An uncommon case of Marine-Lenhart syndrome

The term Marine-Lenhart syndrome describes the association between Graves' disease and autonomously functioning thyroid nodules (AFTN), such as toxic adenoma or toxic multinodular goiter. The two diseases may coexist or may be present at different moments in the same patient. In the literature, there are many reports on the development of Graves' disease after radioiodine treatment for AFTN, but very little information may be found on the occurrence of AFTN after radioiodine therapy for Graves' disease. We describe here the case of a female patient with Graves' disease who was successfully treated with radioiodine for Graves' disease, returning to normal thyroid function. Three years later, biochemical analysis and ultrasound examination identified a thyroid nodule that progressively increased in size. The 99mTc-pertechnetate scintigraphy showed avid uptake in the right lobule, which corresponded to a nodular lesion consistent with AFTN

The unusual association of Graves' disease, chronic spontaneous urticaria, and premature ovarian failure: report of a case and HLA haplotype characterization

Chronic spontaneous urticaria (CSU), defined as the occurrence of spontaneous wheals for more than six weeks, has been associated with autoimmune diseases. Herein, we report the unusual association of CSU, Graves' disease, and premature ovarian failure. Human leukocyte antigen (HLA) studies were performed. A 36-year-old woman presented symptoms and signs of hyperthyroidism for three months. In the same period, the patient complained of widespread urticarial wheals, intensely itchy, and poorly responsive to therapy with antihistaminic agents. Hyperthyroidism was confirmed biochemically, and treatment with methimazole was started. As hyperthyroidism improved, a marked improvement in her urticaria was also observed. However, the patient continued to complain of amenorrhea. Endocrine evaluation, at the age 38, was consistent with premature ovarian failure. This is the first report of coexistence of GD, CSU, and POF. The genetic background of such unusual association is a specific combination of HLA

Ovarian hyperthecosis coexisting with an incidental adrenal lesion: challenges in the diagnostic approach

Ovarian hyperthecosis is the most common cause of hyperandrogenism in women during postmenopausal age. However, its diagnosis is frequently challenging, since several causes must be ruled out, involving both adrenal glands and ovaries. Herein we describe the case of a 62 years old woman addressed to our Unit after the casual detection of an adrenal mass, compatible with an adenoma. Biochemical evaluation revealed gonadotropins in menopausal range, high testosterone and androstenedione, while the patient had been complaining of androgenetic alopecia and hirsutism for some years. Ultrasound imaging revealed only a small increase in ovarian volume, in relationship to the patient’s age. A GnRHa test was performed, demonstrating gonadotropins suppression and testosterone normalization, thus confirming the suspect of ovarian hyperthecosis. The administration of these agonists, together with the slow progression of symptoms over years, play a fundamental role into excluding an androgen-secreting neoplasia, also limiting the use of ovarian veins catheterization as second line test. Besides, they represent a valid therapeutical option, especially when surgery is contraindicated (or cannot be performed)

Hashimoto’s thyroiditis, hypoparathyroidism and coeliac disease: lessons from a rare association

We present the case of a 36 years old woman, affected by euthyroid Hashimoto’s thyroiditis (HT) from the age of 20. She reported the following symptoms for three years: weight reduction, abdominal pain, alternate constipation and diarrhoea, tiredness, paresthesias and cramps. Biochemical evaluation revealed low iron levels (21 ug/dl, with microcytic anemia) and hypocalcemia (6.6 mg/dl), first attributed to coeliac disease (EMA IgG, AGA IgG-A and tTG IgA positivity; Marsh-Oberhuber 3a/3b type at duodenal biopsy). TSH, PTH and 25-OHD3 were in the normal range. Although the patient was on a gluten-free diet for the second year, cramps persisted and facial spasms and tetanic crises appeared. One year later she came to our attention with severe hypocalcemia (Ca 5.1 mg/dl, Ca++ 0.6 nmol/L) and low PTH (2.5 pg/ml). A diagnosis of primary hypoparathyroidism was made and conventional treatment was started. In the following months, symptomatic hypocalcemia persisted (6.7 mg/dl, Ca++ 0.7 nmol/L), despite the gradual increase of calcium and calcitriol supplements. Gastro-intestinal re-evaluation demonstrated gluten contamination, so as to hypothesize that the scarce dietary compliance had caused persistent malabsorption and had made the hypocalcemia difficult to manage. The observation of these three disorders coexisting in a single patient, never reported by the literature, warns us about the virtually unlimited possibilities of autoimmune disease clustering. Clinicians should be aware of the increased risk of developing additional AIDs in patients with one autoimmune disorder

Neuroprotection by the PARP inhibitor PJ34 modulates cerebral and circulating RAGE levels in rats exposed to focal brain ischemia

