Clinical and biological phenotypes in late-onset 21-hydroxylase deficiency.

We analyzed data from 20 patients with late-onset 21-hydroxylase deficiency (LOHD). Three clinical phenotypes could be distinguished among the 18 women. Seven (39%) presented with clinical features suggesting polycystic ovarian disease (PCOD). However, despite androgen levels similar to those of patients with typical PCOD, high serum LH to FSH ratios were not consistently found. Seven other women (39%) presented with isolated hirsutism, suggesting idiopathic hirsutism. The remaining 4 women (22%) had no manifestations of androgen excess and were considered to have the cryptic form of LOHD. Serum 17-hydroxyprogesterone (17-OHP) and androgen levels were similar in the 3 phenotypes, suggesting that the clinical expression of LOHD in women is modulated by individual factors, such as androgen sensitivity. The 2 men were detected by family study and were clinically normal. Since clinical diagnosis of LOHD is impossible, we concentrated on hormonal data with the aim of providing guidelines for the biological diagnosis of LOHD. Assay of basal serum 17-OHD at 0800 h in both sexes and in the early follicular phase in women was sufficient to establish the diagnosis of LOHD in most patients. If doubtful results are obtained, i.e. serum 17-OHP levels between 2 and 5 ng/ml, an ACTH test must be performed. Post-ACTH serum 17-OHP levels exceeding 10 ng/ml confirm the diagnosis of LOHD. Such results should avoid confusion with heterozygotes for 21-hydroxylase deficiency, whose frequency is high within the general population and may be even higher in patients with idiopathic hirsutism or PCOD.

[Water intoxication after polydipsic episodes. (8 cases)]. / Les intoxications par l'eau après accès polydipsiques. (Huit observations).

Eight cases of convulsive coma by water intoxication without predisposing disease in the majority of instances in psychiatric patients, added to 25 cases from the literature make it possible to describe a stereotyped picture of "psychogenic" water intoxication. This includes episodes of polydipsia preceding convulsions and altered conscious level, accompanied by severe hyponatraemia. Cure occurs spontaneously after an acute hypotonic polyuric phase. Study of free water clearances and dynamic ADH suppression tests demonstrate hypovasopressinism which is difficult to inhibit, with "lower osmoreceptor reset". This abnormality is transient and sometimes relapsing.

[Posttraumatic neurogenic hyponatremia with late onset]. / Hyponatrémie neurogène post-traumatique de révélation tardive.

Ten months following a severe head injury, a 26-year-old man developed a syndrome of inappropriate secretion of antidiuretic hormone (ADH) with a grand mal seizure occurring after an increased intake of non alcoholic beverages. The water loading test was negative but the sorbitol infusion test was positive. In the basal state, plasma concentration of ADH was inappropriate to plasma osmolality. ADH has also been measured during dynamic tests (infusions of sorbitol and of normal saline; complete and partial water restriction; propranolol and diphenylhydantoin treatments). In spite of the poor sensitivity of these measurements when ADH concentrations are low, our results indicate that the plasma osmolality threshold at which ADH secretion is inhibited was probably reset at a level lower than normal.

[Postpartum thyroiditis. 31 cases]. / Les thyroïdites du post-partum. 31 cas.

Postpartum thyroiditis. 31 cases. Between 1977 and 1986, 29 women consulted in three internal medicine and endocrinology departments for clinical disorders which could be ascribed to 31 episodes of thyroiditis developed within 9 months of giving birth. Thyroiditis was diagnosed clinically on the basis of acute diffuse (11 cases) or nodular (7 cases) goitre formation, signs of dysthyroidism (16 cases) revealed by menstrual disturbances and/or galactorrhoea (11 cases). A thyrotoxic episode was observed in 9 patients; it was either without sequelae (5 cases) of followed by transient hypothyroidism (4 cases). In other patients transient hypothyroidism was observed in 11 cases and permanent hypothyroidism in 5 cases. Six patients showed no sign of dysthyroidism, and the diagnosis was made by immunological, cytological and/or histological examination of the thyroid gland. Circulating anti-thyroid antibodies were present in two-thirds of the patients. The results of radioisotope scanning varied according to the stage of the disease. In these patients, only the absence of goitre was predictive, in 4 out of 5 cases, of subsequent permanent hypothyroidism; in all other patients the prognosis was highly favourable, even without specific treatment.

