l, at 1 month postpartum (p < 0.05), this level being maintained for up to 3 months postpartum. Foremilk samples on the third day postpartum contained significantly higher concentrations of ET-1, compared to hindmilk samples (10.2 +/- 1.8 vs 7.7 +/- 1.2 pmol/l, p < 0.05). The stable levels of ANP and the initial high and subsequently decreasing levels of ET-1 in human milk, during the first 3 months postpartum, suggest that these peptides might be of importance either in the lactating mammary gland or in the suckling newborn.

Atrial Natriuretic Factor↗

Effects of severe hemorrhage on plasma ANP and glomerular ANP receptors.

Atrial natriuretic peptide (ANP) plays an important role in blood volume and electrolyte homeostasis in normovolemia and in hypervolemic states. The currently available information on the effects of hypovolemia on plasma ANP is contradictory. Moreover, possible regulation of ANP receptors during severe hemorrhagic hypovolemia has not been investigated. This study evaluated the effects of severe hemorrhage on plasma ANP and on the regulation of glomerular ANP receptor subtypes in anesthetized rats. Constant rate bleeding of 50% of total blood volume within 2 h induced a reproducible shock state characterized by marked decreases in blood pressure, heart rate, and hematocrit and an increase in plasma renin activity and aldosterone. Hemorrhaged rats exhibited a gradual significant increase in plasma ANP from 39.3 +/- 2.9 to 114.7 +/- 20.0 pmol/l 1 h after the bleeding (P < 0.001 from the initial value and P < 0.02 from the final value of sham-shock rats). Hemorrhage induced a significant decrease in total glomerular ANP binding sites (172 +/- 25 vs. 363 +/- 39 fmol/mg protein in hemorrhaged and sham-shock rats, respectively, P < 0.05). This decrease was mainly due to a significant decrease in ANPC receptors (132 +/- 22 vs. 312 +/- 40 fmol/mg protein in hemorrhaged and sham-shock rats, respectively, P < 0.05). Hemorrhage did not change glomerular ANPA receptor density. No significant differences in the affinity of the glomerular receptor subtypes for ANP were detected. Our data indicate that plasma ANP increases after prolonged severe hemorrhage. It is suggested that downregulation of renal ANPC receptors leads to reduced clearance of ANP and contributes to elevation of its plasma level after severe hemorrhage.

Animals↗

OKT3 prophylaxis in renal grafts with prolonged cold ischemia times: association with improvement in long-term survival.

The data on patients participating in two randomized, prospective studies with similar immunosuppressive regimens were updated and combined to evaluate the long-term effects of OKT3 according to cold ischemia time (< or = or > 24 hr). Among 159 patients in the OKT3 and 153 in the cyclosporine A (CsA) group, 8 and 12 deaths occurred, respectively (P = NS). In patients with cold ischemia > 24 hours, OKT3 prophylaxis resulted in a lower mean number of rejection episodes per patient than did CsA prophylaxis within one year (mean +/- SEM: 0.87 +/- 0.11 vs. 1.35 +/- 0.14, respectively; P = 0.008) and within five years (1.07 +/- 0.12 vs. 1.49 +/- 0.15, respectively; P = 0.032). In contrast, rejection incidences in patients with cold ischemia < or = 24 hours was not significantly different in the two groups. In all study patients, there was a trend towards higher graft survival rates in the OKT3 group versus the CsA group (at 5 years, 73% vs. 66%, respectively; P = 0.182). Among recipients of kidneys with cold ischemia times > 24 hours, OKT3 patients had significantly higher graft survival than CsA patients at two years (84% vs. 64%, respectively) and at five years (71% vs. 56%, respectively; P = 0.045). Significant differences were not observed in recipients of kidneys with cold ischemia times < or = 24 hours. In conclusion, patients receiving renal grafts with long cold ischemia times strongly benefit from OKT3 prophylaxis.

Adult↗

Flow cytometry crossmatching and primary cadaver kidney graft outcome: relevance of T and B cell targets, historic sera and autologous controls.

