1/45. A new compound heterozygous mutation of the gonadotropin-releasing hormone receptor (L314X, Q106R) in a woman with complete hypogonadotropic hypogonadism: chronic estrogen administration amplifies the gonadotropin defect.We describe a woman with complete hypogonadotropic hypogonadism and a new compound heterozygous mutation of the GnRH receptor (GnRHR) gene. A null mutation L314X leading to a partial deletion of the seventh transmembrane domain of the GnRHR is associated with a Q106R mutation previously described. L314X mutant receptor shows neither measurable binding nor inositol phosphate production when transfected in CHO-K1 cells compared to the wild-type receptor. The disease is transmitted as an autosomal recessive trait, as shown by pedigree analysis. Heterozygous patients with GnRHR mutations had normal pubertal development and fertility. The present study shows an absence of LH and FSH response to pulsatile GnRH administration (20 microg/pulse, sc, every 90 min). However, GnRH triggered free alpha-subunit (FAS) pulses of small amplitude, demonstrating partial resistance to pharmacological doses of GnRH. FSH, LH, and FAS concentrations were evaluated under chronic estrogen treatment and repeat administration of GnRH. Not only were plasma FSH, LH, and FAS concentrations decreased, but FAS responsiveness was reduced. This new case emphasizes the implication of the GnRH receptor mutations in the etiology of idiopathic hypogonadotropic hypogonadism. We also have evidence for a direct negative estrogen effect on gonadotropin secretion at the pituitary level, dependent on the GnRHR signaling pathway.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
2/45. Gonadotropin-secreting pituitary tumor associated with hypersecretion of testosterone and hypogonadism after hypophysectomy.OBJECTIVE: To review gonadotropin-secreting pituitary tumors and report the rare case of one of these tumors that caused high serum testosterone concentrations, followed by hypogonadism after hypophysectomy. methods: A case report is presented of a 61-year-old man who had decreased vision in his left eye, found by computed tomography of the sella to be attributable to a soft tissue pituitary mass with upward extension that caused elevation and deviation of the optic chiasm. Endocrine and pathologic evaluations are presented, and the treatment and follow-up course are discussed. RESULTS: Endocrine evaluation revealed a serum follicle-stimulating hormone (FSH) of 72.48 mIU/mL, luteinizing hormone (LH) of 31.65 mIU/mL, prolactin of 26.42 ng/mL, and total testosterone of 15.24 ng/mL (all values higher than the normal ranges). A soft tissue mass (3.2 by 2.5 by 1.2 cm) with negative immunocytochemical staining for prolactin and growth hormone but positive staining for synaptophysin, FSH, and LH was removed. One month postoperatively, the patient's chief complaints were a decrease in penile size and erectile dysfunction. Endocrine evaluation revealed a decreased LH of <0.3 mIU/mL, total testosterone of <0.2 ng/mL, and FSH of 4.3 mIU/mL. Three months later with testosterone replacement therapy, testosterone levels normalized, LH was <0.3 mIU/mL, and FSH was 3.9 mIU/mL. Thyroid function and adrenal function were normal before and after surgical intervention. CONCLUSION: This rare case indicates that gonadotropin tumors can produce a functional LH that can increase serum testosterone levels.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
3/45. "Hook effect" in prolactinomas: case report and review of literature.OBJECTIVE: To present a case of the "hook effect" occurring in the prolactin immunoassay in a patient with giant prolactinoma and to review this phenomenon. methods: We describe the clinical, biochemical, radiologic, and pathologic data of a patient with a giant prolactinoma, in which dilution testing of serum prolactin levels confirmed the presence of the hook effect. We discuss the historical and mechanistic aspects of the hook effect and then review its occurrence with the prolactin assay. RESULTS: A 65-year-old man sought medical attention because of headaches, personality changes, and "bulging" eyes. Cranial magnetic resonance imaging disclosed a 10-cm-diameter, lobulated, heterogeneous, locally invasive mass in the anterior skull base and cranial fossa. Initial laboratory testing showed a prolactin level of 164.5 ng/mL (normal range, 1.6 to 18.8). The pathology specimen from his surgical debulking procedure was consistent with prolactinoma. Retesting of the original serum prolactin sample with serial dilutions revealed a prolactin level of 26,000 ng/mL. A postoperative diluted prolactin level was 22,000 ng/mL. Both prolactin samples demonstrated the hook effect. Dopamine agonist therapy was initiated, and the prolactin level and size of the tumor decreased substantially. The hook effect most commonly occurs when excess antigen (for example, prolactin) is present during testing. Dilution testing can counteract this assay phenomenon. CONCLUSION: Clinicians should be aware of this laboratory phenomenon when evaluating large pituitary or parasellar masses. When the hook effect is suspected, dilution testing of prolactin samples may prevent incorrect diagnosis and unnecessary surgical intervention in patients with prolactinomas.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