[Proceeding: Production rate, metabolic clearance rate and mean plasma concentration of cortisol in hyperthyroidism (author's transl)]. / Taux de production, clearance métabolique et concentration plasmatique moyenne du cortisol dans l'hyperthyroïdie

The adrenocortical function was studied in 23 patients with hyperthyroidism and compared with a group of 15 normal subjects. Parameters of adrenal function were determined with 1,2(3)H-cortisol. The half-life of cortisol is significantly shortened in hyperthyroidism, as compared to normal subjects (49,5 +/- 6,6 min vs 68,3 +/- 10,5 min) and metabolic clearance rate is increased (418,5 +/- 89,5 L/24 h vs 237,5 +/- 48,5 L/24 h, for normal subjects). The production rate of cortisol, calculated from specific and cumulate activities of THE and THF is increased in hyperthyroidism expressed as mg/24 h or mg/m2/24 h (respectively : 26,7 +/- 7,8 mg/24 h vs 15,7 +/- 3 mg/24 h and 16,9 +/- 4,6 mg/m2/24 h vs 9,5 +/- 1,8 mg/m2/24 h). The mean plasma concentration, calculated as the radio (see article) is not statiscally different in hyperthyroid and normal subjects (6,8 +/- 2,1 microg/100 ml vs 7,3 +/- 1,9 microg/100 ml). 7 patients were reinvestigated after treatment of thyrotoxicosis when they were clinically and biologically in euthyroid state. All the values were normalized, without statistically significant difference from control (T 1/2 = 65,4 +/- 18 min, Metb Cl. Rate : 255 +/- 64,5 L/24 h, production rate : 15,6 +/- 1,8 mg/24 h and 9 +/- 1,4 mg/m2/24 h. mean plasma concentration : 6,8 +/- 2,8 microg/100 ml). Shortened cortisol half life, increased metabolic clearance rate and production rate, and normal mean plasma concentration have been reported in hyperthyroidism (Peterson, Copinschi, Gallagher). These changes, secondary to thyroid hormone excess, are the consequences of increased hepatic catabolism of cortisol. The activity of 11 OH steroid deshydrogenase is increased, as demonstrated by increased ratio (see article) in normal subjects (0,001 less than p less than 0,005). There is a high proportion of 17 kéto metabolites (E, DHE, THE) whose feed-back effect is weak as compared to 17 OH metabolites (F, DHF, THF). The hypothalamo-hypophyso-adrenal system is stimulated to maintain a normal plasma concentration. The fact that the mean plasma concentration is normal despite the increased production rate suggest that changes are rather due to increased catabolism than to central effect of thyroid hormones.

[Phaeochromocytoma with hypokalaemia (two cases) (author's transl)]. / Phéochromocytome avec hypokaliémie. A propos de deux observations.

Two cases of phaeochromocytoma with hypokalaemia are reported. In the first, a carcinoma, hypokalaemia was potentially secondary to hyperreninaemia and hyperaldosteronism in association with probably paraneoplastic hypercorticism. The other was benign and the origin of isotopically demonstrated potassium deficiency was less clear, because hyperreninaemia, hyperaldosteronism and hypercortisolism were moderate.

[Proceedings: Plasma renin activity in management of Addison's disease (author's transl)]. / L'activité rénine plasmatique dans la surveillance du traitement de la maladie d'Addison

