ACTA ENDOCRINOLOGICA (BUC)

Context. Amiodarone use has been associated with Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH) with only 12 cases reported from its first description in 1996. Objective. The clinical use of the antiarrhythmogenic drug amiodarone is frequently complicated by a very broad spectrum of side effects: cardiac toxicity, hypo- and hyper-thyroidism, pulmonary fibrosis and liver function abnormalities. We report the case of a patient with amiodarone-induced SIADH with the particularity of a very late onset of these adverse effects. Case. A 78 years old man on amiodarone therapy for a history of complex ventricular arrhythmia after a myocardial infarction, comes to the Emergency Department of our Hospital for pre-syncopal symptoms. Laboratory test showed a hypo-osmotic hyponatremia (sodium 110 mEq/L, serum osmolality 233 mOsm/kg) associated with liver enzymes increases. A not suppressed urinary osmolality with high urinary sodium excretion associated with normal thyroid and adrenal functions led to the diagnosis of SIADH. Known associated disorders (neoplasms, lung diseases and central nervous system disorders) were suspected and excluded. A pharmacologic aetiology was suspected and, in the absence of diuretics and neurological drugs, amiodarone seemed the most probable cause of the SIADH. Hypertonic saline solution and fluid restriction were initiated and amiodarone discontinued with a gradual normalization of plasma sodium levels and liver enzymes. Conclusion. The clinical case underlines the importance of monitoring amiodarone-related SIADH with frequent electrolytes biochemical assessment not only in relation to an early but also to a late clinical onset.

Chronic ingestion of licorice is known to cause numerous metabolic and electrolyte disturbances. Severe hyponatremia, hypertension, and hypokalemia as well as metabolic alkalosis are amongst the most common consequences of chronic ingestion resulting in an apparent mineralocorticoid excess (AME). Treatment predominantly consists of cessation of licorice ingestion, potassium replenishment and aldosterone antagonists. Given the potentially lethal effects of chronic licorice ingestion, clinicians should be made aware of the presentation of AME and the proper management. We present the rare case of a 62-year-old male with licorice-induced apparent mineralocorticoid excess secondary to excessive licorice tea intake. Initial presentation included severe hypokalemia of 2.2mmol/L and hypertension of 180/110mmHg, while eunatremic (Na, 144meq/L).

Context. Diabetes is a chronic disorder with a complex pathogenetic background including monogenic, polygenic, and environmental causes. Objective. The aim of the present paper is to share the information related to genetic and clinical data of large pediatric diabetes cohort. Design. The present study retrospectively analyzes genetic and clinical findings of subjects diagnosed with diabetes under the age of 18 year and are in follow-up in a pediatric diabetes referral center. Subjects and Methods. Out of 1205 children with diabetes (902 treated with insulin) 246 underwent genetic tests on the basis of clinical selection criteria since 2007. Results. One hundred and ten variants related to diabetes were found in 89 of them. Age at presentation was 9.5±4.02 years (F/M 44/45). In total 49 pathogenic and likely pathogenic, 11 “hot and warm” of unknown significance variants were found in fourteen MODY and fifteen non- MODY genes according to criteria developed by American College of Medical Genetics. Thirty novel mutations were found. GCK (26.6%) and ABCC8 (10%) were two most frequently affected genes. Antibody testing revealed negative results in 80% of cases. Conclusions. Genetic interpretation in selected cases is important to understand the nature of the disease better. Improvement in testing opportunity and awareness might increase the prevalence of genetically explained diabetes cases. The distribution of subtypes differs between countries and even regions of the same country.

Context and objective. Somatostatin analogues and cinacalcet have been suggested to have some role in managing hypophosphatemia. This report highlights challenges in managing surgically incurable tumor induced osteomalacia (TIO) with somatostatin analogues and cinacalcet. Patient and methods. A twenty-two year old patient with severe osteomalacia was diagnosed to have TIO due to left hemipelvis tumor (June 2013). Partial surgical removal of tumor (due to its proximity to neurovascular bundles), led to transient remission for 6 weeks. Clinical worsening in spite of maximum tolerable phosphate and calcitriol dose led to trial of octreotide. Acute improvement in phosphate following subcutaneous octreotide 100 mcg was the basis for use of long acting depot octreotide, which was associated with maximal improvement for 4 months, followed by reduced efficacy. Repeated MRI revealed an increase in residual tumor size. Reevaluation revealed very a high parathyroid hormone. Cinacalcet titrated to 90 mg/day induced hypoparathyroidism, improved hypophosphatemia but caused symptomatic hypocalcemia. Cinacalcet at lower doses (30mg/day), though well tolerated, was less effective in improving hypophosphatemia. There was a near 10-fold reduction (2406 to 246RU/ml) in C-terminal FGF-23 levels with cinacalcet. Reduction in phosphate and calcitriol requirements with cinacalcet may contribute to decreased FGF-23. There was no decrease in tumor size. Conclusion. Octreotide and cinacalcet are effective in controlling hypophosphatemia over short periods. Progressive nature of TIO leading to an increased disease severity, tachyphylaxis may explain decreased efficacy of octreotide, higher cinacalcet requirement, poor tolerability, thus limiting their role in long-term management of TIO.

