ACTA ENDOCRINOLOGICA (BUC)

-

We describe clinical features of women with extremely low bone density, and investigate secondary causes of osteoporosis. Our hypothesis was that this population would be enriched in identifiable causes of osteoporosis. We performed a retrospective review of medical records of all women seen at our university over 4 years with T-score on bone densitometry at/below -4 at any site. Historical and fracture details were abstracted. We considered a thorough work up to include Vitamin D, PTH, CBC, chemistry panel, cortisol, transglutaminase, myeloma screen, tryptase and 24-hour urine calcium. Results. 137 women were identified with T-score at/below -4. Percent identified as Asian was 26% (higher than local prevalence of 8%). Average BMI was 21.6 kg/ m2. Clearly identifiable causes of osteoporosis were noted in 57% (inflammatory disorder, glucocorticoid or antacid exposure, prolonged immobilization and alcoholism were most prevalent). Of the remainder, full work up was performed only in 8%. Endocrine consultation and white race predicted thoroughness of secondary work-up. Conclusion. Fragility fractures, leanness and Asian race were common in women with very low T-score. However, few new causes were identified. Underlying etiology was either immediately evident or inadequately studied, especially in minorities.

Denosumab,a monoclonal IgG2 antibody, is used as neoadjuvant therapy for giant cell bone tumors, particularly in inoperable or metastatic cases. It targets the receptor activator of nuclear factor kappa-β ligand (RANKL), which is overexpressed in tumor stromal cells. However, denosumab treatment can lead to side effects such as hypocalcemia during treatment and rarely but malignant hypercalcemia after discontinuation. The unpredictable onset time and persistent course of hypercalcemia attacks increase the duration of hospitalization and the risk of complications. Case. A 9-year-old girl with a giant cell bone tumor was treated with denosumab for diffuse tumor recurrence. Severe hypercalcemia occurred four months after completing therapy. Evaluation suggested "rebound-linked" hypercalcemia following denosumab discontinuation. IV bisphosphonate treatment normalized calcium levels initially, but hypercalcemia recurred, requiring repeated IV bisphosphonate administration. Oral alendronate was used weekly to prevent further attacks, resulting in stable calcium levels during follow-up. Results. Rebound hypercalcemia, as an unpredictable recurrent episode at any time, is a potential complication of denosumab cessation, and requires close monitoring post-treatment. Children may be at higher risk due to their rapid bone cycle. In long-term follow-up, IV and oral bisphosphonates can be used effectively in the management of especially life-threatening recurrent attacks.

Background. The involvement of IGF 1 in renal pathophysiology has been studied in many details in type 1 diabetes but the role of IGF 1 in early nephropathy in patients with type 2 diabetes is less well characteristic. Objective. To determine whether serum IGF1 and GFBP-1 levels were different between patients with and without diabetic nephropathy and also to investigate the association between them and insulin resistance. Subjects and methods. Insulin resistance (HOMA-IR), IGF 1 and IGFBP-1 were measured in 20 type 2 diabetic patients with nephropathy, 20 type 2 diabetic patients without nephropathy and 15 control subjects. Results. Serum IGF 1 in diabetic nephropathy (333.3 +/-16.44 ng/mL) was significantly higher than in both diabetic patients without nephropathy (133.16 +/- 3.43 ng/mL) and in control subjects (174.33+/-6.23) (P <0.001). A significant negative correlation was observed between IGF 1 and HOMA, (r = -0.72) in diabetic patients without nephropathy and a positive correlation in diabetic nephropathy patients (r = 0.49). Conclusion. High IGF 1 and insulin levels in diabetic nephropathy patients in addition to the significant positive association between IGF 1 and HOMA suggest that both IGF 1 and insulin resistance may play major role in early renal changes in type 2 diabetes.

Calcitonin (CT) is a polypeptidic hormone specifically secreted by the thyroid parafollicular cells (C cells) and tangentially involved in human phosphocalcic and bone metabolism. CT from other species (e.g. salmon) is more potent than human CT and has limited therapeutic applications. The neoplastic proliferation of C cells leads to medullary thyroid carcinoma (MTC) generally characterized by an increase of CT secretion. Serum CT is therefore the ideal marker for MTC and can confirm its presence at an early stage, as well as the follow up of its remission or progression/relapse/survival after surgery. There are, however, controversies such as the necessity of CT screening in patients with thyroid nodules, or particular situations causing false positive or false negative results. Our minireview also deals with an up-to-date of surgical procedures for MTC, as well as with non-surgical therapy.

The conventional treatment of hypoparathyroidism consists of vitamin D analogues in combination with oral calcium\r\nsupplementation. This treatment modalities induce chronic hypercalciuria which leads to nephrocalcinosis, nephrolithiasis and renal insufficiency. Here we report the case of a 32-year-old woman who developed hypocalcemia and hypercalciuria under treatment with high doses of vitamin D\r\nanalogs and oral calcium. She had cerebral calcification, nephrocalcinosis under this treatment. Stable calcium levels were achieved with synthetic human parathyroid hormone treatment that was given in alternate days. PTH appears to be an alternative and effective treatment in hypoparathyroidism.