13 patients with Addison's disease, 7 men and 6 women, 19 to 61 years old, were investigated. Plasma Renin Activity (P.R.A.) is measured by radioimmunoassay of Angiotensin I (ng/ml/h) in the supine (S) and the upright (U) position. These patients are studied before treatment and under normal sodium diet in 11 cases: the P.R.A. value is constantly increased [5 men: MS = 10,09 (range: 6,2-12,5) and MU = 23,22 (range : 17,1-31,09), 6 women : MS = 24,48 (range : 3,46-45,04) and MU = 42,23 (range : 42,23 (range 17,37-69,34), to be compared with our normal values (M +/- S.D.) : MS = 1,02 +/- 0,39 and MU = 2,56 +/- 0,99 for men - MS = 0,82 +/- 0,14 and MU = 2,32 +/- 0,93 for women in follicular phase - MS = 1,45 +/- 0,56 and MU = 4,59 +/- 1,63 for women in luteinic phase. After dietary sodium restriction (10 mEq/24 h) in 2 cases, the P.R.A. is significantly increased with respect to the basal value]. Under Hydrocortisone alone (25 to 30 mg/24 h) and normal sodium diet, 4 patients kept significantly increased P.R.A. values. Under Hydrocortisone (20 to 40 mg/24 h) and 9-alpha-fluorohydrocortisone (50 to 100 microgrammes/24 h) for 6 days to 14 months, the P.R.A. value decrease into the normal range [men : MS = 1,02 (range : 0,54-1,92) and MU = 1,68 (RNAGE : 0,81-2,57) - 2 Menopausal women : MS = 1,55 and MU - 1,16. The P.R.A. measurement seems useful in the adaptation of Addision's disease treatment.

[Production rate and mean plasma concentration of cortisol in hyperthyroidism (author's transl)]. / Taux de production et concentration plasmatique moyenne du cortisol dans l'hyperthyroïdie

The adrenocortical function was studied in 23 patients with hyperthyroidism. The half-life of tritiated cortisol was significantly shortened; metabolic clearance rate was about twice increased, and production rate of cortisol was significantly increased in hyperthyroidism. The mean plasma concentration was unmodified. After return to euthyroid state, all the values were normalized in 7 patients.

Prolactin regulation in 14 cases of galactorrhea and hypogonadism with minimal modifications of the sella turcica (author's transl). / Etude de la fonction prolactinique dans 14 cas de galactorrhée avec hypogonadisme et micro-déformation de la selle turcique

In this study we report 13 cases of amenorrhea-galactorrhea and one of a male patient complaining of gynecomastia, galactorrhea, sexual impotence and sterility with oligoasthénospermy. In these cases, the size of the sella turcica was normal but we found a localized depression of the bottom of the sella turcica; these modifications were situated at the antero-inferior part of the sella in 12 cases and posteriorly in the 2 others. Basal prolactin level was higher than normal values in 13 cases (12 female and 1 male patients): individual values varied between 45 and 367 ng/ml. Nycthermeral rhythm disappeared in the 9 cases studied. Administration of L-Dopa (500 mg orally) significantly suppressed the prolactin values in the 11 cases studied. Oral water loading (20 ml/kg) left prolactin values unchanged (10 cases). After oral glucose tolerance test (1 g/kg) no significant systematic variation occurred. The increase of prolactin values after stimulation by 200 microg. TRH IV as a bolus (4 cases) was not significant. We have found similar prolactin variations in cases of hyperprolactinemia with either normal pituitary fossa (7 cases) or macro-adenoma (6 cases).

[Therapeutical effects of bromocriptine (CB 154) in 10 acromegalic subjects. Study of somatotrophic function and clinical survey (author's transl)]. / Effets thérapeutiques de la bromocriptine (CB 154) chez 10 sujets acromégales. Etude de la fonction somatotrope et évolution clinique.

Plasma GH levels were studied following acute administration of 2.5 mg of bromocriptine (CB 154) in 12 acromegalic patients. In 9 responders, reduction of GH levels was obvious 2 to 4 hours after bromocriptine administration and the lowest values were achieved between 5 and 8 hours following drug absorption. This pattern suggested the use of bromocriptine at a dose of 2.5 mg six-hourly in chronic treatment of acromegaly. Chronic administration of CB-154 in 10 acromegalic patients was followed by a stable reduction of plasma GH levels in seven subjects. No appreciable variation in GH levels were observed in one patient who was unresponsive to acute administration of CB-154 and in two other subjects treated with 2.5 mg 12-hourly. In three patients who had high plasma GH levels inspite of an anterior treatment by hypophyseal surgery and/or physiotherapy, plasma GH values were normalised under bromocriptine therapy. (9 to 24 months). In the four other subjects, high basal plasma GH levels were reduced with at least 50% reduction rate from baseline. Nevertheless, in two subjects from the latter group bromocriptine daily dose was increased to 20 mg divided in four fractions, because of an escape phenomenon to initial dose regimen. Normalisation or reduction of plasma GH levels was associated with considerable clinical improvement. Tolerance of the drug was excellent in all patients but four who experienced nausea and vomiting; these side effects disappeared when treatment was reduced and then increased gradually.

