[Prevention of recurrent amiodarone-induced hyperthyroidism by iodine-131]. / Prévention des récidives d'hyperthyroïdie a l'amiodarone par l'iode131.

Amioradone-induced hyperthyroidism is a common complication of amiodarone therapy. Although definitive interruption of amiodarone is recommended because of the risks of aggravation of the arrhythmias, some patients may require the reintroduction of amiodarone several months after normalisation of thyroid function. The authors undertook a retrospective study of the effects of preventive treatment of recurrences of amiodarone-induced hyperthyroidism with I131. The indication of amiodarone therapy was recurrent, symptomatic, paroxysmal atrial fibrillation in 13 cases and ventricular tachycardia in 5 cases (M = 14, average age 64 +/- 13 years). The underlying cardiac disease was dilated cardiomyopathy (N = 5), ischaemic heart disease (N = 3), hypertensive heart disease (N = 2), arrhythmogenic right ventricular dysplasia (N = 2) or valvular heart disease (N = 2). Two patients had idiopathic atrial fibrillation. An average dose of 576 +/- 184 MBq of I131 was administered 34 +/- 37 months after an episode of amiodarone-induced hyperthyroidism. Amiodarone was reintroduced in 16 of the 18 patients after a treatment-free period of 98 +/- 262 days. Transient post-radioiodine hyperthyroidism was observed in 3 cases (17%). Sixteen patients (89%) developed hypothyroidism requiring replacement therapy with L-thyroxine. There were no recurrences of amiodarone-induced hyperthyroidism. After 24 +/- 17 months follow-up, the arrhythmias were controlled in 13 of the 16 patients (81%) who underwent the whole treatment sequence. The authors conclude that preventive treatment with I131 is an effective alternative to prevent recurrence of amiodarone-induced hyperthyroidism in patients requiring reintroduction of amiodarone to control their arrhythmias.

[Pilot study and preliminary validation of the French version of a quality-of-life questionnaire specific for subjects with growth hormone deficiency]. / Etude pilote et validation préliminaire de la version française d'un questionnaire de mesure de la qualité de vie spécifique des sujets atteints de déficit en hormone de croissance.

This study forms part of a research project seeking to develop a standardized questionnaire by which clinicians can assess the impact of growth hormone (GH) deficiency and its treatment on the "perceived health" or health-related quality of life of adults. The specific aim of this study was to translate and adapt for French patients the AGHDA (Adult Growth Hormone Deficiency Assessment) a standardized health-related quality of life measure for use with GH-deficient adults, initially developed in the United Kingdom, and to collect data which could be used to assess the main psychometric characteristics of its French version the ISPA-HC (Indicateur de Santé Perceptuelle Adulte-Hormone de Croissance). The main properties analyzed are: 1/ The scale's acceptability, as determined by means of face-to-face interviews with a small number of subjects, then by an ad hoc questionnaire administered during a test-retest study; 2/ The scale's reliability, as determined by a test-retest study (with a 15-days interval between tests); 3/ The scale's concurrent validity, as expressed by comparison with scores obtained by means of a generic quality of life scale, the ISPN (the French version of the Nottingham Health Profile). The results of this first trial with the ISPA-HC are conforming to what one can expect from a good instrument. The ISPA-HC has been shown to have very good levels of reliability and internal consistency. Its scores show a close correlation with those of the ISPN (the French version of the Nottingham Health Profile). This instrument can be used to measure variations in the perceived health of subjects with growth hormone deficiency. Its responsiveness to change is to be examined in subsequent studies.

A targeted approach significantly increases the identification rate of patients with undiagnosed haemochromatosis.

