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PubMed2007

Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society.

OBJECTIVE: Low birth weight remains a major cause of morbidity and mortality in early infancy and childhood. It is associated with an increased risk of health problems later in life, particularly coronary heart disease and stroke. A meeting was convened to identify the key health issues facing a child born small for gestational age (SGA) and to propose management strategies. PARTICIPANTS: There were 42 participants chosen for their expertise in obstetrics, peri- and neonatal medicine, pediatrics, pediatric and adult endocrinology, epidemiology, and pharmacology. EVIDENCE: Written materials were exchanged, reviewed, revised, and then made available to all. This formed the basis for discussions at the meeting. Where published data were not available or adequate, discussion was based on expert clinical opinions. CONSENSUS PROCESS: Each set of questions was considered by all and then discussed in plenary sessions with consensus and unresolved issues identified. The consensus statement was prepared in plenary sessions and then edited by the group chairs and shared with all participants. CONCLUSIONS: The diagnosis of SGA should be based on accurate anthropometry at birth including weight, length, and head circumference. We recommend early surveillance in a growth clinic for those without catch-up. Early neurodevelopment evaluation and interventions are warranted in at-risk children. Endocrine and metabolic disturbances in the SGA child are recognized but infrequent. For the 10% who lack catch-up, GH treatment can increase linear growth. Early intervention with GH for those with severe growth retardation (height sd score, <-2.5; age, 2-4 yr) should be considered at a dose of 35-70 microg/kg x d. Long-term surveillance of treated patients is essential. The associations at a population level between low birth weight, including SGA, and coronary heart disease and stroke in later life are recognized, but there is inadequate evidence to recommend routine health surveillance of all adults born SGA outside of normal clinical practice.

Adult↗

PubMed1975

Clinical and endocrinologic characterization of a patients with the syndrome of incomplete testicular feminization.

A 46 XY individual with male pseudohermaphroditism was investigated. The phenotype was distinctive in that the habitus was female in character, but partial fusion of the labioscrotal folds, testes, and male wolffian duct structures that terminated in the vagina were present. Müllerian structures were absent. At the expected time of puberty both feminization (breast development) and virilization (clitoral enlargement) took place. Studies of estrogen and androgen dynamics revealed plasma testosterone levels and production rates characteristic of normal men. Plasma estrogen levels and production rates were greater than those of normal men. Plasma gonadotropin levels were also high. These findings suggest that the fundamental defect in this patient is androgen resistance rather than defective androgen synthesis. Dihydrotestosterone formation from testosterone slices of epididymis and perineal skin was normal. The family history was uninformative. On endocrinologic, genetic, and phenotypic grounds the syndrome of incomplete testicular feminization can be separated from the complete form of testicular feminization and from familial incomplete male pseudohermaphroditism, Type 2. Additional studies will be required to determine whether this disorder is also distinct from the Type 1 form of familial incomplete male pseudohermaphromditism.

Androstenedione↗

PubMed1983

Pituitary adenomas in acromegalic patients: an immunohistochemical and endocrinological study with special reference to prolactin-secreting adenoma.

To establish a functional classification of purification of pituitary adenomas in acromegalic patients, we used immunoperoxidase-staining techniques specific for GH and PRL. Surgical specimens from 55 acromegalic patients were studied. GH was demonstrated in all adenomas and PRL was found in 25 of them (45.5%). Immunohistologically, GH- and PRL-containing adenomas could be divided into 3 types. In type 1 (11 patients), immunoreactive PRL was present in single cells surrounded by immunoreactive GH cells. In type 2 (6 patients), immunoreactive PRL cells formed clusters. In Type 3 (8 patients), immunoreactive PRL and GH cells demonstrated a mosaic pattern, and it was difficult to determine which were in the majority. A double immunostaining method revealed 15 adenomas in which individual cells contained both GH and PRL. Hyperprolactinemia was present in 21 patients, 15 of these had immunoreactive PRL cells (type 1, 4 patients; type 2, 3 patients; type 3, 8 patients). There was no correlation between the size of the adenoma and its type. Endocrinologically, all patients with type 2 and 3 adenomas had an abnormal serum GH response to TRH administration; all type 3 patients had a substantial serum PRL response to TRH administration. Type 3 is considered to be an actively PRL-secreting adenoma, resulting in hyperprolactinemia.

