Etiologic discussion and clinical relevance of thyroid ultrasonography in subclinical hypothyroidism. A retrospective study in 1845 patients.

BACKGROUND: Acquired subclinical hypothyroidism in adulthood is mainly due to autoimmune thyroiditis. In the absence of a goiter or a palpable firm thyroid, measurement of thyroid antibodies can improve the diagnosis. Whether thyroid antibodies are detected or not, what might be the clinical relevance of ultrasonography in this setting? METHODS: We studied 1845 cases of subclinical hypothyroidism in adults recruited for symptoms indicative of hypothyroidism or thyroid pathology. All patients were screened for thyroid antibodies and underwent an ultrasonographic thyroid examination. LOCALISATION: Multicentric retrospective study. RESULTS: Chronic autoimmune thyroiditis was confirmed in 70% of patients. Thyroid antibodies were undetectable in 30% of patients. In all patients, thyroid ultrasound facilitated measurement of the thyroid volume and detection of non-palpable nodules and therefore allowed biopsy. In patients negative for thyroid antibodies, ultrasonography suggested autoimmune thyroiditis in 31% of cases. Ultrasonography did not contribute to diagnosis in a large number of patients without nodules and in case of normal echostructure. The strategy of thyroid hormone replacement therapy was not influenced by ultrasonographic data. Thyroid biopsies detected smears suspected to be cancerous in 10 patients (4%). Cancer was confirmed in nine patients after surgery. Ultrasonography displayed suspicious aspects in six patients. CONCLUSION: In subclinical hypothyroidism, thyroid ultrasonography is not required for the diagnosis of autoimmune thyroiditis but is useful for patients with abnormal thyroid palpation and allows detection of non-palpable thyroid nodules. For patients that were negative for thyroid antibodies, thyroid ultrasonography can improve diagnosis for some patients, allowing detection of autoimmune thyroiditis.

[Frequency of hypothyroidism after De Quervain thyroiditis and contribution of ultrasonographic thyroid volume measurement]. / Fréquence de l'hypothyroïdie après thyroïdite de De Quervain et intérêt de la mesure échographique du volume thyroïdien.

Subacute thyroiditis conventionally recovers without after-effect. Nevertheless some data relate a 5 to 9% occurrence of final hypothyroidism 6 months after the acute stage. We herein studied end-stage hypothyroidism occurrence and effect of thyroid volume alterations on hormonal course during thyroiditis. Twenty-nine cases of subacute thyroiditis were studied. Final thyroid function remained normal in 15 patients (51%) and undetermined in 5 patients (17%). Final hypothyroidism (TSH: 4.5-14.5 microU/mL) occurred in 9 patients (31%). Mean thyroid volume was increased in acute stage in patients with final normal thyroid function (16.6+/-5.7cm(3)) and decreased by 63% during follow-up; final mean thyroid volume was 6.1+/-1.3cm(3). Mean thyroid volume was normal in acute stage in final hypothyroid patients (10.7+/-3.0cm(3)) and decreased by 72% during follow-up; final mean thyroid volume was 3.3+/-1.1cm(3). End-stage mean thyroid volume was significantly lower in final hypothyroid patients (p<0.05) compared to patients with final normal thyroid function. We conclude that the occurrence of final hypothyroidism is underestimated after subacute thyroiditis. Ultrasonographic follow-up might be helpful in the detection of final hypothyroid-risk patients: thyroid volume not increased in acute stage and lower than 5cm(3) during follow-up is one of the ultrasonographic features of these patients.

[Results of ultrasonographic and cytologic follow-up of 311 initially non-suspicious thyroid nodules]. / Résultats de la surveillance échographique et cytologique de 311 nodules thyroïdiens initialement non suspects.

The follow-up of initially non suspect thyroid nodules after fine needle biopsy is not completely worked out. Since 1985, we have entered upon a prospective study concerning the followup of thyroid nodules supposed to be benign after initial evaluation. What are the nature and the frequency of means to be used for their follow-up? Three hundred and eleven nodules are followed up on a mean duration of 2.44 years. The follow-up of 65 of them is 4 years or more. The follow-up of 120 others is 3 to 4 years; 197 nodules are followed up during 2 to 3 years. A physical examination, an ultrasonography completed with a fine needle biopsy or an ultrasonically guided fine needle biopsy are worked out every year. Twenty-three per cent of initial biopsies are non significant and 90% of them are ultrasonically guided biopsies. At the end of the study, the repeating biopsies reduce to 6% the non significant biopsies ratio. Four histological thyroid cancers are detected in three female patients 1 year, 2 years and 5 years after the initial evaluation. Ultrasound alterations of nodules are observed in case of very suspect biopsies. Ninety-six per cent of the followed up thyroid nodules remain not cytologically suspect. These findings allow us to propose the following guidelines for the assessment of a non suspect thyroid nodule: half-yearly or yearly physical examination, yearly or biennial ultrasonography, repeat biopsy after 2 or 3 years when clinical or ultrasound suspect modification is wanting.