OBJECTIVE: To determine the optimal means of identifying patients with undiagnosed haemochromatosis. DESIGN: Case-control study where cases are defined by the presence of specific clinical diagnoses or symptoms. SETTING: Primary care patients were recruited from three Oxfordshire practices and secondary care patients were recruited from those patients attending specialist clinics in Amiens University Hospital. SUBJECTS: A total of 569 patients recruited via hospital clinics and 60 primary care patients (recruited from 4022 consultations) presenting with the following haemochromatosis associated conditions, diabetes, arthralgia/chronic fatigue, osteoporosis or arthropathy were studied. The control group, a total of 991 healthy volunteers, were recruited through a Health Appraisal Centre. Patients and controls were included in the study if they or their family members had not previously been diagnosed with hereditary haemochromatosis. MAIN OUTCOME MEASURES: Serum ferritin concentration, transferrin saturation (Tsat) and presence of HFE mutations, C282Y and H63D. The check-up in controls consisted of a questionnaire, clinical examination, biochemical tests and screening for the presence of the C282Y and H63D mutations. RESULTS: Patient groups presenting with unstable diabetes or chronic fatigue and arthralgia together with a raised serum ferritin concentration showed an enrichment in the haemochromatosis-associated genotype HH/YY, odds ratio (OR) = 40.1, confidence interval (CI) = 8.0-202.1 and OR = 103, CI = 22.9-469.7, respectively. CONCLUSION: Patients presenting to hospital clinics with haemochromatosis associated conditions should be screened biochemically for iron overload. Only those with a serum ferritin >300 microg L-1 or Tsat >40% should subsequently go on to be genotyped for HFE mutations. The patients at greatest risk of having undiagnosed haemochromatosis are those presenting with unstable diabetes, or fatigue and/or arthralgia in the absence of any other explanation.

Iliac muscle abcess and staphylococcal metastatic infection in a diabetic patient.

We report the case of a 44-year-old obese diabetic woman admitted for fever. Blood cultures grew Staphylococcus Aureus and antibiotherapy was started. Iliac abscess was diagnosed and surgical drainage done. Clinical evolution was marked by metastatic dissemination: sacroiliac osteolysis, right shoulder osteoarthritis, spondylitis of the third lumbar vertebra and pulmonary localizations. This case-report shows diagnosis and treatment difficulties of an iliac muscle abscess with metastatic localization in a diabetic patient.

Efficacy of the long-acting octreotide formulation (octreotide-LAR) in patients with thyrotropin-secreting pituitary adenomas.

The presence of somatostatin receptors on TSH-secreting pituitary adenomas allows treatment of central hyperthyroidism with somatostatin analogs. Six women and 5 men (mean +/- SEM age, 43 +/- 3 yr) presented TSH-secreting pituitary adenomas (micro, n = 2; macro, n = 9). Seven patients had previously been treated with partial surgical removal (n = 6) and/or external radiation (n = 4) of their adenoma at least 1 yr before the study, whereas 4 patients had not been treated before somatostatin analog therapy. TSH, free T(4), and free T(3) levels were in the normal range during treatment with sc injections (n = 9) or continuous infusion (n = 2) of octreotide (280 +/- 25 microg/day). Mean thyroid hormone levels increased (P < 0.01) after the washout period (34 +/- 6 days). The patients received monthly im injections of 20 mg Octreotide-LAR. In patients with an elevated free T(4) level after 3 months (n = 1) the Octreotide-LAR dose was increased to 30 mg. After 3 months of Octreotide-LAR treatment, TSH, free T(4)/T(3), and alpha-subunit levels decreased, and 10 patients were euthyroid with normal free T(4) levels. These results remained at the same level over the next 3 months. There were no statistically significant differences in the TSH and free T(4) responses to sc octreotide or im Octreotide-LAR between previously untreated patients and patients who had undergone surgical resection and/or pituitary radiation before somatostatin analog treatment. During Octreotide-LAR treatment, minor digestive problems or moderate discomfort at the injection site, lasting less than 48 h, were reported in 6 and 5 patients, respectively. Gallbladder echographies did not reveal new gallstones during Octreotide-LAR treatment. In conclusion, this study shows that monthly im Octreotide-LAR is as effective as daily sc octreotide in controlling hyperthyroidism in patients with TSH-secreting pituitary adenomas, in both previously untreated patients and patients treated with surgery and/or pituitary radiotherapy. Octreotide-LAR is well tolerated, except for minor digestive problems or mild pain at the injection site. Therefore, Octreotide-LAR appears to be a useful therapeutic tool to facilitate medical treatment of TSH-secreting pituitary adenomas in patients who need long-term somatostatin analog therapy.

Evaluation of the treatment of thyrotropin-secreting pituitary adenomas with a slow release formulation of the somatostatin analog lanreotide.