Acromegaly↗

PubMed1995

The endocrinology of the menopausal transition: a cross-sectional study of a population-based sample.

In a study of the endocrinology of the perimenopausal years, levels of serum FSH, estradiol (E2), immunoreactive inhibin (INH), testosterone, and sex hormone-binding globulin were measured in a population-based sample of 380 women (mean age, 49.4 yr; range, 45.6-56.9 yr). Subjects were divided into women who reported continuing regular menstrual cycles (27%; group I), a change in menstrual flow without a change in frequency (23%; group II), a change in frequency but no change in flow (9%; group III), changes in both frequency and flow (28%; group IV), and at least 3 months since their last menstrual period (13%; group V). After adjusting for age and body mass index, the geometric mean FSH increased across menstrual groups and, compared with group I, was 53% higher in group IV (P < 0.0005) and 253% higher in group V (P < 0.0001). Age- and body mass index-adjusted geometric means for E2 and INH in group V were 54% and 53% of those in group 1, respectively (P < 0.005, P < 0.0001). Women in group V who did not have a menstrual period in the next year had higher FSH and lower E2 and INH levels than those who subsequently went on to have at least one more menstrual period (P < 0.05). FSH was negatively correlated with E2 (r = -0.30) and INH (r = -0.39), whereas INH was positively correlated with E2 (r = 0.45). We conclude that an increase in serum FSH and decreases in E2 and INH are the major endocrine changes associated cross-sectionally with the menopausal transition.

Androgens↗

PubMed2000

A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology.

The aim of this study was to perform a national survey on occasionally discovered adrenal masses [adrenal incidentalomas (AI)] under the auspices of the Italian Society of Endocrinology. This multicentric and retrospective evaluation of patients with AI includes 1096 cases collected in 26 centers between 1980 and 1995. Relevant information was obtained by means of a specifically tailored questionnaire. Of the 1096 forms received, 1004 were retained for final analysis. Patients were 420 males and 584 females, aged between 15-86 yr (median, 58 yr). Mass size (computed tomography measurement) ranged from 0.5-25 cm (median, 3.0 cm). Hormonal work-up demonstrated that 85% of the masses were nonhypersecretory, 9.2% were defined as subclinical Cushing's syndrome, 4.2% were pheochromocytomas, and 1.6% were aldosteronomas. Adrenalectomy was performed in 380 patients with removal of 198 cortical adenomas (52%), 47 cortical carcinomas (12%), 42 pheochromocytomas (11%), and other less frequent tumor types. Patients with carcinoma were significantly younger than patients with adenoma (median, 46; range, 17-84; vs. 57, 16-83 yr; P = 0.05). Adenomas were significantly smaller than carcinomas (3.5, 1-15 vs. 7.5, 2.6-25 cm; P < 0.001), and a cut-off at 4.0 cm had the highest sensitivity (93%) in differentiating between benign and malignant tumors. Hormonal work-up of patients with subclinical Cushing's syndrome showed low baseline ACTH in 79%, cortisol unsuppressibility after 1 mg dexamethasone in 73%, above normal urinary free cortisol in 75%, disturbed cortisol rhythm in 43%, and blunted ACTH response to CRH in 55%. Only 43% of patients with pheochromocytoma were hypertensive, and 86% showed elevated urinary catecholamines. All patients with aldosteronoma were hypertensive and had suppressed upright PRA. These results indicate that mass size is the most reliable variable in separating benign from malignant AI. Adrenalectomy should be recommended for AI greater than 4.0 cm because of the increased risk of malignancy, especially in young patients. Endocrine evaluation should be performed in all patients to identify silent states of hormone excess.

Adolescent↗

PubMed2006

Effects of larval nutrition on the endocrinology of mosquito egg development.