There is limited information regarding the role of flow cytometry crossmatching (FCXM) in primary cadaver kidney allografting and even less about B cell reactivity and graft survival (GS). Furthermore, there is little or no published data concerning reaction strength (cutoff value), the effect of historic sera reactions, and the usefulness of performing autologous crossmatches (XMs) on GS. These factors were examined retrospectively on 214 primary transplants performed from August 1991 to January 1994 with follow-up to July 1995. Three-color FCXMs were done on a 1024-channel BD-FACScan, and the shift in median channel fluorescence (MCF) over the negative control was calculated. All patients had a negative T cell (AHG) and warm B cell (2 was, extended incubation) cytotoxicity XM, and none was excluded in calculating GS. A quantitative effect was noted as stronger MCF shifts vs. T or B cells correlated with decreased GS (r = 0.98 and 0.92, respectively). Significant differences were seen with cutoff values of T = 50 and B = 110 which were 1.7-1.8 times the SD above the mean MCF of normal sera controls T neg patients (n = 198) and 1- and 3-yr actuarial GS of 86% and 79% compared to T pos patients (n = 16) of 75% and 49%, p = 0.008. B neg patients (n = 177) had 1- and 3-yr GS od 86% and 81% compared to B pos patients (n = 37) of 78% and 47%, p = 0.005. Most informative was the analysis of combined T and B cell FCXM results. Three years GS for T neg - B neg patients (n = 171) was 81% and for T pos - B neg patients (n = 6), it was 83%, p = 0.98. The 27 T neg - B pos group's GS was lower at 62% but did reach significance. Poorest GS was seen for T pos - B pos patients (n = 10) at 23%, p = 0.0001. Reaction patterns showed that T cells detected only HLA Class I antibodies, whereas B cells detected both Class I and II. Historic sera (> or = 1 month old) reactivity influenced GS. Patients with > or = 2 past sera positive but current serum negative reactions vs. T or T plus B cells (n = 7) had a poor 29% GS, while those historically positive only vs. B cells (n = 7) had 100% GS. On the other hand, patients positive only with the current serum (n = 16) had 2-yr GS of 100% (false positive test?), while patients whose current and historic sera reactions were positive (n = 21) had a 25-50% GS (true positive test?). About 1 in 15 patients (19%) displayed positive autologous FCXM reactions. Subtraction of autologous MCF shift values from those vs. the donor converted 17 patients to the T neg - B neg or T pos - B neg group whose 2-yr actual GS was not significantly different (p > 0.8) from those initially testing T neg B neg vs. their donors.

Actuarial Analysis↗

Identification and quantification of human kidney atrial natriuretic peptide receptors.

The present study determined 125I-label atrial natriuretic peptide (ANP) binding sites in human kidney glomerular and papillary membranes. The membranes were prepared from non-malignant renal tissue obtained at nephrectomy of patients with renal carcinoma. To evaluate the proportion of ANP receptor classes ANP-R1 (ANPR-A, -B) versus ANP-R2 (ANPR-C), competitive binding studies were performed using [125I]-ANP in the presence of increasing concentrations of ANP or an internally ring-deleted analog, des(Gln116, Ser117, Gly118, Leu119, Gly120)ANP(102-121), called C-ANP, which binds selectively to ANPR-C receptors. Analysis of the competitive binding curve with ANP in glomerular membranes suggested the presence of one group of high-affinity receptors with dissociation constant Kd = 26 +/- 12 pmol/l and density Bmax = 101 +/- 47 nmol/kg protein. A decrease of 10-30% in Bmax with no change in Kd was obtained in the presence of excess (10(-6) mol/l) C-ANP, suggesting the existence of a small amount of a second class of receptors, the ANPR-C class. The densities of ANPR-A, -B versus ANPR-C receptors in human glomeruli, calculated from competitive inhibition experiments, were 75 +/- 42 and 22 +/- 16 nmol/kg protein (N = 8). Autoradiography of the sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions showed two bands: a highly labeled 130kD band and a weakly labeled 66 kD band, both displaced by ANP. Only the 66-kD band was displaced by the C-ANP analog. Human papilla membrane, as shown by competition binding studies and SDS gel electrophoresis, presented only one class of receptors with Kd = 40 +/- 23 pmol/l (mean +/- SD, N = 3) and Bmax = 17 +/- 6.3 nmol/kg protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The evaluation of candidates for renal transplantation. The current practice of U.S. transplant centers.

