GH deficiency in adults: an epidemiological approach.

OBJECTIVE: The prevalence of adult onset GH deficiency (GH-D) is poorly documented. Epidemiological data are now required to estimate the financial cost of GH treatment in adults. The aim of the present study was to estimate the prevalence of GH-D, from a cohort of 1652 adult patients with hypothalamo-pituitary diseases. DESIGN: The hormonal status of all patients presenting with pituitary diseaseand observed during the year 1994 in 15 endocrine units was retrospectively analyzed, irrespective of the date of disease onset, of the nature and date of pituitary investigations, and whether or not they included specific testing of the GH axis. Of the whole population of 1652 patients, a selected group (RG2) was chosen after exclusion of patients with active acromegaly (n=1414). RESULTS: GH stimulation tests had been performed in 549 patients of the RG2 group and a documented GH-D was found in 301. A relationship between the value of the GH peak and the number of pituitary deficits was evaluated. For instance, it was shown that 93% of patients with three deficits had GH-D. These results constituted the basis for estimating the number of GH-D in the group of untested patients. The number of GH-D deduced from the number of established GH-D (n=301) and from the number of GH-D hypothesized from other pituitary deficits (n=406) was 707 cases. Prevalence and annual incidence were calculated from data recorded in a referral center with a well-defined catchment area, Marseilles (Bouches du Rhône department). We projected a prevalence of 2638 for France and an annual incidence of 12 GH-D per million of the adult population.

[Papillary microcarcinoma]. / Les microcarcinomes papillaires.

The incidence of thyroid papillary microcarcinoma has appeared to increase over the last decade, probably because of more extensive use of serial slices for pathology. Prognosis is generally good, but the aggressive nature of certain tumors justifies an examination of the different risk factors such as age, sex, histology type, tumor size, lymph node involvement, and extrathyroid extension in order to develop a management scheme. Published results have been rather heterogeneous and do not allow a clear conclusion.

[A study of biological and histological criteria of thyroid autoimmunity in diffuse goiters with hyperthyroidism]. / Etude des paramètres biologiques et histologiques d'autoimmunité thyroïdienne dans les goitres diffus avec hyperthyroïdie.

Hyperthyroidism is usually classified as follows: with diffuse or with toxic plurinodular goiter, respectively considered as autoimmune and non-autoimmune thyroid disorders. This classification seems partially inadequate as signs of thyroid immunity may be found in some plurinodular toxic goiter and alternatively may by lacking in some cases of Graves' disease. These observations led us to study the intensity of intrathyroidal autoimmune process (IAP) and the levels of TBIAb, TPO- and Thyroglobulin-antibodies in 105 cases with diffuse goiter, hyperthyroidism and elevated RAIU (92 women and 13 men, age 34 +/- 11, mean +/- SD). The intensity of intrathyroidal autoimmune process (IAP) was determined by one pathologist (HT) by semi quantitative method applicable to routine clinical use. Subtotal thyroidectomy was performed because of a large goiter (n = 29), a concomitant cold nodule (n = 20), a recurrent disease (n = 18), intolerance to antithyroid drugs (n = 5) or because patients chose surgical treatment (n = 33). All cases were rendered euthyroid at the time of surgery using antithyroid drugs or iodine. The results show a lack of IAP and undetectable levels of TBIAb, TPO- and Thyroglobulin-antibodies in 10%, 11%, 25% and 47% respectively. The intensity of IAP was not different in case of first episode or recurrence of hyperthyroidism and was not related to type or duration of medical treatment. Comparison of patients with or without IAP show higher levels of TPO- and thyroglobulin-antibodies but not of TBIAb in the former group (P < 0.005). TBIAb were higher when ophthalmopathy and/or dermopathy were present vs absent (p < 0.05) and were correlated with FT4 levels (p < 0.05). The negative predictive value of TBIAb, TPO- and thyroglobulin-antibodies to predict the lack of significant IAP was 42%, 65% and 64%. The total absence of clinical, biological and histological signs of thyroid autoimmunity was found in only one case (female aged 35 with first episode of hyperthyroidism and no family history of thyroid disease) (0.9%). These results suggest that routine available criteria of thyroid immunity (including IAP) have a low specificity. It follows that they are probably inadequate to screen cases of hereditary toxic familial hyperplasia, a rare entity of still unknown prevalence.

