1/80. acromegaly in a family without a mutation in the menin gene.Familial pituitary tumors are rare. Only 45 cases in 20 families with acromegaly have been reported. A third of the cases (30%) is related to multiple endocrine neoplasia type 1 (men 1). We report two cases of acromegaly in one family with pituitary macroadenomas. A 46-year-old woman with elevated serum growth hormone (GH) and insulin-like growth factor (IGF-1) and a failure to supress GH in the glucose tolerance test underwent transsphenoidal surgery 4 years ago. Three years later her 24-year-old son also presented with typical signs of acromegaly. A pituitary macroadenoma was identified by MRT and he also underwent transsphenoidal surgery. There were no symptoms of McCune-Albright syndrome or other forms of endocrine hyperfunction in the two patients. In an attempt to identify the molecular etiology of the tumours dna was extracted from paraffin fixed tissue from both patients. Exon 7 to 13 of the Gsp-protein and exons 1 to 10 of the menin gene were amplified by PCR. Although Gsp mutations have been identified in 40% of somatotroph tumors, direct sequencing of the PCR products showed no mutations in exons 7 to 13 of Gs alpha. Moreover no mutations were found in exons 1 to 10 of the menin gene. Therefore, molecular causes other than Gsp or menin gene mutations have to be considered as the molecular etiology of acromegaly in this family.- - - - - - - - - - ranking = 1keywords = endocrine (Clic here for more details about this article) |
2/80. A rare case of acromegaly associated with pachydermoperiostosis.Pachydermoperiostosis (PDP) is a rare syndrome manifested clinically by finger clubbing, extremity enlargement, hypertrophic skin changes, and periosteal bone formation. The pathogenesis of the disorder has not been clarified and few endocrine abnormalities were apparent. We report here a 58-year-old man with acromegaly associated with PDP, the features of clubbed fingers, coarse skin, and cutis verticis gyrata. acromegaly due to GH-producing pituitary adenoma was confirmed in endocrinological and pathological studies.- - - - - - - - - - ranking = 0.5keywords = endocrine (Clic here for more details about this article) |
3/80. acromegaly associated with a granular cell tumor of the neurohypophysis: a clinical and histological study. Case report.acromegaly is usually caused by a growth hormone (GH)-secreting pituitary adenoma, and hypersecretion of GH-releasing hormone (GHRH) from a hypothalamic or neuroendocrine tumor accounts for other cases. The authors report on the unusual association of acromegaly with a granular cell tumor of the neurohypophysis. A 42-year-old woman with a 10-year history of acral enlargement, headache, and menstrual abnormalities was referred to our department for a suspected GH-secreting pituitary adenoma. The patient's basal GH levels were mildly elevated at 4.8 microg/L, were not suppressed in response to an oral glucose tolerance test, and increased paradoxically after administration of thyrotropin-releasing hormone. The patient's insulin-like growth factor-1 (IGF-1) level was elevated at 462 microg/L, whereas a magnetic resonance image of the sella turcica revealed an intra- and suprasellar lesion that was compatible with a diagnosis of pituitary adenoma. A transsphenoidal approach to remove the lesion, which was mainly suprasellar, was successful during a second operative attempt, resulting in the clinical and biochemical regression of the patient's acromegaly. Four months postoperatively, the patient's basal GH level was 0.9 microg/L and her IGF-1 level was 140 microg/L. Histological analysis of the operative specimen demonstrated a granular cell tumor of the neurohypophysis, which when stained proved negative for pituitary hormones and GHRH. This case represents the first reported association between a granular cell tumor of the neurohypophysis and acromegaly. granular cell tumor of the neurohypophysis could be added to the restricted list of neoplastic causes of acromegaly secondary to hypersecretion of a GH-releasing substance.- - - - - - - - - - ranking = 0.5keywords = endocrine (Clic here for more details about this article) |
4/80. Familial acromegaly: case report and review of the literature.Familial acromegaly is an exceptional clinical entity when not associated with features of multiple endocrine neoplasia type 1 (MEN1). We report here 3 pedigrees in each of which 2 patients have been shown to develop acromegaly. In 4 patients, clinical follow-up, and biological screening allowed to confidently exclude MEN1. Absence of mutation in the MEN1 gene after direct dna analysis in 2 pedigrees reinforces the conviction that the families do not have MEN1. In families 1 and 2, diagnosis was made at a very early age and voluminous adenomas with suprasellar expansion were already present at the time of diagnosis. We review the 20 previous reports of familial acromegaly, some of them questionable. Our 3 families, combined with some other published pedigrees, allow the delineation of a familial form of acromegaly, distinct from MEN1. Dominant inheritance with reduced, age-dependant penetrance is the most parsimonious model to explain the recurrences. Gs protein pathway could be the site of action of the gene responsible of familial acromegaly, but no data have been published to sustain or reject this hypothesis.- - - - - - - - - - ranking = 0.5keywords = endocrine (Clic here for more details about this article) |
