Anna Angelousi

Association between thyroid function tests at baseline and the outcome of patients with sepsis or septic shock: a systematic review

INTRODUCTIONnThe severity of critical illness is associated with various patterns of thyroid hormone abnormalities. We sought to evaluate whether the outcome of patients with, specifically, sepsis or septic shock is associated with the thyroid function tests evaluated at diagnosis or admission in the intensive care unit (ICU).nnnMETHODSnWe performed a systematic review of relevant studies by searching PubMed.nnnRESULTSnWe included nine studies that all had a prospective cohort design. Seven involved children or neonates, and two involved adults. Mortality was the outcome evaluated in eight studies, while the length of ICU stay was evaluated in the remaining study. In univariate analysis, six of the nine included studies showed that either, free or total, triiodothyronine or thyroxine was lower in the group of patients with sepsis or septic shock who had unfavorable outcome than in those who had favorable outcome. Two other studies showed higher TSH values in the group of patients with unfavorable outcome. No significant relevant findings were observed in the remaining study. Regarding the correlation of sepsis prognostic scoring systems with thyroid function tests, the three studies that provided specific relevant data showed variable findings.nnnDISCUSSIONnMost of the relevant studies identified favor the concept that decreased thyroid function at baseline might be associated with a worse outcome of patients with sepsis or septic shock. Although these findings are not consistent, the role of thyroid function in affecting or merely predicting the outcome of sepsis or septic shock merits further investigation.

Mechanisms in endocrinology: primary HT and risk for breast cancer: a systematic review and meta-analysis.

OBJECTIVEnThe association between hypothyroidism and breast cancer has been described from very early on. Breast and thyroid tissue are interconnected on a molecular level mainly through activation of thyroid hormone receptors expressed on cells of the mammary gland as well as on the plasma membrane of breast cancer cells. Despite the experimental evidence the true value of hypothyroidism as a risk factor for breast cancer remains controversial.nnnMETHODSnWe searched the PubMed database through February 2011 to identify studies that evaluated the association between hypothyroidism and risk for breast cancer as well as the effect of thyroid hormone replacement therapy on breast cancer incidence.nnnRESULTSnA meta-analysis performed in 12 studies showed that hypothyroidism was not associated with risk for breast cancer (pooled risk ratio (RR)=1.06, 95% confidence intervals (CIs) 0.82-1.35, P = 0.672). The effect of treatment was assessed in seven studies and no evidence for an association between thyroid hormone replacement and breast cancer was observed with an overall RR of 0.99 (95% CI 0.73-1.35, P = 0.965).nnnCONCLUSIONSnOur meta-analysis showed that hypothyroidism is not associated with increased risk for breast cancer and thyroid hormone replacement therapy does not reduce breast cancer prevalence; however, the heterogeneity of the studies analyzed precludes firm conclusions.

Primary Hypothyroidism and Risk for Breast Cancer: A Systematic Review and Meta-Analysis

OBJECTIVEnThe association between hypothyroidism and breast cancer has been described from very early on. Breast and thyroid tissue are interconnected on a molecular level mainly through activation of thyroid hormone receptors expressed on cells of the mammary gland as well as on the plasma membrane of breast cancer cells. Despite the experimental evidence the true value of hypothyroidism as a risk factor for breast cancer remains controversial.nnnMETHODSnWe searched the PubMed database through February 2011 to identify studies that evaluated the association between hypothyroidism and risk for breast cancer as well as the effect of thyroid hormone replacement therapy on breast cancer incidence.nnnRESULTSnA meta-analysis performed in 12 studies showed that hypothyroidism was not associated with risk for breast cancer (pooled risk ratio (RR)=1.06, 95% confidence intervals (CIs) 0.82-1.35, P = 0.672). The effect of treatment was assessed in seven studies and no evidence for an association between thyroid hormone replacement and breast cancer was observed with an overall RR of 0.99 (95% CI 0.73-1.35, P = 0.965).nnnCONCLUSIONSnOur meta-analysis showed that hypothyroidism is not associated with increased risk for breast cancer and thyroid hormone replacement therapy does not reduce breast cancer prevalence; however, the heterogeneity of the studies analyzed precludes firm conclusions.