[Hormonal suppressive therapy of thyroid nodules]. / Le freinage hormonal des nodules thyroïdiens.

We studied 426 patients in order to analyse the effectiveness of levothyroxine in treating patients with cold thyroid nodules. Nodule volume ranged initially from 0.1 to 10 mL and was measured over a 3 to 18 month-period of treatment using ultrasonography. Nodule variation was studied in each case according to levels of TSH and others factors (age, sex, familial thyroid history, initial volume of nodule and of thyroid gland, date of diagnosis, ultrasonic findings, duration of treatment). Nodule volume increased in 32.6% and significantly decreased (> 50%) in 35.8%. In 2.8% the nodule disappeared. No correlation was found between variation of thyroid nodules and TSH levels under treatment. Similarly no relationship was found between volume variation and other criteria. These results suggest that TSH suppressing doses of levothyroxine are of no advantage in reducing the volume of cold thyroid nodules compared to lower doses.

[Cutaneous manifestations of acromegaly: 4 cases]. / Signes cutanés de l'acromégalie: 4 observations.

INTRODUCTION: Some skin changes in acromegaly belong to the classical dysmorphic syndrome. Furthermore, other minor skin changes can be associated. OBSERVATIONS: We report 3 patients consulting in the department of Dermatology for various skin changes that have lead to the diagnosis of acromegaly. However these patients have also typical dysmorphic syndrome that they have failed to recognize. The fourth patient associated a cutaneous mastocytosis and acromegaly, as reported only once in literature. The evolution of the minor skin changes was parallel with the endocrinopathy. Moreover in one case, they have preceded the recurrence of the acromegaly. COMMENTS: Our observations demonstrate the importance of the minor skin changes that lead the patient to consult more than the dysmorphic syndrome. Moreover these changes that depend of growth hormone and other associated growth factors can be evolutive signs for endocrinopathy.

The PAQUID survey and correlates of subclinical hypothyroidism in elderly community residents in the southwest of France.

The aim of this study was to assess the prevalence of increased thyroid-stimulating hormone (TSH) levels (subclinical or undiagnosed hypothyroidism) in a representative sample of a community-living elderly population and to examine the relationships with cognitive functions and depressive symptoms. An epidemiological study was made of a cohort of 2792 subjects over 65 years of age. A blood sample was obtained from 425 volunteers of this cohort and assayed for TSH. Every subject participating in the study was interviewed and given a battery of neuropsychological tests by a psychologist. Three hundred and eighty-one subjects (89.7%) had normal TSH levels; 18 subjects (4.2%) had TSH lower than 0.4 microU/ml, associated in two of them with hyperthyroxinaemia. Twenty-six subjects (6.1%) had increased TSH levels, associated in 18 of them with a normal free thyroxine level and in eight with a low free thyroxine level. Increased TSH levels were significantly linked with female sex and with the presence of symptoms of depression on the CES-D scale but not with impairment of cognitive function.

[Papillary microcarcinoma of the thyroid]. / Microcarcinome papillaire de la thyroïde.

Treatment of thyroid differentiated carcinoma is controversial. In case of papillary microcarcinoma a low malignancy is usually considered and a limited surgical excision is currently used. We describe 49 cases with papillary tumor < 1 cm. Their high frequency (51% of all differentiated carcinoma discovered in the same period), current mode of their diagnosis (incidental histological findings: N = 48), and constant tumoral situation in extra nodular parenchyma are emphasised. In spite of median tumor size < 2 mm, 8% had extra thyroidal tumoral extent at diagnosis (node metastasis: N = 3; bone: N = 1). In one case with multifocal lesions in both lobes, an unilateral thyroidectomy would have missed contralateral periglandular metastatic nodes. Diagnosis of the case with asymptomatic bone metastasis was clearly attributable to radioiodine therapeutic use. These results suggest an heterogeneous prognosis of papillary microcarcinoma, with some cases requiring total bilateral thyroidectomy and radioiodine remnants ablation (e.g. Tumors invading peripheral thyroid tissue that seem at higher risk of extra glandular extension).