The criteria for acceptance of candidates for renal transplantation varies throughout the United States. The Patient Care and Education Committee of the American Society of Transplant Physicians conducted a survey of all U.S. centers that participate in the United Network for Organ Sharing (UNOS) concerning their evaluation of adult candidates for kidney transplantation. The response to each question was examined according to the specialty of the individual who filled out the questionnaire, as well as the type of transplant center (university or private) and the size of the center. The response rate to the survey was 81% (147/182). We found the following: (1) university-based and larger centers accepted more medically complicated patients; (2) 83% noted that attendance to dialysis was an important indicator of compliance after transplantation; (3) 79% did not require preoperative blood transfusions for cadaver kidney recipients; (4) 66% set no specific upper age limit for transplantation; (5) 56% excluded patients with chronic active hepatitis in the setting of hepatitis B antigenemia; (6) 50% had no specific policy for evaluating hepatitis C antibody-positive patients, while 54% excluded the use of hepatitis C antibody-positive donors, and (7) 15% obtained coronary angiography on all diabetic patients. U.S. transplant centers have a heterogeneous approach to the evaluation of patients for renal transplantation, particularly in the areas of viral hepatitis, cardiovascular disease, and noncompliance. University-based centers and centers that perform a larger number of transplants accept more medically complicated patients.

Adult↗

Native gonadotropin-releasing hormone for triggering follicular maturation in polycystic ovary syndrome patients undergoing human menopausal gonadotropin ovulation induction.

OBJECTIVE: To evaluate the role of GnRH administration instead of hCG for triggering follicular maturation in patients with polycystic ovaries (PCO) undergoing hMG ovulation induction when the late follicular 17-beta-E2 levels are > 1,600 pg/mL (> 6,000 pmol/L). DESIGN: Prospective study. SETTING: Infertility outpatient clinic of Rambam Medical Center (general hospital), Haifa, Israel. PATIENTS AND INTERVENTIONS: High serum E2 concentrations from 1,600 to > 3,600 pg/mL (2,800 +/- 68, mean +/- SD [6,000 to > 13,000 pmol/L, 10,279 +/- 2,500]) were experienced in 44 hMG cycles. The number of preovulatory follicles visualized by transvaginal sonography was between 8 and 25. An IV injection of 200 micrograms GnRH was administered for triggering final follicular maturation and ovulation, instead of 10,000 IU IM hCG, usually injected for this purpose, when the E2 levels are < or = 1,600 pg/mL (6,000 pmol/L). Serum E2 and P levels were monitored in the luteal phase. In cycles where E2 decreased to < or = 1,360 pg/mL (5,000 pmol/L), 2,500 IU hCG was administered once or twice at 3-day intervals for luteal support. MAIN OUTCOME MEASURES: Pregnancy and abortion rates and the rate of ovarian hyperstimulation syndrome (OHSS). RESULTS: Ten pregnancies were generated by the hMG and GnRH co-treatment in 32 patients (31.2%), in 44 cycles (23%). Two pregnancies aborted (20%), and eight generated eight healthy neonates. Ovarian hyperstimulation syndrome occurred in two cycles of patients who were both pregnant. All but two of these PCO patients also have undergone 69 hMG and hCG cycles. Only 7 patients conceived (23%) 10 times (10/69, 14.5%); 5 of these pregnancies (50%) were multiple gestations (3 twins, 1 sextuplet, and 1 heptuplet gestation). The pregnancy wastage rate was 30% (3/10). CONCLUSION: The use of native GnRH to trigger ovulation in PCO patients with late follicular E2 levels > 1,600 pg/mL (6,000 pmol/L) appears to be comparable with prior hMG and hCG cycles in terms of pregnancy rate, pregnancy wastage, risk of multiple gestation, and incidence of severe ovarian hyperstimulation. Unlike hMG and GnRH-agonist, which is associated with luteal phase dysfunction, hMG and GnRH offers a preferable alternative due to the ability of hCG luteal support and rescue, providing the E2 levels are not dangerously increased.

Estradiol↗

Haemodynamic and neurohumoral effects of flosequinan in severe heart failure: similarities and differences compared with intravenous nitroglycerin therapy.

