Reduced fibre size, capillary supply and mitochondrial activity in constitutional thinness' skeletal muscle.

AIM: Constitutional thinness (CT) is a rare condition of natural low body weight, with no psychological issues, no marker of undernutrition and a resistance to weight gain. This study evaluated the skeletal muscle phenotype of CT women by comparison with a normal BMI control group. METHODS: Ten CT women (BMI < 17.5 kg/m2 ) and 10 female controls (BMI: 18.5-25 kg/m2 ) underwent metabolic and hormonal assessment along with muscle biopsies to analyse the skeletal muscular fibres pattern, capillarity, enzymes activities and transcriptomics. RESULTS: Constitutional thinness displayed similar energy balance metabolic and hormonal profile to controls. Constitutional thinness presented with lower mean area of all the skeletal muscular fibres (-24%, P = .01) and percentage of slow-twitch type I fibres (-25%, P = .02, respectively). Significant downregulation of the mRNA expression of several mitochondrial-related genes and triglycerides metabolism was found along with low cytochrome c oxidase (COX) activity and capillary network in type I fibres. Pre- and post-mitochondrial respiratory chain enzymes levels were found similar to controls. Transcriptomics also revealed downregulation of cytoskeletal-related genes. CONCLUSION: Diminished type I fibres, decreased mitochondrial and metabolic activity suggested by these results are discordant with normal resting metabolic rate of CT subjects. Downregulated genes related to cytoskeletal proteins and myocyte differentiation could account for CT's resistance to weight gain.

Specific appetite, energetic and metabolomics responses to fat overfeeding in resistant-to-bodyweight-gain constitutional thinness.

BACKGROUND: Contrasting with obesity, constitutional thinness (CT) is a rare condition of natural low bodyweight. CT exhibits preserved menstruation in females, no biological marker of undernutrition, no eating disorders but a bodyweight gain desire. Anorexigenic hormonal profile with high peptide tyrosine tyrosine (PYY) was shown in circadian profile. CT could be considered as the opposite of obesity, where some patients appear to resist diet-induced bodyweight loss. OBJECTIVE: The objective of this study was to evaluate appetite regulatory hormones in CTs in an inverse paradigm of diet-induced weight loss. METHODS: A 4-week fat overfeeding (2640 kJ excess) was performed to compare eight CT women (body mass index (BMI)<17.5 kg m(-)(2)) to eight female controls (BMI 18.5-25 kg m(-)(2)). Appetite regulatory hormones profile after test meal, food intake, bodyweight, body composition, energy expenditure and urine metabolomics profiles were monitored before and after overfeeding. RESULTS: After overfeeding, fasting total and acylated ghrelin were significantly lower in CTs than in controls (P=0.01 and 0.03, respectively). After overfeeding, peptide tyrosine tyrosine (PYY) and glucagon-like-peptide 1 both presented earlier (T15 min vs T30 min) and higher post-meal responses (incremental area under the curve) in CTs compared with controls. CTs failed to increase bodyweight (+0.22±0.18 kg, P=0.26 vs baseline), contrasting with controls (+0.72±0.26 kg, P=0.03 vs baseline, P=0.01 vs CTs). Resting energy expenditure increased in CTs only (P=0.031 vs baseline). After overfeeding, a significant negative difference between total energy expenditure and food intake was noticed in CTs only (-2754±720 kJ, P=0.01). CONCLUSION: CTs showed specific adaptation to fat overfeeding: overall increase in anorexigenic hormonal profile, enhanced post prandial GLP-1 and PYY and inverse to controls changes in urine metabolomics. Overfeeding revealed a paradoxical positive energy balance contemporary to a lack of bodyweight gain, suggesting yet unknown specific energy expenditure pathways in CTs.

The value of the immunohistochemical exam in the diagnosis of the secondary malignant tumors to the thyroid gland.