Somatostatin analogs have been shown to be effective for the treatment of TSH-secreting pituitary adenomas. However, their use in this indication is limited by the fact that available analogs require several daily sc injections. The present study was performed to evaluate the effects of a slow release formulation of the somatostatin analog lanreotide (SR-L) on both hormone secretion and tumor size and to assess the tolerance in a series of thyrotropinomas treated for 6 months. Eighteen patients with hyperthyroidism related to a TSH-secreting pituitary adenoma, evidenced by pituitary magnetic resonance imaging, were studied. After a basal assessment, each patient received 30 mg SR-L, im, every 14 days for 1 month. Then, according to the free T3 (fT3) plasma level measured, 9 of 18 patients were injected twice monthly, and 7 of 18 patients received SR-L every 10 days for 5 additional months. One patient was dismissed from the study in month 1 of the study for side-effects and another in month 3 for noncompliance to the protocol. Clinical and biological evaluations (plasma TSH, free alpha-subunit, fT4, fT3, and lanreotide levels) were performed before and in months 1, 3, and 6 of treatment. Pituitary magnetic resonance imaging and gallbladder ultrasonography were performed both at entry and at the end of the study. Clinical signs of hyperthyroidism improved within 1 month in all 16 evaluable patients. Mean (+/- SEM) plasma lanreotide levels reached 1.11 +/- 0.43 and 1.69 +/- 0.65 ng/mL in month 3 using 2 and 3 injections/month, respectively, then remained stable until the end of the study. During therapy, the plasma TSH level decreased from 2.72 +/- 0.32 to 1.89 +/-0.27 mU/L (P < 0.01), with parallel significant changes in free alpha-subunit. During the same period, plasma fT4 and fT3 levels decreased from 37.9 +/- 2.9 to 19.7 +/- 2.3 pmol/L (P < 0.01) and from 14.6 +/- 1.1 to 8.3 +/- 0.8 pmol/L (P < 0.01), respectively. No statistically significant change in mean adenoma size was observed after 6 months of treatment. Side-effects, including pain at the injection point, abdominal cramps, and diarrhea, were mild and transient and did not lead to interruption of the treatment. No gallstones occurred during the study. SR-L appears to be able to suppress clinical signs of hyperthyroidism in our series of patients with TSH-secreting pituitary adenomas. The analog also reduces plasma TSH and thyroid hormone levels, which were normalized in 13 of 16 cases. The effect was maintained throughout the treatment using 2 or 3 SR-L injections monthly without any problem of tolerance. We conclude that SR-L is a safe and effective treatment of thyrotropinomas and avoids the drawbacks of the modes of administration of other somatostatin analogs, given three times daily.

Relationship between insulin sensitivity and circulating sex hormone-binding globulin levels in hyperandrogenic obese women.

The aim of this work was to examine the effect of an insulin infusion on SHBG levels as well as the relationship between SHBG levels and insulin sensitivity. Acute insulin infusion was used with the insulin-glucose clamp technique. The subjects were 14 consecutive well-characterized hyperandrogenic non-diabetic obese women without biological and echographic symptoms of polycystic ovary syndrome. Adiposity and fat distribution were assessed respectively by the body mass index (BMI: 38.7 +/- 1.6 kg/m2) and by the waist hip ratio (WHR: 0.91 +/- 0.01). Hyperandrogenism was evidenced by hirsutism and serum testosterone greater than 2.8 nM. Circulating SHBG levels were determined in the fasting state by RIA. Insulin sensitivity was assessed using the euglycemic hyperinsulinemic glucose clamp technique with three incremental doses of insulin. Seven non-obese non-hyperandrogenic subjects (BMI: 21.0 +/- 0.6 kg/m2) served as controls for the study of the insulin resistance state. Because of supraphysiological insulin infusion rates (40, 100, and 350 mU/min.m2, each dose for 2 h), insulin sensitivity was mainly studied at peripheral level. We calculated the Km, i.e. the ED50 of the dose-response curve, the glucose disposal rate, and the maximal glucose disposal rate per U insulin (M/I). The hyperandrogenic obese subjects exhibited marked insulin resistance. SHBG levels, although already in the lower half of normal in the basal state, decreased from 34.8 +/- 3.4 nmol/l to 29.7 +/- 3.3 nmol/l (P = 0.001; normal values are 18-83 nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

[Female obesity: testosteronemia is positively correlated with peripheral insulin resistance]. / Obésité féminine: la testostéronémie est postivement corrélée à l'insulinorésistance périphérique.

