Georgios Boutzios

Anxiety is associated with hormonal and metabolic profile in women with polycystic ovarian syndrome

Background  Increased prevalence of psychological morbidities, including anxiety, depression and eating disorders, has been reported in women with polycystic ovary syndrome (PCOS) in comparison with normal ovulating, nonhyperandrogenemic women.

Liver failure due to antithyroid drugs: report of a case and literature review

Hyperthyroidism is a common endocrine disorder affecting 2% of females and 0.5% of males worldwide and antithyroid drugs constitute the first line of treatment in the majority of cases. These agents may cause severe adverse effects and among them liver failure, although rare, is a potential lethal one. This case illustrates the sudden and abrupt deterioration of hepatic function due to antithyroid drug administration. This case along with a concise literature review is presented aiming to increase the awareness of endocrinologists of possible fatal complications from the everyday use of common agents such as antithyroid drugs.

Endocrine and metabolic aspects of the Wolfram syndrome

Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness), is a neurodegenerative disease with autosomal recessive inheritance with incomplete penetrance. DIDMOAD is a very rare disease with an estimated prevalence of 1 in 770,000 and it is believed to occur in 1 of 150 patients with juvenile-onset insulin-dependent diabetes mellitus. Additionally, WS may also present with different endocrine and metabolic abnormalities such as anterior and posterior pituitary gland dysfunction. This mini-review summarizes the variable presentation of WS and the need of screening for other metabolic and hormonal abnormalities, coexisting in this rare syndrome.

Common pathophysiological mechanisms involved in luteal phase deficiency and polycystic ovary syndrome. Impact on fertility

Luteal phase deficiency (LPD) is a consequence of the corpus luteum (CL) inability to produce and preserve adequate levels of progesterone. This is clinically manifested by short menstrual cycles and infertility. Abnormal follicular development, defects in neo-angiogenesis or inadequate steroidogenesis in the lutein cells of the CL have been implicated in CL dysfunction and LPD. LPD and polycystic ovary syndrome (PCOS) are independent disorders sharing common pathophysiological profiles. Factors such as hyperinsulinemia, AMH excess, and defects in angiogenesis of CL are at the origin of both LPD and PCOS. In PCOS ovulatory cycles, infertility could result from dysfunctional CL. The aim of this review was to investigate common mechanisms of infertility in CL dysfunction and PCOS.

Clinical Syndromes Related to Gastrointestinal Neuroendocrine Neoplasms

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumors derived from multipotent neuroendocrine cells that have the inherent ability to synthesize and secrete a variety of substances (peptides and amines). When these substances are bioactive, NENs can present with a related clinical syndrome (functioning NENs) and/or symptoms of mass effects (functioning and nonfunctioning NENs). NENs differ in their pathogenesis, clinical syndromes produced, aspects of biological behavior and response to certain antitumor treatment. The carcinoid syndrome (CS) is the clinical constellation of secretory diarrhea, flushing, wheezing and dyspnea as a result of serotonin production mainly from small intestinal NENs. Complications of CS are frequent and include extensive mesenteric fibrosis, carcinoid heart disease and the life-threatening carcinoid crisis. A variety of substances (mainly hormones) are produced from NENs originating from the pancreas associated with specific symptoms that can lead to their precise diagnosis. NENs may also secrete substances characteristic of other sites of origin and produce a variety of paraneoplastic syndromes and/or change their secretory status with time. Surgery remains the best option for complete tumor resection and symptom relief. Surgery may also be used when medical treatment fails to obtain control of the symptoms along with cytoreductive techniques. Somatostatin analogs (octreotide and lanreotide) constitute the backbone of medical treatment for the majority of functioning NENs as they can alleviate symptoms, stabilize tumor growth and improve the quality of life. Telotristat etiprate is a novel oral agent that inhibits tryptophan hydroxylase, the key enzyme responsible for serotonin production, and can improve the symptoms of CS. Nonspecific and supportive therapies are also used for refractory cases. In this chapter the clinical features of functioning NENs will be analyzed as well as aspects of their diagnosis based on secretory substances and treatment of the hormonal excess.

The effect of oral micronized progesterone on hormonal and metabolic parameters in anovulatory patients with polycystic ovary syndrome

OBJECTIVE To investigate the effects of oral natural micronized P on hormonal and metabolic parameters in patients with polycystic ovary syndrome (PCOS) and to answer the clinical question whether induction of withdrawal bleeding is a necessity for the comparison of hormonal and metabolic data in subjects with PCOS. DESIGN Prospective clinical study. SETTING Academic medical center. PATIENT(S) Twenty-eight reproductive-aged women with PCOS. MAIN OUTCOME MEASURE(S) Blood sampling was collected at baseline, after 7 days of oral natural micronized P (200 mg) administration, and after withdrawal bleeding. At these three stages hormonal parameters and homeostasis assessment model (HOMA-IR) index were assessed in all patients. RESULT(S) Oral natural micronized P administration did not alter significantly insulin sensitivity index and androgen levels; however, LH was decreased when postbleeding values were compared to baseline. Nevertheless, after oral natural micronized P administration, P and 17alpha-hydroxyprogesterone (17-OHP) concentrations were increased, and HOMA-IR was decreased, whereas androgens levels were not altered, in comparison with baseline. CONCLUSION(S) The induction of withdrawal bleeding, with this regimen, does not appear to be a necessity for the assessment of hormonal and metabolic profile in anovulatory women with PCOS.