4/45. Cyclic estrogen-progestin hormone therapy as a new therapeutic approach in the treatment of functional alterations of the hypothalamus-pituitary-ovary axis: case reports.amenorrhea is a clinical condition characterized by failure of menarche or by the absence of menstruation for six months in a woman with previous periodic menses. We report a first case of a 30 year-old woman affected by polycystic ovarian disease (PCOD) whose amenorrhea ceased after a 6-month combination treatment with cyclic estradiol-norethisterone acetate. After the withdrawal of the hormone therapy, a stable recovery of periodic menses was observed. We describe a second case of a 23 year-old woman whose amenorrhea was caused by a hypogonadotropic hypogonadism due to a non-functioning pituitary adenoma. After the administration of the previously described therapy both a disappearance of the adenoma and a recover of periodic menses were observed. We hypothesized that the outcomes in our cases could be the consequence of a balancing action induced by the exogenous hormone administration. The exogenous hormones may have reset the feedback between the hypothalamus and pituitary gland through mimicking the physiological hormones pattern of the 28-day cycle.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
5/45. x chromosome-linked kallmann syndrome: clinical heterogeneity in three siblings carrying an intragenic deletion of the KAL-1 gene.kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia. The gene underlying the x chromosome-linked form of the disease, KAL-1, consists of 14 coding exons. It encodes a glycoprotein, anosmin-1, which is involved in the embryonic migration of GnRH-synthesizing neurons and the differentiation of the olfactory bulbs. We describe herein the clinical heterogeneity in three affected brothers who carry a large deletion (exons 3-13) in KAL-1. All three had a history of hypogonadotropic hypogonadism with delayed puberty. Although brain magnetic resonance imaging showed hypoplastic olfactory bulbs in the three siblings, variable degrees of anosmia/hyposmia were shown by olfactometry. In addition, these brothers had different phenotypic anomalies, i.e. unilateral renal aplasia (siblings B and C), high-arched palate (sibling A), brachymetacarpia (sibling A), mirror movements (siblings A and B), and abnormal eye movements (sibling C). Last but not least, sibling A suffered from a severe congenital hearing impairment, a feature that had been reported in KS but had not yet been ascribed unambiguously to the X-linked form of the disease. The variable phenotype, both qualitatively and quantitatively, in this family further emphasizes the role of putative modifier genes, and/or epigenetic factors, in the expressivity of the X-linked KS.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
6/45. Revelation of a new mitochondrial dna mutation (G12147A) in a MELAS/MERFF phenotype.BACKGROUND: A 26-year-old man presented at onset with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) and later with a phenotype for MELAS and myoclonic epilepsy and ragged red fiber disease (MELAS/MERRF). OBJECTIVE: To identify the possible defects in the mitochondrial genome in blood and muscle samples of the patient. DESIGN: Case study of a patient clinically exhibiting strokelike episodes and then epilepsy with myoclonic features, ataxia, and dementia. SETTING: research unit of a university hospital. MAIN OUTCOME MEASURES: Electromyographic, morphologic, and biochemical studies of muscle and molecular analysis of blood and muscle to investigate mitochondrial dna (mtDNA) size and quantity. RESULTS: Morphologically, we found abnormal mitochondrial proliferation with several cytochrome-c oxidase (COX)-negative fibers in muscle biopsy specimens; the analysis of serial sections showed a decreased immunoreactivity for the mtDNA-encoded subunits COXII and, partially, COXI. Biochemically, we found a partial and isolated COX deficiency. The complete mtDNA sequence analysis identified 3 sequence changes, 2 of which were reported polymorphisms. The remaining change, a G12147A transition in the transfer rna(His) gene, appeared to be the likely pathogenic mutation. CONCLUSIONS: Our data propose that the G12147A change, the first mutation in the transfer rna(His) gene associated with an overlapped MELAS/MERFF phenotype, is the cause of the encephalomyopathy in this patient interfering with the overall mitochondrial protein synthesis.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