Metastatic pheochromocytoma and paraganglioma

Metastatic pheochromocytomas (PCs) and paragangliomas (PGLs) are rare neuroendocrine tumours with a strong genetic background.

Paraneoplastic endocrine syndromes

The majority of neoplasms are responsible for symptoms caused by mass effects to surrounding tissues and/or through the development of metastases. However, occasionally neoplasms, with or without endocrine differentiation, acquire the ability to secrete a variety of bioactive substances or induce immune cross-reactivity with the normal tissues that can lead to the development of characteristic clinical syndromes. These syndromes are named endocrine paraneoplastic syndromes when the specific secretory components (hormones, peptides or cytokines) are unrelated to the anticipated tissue or organ of origin. Endocrine paraneoplastic syndromes can complicate the patients clinical course, response to treatment, impact prognosis and even be confused as metastatic spread. These syndromes can precede, occur concomitantly or present at a later stage of tumour development, and along with the secreted substances constitute the biological fingerprint of the tumour. Their detection can facilitate early diagnosis of the underlying neoplasia, monitor response to treatment and/or detect early recurrences following successful initial management. Although when associated with tumours of low malignant potential they usually do not affect long-term outcome, in cases of highly malignant tumours, endocrine paraneoplastic syndromes are usually associated with poorer survival outcomes. Recent medical advances have not only improved our understanding of paraneoplastic syndrome pathogenesis in general but also enhanced their diagnosis and treatment. Yet, given the rarity of endocrine paraneoplastic syndromes, there is a paucity of prospective clinical trials to guide management. The development of well-designed prospective multicentre trials remains a priority in the field in order to fully characterise these syndromes and provide evidence-based diagnostic and therapeutic protocols.

Chemotherapy in NETs: When and how

The majority of neuroendocrine tumours (NETs) are well-differentiated tumours that follow an indolent course, in contrast to a minority of poorly differentiated neuroendocrine carcinomas (NECs) which exhibit an aggressive course and assocaited with an overall short survival. Although surgery is the only curative treatment for NETs it is not always feasible,necessitating the application of other therapies including chemotherapy. Streptozotocin (STZ)-based regimens have long been used for advanced or metastatic well-to-moderately differentiated (G1-G2) NETs, especially those originating from the pancreas (pNETs). In poorly differentiated grade 3 (G3) tumours, platinum-based chemotherapy is recommended as first-line therapy, albeit without durable responses. Although data for temozolomide (TMZ)-based chemotherapy are still evolving, this treatment may replace STZ-based regimens in pNETs due to its better tolerability and side effect profile. In addition, there is evidence that TMZ could also be used in the subgroup of well-differentiated G3 NETs. There is less clear-cut evidence of a benefit for chemotherapy in intestinal NETs, but still evolving data suggest that TMZ may be efficacious in particular patients. In lung and thymic carcinoids, chemotherapy is reserved for patients with progressive metastatic disease in whom other treatment options are unavailable. Overall, chemotherapy is indicated in patients who have progressed on first-line treatment with somatostatin analogues, have extensive tumour load or exhibit rapid growth following a period of follow-up, and/or have a high proliferative rate; it may occasionally can be used in a neo-adjuvant setting. Prospective randomised studies are awaited to substantiate the role of chemotherapy in the therapeutic algorithm of NETs along with other evolving treatments.

Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies

Tumourigenesis is a relatively common event in endocrine tissues. Currently, specific guidelines have been developed for common malignant endocrine tumours, which also incorporate advances in molecular targeted therapies (MTT), as in thyroid cancer and in gastrointestinal neuroendocrine malignancies. However, there is little information regarding the role and efficacy of MTT in the relatively rare malignant endocrine tumours mainly involving the adrenal medulla, adrenal cortex, pituitary, and parathyroid glands. Due to the rarity of these tumours and the lack of prospective studies, current guidelines are mostly based on retrospective data derived from surgical, locoregional and ablative therapies, and studies with systemic chemotherapy. In addition, in many of these malignancies the prognosis remains poor with individual patients responding differently to currently available treatments, necessitating the development of new personalised therapeutic strategies. Recently, major advances in the molecular understanding of endocrine tumours based on genomic, epigenomic, and transcriptome analysis have emerged, resulting in new insights into their pathogenesis and molecular pathology. This in turn has led to the use of novel MTTs in increasing numbers of patients. In this review, we aim to present currently existing and evolving data using MTT in the treatment of adrenal, pituitary and malignant parathyroid tumours, and explore the current utility and effectiveness of such therapies and their future evolution.

Is there an association between thyroid function abnormalities and breast cancer

ObjectivenThe aim of this study was to evaluate the association between thyroid function abnormalities and breast cancer and, in particular, the prognostic markers of breast cancer..nnnSubjects and methodsnBaseline levels of thyrotropin, free triiodothyronine, free thyroxine and thyroid autoantibodies were measured in 97 women with primary breast cancer, 27 women with benign breast disease, and 4 women with atypical ductal hyperplasia. Their baseline levels were compared with those in 48 healthy women with a normal mammography in the last 2 years.nnnResultsnThere were no significant associations between history of thyroid disease and breast cancer (p = 0.33). The mean baseline levels of triiodothyronine and thyrotropin did not differ significantly between the compared groups. The mean baseline levels of free thyroxine were found to be significantly higher in the breast cancer group, even after adjusting for thyroid replacement therapy. The presence of thyroid antibodies did not differ significantly between the compared groups. In a subgroup analysis, breast cancer cases with thyroid disease and particularly hypothyroidism had a significantly lower incidence of lymph node metastases compared with breast cancer cases without thyroid disease.nnnConclusionsnOur data confirmed the proliferative effect of thyroid hormones on breast cells, which had previously been shown in vitro. Additionally, thyroid disease and particularly hypothyroid function appeared to be associated with a lower incidence of lymph node metastases. Further studies to determine the prognostic role of thyroid hormones in breast cancer are warranted.

Management of the rare entity of primary pancreatic cystic neoplasms

Primary cystic neoplasms of the pancreas constitute a rare entity and are composed of a variety of neoplasms with a wide range of malignant potential. Approximately 90% of these lesions are serous cystic neoplasms or mucin‐producing neoplasms. In contrast to serous cystadenomas which are nearly always benign, the mucinous cystic neoplasms represent a more diverse, heterogenous spectrum of related neoplasms. Intraductal papillary mucinous neoplasms manifest a much greater latent or overt malignant potential than other cystic neoplasms of the pancreas. The various subgroups of cystic neoplasms of the pancreas are evaluated and compared through a review of current literature. No symptoms or signs are pathognomonic for the cystic pancreatic neoplasms. While identification of a cystic tumor is relatively easy, the identification of the specific tumor type may be difficult. Most investigators agree that accurate differentiation of benign from malignant neoplasms can be made only at histopathologic examination of the entire resected segment of the pancreas. Because of the low mortality and low postoperative morbidity, surgical resection is indicated in all patients with cystic tumors.

Current Issues in the Diagnosis and Management of Adrenocortical Carcinomas

Adrenocortical carcinoma is a relatively rare and heterogenous malignancy with evolving diagnostic and therapeutic approaches. The majority of previous information, mainly derived from small-sized series, considered it as a highly malignant tumor with imminent prognosis. However, recent expanded multicenter and multinational databases have produced a considerable amount of information regarding the relation of tumor extent and prognosis, predictors of biological behavior and response to established and evolving therapeutic modalities. Current management of adrenocortical carcinoma involves a multidisciplinary approach and is based on near-total surgical excision and adjuvant therapy with one or more therapeutic schemes based on tumor biology and staging. Mitotane, with or without chemotherapy, remains the cornerstone of treatment, whereas the role of radiotherapy is evolving. Molecular markers are vigorously explored to stratify patients at high risk for recurrence and exploit newer therapeutic approaches.