The acute haemodynamic and neurohumoral effects of flosequinan, a new direct-acting vasodilator, were studied in 12 patients with severe (eight in New York Heart Association grade 3, four in grade 4) cardiac failure. Flosequinan was administered in a single oral dose of 100 mg, with haemodynamic monitoring over a 22 h period. The effects were compared with those observed during high dose intravenous nitroglycerin therapy (276 +/- 100 micrograms.min-1), given to the same patients for an identical period on the previous day. Both flosequinan and nitroglycerin produced significant haemodynamic improvement during the 22 h monitoring period. Cardiac and stroke indices increased with both drugs. However, while systemic and pulmonary vascular resistance were reduced similarly by both drugs, the decrease in right atrial and pulmonary capillary wedge pressures was greater with nitroglycerin and less with flosequinan, indicating a greater venodilator effect for nitroglycerin and a more balanced arterial and venodilator effect for flosequinan. Systemic arterial pressure and heart rate tended to increase with flosequinan and to decrease with nitroglycerin. In contrast to nitroglycerin, flosequinan did not increase plasma renin activity and serum aldosterone levels. Atrial natriuretic peptide decreased appropriately after both drugs, in keeping with the decreases in left and right heart filling pressures. The favourable haemodynamic and neurohumoral profiles of flosequinan suggest that it may be a useful vasodilating drug in the management of patients with severe heart failure.

Administration, Oral↗

A randomized clinical trial of induction therapy with OKT3 in kidney transplantation.

A randomized, prospective multicenter trial was conducted to compare the safety and efficacy of OKT3 as an induction therapy with that of conventional immunosuppressive therapy administered to cadaveric renal allograft recipients. Two hundred fifteen patients were treated either with OKT3 plus azathioprine and steroids for 14 days with the delayed addition of cyclosporine on day 11, or with conventional immunosuppression (steroids, azathioprine, and cyclosporine). OKT3 patients had significantly fewer rejection episodes (51% vs. 66%, P = 0.032), a longer time to initial rejection (46 days vs. 8 days, P = 0.001), and fewer rejection episodes per patient (0.82 vs. 1.14, P = 0.014) than conventionally treated patients. Kaplan-Meier estimates of two-year graft and patient survival rates were 84% and 95%, respectively, for the OKT3-treated group, and 75% and 94%, respectively, for the conventionally treated group. Following a subsequent first rejection episode, OKT3 reversed 93% of the rejections in patients receiving OKT3 induction therapy and 94% in patients receiving conventional therapy. Adverse experiences reported during OKT3 induction therapy were similar to those seen when the drug was used for rejection. Following initial exposure, 40.3% of the patients tested were positive for anti-OKT3 antibody, only 6.7% of which were of high titer (1:1000). In the presence of low titer (1:100 or less) antibody, OKT3 was successful in reversing rejection in five of six retreated patients tested. In conclusion, treatment with OKT3 (in combination with azathioprine, steroids, and the delayed addition of cyclosporine) is an effective approach for renal allograft maintenance.

Adolescent↗

Regulation of renal glomerular and papillary ANP receptors in rats with experimental heart failure.

Rats with aortocaval (A-V) fistula, an experimental model of congestive heart failure (CHF), display high circulating atrial natriuretic peptide (ANP) levels and a markedly blunted natriuretic response to ANP infusion. The present study was designed to evaluate whether alterations in renal ANP receptors may contribute to renal hyporesponsiveness to ANP in experimental CHF. Densities (Bmax) and dissociation constants (Kd) of both the biologically active (ANPA) and clearance receptors (ANPC) were evaluated in glomerular and papillary membranes from A-V fistula rats (n = 18) and sham-operated controls (n = 20). ANPA and ANPC receptor subtypes were assayed by displacement of 125I-ANP-(99-126) bound to glomerular or papillary membranes by increasing concentrations of unlabeled ANP-(99-126) or des-(18-22)-ANP-(4-23), an analogue which binds only to ANPC. Seven days after the operation, rats with A-V fistula displayed avid sodium retention, elevated plasma renin activity, and approximately a 10-fold increase in plasma ANP levels. Bmax of total ANP binding sites was significantly decreased in rats with A-V fistula compared with controls (220 +/- 61 vs. 399 +/- 88 fmol/mg protein, P < 0.05). The decrease was mainly due to a reduction in ANPA receptor density (51 +/- 10 vs. 110 +/- 15 fmol/mg protein, P < 0.05) with no change in receptor affinity. Likewise, a significant reduction in the density of ANPA (23 +/- 5 vs. 64 +/- 10 fmol/mg protein, P < 0.05) with no change in receptor affinity was observed in papillary membranes of rats with A-V fistula.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Atrial natriuretic peptide in severe heart failure: response to controlled changes in atrial pressures during intravenous nitroglycerin therapy.

