Modified release and conventional glucocorticoids and diurnal androgen excretion in congenital adrenal hyperplasia.

Modified release and conventional glucocorticoids and diurnal androgen excretion in congenital adrenal hyperplasia.

J Clin Endocrinol Metab. 2016 Nov 15;:jc20162855

Authors: Jones CM, Mallappa A, Reisch N, Nikolaou N, Krone N, Hughes BA, O'Neil DM, Whitaker MJ, Tomlinson JW, Storbeck KH, Merke DP, Ross RJ, Arlt W

Abstract
CONTEXT: The classic androgen synthesis pathway proceeds via DHEA, androstenedione and testosterone to 5α-dihydrotestosterone (DHT). However, DHT synthesis can also be achieved by an alternative pathway originating from 17α-hydroxyprogesterone (17OHP), which accumulates in congenital adrenal hyperplasia (CAH). Similarly, recent work has highlighted androstenedione-derived 11-oxygenated 19-carbon steroids as active androgens and, in CAH, androstenedione is generated directly from 17OHP. The exact contribution of alternative pathway activity to androgen excess in CAH and its response to glucocorticoid therapy is unknown.
OBJECTIVE: We sought to quantify classic and alternative pathway-mediated androgen synthesis in CAH, their diurnal variation and their response to conventional glucocorticoid (GC) therapy and modified release hydrocortisone.
METHODS: We employed urinary steroid metabolome profiling by gas chromatography-mass spectrometry for 24-h steroid excretion analysis, studying the impact of conventional GCs (hydrocortisone, prednisolone, dexamethasone) in 55 adults with CAH and 60 controls. We studied diurnal variation in steroid excreton by comparing 8-hourly collections (23:00-7:00h, 7:00-15:00h, 15:00-23:00h) in 16 CAH patients on conventional glucocorticoids and during six months of treatment with modified release hydrocortisone, Chronocort.
RESULTS: CAH patients on conventional GCs showed low excretion of classic pathway androgen metabolites but excess excretion of the alternative pathway signature metabolites 3α,5α-17-hydroxypregnanolone and 11β-hydroxyandrosterone. Chronocort reduced 17OHP and alternative pathway metabolite excretion to near normal levels more consistently than other GC preparations.
CONCLUSIONS: Alternative pathway mediated androgen synthesis significantly contributes to androgen excess in CAH. Chronocort therapy appears superior to conventional GC therapy in controlling androgen synthesis via alternative pathways through attenuation of their major substrate, 17OHP.

PMID: 27845856 [PubMed - as supplied by publisher]

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[Stomal Cancer Recurrency, A Clinic-Pathological Consideration].

[Stomal Cancer Recurrency, A Clinic-Pathological Consideration].

Laryngorhinootologie. 2016 Nov 15;

Authors: Teutsch S, Bas M, Bier H, Knopf A

Abstract
Objectives: Analysis of pre-operative tracheostomy and circumjacent tumour free margins as risk factors in the development of stomal recurrent disease after (pharyngo)laryngectomy. Material and Methods: 124 patients after (pharyngo)laryngectomy were analyzed for disease related data and tumour samples were analyzed for tumour free margins. The overall cohort was divided into patients with/withour pre-operative tracheostomy. Results: 18 patients suffered from recurrent disease (10 stomal, 8 distant metastases). Advanced T-status, female gender, and sub-/glottic tumour manifestation resulted in a higher rate of prior tracheostomy. Pre-operative tracheostomy did not influence the development of stomal recurrency. R0 resection was achieved in 94% of our patients, with significant reduced tumour free margins in patients with stomal recurrency (p=0.002) Conclusion: Pre-operative tracheostomy did not influence the development of stomal recurrent disease. The clinical identification of ventral soft tissue infiltration should result in extensive surgical concepts.

PMID: 27846642 [PubMed - as supplied by publisher]

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Editorial.

Editorial.

J Cosmet Laser Ther. 2016 Nov;18(7):363

Authors: Goldberg DJ

PMID: 27845619 [PubMed - in process]

http://ift.tt/2fwIfHQ

Painful Radiation Thyroiditis after (131)I Therapy for Graves' Hyperthyroidism: Clinical Features and Ultrasonographic Findings in Five Cases.

Related Articles

Painful Radiation Thyroiditis after (131)I Therapy for Graves' Hyperthyroidism: Clinical Features and Ultrasonographic Findings in Five Cases.

