Transient Peripartum Osteoporosis of the Femoral Head in First and Third Pregnancy

The aim of this article was to present transient peripartum femoral head osteoporosis. This very rare condition occurred twice in our patient—a woman in her 30s. The cases described in the literature were mostly unilateral, with bilateral hip involvement noted much less frequently. In our patient, transient osteoporosis occurred in the third trimester of her first pregnancy in the right hip, her second pregnancy was uncomplicated, and in the third trimester of the patient's third pregnancy, osteoporotic changes were noted in the left hip joint. The patient breastfed her first and third babies only 3 wk each. She breastfed her second baby for 4 mo. The diagnostic workup was based on the clinical examination and radiographic/magnetic resonance imaging, which revealed bone marrow edema, and the dual-energy X-ray absorptiometry scans. The treatment consisted in core decompression of the femoral head (foragé), unloading of the hip using crutches as well as administration of calcitonin and calcium supplements. Complete recovery of the femoral heads was achieved. The follow-up time was 7 yr.     

Persistence of mixed chimerism in patients transplanted for the treatment of thalassemia

Molecular genetic techniques permit sensitive assessment of host hematopoiesis after marrow transplantation for thalassemia. Information on this persistence and the cell lines in which it occurs may permit therapeutic intervention in patients at high risk for rejection and/or relapse. The objective of this study, therefore, was to determine the evolution and cell line distribution of persistent mixed chimerism detected in 55 patients treated for beta thalassemia. Our findings indicated that rejection occurred in 20 patients, the host component disappeared in 20, and mixed chimerism without transfusion need persisted for 1 to 7 years in 15. In three patients with stable mixed chimerism for 4, 5, and 7 years, host hematopoiesis fluctuated between 25% and 75%. Despite this, donor pattern beta-globin chain synthesis maintained hemoglobin levels between 10 and 13.5 g/dL without transfusion. In these three patients, the polymerase chain reaction of the VNTR and the fluorescent in situ hybridization analysis revealed the coexistence of donor and host cells in the different peripheral blood cell subpopulations and precursors studied (CD2+, CD4+, CD8+, and CD19+ granulocytes; glycophorin-A+, erythroid burst-forming units, CD33+, granulocyte-macrophage colony-forming units). We found that rejection and disease recurrence occur in approximately one third of patients with early mixed chimerism. High levels of host type hematopoiesis can be present in patients not requiring transfusion.     

Poorly Differentiated Thyroid Carcinoma: Diagnostic Features and Controversial Issues

Poorly differentiated thyroid carcinomas are a heterogeneous group of tumors occupying an area intermediate between well-differentiated follicular or papillary carcinoma and anaplastic carcinomas, from both a histopathogenetic and a clinical point of view. Large tumor series selected on the basis of structural and/or other morphological criteria showed that poorly differentiated carcinomas have a distinct biological behavior, and the classification of these tumors into a separate group appears justified, although strict homogeneous diagnostic criteria should be achieved and widely accepted to better characterize such tumor entity. Moreover, the identification of the prognostic parameters segregating aggressive from indolent cases has important clinical implications. Molecular data in the literature, although limited by the heterogeneous case series analyzed, identify ras alterations as the most common molecular alteration in poorly differentiated carcinomas, thus, depicting a peculiar molecular pathway in this tumor type as compared to well-differentiated follicular and papillary carcinomas. The present paper aims to review the various aspects of this tumor type, from morphology to immunohistochemistry and molecular abnormalities from a practical and daily practice-oriented point of view.     

