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M Danon

Publications and source records attributed to M Danon.

24 records · Page 2Linked to original sources
PubMed1975

Cushing syndrome, sexual precocity, and polyostotic fibrous dysplasia (Albright syndrome) in infancy.

The sexual precocity of polyostotic fibrous dysplasia is occasionally accompanied by other endocrine disorders, but in only two previous instances has Cushing syndrome been reported. The history of a 6-month-old girl is presented, in whom this syndrome was complicated by congenital Cushings syndrome. Although endocrinopathies of polyostotic fibrous dysplasia have usually been ascribed to a central (hypothalamic) origin, the findings in this patient suggest autonomous hyperfunction of the peripheral endocrine glands, with the Cushing syndrome caused by hyperplastic nodules in the adrenal glands and the precocity by luteinized follicular cysts of the ovary.

Adrenal Glands↗
PubMed1973

Partial target organ resistance to thyroid hormone.

An 8-year old boy with a small goiter, normal basal metabolic rate (BMR), and elevated serum thyroid hormone levels (thyroxine [T(4)] 19.5 mug per 100 ml, free T(4) 4 ng per 100 ml, triiodothyronine [T(3)] 505 ng per 100 ml) was studied. He had measurable serum thyroid-stimulating hormone (TSH) levels (average 5.5 muU per ml), and the thyroxine-binding proteins, hearing, and epiphyseal structures were normal. There was no parental consanguinity nor were there thyroid abnormalities either in the parents or six siblings.Methimazole, 50 mg daily, depressed thyroxine synthesis (T(4) 10.5, free T(4) 2.5) and caused a rise in TSH to 11 muU per ml. After discontinuation of treatment, TSH declined to 4.2 muU per ml and chemical hyperthyroidism returned (T(4) 21.0 mug per 100 ml, free T(4) 4.2, and total T(3) 475 ng per 100 ml, radioactive iodine [RAI] uptake 68%), but studies of BMR and insensible water loss showed the patient to be clinically euthyroid. Thyrotropin-releasing hormone (TRH), 200 mug i.v., caused a brisk rise in TSH to 28 muU per ml, with T(4) rising to 28 mug per 100 ml, free T(4) to 5.6, and T(3) to 730 ng per 100 ml, thus indicating that the pituitary-thyroid system was intact and that the patient's TSH was biologically active. The unusual sensitivity of the pituitary cells to TRH in spite of the markedly elevated serum thyroid hormone levels also suggested that the pituitary was insensitive to suppression by T(3) or T(4). Serum dilution studies gave immunochemical evidence that this patient's TSH was normal. Neither propranolol, 60 mg, chlorpromazine, 30 mg, nor prednisone, 15 mg daily, influenced thyroid indices. Steroid treatment, however, suppressed the pituitary response to TRH, T(3) in doses increased over a period of 12 days to as much as 150 mug daily caused a rise in serum T(3) to above 800 ng per 100 ml, a decline of T(4) to euthyroid levels (T(4) 9.5 mug per 100 ml, free T(4) 1.6 ng per 100 ml), suppression of the RAI uptake from 68% to 35%, and marked blunting of the responses to TRH, but the BMR and insensible water loss remained normal. The data suggest that the patient's disorder is due to partial resistance to thyroid hormone.

Child↗
PubMedDate not supplied

Enzyme replacement therapy in the mouse model of Pompe disease.

Deficiency of acid alpha-glucosidase (GAA) results in widespread cellular deposition of lysosomal glycogen manifesting as myopathy and cardiomyopathy. When GAA-/- mice were treated with rhGAA (20 mg/kg/week for up to 5 months), skeletal muscle cells took up little enzyme compared to liver and heart. Glycogen reduction was less than 50%, and some fibers showed little or no glycogen clearance. A dose of 100 mg/kg/week resulted in approximately 75% glycogen clearance in skeletal muscle. The enzyme reduced cardiac glycogen to undetectable levels at either dose. Skeletal muscle fibers with residual glycogen showed immunoreactivity for LAMP-1/LAMP-2, indicating that undigested glycogen remained in proliferating lysosomes. Glycogen clearance was more pronounced in type 1 fibers, and histochemical analysis suggested an increased mannose-6-phosphate receptor immunoreactivity in these fibers. Differential transport of enzyme into lysosomes may explain the strikingly uneven pattern of glycogen removal. Autophagic vacuoles, a feature of both the mouse model and the human disease, persisted despite glycogen clearance. In some groups a modest glycogen reduction was accompanied by improved muscle strength. These studies suggest that enzyme replacement therapy, although at much higher doses than in other lysosomal diseases, has the potential to reverse cardiac pathology and to reduce the glycogen level in skeletal muscle.

Animals↗