[Bone risk of hormone-suppressing therapy in differentiated thyroid epithelioma. Study by dual photon absorptiometry]. / Risque osseux de l'opothérapie freinatrice dans l'épithélioma différencié de la thyroïde. Etude par absorptiométrie biphotonique.

A decreased bone mineral density is a well known complication of thyrotoxicosis. If bone is also adversely affected by a subclinical hyperthyroidism is still debated. Such a situation is deliberately induced for treatment of thyroid differentiated carcinoma. We compared bone mineral measurements in case of thyroid carcinoma exposed to prolonged suppressive hormonal treatment (288 patient year, LT3 in 87%) and in age and weight matched controls. We did not find any difference in both sexes between the two populations in term of fracture rate and vertebral mineral density measured by dual photon absorptiometry, nor any influence of gonadal status in women.

Usefulness of the corticotropin-releasing hormone test during bilateral inferior petrosal sinus sampling for the diagnosis of Cushing's disease.

Inferior petrosal sinus blood sampling for ACTH measurement (IPSS) is used for the differential diagnosis of ACTH-dependent Cushing's syndrome and for the preoperative location of pituitary microadenomas. Intermittent ACTH secretion from pituitary adenomas may result in insignificant differences between petrosal and peripheral ACTH levels at the time of sampling. Thus, pituitary stimulation during IPSS may improve the procedure. The aim of the study was to evaluate the usefulness of CRH injection in combination with IPSS. Twenty-two patients with Cushing's disease (CD; 5 macroadenomas, 16 microadenomas, and 1 corticotroph hyperplasia) and 5 patients with ectopic ACTH syndrome were studied. Bilateral IPSS was successfully carried out on 25 patients. Patients with ectopic ACTH syndrome had, before and after CRH injection, central to peripheral ACTH gradients below 1.7. Four patients with CD had basal gradients below 1.4. After CRH administration all patients with CD had gradients above 3.2. Despite correct location of central catheters, the predicted location of pituitary microadenomas was erroneous in 41% of the cases. It was not improved after CRH injection. In conclusion, the combination of CRH injection with IPSS was useful for the differential diagnosis of ACTH-dependent Cushing's syndrome, as it increased the discrimination of the procedure. On the contrary, it was useless for the preoperative location of pituitary microadenomas, which was poorly predicted by IPSS.

[Macronodule associated with bilateral adrenal hyperplasia. A rare misleading cause of primary aldosteronism (two cases)]. / Macronodule associé à une hyperplasie bilatérale des surrénales. Une cause rare et trompeuse d'hyperaldostéronisme primaire (2 cas).

Aldosterone-producing adrenal adenoma and bilateral hyperplasia are the two predominant subtypes of primary aldosteronism. Their recognition is based essentially on adrenal CT scan and on measurements of plasma aldosterone and 18-hydroxycorticosterone (18-OHB) concentrations in response to postural testing. We report 2 cases of primary aldosteronism associated with a unilateral hyperplastic macronodule resembling an aldosterone-producing adenoma on CT scan. Plasma aldosterone and 18-OHB concentrations were consistent with this diagnosis in one patient. In the light of these two cases and of those previously published, the investigations needed for the etiological diagnosis of primary aldosteronism are discussed.

The corticotropin-releasing factor test in the differential diagnosis of Cushing's syndrome: a comparison with the lysine-vasopressin test.

