Maternal uniparental disomy of the chromosome 14: need for growth hormone provocative tests also when a deficiency is not suspected.

Uniparental disomy (UPD) is a congenital disease characterised by the presence of two homologous chromosomes inherited from one parent in a diploid offspring. Maternal UPD of the chromosome 14 (UPD(14)mat, Temple syndrome) is a rare disorder with heterogeneous clinical presentation. Here, we report a case of UPD(14)mat with a small supernumerary marker chromosome in a 6-year-old baby girl, presenting endocrinological disorders and incomplete clinical presentation. She came to our attention because of precocious beginning of pubarche and normal stature. Most of Temple syndrome signs were lacking. Provocative tests diagnosed incomplete growth hormone (GH) response and confirmed precocious puberty. One year treatment with recombinant human GH and gonadotropin-releasing hormone (GnRH) agonists proved successful, increasing height and arresting puberty. We recommend provocative tests for GH in UPD(14)mat as a GH deficiency can be hidden by a concurrent precocious puberty. Concomitant human GH and GnRH analogue treatment can be pursued.

Switch from tablet levothyroxine to oral solution resolved reduced absorption by intestinal parasitosis.

Reduced intestinal absorption of levothyroxine (LT4) is the most common cause of failure to achieve an adequate therapeutic target in hypothyroid patients under replacement therapy. We present the case of a 63-year-old woman with autoimmune hypothyroidism previously well-replaced with tablet LT4 who became unexpectedly no more euthyroid. At presentation, the patient reported the onset of acute gastrointestinal symptoms characterized by nausea, loss of appetite, flatulence, abdominal cramps and diarrhea, associated with increase of thyrotropin levels (TSH: 11 mIU/mL). Suspecting a malabsorption disease, a thyroxine solid-to-liquid formulation switch, at the same daily dose, was adopted to reach an optimal therapeutic target despite the gastrointestinal symptoms persistence. Oral LT4 solution normalized thyroid hormones. Further investigations diagnosed giardiasis, and antibiotic therapy was prescribed. This case report is compatible with a malabsorption syndrome caused by an intestinal parasite (Giardia lamblia). The reduced absorption of levothyroxine was resolved by LT4 oral solution. Learning points: The failure to adequately control hypothyroidism with oral levothyroxine is a common clinical problem. Before increasing levothyroxine dose in a patient with hypothyroidism previously well-controlled with LT4 tablets but no more in appropriate therapeutic target, we suggest to investigate non adhesion to LT4 therapy, drug or food interference with levothyroxine absorption, intestinal infection, inflammatory intestinal disease, celiac disease, lactose intolerance, short bowel syndrome after intestinal or bariatric surgery, hepatic cirrhosis and congestive heart failure. LT4 oral solution has a better absorptive profile than the tablet. In hypothyroid patients affected by malabsorption syndrome, switch of replacement therapy from tablet to liquid LT4 should be tested before increasing the dose of LT4.

Human exposure to bisphenol AF and diethylhexylphthalate increases susceptibility to develop differentiated thyroid cancer in patients with thyroid nodules.

Pollutants represent potential threats to the human health, being ubiquitous in the environment and exerting toxicity even at low doses. This study aims at investigating the role of fifteen multiclass organic pollutants, assumed as markers of environmental pollution, most of which exerting endocrine-disrupting activity, in thyroid cancer development. The increasing incidence of differentiated thyroid cancer (DTC) may be related to the rising production and environmental dissemination of pollutants. Fifty-five patients, twenty-seven with diagnosis of benign thyroid nodules and twenty-eight suffering from differentiated thyroid cancer, were enrolled and the concentration levels of seven bisphenols, two phthalates (i.e. di(2-ethylhexyl) phthalate (DEHP) and its main metabolite, mono-(2-ethyl-hexyl) phthalate) (MEHP)), two chlorobenzenes, (1,4-dichlorobenzene and 1,2,4,5-tetrachlorobenzene), and 3 phenol derivatives (2-chlorophenol, 4- nonylphenol, and triclosan) were determined in their serum by using a validated analytical method based on high performance liquid chromatography with ultraviolet tandem fluorescence detection. A significant relationship was found between malignancy and the detection in the serum of both bisphenol AF and DEHP. Indeed, their presence confers a more than fourteen times higher risk of developing differentiated thyroid cancer. Relationship between these two pollutants and the risk of malignancy was dose-independent and not mediated by higher thyroid stimulating hormone levels. Even if a conclusive evidence cannot still be drawn and larger prospective studies are needed, the exposure to low doses of environmental endocrine-disrupting contaminants can be considered consistent with the development of thyroid cancer.

Interaction between HIV-1 Tat and pRb2/p130: a possible mechanism in the pathogenesis of AIDS-related neoplasms.

Tat protein is an early nonstructural protein necessary for virus replication, which is secreted by infected cells and taken up by uninfected cells. Extensive evidence indicates that Tat may be a cofactor in the development of AIDS-related neoplasms. The molecular mechanism underlying Tat's oncogenic activity may include deregulation of cellular genes. Among these genes, it has recently been shown that pRb2/p130 oncosuppressor protein is one of the targets in the interaction between HIV gene product Tat and host proteins. However, whether the HIV-1 gene product Tat may inactivate the oncosuppressive function of pRb2/p130 has not yet been elucidated. Here, we show that mRNA levels of pRb2/p130 increase in the presence of Tat, whereas no change in the phosphorylation status of pRb2/p130 is observed. In addition, Tat can inhibit the growth control activity exerted by pRb2/p130 in the T98G cell line. Finally, Tat does not compete with E2F-4 in binding to pRb2/p130. The interaction between Tat and pRb2/p130 seems to result in the deregulation of the control exerted by pRb2/p130 on the cell cycle. Taken together, these results open a window on the role of pRb2/p130 in AIDS-related oncogenesis.