1/8. growth hormone excess and sexual precocity in polyostotic fibrous dysplasia (McCune-Albright syndrome): evidence for abnormal hypothalamic function.A 5-5/12-year-old boy with gigantism and precocious puberty associated with the McCune-Albright syndrome is presented. serum concentrations of growth hormone were extremely elevated (128-163 ng/ml) and were not suppressed by hyperglycemia or chlorpromazine. serum LH (7.4 /- 1.0 SD mIU/ml) and FSH (5.3 /- 0.3 SD mIU/ml) concentrations were in the range observed in midpuberty. The secretion pattern of LH was episodic. The administration of estradiol suppressed the secretion of FSH and had an apparent positive feedback effect on release of LH. These findings are compatible with abnormal hypothalamic function as the mechanism for the endocrinopathies associated with the McCune-Albright syndrome.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
2/8. Management of infertility in a patient presenting with ovarian dysfunction and McCune-Albright syndrome.Persistent autonomous ovarian dysfunction in McCune-Albright syndrome (MAS) patients is associated with the development of multiple dominant follicles, premature luteinization, cyst formation, and anovulatory infertility. Due to the mosaic distribution of the mutation, ovaries may be unequally affected. In the current patient, the least affected ovary became quiescent upon GnRH agonist-induced gonadotropin suppression. Normoovulatory cycles were restored after subsequent removal of the affected right ovary, and a pregnancy was established within 3 months. A healthy unaffected girl was born at term after an uneventful pregnancy. The placental tissue was normal, and the mutation was not detected in the placenta, umbilical cord structures, or umbilical cord blood. GnRH analog administration may help to identify those MAS patients who might benefit from unilateral ovariectomy. Because a healthy baby was born, evidence is provided suggesting that MAS is not passed on to the children from the parents.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
3/8. Pathologic hepatic Tc-99m-MDP uptake in polyostotic fibrous dysplasia.fibrous dysplasia of bone is a congenital, sporadic developmental disorder characterized by immature fibrous connective tissue and bone deformities. Hepatic Tc-99m-MDP uptake is a rare, serendipitous finding during bone scanning studies. The present patient was a 25-year-old male who had severe polyostotic fibrous dysplasia. On Tc-99m-MDP (methylene diphosphonate) bone scintigraphy, increased activity accumulations were seen on multiple ribs, vertebrae and base of the cranium. In addition, diffuse increased pathologic uptake of Tc-99m-MDP in the liver was shown. Intravenous pamidronate was administered monthly for two months. In the third week of the last administration Tc-99m-MDP bone scintigraphy was performed again, but despite sustained bone involvement, pathologic hepatic uptake was not seen on the scan. We thought that pathologic hepatic Tc-99m-MDP accumulation, may be related to the formation and aggregation of calcium oxalate and phosphate crystals which improved with pamidromat treatment.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
4/8. Fibroblast growth factor-23 is regulated by 1alpha,25-dihydroxyvitamin D.serum FGF-23 regulation was studied in patients with hypoparathyroidism or pseudohypoparathyroidism treated with calcitriol. serum FGF-23 levels changed in parallel in response to changes in serum 1,25-D, suggesting that FGF-23 may be regulated by 1,25-D. In addition, the phosphaturic effect of FGF-23 may be diminished in the absence of PTH action on the kidney. INTRODUCTION: Fibroblast growth factor (FGF)-23 is a recently described hormone that has been shown to be involved in the regulation of phosphate and vitamin d metabolism. The physiologic role of FGF-23 in mineral metabolism and how serum FGF-23 levels are regulated have yet to be elucidated. Three patients with mineral metabolism defects that allowed for the investigation of the regulation of FGF-23 were studied. MATERIALS AND methods: Patient 1 had postsurgical hypoparathyroidism and Munchausen's syndrome and consumed a pharmacologic dose of calcitriol. Patient 2 had postsurgical hypoparathyroidism and fibrous dysplasia of bone. She was treated with increasing doses of calcitriol followed by synthetic PTH(1-34). Patient 3 had pseudohypoparathyroidism type 1B and tertiary hyperparathyroidism. She underwent parathyroidectomy, which was followed by the development of hungry bone syndrome and hypocalcemia, requiring treatment with calcitriol. serum FGF-23 and serum and urine levels of mineral metabolites were measured in all three patients. RESULTS: Patient 1 had an acute and marked increase in serum FGF-23 (70 to 670 RU/ml; normal range, 18-108 RU/ml) within 24 h in response to high-dose calcitriol administration. Patient 2 showed stepwise increases in serum FGF-23 from 117 to 824 RU/ml in response to increasing serum levels of 1alpha,25-dihydroxyvitamin D (1,25-D). Finally, before parathyroidectomy, while hypercalcemic, euphosphatemic, with low levels of 1,25-D (10 pg/ml; normal range, 22-67 pg/ml), and with very high serum PTH (863.7 pg/ml; normal range, 6.0-40.0 pg/ml), patient 3 had high serum FGF-23 levels (217 RU/ml). After surgery, while hypocalcemic, euphosphatemic, and with high serum levels of serum 1,25-D (140 pg/ml), FGF-23 levels were higher than preoperative levels (305 RU/ml). It seemed that the phosphaturic effect of FGF-23 was diminished in the absence of PTH or a PTH effect. CONCLUSIONS: serum FGF-23 may be regulated by serum 1,25-D, and its phosphaturic effect may be less in the absence of PTH.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