Atrial natriuretic peptide (ANP) levels were measured in 17 patients with severe congestive heart failure (New York Heart Association functional class IV), and the response of the peptide was studied during changes in cardiac filling pressures induced by a 24-hour infusion of nitroglycerin. In the control state plasma ANP levels (687 +/- 551 pg/ml) were 10-fold normal. During the administration of nitroglycerin, natriuretic peptide levels decreased (p less than 0.005) with changes matching very closely the decreases in pulmonary arterial wedge and right atrial pressures, a 1% mean decrease in the peptide level for every 1.5 to 2% mean change in atrial filling pressures. In patients with hemodynamic tolerance to constant-dose nitroglycerin infusion, the resulting increase in atrial pressures was accompanied by an appropriate secondary increase in the plasma ANP level. During the 24-hour study period there was a direct linear relationship between both wedge (r = 0.93, p = 0.007) and right atrial (r = 0.93, p = 0.008) pressures and the plasma ANP level, with a zero-pressure ANP intercept near normal (69 pg/ml for wedge, 174 pg/ml for right atrial pressure). The findings were no different in a subgroup of five patients receiving simultaneous treatment with captopril, except that plasma renin activity was higher and the aldosterone level lower than in the control group by a factor of approximately 2.5. The close relationship and tracking of atrial pressure and natriuretic peptide curves suggested that the sensitivity of the atrial stretch response to changes in atrial filling pressures was maintained in severe congestive heart failure.

Aged↗

Relative performance of specific and nonspecific fluorescence polarization immunoassay for cyclosporine in transplant patients.

The analytical performance of specific and nonspecific fluorescence polarization immunoassays (FPIAs, Abbott Laboratories) for cyclosporine was compared. Both specific and nonspecific FPIAs demonstrated excellent between-run coefficients of variation (5.9% vs. 3.9%) at three levels of control, and a high degree of between-center reproducibility (r2 greater than 0.96). In addition, the correlation between cyclosporine levels measured by specific and nonspecific FPIAs was statistically significant, though imperfect, in both renal (r2 = 0.70) and cardiac transplant patients (r2 = 0.55). In kidney transplant patients, the nonspecific/specific ratio was significantly higher in patients with serum bilirubin concentration exceeding 3 mg/dl (5.9 +/- 2.6 vs. 2.8 +/- 1.1), due to impaired elimination of cyclosporine metabolites in the bile. The nonspecific/specific ratio was also significantly higher in heart transplant patients early (less than 1 month) posttransplant compared with patients in the late posttransplant period (3.4 +/- 0.8 vs. 2.9 +/- 0.8). The Abbott FPIA provides a highly precise method for measuring cyclosporine, with a turnaround time of 15-20 min. The specific monoclonal FPIA has the additional advantage of measuring primarily unchanged cyclosporine and thus has an imperfect correlation with the nonspecific polyclonal FPIA. Together with clinical data, the use of FPIAs may help to improve the efficiency of cyclosporine therapeutic drug monitoring.

Adolescent↗

Changes in stimulating and blocking TSH receptor antibodies in a patient undergoing three cycles of transition from hypo to hyper-thyroidism and back to hypothyroidism.

We report a patient who underwent, over a mere 3-year period, three successive cycles of oscillation from hypo to hyper-thyroidism and back to hypothyroidism. This unusual sequence of events originated in a rare passage of primary hypothyroidism to hyper-thyroidism. The hyperthyroidism seemed typical of the autoimmune subgroup of toxic multinodular goitre. Stimulating and blocking TSH receptor antibody activities were measured (by cAMP functional bioassays using cultured human thyrocytes) during the course of the fluctuating phases of hypo and hyper-thyroidism. Measurement of such antibody activities revealed the coexistence of both stimulatory and blocking types of antibody in several serum samples from the patient. Throughout the whole course of alterations in thyroid function, thyroid stimulating antibodies were present. This was not the case with thyrotrophin receptor antibodies exhibiting TSH antagonist activity which seemed to appear and disappear. Monitoring such activity indicated that the emergence of blocking antibody seems to herald the onset of hypothyroidism.

Autoantibodies↗