Endocrine morbidity in midline brain defects: Differences between septo-optic dysplasia and related disorders.

BACKGROUND: Septo-optic dysplasia (SOD) is a heterogeneous congenital condition. The aim of this study was to investigate the clinical phenotypes of a large cohort of children with SOD, Multiple Pituitary Hormone Deficiency (MPHD) and Optic Nerve Hypoplasia (ONH), with a focus on endocrine testing. METHODS: Retrospective single-centre longitudinal study of children with SOD (n:171), MPHD (n:53) and ONH (n:35). SOD+ and SOD- indicate patients with or without hypopituitarism, respectively. FINDINGS: All deficits were more frequent and occurred earlier in MPHD than SOD+ [Hazard Ratios (HR): 0·63(0·45,0·89) for GH, 0·48(0·34,0·69) for TSH, 0·55(0·38,0·80) for ACTH, 0·28(0·11,0·68) for gonadotropins], except Diabetes Insipidus (DI) [HR: 2·27(0·88,5·9)]. Severe hypothalamo-pituitary (H-P) abnormalities were more frequent in MPHD [80·0% vs 41·6%, p<0·0001 for Ectopic Posterior Pituitary (EPP)]. Stalk and PP abnormalities were associated with more severe endocrine phenotypes and placed a subgroup of SOD+ at risk of developing deficits earlier. SOD and ONH shared heterogeneous phenotypes ranging from pubertal delay to precocity and from leanness to extreme obesity, whilst MPHD had GnD and obesity only. Mortality was recorded in 4·2% (6/144) SOD and 3·2% (1/31) ONH, and only in patients with multisystem phenotypes. INTERPRETATION: More than a single disease, SOD represents a spectrum of malformative conditions involving different brain structures and characterised by a dynamic and sequential nature of endocrine. In contrast, MPHD displays a more homogeneous phenotype of (mainly) anterior pituitary early-onset failure. Stalk and PP abnormalities place a subgroup of SOD+ at a higher risk of early-onset deficits. Additionally, there are striking differences between the SOD and MPHD cohorts in terms of pubertal progression. The shared phenotypes between ONH and SOD could be partly explained by common hypothalamic dysfunction. The differences between the cohorts are important as they may aid in planning management and preventing morbidity by dictating earlier interventions. FUNDING: M.C., M.G., and N.I. were supported by the European Society of Paediatric Endocrinology (ESPE) through ESPE Clinical Fellowships.

Enteroinsular hormones in two siblings with Donohue syndrome and complete leptin deficiency.

The main biochemical hallmark of the rare and lethal condition of Donohue syndrome (DS) is hyperinsulinemia. The roles of the gut and other pancreatic hormones involved in glucose metabolism, satiety and energy expenditure have not been previously reported in DS. Two siblings with genetically confirmed DS and extremely low weight underwent a mixed meal (MM) test where pancreatic hormones insulin, C-peptide, glucagon, active amylin, pancreatic polypeptide (PP) as well as gut hormones active glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), ghrelin, peptide YY (PYY) and leptin were analyzed using a Multiplex assay. Results were compared to those of 2 pediatric controls. As expected, concentrations of insulin, C-peptide and amylin were very high in DS cases. The serum glucagon concentration was undetectable at the time of hypoglycemia. GIPs concentrations were lower in the DS, however, this was not mimicked by the other incretin, GLP-1. Ghrelin concentrations were mainly undetectable (<13.7 pg/mL) in all participants. DS cases had higher PYY and dampened PP concentrations. Leptin levels remained completely undetectable (<137.0 pg/mL). Patients with DS have extremely high amylin levels, completely undetectable serum glucagon and leptin levels with abnormal satiety regulating hormone PP with a relatively normal ghrelin response during a MM test. The low serum GIP might be acting as physiological brake on insulin secretion. The undetectable serum leptin levels suggest the potential of using leptin analogues as therapy for DS patients.

Miofibroma cutáneo solitario “ulcerado” del adulto. Descripción de un caso / Solitary ulcerated cutaneous myofibroma in an adult. Case report

El miofibroma cutáneo solitario del adulto representa la variante adulta de la miofibromatosis infantil y se caracteriza, como su nombre indica, por lesiones únicas que se desarrollan en la dermis, sin tendencia a la regresión pero de naturaleza y comportamiento benignos. Presentamos un caso de miofibroma cutáneo solitario con ulceración de su superficie localizado en la palma derecha en una paciente de 24 años. No hemos encontrado referencias bibliográficas de miofibromas cutáneos del adulto ulcerados (AU)

Adult solitary cutaneous myofibroma is an adult counterpart of infantile myofibromatosis, characterized by solitary lesions that have a predilection for involvement of the dermis and show no tendency to regression, although their biological behaviour is entirely benign. We present a 24-year-old woman with a solitary, ulcerated lesion on her right palm. To our knowledge, there are no previous reports of solitary ulcerated cutaneous myofibroma in adults (AU)

Socio-sexual behavior in male rats after lesions of the dorsolateral tegmentum.