Anorchia is a syndrome characterized by unilateral or bilateral absence of testicular tissue.\r\nAt puberty, growth and development are normal but secondary sexual development fails to\r\noccur if anorchia is bilateral.\r\nWe present the case of a 21 year-old male with a late diagnosis of bilateral anorchia. The\r\ndiagnosis was suggested by a bilateral empty scrotum, in a patient with male phenotype and\r\npoor secondary sexual development and established by karyotype analysis, hormonal profile\r\nand surgical exploration. The lack of testosterone response to hCG stimulation is the hormonal\r\nhallmark of bilateral congenital anorchia. In the absence of any information about germinal cell\r\npresence, bilateral excision of the testicular nubbins, implantation of testicular prostheses and\r\nhormonal replacement therapy were indicated.

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Introduction. Agranulocytosis induced by thioamides is rare, occurring only in 0.2-0.5% of cases. Case presentation. We present the case of a 45-year-old woman previously diagnosed with Graves’ disease that discontinued the use of methimazole on her own. She attended the Emergency Department presenting fever (40.5¯C), agitation and diaphoresis. A thyroid storm diagnosis was initially thought, but after laboratory results showing neutrophil count near 0.06x109/L, sepsis due to neutropenia seemed the most logical hypothesis. Cephepime was promptly initiated. For thyrotoxicosis management, cholestyramine and atenolol were prescribed. In her second day of hospitalization, subcutaneous granulocyte colonystimulating factor was started for an earlier medullar response. The patient was discharged after 7 days with atenolol 50mg/ day and instructed to have a definite treatment for Graves disease as soon as possible. Conclusion. Such case purpose is to remember clinicians that sepsis diagnosis can be challenged, especially when a thyroid storm is a possible diagnosis as well. In this particular case, both conditions should be treated, but life-threatening sepsis should have the focus for a quick therapeutic approach.

Aim. Histology and cytology consultations of thyroid fine needle aspiration biopsy (FNAB) of thyroidectomy specimens can change management of the patient. We aimed to determine compliance rates of pathology results between urban centers and a tertiary institution and its impact on patient management.\r\nMethods. This retrospective study includes 101 patients, who were referred to our center, between January 2008 and December 2008. After admission, all FNAB or thyroidectomy specimens of patients managed elsewhere were consulted by the pathology department. Comparison of FNAB and histology reports of our institution and the medical centers elsewhere had been carried out.\r\nResults. A total of 76% concordance rate was found between the FNAB results of other centers and consultation results. The highest concordance was observed in the malignant cytology group (77%). The cytological or histological outcomes of 24 (23.7%) patients were interpreted differently. After second opinion, patient management\r\nchanged in 21 of the 101 patients.\r\nConclusion. Since FNAB results can change the type of surgical treatment and the management plan, the results especially reported as suspicious may need a second\r\nopinion. We suggest that cytology or histology results of thyroid patients referred to tertiary centers for further evaluation and treatment should always be reviewed.

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Background. Glycogen synthase kinase.3β (GSK.3β) has an important role in several signaling pathway including Wnt signaling pathway. Recent evidence has shown that this pathway is involved in follicle development, ovulation and Corpus luteum formation. Aim. In this study we have investigated the effect of LiCl (as a GSK.3β inhibitor) on the ovulation and corpus luteum formation in rat. Materials and methods. Immature 23-day female rats were injected with PMSG (15 IU) to induce follicular development, followed 48h later by HCG (15IU) to induce ovulation. To inhibit GSK3β activity 250 mg/kg LiCl were administerted at the time of LiCl injection. The ovaries were removed at 1,4,8,12,24 h after LiCl treatment and prepared for histological studies. Results. Our results show that the number of preovulatory follicle in LiCl treatment rats was not increased compared with control group. The number of corpus luteum blood vessels were decreased in comparison with control group (p<0.05). Conclusions. These findings show that although LiCl does not inhibit ovulation, it disrupts blood vessel formation in the corpus luteum.