Endocrinology is a branch of medicine dealing with disorders of the endocrine system and its specific secretions called hormones. Hormones are molecules that act as signals from one type of cells to another. Most hormones reach their targets via the blood. Although every organ system secretes and responds to hormones (including the brain, lungs, heart, intestine, skin, and the kidney), the clinical specialty of endocrinology focuses primarily on the endocrine organs, meaning the organs whose primary function is hormone secretion. These organs include the pituitary, thyroid, adrenals, ovaries and testes, and pancreas.

An endocrinologist is a doctor who specializes in treating disorders of the endocrine system, such as diabetes, hyperthyroidism, and many others (see list of diseases below). A disease due to a disorder of the endocrine system is often called a "hormone imbalance," but is technically known as an endocrinopathy or endocrinosis.

Background

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All multicellular organisms need “Coordinating systems to regulate and integrate the function of differentiating cells.” Two mechanisms perform this function in higher animals: the nervous system and the endocrine system. The endocrine system acts through the release (generally into the blood) of chemical agents and is vital to the proper development and function of organisms. As Hadley (2000) notes, the integration of developmental events such as proliferation, growth, and differentiation (including histogenesis and organogenesis) and the coordination of metabolism, respiration, excretion, movement, reproduction, and sensory perception depend on “chemical cues, substances synthesised and secreted by the specialised cells within the animal.”

More on [ Endocrinology ]

