ACTA ENDOCRINOLOGICA (BUC)

-

Context. Cholelithiasis in childhood is uncommon, while in infancy it is rarely reported. An extremely rare form of cholelithiasis occurs with pseudohypoaldosteronism (PHA). In these patients gallstone formation has been attributed to dehydration and salt-wasting, starting from fetal life. Case report. A neonate with PHA presented with dystrophy, vomiting, hyponatraemia, hyperkalaemia, metabolic acidosis and gallstone formation. Plasma renin activity and aldosterone concentrations were elevated and urinary Na excretion was increased. Gallstones automatically subsided at the age of six months after appropriate sodium chloride supplementation. Conclusions. Infants with PHA , even without signs of salt wasting, should be investigated for cholelithiasis. Inversely, in infants with pertinent electrolyte abnormalities and cholelithiasis, PHA should be considered among the possible diagnoses.

Context. This is a case of gonadotropinoma presented with Rathke's cleft cyst.\r\nObjective. We are presenting a case of gonadotropinoma along with Rathke's cleft cyst which is unique case as being male and symptomatic gonadotropin releasing adenoma.\r\nMethod. A 51 year old man was referred to our institution for evaluation of impotence and loss of libido. His endocrine screening evaluations revealed hypopituitarism with low levels of blood cortisol and ACTH, and high levels of prolactin.\r\nResults. An endonasal transsphenoidal endoscopic approach was performed and upon inspection via endoscope the floor of sella was eroded and following dural incision soft dark\r\ncolored tumor overflowed through sella. Pathology revealed gonadotropinoma with unexpected remnants of Rathke's cleft cyst.\r\nConclusion. Pituitary adenomas and Rathke's cleft cysts have a common embryologic ancestry. Our case was a symptomatic gonadotropinoma consisting of multicystic\r\ncomponent which was then demonstrated as Rathke's cleft cyst in pathological work up.\r\nThis combination may be the result of a coincidence or Rathke's cleft cysts may be the\r\norigin of the pituitary adenomas.

Objective. Parathyroid gland hyperplasia is diffuse or nodular in secondary hyperparathyroidism (sHPT) in patients with renal failure. Whether the nodular growth starts from the beginning or is the transformation of a diffusely-growing gland into nodular hyperplasia in parallel\r\nwith increases in the severity of the disease is unknown. The disease might be unresponsive to medical treatment when\r\nnodular hyperplasia develops. This study aims to differentiate the characteristics of the parathyroid glands with and without nodular hyperplasia in sHPT, and to\r\ninvestigate if there is any similarity between the nodular hyperplastic glands of sHPT and the parathyroid adenomas of primary hyperparathyroidism.\r\nMaterials and Methods. Hyperplasia types (nodular or diffuse) and parathyroid cell types, and the expression of\r\nproliferating cell nuclear antigen (PCNA) and Ki-67 in parathyroid tissue were investigated histopathologically and\r\nimmunohistochemically in 94 parathyroid glands of 42 patients with hyperparathyroidism.\r\nResults and Discussion. 63 glands showed nodular hyperplasia and 16 diffuse hyperplasia in sHPT. Chief cells predominated across the whole series. Vacuolated chief cells most frequently accompanied chief cells in both nodular\r\nhyperplasia (28.6%) and adenomas (53%). The median ratio of PCNA LI (labelling index) was 30/10? (min: 4-max: 720) cells in nodular hyperplasia, 16/10? (min: 2-max: 180) cells in diffuse hyperplasia and 30/10? (min: 10-max: 707) cells in adenomas (p>0.05). The highest PCNA LI according to all the cell types in the series was in chief cell and vacuolated chief cell combinations (53/10?, p=0.04). These findings suggest that parathyroid adenoma and nodular hyperplasia have histopathologically- and immunohistochemically - simil ar characteristics suggesting that both have aggressive cell proliferation.

