ACTA ENDOCRINOLOGICA (BUC)

Context. Patients with renal malignancies present high risk of adrenal hyperplasia and adenoma, and part of these are primary lesions, mostly non-functional. Here we presented a case diagnosed as primary adrenal adenoma with autonomous cortisol secretion accompanied by homolateral renal cell carcinoma. Case presentation. A 79-year-old woman was referred for evaluation of a left adrenal mass, with a past medical history of severe hypertension, diabetes, and hyperlipidemia. On examination, no clinical signs of cushingoid features were found. Biochemical measurements showed plasma cortisol was 12.77 μg/dL and was not suppressed by 1 mg dexamethasone (DXM) overnight test (13.6 μg/dL). The contrast CT scan presented a 2.2 cm diameter adrenal mass and revealed, unfortunately, a hyperdense mass at the middle-upper pole of the left kidney. Laparoscopic nephrectomy with left adrenalectomy was performed and pathological examination indicated a final diagnosis of benign adrenocortical adenoma and renal clear cell carcinoma. At 2 months postoperatively, without replacement treatment of cortisol, a recovery of circadian rhythm of cortisol secretion was detected, indicated recovery of the hypothalamic-pituitary-adrenal axis. Conclusions. Patients with renal cancer might be accompanied with functional adrenal adenoma. Therefore, screening for adrenal function should be recommended in patients with renal tumors and/or adrenal incidentaloma.

Prolonged target gland failure causes pituitary hyperplasia, but rarely, secondary hyperplasias develop into autonomous neoplasms. We report herein a rare example of gonadotroph adenoma arising in a patient with prolonged hypogonadism due to Klinefelter syndrome. A pituitary macroadenoma with suprasellar extension was discovered incidentally by magnetic resonance imaging (MRI), in search for the cause of chronic saliva retention. His pre-operative serum concentrations of both luteinizing hormone (LH) and mostly follicle-stimulating hormone (FSH) were distinctly higher than normal, as expected, but the levels decreased after complete removal of the tumor, suggesting partial secretion of gonadotropins by the tumor. The surgically removed tissue showed a typical pituitary adenoma with distinct immunoreactivity for FSH (intense, homogeneous) and LH (scattered). In the fragmented parts of adjacent gland tissue, no hormone producing cell hyperplasia or presence of gonadal deficiency cells were detectable. In conclusion, our case is the description of a rare example of gonadotropin producing pituitary adenoma (FSH and LH) with increased serum levels of both gonadotropins in a patient with untreated Klinefelter syndrome.

Background. Thyroid hormone participates in lipid metabolism regulation. However, the effects on triacyleride or triacylglycerol metabolism are complex and not fully clarified yet. In this study, we try to identify novel thyroid hormone-targeting lipogenic metabolic genes and analyze their molecular regulative mechanism. Method. Thirty-five promoters of twenty-nine human lipogenic regulative enzyme genes were constructed into pXP1 luciferase reporter plasmid (PFK2/FBP2-luc) and transfected into HeGP2 cells, respectively. Gene expression induced by triiodothyronine (T3) was detected by luciferase assay. The T3-activated gene promoter was then analyzed by sequence analysis, deletion and mutation, and electrophoretic mobility shift assay (EMSA). Results. After 10 nM T3 stimulation for 36 h, phosphogluconate dehydrogenase, malic enzyme, Glycerol- 3-phosphate acyltransferase (GPAT) 3, and 1-acylglycerol-3- phosphate O-acyltransferase (AGPAT) 2 were significantly activated, respectively. A AGGTCA-like-direct-repeat-4 consensus thyroid hormone response element (DR4-TRE)- like sequence was found in the GPAT3 promoter, which was then verified to be necessary for T3-induced GPAT3 activation by gene deletion and mutation analysis. EMSA further identified that T3-thyroid receptor (TR) α-retinoid-X receptor (RXR) complex directly bound on the GPAT3 promoter. Conclusion. Triiodothyronine could activate the GPAT3 through DR4-TRE-like sequence binding to participate in lipogenic regulation. AGPAT2 may be another thyroid hormone target enzyme.

Objective. Endoplasmic reticulum stress (ERS) is suspected as an important factor in the initiation of insulin resistance. Aim. To explore the effects of exendin-4 (Ex- 4) on the endoplasmic reticulum stress (ERS)-mediated insulin resistance in 3T3-L1 adipocytes. In our study, 3T3-L1 adipocytes were pre-treated with ERS inhibitors tauroursodeoxycholic acid (TUDCA), Ex-4 and an ERS inducer tunicamycin (TM) then induced insulin resistance. Glucose consumption of the adipocytes was measured. Western blots determined the protein levels of ERS markers and insulin signaling pathway. Results. TM treatment reduced insulin-stimulated glucose consumption by 19.7% in 3T3-L1 adipocytes. This repression was blunted by 24h pre-treatment with TUDCA or Ex-4. Ex-4 augmented insulin-stimulated glucose consumption in adipocytes by 14.9%. Western blotting showed that TM treatment significantly increased the ER stress markers including p-IRE, p-JNK, p-PERK, p-eIF2a and ATF6 expression, whereas 24h pre-treatment of adipocytes with TUDCA or Ex-4 alleviated the ER stress. Ex-4 alleviates ERS-induced insulin resistance by upregulating the expression of phosphorylated Akt. Conclusion. ERs mediates insulin resistance in 3T3-L1 adipocytes, and exendin-4 significantly improves this insulin resistance.

