Spontaneous rupture of Achilles tendon and Cushing's disease. Case report.

Spontaneous rupture of Achilles tendon is observed in patients with tumors, metabolic disorders, infections and systemic diseases. Fluoroquinolones may cause tendinopathies. In addition, spontaneous rupture uncommonly occurs in Cushing's syndrome. We report a case of Cushing's disease revealed by recurrent rupture of Achilles tendon. Tendon tears are described in patients receiving long-term steroid treatment, probably via a mechanism similar to that one occurring in Cushing's syndrome. Although exceptional, this diagnosis should be discussed in patients with spontaneous rupture of Achilles tendon.

[Steroid responsive encephalopathy associated with auto-immune thyroiditis]. / Encéphalopathie corticosensible associée à une thyroidite auto-immune: données actuelles.

Since the first description of encephalopathy associated with Hashimoto's thyroiditis in 1966, more than 100 cases of this entity called Hashimoto's encephalopathy or SREAT [steroid-responsive encephalopathy associated with auto-immune thyroiditis] have been reported. The two cases reported here illustrate different diagnostic criteria and offer the opportunity to discuss the many pathophysiological hypotheses based on particularly pertinent biological data, especially the activity of anti-TPO and anti-TG antibodies present in serum and cerebrospinal fluid and the recent discovery of anti-alpha-enolase antibody. Different treatment options are also discussed, in particular corticosteroid therapy.

Reversible gonadotropin deficiency in male Cushing's disease.

Twelve adult males with documented active Cushing's disease were studied. Mean plasma testosterone (T) was significantly decreased: 1.8 +/- 0.3 (SEM) ng/ml (N=6.8 +/- 0.5); gonadotropin measurements in 8 patients, in basal conditions and under LH-RH iv, showed a significant decrease in both FSH and LH. A further study of 11 patients in remission of Cushing's disease indicated a significant increase in plasma T and gonadotropins up to the normal range. One patient with an initial low T value had a normalized T while in remission, then a dramatic decrease when the disease relapsed. We conclude: a hypogonadotropic hypogonadism is found in male Cushing's disease; it disappears as early as hypercortisolism is suppressed. Some possible mechanisms are discussed.

Glucocorticoids do not regulate the expression of proteolytic genes in skeletal muscle from Cushing's syndrome patients.

Glucocorticoids signal enhanced proteolysis in various instances of muscle atrophy and increased gene expression of components of the lysosomal, Ca(2+)-dependent, and/or ubiquitin-proteasome proteolytic pathways in both rat skeletal muscle and myotubes. Cushing's syndrome is characterized by chronic excessive glucocorticoid production, which results in muscle wasting. We report here no change in messenger RNA levels for cathepsin D (a lysosomal proteinase), m-calpain (a Ca(2+)-activated proteinase), ubiquitin, 14-kDa ubiquitin-activating enzyme E2, and 20S proteasome subunits (i.e. critical components of the ubiquitin-proteasome proteolytic process) in skeletal muscle from such patients. Thus, in striking contrast with animal studies, glucocorticoids did not regulate the expression of muscle proteolytic genes in Cushing's syndrome. In humans, messenger RNA levels, for at least ubiquitin and proteasome subunits, are elevated in acute situations of muscle wasting, such as head trauma or sepsis. Because Cushing's syndrome is a chronic catabolic condition, we suggest that the lack of regulation of proteolytic genes in such patients may represent an adaptive regulatory mechanisms, preventing sustained increased protein breakdown and avoiding rapid muscle wasting.

Response of leucine metabolism to hyperinsulinemia in hypothyroid patients before and after thyroxine replacement.

We have investigated the effect of hypothyroidism and insulin on protein metabolism in humans. Six hypothyroid patients were studied in a postabsorptive state before and after 5 months of regular treatment for hypothyroidism (153 +/- 17 microg/day of L-T4). The effect of insulin was assessed under hyperinsulinemic euglycemic and eukalemic conditions. Insulin was infused for 140 min at 0.0063 +/- 0.0002 nmol/kg x min. An amino acid infusion was used to blunt insulin-induced hypoaminoacidemia. Whole body protein turnover was measured using L-[1-13C] leucine. When compared to L-T4-induced subclinical thyrotoxic state, hypothyroidism induced a significant decrease (P < 0.05) in leucine endogenous appearance rate (a reflection of proteolysis; 0.89 +/- 0.09 vs. 1.33 +/- 0.05 micromol/kg x min), oxidation (0.19 +/- 0.02 vs. 0.25 +/- 0.03 micromol/kg x min), and nonoxidative disposal (a reflection of protein synthesis; 0.87 +/- 0.11 vs. 1.30 +/- 0.05 micromol/ kg x min). Insulin lowered proteolysis during both the subclinical thyrotoxic and hypothyroid states. Hypothyroidism impaired the antiproteolytic effects of insulin. Thyroid hormones are, therefore, essential for the normal antiproteolytic action of insulin.