The receptor for advanced glycation end products (RAGE) has a potential role as a damage-sensing molecule; however, to date, its involvement in the pathophysiology of stroke and its modulation following neuroprotective treatment are not completely understood. We have previously demonstrated that expression of distinct RAGE isoforms, recognized by different antibodies, is differentially modulated in the brain of rats subjected to focal cerebral ischemia. Here, we focus on the full-length membrane-bound RAGE isoform, showing that its expression is significantly elevated in the striatum, whereas it is reduced in the cortex of rats subjected to transient middle cerebral artery occlusion (MCAo). Notably, the reduction of cortical levels of full-length RAGE detected 24h after reperfusion is abolished by systemic administration of a neuroprotective dose of the poly(ADP-ribose) polymerase (PARP) inhibitor, N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide (PJ34). More interestingly, a significant reduction of plasma soluble RAGE (sRAGE) occurs 24h after reperfusion and this effect is reverted by a neuroprotective dose of PJ34. Soluble forms of RAGE, generated either by alternative splicing or by proteolysis of the full-length form, effectively bind advanced glycation end products, thereby competing with the cell surface full-length RAGE, thus providing a 'decoy' function that may counteract the adverse effects of receptor signaling in neurons and may possibly exert cytoprotective effects. Thus, our data confirm the important role of RAGE in ischemic cerebral damage and, more interestingly, suggest the potential use of sRAGE as a blood biomarker of stroke severity and of neuroprotective treatment efficacy

Anti-angiogenic activity and phytochemical screening of fruit fractions from <i>Vitex agnus castus</i>

<p>Although the antitumour activity of <i>Vitex agnus castus</i> fruits has been already addressed, no work has yet assessed their anti-angiogenic potential. To this purpose, several extractive fractions of such fruits were tested on zebrafish embrios by EAP assay, so that only the bioactive fractions could be subsequently tested on the chick chorioallantoic membrane by CAM assay. Bioactive fractions were also phytochemically screened to identify those bioactive compounds responsible for anti-angiogenic activity. A marked inhibition of vessel formation was detected only in zebrafish embryos treated with chloroform or ethyl acetate fractions. Considering CAM assay, chloroform fraction induced a strong reduction of microvasculature and haemoglobin content; while lower anti-angiogenic effects of the ethyl acetate fraction were determined. Phytochemical analyses confirmed the presence of several bioactive anti-angiogenic compounds. Overall, obtained preliminary results highlighted a potential anti-angiogenic activity of <i>V. agnus castus</i> fruits.</p

Targeting Tyrosinase: Development and Structural Insights of Novel Inhibitors Bearing Arylpiperidine and Arylpiperazine Fragments

The inhibition of tyrosinase (Ty, EC 1.14.18.1) represents an efficient strategy of decreasing melanogenesis and skin hyperpigmentation. A combination of crystallographic and docking studies on two different tyrosinases, that from <i>Bacillus megaterium</i> (TyBm) and that from a mushroom (TyM), has contributed to increasing our knowledge about their structural information and translating that information to the most druggable human Ty (TyH) isozyme. In particular, we designed and synthesized a series of 1-(4-fluorobenzyl)­piperazine and 1-(4-fluorobenzyl)­piperidine derivatives showing inhibitory activities on TyM at micromolar ranges and more potency than that of the reference compound, kojic acid. The crystal structures of TyBm with inhibitor <b>3</b> (IC₅₀ value of 25.11 μM) and <b>16</b> (IC₅₀ value of 5.25 μM) were solved, confirming the binding poses hypothesized by in silico studies and revealing the main molecular determinants for the binding recognition of the inhibitors

Targeting Tyrosinase: Development and Structural Insights of Novel Inhibitors Bearing Arylpiperidine and Arylpiperazine Fragments

The inhibition of tyrosinase (Ty, EC 1.14.18.1) represents an efficient strategy of decreasing melanogenesis and skin hyperpigmentation. A combination of crystallographic and docking studies on two different tyrosinases, that from <i>Bacillus megaterium</i> (TyBm) and that from a mushroom (TyM), has contributed to increasing our knowledge about their structural information and translating that information to the most druggable human Ty (TyH) isozyme. In particular, we designed and synthesized a series of 1-(4-fluorobenzyl)­piperazine and 1-(4-fluorobenzyl)­piperidine derivatives showing inhibitory activities on TyM at micromolar ranges and more potency than that of the reference compound, kojic acid. The crystal structures of TyBm with inhibitor <b>3</b> (IC₅₀ value of 25.11 μM) and <b>16</b> (IC₅₀ value of 5.25 μM) were solved, confirming the binding poses hypothesized by in silico studies and revealing the main molecular determinants for the binding recognition of the inhibitors