pubmed: 0013-7227

Epithelial Cell Transforming Protein 2 (ECT2) Depletion Blocks Polar Body Extrusion and Generates Mouse Oocytes Containing Two Metaphase II Spindles.
Elbaz J, Reizel Y, Nevo N, Galiani D, Dekel N Epithelial Cell Transforming Protein 2 (ECT2) Depletion Blocks Polar Body Extrusion and Generates Mouse Oocytes Containing Two Metaphase II Spindles. Endocrinology. 2009 Dec 8; Authors: Elbaz J, Reizel Y, Nevo N, Galiani D, Dekel N Completion of the first meiosis in oocytes is achieved by the extrusion of the first polar body (PBI), a particular example of cell division. In mitosis, the small GTPase RhoA, which is activated by epithelial cell transforming protein 2 (ECT2), orchestrates contractile ring constriction, thus enabling cytokinesis. However, the involvement of this pathway in mammalian oocytes has not been established. To characterize the role of ECT2 in PBI emission in mouse oocytes, the small interfering RNA approach was employed. We found that ECT2 depletion significantly reduces PBI emission, induces first metaphase arrest, and generates oocytes containing two properly formed spindles of the second metaphase. Moreover, we describe, for the first time, that before PBI emission, RhoA forms a ring that is preceded by a dome-like accumulation at the oocyte cortex, next to the spindle. This unique mode of RhoA translocation failed to occur in the absence of ECT2. We further found that the Rho-dependent kinase, a main RhoA effector, is essential for PBI emission. In addition, we demonstrate herein that ECT2 is subjected to phosphorylation/dephosphorylation throughout meiosis in oocytes and further reveal that PBI emission is temporally associated with ECT2 dephosphorylation. Our data provide the first demonstration that an active cyclin-dependent kinase 1, the catalytic subunit of the maturation-promoting factor, phosphorylates ECT2 during the first meiotic metaphase and that cyclin-dependent kinase 1 inactivation at anaphase allows ECT2 dephosphorylation. In conclusion, our study demonstrates the indispensable role of the maturation-promoting factor/ECT2/RhoA pathway in PBI extrusion in mouse oocytes. PMID: 19996184 [PubMed - as supplied by publisher]
Hypothalamic Actions of Tumor Necrosis Factor {alpha} Provide the Thermogenic Core for the Wastage Syndrome in Cachexia.
Arruda AP, Milanski M, Romanatto T, Solon C, Coope A, Alberici LC, Festuccia WT, Hirabara SM, Ropelle E, Curi R, Carvalheira JB, Vercesi AE, Velloso LA Hypothalamic Actions of Tumor Necrosis Factor {alpha} Provide the Thermogenic Core for the Wastage Syndrome in Cachexia. Endocrinology. 2009 Dec 8; Authors: Arruda AP, Milanski M, Romanatto T, Solon C, Coope A, Alberici LC, Festuccia WT, Hirabara SM, Ropelle E, Curi R, Carvalheira JB, Vercesi AE, Velloso LA TNFalpha is an important mediator of catabolism in cachexia. Most of its effects have been characterized in peripheral tissues, such as skeletal muscle and fat. However, by acting directly in the hypothalamus, TNFalpha can activate thermogenesis and modulate food intake. Here we show that high concentration TNFalpha in the hypothalamus leads to increased O2 consumption/CO2 production, increased body temperature, and reduced caloric intake, resulting in loss of body mass. Most of the thermogenic response is produced by beta3-adrenergic signaling to the brown adipose tissue (BAT), leading to increased BAT relative mass, reduction in BAT lipid quantity, and increased BAT mitochondria density. The expression of proteins involved in BAT thermogenesis, such as beta3-adrenergic receptor, peroxisomal proliferator-activated receptor-gamma coactivator-1alpha, and uncoupling protein-1, are increased. In the hypothalamus, TNFalpha produces reductions in neuropeptide Y, agouti gene-related peptide, proopiomelanocortin, and melanin-concentrating hormone, and increases CRH and TRH. The activity of the AMP-activated protein kinase signaling pathway is also decreased in the hypothalamus of TNFalpha-treated rats. Upon intracerebroventricular infliximab treatment, tumor-bearing and septic rats present a significantly increased survival. In addition, the systemic inhibition of beta3-adrenergic signaling results in a reduced body mass loss and increased survival in septic rats. These data suggest hypothalamic TNFalpha action to be important mediator of the wastage syndrome in cachexia. PMID: 19996183 [PubMed - as supplied by publisher]
Consequences of Monocarboxylate Transporter 8 Deficiency for Renal Transport and Metabolism of Thyroid Hormones in Mice.
Trajkovic-Arsic M, Visser TJ, Darras VM, Friesema EC, Schlott B, Mittag J, Bauer K, Heuer H Consequences of Monocarboxylate Transporter 8 Deficiency for Renal Transport and Metabolism of Thyroid Hormones in Mice. Endocrinology. 2009 Dec 8; Authors: Trajkovic-Arsic M, Visser TJ, Darras VM, Friesema EC, Schlott B, Mittag J, Bauer K, Heuer H Patients carrying inactivating mutations in the gene encoding the thyroid hormone transporting monocarboxylate transporter (MCT)-8 suffer from a severe form of psychomotor retardation and exhibit abnormal serum thyroid hormone levels. The thyroidal phenotype characterized by high-serum T3 and low-serum T4 levels is also found in mice mutants deficient in MCT8 although the cause of these abnormalities is still unknown. Here we describe the consequences of MCT8 deficiency for renal thyroid hormone transport, metabolism, and function by studying MCT8 null mice and wild-type littermates. Whereas serum and urinary parameters do not indicate a strongly altered renal function, a pronounced induction of iodothyronine deiodinase type 1 expression together with increased renal T3 and T4 content point to a general hyperthyroid state of the kidneys in the absence of MCT8. Surprisingly, accumulation of peripherally injected T4 and T3 into the kidneys was found to be enhanced in the absence of MCT8, indicating that MCT8 deficiency either directly interferes with the renal efflux of thyroid hormones or activates indirectly other renal thyroid hormone transporters that preferentially mediate the renal uptake of thyroid hormones. Our findings indicate that the enhanced uptake and accumulation of T4 in the kidneys of MCT8 null mice together with the increased renal conversion of T4 into T3 by increased renal deiodinase type 1 activities contributes to the generation of the low-serum T4 and the increase in circulating T3 levels, a hallmark of MCT8 deficiency. PMID: 19996182 [PubMed - as supplied by publisher]