Eur Thyroid J. 2016 Sep;5(3):201-206

Authors: Mizokami T, Hamada K, Maruta T, Higashi K, Tajiri J

Abstract
BACKGROUND: Radiation thyroiditis caused by (131)I therapy for Graves' hyperthyroidism is asymptomatic in most patients and is rarely associated with pain or fever. Currently, there are few reports on the ultrasonographic findings of radiation thyroiditis after (131)I therapy for Graves' hyperthyroidism.
CASE REPORT: We herein report 5 cases with painful radiation thyroiditis (including 2 febrile cases) after (131)I therapy for Graves' hyperthyroidism. The cases included 4 women, aged 49, 50, 76, and 81 years, and 1 man, aged 60 years. Anterior neck pain developed 0-10 days after (131)I administration (fixed dose of 481 MBq). Each patient visited our clinic 0-4 days after the development of anterior neck pain. The thyroid glands were noticeably enlarged (increasing from 18 g at (131)I administration to 35 g after the development of anterior neck pain in 1 patient, and from 20 to 33 g, 21 to 39 g, 21 to 51 g, and 40 to 51 g in the other patients) and tender. The echogenicity of the thyroid parenchyma was increased, and the parenchyma was more heterogeneous. Granular hyperechoic lesions were scattered throughout the thyroid gland in the most severe case. The border between the thyroid gland and the surrounding tissue was blurred, and the surrounding tissue was hyperechoic.
CONCLUSION: Painful radiation thyroiditis should be reacknowledged as one of the complications of (131)I therapy for Graves' hyperthyroidism. Ultrasonography demonstrated the characteristic changes caused by (131)I-induced radiation thyroiditis.

PMID: 27843811 [PubMed - in process]

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Targeted therapy and elderly people: A review

Publication date: December 2016
Source:European Journal of Cancer, Volume 69
Author(s): Amaury Daste, Camille Chakiba, Charlotte Domblides, Marine Gross-goupil, Amandine Quivy, Alain Ravaud, Pierre Soubeyran
The use of targeted therapy (TT) has radically changed the outcome of various cancers and introduces the era of personalised medicine. Elderly patients (≥65 years) represent the majority of cancer diagnoses and deaths by age group with an increase expected over the next decade. This group of patients is heterogeneous with three categories of patients: fit, vulnerable and frail, with specific treatment for each subgroup. In this review, we assess safety and efficacy of TT in elderly patients, principally from data of pivotal clinical trials with subgroup analysis, but elderly people represented a small percentage of the total number of patients. Few specific trials have been carried out for TT in elderly people with most patients considered to be fit. However, tolerance and efficacy of TT in elderly patients seems similar to that for younger patients, with an increase in incidence of specific adverse events in elderly patients for selected TTs. An adapted geriatric selection and strict monitoring could help to decrease toxicity, and specific clinical trials for elderly cancer patients would be useful.



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Bullous pemphigoid-like reaction in a patient with metastatic melanoma receiving pembrolizumab and previously treated with ipilimumab

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The need for fundamental reforms in the pain research field to develop innovative drugs.

Related Articles

The need for fundamental reforms in the pain research field to develop innovative drugs.

Expert Opin Drug Discov. 2016 Nov 14;

Authors: Nagakura Y

Abstract
INTRODUCTION: Chronic pain is a major healthcare issue owing to its high prevalence, significant physical and emotional burden on the patients, and huge financial burden on the society. The efficacy of currently available medications is unsatisfactory owing to their limited effect size and the low responder rate (less than 50%). Thus, there is a large unmet need for innovative therapies for chronic pain. Areas covered: In this review, the author points out the need for fundamental reforms in pain research. For the last several decades, drug discovery research has extensively focused on designing new therapies using animal models of chronic pain. It has, however, made insufficient progress with respect to the launch of innovative analgesic drugs, because the translation from preclinical to clinical stages has not been satisfactory. Thus, the strategies for developing innovative analgesic drugs are discussed. Expert opinion: Points to be considered in the discovery of drugs for pain relief include: (1) the exclusion of bias incorporation and the alignment of clinical and preclinical endpoints in the assessment of analgesic efficacy; (2) the understanding of primary unmet needs; (3) the assessment of new therapies by biomarker-prioritized frameworks, and (4) the stratification of chronic pain sufferers.

PMID: 27838932 [PubMed - as supplied by publisher]

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