Reproduction by female mosquitoes is dependent on energy resources but modulated by hormones. Our study focused on blood-meal-dependent, anautogenous Aedes aegypti and autogenous Ochlerotatus atropalpus that rely on larval-derived nutrient stores to develop eggs. To determine how larval nutrition affects the endocrinology of egg development in these females, we manipulated the quantity of larval food and measured in vitro production of juvenile hormone (JH) by corpora allata (CA) and ecdysteroids by ovaries. Newly emerged A. aegypti contain lower larval-derived protein reserves, and their CA produce high amounts of JH, in comparison with similarly staged Oc. atropalpus. Ecdysteroid production was initiated in newly emerged Oc. atropalpus females, which have higher protein reserves and which develop eggs without a blood meal, which is required by A. aegypti females to complete egg development.

Aedes↗

PubMed1986

Haematological, immunological and endocrinological aspects of chronic high frequency blood sampling in rats with replacement by fresh or preserved donor blood.

Haematological, immunological and endocrinological aspects of blood transfusions with either freshly collected or preserved donor blood were investigated in chronically cannulated unrestrained rats. Three anticoagulant preservatives were tested: citrate, citrate-dextrose and citrate-phosphate-dextrose-adenine (CPDA-1). Prolactin was used as an indicator of stress in endocrine studies. The repeated collection of 4 ml blood at 2-week intervals did not affect normal blood composition. Whole blood of rats could be stored in citrate, citrate-dextrose or CPDA-1 for 8, 22 or 35 days, respectively. Blood transfusions with fresh or preserved donor blood of F1 (R X U) rats did not affect normal blood composition nor did it induce immunological responses in F1 rats. Frequent blood sampling for several hours at highest rates of 1 sample/min did not affect prolactin secretion when blood volume reduction was replaced by blood transfusions with fresh donor blood. However, compensation with preserved blood affected prolactin secretion significantly. Blood transfusions did not affect health, behaviour, cyclicity or pseudopregnancy. The application of blood transfusion in chronically cannulated rats appeared to be quite simple. Its advantages are the possibility of following individual secretion patterns of blood-bound substances, the repeated use of animals and the reduction of the number of animals.

Animals↗

PubMed2003

Endocrinological changes before and after removal of the granulosa theca cell tumor (GTCT) affected ovary in 6 mares.

To clarify the endocrinological characteristics of the mares with granulosa theca cell tumor (GTCT), peripheral plasma samples from the 6 mares affected with GTCT were collected before and after the surgical removal of the affected ovary. Concentrations of testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), immunoreactive-inhibin (ir-INH), progesterone (P) and estradiol-17beta (E(2)) in the plasma samples were measured by radioimmunoassay. Before removal of GTCT in all cases, the concentrations of T were significantly higher than those of normal mares at the breeding and non-breeding seasons, whereas plasma concentrations of FSH, LH, ir-INH, P and E(2) were lower. After surgical removal of the affected ovary, the circulatory concentrations of T was declined, but the concentrations of other hormones were constantly low as compared with those of normal mares. The present study suggests that 1) the source of higher T may be due to the abnormal follicles in ovary of GTCT, 2) in the case of GTCT the elevated level of T is observed due to the lack of aromatase, and 3) the high level of T is a typical characteristics for GTCT in mares. It is also suggested 4) due to the elevated levels of T the concentrations of gonadotropins may be suppressed.

Animals↗

PubMed1999

Physiologic and endocrinologic characterization of male sex-biased diabetes in C57BLKS/J mice congenic for the fat mutation at the carboxypeptidease E locus.

The fat gene in mice represents a recessive mutation at the carboxypeptidase E (Cpe) locus. The mutant allele (Cpe(fat)) encodes a highly unstable enzyme and produces an obesity phenotype characterized by attenuated processing of prohormones such as proinsulin that require this exopeptidase for full maturation. This article presents a preliminary physiologic and endocrinologic characterization of the stock of C57BLKS/LtJ-Cpe(fat)/Cpe(fat) mice at the backcross generation (N10) currently distributed by The Jackson Laboratory. Although previously reported not to be diabetogenic at N5, an additional five backcrosses to the C57BLKS/J background resulted in a male-biased development of both obesity and diabetes. Major differences distinguishing this mutant stock from the phenotypes produced by either the diabetes (Lepr(db)) or obese (Lep(ob)) mutations on the same inbred strain background are lack of hyperphagia and hypercorticism, sensitivity of diabetic males to exogenous insulin, and a milder and male-biased diabetes syndrome that is not associated with widespread beta-cell necrosis and islet atrophy, and that often remits with age.