We present the case of severe hypocalcaemia in a 5 weeks old baby, secondary to pre and postnatal vitamin D deficiency. The symptomatic hypocalcaemia led to several life threatening episodes of seizures. Following initial calcium gluconate infusion, multiple phospho-calcic deposits in the soft tissue and cerebral tissue were observed. A multifactorial etiology of calcinosis cutis was suggested by the association between infusion of high and repeated doses of calcium gluconate in a severely hypocalcaemic baby, with a low 25- hydroxyvitamin D3 level, associated to a renal and bone relative resistance to the high level of PTH. The aim of this report is to raise pediatric health care professionals awareness on the relatively rare entity known as calcinosis cutis.

Context. Trabecular Bone Score (TBS) has been recently proposed as a good tool to investigate secondary osteoporosis. Objective. The aim of this study was to assess TBS from spine DXA images in patients with primary hyperparathyroidism (PHPT) and look at its correlates. Subjects and Methods. 153 patients, mean age 59.1 ± 12.1 yrs, females and males (10%), mean BMI 26.2 ± 4.8 kg/m2, mean serum calcium and PTH of 11.3 ± 1.2 mg/dL and 232 ± 329 pg/mL, respectively; 89% had osteoporosis/ osteopenia by LS DXA and 46% had renal involvement. There were 7.6% patients with vertebral fractures, 13.2% patients with nonvertebral fractures. TBS indices were derived from LS-DXA images and cutoff points used were those previously reported. Results. Mean TBS was in the partially degraded range (1.258 ± 0.115); 32% of patients had degraded microarchitecture (TBS ≤ 1.20), 51% had partially degraded microarchitecture (TBS > 1.20 and < 1.35) and 17% had normal TBS. TBS was significantly correlated with areal BMD both at the LS (r=0.544; p<0.001) and FN (r = 0.315; p < 0.001), and negatively with age (r= - 0.354; p < 0.001) and years since menopause - YSM (r = - 0.257, p = 0.005). Patients with vertebral fractures had mean values of TBS in the degraded range, significantly lower than those without vertebral fractures (1.173 ± 0.076 vs. 1.263 ± 0.115; p = 0.006). The presence of vertebral fracture was independently associated only with YSM (OR = 1.131, 95% CI = 0.032 – 0.214, p = 0.008) but not with TBS. Conclusions. In a cohort of symptomatic PHPT patients, including postmenopausal, premenopausal and male patients, we have shown that TBS was in the partially degraded range, but it was not independently associated with fractures.

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Hematopoietic stem cell transplantation (HSCT) is an effective treatment for various types of hereditary hematologic disease, hematological malignancy, primary immunodeficiency and metabolic disease. Thyroid dysfunction is a common complication of HSCT, which situation is mainly manifested as hypothyroidism and rarely as hyperthyroidism. This report presents a 28-yearold man who developed hyperthyroidism 9 years after sibling allogeneic HSCT, which was most likely caused by chronic GVHD. In the meantime, the patient also suffered from liver dysfunction and pancytopenia, for which he was inappropriate to take antithyroid drugs (ATD) for treatment of hyperthyroidism. The patient was orally administered 259 MBq 131I, an individualized dose. The symptoms of hyperthyroidism were mitigated by 131I treatment.

Background. Isolated methylmalonic acidemia refers to a group of inborn errors of metabolism characterized by elevated methylmalonic acid concentrations in the blood and urine. It occurs in approximately one to three out of every 100 thousand Chinese newborns. Mutations in the MMAA gene cause isolated methylmalonic acidemia. Case presentation. A 13-month-old boy was diagnosed with isolated methylmalonic acidemia. We identified two mutations in the MMAA gene in this case: c.491G>A and c.650T>A. The c.491G>A is a novel mutation in the MMAA gene. The boy is a heterozygous carrier of both mutations. The boy was treated with intravenous sodium benzoate and fluids. His sensorium gradually improved and he recovered from the acute illness. Other family members are heterozygous carriers of either mutations but with no symptoms. Conclusions. We identified a novel c.491G>A mutation in the MMAA gene. Heterozygous carriers of both c.491G>A and c.650T>A mutations are associated with isolated methylmalonic acidemia.

Acute pancreatitis is a common and potentially fatal gastrointestinal disease. We report a case of acute pancreatitis induced by iodine-131 therapy for hyperthyroidism. Iodine 131 is distributed through the blood, so it can accumulate and damage normal tissues in other parts of the body that are involved in thyroid hormone metabolis.