Hyperinsulinemia and hyperandrogenemia are frequent in obese women. The aim of this study is to examine the relationship between the degree of insulin resistance and plasma androgens, and the role of android obesity. We studied 16 obese (BMI = 39.3 +/- 1.6 kg/m2) premenopausal non diabetic women (age = 28.2 +/- 1.4 years). The peripheral insulin sensitivity was determined during an euglycemic insulin clamp study. Serum total testosterone (TT), free testosterone (FT), androstenedione (A) were measured in each women. We compared these results to those of 5 control subjects (BMI = 20 +/- 1 kg/m2). Insulin resistance was more severe in the obese women than in the control subjects: Vmax = 9.1 +/- 0.5 mg/kg/mm vs 19.1 +/- 1.0 mg/kg/mn (p < 0.01) and Km = 152.2 +/- 13.9 microU/ml vs 42.6 +/- 5.8 microU/ml (p < 0.01). Significant positive correlations were demonstrated in the obese women between Km and both total testosterone (r = 0.74; p < 0.01) and free testosterone (r = 0.52; p < 0.05). There was no correlation between Km and Androstenedione. The waist to hip ratio (WHR) differentiated two groups of age--and weight-matched obese women; Gr 1:10 upper body obese women (WHR = 0.90 +/- 0.10; BMI = 39.0 +/- 1.9 kg/m2); Gr 2: 6 lower body obese (WHR = 0.77 +/- 0.02; BMI = 40.0 +/- 3.1 kg/m2. Insulin resistance was more severe in the Gr I: Km = 174 +/- 17 microU/ml, than in the Gr 2: Km = 101 +/- 8 microU/ml (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[The estrogen-androgen profile is unchanged in men with cholelithiasis]. / Le statut estro-androgénique n'est pas modifié chez les hommes atteints de lithiase biliaire.

It is well established that cholelithiasis is more frequent in women than in men. This difference is usually explained by the effects of estrogens and progesterone on the metabolism of bile acids, biliary cholesterol secretion and saturation, and gallbladder motility. Another explanation could be a protective effect of androgens against cholelithiasis in men. To test this hypothesis, we determined the hormonal, androgenic and estrogenic, status of 15 male patients with asymptomatic gallstone disease and in 15 control patients with normal gallbladder matched for age and body weight. No significant difference in the plasma concentrations and the urinary excretion rate of sex hormones (testosterone, dihydrotestosterone, androstenedione, testosterone and androstanediol glucuronides, estradiol, estrone, total estrogens), as well as in the plasma sex hormone binding globulin, was found between the 2 groups of patients. The development of cholelithiasis in men, therefore, does not appear to be related to modification of sex steroids.

Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment.

Myxoedema coma is a medical emergency with high mortality. In this study, clinical response and plasma variations of thyroid hormones were analysed in 7 patients, 6 presenting with myxoedema coma and one with myxoedema ileus. These patients were treated with intravenous or oral l-thyroxine (l-T4). 1000 mu l-T4 iv were administered in two patients. Within 3 h, plasma T4 and triiodothyronine (T3) reached a peak upper normal range, then diminished slowly during 5-9 days. The 5 remaining patients were treated with 500 micrograms l-T4 po on the first day, then 100 micrograms l-T4 daily by mouth. Plasma T4 and T3 increased slowly, remaining in hypothyroid range but clinical response (assessed on mental status, pulse rate and body temperature) occurred within 24-72 h. Cortisone therapy was used in 3 patients. Two patients died of myocardial infarction, or septicemia, one while receiving cortisone therapy and i.v. l-T4, another one treated only by oral l-T4. This study suggests: 1) oral absorption of l-T4 is variable, but clinical response occurs quickly even in myxoedema ileus; 2) the intravenous route involves high peaks of plasma T4 and T3; 3) peripheral conversion of T4 to T3 allows gradually T3 delivery to organ systems, even if only l-T4 is used and 4) initial and daily dosage determinations need further studies.

[Preliminary study of the use of intranasal buserelin in the long-term protocol of ovarian stimulation with the view toward fertilization in vitro]. / Etude préliminaire de l'utilisation de la busereline par voie nasale dans le protocole long de stimulation ovarienne en vue de fécondation in vitro.

A study conducted in 22 patients who used intranasal buserelin, in a long-term protocol for IVF, showed that pituitary desensitization is obtained between 14 days and 1 month. Analysis of the trials in this series, where the results were not satisfactory, suggests that the bioavailability of the product used intranasally, may be in question. A better distribution of nasal sprays causes more discomfort than when used subcutaneously.

[Contraception for the diabetic woman]. / Contraception chez la femme diabetique.