The diagnostic accuracy of the CRH test was compared with that of the LVP test in 28 consecutive patients with ACTH-dependent Cushing's syndrome. A false negative response to CRH was found in 3 of 21 patients with pituitary-dependent Cushing's disease and to LVP in 4. The 7 patients with ectopic ACTH secretion were unresponsive to CRH, whereas 2 did respond to LVP. CRH and high-dose dexamethasone tests combination led to concordant results in 79% of patients. In all cases the etiological diagnosis suggested was correct. LVP and high-dose dexamethasone tests combination led to concordant results in only 71% of patients and the etiological diagnosis suggested was erroneous in one. Individual tolerance to the CRH test was also clearly better than that to the LVP test. It is concluded that the CRH test, alone or in combination with the high-dose dexamethasone test must be preferentially used to the LVP test in the differential diagnosis of ACTH-dependent Cushing's disease.

[Value of the corticoliberine test in the etiologic diagnosis of Cushing's syndrome]. / Intérêt du test à la corticolibérine dans le diagnostic étiologique du syndrome de Cushing.

Several studies have demonstrated that the corticotropin-releasing factor test (CRF) is useful for the aetiological diagnosis of Cushing's syndrome: in Cushing's disease, as opposed to ectopic ACTH secretion syndrome, the hypothalamus-pituitary-adrenal (HPA) axis can still be stimulated by CRF. In the present study, we compared the CRF test with the reinforced dexamethasone suppression test in 18 patients: 11 with Cushing's disease, 6 with ectopic ACTH secretion and 1 with adrenal gland adenoma. We obtained 2 false-negative results with the CRF test and 1 false-positive result with the dexamethasone suppression test. Our study, together with published data, suggests that the CRF test is useful in the exploration of Cushing's syndromes of uncertain origin. However, the results obtained with this test must be compared with those of other methods used to explore the HPA axis and which are still necessary.

[Hypoglycemia caused by overdose of a new anti-arrhythmia agent: cibenzoline. 3 cases]. / Hypoglycémies au cours de surdosages par un nouvel antiarythmique: la cibenzoline. Trois observations.

Severe fasting hypoglycaemia were observed in three patients treated with cibenzoline, a new class I antiarrhythmic drug. Retrospective analysis of electrocardiographic changes and serum level determinations showed that these reactions were contemporaneous with intoxication by overdosage of the drug. None of the patients was taking any other drug known to produce this adverse reaction, and in the absence of any other cause of hypoglycaemia, we concluded that it was related to the administration of cibenzoline. Thus, cibenzoline is yet another class I antiarrhythmic agent producing hypoglycaemia as an adverse reaction. Serum insulin levels measured in two of the three patients during hypoglycaemia were inappropriately high, suggesting that cibenzoline might stimulate insulin secretion.

[Evolution of serum gammaglutamyl transpeptidase activity in treated hyperthyroid and hypothyroid patients]. / Evolution de l'activité sérique gammaglutamyl transpeptidase (GGT) au cours des hyperthyroïdies et des hypothyroïdies traitées.

The pattern of gammaglutamyl transpeptidase levels was studied in the sera of 25 subjects with hyperthyroidism and 11 subjects with hypothyroidism, before and after treatment, and in 14 age- and sex-matched control subjects. Gammaglutamyl transpeptidase levels were significantly increased in hyperthyroidism (65 +/- 59 U/l) (p less than 0.01) and significantly decreased under treatment (40 +/- 27 U/l) (p less than 0.001). Before treatment, gammaglutamyl transpeptidase levels correlated with alkaline phosphatase levels and 5'-nucleotidase levels, the correlation persisting after treatment with 5'-nucleotidase. Alkaline phosphatase levels significantly increased under treatment (p less than 0.01). The percentages of gammaglutamyl transpeptidase variation correlated with thyroxine (r = 0.44, p less than 0.03), triiodothyronine (r = 0.47, p less than 0.02) and latent fixation capacity (r = 0.44, p less than 0.03) variations. Subjects with hypothyroidism had significantly decreased gammaglutamyl transpeptidase levels before treatment (18 +/- 9 U/l, p less than 0.01). Alkaline phosphatase levels were significantly decreased before treatment, and significantly increased after treatment. For all subjects with hyperthyroidism of hypothyroidism, the percentages of gammaglutamyl transpeptidase variations correlated with thyroxine (r = 0.48, p less than 0.003) and triiodothyronine (r = 0.39, p less than 0.016) variations. These results suggest that variations in gammaglutamyl transpeptidase levels in hyperthyroidism and hypothyroidism are, at least in part, in relation with variations in thyroid hormone levels.