Divergence in plasmatic and urinary isoprostane levels in type 2 diabetes.

BACKGROUND: Oxidative stress is currently suggested as a mechanism underlying diabetes. The present study was designed to evaluate isoprostane levels in plasma and in urine in type 2 diabetic patients, and to compare them to other currently used biomarkers of oxidative stress. METHODS: The work was performed in a control group (n = 10) and in a type 2 diabetic group (n = 10). Besides the traditional biochemical parameters, we evaluated the plasma and urine levels of isoprostanes and malondialdehyde (MDA) as markers of oxidative stress. RESULTS: We found increased plasma and urine MDA in the diabetic patients and almost significantly decreased plasma vitamin E. Urinary isoprostane levels in diabetic patients were increased but they presented a strong tendency to a decrease in plasma isoprostanes. It is therefore suggested that, in the studied diabetic patients, although the production of isoprostanes in the body was increased (as other plasma oxidative stress biomarkers were altered) it did not lead to an increase in plasma isoprostane levels. It could be hypothesised that this results from an increased elimination of this metabolite and therefore an increased excretion in urine. CONCLUSION: Our results showed that the measurement of same oxidative stress biomarker, isoprostane, in two different biologic fluids, plasma and urine, led to divergent results and emphasised the importance to measure a biomarker both in the circulation fluid (plasma) and in the elimination fluid (urine), to have a general idea of what is occurring in the organism.

[Mediastinal hemangiopericytoma. Apropos of a case]. / Hémangiopéricytomes médiastinaux. A propos d'un cas.

The authors report a new case of hemangiopericytoma in an elderly man. An asymptomatic mediastinal mass was found on a routine chest film. C.T. guided fine-needle biopsy was diagnostic. These rare lesions are clinically and radiologically aspecific and require pathologic proof. The value of percutaneous biopsy before therapeutic decision is emphasized.

[Carbimazole and leukocytoclastic vasculitis: apropos of a case]. / Carbimazole et vascularite leucocytoclasique: à propos d'un cas.

INTRODUCTION: The authors describe the case of biopsy-proven cutaneous leukocytoclastic vasculitis secondary to treatment with carbimazole. EXEGESIS: A 78-year-old white female developed erythematous macules on the lower limbs which cleared after discontinuation of her current treatment and implementation of oral steroid therapy. Causal explorations (lack of systemic disorder or infectious disease) remain negative, except for positive immune complexes. This case clearly differs from the two cases of microvasculitis (myositis and nephritis) secondary to treatment with carbimazole previously mentioned in the literature. CONCLUSION: To our knowledge this is the first report of biopsy-proven cutaneous leukocytoclastic vasculitis associated with this antithyroid agent. Its widespread use makes awareness of the side-effect important.

[Vitiligo in multiple autoimmune syndrome: a retrospective study of 11 cases and a review of the literature]. / Le vitiligo au cours des syndromes auto-immuns multiples: étude rétrospective de 11 observations et revue de la littérature.

PURPOSE: The occurrence in the same patient of three or more autoimmune diseases defines multiple autoimmune disease. Multiple autoimmune disease is an unusual condition in which dermatological autoimmune diseases and especially vitiligo have an important place. METHODS: We examined retrospectively 11 cases of multiple autoimmune diseases associating vitiligo. We studied the clinical characteristics of vitiligo and those of the associated autoimmune disorders. RESULTS: Type III multiple autoimmune disease was diagnosed in all the 11 cases observed. Autoimmune vitiligo was the first autoimmune disorder observed in seven cases and was bilateral, symmetrical and acrofacial in eight cases. Autoimmune thyroid disorder was associated in ten cases. Our data confirms the important association between vitiligo and thyroid autoimmune disorders. CONCLUSION: The predominant female ratio and the acrofacial topography of skin lesions could predict association with others autoimmune disorders in patients with vitiligo.

