Carmen Vulpoi

Anaplastic Thyroid Carcinoma or Thyroid Metastasis fromCholangiocarcinoma? A Case Report

Anaplastic thyroid carcinoma presents as an extremely localy invasive neck mass while metastases in the thyroid are most commonly described as small, indolent, solitary nodules usually originating from kidney, breast, lungs and skin tumors. We report the case of a 74-year old male patient illustrating the difficulties of differential diagnosis between an anaplastic thyroid carcinoma and a thyroid metastasis of a peripheral cholangiocarcinoma in a cirrhotic patient diagnosed and operated for a locally advanced thyroid tumor. The history, clinical and imagistical features strongly pleaded for the diagnosis of anaplastic thyroid carcinoma presumably with liver metastases, also supported by the rapid recurrence following total thyroidectomy. Immunohistochemical tests showed a malignant carcinomatous proliferation with anaplastic prophile. Positive immunochemical staining for cytokeratin AE1/AE3, CK7 and negative CK20, AFP, CD15, CD30, CD5, TTF1 and thyroglobulin directed the possible diagnosis toward a secondary thyroid tumor from a peripheral cholangiocarcinoma. Immunohistochemical tests showed a malignant carcinomatous proliferation with anaplastic prophile. Positive immunochemical staining for cytokeratin AE1/AE3, CK7 and negative CK20, AFP, CD15, CD30, CD5, TTF1 and thyroglobulin directed the possible diagnosis toward a secondary thyroid tumor from a peripheral cholangiocarcinoma. A CT-guided percutaneous hepatic punction biopsy was planned but the patient presented an ischemic stroke with fatal outcome. In conclusion, in spite of surgical treatment the rapid recurrent thyroid cancer either primary or metastatic had a poor prognosis with fatal outcome mainly in the presence liver cirrhosis and cardio-vascular co-morbidities.

DICENTRIC CHROMOSOME 14;18 PLUS TWO ADDITIONAL CNVs IN A GIRL WITH MICROFORM HOLOPROSENCEPHALY AND TURNER STIGMATA

ABSTRACT We report a 20-year-old female with features evocative of Turner syndrome (short stature, broad trunk, mild webbed neck), dysmorphic face, minor features of holo-prosencephaly (HPE), small hands and feet, excessive hair growth on anterior trunk and intellectual disability. Cytogenetic analysis identified a pseudodicentric 14;18 chromosome. Genome wide single nucleotide polymorphism (SNP) array showed a terminal deletion of approximately 10.24 Mb, from 18p11.32 to 18p11.22, flanked by a duplication of approximately 1.15 Mb, from 18p11.22 to 18p11.21. In addition, the SNP array revealed a duplication of 516 kb in 16p11.2. We correlated the patient’s clinical findings with the features mentioned in the literature for these copy number variations. This case study shows the importance of microarray analysis in the detection of cryptic chromosomal rearrangements in patients with intellectual disability and multiple congenital anomalies

Serum Uric Acid Concentration in Overweight and Obese Women with Polycystic Ovary Syndrome / Nivelul acidului uric la femeile supraponderale și obeze cu sindromul ovarelor polichistice

Abstract Background: Women with polycystic ovary syndrome (PCOS) are at high risk for the development of diabetes mellitus, hypertension and coronary heart disease. Due to the inverse correlation between serum uric acid and insulin sensitivity, the measurement of uric acid may provide a marker of insulin resistance. Objective: To establish the relationship between uric acid and markers of insulin resistance in obese and overweight women with PCOS. Methods: Serum uric acid levels were measured in 38 PCOS obese and overweight patients and 30 controls matched for age and body mass index (BMI). Anthropometric variables, plasma glucose and insulin levels were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR). Results: No statistically significant differences in uric acid levels between PCOS and non-PCOS women were found. Serum uric acid levels were positively correlated with BMI, waist circumference, insulin and HOMA. Following the use of stepwise linear regression analysis, BMI was the only parameter retained by the regression model, responsible for 42.1% of the variability of serum uric acid levels. Conclusions: In PCOS women obesity seems to be the main determinant of plasma uric acid levels. Insulin and HOMA are also involved to a lesser extent, but their role remains to be clarified by further studies. Rezumat Femeile cu sindromul ovarelor polichistice (PCOS) au un risc crescut de a dezvolta diabet zaharat, hipertensiune arterială și afectare coronariană. Datorită corelației negative dintre nivelul seric al acidului uric și sensibilitatea la insulină, determinarea acidului uric ar putea reprezenta un marker al rezistenței la insulină. Obiectiv: Stabilirea relației dintre acidul uric și markeri ai rezistenței la insulină la femeile supraponderale și obeze cu PCOS. Metodă: Nivelul seric al acidului uric a fost măsurat la un lot de 38 de paciente supraponderale și obeze cu PCOS comparativ cu un lot control alcătuit din 30 de femei cu aceeași vârstă și indice de masă corporală (BMI). Au fost evaluați parametri antropometrici, nivelul glicemiei și insulinemiei. Rezistența la insulină a fost apreciată prin calcularea indicelui HOMA (HOmeostasis Model Assessment). Rezultate: Nu au existat diferențe statistic semnificative între nivelurile de acid uric la femeile cu PCOS comparativ cu femeile fără PCOS. Nivelul acidului uric s-a corelat pozitiv cu BMI, circumferința taliei, insulină și HOMA. Aplicând analiza regresiei liniare, am observat că BMI a fost singurul parametru responsabil de 42,1% din variabilitatea nivelului acidului uric. Concluzii: La femeile cu PCOS obezitatea pare principalul determinat al nivelului de acid uric. Insulina și HOMA sunt implicate de asemenea în mai mică măsură, rolul lor urmând a fi clarificat în studii viitoare.