[Endemic goiter in the Man region (Ivory Coast)]. / Le goitre endémique dans la région de Man (Côte-d'Ivoire).

An epidemiological study involving 616 subjects carried out in the Man region, Côte-d'Ivoire, showed endemic goitre in 54,4% of the group overall and in 80 % of females. Thyroid function of subjects chosen at random in the goitrous and nongoitrous group (105 G and 71 NG respectively) was identical. Compared with a French control group T4 was significantly lower but T3 and TSH were higher, which represents a high TBG level with low iodine elimination. High levels of TSH are not necessarily associated with low T3 or T4 levels, or with clinical signs of a hypothyroid condition. They are probably the result of a transient reaction. T4-TSH and T3-TSH correlations for NG subjects were (--0,40) but the T3-TSH correlation for the G subjects was significantly lower (--0,23). These differences could be explained by the simultaneous high levels of T3 and TSH more frequently encountered in G subjects and by the fact that serious hypothyroid conditions are more frequent in the NG group (6 out of 9). The percentage of hypothyroid conditions is high in both clinical and biological investigations. No anti-thyroglobulin antibodies were found in any of the hypothyroid cases with goitre. The histograms illustrate the clinical and biological heterogeneity of a homogeneous non-medicalised population.

[Clinical and laboratory features of endemic goiter in the Man region (Ivory Coast) (author's transl)]. / Aspect clinique et biologique du goitre endémique dans la région de Man (Côte d'Ivorie).

An epidemiological study involving 616 subjects carried out in the Man region, Côte d'Ivoire, showed endemic goiter in 54,5% of the group overall and in 80% of females. Thyroid function of subjects chosen at random in the goitrous and non-goitrous group (105 G and 71 NG respectively) was identical. Compared with a French control group T4 was significantly lower but T3 and TSH were higher. TBG level is high with low iodine elimination. High levels of TSH are not necessarily associated with low T3 or T4 levels, or with clinical signs of a hypothyroid condition. They are probably the result of a transient reaction. T4-TSH and T3-TSH correlations for NG subjects were (-0,40) but the T3-TSH correlation for the G subjects was significantly lower (-0,23). These differences could be explained by the simultaneous high levels of T3 and TSH more frequently rencountered in G subjects and by the fact that serious hypothyroid conditions are more frequent in the NG group (6 out of 9). The percentage of hypothyroid conditions is high in both clinical and biological investigations. No anti-thyroglobulin antibodies were found in any of the hypothyroid cases with goitre. The histograms illustrate the clinical and biological heterogeneity of a homogeneous non-medicalised population.

[Radioimmunological assay for antithyroglobulin antibodies, with the use of staphylococcal protein A as separating agents (author's transl)]. / Dosage des anticorps antithyroglobuline par une mêthode radio-immunologique utilisant la proténe A staphylococcique comme agent de séparation.

The staphylococcal cell wall protein A is known to bind specifically and rapidly to most of human immunoglobulin G. We have utilised this immunoadsorbent in a radio-immunoassay for antithyroglobulin antibodies (anti-Tg), to separate autoantibodies-125I thyroglobulin complexes from free 125I thyroglobulin (125I Tg). There was no specific precipitation of 125I Tg in the presence of 95,6% of sera from normal subjects (N = 45). In graves' disease, 56/65 hyperthyroid patients sera were positive, and so were 12/13 sera from patients with primary hypothyroidism. This assay showed a good correlation with the second antibody method, while much more rapid and slightly more sensitive. Compared with the new assay, the red cell agglutination test exhibited a high frequency of false negative results. This rapid, sensitive and inexpensive method provide an easy and reliable tool to screen sera acceptable for thyroglobulin measurement.