The medial preoptic area of the anterior hypothalamus (MPOA/AH) and the dorsolateral tegmentum (DLT) play an important role in the control of sexual behavior. Unilateral lesions of the MPOA/AH (medial preoptic area of the anterior hypothalamus) combined with unilateral lesions of the contralateral DLT result in deficits in male sexual behavior, while bilateral electrolytic lesions of the DLT have similar effects. In the present study, coital and socio-sexual interactions were recorded before and after bilateral electrolytic DLT lesions. Coital behavior was monitored for 15 weeks after surgery and socio-sexual interactions one 1 and 3 weeks after lesion. DLT-lesioned animals showed reduced copulatory behavior throughout the 15 weeks postlesion. This inhibition was associated with changes in exploratory (sniffing), precopulatory (pursuit and genital exploration), and postcopulatory behaviors (self-grooming). No differences were found in the weights of the testicles, prostate and seminal vesicles. These results indicate that lesions of the DLT produced permanent deficits in sexual behavior associated with a generalized modification of sociosexual behavior. These deficits indicate reduced sexual motivation possibly due to the disruption of the output pathway from the MPOA/AH (medial preoptic area of the anterior hypothalamus) to the DLT.

Allergic contact dermatitis from naftifine in a child without cross-reaction to terbinafine.

Allergic contact dermatitis from naftifine has been scarcely described in the English literature, all of them in adults. We report a case of a 12-year-old girl who developed an acute eczema on her neck after application of a naftifine cream. This fact was confirmed by a patch-test study. We did not find a cross-reaction to terbinafine, a structurally linked allylamine.

Sclerosing sweat duct carcinoma mimicking dermatofibroma.

Sclerosing sweat duct carcinoma is an infrequent adnexal tumor, locally aggressive and with a high incidence of local recurrences. Its location is preferably cephalic and its clinical presentation often unspecific. We present a new case with an atypical location and the clinical appearance of a benign cutaneous lesion. Diagnosis was established after a histological and immunohistochemical study. A terminological review was done.

Spontaneous regression of Merkel cell carcinoma of the skin.

We report a 65-year-old man who presented with a Merkel cell carcinoma on his right ear, a small satellite nodule and regional lymph node metastases. No treatment was given because of his generally poor state of health. Spontaneous regression of all the lesions was observed within a month. Merkel cell carcinoma is a potentially aggressive tumour. Only four cases of spontaneous regression have been reported previously.

Cutaneous leiomyosarcoma in a child.

Superficial leiomyosarcomas are infrequent tumors that are very rare in childhood. We report on a 12-year-old white boy with a cutaneous leiomyosarcoma of his left groin. Immunohistochemical study revealed positive immunostaining with antibodies to vimentin, desmin, and smooth muscle actin. The tumor was removed with wide surgical margins.

Role of presynaptic purinoceptors and cyclic AMP on the noradrenaline release in cat cerebral arteries.

Field electrical stimulation (ES), K+ (50 mM) or ionophore X-537A (0.01 mM) induced tritium release from cat cerebral arteries preincubated with [3H]noradrenaline (NA). Adenosine and AMP (0.5 mM) did not modify tritium release caused by ionophore X-537A, but these agents and ATP (0.5 mM) significantly reduced that elicited by ES and K+; this reduction was antagonized by 1-methyl-3-isobutylxanthine (MIX; 0.05 mM). Inosine (0.5 mM) and the agonist of purinergic A2-receptors, 5'N-ethyl-carboxamide adenosine (NECA; 0.5 mM) had no effect, but the agonist of purinergic A2-receptors L-N6-phenylisopropyl adenosine (L-PIA; 0.1 mM) diminished tritium efflux caused by ES and K+. The adenosine inhibition of ES-induced radioactivity release was not affected by indomethacin (0.05 mM). MIX (0.05 mM) increased tritium release evoked by ES and K+. Agents that increase intracellular cyclic (c)AMP levels, such as dibutyryl cAMP (0.5 mM), the phosphodiesterase inhibitor Ro 20-1724 (0.1 mM), and the activators of adenylate cyclase, forskolin (0.005 mM) and NaF (2 mM) reduced tritium secretion elicited by ES and K+. However, the intracellular increase of cyclic GMP (cGMP) caused by 8-Br-cGMP did not affect this secretion. Dipyridamole (0.05 mM) and the adenosine deaminase inhibitor erythro-9-2-hydroxy-3 nonyl adenosine (EHNA; 0.1 mM) also produced inhibition of tritium secretion elicited by ES and K+. Dipyridamole reduced both the uptake of [3H]NA and [3H]adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Purinergic and cyclic AMP modulation of noradrenaline release in cat femoral arteries.

1. Adenosine, AMP, ATP (5 x 10(-4) M), 5'-N-ethylcarboxamide adenosine (NECA) and N6-L-phenylisopropyl adenosine (L-PIA) (10(-4) M) decreased tritium release elicited by electrical stimulation (ES) or 50 mM K+ in cat femoral arteries preincubated with [3H]noradrenaline (NA). 2. This effect was antagonized by 1-methyl-3-isobutylxanthine (MIX, 5 x 10(-5) M). 3. The release induced by ionophore X-537A (10(-5) M) was unaffected by adenosine and AMP. 4. The increase of intracellular cAMP levels caused by dibutyryl cAMP (5 x 10(-4) M), Ro-20 1724 (10(-4) M), forskolin (5 x 10(-6) M), NaF (2 x 10(-3) M) reduced, but MIX (5 x 10(-5) M) increased tritium release elicited by ES and K+. 5. Dipyridamole (5 x 10(-5) M) and erythro-9-2-hydroxy-3 nonyl adenosine (EHNA) (10(-4) M) also reduced tritium release. 6. Dipyridamole decreased both the uptake of [3H]NA and [3H]adenosine. 7. These data indicate: (a) the existence of A1 and A2 subtypes of purinoceptors situated presynaptically, which modulates NA release, (b) the intracellular increase of cAMP negatively modulates this secretion, and (c) these arteries possess an active system for incorporating and degrading adenosine.