[Inhibition of prolactin release by methysergide and bromocriptine in hyperprolactinemic subjects: comparative dynamic studies (author's transl)]. / Variations comparées de la prolactinémie sous méthysergide et bromocriptine dans les états d'hyperprolactinisme.

Reduction of hyperprolactinemia by Methysergide (4.4 mg p.o.) and Bromocriptine (2.5 ng p.o.) was studied in 20 patients (7 subjects with pituitary macroadenoma and 13 hyperprolactinemic patients with normal sella turcica). No difference was observed between the effects of the two drugs 4 hours after their administration, with and without respect of the aetiologies of hyperprolactinemia. However the serum prolactin levels were significantly lower 6 hours (n = 11 p = 0,01) and 12 hours (n = 10 p less than 0,01) after Bromocriptine than after methysergide. The difference observed between the two drugs seems to be inherent to their different half-lives.

[Blood amylase and lipase in diabetic ketoacidosis]. / Amylasémie et lipasémie au cours de la céto-acidose diabétique.

The relation between increase of amylasaemia and increase of lipasaemia was studied during ketoacidosis in 31 insulin-dependent diabetics. The effects of metabolic disturbances on amylase production during the acute phase of ketoacidosis were also evaluated. The greatest increase of amylasaemia was observed after 24 hours in 17 cases (55%), with return to normal values after 3 to 7 days. Amylasuria was closely correlated with amylasaemia (r = 0.7; P less than 0.01). No correlation was found between hyperamylasaemia and the degree of ketoacidosis, but there was a correlation between plasma osmolality and hyperamylasaemia (r = 0.44; P less than 0.02). The increase of lipasaemia, considered more specific of pancreatic damage, was closely correlated with that of amylasaemia (r = 0.63: P less than 0.01). The electrolyte disturbances associated with ketoacidosis are responsible for cellular damage with release of enzymes in many tissues. The hyperamylasaemia consecutive to pancreatic damage might be of similar origin and aggravated by splanchnic hypoperfusion.

[Craniopharyngioma in the same family]. / Craniopharyngiome dans une même fratrie.

Within 2 years, two sisters, aged 23 and 33, were operated on for a craniopharyngioma. With regard to this exceptional feature, relation between neuroectodermal affections and craniopharyngiomas is discussed, and genetic determination of the occurrence of those tumors is evoked.

[New elements in the diagnosis and treatment of thyrotropic pituitary adenomas with hyperthyroidism]. / Eléments nouveaux dans le diagnostic et le traitement des adénomes hypophysaires thyréotropes avec hyperthyroïdie.

Although thyrotropin-secreting pituitary tumors are rather exceptional, the authors have studied 5 new cases from 1982 to 1988. This apparently growing pattern is due to a more accurate diagnosis because of new laboratory measurements: --Immunoradiometric assay (IRMA) of ultra-sensitive thyrotropin (TSH); --Radioimmunoassay (RIA) of free alpha subunit of TSH; --Molar ratio of free alpha subunit/TSH before and after TRH stimulation; --Morphologic assessment of pituitary adenoma by computed tomographic scanning and nuclear magnetic resonance imaging; --Characterization of thyrotropin-secreting cells by immunohistochemical technics and identification of secretion products in cultured cells. The authors illustrate these new topics with a case report harboring a partial resistance to thyroid hormones. A 6-month treatment with somatostatin analogue (SMS 201.995) is reported, before transphenoidal ablation of the adenoma.