ACTA ENDOCRINOLOGICA (BUC)

Objectives. Maternal antibodies in cases of chronic autoimmune thyroiditis may be transferred to the baby via the transplacental route, leading to transient hyperthyroidism or hypothyroidism. The development of hyperthyroidism in one sibling and hypothyroidism in the other, however, is an extremely rare condition. We present two siblings, one with transient neonatal hyperthyroidism and the other with transient neonatal hypothyroidism, born to a euthyroid mother who was being treated for Hashimoto's thyroiditis. Case Presentation. Case 1: A term male baby was evaluated due to tachycardia, high fT4 and low TSH. Following a diagnosis of Neonatal thyrotoxicosis, the patient was started on methimazole and propranolol treatments. The doses were gradually reduced and methimazole was stopped in the 5th month of treatment. Case 2: A male baby was referred with elevated TSH identified in the neonatal screening program, with TSH >100 mIU/L and fT4 7.5 pmol/l (N: 12-22) found in a venous blood sample. The patient was started on 50 μg/day LT4, which was gradually decreased and stopped when the baby was 5.5 months old. Conclusion. It should be kept in mind that antibodies may change character in mothers with autoimmune thyroiditis, and may cause different clinical pictures in babies in different pregnancies.

Context. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder, which is characterized by renal phosphate wasting, hypercalciuria, increased 1,25-dihydroxyvitamin D, and decreased parathormone (PTH) levels. Objective. Here we report different clinical features of two siblings with HHRH, confirmed with molecular diagnosis. Subjects and methods. 16.4 years old boy (P1), and 8.7 years old girl (P2) were referred to our outpatient clinic due to clinical suspicion of metabolic bone diseases. Results. P1 had severe hypophosphatemia. Additionally, PTH concentration was near to the lower limit, 1,25-dihydroxyvitamin-D concentration was near to the upper limit. P2 had relatively milder clinical and laboratory findings. Bilateral renal calculi were detected on ultrasound in both of them. HHRH was suspected due to their described biochemistry and the presence of bilateral renal calculi. Molecular analysis of SLC34A3 gene revealed a homozygous variant c.756G>A (p.Gln252=) and a splice donor variant c.1335+2T>A. After oral phosphate treatment, clinical and biochemical improvements were observed. However treatment nonadherence of patients was a barrier to reach treatment goal Conclusion. The clinical phenotype due to the same mutation in the SLC34A3 gene may vary even among the members of the same family. An accurate diagnosis is important for the appropriate treatment.

Aim. The epidemic of metabolic syndrome increases worldwide and correlates with elevation in serum uric acid and marked increase in total fructose intake. Fructose raises uric acid and the latter inhibits nitric oxide bioavailability. We\r\nhypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome and treatment of\r\nhyperuricemia or increased nitric oxide may improve it.\r\nMethods. Two experiments were performed. Male Sprague-Dawley rats were fed a control diet or a high fructose diet to\r\ninduce metabolic syndrome. The latter received either sodium nitrate or allopurinol for 10 weeks starting with the 1st day of fructose to evaluate the preventive role of the drugs or after 4 weeks to evaluate their therapeutic role.\r\nResults. A high-fructose diet was associated with hyperuricemia, hypertension, dyslipidemia, insulin resistance, decreased tissue nitrite and increased adiposity index. Sodium nitrate or allopurinol was able to reverse these features in the preventive study better than the therapeutic study.\r\nConclusion. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid. Either sodium nitrate or allopurinol can\r\nprevent this pathological condition by different mechanisms of action.

Context. Thyroid cancer is the most common endocrine malignancy. Within various subtypes of thyroid neoplasms, those with follicular growth pattern usually make diagnostic problems. Objectives. To examine ck19 expression as a diagnostic marker in thyroid neoplasms with follicular growth pattern. Design. In this cross sectional study, 86 patients were enrolled. Subjects and Methods. Totally 22 follicular adenoma (FA), 18 well differentiated tumors with undetermined malignant potential (WT-UMP) and 46 follicular variants of papillary thyroid carcinoma (FV-PTC) were enrolled and examined for Ck19 expression by immunohistochemistry staining. Membranous/cytoplasmic staining patterns were considered as positive. Specimens without staining were considered as 0, < 5% positively stained cells as 1+, 5%-25% as 2+, 25%-75% as 3+ and >75% as 4+. Result. CK19 was negative in most cases of FA while positive in most WDT-UMP and FV-PTCs, p<0.001. Additionally, most cases with 2+ and 3+ staining patterns were FV-PTC (75% and 81%, respectively, p<0.001) and none of FAs showed 3+ positivity (p<0.001). Additionally, most of strongly positive results in patients > 45 y/o were PTC (p<0.001). Conclusion. Ck19 is a useful marker in differentiating FA from FV-PTC. We found diffuse and strong (3+) staining pattern in FV-PTC but none of FAs were so. We concluded that diffuse and strong staining for ck19 in a thyroid lesion with follicular pattern of growth, especially in a patient older than 45 y/o should raise the possibility of malignancy.