Concomitant autoimmune thyroiditis and primary hyperparathyroidism – random association? Two cases report

Autoimmune thyroiditis and primary hyperparathyroidism are frequent diseases, mainly affecting postmenopausal women. The association between the two pathologies has been described in the literature but the underlying mechanism is not yet elucidated. We present two female patients with autoimmune thyroiditis who developed primary hyperparathyroidism. Both had normal thyroid function, high antithyroid antibodies, and high PTH and calcium values. Thyroid ultrasonography and 99mTc-MIBI scintigraphy localized the lesion but only one patient underwent surgery. Vitamin D and selenium values were normal or slightly reduced. Both patients had osteoporosis, treated with bisphosphonates. Their evolution is, till now, satisfactory. More theories are trying to explain the correlation between autoimmune thyroiditis and primary hyperparathyroidism: the inflammatory process, the high TSH or PTH values, high calcium, low vitamin D. The possible selenium intervention would correlate environmental and genetic factors. However, all these theories are controversial and not yet proved by experimental or randomized clinical studies.

Malignant Paraganglioma; a Story of a Long Time Survival

Pheochromocytoma and paraganglioma are catecholamine secreting tumors. Malignancy is uncommon - approximately 10% for pheochromocytoma and 20% for paraganglyoma. Surgery, when possible, is the first line treatment. Prognosis is poor because of a frequent local recurrence and/or metastases and the lack of specific chemotherapeutic agents. We report the case of a 60 years old man who was hospitalized at the age of 48 for episodes of paroxystic hypertension with spells. The high levels of vanillylmandelic acid (VMA), more than 50 mg/24h at 3 determinations, confirmed the excess of catecholamine, but the CT scan failed to reveal the tumor. The iodine-131- meta-iodobenzylguanidine (I-MIBG) scintigraphy showed the presence of a 1.5 cm nodule in the left abdominal paraaortic region. The patient refused surgery and had a satisfactory evolution with antihypertensive therapy. 11 years later he was admitted in the Vascular Surgery Department for acute ischemia of inferior limbs; a voluminous para-aortic tumor was diagnosed and resected. The pathology confirmed paraganglioma and described some atypical cells without being able to discriminate between benign or malignant pattern. Anamnesis could not identify any other case in the family. After another year he was admitted in the Endocrine Department for the reappearance of the adrenergic syndrome, with VMA at 30.8 mg/24h. The thoracic and abdominal CT-scan showed abdominal and thoracic metastatic tumors. The patient was referred to a specialized center were octeotride scintigraphy confirmed local recurrence and metastatic tumors in the lungs. He was treated with Sunitinib with a good initial response and he died after 16 years from the initial diagnostic of paraganglioma.

The neuro-cardio-facial-cutaneous syndrome – unity in diversity

The neuro-cardio-facial-cutaneous syndrome (NCFCS) concept was recently established in order to group a number of hereditary disorders characterized by a variable degree of growth and mental retardation, cardiac defects, dysmorphic facial features and skin abnormalities, and having a common background, germline mutations in genes of the RAS-MAPKinase pathway. The included entities are Noonan and Leopard syndrome (the most frequents), Costello syndrome, cranio-facio-cutaneous syndrome, as well as some forms of type 1 neurofybromatosis and the newly defined Legius syndrome. We present illustrative cases of 2 of this syndromes, Noonan (NS) and Leopard syndrome (LS), illustrative for both the common elements and the variety of the characteristics. Four of the six cases of Noonan syndrome are treated with growth hormone, with a good response, proving the importance of an early diagnostic. Two cases are fronm the same family (mother and son), the mother of another case has patognomic features but the diagnostic had not yet been confirmed. One of the children with NS, recently diagnosed, with important vertebral deformation needing specific treatment cannot, for the moment, be treated with hGH in spite of the important growth delay (>-3SD). LEOPARD is an acronym for the major features of the disorder: Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, Deafness. The probant case of LS, a 15 years old boy, presented almost all these features, with the exception of deafness. He associated a cerebral tumor, rare in LS, but which could be considered as a NCFCS feature, the MAPK pathway being involved in tumorigenesis. He presented with short stature and neurologic symptoms, both improved after the (partial) tumor resection (pylocytic astrocytoma). The genetic investigation of the family confirmed the syndrome at 4 other members (father, two brothers and a sister), each one with various manifestations, from only cafe-au-lait spots to cardiac malformations. The absence of patognomonic symptoms as well as the overlap of numerous features makes the diagnosis of the components of NCFCS difficult, the molecular diagnosis offering the chance to exceed the clinical difficulties. More than that, specific mutations are associated with specific fenotypes, which has a great importance for the diagnostic and prognostic. An early diagnostic is important not only for the rapid treatment of life threatening elements (cardiac malformations, tumors) and chronic treatment of some features (like short stature), but also for an appropriate genetic counseling.