Laron Syndrome - A Historical Perspective

Overview

Journal Rev Endocr Metab Disord

Publisher Springer

Specialty Endocrinology

Date 2020 Sep 23

PMID 32964395

Citations 24

Authors

Zvi Laron

Haim Werner

Affiliations

Soon will be listed here.

Abstract

Laron Syndrome (LS) [OMIm#262500], or primary GH insensitivity, was first described in 1966 in consanguineous Jewish families from Yemen. LS is characterized by a typical phenotype that includes dwarfism, obesity and hypogenitalism. The disease is caused by deletions or mutations of the GH-receptor gene, causing high serum GH and low IGF-I serum levels. We studied 75 patients from childhood to adult age. After early hypoglycemia due to the progressive obesity, patients tend to develop glucose intolerance and diabetes. The treatment is by recombinant IGF-I, which improves the height and restores some of the metabolic parameters. An unexpected finding was that patients homozygous for GH-R defects are protected from malignancy lifelong, not so heterozygotes or double heterozygote subjects. We estimate that there are at least 500 patients worldwide, unfortunately only few treated.

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References

Laron Z . Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958-2003. J Clin Endocrinol Metab. 2004; 89(3):1031-44. DOI: 10.1210/jc.2003-031033. View

Laron Z, KOWADLO-SILBERGELD A, Eshet R, Pertzelan A . Growth hormone resistance. Ann Clin Res. 1980; 12(5):269-77. View

Glick S, Roth J, Yalow R, Berson S . IMMUNOASSAY OF HUMAN GROWTH HORMONE IN PLASMA. Nature. 1963; 199:784-7. DOI: 10.1038/199784a0. View

Laron Z, Mannheimer S . Measurement of human growth hormone. Description of the method and its clinical applications. Isr J Med Sci. 1966; 2(1):115-9. View

Laron Z, Pertzelan A, Mannheimer S . Genetic pituitary dwarfism with high serum concentation of growth hormone--a new inborn error of metabolism?. Isr J Med Sci. 1966; 2(2):152-5. View

Laron Z, Pertzelan A, Karp M . Pituitary dwarfism with high serum levels of growth hormone. Isr J Med Sci. 1968; 4(4):883-94. View

KERET R, Pertzelan A, Zeharia A, Zadik Z, Laron Z . Growth hormone (hGH) secretion and turnover in three patients with Laron-type dwarfism. Isr J Med Sci. 1988; 24(2):75-9. View

Adam A, Josefsberg Z, Pertzelan A, Zadik Z, Chemke J, Laron Z . Occurrence of four types of growth hormone-related dwarfism in Israeli communities. Eur J Pediatr. 1981; 137(1):35-9. DOI: 10.1007/BF00441167. View

Merimee T, Hall J, Rabinowitz D, MCKUSICK V, Rimoin D . An unusual variety of endocrine dwarfism: subresponsiveness to growth hormone in a sexually mature dwarf. Lancet. 1968; 2(7561):191-3. DOI: 10.1016/s0140-6736(68)92623-8. View

10.

Kastrup K, Andersen H, Hanssen A . Increased immunoreactive plasma and urinary growth hormone in growth retardation with defective generation of somatomedin a (Laron's Syndrome). Acta Paediatr Scand. 1975; 64(4):613-8. DOI: 10.1111/j.1651-2227.1975.tb03891.x. View

11.

Najjar S, KHACHADURIAN A, Ilbawi M, BLIZZARD R . Dwarfism with elevated levels of plasma growth hormone. N Engl J Med. 1971; 284(15):809-12. DOI: 10.1056/NEJM197104152841502. View

12.

Elders M, Garland J, Daughaday W, Fisher D, WHITNEY J, Hughes E . Laron's dwarfism: studies on the nature of the defect. J Pediatr. 1973; 83(2):253-63. DOI: 10.1016/s0022-3476(73)80485-8. View

13.

Eshet R, Laron Z, Brown M, Arnon R . Immunoreactive properties of the plasma hGH from patients with the syndrome of familial dwarfism and high plasma IR-hGH. J Clin Endocrinol Metab. 1973; 37(5):819-21. DOI: 10.1210/jcem-37-5-819. View

14.

Eshet R, Peleg S, Josefsberg Z, Fuchs C, Arnon R, Laron Z . Some properties of the plasma hGH activity in patients with Laron-type dwarfism determined by a radioreceptor assay using human liver tissue. Horm Res. 1985; 22(4):276-83. DOI: 10.1159/000180106. View

15.

RUSSELL R, Parks J, McKean M, Bell G, KERET R, Kelijman M . Laron-type dwarfism is associated with normal growth hormone and insulin-like growth factor I gene restriction patterns. Isr J Med Sci. 1989; 25(6):342-4. View

16.

Laron Z, Pertzelan A, Doron M, Assa S, KERET R . The effect of dihydrosomatostatin in dwarfism with high plasma immunoreactive growth hormone. Horm Metab Res. 1977; 9(4):338-9. DOI: 10.1055/s-0028-1095565. View

17.

Daughaday W, Laron Z, Pertzelan A, Heins J . Defective sulfation factor generation: a possible etiological link in dwarfism. Trans Assoc Am Physicians. 1969; 82:129-40. View

18.

Laron Z, Pertzelan A, Karp M, KOWADLO-SILBERGELD A, Daughaday W . Administration of growth hormone to patients with familial dwarfism with high plasma immunoreactive growth hormone: measurement of sulfation factor, metabolic and linear growth responses. J Clin Endocrinol Metab. 1971; 33(2):332-42. DOI: 10.1210/jcem-33-2-332. View

19.

Eshet R, Laron Z, Pertzelan A, Arnon R, Dintzman M . Defect of human growth hormone receptors in the liver of two patients with Laron-type dwarfism. Isr J Med Sci. 1984; 20(1):8-11. View

20.

Geffner M, Golde D, Lippe B, Kaplan S, Bersch N, Li C . Tissues of the Laron dwarf are sensitive to insulin-like growth factor I but not to growth hormone. J Clin Endocrinol Metab. 1987; 64(5):1042-6. DOI: 10.1210/jcem-64-5-1042. View