pubmed: 0804-4643

Do we need still more trials on T4 and T3 combination therapy in hypothyroidism?
Wiersinga WM Related Articles Do we need still more trials on T4 and T3 combination therapy in hypothyroidism? Eur J Endocrinol. 2009 Dec;161(6):955-9 Authors: Wiersinga WM Approximately 10% of hypothyroid patients are dissatisfied with the outcome of levothyroxine replacement. It is unlikely that slight over- or under-treatment with thyroxine (T(4)) explains remaining complaints. Meta-analysis of randomized clinical trials shows no advantage of T(4)/tri-iodothyronine (T(3)) combination therapy over T(4) monotherapy. However, each of these trials can be criticized, and none is perfect: most of them failed to mimic the physiological ratio of serum free T(4) (FT(4)) to free T(3) (FT(3)) concentrations. Development of a sustained-release T(3) preparation given as a single nighttime dose (together with levothyroxine once daily) might maintain physiological serum FT(4)-FT(3) ratio's throughout 24 h. Genetic polymorphisms in deiodinase 2 and thyroid hormone transporters have been associated with well-being, fatigue, depression, and greater improvement on combination therapy. Future trials should target carriers of these polymorphisms to see whether they do better on T(4)/T(3) combination therapy than on T(4) monotherapy. PMID: 19808902 [PubMed - indexed for MEDLINE]
Benign fine-needle aspiration cytology of thyroid nodule: to repeat or not to repeat?
Gabalec F, Cáp J, Ryska A, Vasátko T, Ceeová V Related Articles Benign fine-needle aspiration cytology of thyroid nodule: to repeat or not to repeat? Eur J Endocrinol. 2009 Dec;161(6):933-7 Authors: Gabalec F, Cáp J, Ryska A, Vasátko T, Ceeová V CONTEXT: Fine-needle aspiration cytology (FNAC) is the gold standard for evaluating thyroid nodules. It has a sensitivity rate of about 95%, i.e. false negative results represent up to 5% of cases. The value of repeated FNAC during follow-up is still controversial. OBJECTIVE: To evaluate the usefulness of repeating the FNAC for initially benign nodules. DESIGN AND METHODS: All 5017 patients who underwent FNAC of the thyroid nodule in years 1991-2008 were retrospectively evaluated. RESULTS: Repeated FNAC was performed in 574 nodules with initially benign results. The number of repetitions varied from one to six. Repeatedly benign results were found in 498 cases, and malignant/suspicious results with initially benign cytology were found in 76 nodules (13.2%). Carcinoma was present in 13 out of the 58 surgically treated malignant/suspicious results of initially benign cytology. CONCLUSIONS: A change from a benign FNAC result to a malignant/suspicious one was present in more than 13% of the patients with initially benign cytology; malignancy has been recognised on the basis of repeated FNAC in 2.3% patients. In the majority of cases, the repetition corrected wrong cytological interpretation of results other than colloidal goitre, especially Hashimoto's thyroiditis and regressive changes. We believe that repeating FNAC in patients with benign cytology in about a 1-year horizon can reduce the rate of undiagnosed tumours. PMID: 19776203 [PubMed - indexed for MEDLINE]
Free leptin index and thyroid function in male highly trained athletes.
Perseghin G, Lattuada G, Ragogna F, Alberti G, La Torre A, Luzi L Related Articles Free leptin index and thyroid function in male highly trained athletes. Eur J Endocrinol. 2009 Dec;161(6):871-6 Authors: Perseghin G, Lattuada G, Ragogna F, Alberti G, La Torre A, Luzi L OBJECTIVE: Exercise training may cause changes in thyroid function. This thyroid response may be due to exercise-induced modulation of energy metabolism but also of the adipocytes endocrine function. In particular, the role of leptin and of circulating soluble leptin receptor (sOB-R) was unexplored. The aim of this study was to assess the relationships between thyroid function, whole body energy metabolism, and adipokines--mainly leptin and its receptor, sOB-R. METHODS: We measured serum TSH, free tri-iodothyronine (FT(3)), free thyroxine, leptin, and sOB-R and assessed energy homeostasis by means of indirect calorimetry, in 27 highly trained athletes and 27 sedentary, healthy men. RESULTS: TSH-FT(3) ratio was lower in athletes (P<0.03), either in sustained power or anaerobic power-sprint athletes (n=13) or marathon runners (n=14). Whole body respiratory quotient was lower in athletes. Fasting serum sOB-R was higher and leptin lower in athletes than controls. Also serum adiponectin, resistin, and retinol binding protein-4 concentrations were different in athletes than in controls. The ratio between leptin and sOB-R, the free leptin index (FLI), was lower in athletes than in controls (0.025+/-0.014 vs 0.085+/-0.049; P<0.001). In multivariate analysis, FLI retained independent association with TSH-FT(3) ratio. CONCLUSION: Male, elite athletes had lower TSH-FT(3) ratio and FLI than controls while FLI was independently associated with TSH-FT(3) ratio supporting the hypothesis that the level of biologically active leptin is involved in the adaptive response of thyroid function in professional athletes. PMID: 19773373 [PubMed - indexed for MEDLINE]
Acylated and nonacylated ghrelin levels and their associations with insulin resistance in obese and normal weight children with metabolic syndrome.
Pacifico L, Poggiogalle E, Costantino F, Anania C, Ferraro F, Chiarelli F, Chiesa C Related Articles Acylated and nonacylated ghrelin levels and their associations with insulin resistance in obese and normal weight children with metabolic syndrome. Eur J Endocrinol. 2009 Dec;161(6):861-70 Authors: Pacifico L, Poggiogalle E, Costantino F, Anania C, Ferraro F, Chiarelli F, Chiesa C BACKGROUND: Ghrelin, a peptide mainly derived from the stomach, plays a pivotal role in the regulation of food intake, energy metabolism, and storage, as well as in insulin sensitivity. Ghrelin circulates in acylated (A-Ghr) and nonacylated (NA-Ghr) forms, and their potential differential associations with insulin resistance (IR) in childhood obesity remain undefined. OBJECTIVE: We investigated the associations of ghrelin forms with IR in normal weight and obese children and the impact of metabolic syndrome (MS) on their plasma values. DESIGN: A total of 210 children in four subgroups of normal weight/obese children with and without components of MS were studied. Fasting blood glucose, insulin, lipid profile, and acylated and total ghrelin were examined. IR was determined by a homeostasis model assessment (HOMA) of IR. RESULTS: In the entire population, plasma insulin and HOMA-IR were associated negatively with T-Ghr and NA-Ghr, but positively with the ratio of A/NA-Ghr after adjustment for age, gender, and Tanner stage. Obese metabolically abnormal children had lower T-Ghr and NA-Ghr, but comparable A-Ghr and a higher A/NA-Ghr ratio than obese metabolically normal subjects. Compared with lean healthy children, lean metabolically abnormal subjects had higher A-Ghr and the A/NA-Ghr ratio, but comparable T-Ghr and NA-Ghr. A multiple regression analysis showed that A-Ghr and the A/NA-Ghr ratios were positively associated with HOMA-IR, independent of age, gender, Tanner stage, and body mass index (or waist circumference) and other components of MS. CONCLUSIONS: A-Ghr excess may negatively modulate insulin action in obese and nonobese children, and may contribute to the association of IR and MS. PMID: 19773372 [PubMed - indexed for MEDLINE]
Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma.
