A very rare case of extranodal B-cell non-Hodgkin lymphoma presenting with adrenal and heart involvement.

We report an extremely rare case of extranodal B-cell NHL: DLBCL (diffuse large B-cell non-Hodgkin lymphoma), stage IVE, presenting with heart and bilateral adrenal involvement. On admission, adrenal and thorax imaging identified large bilateral adrenal masses and a 4.6 cm mass in the right atrium wall. An adrenal biopsy revealed the presence of a DLBCL, with triple expression of bcl2, bcl6, C-MYC(+70%). Following six cycles of systemic immunochemotherapy with R-DA-EPOCH, and high methotrexate dose for CNS prophylaxis a marked decrease of lymphoma infiltration was observed. The selection of the appropriate treatment modality can lead to profound response and improve patient's outcome.

Juxtaglomerular cell tumour of the kidney: a rare cause of resistant hypertension.

SUMMARY: Juxtaglomerular cell tumour (JGCT) is an unusually encountered clinical entity. A 33-year-old man with severe long-standing hypertension and hypokalaemia is described. The patient also suffered from polyuria, polydipsia, nocturia and severe headaches. On admission, laboratory investigation revealed hypokalaemia, kaliuresis, high aldosterone and renin levels, and the abdomen CT identified a mass of 4 cm at the right kidney. Kidney function was normal. Following nephrectomy, the histological investigation revealed the presence of a JGCT. Immunostaining was positive for CD34 as well as for smooth muscle actin and vimentin. Following surgery, a marked control of his hypertension with calcium channel blockers and normalization of the serum potassium, renin or aldosterone levels were reached. According to our findings, JGCT could be included in the differential diagnosis of secondary hypertension as it consists of a curable cause. The association of JGCT with hypertension and hypokalaemia focusing on the clinical presentation, diagnostic evaluation and management is herein discussed and a brief review of the existing literature is provided. LEARNING POINTS: Juxtaglomerular cell tumours (JGCT), despite their rarity, should be included in the differential diagnosis of secondary hypertension as they consist of a curable cause of hypertension. JGCT could be presented with resistant hypertension along with hypokalaemia, kaliuresis and metabolic alkalosis. Early recognition and management can help to prevent cardiovascular complications. Imaging (enhanced CT scans) may be considered as the primary diagnostic tool for the detection of renal or JGCT. For the confirmation of the diagnosis, a histopathologic examination is needed.

Association of growth hormone deficiency (GHD) with anxiety and depression: experimental data and evidence from GHD children and adolescents.

Anxiety and depression are among the commonest emotional problems in children and young adolescents. They are encountered with even higher prevalence in children and adults with growth hormone deficiency (GHD). Alterations in the somatotropic axis, as observed in both GH/IGF1 deficiency and excess, can produce permanent changes in brain tissue structure. The growth hormone/insulin-like growth factor 1 (GH/IGF1) axis seems to exert a regulatory effect on brain function and neurogenesis, especially in the hippocampus, a brain region associated with mental and emotional disorders, such as depression and anxiety. There is evidence from animal models of the possible interrelationship of the endocrine system with the pathogenesis of emotional disorders. Moreover, clinical data support the association of GHD and mood disorders, which are often reversed by GH replacement therapy. However, the causal relationship and the mechanism underlying this association are to date obscure and remain to be clarified. The present review reports experimental data from animal models regarding the role of GH/IGF1 in emotional disorders and focuses on clinical data on the presence of these disorders in children with GHD and their response to GH therapy.

Energy deficiency, menstrual disorders, and low bone mineral density in female athletes: a systematic review.

PURPOSE: Low energy availability (LEA) may lead to menstrual disorders and low bone mineral density, predisposing to the female athlete triad. The primary aim of the present review was to systematically investigate the impact of chronic strenuous exercise on the energy status of professional female athletes compared to sedentary, recreationally active controls as concerns their menstrual status and bone mineral density (BMD). A secondary aim was evaluation of the combined prevalence of the components of the female athlete triad in athletes as compared to non-athletes. METHODS: A systematic review was conducted from 2007 to February 2018. The inclusion and exclusion criteria of the studies were established in advance of the literature search according to the clinical inquiry and the study design. RESULTS: Four studies were included in this systematic review. The female athlete triad was more prevalent in professional athletes compared to non-athletes. The same results were obtained for both LEA and menstrual disorders. However, BMD and Z-scores showed high heterogeneity among the studies. CONCLUSION: Both female athletes and non-athletes are prone to LEA and subsequent menstrual disorders and low BMD or osteoporosis. Future studies are needed to examine energy availability in elite female athletes as well as in non-athletes.

Parietal aplasia and hypophosphatasia in a child harboring a novel mutation in RUNX2 and a likely pathogenic variant in TNSALP.