Advances and Current Concepts in the Medical Management of Gastroenteropancreatic Neuroendocrine Neoplasms

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare and heterogeneous group of tumors presenting as localised or metastatic disease and in a subset with distinct clinical syndromes. Treatment is aimed at controlling the functional syndrome, eradicating the tumor, and/or preventing further tumor growth. Surgery is the treatment of choice in removing the primary tumor and/or reducing tumor burden but cannot be applied to all patients. Somatostatin analogs (SS-analogs) obtain control of functional syndromes in the majority of GEP-neuroendocrine tumors (NETs); phase III trials have shown that SS-analogs can be used as first-line antiproliferative treatment in patients with slow-growing GEP-NETs. The role of the recently approved serotonin inhibitor, telotristat ethyl, and gastrin receptor antagonist, netazepide, is evolving. Streptozotocin-based chemotherapy has been used for inoperable or progressing pancreatic NENs but the orally administered combination of capecitabine/temozolomide is becoming more popular due to its better tolerability and potential effect in other GEP-NENs. Phase III trials have shown efficacy of molecular targeted therapies in GEP-NETs and of radionuclide treatment in patients with midgut carcinoid tumors expressing somatostatin receptors. Most patients will develop disease progression necessitating further therapeutic options. A combination of currently available treatments along with the molecular signature of each tumor will guide future treatment.

Thyroglobulin antibodies as a potential predictive marker of papillary thyroid carcinoma in patients with indeterminate cytology

BACKROUND We investigated the efficacy of thyroglobulin antibodies (TgAb) in detecting malignancy in indeterminate thyroid nodules and evaluated the possible association between TgAb and autoimmunity in papillary thyroid carcinoma (PTC). METHODS This retrospective, nonrandomized study included 1,646 patients who had undergone preoperative fine-needle aspiration biopsy to evaluate their thyroid nodules, and then standard total thyroidectomy. Of 194 patients (11.8%) with indeterminate nodules, 61 (31.4%) had PTC and 133 (68.6%) had benign nodules at the final histologic examination. RESULTS Univariate analysis showed that multifocality (P = .002), bilaterality (P = .003), lymph-node metastasis (P = .030), and capsule penetration (P = .003) were significantly associated with positive TgAb in patients with indeterminate cytology and histopathologic diagnosis of PTC. The multivariate analysis showed that TgAb positivity (P < .001) and preoperative thyroid-stimulating hormone levels (P = .022) were independent predictive factor for PTC diagnosis in patients with indeterminate cytology. CONCLUSIONS Preoperative TgAb could be a marker for PTC in patients with indeterminate thyroid nodules, increasing diagnostic accuracy. TgAb positivity could also influence the clinical assessment and subsequent selection of total thyroidectomy.

The validity of current guidelines regarding surgical management of patients with gastric neuroendocrine neoplasms type 1: a report of a series of seven patients.

OBJECTIVE: Gastric neuroendocrine neoplasms Type 1 (GEN type 1) are mostly localized indolent tumors, with only a minority developing lymph node or distant metastasis. Although they are usually managed conservatively, large, invasive, recurrent and grade 2 lesions may require surgical treatment. The aim of this case series is to evaluate the validity of current guidelines regarding surgical management of patients with GEN type 1. CASES: Seven patients (5 female) with GEN type 1 underwent peri-gastric lymphadenectomy when at least one of the following criteria employed in previous guidelines was present: (i) multiple recurrent lesions, (ii) lesions with positive margins following endoscopic resection, (iii) lesions with malignant potential (deep gastric parietal wall invasion, lymph node enlargement, Ki67 proliferative index >2%), or (iv) presence of metastatic disease. Four patients met one and three two of the previously defined criteria; fifteen to thirty-six peri-gastric lymph nodes were resected. Following surgery there was no alteration in tumor staging status compared to pre-surgical staging. During a median follow-up of 34 months, all patients remain without any evidence of disease recurrence. CONCLUSION: Peri-gastric lymphadenectomy did not prove to be necessary for localized GEN type 1, neither for staging nor for therapeutical reasons. Further parameters need to be evaluated to identify the small subset of patients that will develop more aggressive disease.

Management of neuroendocrine tumors of unknown primary

Neuroendocrine neoplams (NENs) are mostly relatively indolent malignancies but a significant number have metastatic disease at diagnosis mainly to the liver. Although in the majority of such cases the primary origin of the tumor can be identified, in approximately 11–22% no primary tumor is found and such cases are designated as NENs of unknown primary origin (UPO). This has significant therapeutic implications with respect to potentially resectable hepatic disease and/or application of appropriate medical therapy, either chemotherapeutic agents or targeted treatment, as the response to various treatments varies according to the origin of the primary tumor. This lack of tumor specific orientated treatment may also account for the relatively poorer prognosis of NENs of UPO compared to metastatic NENs with a known primary site. In the majority of cases the primary tumors are located in the small bowel and the lung, but a number may still elude detection. Occasionally the presence of a functional syndrome may direct to the specific tissue of origin but in the majority of cases a number of biochemical, imaging, histopathological and molecular modalities are utilized to help identify the primary origin of the tumor and direct treatment accordingly. Several diagnostic algorithms have recently been developed to help localize an occult primary tumor; however, in a number of cases no lesion is identified even after prolonged follow-up. It is expected that the delineation of the molecular signature of the different NENs may help identify such cases and provide appropriate treatment.