Background. The modern management of phenylketonuria (PKU) consists of generalized newborn screening (NBS) for hyperphenylalaninemia (HPA), confirmation of HPA in children detected in the NBS, introduction of dietary treatment in the first weeks of life, followed by monitoring the treatment of PKU for decades to maintain phenylalaninemia within the limits that will not affect the brain. The present study aimed to evaluate the usefulness of two chromatographic methodologies for determination of plasma Phe level in the routine management of PKU: the two dimensional thin layer chromatography (2D - TLC) and the high performance liquid chromatography (HPLC) procedures, respectively. Material and Methods. Samples of blood from 23 children with HPA detected by neonatal screening or with confirmed PKU who received treatment by low-Phe diet were analyzed to estimate the plasma Phe level by the two chromatographic procedures. Results. In case of three subjects the very low concentrations of plasma Phe could not be detected by the 2D - TLC methodology, since the spot was not visible on the chromatogram. In four patients the differences between the values of plasma Phe determined by the two methodologies are not statistically significant, while in fifteen subjects the differences are highly statistically significant. This is due to the greater errors that appear in the case of 2D - TLC methodology. In the range of concentrations of plasma Phe higher than 360 μmol/L (which is the cut-off value for HPA), although in four cases there were statistically significant differences in the level of plasma Phe determined by the two methodologies, the value obtained by the 2D - TLC methodology was high enough to influence the decision of changing the diet so that HPA is kept under control. In addition, the intense spot of Phe on the 2D - TLC chromatogram may be detected even by un unexperienced laboratory specialist. Conclusion. The HPLC procedure for measurement of plasma Phe level is very suitable to be used in the routine management of PKU. The 2D - TLC procedure may be accompanied by relatively high errors; however, it detects patients with severe PKU.

-

Bardet Biedl syndrome (BBS) is a rare autosomal recessive disease, characterized by clinical and genetic heterogeneity. Many genes are involved. BBS seems to be\r\ndifferent from Lawrence Moon BBS, although they share some clinical symptoms. The main clinical signs are obesity, pigmentary retinopathy, kidney malformations, and hypogenitalism. Our aim is to report a case with typical\r\nretinis pigmentosa, hypergonadotrophic hypogonadism and cerebellum cyst. Case report. A man aged 18 was referred for obesity and blindness. His family history was marked by obesity and diabetes mellitus type II. His medical history began very soon, as he was born with polydactyly, then he became obese and had difficulty to learn and to see. His blindness was progressive, and his puberty was delayed.\r\nClinical and biological exams showed: severe android obesity (BMI = 40kg/m?, waist circumference = 130cm), pigmentary\r\nretinopathy, small testes with high FSH = 17 mU/mL (1-8), and normal LH = 6.13 mU/mL (0.6-12)], empty sellae, cerebellum cyst, renal malformations, and signs of chronic infections. He did not have any spasticity or ataxia.\r\nGenetic study was not done. Conclusion. In this case, all features argued for typical BBS, except for testicular\r\ninsufficiency which is classically described as hypogonadotrophic. Infections should be treated vigorously to avoid renal insufficiency.

Obesity involves both genetic and environmentl influences, but the mechanisms of the genetic effects are not well understood.\r\nObjective. The aims of the study were to investigate the frequency of perilipin gene polymorphism in order to identify the relationship between insulin resistance and gene polymorphism in obese women.\r\nSubjects and methods. Study population included 31 obese women and 10 women with normal weight as a control group. All of the entire coding exons of PLIN gene were amplified by polymerase chain reaction (PCR). Insulin resistance (IR) was estimated using the homeostasis model assessment (HOMA-IR).\r\nResults. In the obese group, 29 (93.6%) patients were homozygous and 1 patients (3.2%) was heterozygous for the c.580C>.G (p.Pro194A1a)(rs. 6496589) mutation and 1 patient (3.2%) was Pro194A1a. Homozygous. Val156Leu. Heterozygous mutation at exon 5 at PLIN gene (p=0.072). As for exon 8 at PLIN gene in obese group, 6 patients (19.3%) had heterozygous for the c.1113T>C (Pro371Pro) (rs2304796) mutation, and 12 patients (38.7%) had heterozygous for the c.1113T>C and c.1119C>T (p. Val373Val) (rs2304795) mutation, and 4 patients (12.9%) had homozygous for the c.113T>C and c.1119C>T mutatons (p=0.009). In obese patients with no nucleotide substitution at exon 8, mean levels of systolic and diastolic blood pressures were higher than those of obese subjects with gene polymorphism. However, there were no statistically significant differences for HOMA-IR levels between obese women with and without perilipin gene polymorphism.\r\nConclusions: Perilipin gene polymorphisms such as heterozygous and homozygous for the c.1113T>C and c. 1119C>T (rs2304795) at exon 8 were associated with obesity risk. However, no relationship was found between insulin resistance and polymorphisms of perilipin gene in obese women.