Animals↗

PubMed1987

[The role of nuclear medicine in endocrinology].

Radioisotopes have been widely used in both in vitro and in vivo studies of endocrine organs. In this lecture, results of our recent in vitro studies on calcium regulating hormones, thyroid-stimulating hormone, and gastro-intestinal hormones are reviewed. 1) Clinical evaluation of measurement of calcium regulating hormones such as PTH, calcitonin and vitamin D metabolites was demonstrated. Furthermore, problems of those assays were also discussed. Especially, simpler methods which measure intact PTH or vitamin D metabolites are to be developed. PTH-like factor, which should play the major role in hypercalcemia of malignancy, was assayed biologically. After determination of amino-acid sequence of this protein, clinical measurement should reveal mechanism of hypercalcemia of malignancy. 2) Studies on TSH-receptor antibodies by using radioreceptor assay. TSH-binding inhibitor immunoglobulins (TBII) were detected not only in 93% of untreated patients with Graves' disease, but also in 21% of patients with primary myxedema. In contrast to the thyroid-stimulating nature of TBII in Graves' patients, TBII in hypothyroid patients were disclosed to be blocking in their nature. Clinical and laboratory findings supported pathogenetic role of the blocking antibodies in the latter condition. 3) Mutual regulation between CCK and muscarinic receptors on dispersed pancreatic acini. CCK and carbachol in their higher concentrations regulated muscarinic receptor and CCK receptor, respectively. The mode of regulation of both receptors was disappearance of their high affinity binding site. TPA, an activator of protein kinase C, modulated both receptors in the same manner as CCK or carbachol. These effects of CCK and carbachol on receptors were well compatible to the restriction of carbachol or CCK induced amylase secretion by CCK or carbachol. These in vitro studies, in association with the results of in vivo studies, contribute to the developments of nuclear endocrinology.

Animals↗

PubMed1994

Antiandrogenic activity and endocrinological profile of a novel antiandrogen, TZP-4238, in the rat.

TZP-4238 is a new potent, orally active steroidal antiandrogen. Antiandrogenic activity and endocrinological profile of TZP-4238 were investigated in rats, except that progestational activity was determined in rabbits. TZP-4238 suppressed the testosterone propionate-induced increases in the weights of the ventral prostate, seminal vesicle and levator ani in castrated immature male rats. TZP-4238 also decreased the weights of the ventral prostate, seminal vesicle and levator ani in intact adult male rats, but did not affect the weight of the testis or the serum concentrations of luteinizing hormone and testosterone. TZP-4238 did not have such an inhibitory effect on the weight of the adrenal gland as seen in other steroidal antiandrogens. It exhibited potent progestational activity. Although TZP-4238 did not exert androgenic or estrogenic activity, it had weak antiestrogenic activity. These results suggest that TZP-4238 exerts an antiandrogenic effect on the prostate without any compensatory change in the serum concentration of luteinizing hormone or testosterone in rats, and it is a useful drug for the treatment of androgen-dependent diseases such as prostatic hypertrophy and prostatic cancer.

Administration, Oral↗

PubMed2000

Genetic and endocrinological evaluations of three 46,XX patients with congenital lipoid adrenal hyperplasia previously reported as having presented spontaneous puberty.

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive disorder characterized by impaired synthesis of adrenal and gonadal steroids. It was demonstrated that loss-of-function mutations in the steroidogenic acute regulatory protein (StAR) gene cause CLAH and that 46,XX patients with CLAH develop spontaneous puberty. We had reported that three 46,XX patients with CLAH had presented spontaneous puberty and one of the patients had developed life-threatening ovarian cysts, before the etiology of CLAH had been clarified. In the present study, we analyzed their StAR gene and demonstrated mutations. Endocrinological examinations of the patients revealed that serum LH and FSH levels and their responses to the LHRH stimulation were not exaggerated before the onset of puberty. Serum LH levels and its response to LHRH were increased during puberty, whereas serum FSH levels remained within the normal range. Serum estradiol increased after the administration of human menopausal gonadotropins in the pubertal patient, suggesting that the ovary might have another system than StAR to facilitate cholesterol transport into the mitochondria. Although the patients had menstrual cycles, they remained anovulatory, and the resultant increased secretion of LH was speculated to be responsible for the development of ovarian cysts.