Background. The incidence of adrenal incidentaloma has been increasing proportional to the use of radiologic examination. Multiple endocrine neoplasia1 (MEN1) syndrome may present with various tumors. The present study reports a case of adrenal incidentaloma with unrecognised MEN1 syndrome associated with breast cancer. Clinical case. A 48-year-old woman presented with a 2.4cm left adrenal incidentaloma on abdominal computed tomography. Her history revealed primary amenorrhea, recurrent peptic ulcer and nephrolithiasis. Laboratory and radiologic examination revealed two pancreatic tail mass lesions with markedly elevated gastrin levels (1462 pg/mL), hypercalcemia with increased parathyroid hormone levels (72 pg/mL), a 1.5cm pituitary mass with hyperprolactinemia (234 ng/mL), a 1.0cm meningioma and a nonfunctional left adrenal mass. During this image work up, a 0.6cm nodule in the right breast was incidentally detected. Surgeries (laparoscopic distal pancreatectomy, parathyroidectomy and wide local excision of breast) and pathologic findings confirmed pancreatic neuroendocrine tumors, parathyroid gland hyperplasia, and breast cancer. Carbergoline treatment for 12 months decreased prolactin levels to 27 ng/mL. Genetic testing using peripheral blood revealed a pathogenic variant in MEN1 on chr11q13 (NM_000244.3:c.1365+1_1365+11 del, GTGAGGGACAG, heterozygous). Conclusion. Considering the increasing incidence of adrenal incidentaloma and 20% prevalence of adrenal tumors in patients with MEN1, it is important to rule out MEN1 association in patients with adrenal incidentaloma. Additionally, breast cancer was detected during MEN1 workup in this case. Female patients with MEN1 are at increased risk for breast cancer. Therefore, intensified breast cancer screening at a relatively young age should be considered in female MEN1 patients.

-

Context. Red cell distribution width (RDW) has been associated with type 2 diabetes (T2DM), however data in relation to diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar non-ketotic acidosis (HONK) remains unclear. Objective. The aim of this study was to evaluate the association between RDW, MCV, and RDW/MVC values and acute complications in T2DM. Patients and Methods. RDW was measured in 90 T2DM patients (30 DKA, 30 HONK and 30 T2DM without acute complications). Clinical variables were analyzed by One –Way ANOVA, Kruskal-Wallis and Pearson analysis with SPSS software. Diagnostic screening tests and ROC curve analysis determined the cut-off point of MCV,RDW and RDW/MCV values. Results. DKA patients had higher levels of plasma glucose (524.20±201.43mg/dL, p<0.001), HbA1c (10.73±2.29%, p<0.001), osmotic pressure (310.32 mosm/L, p<0.001), RDW (14.61±1.75g/L, p<0.01), and the RDW/MCV ratio (0.17±0.04%, p<0.01), compared to HONK patients. RDW/MCV cut-off value was 0.15 with 90% sensitivity 50% specifity these values for only MCV were 76.67%-70%, for only RDW were 76.67%- 63.33% respectively. The area under curve values for the ability to reflect DKA for RDW and the RDW/MCV ratio were 0.708 and 0.766, respectively (p<0.001). Conclusions. RDW and RDW/MCV ratio were found associated with DKA and valuable in predicting DKA. However these parameters were not valuable in predicting HONK.

Objective. The non-effectiveness of levothyroxine administration in hypothyroidism depends on many factors and mechanisms influencing its absorption in small intestins or bounding of circulating hormone with different active molecules. Methods. Thyroid hormones, TSH, rT3, TGl, TPOAb, TG-Ab, were measured using commercially available assays. For anti-T4ab, radioiodine-labeled T4 was added to the patient’s serum and the IgG fraction subsequently precipitated by addition of 15% polyethylene glycol. Background was determined by testing 100 control sera from individuals without autoimmune thyroid disease. Results. A 42-year old woman (71.5 kg) with Hashimoto thyroiditis receiving levothyroxine (L-T4) 150 μg and liothyronine (L-T3) 37.5 μg was admitted to the hospital with clinical data of hypothyroidism, TSH-23.8 mU/L, FT4- 6.18 pmol/L (n.range 9-19 pmol/L), TPO-Ab 696 IU/mL, TGAb 818 IU/mL, circulating T4- antibodies positive. She has a good adherence to medication, malabsorption or administration of other drugs were excluded. L-T4 absorption test revealed 44% increase of serum FT4 at 120 min after ingestion of 150 mcg L-T4 (2.1 mcg/kg). Methylprednisolone pulses of 500 mg i.v. administered in three consecutive days at equal doses of L-T4/L-T3 resulted in a rapid increase of FT4 to 14.5 pmol/L, fall of TSH to 0.18 mU/L and decrease of anti-T4 antibodies to referent range; TPO-Ab and TG-Ab also decreased significantly. Monotherapy by 150 mcg L-T4 was continued in the next three months. A recurrence of hypothyroidism with increase of circulating T4-Ab was observed 100 days later. New administrations of methylprednisolone two pulses of 500 mg revealed a similar normalization of thyroid hormones and anti-T4 antibodies. Conclusion. The data showed that T4-antibodies might be a cause of insufficient effects of levothyroxine therapy in autoimmune hypothyroidism. This could be overcome by glucocorticoid administration probably resulting in FT4 release from circulating immune complexes.