5/80. Study of the multiple endocrine neoplasia type 1, growth hormone-releasing hormone receptor, Gs alpha, and Gi2 alpha genes in isolated familial acromegaly.Familial acromegaly may occur as an isolated pituitary disorder or as a feature of hereditary syndromes, such as multiple endocrine neoplasia type 1 (MEN1) or the carney complex. Herein, we characterized a newly identified kindred with isolated acromegaly and searched for germline mutation in genes that have been associated with endocrine tumors [i.e. MEN1, Gs alpha (GNAS1), and Gi2 alpha (GNAI2)], as well as the GHRH receptor (GHRH-R) gene. Genomic dna was used to amplify exons 2-10 of MEN1, followed by dideoxy fingerprinting mutation analysis and direct sequencing. The GHRH-R gene was analyzed via direct sequencing of PCR-amplified fragments representing the coding exons and intron-exon junctions. To exclude mutation at hot spot areas of GNAS1 and GNAI2, exons 8 and 9 of GNAS1 and exons 5 and 6 of GNAI2 were amplified and screened for mutation via denaturing gradient gel electrophoresis. No mutations were detected in any of the four genes. The present data extend prior reports of the absence of mutation in MEN1, GHRH-R, and GNAS1 and describe the first family with isolated acromegaly in which germline mutation in GNAI2 has been searched.- - - - - - - - - - ranking = 3keywords = endocrine (Clic here for more details about this article) |
6/80. Pituitary adenomas in childhood and adolescence. Clinical analysis of 10 cases.Pituitary adenomas in childhood and adolescence constitute 2-6% of all operated pituitary adenomas. We report the clinical features, treatment and follow-up of 10 pediatric patients affected by pituitary adenomas. All patients underwent clinical evaluation, endocrine tests, magnetic resonance imaging and visual field assessment. Follow-up ranged from 8 to 132 months (median 52.6). All patients were older than 10 years of age; 60% were males. In 50% the initial complaints were headache and/or visual impairment, all except one had clear evidence of endocrine dysfunction. Ninety percent were macroadenomas. According to hormone measurements and immunostaining 50% were prolactinomas, 20% were pure GH-secreting and 30% were non-functioning adenomas. Prolactinomas in two females were successfully treated with cabergoline. The other patients underwent surgery: three prolactinomas are still being treated with dopamine agonists and a GH-secreting adenoma is being treated with octreotide LAR and cabergoline. Two patients were also treated with conventional radiotherapy. Treatments were completely successful in 50% of patients: these have normal hormone secretion, full pubertal development, no significant tumor mass and normal visual field. Hypersecretion of prolactin persists in two cases; partial or complete hypopituitarism is present in four, relevant tumor remnant in another four and impairment of visual field is present in two cases. In conclusion, pediatric adenomas occur mostly in pubertal age, are prevalently macroadenomas and clinically functioning. Medical therapy should be preferred for secreting adenomas, but in some cases, notably prolactinomas in males, surgery and eventual radiotherapy may be needed.- - - - - - - - - - ranking = 1keywords = endocrine (Clic here for more details about this article) |
7/80. Carcinoid syndrome, acromegaly, and hypoglycemia due to an insulin-secreting neuroendocrine tumor of the liver.We report a patient with a hepatic neuroendocrine tumor showing an extraordinary change of the tumor's humoral manifestations from a clinically documented extrapituitary acromegaly and a typical carcinoid syndrome toward a hyperinsulinemic hypoglycemia syndrome. At the primary manifestation of the tumor, an increased serum level of insulin-like growth factor i due to overproduction of GHRH and an increased urinary excretion of 5-hydroxyindoleacetic acid were found. The clinical manifestation of the GHRH excess was an arthralgia, which resolved completely after operative tumor debulking and normalization of insulin-like growth factor i and GHRH serum levels. The secretion of serotonin from the tumor resulted in a typical carcinoid syndrome including right-sided valvular heart disease. On the later course of the disease, the humoral manifestations of the tumor were supplemented by the secretion of insulin, leading to recurrent severe hyperinsulinemic hypoglycemia. The hepatic origin of hyperinsulinism was demonstrated by selective arterial calcium stimulation. Moreover, tumor cells revealed insulin and c-peptide immunoreactivity in the immunohistochemical analysis. The patient died 8 yr after the initial diagnosis of the tumor, and a carefully performed autopsy procedure confirmed the absence of any extrahepatic tumor manifestation.- - - - - - - - - - ranking = 2.5keywords = endocrine (Clic here for more details about this article) |