[Critical study of the characterization of hyperandrogenism in a group of obese women]. / Etude critique de la caractérisation de l'hyperandrogénie dans un groupe de femmes obèses.

The authors report the hormonologic characteristics of 20 obese and hirsute women meeting the criteria for adrenaltype hyperandrogenism, suppressible by dexamethasone, without hyperprolactinemia and without any late developing partial enzyme block appearance. The laboratory profile of these women differed from that of a group of women with type 1 polycystic ovaries syndrome. In this same group obese women in whom LH/FSH ratio was below 1, there was evidence under baseline conditions of a moderate increase in testosterone and delta 4-androstenedione in relation to increased plasma levels of DHA and SDHA, plasma delta 4 and delta 5-androgen levels falling precipitalely during the dexamethasone suppression test. The ACTH stimulation test revealed greater reactivity for 17 hydroxy-pregnenolone (p < 0.001) and less for 21-deoxycortisol than in the control group of normal women (p < 0.01). The essentially adrenal origin of plasma hyperandrogenism in certain cases of obesity is discussed. Insulin could increase adrenal sensitivity to ACTH and its possible action in vivo on the activity of adrenal enzymes requires clarification. The accumulation of certain androgens in the adrenal cortex could also be responsible for dysregulation of 3 beta ol-dehydrogenase and 11-hydroxylase.

[Nodular or pseudo-nodular Hashimoto thyroiditis. Value of cytologic examination]. / Thyroïdites de hashimoto à aspect nodulaire ou pseudo-nodulaire. Intérêt de l'examen cytologique.

OBJECTIVES: Nodular or pseudo-nodular aspects of Hashimoto's thyroiditis raise the problem of the association with a differentiated carcinoma or a non Hodgkin's lymphoma. METHODS: We looked for patients needing surgery in 165 cases of Hashimoto's thyroiditis. For this purpose, we used fine needle aspiration cytology. RESULTS: We found a differentiated carcinoma in 4% of cases and a non Hodgkin's lymphoma in 1% of cases. CONCLUSION: In nodular or pseudo-nodular aspects of Hashimoto's thyroiditis, fine needle aspiration cytology is helpful for the nodule diagnosis and for the selection of suspicious nodules only to be referred to surgery.

[Recent findings concerning follicular growth]. / Données récentes concernant la croissance folliculaire.

Recent advances in molecular genetics now enable the study in vitro of follicular maturation using human recombinants of gonadostimulins (FSH and LH) and certain autocrine and paracrine ovarian regulation factors. This is leading to reevaluation of the precise role played by the various hormonal protagonists of folliculogenesis. FSH, in the presence of low levels of LH at the start of the follicular phase, has a mitotic action on estrogen-producing granulosa cells, encourages their differentiation and activates the synthesis of their genetically-determined products (essentially somatomedin, inhibin and activin) and of the LH receptor. High LH levels, during the second half of the follicular phase, stop proliferation of granulosa cells, and, synergistically with insulin-like growth factor 1, bring about an increase in estrogen synthesis from aromatisable androgens. In common with FSH, LH facilitates the production of cybernins and of essential growth factors, as well as of preovulatory progesterone. Abnormalities of endocrine, paracrine or autocrine regulation of follicular maturation may lead to atresia. Future rational uses of human FSH and LH are obvious and involve the optimisation of ovulation induction and in vitro fertilisation in sterile women.

[Diagnostic strategy in infertility due to hyperandrogenism. Development of a decision tree]. / Stratégie diagnostique au cours de l'infertilité avec hyperandrogénie. Elaboration d'un arbre décisionnel.