5/8. gigantism associated with McCune-Albright's syndrome.The case of a 16 year-old boy with McCune-Albright's syndrome which is rarely accompanied by gigantism was studied endocrinologically. The stimulation of growth hormone (GH) release by hypoglycemia, the decline of elevated GH by hyperglycemia and a little lower somatostatin like immunoreactivity (SLI) may support abnormalities of hypothalamic function, but the existence of pituitary microadenoma cannot be ruled out because of the paradoxical suppression of GH release by oral administration of bromocriptine (CB-154) and L-DOPA and the stimulation of GH release by intravenous administration of TRH.- - - - - - - - - - ranking = 2keywords = administration (Clic here for more details about this article) |
6/8. McCune-Albright syndrome and acromegaly: clinical studies and responses to treatment in five cases.We report here five new patients with McCune-Albright syndrome and acromegaly. In the five patients studied (three males and two females aged 18-42 years), acromegaly began before the age of 20 years and was recognized after the diagnosis of fibrous dysplasia, which was polyostotic in three cases and monostotic in two. Bone fibrous dysplasia always involved the base of the skull and in four patients prevented surgical removal of the pituitary adenoma, which was visualized easily by magnetic resonance imaging. serum growth hormone (GH) levels ranged between 20 and 48 micrograms/l and were not suppressed by an oral glucose load. thyrotropin-releasing hormone administration produced a paradoxical increase in serum GH levels in all the patients. Four of the five patients had hyperprolactinemia (43-670 micrograms/l). In the sole patient who could be operated on, a typical adenoma with positive immunostaining for GH was incompletely removed and postoperative radiation therapy failed to cure the acromegaly. In two patients, medical therapy with bromocriptine and/or octreotide was partially or totally ineffective whatever the dose (up to 1.5 mg per day) and duration (2-4 years) of octreotide treatment.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
7/8. Familial Albright's hereditary osteodystrophy with hypoparathyroidism: normal structural Gs alpha gene.Albright's hereditary osteodystrophy (AHO) is a characteristic skeletal phenotype, including short stature, obesity, round face, and brachydactyly. AHO appears in patients with pseudohypoparathyroidism (PHP) who have resistance to PTH and in their eumetabolic family members who have pseudopseudohypoparathyroidism (PPHP). The differential diagnosis of AHO in families without PHP includes brachydactyly E, whose existence as a distinct entity has been questioned. We studied a patient with familial AHO who presented with hypocalcemia. To our surprise, PTH levels were low, and the response to PTH administration was normal. This is the first case of familial AHO with hypoparathyroidism. The proband's family included 22 affected subjects spanning 3 generations, who had variable degrees of AHO manifestations, with an autosomal dominant inheritance trait. The metacarpophalangeal pattern profile was typical of that of PHP-PPHP. As deficient activity and inactivating mutations of Gs alpha were described in PHP as well as in PPHP, we measured the biological activity of Gs in family members, which was normal. To exclude subtle abnormalities in the Gs alpha gene, we sequenced the entire coding region of Gs alpha in the propositus, which was normal. We conclude that hypocalcemia should be adequately evaluated even in the presence of familial AHO, and that familial AHO can occur with a normal coding structural Gs alpha gene. Identification of the molecular defect in familial AHO without PHP will shed light on the pathogenesis of AHO in general.- - - - - - - - - - ranking = 1keywords = administration (Clic here for more details about this article) |
8/8. hyperthyroidism in McCune-Albright syndrome with a review of thyroid abnormalities sixty years after the first report.We present a patient with hyperthyroidism associated with McCune-Albright syndrome (MAS). MAS is a sporadic genetic disease characterized by polyostotic fibrous dysplasia, cafe au lait cutaneous spots and endocrinopathies (peripheral precocious puberty, thyroidopathies, acromegaly, etc.). It is caused by an activating mutation of the gene for the Gs alpha membrane-associated protein, which mediates the thyrotropin (TSH)-induced and other hormone-induced activation of adenylyl cyclase. A 13-month-old girl was diagnosed with MAS. Precocious puberty was treated initially with testolactone and later with oophorectomy. Subclinical hyperthyroidism was detected biochemically at birth, and 10 months later, it became clinically evident, albeit mild, with absence of goiter. A concomitant liver dysfunction precluded treatment with thionamides and she was sporadically treated with beta-blockers. The combination of increased free thyroxine (T4) and triiodothyronine (T3) with low plasma thyrotropin (TSH) levels in the absence of thyroid-stimulating autoantibodies persisted until the age of 6 years, when she was referred to our unit. hyperthyroidism was then clinically evident with cardiac hyperactivity, and it was cured with administration of radioiodine (131I). Thyroid disease is the second most common endocrinopathy associated with MAS, and since 1936, 63 cases of thyroidopathies have been described, including 19 nodular (14 with and 5 without hyperthyroidism) and 23 diffuse (20 with and 3 without hyperthyroidism) goiters, and 18 cases of hyperthyroidism without goiter. The previously described somatic activating mutation of the gs alpha gene in the ovaries, the liver and the peripheral blood of our patient, in the absence of stigmata, autoimmunity might be incriminated for the secretory and mitotic activation of the thyroid gland. We suggest the treatment of choice of hyperthyroidism in MAS patients should be 131I administration because: (a) hyperthyroidism is very likely to recur after withdrawal of antithyroid medication; (b) the morbidity of these patients is elevated; (c) oophorectomized patients do not need to be advised to avoid procreation during the months after 131I administration; and (d) finally, even in the usual cases of hyperthyroidism in childhood, 131I treatment is becoming more popular worldwide.- - - - - - - - - - ranking = 3keywords = administration (Clic here for more details about this article) |