PIP: Because of their vascular and metabolic risks for diabetic women, pregnancies must be carefully programmed to occur before the onset of degenerative diabetic manifestations. Diabetic women need an effective contraceptive method without undesirable side effects. The numerous side effects of combined oral contraceptives (OCs) are due to both the estrogens and progestins. Combined OCs have a diabetogenic effect whose mechanism is not clearly understood. Blood sugar levels are elevated under OCs and the insulin response is retarded and exaggerated. The number and affinity of insulin receptors are reduced. Norsteroid- derived progestins increase the state of insulin resistance. Combined OCs usually increase triglyceride levels. Changes in the level of high- density lipoprotein cholesterol under combined OCs vary with the estrogen and progestin content. Synthetic estrogens increase platelet aggregability, and blood pressure increases during OC use. Use of combined OCs represents increased vascular risk for diabetic women, with the risk of thrombosis multiplied by 4. Low dose progestin pills permit continued secretion of a small amount of luteinizing hormone and follicle stimulating hormone which may cause a relative hyperestrogenism and undesirable side effects. The secondary effects are often poorly tolerated. Use of this type of pill is limited except among diabetic women, 25% of whom are users. The failure rate is estimated at .2-2%. Standard-dosed norsteroids are unsuitable for diabetic women because of their metabolic and vascular side effects. 2nd and 3rd generation progestins have yielded more promising results. IUDs are used by about 12% of the overall female population but 32% of diabetic women, mostly multiparas, despite the increased risk of infection. Local methods have a higher failure rate and their success depends on patient compliance with instructions. 14% of diabetic women in a recent survey reported having undergone tubal ligation, which is not strictly speaking a contraceptive method. Combined OCs should be avoided in insulin- dependent diabetics because of their metabolic and vascular effects. Diabetic retinopathy should be added to the list of absolute contraindications to these methods. Low-dose progestins can be used in insulin-dependent diabetics or if they are poorly tolerated a standard dose pill can be substituted. IUD is the method of choice for older, multiparous insulin-dependent diabetics. Sterilization may be considered, especially if pregnancy is absolutely contraindicated. Combined OCs are formally contraindicated for noninsulin-dependent diabetics. Low-dose progestins could be tried. IUDs are suitable for multiparas.^ieng

[Intrasellar carotid aneurysm simulating prolactin adenoma]. / Anévrysme de la carotide intrasellaire simulant un adénome à prolactine.

A 52-year-old woman with secondary amenorrhea presented with ophthalmoplegia, subarachnoidal bleeding. Pituitary function tests showed mild hyperprolactinemia and deficiencies of other functions of adenohypophysis. X-ray films of the skull showed enlarged sella turcica, and CT scan was interpreted as demonstrating pituitary tumour. Carotid arteriography led to diagnosis of intrasellar aneurysm of the right internal carotid, without any pituitary tumour. After embolisation of the aneurysm, followed, by a temporo-sylvian anastomosis, endocrine functions did not improve. The mechanism of hyperprolactinemia is discussed, probably due to pituitary ischemia. This case provides evidence of interest of further investigations before a transsphenoidal surgery in pituitary tumours, in particular if subarachnoidal bleeding occurs.

[Male pseudohermaphroditism caused by partial insensitivity to androgens. Clinical and biochemical heterogeneity]. / Pseudo-hermaphrodisme masculin par insensibilité partielle aux androgènes. Hétérogénéité clinique et biochimique.

Male pseudohermaphroditism due to partial androgen insensitivity (PAI) may be suspected clinically in case of incomplete masculinization of external genitalia in spite of age related plasma androgen levels. In 25 children or adolescents in whom PAI was suspected, the 5 alpha-reductase activity of external genitalia fibroblasts, the number of androgen receptor sites (Bmax) and the affinity of receptors for dihydrotestosterone (Kd) were studied. Clinical expression of PAI is highly polymorphic (Prader's type I to type IV), when most children (18/25) were considered as males. In a single patient the very low 5 alpha-reductase activity permitted the diagnosis of 5 alpha-reductase deficiency. The number of receptor sites (fmoles/mg DNA) varied from 0 to 730. Mean Bmax of patients (282 +/- 187 fmoles/mg DNA) was statistically lower than that of normal subjects (642 +/- 220 fmoles/mg DNA), p less than 0.05. The 5 cases in whom receptor concentrations were normal may be related to a qualitative abnormality of the androgen receptor or to a "post-receptor" defect. On the contrary no significant differences in Kd values were found. Correlation between sexual ambiguity and the number of measured receptors was not possible. These results emphasize the clinical and biochemical heterogeneity of PAI. Nevertheless, the decrease in number of androgen receptor sites remains the major data for the biochemical diagnosis of PAI. Study of post-receptor "markers" (3 alpha-reductase activity, aromatase, collagen) might allow better analysis of cases with PAI in whom androgen receptor concentrations are normal.