Ethmoid glomangioma and oncogenic osteomalacia: a case report.

BACKGROUND: Glomangioma is a benign tumor of mesenchymal origin, derived from the glomus body. It is responsible for the thermal regulation of the dermis. The occurrence of oncogenic osteomalacia related to glomangioma is rare. Only two cases have been reported thus far. CASE PRESENTATION: A 32-year-old female, Brazilian, presented diffuse pain, during pregnancy, that developed progressively, limiting her mobility. Imaging showed a femoral neck fracture, and rheumatological laboratory examination showed hypophosphatemia. Also, the patient reported episodes of epistaxis during childhood and recurrence along with progressively right nasal obstruction. Endoscopic resection of the tumor was performed, and immunohistochemistry was conclusive for glomangioma. This case report describes the third case in which endonasal endoscopic surgery resulted in a favorable outcome. CONCLUSION: This case of glomangioma-induced oncogenic osteomalacia suggests that surgeons and clinicians should consider sinonasal tumors as a differential diagnosis of osteomalacia, and endonasal endoscopic surgery should be a possible curative resection.

Sex steroids in androgen-secreting adrenocortical tumors: clinical and hormonal features in comparison with non-tumoral causes of androgen excess.

OBJECTIVE: Adrenocortical tumors (ACT) account for no more than 0.2% of the causes of androgen excess (AE). Conversely, these rare tumors have a very poor prognosis. It is difficult and important to exclude this diagnosis whenever there is AE. DESIGN: Retrospective investigation of androgen profiles in a large consecutive series of androgen-secreting (AS) ACT to assess their relative diagnostic value. METHODS: A total of 44 consecutive female patients with ACT-AS and a comparison group of 102 women with non-tumor causes of AE (NTAE). RESULTS: Patients with ACT-AS were older than the ones with NTAE (37.7 vs 24.8 years; P<0.001) and the prevalence of hirsutism, acne, and oligo/amenorrhea were not different. Free testosterone was the most commonly elevated androgen in ACT-AS (94%), followed by androstenedione (90%), DHEAS (82%), and total testosterone (76%), and all three androgens were simultaneously elevated in 56% of the cases. Androgen serum levels became subnormal in all ACT-AS patients after complete tumor removal. In NTAE, the most commonly elevated androgen was androstenedione (93%), while all three androgens were elevated in only 22% of the cases. Free testosterone values above 6.85 pg/ml (23.6 pmol/l) had the best diagnostic value for ACT-AS (sensitivity 82%, confidence interval (CI): 57-96%; specificity 97%, CI: 91-100%). Basal LH and FSH levels were significantly lower in the ACT-AS group. CONCLUSION: Free testosterone was the most reliable marker of ACT-AS. However, the large overlap of androgen levels between ACT-AS and NTAE groups suggests that additional hormonal and/or imaging investigations are required to rule out ACT-AS in case of increased androgens.

Absence of mutation in the follicle-stimulating hormone receptor gene in severe primary hypothyroidism associated with gonadal hyperstimulation.

BACKGROUND: Severe hypothyroidism can cause a distinct form of precocious puberty in children, characterized by delayed skeletal maturation, predominance of FSH-mediated effects over LH-mediated function, and reversal of sexual precocity upon thyroid hormone replacement. The etiology of this unusual form of precocious puberty in children remains poorly understood. Recently, three mutations of the FSH receptor gene have been identified in women with spontaneous ovarian hyperstimulation during pregnancy. All three mutated receptors displayed abnormally high sensitivity to hCG which caused gonadal stimulation. Two of these mutations displayed concomitant increase in sensitivity of the mutated receptor to TSH. In this report, we describe four children with primary hypothyroidism and gonadal hyperstimulation. The aim of this study was to determine whether these patients' gonadal hyperstimulation is due to a mutation in their FSH receptor gene. METHODS: DNA was extracted from all four patients with primary hypothyroidism and gonadal stimulation. The entire FSH receptor gene was sequenced and analyzed. RESULTS: Direct sequencing of these patients' FSH receptor gene did not demonstrate any mutation, proving that the cause of gonadal stimulation in these patients is not due to the increased sensitivity or constitutive activation of a mutated FSH receptor. CONCLUSIONS: The elevated TSH in these patients and prior demonstration of the in vitro ability of TSH to bind to the FSH receptor lead us to hypothesize that the gonadal stimulation in these patients is TSH-mediated. The fact that gonadal stimulation is not seen in all patients with severe hypothyroidism raises the question as to whether polymorphisms of the FSH receptor gene and/or possible changes in the TSH molecular structure may contribute to the TSH-mediated activation of the FSH receptor.

A signal peptide mutation of the arginine vasopressin gene in monozygotic twins.

Familial neurohypophysial diabetes insipidus (FNDI) is a rare autosomal dominant syndrome stemming from the absence of arginine vasopressin (AVP). More than thirty-five different germline mutations in the arginine vasopressin-neurophysin II gene have been reported. These mutations are either in the signal peptide or scattered throughout the neurophysin II domain. A missense mutation altering alanine at position -1 to either valine or threonine in the signal peptide domain has previously been found in ten unrelated families. In the present report, Brazilian female monozygotic twins with clinically typical central DI in whom biochemical and molecular characterization were carried out are described. Direct mutational analysis by sequencing of the vasopressin gene in germline DNA revealed a heterozygous missense mutation (G-->A) at nucleotide 279, predicting the substitution of alanine by threonine at position -1 of the signal peptide moiety. In summary, we present an extremely rare case of familial central diabetes insipidus in monozygotic Brazilian twins with a seemingly common missense mutation in the AVP gene.