The detection of clinical hyperandrogenism in women presenting with infertility requires detailed hormonal investigations using the decisional plan suggested here. Initial studies including measurement of plasma androgen, gonadotrophic hormones and prolactin levels, may be sufficient to reveal an adrenal origin or pure ovarian origin. Non-tumor androgenic hypercorticism is seen classically in late-presenting enzyme deficits, but also in other situations: excessive adrenarche, hyperprolactinemia, obesity, chronic stress. The immediate Synacthene test can then eliminate diagnostic uncertainties if it leads to the discovery of appearances of 21- or 11-hydroxylase or 3 beta-ol dehydrogenase blocks. Intense virilisation in a woman with a testosterone level above 2 ng/ml (7 nM/l) should lead to suspicion of an androgen-secreting tumor of the ovary or adrenal. CT scan of the abdomen and true pelvis is essential here since it may reveal the presence of an adrenal or ovarian mass. If no morphological abnormality is shown by this investigation, an endocrine lesion of a small ovary should be strongly suspected, the demonstration of which requires isotope techniques and/or catheterisation of the ovarian veins. Two situations also exist which are responsible for severe hyperandrogenism but less alarming in terms of their course and significance: certain homozygous forms of 21-hydroxylase deficit diagnosed late and ovarian hyperthecosis. It may happen that these hormonal investigations do not suffice alone to determine the precise origin of hyperandrogenism and its cause. The dexamethasone adrenal suppression test is useful in the diagnosis of type II micropolycystic dystrophy, in order to define the essentially ovarian, adrenal or mixed origin of hyperandrogenism.

[Treatment of female infertility due to hyperandrogenism]. / Traitement des infertilités féminines par hyperandrogénie.

This study reviews the various types of treatment used in infertility due to hyperandrogenism, with the aim of answering the following three questions: How should these drugs be prescribed? What are their side-effects? What are the best diagnostic indications? Possibilities include ovulation inducers but also all types of treatment capable of improving the fertility of these women. The treatment of infertility due to adrenal hyperandrogenism is based upon glucocorticoids. This treatment must be continued for 3 months after conception, to attempt to avoid early spontaneous abortion. The first-line inducer in ovarian hyperandrogenism is clomiphene citrate. The good results obtained using the combination of dexamethasone and clomiphene citrate are explained by an adrenal participation in this type of hyperandrogenism. In case of failure, and in addition to classical menotrophins:--pre-treatment using LHRH agonists avoids the onset of premature luteinisation but does not prevent the possibility of multiple pregnancies;--use of purified FSH reduces, though not sufficiently, the risks of multifollicular maturation but does not greatly increase the overall pregnancy rate;--the "slow" protocol with purified FSH reduces the incidence of multifollicular maturation. Should this fail, prior treatment with an LHRH agonist and if not the pulsed administration of LHRH in non-obese women can be suggested. Surgical treatment provides useful results in severe forms of sterility due to polycystic ovaries syndrome, with new per-celioscopic techniques.

[Fertility disorders in 49 hyperandrogenic women desiring pregnancy. Treatment results aimed at obtaining a pregnancy in 40 hyperandrogenic infertile women and in 9 hyperandrogenic women desiring pregnancy]. / Troubles de la fertilité chez 49 femmes hyperandrogéniques désirant une grossesse. Résultats des traitements visant à obtenir une grossesse chez 40 femmes hyperandrogéniques infertiles et chez 9 femmes hyperandrogéniques désirant une grossesse.

The clinical and therapeutic aspects of fertility due to hyperandrogenism were studied in 49 women (40 presenting with sterility and 9 for another reason but seeking to become pregnant). Patients were divided into three main etiological groups on the basis of hormonal findings: ovarian (15 cases), adrenal (16 cases) and mixed (11 cases) hyperandrogenism. This study highlighted several points. 22% of infertile women had no cutaneous signs of hyperandrogenism and menstrual disturbances were missing in 46% of cases of adrenal hyperandrogenism. Primary infertility was seen more often in all types of hyperandrogenism (28 cases) than secondary infertility (12 cases). Secondary infertility was explained by a high early spontaneous abortion rate in hyperandrogenism (40%). This was much commoner in adrenal hyperandrogenism than in ovarian or mixed hyperandrogenism. Inducing treatment based upon a combination of dexamethasone and clomiphene citrate proved to be the most effective in these infertile women (86% pregnancy rate). The frequency of spontaneous abortions in infertility due to ovarian or mixed hyperandrogenism treated by clomiphene citrate alone can probably be explained by the persistence of hyperandrogenism.

[Adrenal enzymatic block with late-onset caused by 11-hydroxylase deficiency. Apropos of 29 cases]. / Blocs enzymatiques surrénaliens à révélation tardive par déficit de la 11-hydroxylase. A propos de 29 observations.