8/80. growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) isoform expression in ectopic acromegaly.Bronchial endocrine neoplasms causing acromegaly due to ectopic production of growth hormone (GH)-releasing hormone (GHRH) have been reported. We describe the case of a 39-year-old man with clinical and biochemical acromegaly. magnetic resonance imaging revealed an enlarged pituitary, which was confirmed histologically to harbour somatotroph hyperplasia. Further investigations identified a circumscribed central mass in the right lung which was surgically resected and histologically confirmed to be an endocrine tumour with strong immunopositivity for GHRH, synaptophysin and chromogranin; the lesion also exhibited mild positivity for peptide yy, calcitonin gene-related peptide (CGRP), glucagon-like peptide (GLP)-1, corticotrophin-releasing hormone (CRH), tyrosine hydroxylase, vasoactive intestinal peptide (VIP) and enkephalin. S100 protein was identified in stellate cells surrounding nests of epithelial tumour cells. The MIB-1 antibody labelled about 10% of the tumour cells. We established that the tumour not only produced GHRH but the GHRH-receptor (GHRH-R) as well. GHRH and GHRH-R mRNA were identified and the latter was characterized as two variants, a full-length transcript and a truncated splice variant that has been described in human pituitary somatotroph adenomas. We suggest that GHRH expression by this tumour and the presence of its receptor may be responsible for enhanced growth. The expression of a truncated splice variant that is unable to transduce GHRH signalling may be implicated in the less aggressive behaviour of well-differentiated endocrine tumours that produce GHRH compared with small-cell lung carcinomas that are very responsive to GHRH growth stimulation.- - - - - - - - - - ranking = 1.5keywords = endocrine (Clic here for more details about this article) |
9/80. A rare association between acromegaly and pheochromocytoma.The occurrence of multiple endocrine tumors is rare; however, they may be found with hereditary diseases such as multiple endocrine neoplasia (men). The endocrine tumors involved with these diseases are well documented. We present a case of a patient with a pheochromocytoma and a growth hormone (GH) secreting pituitary adenoma. This association is not described with any of the known men syndromes. The association may be a cross-over men syndrome or a secondarily induced GH-secreting pituitary adenoma from a pheochromocytoma producing growth hormone releasing hormone (GHRH) instead of catecholamines.- - - - - - - - - - ranking = 1.5keywords = endocrine (Clic here for more details about this article) |
10/80. acromegaly and pheochromocytoma: report of a rare coexistence.OBJECTIVE: To describe a patient with the rare coexistence of acromegaly and pheochromocytoma. methods: We report a case of a 57-year-old woman, who was initially examined because of polyarthritis, she was also diagnosed with type 2 diabetes mellitus and hypertension at age 56 years. Her history, clinical findings, laboratory results, and management are summarized, and etiologic hypotheses are discussed. RESULTS: The patient had recurrent headaches and reported an increasing size of her shoes and gloves during the previous 4 years. Enlargement of her hands and feet and a bilateral temporal field defect were noted on examination. Laboratory studies revealed high levels of insulin-like growth factor i (IGF-I) and growth hormone (GH). magnetic resonance imaging (MRI) showed a 3-cm sellar mass with impingement on the optic chiasm. The plasma level of growth hormone-releasing hormone (GHRH) was normal. She underwent transsphenoidal adenomectomy. Histologic examination confirmed a pituitary adenoma, immunoreactive for GH. Postoperatively, her headaches and arthritic pain diminished, and her levels of IGF-I and GH normalized; however, labile hypertension persisted. The urinary metanephrines and plasma catecholamines were increased. A 3-cm left adrenal mass, seen on abdominal MRI, was removed laparoscopically, after which urinary metanephrines normalized and both the diabetes and the hypertension resolved. Histopathologic analysis confirmed the diagnosis of pheochromocytoma. Immunohistochemical staining was negative for GHRH. CONCLUSION: The finding of a pheochromocytoma and acromegaly could be a fortuitous coexistence of two separate endocrine tumors; however, the probability of such an event is extremely low. A cause-and-effect relationship has been suggested because of previous reports of GHRH production by pheochromocytomas. Some investigators have also suggested that this coexistence might be a multiple endocrine neoplasia variant. Our patient had no evidence of GHRH production, nor did we document any familial autosomal dominant transmission pattern.- - - - - - - - - - ranking = 1keywords = endocrine (Clic here for more details about this article) |
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