ACTA ENDOCRINOLOGICA (BUC)

Introduction. Wolfram Syndrome (WS) is a rare autosomal recessively inherited disorder characterized by juvenile-onset diabetes mellitus (DM), diabetes insipidus, optic atrophy (OA), hearing loss and neurodegeneration. This report describes three cases with WS. Case report. The first case was diagnosed with DM and OA at the age of 6 and 11 years, respectively. Second patient was the sibling of the first patient, also had DM and was investigated for WS after his brothers’ diagnosis. The third patient was diagnosed with DM at the age of 5 years and developed bilateral sensorineural hearing loss and OA at the ages of 7 and 12 years, respectively. Preliminary diagnoses of all patients were confirmed by Sanger sequencing of the WFS1 gene. Two previously reported and a novel mutation were detected. While our first patient was diagnosed with attention deficit hyperactivity disorder previously described in WS patients, obsessive compulsive disorder observed in case 2, was not previously reported in WS to the best of our knowledge. Puberty delay was detected in our first patient and was diagnosed as constitutional delay of puberty and growth. Conclusion. Early diagnosis of WS can lead to early detection of associated pathologies and to decrease complications, morbidity and mortality.

Hypothyroidism is a frequently diagnosed endocrine disorder that has characteristic\r\nclinical signs and symptoms. The frequency of myopathy in hypothyroidism ranges from 30 to\r\n80%. The major symptoms related are: weakness, muscular cramps and myalgia. The\r\npseudohypertrophic form is called Hoffman's syndrome and is quite rare, reassign diagnosis\r\ndifficulties both to endocrinologists and neurologists. The pathogenesis of this form of\r\nmyopathy is still unclear. We report the case of two patients, daughter and father with\r\npseudohypertrophic myopathy and hypothyroidism by Hashimoto's thyroiditis. The two were\r\npreviously treated for hyperthyroidism: first by antithyroid drugs and secondary by surgery (the\r\ndaughter) and radioiodine (the father). Both developed iatrogenic hypothyroidism that vas\r\ntreated by thyroxin replacement therapy. The muscular symptoms: progressive proximal\r\nweakness, muscle hypertrophy accompanied by stiffness, spontaneous muscular pain, muscular\r\ncramps and fatigue during mild exercise have developed during the year before admittance. In\r\nboth patients Hashimoto's thyroiditis was revealed by the high level of TPO antibodies and the\r\nthyroid appearance in sonography. Hormonal dosages confirmed hypothyroidism. Elevated\r\nvalues of CPK and electromyography established the diagnosis of thyroid myopathy. Muscular\r\nsymptoms were improved but not remitted by the thyroxin replacement therapy in adequate\r\ndoses, but CPK normalized. It is the first time that a familial case of Hoffmann syndrome is\r\ndescribed, suggesting a genetic susceptibility to the development of the syndrome.

Increased frequency of adrenal tumours and adrenal myelolipoma has been reported in patients with 21-hydroxylase deficiency (21-OHD). Adrenal myelolipoma is an uncommon, benign, biochemically non-functioning tumor and occasionally reported in association with endocrine disorders. Diagnosis of myelolipomas is based on imaging with ultrasonography, CT or MRI being effective in more than 90% of cases. We present a 34-year-old man with massive bilateral adrenal masses which was detected on computed tomography and was diagnosed as 21-hydroxylase deficiency (21-OHD) based on biochemical findings. Computerized tomography of the abdomen demonstrated bilaterally very low-density adrenal masses (16x28 mm on the right side and 91x88 and 33x30 mm on the left side) consistent with adrenal myelolipomas. Since myelolipomas are considered as benign tumors, he was not operated. Tumor size did not increase during two year follow-up periods. It is recommended to the physicians to be aware of increased frequency of benign adrenal tumors that occur frequently in patients with 21-OHD. Untreated CAH with prolonged excessive ACTH stimulation might contribute to the growth of adrenal masses. CAH should always be ruled out in incidentally detected adrenal masses to avoid unnecessary surgical procedures.

Craniopharyngioma is part of a spectrum of suprasellar cystic neoplasms, with two distinct clinicopathological entities: most are adamantinomatous tumors occurring more\r\noften in children and young adults, and radiographically are calcified, while papillary form develops more often in adults, lacks calcification, and have a better outcome.\r\nIn this report we describe clinical, CT and MRI features, together with histopathological findings of an early recurrent papillary craniopharyngioma. Reviewing the\r\nCT and MRI findings and microscopic specimens of both the initial and the recurred craniopharyngioma, we identified the rapid relapse of the solid tumoral component and\r\ncorrelate it with low-grade basal cell dysplasia of the epithelial component that evolves from small patchy foci to more extensive areas in length and width. While low-grade basal cell dysplasia is not clearly malignant, once the pathologist sees these cellular changes in a papillary cranyopharyngioma, he must note them in his report as basal cell dysplasia could be the cause of an early tumoral recurrence. Although low-grade basal cell dysplasia in\r\nsquamo-papillary craniopharyngioma is uncommon, when such a diagnosis is established, the radiologist must pay attention to MRI characteristic findings of the solid part (maximum diameters, enhancing aspects, shape, and location) and compare them with those from the previous data.