The aim of the study was to analyze several cases of secondary tumors to the thyroid, by focusing on the role of the immunohistochemical (IHC) exam in specifying the origin of the tumoral process. The studied group included 16 patients, investigated by fine-needle aspiration biopsy, frozen sections at the surgical moment, routine histopathological exam and immunohistochemical staining, using different antibodies, in accordance with the histological aspects. The final diagnosis was established as follows: metastases of squamocellular carcinoma with different degree of differentiation (seven cases), metastases of adenocarcinoma (four cases), metastases of renal cell carcinoma (two cases), metastases of Hodgkin (one case) and non-Hodgkin lymphoma (two cases). In four cases, the primary tumors were identified after the diagnosis of their metastases in thyroid. The immunohistochemical staining was useful in the diagnosis of squamocellular carcinoma metastases, poorly differentiated (CK19 positive), of renal cell carcinoma with clear cells (CK18, CK19 and CD10 positive) and in the establishing of the tumoral origin for adenocarcinomas (CK7 positive--respiratory tract, CK20 positive--digestive tract). Secondary tumors to the thyroid are rare tumors, with miscellaneous histological aspects, reason for which the diagnostic may be difficult. In these cases IHC is a useful method, allowing to the identification of the primary tumor.

[The role of lymphadenectomy in the treatment of differentiated thyroid cancer]. / Locul limfadenectomiei in tratamentul cancerului tiroidian diferentiat.

Papillary and follicular carcinoma represent almost 90% of the thyroid malignancies, being responsible for 70% of the mortality generated by thyroid cancer. Lymph node involvement, far more significant in the papillary form, increases the risk of local recurrence and affects long-term survival. Due to the lack of prospective randomised studies to assess the benefit of lymph node dissection in addition to total thyroidectomy, there is no consensus regarding the need of routine vs elective central compartment lymphadenectomy. Routine lymph node dissection of the central compartment is supported by the argument that it reduces the amount of neoplastic thyroid tissue and, therefore, optimises the effectiveness of radioiodine in DTC patients. Moreover, it provides an accurate staging by the detailed histopathological analysis and allows an optimal postoperative thyroid scanning. No additional morbidity of central lymphadenectomy is reported, compared to total thyroidectomy alone, if performed by a specialised surgeon. However, reinterventions for recurrence in the central compartment, carry a significantly higher risk of recurrent nerve and parathyroids damage. Unlike central compartment, it is generally agreed that lymphadenectomy of the lateral neck, as modified radical neck dissection, is employed when there is evidence of neoplastic lymph node involvement, wether macroscopic, imaging or by pathological data.

Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling.

INTRODUCTION: In anorexia nervosa (AN) patients osteoporosis occurs within a framework of multiple hormonal abnormalities as a result of bone turnover uncoupling, with decreased bone formation and increased bone resorption. The aim of study was to evaluate the hormonal and nutritional relationships with both of these bone remodeling compartments and their eventual modifications with age. PATIENTS AND MEASUREMENTS: In a cohort of 115 AN patients (mean BMI:14.6 kg/m2) that included 60 mature adolescents (age: 15.5-20 years) and 55 adult women (age: 20-37 years) and in 28 age-matched controls (12 mature adolescents and 16 adults) we assessed: bone markers [serum osteocalcin, skeletal alkaline phosphatase (sALP), C-telopeptide of type I collagen (sCTX) and tartrate-resistant acid phosphatase type 5b (TRAP 5b)], nutritional markers [ body mass index (BMI, fat and lean mass), hormones (free tri-iodothyronine (T3), free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), 17 beta estradiol, free testosterone index (FTI), dehydroepiandrosterone (DHEAS), insulin-like growth factor 1 (IGF-1), growth hormone (GH) and cortisol], plasma methoxyamines (metanephrine and normetanephrine) and calcium metabolism parameters [parathyroid hormone (PTH), Ca, vitamin D3]. RESULTS: Osteocalcin reached similar low levels in both AN age subgroups. sCTX levels were found to be elevated in all AN subjects and higher in mature adolescents than in adult AN (11,567+/-895 vs. 8976+/-805 pmol/l, p<0.05). sALP was significantly lower only in mature adolescent AN patients, while there were no significant differences in the levels of TRAP 5b between AN patients and age-matched control groups. Osteocalcin correlated with sCTX in the control subjects (r=0.65) but not in the AN patients, suggesting the independent regulation of these markers in AN patients. Osteocalcin levels strongly correlated with freeT3, IGF-I, 17 beta estradiol and cortisol, while sCTX correlated with IGF-I, GH and cortisol in both age subgroups of the AN patients. Other hormones or nutritional parameters displayed age-related correlations with bone markers, leading to different stepwise regression models for each age interval. In mature adolescent AN patients, up to 54% of the osteocalcin variance was due to BMI, cortisol and 17 beta estradiol, while 54% of the sCTX variance was determined by GH. In adult subjects, freeT3 and IGF-I accounted for 64% of osteocalcin variance, while 65% of the sCTX variance was due to GH, FTI and methoxyamines. CONCLUSIONS: We suggest a more complex mechanism of AN bone uncoupling that includes not only "classical" influence elements like cortisol, IGF-I, GH or 17 beta estradiol but also freeT3, catecholamines and a "direct" hormone-independent impact of denutrition. Continuous changes of these influences with age should be considered within the therapeutic approach to AN bone loss.