Late-onset congenital adrenal hyperplasia is a cause of a spectrum of clinical manifestations of postnatal androgen excess. In these cases, ACTH stimulation test with measurement of 17-Hydroxyprogesterone (17OHP) is usually done to assess 21-hydroxylase (21-OH) deficiency. Determination of the 11-deoxycortisol (S) and the S to cortisol ratio is rarely done, so that 11 beta-hydroxylase (11-OH) deficiency seems unusual. We systematically investigated this biosynthetic defect among women complaining of hyperandrogenism (n = 519) and, comparing the patient's hormonal responses to ACTH with those of 31 normal women, found 29 11-OH deficiency (5.6%): this is the largest group ever reported. S was elevated only 9 times, so that using this single determination, diagnosis of 20 enzymatic defects would not have been made. Only three of the patients (10%) had hypertension, even though the pathway of aldosterone was involved in 33% of cases (criteria: elevation of the ratio desoxycorticosterone to corticosterone). We also described one new patient with both 11-OH and 3-beta-hydroxysteroid dehydrogenase deficiencies. The patho-physiology is particularly interesting in these cases. It is concluded that the single research for 21-OH deficiency is inadequate among women complaining of hyperandrogenism: the screening for 11-OH deficiency should be made, even if blood pressure is normal.

[Hyalinizing trabecular adenoma of the thyroid gland. Histologic and immunohistochemical study. Report of 2 cases]. / Adénome trabéculaire à stroma hyalinisé de la thyroïde. Etude histologique et immunohistochimique. A propos de deux observations.

Hyalinizing trabecular adenoma of the thyroid gland is an uncommon neoplasm that was recently described by Carney et al. (1987). It is important to recognize this tumor, considered benign, as it may mimic papillary carcinoma, medullary carcinoma or paraganglioma. We present two cases with histological and immunohistochemical criteria and discuss the diagnostic problems. Grossly, this small tumor is yellow tan and well circumscribed. The epithelial cells, polygonal or elongated and sharply outlined, have an eosinophilic or clear cytoplasm. The nuclei are oval or elongated, with often non-visible nucleoli. Grooved nuclei are quite frequent. Mitotic figures are very uncommon. The cells are arranged in clusters or trabeculae or pseudofollicles containing colloid material. Characteristically the cells, arranged shoulder to shoulder, can show a palisade pattern. The fibrovascular stroma appears hyaline, pseudoamyloid (Congo red staining is negative). The tumor cells show intense staining for thyroglobulin and no staining for thyrocalcitonin. Immunoreactivity for cytokeratin, vimentin, protein S100, NSE is positive but staining is negative for EMA and desmin. In one case, the tumor cells show little positivity for chromogranin A. The variable patterns of this tumor can lead to diagnostic problems. We can exclude the diagnosis of papillary carcinoma as this tumor lacks any true papillary architecture. We reject the diagnosis of medullary carcinoma because of its thyroglobulin and calcitonin immunoreactivity. Paraganglioma never shows immunoreactivity for thyroglobulin. Very often the surrounding thyroid tissue shows focal thyroiditis. The association of the tumor with Hashimoto's thyroiditis can be explained by an autoimmune process.

Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine.

We studied ovarian function retrospectively in 66 women who had regular menstrual cycles before undergoing complete thyroidectomy for differentiated thyroid cancer and subsequent thyroid remnant ablation with 131I. Eighteen women developed temporary amenorrhea accompanied by increased serum gonadotropin concentrations during the first year after 131I therapy. No correlation was found between the radioactive iodine dose absorbed, thyroid uptake before treatment, oral contraceptive use, or thyroid autoimmunity. Only age was a determining factor, with the older women being the most affected. We conclude that radioiodine ablation therapy is followed by transient ovarian failure, especially in older women.

Follow-up of children born of bromocriptine-treated mothers.

A survey carried out in France at the beginning of 1984 concerning development of children born of mothers treated with bromocriptine (BC) during part or all of the pregnancy showed the absence of any adverse effects of BC in 64 children born from 53 mothers. In 60 cases, BC was prescribed (2.5-7.5 mg/day) for hyperprolactinemia; 23 mothers were treated with BC for 4 weeks or less, and 23 others for 30 weeks or more. After a follow-up of between 6 months and 9 years, all children are normal. Psychological development in the 23 children born to mothers treated with BC during more than 30 weeks of pregnancy actually appears more precocious, with excellent scholastic performance in the oldest.

Continuous administration of bromocriptine in the prevention of neurological complications in pregnant women with prolactinomas.

Continuous bromocriptine treatment was given throughout pregnancy to 10 pregnant women with prolactinomas. The dosage of bromocriptine was modified to reduce the serum prolactin level to below 20 ng/ml. Eight patients had continuous bromocriptine treatment started early in their pregnancies, and no tumor-related neurological complications were observed. Continuous bromocriptine treatment was not started at the onset of pregnancy in two patients, and bitemporal hemianopia occurred (at 5 and 7 months of pregnancy). With the start of continuous bromocriptine treatment, a normalization of the visual fields rapidly ensued. The course of the pregnancies and the condition of the newborn infants at birth were normal. The subsequent mental and physical development of the newborn infants (observed up to the age of 6 years) was also normal.