Adrenal Hyperplasia, Congenital↗

PubMed2004

Translational medicine in fish-derived peptides: from fish endocrinology to human physiology and diseases.

Recent studies have revealed the importance of fish-derived peptide hormones to human endocrinology. These peptides include melanin-concentrating hormone (MCH), urocortins (human urotensin-I), and urotensin-II. MCH, a hypothalamic peptide, is a potent stimulator on appetite. Urocortins, e.g. urocortin 1 and urocortin 3 (stresscopin), are endogenous ligands for the corticotropin-releasing factor (CRF) receptors, particularly CRF type 2 receptor, that mediates a vasodilator action, a positive inotropic action and a central appetite-inhibiting action. These actions mediated by CRF type 2 receptor may ameliorate the stress response. Human urotensin-II is a potent vasoconstrictor peptide, while it acts as a vasodilator on some arteries. Human urotensin-II is expressed in various types of cells and tissues, including cardiovascular tissues, as well as many types of tumor cells. Thus, these fish-derived peptides appear to play important roles in human physiology, such as appetite regulation, stress response and cardiovascular regulation, and also in diseases, for example, obesity, cardiovascular diseases and tumors. Development of antagonists/agonists against the receptors for these peptides may open new strategies for the treatment of various diseases, including obesity-related diseases, hypertension, heart failure and malignant tumors.

Animals↗

PubMed2004

Adrenocortical hyperplasia associated with ACTH-dependent Cushing's syndrome: comparison of the size of adrenal glands with clinical and endocrinological data.

Diffuse or nodular hyperplasia of adrenal glands is associated frequently with ACTH-dependent Cushing's syndrome. We carried out a retrospective analysis of 28 patients with ACTH-dependent Cushing's syndrome admitted to our institution between 1984 and 1999 in order to clarify the incidence of adrenal hyperplasia in ACTH-dependent Cushing's syndrome and also to determine the correlation between adrenal gland images and clinical, biochemical and endocrinological data. Of the 28 patients, 16 (57%) showed diffuse adrenal hyperplasia while only 3 had focal adrenal nodules in the hypertrophied adrenals. There was a positive, significant correlation between the width of the adrenal glands measured on CT and circulating plasma ACTH, cortisol levels and urinary free cortisol (UFC) levels. Duration of the disease also correlated positively with adrenal width. No correlation was found between age and adrenal size and there was no difference in the prevalence of diffuse hyperplasia between normotensive and hypertensive patients. These results suggest that chronic ACTH hypersecretion may lead to diffuse adrenal hyperplasia in patients with ACTH-dependent Cushing's syndrome.

ACTH Syndrome, Ectopic↗

PubMed2001

Clinical, endocrinological and radiography features in a child with McCune-Albright syndrome and pituitary adenoma.

McCune-Albright syndrome is a rare syndrome presenting with polyostotic dysplasia, cafe-au-lait spots and multiple endocrinopathies that is very often combined with precocious puberty. We examined the clinical, endocrinological and radiological features in a boy with McCune-Albright syndrome and pituitary adenoma. X-rays, magnetic resonance (MRI) scan, whole body scintigraphy, single photon emission computer tomography (SPECT) and 3D-reconstruction from bone SPECT was performed to evaluate clinical improvement after treatment with sandostatin and pamidronic acid. After a six-month period of treatment with sandostatin and pamidronate, bone scintigraphy revealed significantly reduced activity. Treatment with bromocriptine and methimazole led to normalization of prolactin and thyroid hormone levels. Mobility of the patient improved. A significant improvement as a result of treatment with sandostatin and pamidronic acid was found in this patient with generalized fibrous dysplasia. So far, this condition has been treated with pamidronate only in adults, but severely affected children also benefit from this treatment regimen.

Adenoma↗

PubMed1984

Endocrinological effects of single daily ketoconazole administration in male beagle dogs.

