Diaphragma sellae: a surgical reference for transsphenoidal resection of pituitary macroadenomas.

OBJECTIVE: To classify patterns of descent of the diaphragma sellae (DS) to the sella turcica after transsphenoidal resection of pituitary macroadenomas and to determine whether there is any correlation between type of descent and volume or growth pattern of the tumor, as well as the presence of any postoperative hormone alteration, cerebrospinal fluid leak, and/or residual tumor. METHODS: One hundred patients with pituitary macroadenomas in which microsurgical transsphenoidal approach was indicated were prospectively included. We classified patterns of descent of the DS into four types: type A: symmetrical descent with a central fold corresponding to the pituitary stalk; type B: asymmetrical with a lateralized fold; type C: symmetrical and uniform descent without any fold; and type D: minimal or no descent in absence of visible residual tumor. A correlation was made between these types of descent and clinical and radiological findings. RESULTS: The largest tumors were types A and B; endocrine deficit was more frequent in types A and C, whereas the possibility of residual tumor was more elevated in types B and D. No statistically significant differences were found regarding tumor morphology and cerebrospinal fluid leakage. CONCLUSIONS: Our results suggest that pattern of descent of the DS may serve as a reference to determine the risk of leaving residual tumor as well as the possibility of developing postoperative endocrine deficit. It is apparent that tumor volume, more than morphology, is the main factor determining type of descent of the DS.

In vitro biological-to-immunological ratio of serum gonadotropins throughout male puberty in children with insulin-dependent diabetes mellitus.

Information on the impact of prolonged deficient glycemic control in the quality of the gonadotropin signal delivered by the pituitary gland during puberty in children with insulin-dependent diabetes mellitus (IDDM) is scarce. In the present study, we examined the impact of deficient glycemic control on bioactive LH and FSH concentrations and their corresponding biological-to-immunological (B:I) ratio in boys with poorly controlled, but systemically uncomplicated IDDM. Dual control groups comprising patients with well-controlled IDDM and healthy boys of comparable age and body mass index were included for appropriate comparisons within and between each pubertal stage. Patients with poorly controlled and well-controlled IDDM exhibited serum bioactive FSH levels and B:I FSH ratio similar to those showed by the healthy control group. In contrast, in early and mid-pubertal boys with poorly controlled IDDM bioactive LH levels were normal, but its B:I LH relationship was significantly (P < 0.05) decreased. This attenuation in the quality of the LH signal did not affect total serum T concentrations, and apparently, progression of puberty. Long-standing uncontrolled diabetes and the consequent metabolic disturbances and/or complications may aggravate the reproductive axis dysfunction and eventually provoke pubertal arrest.

Serotonin-related tryptophan in children with insulin-dependent diabetes.

In the course of the present research in school children with insulin-dependent diabetes mellitus, we observed that the free fraction of L-tryptophan, the free fraction of L-tryptophan/total L-tryptophan, and the free fraction of L-tryptophan/neutral amino acids ratios, are significantly reduced. The decrease of free fraction of L-tryptophan in plasma with a concomitant decrease of the free fraction of L-tryptophan/neutral amino acids ratio suggest a decrease in the transport of the precursor amino acid to the brain and in the serotonin synthesis rate, similar to that observed in diabetic animals. This finding may be of relevance in the pathophysiology and in the clinical picture, which could be related to an alteration of serotonin metabolism and neurotransmission in the brain and may be possibly related to neuropsychiatric disorders in diabetic school children. Thus we propose that the free fraction of L-tryptophan and the free fraction of L-tryptophan/neutral amino acids ratios may be clinically useful as indicators of brain serotonergic activity in these patients. In our laboratory, we are currently obtaining additional data on the functional role of the brain serotonergic system in humans to further support the relevance of our results.

A novel mutation of the insulin-like 3 gene in patients with cryptorchidism.

Two independent studies demonstrated that transgenic mice with a targeted deletion of the insulin-like 3 ( INSL3) gene presented bilateral cryptorchidism. Studies in humans have investigated the possibility that mutations in the INSL3 gene are the cause of cryptorchidism. In the present study, genomic DNA was obtained from 150 patients with idiopathic cryptorchidism. DNA was amplified and the polymerase chain reaction products of both exons were sequenced. A previously unidentified missense mutation was found in only one of the patients studied. In exon 2, a heterozygous C/G substitution at nucleotide 2560, which turned asparagine into lysine at codon 86, was documented. The familial study revealed that the mother was a heterozygous carrier of the mutation and the father was a homozygote wild type. We also found three polymorphic changes, previously reported in exon 1. The Asn-into-Lys change is likely deleterious because it leads to a nonconservative amino acid substitution, changing a highly conserved residue. This mutation, located in the A-chain of the INSL3 protein, is the first mutation reported in this region. This finding provides new evidence that INSL3 is involved in testicular descent in humans; however, mutations of this gene are not a frequent cause of cryptorchidism.

Primary empty sella syndrome: the role of visual system herniation.

BACKGROUND: It has been traditionally accepted that ophthalmologic alterations in cases of primary empty sella syndrome are caused by the herniation of the visual system in the pituitary fossa, but this cannot be stated categorically. METHODS: Two female patients with primary empty sella syndrome and visual field defects were included in this series. The peculiarity of these cases was that in neither of them was there an evident herniation of the visual system. In the absence of other causes that could explain the visual defects, the patients were operated on through a transsphenoidal approach. RESULTS: Both patients showed immediate improvement of their visual deficits without recurrence. Postoperative imaging studies have shown continuance of an adequate elevation of the sellar contents during the 5-year follow-up period. CONCLUSIONS: Visual field defects in cases of primary empty sella syndrome may occur even without radiological evidence of herniation of the visual system. The fact that the two patients described in this paper improved after surgery supports other reports that in this syndrome traction on the infundibular stalk may cause some microscopic anatomic alteration in the visual system or in its vascular supply that is not evident on imaging studies.

Mutational analysis of the luteinizing hormone receptor gene in two individuals with Leydig cell tumors.

Inactivating mutations of the luteinizing hormone receptor (LHR) gene in males induce Leydig cell agenesis or hypoplasia, while activating mutations cause testotoxicosis. Recently, it was demonstrated that a somatic heterozygous activating mutation of the LHR gene (Asp578His), limited to the tumor, was the cause of Leydig cell adenomas in three unrelated patients. We describe the molecular study of two unrelated boys with gonadotropin-independent hypersecretion of testosterone due to Leydig cell adenomas. Genomic DNA was extracted from the tumor, the adjacent normal testis tissue, and blood leukocytes. Both individuals exhibited an heterozygous missense mutation, limited only to the tumor, consisting of a guanine (G) to cytosine (C) substitution at codon 578 (GAT to CAT), turning aspartic acid into histidine. The presence of the same mutation in different ethnic groups demonstrates the existence of a mutational hot spot in the LHR gene. Indeed, this mutation occurs at the conserved aspartic acid residue at amino acid 578, where a substitution by glycine is the most common mutation observed in testotoxicosis and where a substitution by tyrosine has been linked to a more severe clinical phenotype where diffuse Leydig cell hyperplasia is found. Our results confirm the fact that somatic activating mutations of gonadotropin receptors are involved in gonadal tumorigenesis.