Background. ROHHADNET syndrome is a pleiotropic disorder defined by rapid onset of obesity, hypothalamic-pituitary endocrine dysfunctions, alveolar hypoventilation and hypothalamic autonomic dysregulation and neural tumors. Case presentation. We report the case of a 5.8-year-old female patient with rapid onset of obesity and growth arrest, hypercortisolism, hyperprolactinemia, low IGF1, severe hypernatremia (with no signs of diabetes insipidus) and chronic hyperchloremic metabolic acidosis. Additional symptoms included sleep apnea and two episodes of cardiopulmonary arrest after mild sedation. Brain MRI, chest and abdominal enhanced CT scans were all negative. As no tumors were revealed at the time of diagnosis, ROHHAD syndrome was suspected. Treatment with potassium bicarbonate was initiated in an attempt to control both the severe hypernatremia and chronic hyperchloremic metabolic acidosis. Patient developed dilated cardiomyopathy and kaliopenic nephropathy. Conclusion. The presence of dilated cardiomyopathy is in keeping with only one other reported case, while the severe hypernatremia joined by hyperchloremic metabolic acidosis seen in our patient has not been presented previously. Although it is a very rare medical condition, ROHHAD syndrome has to be considered in the differential diagnosis of any case with rapid onset obesity associated with hypothalamic-pituitary endocrine dysfunctions, and alveolar hypoventilation.

Aim. To explore the effects and underlying mechanisms of pioglitazone (pio) on insulin sensitivity in insulin-resistant KKAy mice. Methods. Sixteen eight-week-old male KKAy mice were randomly assigned to two groups based on body weight: an insulin resistance model group and a pioglitazone treatment group (hereafter referred to as the pio-group). Eight male C57BL/6J mice were used as an insulin resistance control group. Mice in all three groups were fed an AIN-93G diet, and pio was added to the diet in the pio-group. After twelve weeks of treatment, blood glucose, serum insulin, glucose tolerance, and insulin tolerance were measured. ELISA was used to determine adiponectin and leptin in serum. A real time PCR assay was used to detect the mRNA of adiponectin and leptin in epididymal adipose tissue. A Western blot assay was used to analyze protein expression and/ or phosphorylation levels of peroxisome proliferator activated receptor γ (PPARγ), insulin receptor substrate 1 (IRS1), and protein kinase B (PKB/AKT) in the liver and epididymal adipose tissue.Results. The results showed that Pio treatment may effectively reduce levels of blood glucose and serum insulin, improve insulin tolerance and glucose tolerance, increase serum adiponectin, decrease serum leptin, and enhance mRNA expression of adiponectin in epididymal adipose tissue. Furthermore, with pio treatment, protein expression of PPARγ and phosphorylation levels of IRS1 and AKT were increased in the liver and epididymal adipose tissue. Conclusion. These results suggested that Pio intervention may ameliorate insulin resistance and improve insulin sensitivity in KKAy mice, which may be due to an increase of PPARγ and further activation of the insulin signaling transduction pathway (IRS1 and AKT) in the liver and epididymal adipose tissue of KKAy mice.