The nutritional control of ghrelin secretion in humans

Background The nutritional control of ghrelin has not been fully clarified yet. Particularly, the influence of aminoacids and lipids is controversial and, moreover, whether the intraluminal gastric contact with nutrients is required or if the modulatory action of nutrients on ghrelin secretion is mediated by insulin is still matter of debate. Aim of the study To clarify the role of nutrients in the control of ghrelin secretion evaluating the effects of intravenous and oral lipids and aminoacids compared with glucose and fructose load in healthy subjects. Methods A total of 6 healthy overnight-fasted volunteers underwent the following testing sessions: (a) iv arginine (ARG, 0.5 g/kg); (b) oral protein load (PRO, 50 g); (c) iv lipid-heparin infusion (Li He, Intralipid 10% 250 ml); (d) oral fat load (OIL, soy oil 40 g); (e) oral glucose load (OGL, 100 g); (f) oral fructose load (OFL, 100 g); (g) iv saline (SAL, 3 ml); (h) oral water load (WL, 200 ml). Total ghrelin, insulin, and glucose were assayed every 15 min from 0 up to +180 min. Results WL and SAL did not modify insulin, glucose and ghrelin. ARG induced a prompt but transient increase (P < 0.05) of insulin and glucose (P < 0.01), without modifying ghrelin secretion. PRO induced a mild but sustained increase of insulin secretion (P < 0.05) without affecting glucose and ghrelin. Li-He progressively increased circulating glucose (P < 0.01) without modifying insulin and ghrelin secretion. No significant variations in circulating glucose, insulin, and ghrelin occurred after OIL. OGL significantly (P < 0.01) increased insulin and glucose levels and progressively decreased (P < 0.05) ghrelin levels. OFL induced a mild (P < 0.05) increase of insulin without modifying glucose levels. Similarly, OFL was followed by a milder decrease (P < 0.05) of ghrelin levels. Conclusions Differently from carbohydrates and independently from their modulatory effect on insulin secretion and glucose levels, both lipids and aminoacids play a negligible role in the acute control of ghrelin secretion either after acute enteral and parenteral administration.     

Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygotes

OBJECTIVE: TSH resistance ranges from overt nonautoimmune hypothyroidism to subclinical hypothyroidism, defined as mild hyperthyrotrophinaemia but a euthyroid state clinically. To date, 23 inactivating mutations of the TSH receptor (TSHR) gene have been proven responsible for the clinical condition, but an absence of mutations in the TSHR gene has been reported for several cases of TSH resistance as well. In this paper, we aimed to investigate the actual role of the TSHR gene in the development of both subclinical and congenital hypothyroidism. PATIENTS: 14 hypothyroid newborns, 116 subclinical hypothyroid subjects and 120 healthy controls. MEASUREMENTS: Through denaturing high performance liquid chromatography (DHPLC), we screened for mutations the TSHR gene (the proximal promoter, the exons and their flanking regions), and evaluated the association between serum TSH and functionally characterized alleles identified. RESULTS: In the hypothyroid patients, one patient was heterozygous for a new missense variation, E34K, whereas two others patients were either homozygous or heterozygous for the P162A substitution. In the subclinical hypothyroid subjects, we detected only heterozygous substitutions: they are mostly new (123-124insTGCA, P27T, R46P, 555-561delTATTCTT, D403N, W488R, M527T), while six correspond to already published mutations (P162A, R109Q, L252P and three C41S). We only focused on those mutations that had been functionally characterized in vitro, and in whom serum TSH was available from family members. CONCLUSIONS: A single grossly mutated allele (such as C41S or 555-561del) invariably leads to a condition of subclinical hypothyroidism, whereas in case of heterozygous carriers of mutations partially affecting the receptor function (such as P162A or L252P), a remarkable variable expressivity was detected among individuals belonging to different generations.     

Tissue Expression and Pharmacological In Vitro Analyses of mTOR and SSTR Pathways in Adrenocortical Carcinoma

New therapies for advanced adrenocortical carcinoma (ACC) are urgently needed, as the majority of the patients experience a rapid and inexorable progression despite surgery and adjuvant mitotane. In vitro data suggest that somatostatin receptors (SSTRs) and mTOR pathway might represent reasonable targets for novel therapies, being involved in functionality and growth of ACC cells. However, in vitro analysis of combination treatments targeting both mTOR and SSTR as compared to mitotane are poorly explored in ACC. This study aimed to investigate in vitro the effects on cell growth of pasireotide, everolimus, and mitotane, alone or combined, in the two ACC cell lines H295R and SW13 (mitotane sensitive and resistant, respectively). Moreover, the tissue expression of mTOR pathway molecules and SSTR (types 1–5) was assessed in 58 ACCs. In both cell lines, only everolimus induced a significant inhibition of cell growth. Conversely, the combinations among mitotane, pasireotide, and everolimus produced antagonistic effects on mitotane-induced growth inhibition on H295R cell line. A heterogeneous profile of mTOR-related molecules and SSTR expression was observed in ACC samples, being the mTOR pathway found activated in approximately 30% of cases. In conclusion, our data suggest caution in designing combinations of mitotane with other drugs potentially active in ACC, such as mTOR inhibitors or somatostatin analogs.