[Pituitary gland MRI and Cushing disease: report of 14 operated patients]. / IRM hypophysaire et maladie de Cushing: à propos de 14 patients opérés.

PURPOSE: Evaluate the MR sensibility for detection and localisation of ACTH-secreting microadenomas of the pituitary gland. PATIENTS: and method. The MRI studies of the pituitary gland, performed before transsphenoidal surgical exploration, about 14 patients who present clinical and biological signs of Cushing disease, were reviewed retrospectively. We have always used unenhanced sagittal and coronal spin-echo T1 sequences, and coronal T1 after injection of gadolinium (1 Tesla). RESULTS: The global sensibility for detection of an adenoma was 100% (84 to 92% when the lesional localisation was considered). The injection of gadolinium increased the sensibility of 38 to 42% according the readers. 7 to 14% of the lesions were isointense after injection. The estimation of lesional size after injection was the nearer to the surgical results. The indirect sign most frequently seen (35.7 to 64.3%) was focal bulging of the sellar diaphragm. The only differences between the different radiologists, statistically significant, concerned the lesional size before injection and location of the lesion in the sagittal plane. CONCLUSION: This study confirmed the good sensibility of contrast-enhanced MRI in detection of ACTH-secreting microadenomas. The anatomo-radiological correlations are nevertheless incomplete.

[Epidemiology of goiter in Auvergne]. / Epidémiologie du goitre en Auvergne.

An epidemiological study about goiter, related to the French national survey concerning school children aged 10-16, was carried out in region Auvergne. The prevalence of goiter was 12.52%, including 2.8% patients with WHO stages I and II, thus being slightly below national average (16.7%). Iodine urinary excretion was 62.9 +/- 34.3 micrograms per gram creatinine (French mean value 85.0), although sometimes major variation was noted in the same area. Later, two studies were performed in adults, in two places of Haute-Loire and Puy-de-Dôme, respectively Arsac-en-Velay and Besse-en-Chandesse. Both places were selected because of high frequency of goiter in children. Prevalence in adults was 16.1% in Arsac-en-Velay including 12.5% stages I and II, and 8.9% in Besse-en-Chandesse including 5.9% stages I and II. Mean iodine urinary excretion was respectively 59.78 micrograms/gram creatinine and 43.45 micrograms/liter. Thus, these surveys confirm a significant prevalence of goiter in Region Auvergne, with endemic places, and a generally low iodine urinary excretion.

[Painful chronic thyroiditis. A rare cause of thyroid pain]. / Thyroïdite chronique douloureuse. Une cause rare de douleur thyroïdienne.

The usual clinical presentation of Hashimoto's chronic lymphocytic thyroiditis is a firm and painless goiter. We report two atypical observations with painful symptoms. Case 1: a 33 year old woman with a two months history of L-thyroxine treated primary hypothyroidism associated with elevated antithyroglobulin and antithyroperoxydase antibodies (respectively 36.000 and 7.000 U/l, normal values < 100 U/l) presents with anterior cervical pain. She is euthyroid, but displays biological inflammatory syndrome. Neck ultrasonography reveals low amplitude echoes of the thyroid gland. Antithyroid antibodies remain at high titers. After failure of NSAI drugs, prednisolone (oral 30 mg/day for 10 days, followed by degression) allows rapid disappearance of both pain inflammatory syndrome. When treatment was stopped pain recurred and required steroids for 3 months. After one year, the patient is painless and only receives L-thyroxine. Case 2: a 36 year old woman is referred for anterior neck pain, fever and hypothyroidism. Biological inflammation is also noted. High levels of antithyroglobulin and antithyroperoxydase antibodies are found. Thyroid uptake was maintained. L-thyroxine and prednisolone (oral 20 mg/day) therapies are associated with rapid pain relief. After two months, steroids are stopped. The patient remains normothyroid under L-thyroxine. Antithyroid antibodies persist at high levels. Other aetiological diagnosis of painful thyroid include acute infectious thyroiditis, cancers, intracystic hemorrhages and mainly subacute De Quervain's thyroiditis. Beyond clinical symptoms (revelation with hypothyroidism), persistent scintiscan uptake and prolonged elevated levels of antithyroglobulin and antithyroperoxydase antibodies remain the strongest arguments in favor of the 33 reported cases of painful Hashimoto's chronic lymphocytic thyroiditis. Eventually, among various therapies used, steroids in conjunction with thyroid hormones, seem the most efficient.