Comparison between the plasma concentrations of prolactin and parathyroid hormone in normal subjects and in patients with hyperparathyroidism or hyperprolactinemia.

In 30 normal subjects, the mean (+/- SEM) plasma concentration of PRL was 5.90 +/- 0.40 ng/ml and that of PTH was 0.51 +/- 0.03 ng/ml. There was no significant difference in plasma hormone levels according to age or sex. Ten cases of primary hyperparathyroidism showed PRL concentrations (8.90 +/- 1.80 ng/ml) significantly (P less than 0.01) higher than those of the normal subjects. After adenomectomy, the PRL concentration decreased (5.35 +/- 0.50 ng/ml). However, this decrease was only significant in the 5 of 10 patients who had preoperative plasma PRL levels of 10 ng/ml or more (P less than 0.01). The increase in PRL concentration in 10 cases of secondary hyperparathyroidism with normal glomerular function was also significant (14.25 +/- 3.9 ng/ml; P less than 0.001). Fourteen patients with prolactinoma showed PTH plasma levels (1.25 +/- 0.15 ng/ml) significantly higher than those of normal subjects (P less than 0.001). Eight of the 14 patients received 7.5 mg/24 h of bromocriptine for 3 months; their mean plasma PTH level decreased significantly from 1.60 +/- 0.35 to 0.50 +/- 0.11 ng/ml (P less than 0.01). In 9 cases of secondary hyperprolactinemia, the increase in PTH (0.80 +/- 0.16 ng/ml) was significant compared to the plasma PTH levels in the normal group (P less than 0.05). These results show that an excess of plasma PRL is associated with an excess of plasma PTH and vice versa. The mechanisms of these relationships remain unclear.

Dexamethasone-suppressible hypercorticosteronism in two 46,XX subjects with ambiguous genitalia and ovarian cysts. Partial defect of 17 alpha-hydroxylase or 17-20-desmolase.

The paradoxical association of female pseudohermaphroditism and androgen deficiency was observed in two 46,XX subjects with high corticosterone plasma levels. Subject 1 has been declared a boy due to clitoris enlargement; she had no vagina and uterus. Subject 2 had ambiguous external genitalia. In both, at age 27 and 17 years, fusion of outer labia, impuberism, ovarian cysts, and histologically normal ovarian tissue were observed. Blood pressure was normal. Basal cortisol levels were normal but unresponsive to ACTH. Progesterone levels were 40 and 62 ng/ml and rose after ACTH (50 and 79 ng/ml). 17-hydroxyprogesterone levels were 25 and 21 ng/ml and did not rise after ACTH. Corticosterone levels were 70 and 92 ng/ml and rose after ACTH (110 and 180 ng/ml). All three steroids were suppressed by dexamethasone. Androgen and estrogen levels were at or below the lower limit for normal women. The sex steroid levels obtained by radioimmunoassay in plasma and a follicular cyst fluid were confirmed by isotope dilution-mass spectrometry. We suggest that the sexual ambiguousness resulted from an excessive production of gestagenic steroids during fetal life, and that the enzyme defect is either a partial 17 alpha-hydroxylase defect combined with a peripheral production of 17-hydroxyprogesterone, or else a partial 17-20-desmolase defect with a secondary 21-hydroxylase defect limited to the cortisol pathway.

[Reversible lactic acidosis in a diabetic on high dose metformin (author's transl)]. / Hyperlactacidémie reversible chez un diabétique prenant une posologie excessive de metformine: étude clinique et pharmacocinétique.

In a diabetic, who took a high dose of 5.85 g metformin daily for 75 days, urinary retention caused by a prostatic adenoma induced functional renal insufficiency and hyperlactacidemia, rapidly reversed with treatment. Plasma and urine levels of metformin were measured at the same time as lactate and pyruvate levels, until all returned to normal. Clinical and biological improvement occured at the same time. The case is discussed in the context of lactic acidosis in diabetics with functional or organic renal insufficiency, treated with metformin.

[25 OH CC (25-hydroxycholecalciferol in spasmophilia) (author's transl)]. / Le 25 hydroxycholecalciferol (25 OH CC) dans la spasmophilie.

The level of 25 OH CC in plasma was evaluated in spasmophilia (126 cases) comparatively with normal persons. This level is significantly decreased in spasmophilia. Therapeutic by 25 OH CC of the calcipenic symptoms was tested with good clinical results. Some precautions are necessary when spasmophilia is associated with idiopathic hypercalciura.