Cleidocranial dysplasia is a dominantly inherited skeletal dysplasia resulting from inherited or spontaneous mutations of Runt-related transcription factor 2 gene (RUNX2). It represents a clinical continuum typically characterized by wide calvarial sutures, clavicular hypoplasia and dental abnormalities. CDD has been rarely associated with skeletal and biochemical features that mimic hypophosphatasia. We report clinical, biochemical and molecular profile of a 3-year-old female with CCD, presented in utero with large cranial defects. She displayed severe parietal dysplasia, wide cranial sutures, clavicular abnormalities and biochemical features of hypophospatasia (HHP). She was preliminary diagnosed with benign perinatal HHP, harboring a likely pathogenic heterozygous TNSALP variant (p.Ser181Leu) inherited by the mother, who also displayed low levels of ALP. Asfotase alfa was introduced for a six-month-period with rather positive impact on cranial ossification. Nevertheless, focal skeletal disease (cranium and clavicles) and absence of clinical symptoms in the mother, carrier of the same genetic variant, posed diagnosis into question and further genetic analysis detected the novel spontaneous frameshift mutation c.1191delC (p.Phe398Leufs*86) in RUNX2 gene, establishing the CCD diagnosis. Although genotype-phenotype correlations are difficult, p.Phe398Leufs*86 appears to be associated with a severe cranial phenotype and absence of parietal bones, similarly to other adjacent frameshift/splicing mutations. The TNSALP variant (p.Ser181Leu) may contributed to patient's final phenotype, as well as to maternal low ALP levels. However, since low ALP levels have been also reported in few CCD patients with no alterations in TNSALP gene, studies to elucidate RUNX2 and TNSALP interactions could shed more light on differential diagnosis between CCD and HHP, CCD appropriate therapy and genetic counselling. ACCESSION NUMBER: (SUB8185506).

Diabetic ketoacidosis in patients treated with SGLT2 inhibitors: experience at a tertiary hospital.

PURPOSE: Diabetic ketoacidosis (DKA) is a rare and life-threatening complication in patients with diabetes. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have rarely been associated with ketoacidosis. The aim of this retrospective study was to investigate DKA episodes occurring after SGLT2i treatment and to compare them to DKA episodes due to other causes. METHODS: The medical records of the years 2018-2020 related to clinical and biochemical characteristics and to treatment of six patients with DKA due to SGLT2i were reviewed. They were compared to those of 12 patients with DKA due to other causes. RESULTS: On admission, the most common symptom was abdominal pain. Glucose levels (median, min-max) were lower in patients with SGLT2i-induced DKA compared to those with DKA due to other causes (229 (150-481) vs. 458.5 (332-695) mg/dl, p = 0.007), whereas no statistical difference was observed in HbA1c and in the severity of DKA (pH, HCO3, CO2, and anion gap). The duration of insulin infusion (41 (33-124) vs. 21.50 (11-32) h, p < 0.001) and the time required until DKA resolution (39 (31-120) vs. 19 (9-28) h, p < 0.001) were higher in patients with SGLT2i-induced DKA than those with DKA due to other causes. In addition, there were increased fluid requirements (14 (8-22.75) vs. 5.5 (2-24) L, p = 0.013) and longer hospitalization time (11 (6-22) vs. 5.5 (2-14) days, p = 0.024) in patients with SGLT2i-induced DKA. No statistically significant differences were observed in total intravenous insulin and potassium administration until DKA resolution. CONCLUSIONS: Patients with SGLT2i-induced DKA had lower serum glucose levels on admission and required increased fluid administration and longer time to recover from acidosis compared to patients with DKA from other causes.

Evolution of Hashimoto thyroiditis in children with type 1 diabetes mellitus (TIDM).

OBJECTIVES: Treatment of children with Hashimoto thyroiditis (HT) and particularly of those with coexistent diabetes mellitus type 1 (TIDM) and normal/mildly elevated serum TSH is controversial. The aim of the study was to evaluate the natural course of HT in children with TIDM compared with children with no other coexistent autoimmunity and investigate for possible predictive factors of thyroid function deterioration. METHODS: Data from 96 children with HT, 32 with T1DM (23 girls, nine boys) mean (sd) age: 10.6 (2.3) years, and 64 age and sex-matched without T1DΜ (46 girls, 18 boys), mean (sd) age: 10.2 (2.9) years were evaluated retrospectively. They all had fT4 and TSH values within normal ranges and available data for at least three years' follow-up. RESULTS: During the follow-up period, 11 children (34.4%) with TIDM exhibited subclinical hypothyroidism and two children (6.2%) progressed to overt hypothyroidism compared to 12 (18.8%) and two (3.1%) among children without TIDM, respectively. Among children with HT, a higher percentage (40.6%) of children with T1DM progressed to subclinical or overt hypothyroidism, compared with children (21.9%) with similar characteristics but without TIDM or other coexistent autoimmunity. CONCLUSIONS: The annual conversion rate from euthyroidism to hypothyroidism in children with T1DM was significantly higher compared to sex and age-matched children without TIDM. Prospective randomized trials are needed to support the view of an earlier intervention therapy even in milder degrees of thyroid failure in these children.