7/45. Acute stress masking the biochemical phenotype of partial androgen insensitivity syndrome in a patient with a novel mutation in the androgen receptor.hypogonadism has traditionally been classified as either hypogonadotropic or hypergonadotropic based on serum gonadotropin levels. However, when hypothalamic suppression of GnRH secretion occurs, it can mask an underlying hypergonadotropic state. In this report we document the unusual case of a 61-yr-old man with androgen insensitivity and coincidental functional hypogonadotropic hypogonadism (HH). Although functional HH is not a well-recognized entity in the male, major stress has been reported to cause transient suppression of the hypothalamic-pituitary-gonadal axis in men. The patient in question was noted to have undervirilization, minimal pubertal development, hypogonadal testosterone, and low gonadotropin levels consistent with congenital HH during a hospital admission for myocardial infarction. However, the patient had also had surgery for hypospadias, a clinical feature not typically part of the phenotypic spectrum of congenital HH. We therefore hypothesized that the combination of acute stress and chronic glucocorticoid administration for temporal arteritis induced transient HH in a patient with a disorder of sexual differentiation in whom gonadotropin levels would have otherwise been elevated. Using clinical, molecular, and genetic studies, the patient was found to have partial androgen insensitivity syndrome (PAIS) caused by a novel mutation (Ser(740)Cys) in the ligand-binding domain of the androgen receptor. Subsequent studies of the patient confirmed the characteristic gonadotropin and sex steroid abnormalities of PAIS. We describe for the first time a patient with PAIS presenting with a reversible hypogonadotropic biochemical profile triggered by an acute illness and corticosteroid therapy. This case highlights the necessity for caution when interpreting gonadotropin levels during acute stress.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
8/45. diabetes insipidus from neurosarcoidosis: long-term follow-up for more than eight years.Four patients with sarcoidosis presented as hypothalamic-hypophyseal syndrome including diabetes insipidus (DI) were followed up for more than 8 years from the onset of clinical manifestation. The mean age was 26 years, male : female ratio was 3 : 1 and the mean disease duration of 10 years. All patients had hypogonadism, hyperprolactinemia. Pituitary enlargement with thickening of the pituitary stalk were detected by magnetic resonance imaging (MRI) with gadolinium enhancement and attenuation in the intensity of the posterior lobe of the pituitary was detected without enhancement. Corticosteroid therapy resulted in the initial improvement of symptoms and gradual decrease in the tumor size but failed to cure polyuria due to DI. The use of desmopressin was necessary for a long period. None of these patients died from DI or central neurosarcoidosis.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
9/45. Familial variable expression of dilated cardiomyopathy in alstrom syndrome: a report of four sibs.alstrom syndrome is an autosomal recessive disorder comprised of progressive vision loss (nystagmus, photophobia, and pigmentary retinopathy), progressive sensorineural hearing loss, morbid obesity, male hypogonadism, insulin resistant diabetes, renal failure, and dilated cardiomyopathy. We report on four sibs with alstrom syndrome with intra-familial variability in onset, severity, and spectrum of manifestations; the most serious manifestation being dilated cardiomyopathy. This report emphasizes the difficulty of recognizing this constellation of symptoms as alstrom syndrome at an early age, the seriousness of cardiac involvement, and the intra-familial variability of phenotypic expression.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
10/45. testosterone replacement-induced hyperprolactinaemia: case report and review of the literature.Half of all men with prolactin (PRL)-producing macroadenomas present with hypogonadism, decreased libido and impotence, and therefore require testosterone replacement. However, very little is known about the effect of testosterone on prolactinomas. We report a case of an 18-year-old obese man who presented with hypogonadism and hyperprolactinaemia and underwent a transphenoidal hypophysectomy after a computer tomography scan showed the presence of a suprasellar macroadenoma. On separate occasions, we documented a rise in PRL when testosterone replacement was started and a fall in PRL when testosterone replacement was stopped (r = 0.6090, P = 0.0095). Furthermore, imaging studies suggested the possibility of tumour re-growth after testosterone therapy. We hypothesize that the exogenous testosterone was aromatized to oestradiol, which stimulated the release of PRL by the anterior pituitary. This was supported by the increase in oestradiol levels after testosterone replacement, although statistical significance was not achieved due to the availability of only a few data points. This case highlights the need to be aware of testosterone-replacement-induced hyperprolactinaemia, an under-recognized complication of androgen replacement in this setting. The use of aromatase inhibitors together with testosterone-replacement therapy or the use of non-aromatizable androgens might be indicated in such patients. Taken together, this report and previous studies show that dopamine agonists apparently do not suppress the hyperprolactinaemia induced by testosterone replacement.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
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