[Retrospective study of anorexia nervosa: reduced mortality and stable recovery rates]. / Diminution de la mortalité et stabilité du taux de guérison dans le suivi de l'anorexie mentale.

OBJECTIVES: Anorexia nervosa is an eating disorder that combines malnutrition, amenorrhea, and distorted body image. To learn more about the course of this disease we undertook a retrospective study of girls diagnosed with anorexia nervosa in the Saint Etienne Endocrinology Department between 1979 and 2004. METHODS: Patients were diagnosed according to DSMIV criteria. Data collected to complete the Morgan-Russell outcome assessment schedule included chronology of illness, patients' morphological features, anorexia type, treatment choice, patient's gynecological history, and social status. RESULTS: The study included 206 cases. The average follow-up period was 8.3 +/- 5.3 years. Defining recovery as stable BMI>17.5 kg/m2 for at least one year and recovery of normal menstruation, full recovery was observed in 55.8% and partial recovery in 25.7%, while 18.5% remained chronically ill. Early onset (i.e., during adolescence) was associated with good prognosis, and advanced emaciation and delayed or insufficient medical care with poor prognosis. CONCLUSIONS: The seriousness of this disease is due more to the incidence of cases that become chronic than to the mortality rate. Prediction of severity would be improved by taking into account underlying personality traits, such as addictive tendencies and depression.

[Differentiated thyroid cancer--staging and prognostic systems]. / Cancerul tiroidian diferentiat stadializare si sisteme de scor prognostic.

Differentiated thyroid cancer (DTC), including papillary and follicular carcinoma with histological variants, has an excellent prognosis; nevertheless a subset of these tumours is clinically aggressive and, in some patients, fatal. Treatment of DTC remains controversial, regarding the extent of primary surgical resection, the need for lymph node dissection and the role of postoperative radioactive iodine ablation. In addition to the widely accepted TNM classification, recognition of significant risk factors and developing of staging systems, such as AMES, AGES, MACIS, MSKCC and NTCTCS, has helped to identify the patients with a potential aggressive course of the disease and high risk of recurrence. This has allowed the development of a rational and selective approach to therapy, thus, avoiding excessive treatment and subsequent morbidity without compromising the oncological outcome.

[Differentiated thyroid cancer--peculiar morphological and clinical forms]. / Cancerul tiroidian diferentiat forme anatomoclinice particulare.

The most common clinical presentation of differentiated thyroid cancer (DTC), consisting of papillary and follicular adenocarcinoma (with their histological variants), is the solitary thyroid nodule. A review of the literature is performed in order to describe particular forms of DTC, in terms of incidence, diagnosis and treatment: occult carcinoma, carcinoma on aberrant thyroid tissue, "functional" thyroid carcinoma and familial non-medullary carcinoma. A particular interest is shown to the coexistence of malignancy with benign thyroid diseases, such as goiter, hyperthyroidism and Hashimoto's thyroiditis, as well as parathyroid adenoma. In conclusion, the authors emphasize that the association of carcinoma with benign thyroid conditions is not rare and it substantiate an aggressive approach in regard to diagnosis and treatment, increasing the indication for surgery and, moreover, for total thyroidectomy.