Hoftijzer H, Heemstra KA, Morreau H, Stokkel MP, Corssmit EP, Gelderblom H, Weijers K, Pereira AM, Huijberts M, Kapiteijn E, Romijn JA, Smit JW Related Articles Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma. Eur J Endocrinol. 2009 Dec;161(6):923-31 Authors: Hoftijzer H, Heemstra KA, Morreau H, Stokkel MP, Corssmit EP, Gelderblom H, Weijers K, Pereira AM, Huijberts M, Kapiteijn E, Romijn JA, Smit JW OBJECTIVE: Treatment options for patients with radioactive iodine (RaI) refractory metastases of differentiated thyroid carcinoma (DTC) are limited. We studied the effects of the multitarget tyrosine kinase inhibitor sorafenib on the reinduction of RaI uptake and tumor progression. DESIGN: Open, single center, single arm 26-week prospective phase II study with open-ended extension. METHODS: We treated 31 patients with progressive metastatic or locally advanced RaI refractory DTC with sorafenib 400 mg b.i.d. The primary endpoint was reinduction of RaI uptake at 26 weeks. Additional endpoints were the radiological response and the influence of bone metastases. RESULTS: At 26 weeks of sorafenib therapy, no reinduction of RaI uptake at metastatic sites was observed, but 19 patients (59%) had a clinical beneficial response, eight of whom had a partial response (25%) and 11 had stable disease (34%). Seven patients had progressive disease (22%). Sorafenib was significantly less effective in patients with bone metastases. The estimated median progression free survival was 58 weeks (95% confidence interval, CI, 47-68). In general, thyroglobulin (Tg) response (both unstimulated and TSH stimulated) reflected radiological responses. The median time of the nadir of Tg levels was 3 months. Responses were not influenced by histological subtype, mutational status or other variables. No unusual side effects were observed. CONCLUSIONS: Sorafenib has a beneficial effect on tumor progression in patients with metastatic DTC, but was less effective in patients with bone metastases. Diagnostic whole body scintigraphy did not reveal an effect of sorafenib on the reinduction of RaI uptake. PMID: 19773371 [PubMed - indexed for MEDLINE]
Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women.
Boas M, Forman JL, Juul A, Feldt-Rasmussen U, Skakkebaek NE, Hilsted L, Chellakooty M, Larsen T, Larsen JF, Petersen JH, Main KM Related Articles Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women. Eur J Endocrinol. 2009 Dec;161(6):903-10 Authors: Boas M, Forman JL, Juul A, Feldt-Rasmussen U, Skakkebaek NE, Hilsted L, Chellakooty M, Larsen T, Larsen JF, Petersen JH, Main KM BACKGROUND: Adaptive alterations in maternal physiology cause changes in thyroid hormone levels throughout pregnancy, and precise biochemical evaluation is thus highly dependent on gestation-specific reference intervals and expected intra-individual variation. OBJECTIVE: The aim of the study was the assessment of the intra-individual variation as well as the longitudinal course of thyroid hormones during normal pregnancy and factors that influence the normal reference range for thyroid function. For this purpose, a longitudinal statistical model was applied. DESIGN: In a cohort of 132 pregnant women, serial blood samples were obtained and ultrasound scans were performed throughout pregnancy. METHODS: Serum levels of TSH, free and total thyroxine (T(4)), free and total triiodothyronine (T(3)) as well as autoantibodies against thyroid peroxidase and thyroglobulin were measured in 979 serum samples. RESULTS: Intra-individual variations of thyroid hormone concentrations were smaller than inter-individual variations (individuality index range: 0.38-0.71). Maternal height was positively associated with free T(4) (FT(4)) (b=0.003; P=0.031) and pre-pregnancy body mass index with T(3) and free T(3) (b=0.017; <0.001 and b=0.007; P<0.001). Smoking was positively associated with T(4) and FT(4), but it was modulated by gestational age. Gestation-specific reference intervals for thyroid function variables from autoantibody-negative participants are presented. CONCLUSIONS: In accordance with the data from nonpregnant adults, intra-individual variations of thyroid hormones were smaller than inter-individual variations also during pregnancy. In the evaluation of thyroid function in pregnancy, the individual longitudinal course of thyroid hormones rather than absolute values should be considered. We present a longitudinal model for the prediction of maternal thyroid function tests in pregnant women. PMID: 19773370 [PubMed - indexed for MEDLINE]

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