The study comments unusual associations between thyroid and cutaneous autoimmunity: Graves-Basedow disease (GBD), vitiligo and alopecia areata (AA) starting from two cases. In the first case, a woman with systemic lupus erythematosus (SLE), data were recorded from 38 to 49 years as follows: vitiligo (at 38 ys), alopecia areata (4-6 months afterwards), SLE (after 2 ys) and then GBD (after 8 ys). After 3 years, hyperthyroidism has spontaneously vanished, but vitiligo, AA, leucothrichia, SLE, goiter and ophthalmopathy persisted. In the second case, a man, data were recorded from 26 to 70 years and the disease was associated with psoriasis. The sequence of diseases was: vitiligo (at 26 ys), AA and GBD (after 8 ys), followed by iatrogenic 131I hypothyroidism, and psoriasis (after 33 ys). Vitiligo and AA have spontaneously vanished before GBD began. These multiple immune syndrome associations bring up the question: ?Are these diseases multiple associations or a unique immune disease?? A possible point of view, related to immune network, suggests that these multiple associations represent in fact only one process, therefore they represent not many diseases, but different expressions in time (sequence) and space (organ-lesion) of the disease of the immune network.

Cervical lymph nodes could be a starting sign for a complex diagnosis work-up. Depending on co-morbidities, medical unit and physician’s previous experience, the differential diagnosis includes thyroid malignancy, lymphoma, chronic infectious disorders, etc.

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A 55-year-old female patient was admitted for flushing and abdominal pain in the right upper quadrant. Her past medical history revealed high blood pressure and a recent echocardiography showed thickened appearance of tricuspid valve with coaptation defect and grade II tricuspid regurgitation. Contrast enhanced abdominal CT scan and MRI were subsequently performed and revealed a large macronodular liver mass, as well as other micronodular lesions disseminated in the liver parenchyma. CT guided biopsy from the main liver mass revealed neuroendocrine tumor of unknown origin (probably GI) with Ki-67 of 8%. Surgical exploration was decided. During laparotomy, the primary tumor was found in the proximal ileum and the patient underwent segmental enterectomy. Non-anatomical hepatectomy was also performed to remove the bulk of the tumor burden (more than 90%). Postoperative course was uneventful and the carcinoid syndrome relieved. At present, 15 months postoperatively, the patient is under treatment with somatostatin analogue for its antiproliferative effect, with good clinical, biochemical and tumoral control and stable heart disease. In patients with neuroendocrine liver metastases from unknown primary, surgical exploration could allow detection (and resection) of the primary tumor and surgical debulking of liver metastases to control carcinoid syndrome and carcinoid heart disease.

Introduction. The prevalence of obesity has reached alarming levels in the European Union, including in Romania. Data on the prevalence of obesity is only available at the national populational level, but this may hide the increased levels in disadvantaged groups. The purpose of this study was to evaluate the prevalence of overweight and obesity in the Roma population in Southern Romania. Material and method. This cross-sectional, epidemiological, non-interventional study was conducted from March 2014 to May 2017 in several settlements from Calarasi County. Screening procedures included interviews about medical history, lifestyle, anthropometric and clinical measurements and fasting capillary glucose. Results. The study population consisted of 1120 adult subjects, of which 735 Roma. In Roma population group, the prevalence of underweight, normal weight, overweight and obesity was 4.5% (n=33), 25% (n=184), 25.3% (n=186) and 45.2% (n=332) respectively. In Romanian Caucasians group, the prevalence of underweight, normal weight, overweight and obesity was 2.3% (n=9), 20% (n=77), 33.8% (n=130) and 43.9% (n=169) respectively. Among the Romanian Caucasians significant predictors of obesity were a sedentary lifestyle and current smoking. The odds of being obese in Roma population were higher in sedentary lifestyle persons and lower in current smokers, with primary education, and in those living in rural settlements. The family history of obesity had a significant association with obesity only in Roma population. Conclusions. Our results confirm the need to implement prevention programs in high-risk populations due to the double burden of malnutrition, lack of medical education and preventive healthcare, low socio-economic level.

The discovery of thyrotropin releasing hormone (TRH) in 1969 was the definitive step in decoding the hypothalamic-pituitary thyroid (HPT) axis, thereby opening up the era of neuroendocrinology, while it also revolutionized the diagnostic and therapeutic approach to patients with thyroid diseases. TRH, produced in the hypothalamus, is the central regulator of the HPT. It functions via neurons originating in the paraventricular nucleus (PVN), which integrates multiple neuronal and humoral signals and resets the HPT axis according to variations of external and internal environmental conditions. The TRH activates TSH in the pituitary that stimulates the secretion of thyroxine from thyroid which, in turn, exerts a negative feedback on TSH and TRH secretion. However, various factors are involved in the regulation of the HPT axis. Leptin has both indirect and direct effects on TRH regulation, the former by regulating agouti-related peptide (AGRP) in the arcuate nucleus (ARN) that antagonizes the α-MSH stimulatory activity on pro-TRH gene expression in the PVN, and the latter by stimulating hypothalamic TRH expression, TRH transcription via stimulation of proconvertase 1 and 2 expression, which lead to enhanced processing of pro-TRH into TRH. The interplay of TRH with leptin and the recently reported influence of ghrelin on the HPT axis can alter the setpoint of the axis. The polyphenol resveratrol, as recently observed, exerts an anxiolytic and antidepressant activity in subclinical hypothyroid (SCH) rats. Resveratrol, by decreasing both TSH and TRH mRNA expression, regulates the HPT axis, while in parallel it regulates the Wnt/β-catenin pathway in the hippocampus. These findings open up possibilities for the therapeutic use of resveratrol as coadjuvant, especially in overt and SCH states marked by anxiety and depression. The clinician should be aware of clinical changes that can invalidate the normal regulation of the HPT axis, the most commonly observed being medications and comorbidities.