[Partially hormone dependent bilateral malignant polyadenomatous hyperplasia]. / Hyperplasie polyadénomateuse maligne bilatérale des surrénales partiellement hormono-dépendantes.

Bilateral malignant polyadenomas of adrenals seem to be rare. They involve either a double primary adrenal tumour, or a metastasis of a controlateral tumour. In the observation reported here, the evolution is characterized by periods of central stimulation with partial autonomy, and periods of tumoral autonomy with central inertness. Pathological findings consist of coexistence of various histological aspects (atrophy, hyperplasia, benign adenoma, carcinoma) suggesting the successive steps of a very particuliar adrenal carcinogenesis. Such findings allow to discuss the following physiopathological mechanism: a stimulation by ACTH might have resulted initially in a preneoplasic hyperplasia, then in an incompletely autonomous tumour, and finally in an autonomous tumour. Accordingly, from a practical and therapeutic point of view, it would be suitable, after removal of an adrenal tumour, especially of one with demonstrated ACTH-dependance, to suppress totally endogenous ACTH by cortisol or cortisone therapy, in order to reduce the occurence of corticotropin stimulation of possibly remaining malignant adrenal cells.

[Gonadotropic function in female Cushing syndrome (author's transl)]. / Etude de la fonction gonadotrope dans le syndrome de Cushing chez la femme.

A study of 38 female Cushing syndromes showed decreased levels of FSH and LH, with normal LH-RH stimulation in most adrenal hyperplasia and benign adenoma, and absent stimulation in carcinoma. The levels were normalized by suppression of hypercorticism. This suggests a blunted gonadotropic function, in female Cushing syndrome, probably at the hypothalamic level. The predominant respective roles of hyperandrogeny in carcinoma and of hypercortisolism in adrenal hyperplasia and benign adenoma seem probable.

[Gonadotropic function in female Cushing's syndrome (author's transl)]. / La fonction gonadotrope dans le syndrome de Cushing chez la femme.

Gonadotropic function has been studied without selection in 38 female patients with Cushing's syndrome followed during four years. The level of gonadotropins FSH and LH was low in all etiologies of the syndrome. LH-RH stimulation is normal in adrenal hyperplasia and adenoma, and very low in carcinoma. These abnormalities are cured after reduction of hypercorticism. The share of either cortisol or androgens is discussed. A predominant hypercortisolism blunting action on gonadotropic function is possible, cortisol being the common factor of Cushing's syndrome.

[Purification of pineal antigonadotropic factor (author's transl)]. / Purification du facteur antigonadotrope de la glande pinéale.

Pineal activity on hypothalamo-hypophyso genital axis is well established. The mechanism is not simple, since progonadotropic or/an antigonadotropic activity were described. The biochemical isolation of the potent factor has been assayed. Several substances: melatonin, AVT, peptides have antigonadotropic properties. In this paper, we report many experiments concerning isolation and purification by several chromatographies of the factor (probably peptidic), that we believe to be responsible of antigonadotropic activity. Biological activity of the substance is proved by "in vitro" methods and radio immunoassays. This component is quite pure because electrophoresis on gel polyacrylamid reveals only one strip. Gel Sephadex G10 chromatography indicates a probable MW is between 500 and 1,000. This component causes an important inhibition of pituitary LH discharge (in vitro methods).

[Epidemiologic characteristics of 336 thyroid cancers observed in the Auvergne region]. / Caractéristiques épidémiologiques de 336 cancers de la thyroïde observés en région Auvergne.