Introduction. Disorders of sexual development can present isolated or as a part of complex genetic syndromes. Case presentation. A newborn with ambiguous genitalia and prenatally diagnosed brain malformations was referred to our hospital. Prenatal ultrasound examination and MRI showed lissencephaly and absence of the corpus callosum. At admission, physical examination revealed microphallus, hypospadia and complete fusion of labioscrotal folds with nonpalpable gonads, normal blood pressure and serum biochemistry. Cortisol level was normal (201 nmol/L), testosterone elevated (14.4 nmol/L), FSH 0.1 IU/L, LH 0.7 IU/L, estradiol 241 pmol/L. Seizures were noted on the 2nd day and the child was started on anticonvulsives. When 17-OHP level results came back elevated (200 nmol/L), ACTH test was performed and the child was started on hydrocortisone and fludrocortisone treatment. Congenital adrenal hyperplasia became unlikely when karyotype result showed normal male karyotype (46, XY, SRY+) with no Mullerian structures seen on ultrasonographic exam. As association of ambiguous genitalia and lissencephaly strongly suggested a mutual genetic background, diagnosis of X-linked lissencephaly with ambiguous genitalia (X-LAG) became apparent. Conclusions. The presented case highlights the importance of looking at the whole clinical picture instead of separate isolated findings with emphasis on patient-centered approach guided by clinical findings and patient history.

Background. Thyroid hormone resistance (RTH) is defined as a decrease in response to thyroid hormones in the target tissue. Most patients present with nonspecific findings. In this article, we aimed to represent a 22-yearold female patient who presented with palpitation, fatigue, and heat intolerance. She was thought to have thyroid hormone resistance and her genetic examination revealed NM_001128177.1 (THRβ): c.1034G > A (p.Gly345Asp) pathogenic variation in the THRβ gene. Case report. A 22-year-old female patient presented with complaints of fatigue, heat intolerance and palpitations. She was taking Propranolol twice daily at admission. Her family history revealed hypothyroidism in her grandmother. Her physical examination results were as follows: height 160 cm, weight 65 kg, body mass index 25.4kg/m2, body temperature 36.5˚C, respiratory rate 18/min, heart rate 86 beats/min, blood pressure 120/80 mmHg. Her palms were sweaty. The heart sounds were normal, and no heart murmur was auscultated. The laboratory results were TSH: 5.31uU/mL, fT3: 6.83 pg/mL, and fT4: 2.43 ng/dL. THRβ gene mutation analysis was requested for our patient whose clinical history and laboratory results were compatible with thyroid hormone resistance. The pathogenic variation NM_001128177.1(THRβ):c.1034G>A (p.Gly345Asp) was detected after analysis. Conclusion. A diagnosis of RTH requires high clinical suspicion and a genetic mutation analysis should be requested in the case of clinical suspicion. In this way, unnecessary anti-thyroid treatment can be prevented.

We aim to describe a patient diagnosed with a rare and aggressive metastatic pattern of an ileal neuroendocrine tumor (NET). A 53-year-old male patient was referred to our cancer care center following the diagnosis of an ileal NET for further evaluation. As part of the initial diagnostic workup, 68Ga-DOTATOC positron emission tomography/computed tomography was conducted. The scan revealed a fulminant metastatic pattern of somatostatin-positive lesions affecting the axial and peripheral skeleton, liver, and a few lesions involving the brain leptomeninges and right extra-orbital eye muscle. Despite the prompt diagnosis and systematic therapeutic approach offered according to institutional guidelines, the patient did not achieve an optimal clinical response, resulting in his demise 18 months after his initial diagnosis. This case is shared with the primary aim of raising awareness of such an unreported aggressive metastatic pattern and encouraging further clinical investigations for patients with similar aggressive metastatic patterns to achieve optimal therapy and care.

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