Some endocrinological effects of single daily oral administration of 150 mg ketoconazole for 15 days were investigated in 4 male beagle dogs. Plasma testosterone fell markedly within 3-4 h and then progressively returned to control concentrations by 10 h after drug administration. On the other hand, plasma 17 alpha-hydroxyprogesterone, progesterone and 17 alpha, 20 alpha-dihydroxyprogesterone increased within 3-10 h before returning to basal values after 24 h. Plasma LH did not rise significantly though some high individual levels were noted. Plasma cortisol and oestradiol-17 alpha levels were not significantly modified by the treatment. These results confirm that a high therapeutic dose of ketoconazole, given orally once a day, transiently inhibits in vivo the 17-20 lyase enzyme of the testis, without modifying basal cortisol and oestradiol-17 beta plasma concentrations and that enzymatic inhibition still occurs after daily treatment for up to 2 weeks but remains transient and parallels the resorption profile of the drug so that normal plasma testosterone levels are observed from 10 to 24 h after drug intake. However, permanent inhibition of androgen biosynthesis might be obtained by the administration of high doses of ketoconazole given several times a day.

17-alpha-Hydroxyprogesterone↗

PubMed2006

Phenotype and HFE genotype in a population with abnormal iron markers recruited from an Endocrinology Department.

OBJECTIVE: The aim of this study was to describe HFE genotype in a population of patients with altered iron markers recruited in an Endocrinology Department and to define the possible phenotype-genotype relationships. METHODS: A total of 156 patients with high serum ferritin concentrations (>300 ng/ml) or transferrin saturation (>45%) (I group), and a control group of 106 healthy subjects (C group) underwent HFE genotyping (classical C282Y and H63D mutations). We also examined the main genetic features of subgroups in I according to the presence (D) or the absence (ND) of diabetes. RESULTS: (1) The genotypes were significantly different in the I and C groups (P<0.001), with an increased frequency of major 282Y allele in the I group (35% vs 7.5%), but not of minor 63D allele (17 vs 18.5%). (2) The genotype of D and ND groups also differed (P<0.0001), with a lower frequency of C282 heterozygosity (P<0.0001) in the D group, and a higher prevalence of H63D heterozygosity in the D vs ND groups (P<0.01). (3) The phenotypic comparison of D and ND groups also showed a higher mean body mass index, age, and serum ferritin concentration, as well as an increased proportion of males with increased liver enzymes in the D group. CONCLUSION: This population harboring abnormal iron markers had a different HFE genotype and a higher 282Y allele frequency than the control population. This suggests that blood iron markers could be checked in etiological investigations of metabolic disturbances to identify patients who should undergo genotyping, since approximately 20% were diagnosed with C282Y homozygosity.

Adult↗

PubMed1985

Plasma progesterone concentrations, ovarian and endocrinological response and sperm transport in ewes with synchronized oestrus.

Two experiments involving 24 and 54 Australian Merino ewes were conducted in which the establishment of a cervical population of spermatozoa and several endocrinological events were studied after several regimens for the synchronization of oestrus. Intravaginal sponges impregnated with 500 mg (Exp. 1) or 200, 400 or 600 mg (Exp. 2) progesterone resulted in the maintenance of plasma progesterone concentrations of 1.5-4.9 ng/ml over a 12-day insertion period compared with 1.9-6.9 ng/ml during dioestrus in control ewes. In Exp. 1 basal concentrations of less than or equal to 0.25 ng/ml plasma were attained by 4 h after sponge withdrawal and this decline was much more rapid than in normal luteolysis. This was associated with fewer spermatozoa recovered from the cervix 2 h after insemination, and PMSG had no significant effect. In Exp. 2 injection of a supplementary dose of progesterone at sponge withdrawal resulted in a rapid increase in plasma progesterone concentrations followed by an equally rapid decrease and an attenuation of the rise in plasma oestradiol-17 beta, the LH surge, and the onset of oestrus. The numbers of spermatozoa recovered 4 h after insemination were not increased, and PMSG had no significant effect. Two factors were significant, namely the dose of progesterone in the sponge (600 mg greater than 400 or 200 mg, P less than 0.05) and stage of oestrus when inseminated (mid- or late oestrus greater than early). The data demonstrated that an adequate dose of progesterone/progestagen incorporated into intravaginal sponges and accurate timing of insemination relative to the LH surge are the most important factors involved in penetration of the cervix by spermatozoa.

Animals↗