Patients treated and followed for thyroid cancer by a multidisciplinary group were studied between 1989 and 1993, 336 patients living in the French region Auvergne underwent total or partial thyroidectomy for thyroid carcinoma. The sex ratio was 4.3 and the median age was 52 (14-57) and 49 (17-83) in females and males respectively. Papillary carcinoma was the most common form: 76.5 of all thyroid tumors. The incidence of occult thyroid cancer was 17.4%; tumor size was smaller than for intranodular cancer (p < 0.00001). Tumor size at diagnosis of patients who died was higher than in patient who survived (p < 0.0001) and changed with histological type. It decreased between 1989 and 1993 (p < 0.01). 73% of the patients were asymptomatic before surgery, 23% described a rapid growth of their nodule. Clinically, 43.9% of the patients had a single nodule, 83% of these nodules were suspect because of their hardness. Median follow-up was 2.8 years. 279 patients are living and well, 28 were lost to follow-up and 39 died. There were 30 (8.93%) deaths due to thyroid carcinoma. In our study, significant prognostic factors for death were age at diagnosis (p < 0.0001), histological type (p < 0.0001) and nodular size (p < 0.01).

[Lipotropins (beta- and gamma-LPH). Valid indicators of corticotropic function]. / Les lipotropines (beta-et gamma-LPH). Marqueurs fiables de la fonction corticotrope.

Plasma levels of ACTH and LPH which derive from a common precursor, were determined simultaneously to study the value of LPH as a marker of the corticotropic function, and evaluate its advantage over that of ACTH plasma determination. ACTH and LPH plasma levels were measured: a) in control subjects under basal conditions and after dynamic explorations of the corticotropic axis. Furthermore, in some control subjects plasma LPH levels were measured after a 24 h incubation in blood at room temperature; b) in the venous and arterial blood of the kidney of subjects in whom a nephrectomy of a perfused and functional kidney was to be performed; c) in patients either under hemodialysis for chronic renal failure, or with adrenal insufficiency due to a primary adrenal failure or secondary to a corticotropic deficiency. This study permitted to establish: a) the normal values of basal plasma hormone levels (ACTH less than 10-80 pg/ml, LPH less than 20-200 pg/ml 8-9 a.m.) and to confirm their parallel secretions in physiological conditions; b) the stability of the LPH in blood at room temperature, whereas ACTH is rapidly destroyed in the same conditions; c) the primordial role of the kidney in the LPH catabolism; d) the value of LPH determinations in the diagnosis of primary adrenal insufficiency and corticotropic deficiency. Thus, except for the known situations where ACTH and LPH plasma levels are dissociated, the LPH plasma levels either basal or after dynamic explorations of the corticotropic axis, provide a reliable index of the corticotropic function.

[Neurologic manifestations of basal cell nevomatosis. A case]. / Manifestations neurologiques de la naevomatose baso-cellulaire. Un cas.

The naevoid basal cell syndrome, also called Gorlin's syndrome, is a dysembryoplasia akin to the phakomatoses and which may affect the skin, the bones, the nervous system, the eyes, the endocrine glands and the genitalia. A case with numerous tumours and malformations is presented, together with a review of the literature.

[Primary hypothyroidism in the adult older than 60 years. Characteristics and follow-up after initiation of replacement treatment in hospital]. / Hypothyroïdie primaire de l'adulte de plus de 60 ans. Caractéristiques et suivi après initiation du traitement substitutif en milieu hospitalier.

OBJECTIVE: Primary hypothyroidism is common in the elderly. Yet its care remains unclear. PATIENTS AND METHODS: Clinical, biological characteristics and outcome of 45 patients aged over 60 years admitted for in-hospital initiation of treatment for primary hypothyroidism were recorded. Causes and tolerance of treatment (clinical and ECG monitoring in hospital) were seek for. RESULTS: Initial symptoms, predominantly fatigue (84.4%), were moderate, contrasting with severe biological hormonal deficiency. The most common routine biological change was hypercholesterolemia (57.6%). Female predominance was obvious (77.8%) and the most usual aetiology autoimmune chronic thyroiditis. Despite variability of symptoms, long term follow-up demonstrates a positive response to treatment, including an improvement in fatigue, eye-lid swelling, bradycardia and overweight. This clinical improvement was achieved on an average dose of 1.22 +/- 0.47 mg/kg/day L-T4 in order to maintain normal TSH (3.76 +/- 2.93 mUI/l). Cardiovascular incidents while starting treatment require experienced care and low dose initial treatment. CONCLUSION: Primary hypothyroidism is still lately discovered in the elderly. Yet, since treatment is efficacious and simple, the disease should be searched for and cared after whenever a related symptom occurs.