Familial Gynecomastia with Increased Extraglandular Aromatization of Plasma Carbon19-steroids

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1985 Jun 1

PMID 3924954

Citations 11

Authors

G D Berkovitz

A Guerami

T R Brown

P C MACDONALD

C J Migeon

Affiliations

Soon will be listed here.

Abstract

We evaluated a family in which gynecomastia occurred in five males in two generations. In each affected subject, gynecomastia and male sexual maturation began at an early age. The ratio of the concentration of plasma estradiol-17 beta to that of plasma testosterone was elevated in each affected subject. In the three siblings with gynecomastia, the transfer constant of conversion of androstenedione to estrone (i.e., the fraction of plasma androstenedione that was converted to estrone as measured in the urine) was 10 times that of normal persons. The transfer constant of conversion of testosterone to estradiol-17 beta in the one subject studied also was 8-10 times that of normal men, whereas the transfer constants of conversion of estrone to estradiol-17 beta and of estradiol-17 beta to estrone were normal. Despite the elevation in extraglandular aromatase activity, there was a normal response of the hypothalamic-pituitary axis to provocative stimuli. This is the second documentation of gynecomastia that is associated with increased extraglandular aromatase activity, and the first time that the defect was found to be familial with a probable X-linked (or autosomal dominant, sex limited) mode of inheritance.

Citing Articles

The effect of androstenedione supplementation on testosterone, estradiol, body composition, and lipid profile: a systematic review and meta-analysis of randomized controlled trials.

Pang Q, Jia A, Al Masri M, Kord Varkaneh H, Abu-Zaid A, Gao X Hormones (Athens). 2022; 21(4):545-554.

PMID: 35841524 DOI: 10.1007/s42000-022-00385-8.

Prepubertal unilateral gynecomastia in the absence of endocrine abnormalities.

Kang M, Lee C, Hwang I, Lee K, Kang M Ann Pediatr Endocrinol Metab. 2014; 19(3):159-63.

PMID: 25346921 PMC: 4208259. DOI: 10.6065/apem.2014.19.3.159.

Understanding the pathological manifestations of aromatase excess syndrome: lessons for clinical diagnosis.

Shozu M, Fukami M, Ogata T Expert Rev Endocrinol Metab. 2014; 9(4):397-409.

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Aromatase excess syndrome presenting with prepubertal gynecomastia in an Egyptian child with type 1 neurofibromatosis.

Metwalley K, Farghaly H Indian J Hum Genet. 2014; 19(4):472-4.

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An aroma of complexity: how the unique genetics of aromatase (CYP19A1) explain diverse phenotypes from hens and hyenas to human gynecomastia, and testicular and other tumors.

Stratakis C J Clin Endocrinol Metab. 2013; 98(12):4676-81.

PMID: 24311795 PMC: 3849672. DOI: 10.1210/jc.2013-3990.

References

Odell W, ROSS G, Rayford P . Radioimmunoassay for human luteinizing hormone. Metabolism. 1966; 15(4):287-9. DOI: 10.1016/0026-0495(66)90142-9. View

Longcope C, Sato K, Mckay C, Horton R . Aromatization by splanchnic tissue in men. J Clin Endocrinol Metab. 1984; 58(6):1089-93. DOI: 10.1210/jcem-58-6-1089. View

Foley Jr T, Jacobs L, Hoffman W, Daughaday W, BLIZZARD R . Human prolactin and thyrotropin concentrations in the serums of normal and hypopituitary children before and after the administration of synthetic thyrotropin-releasing hormone. J Clin Invest. 1972; 51(8):2143-50. PMC: 292371. DOI: 10.1172/JCI107021. View

Weinstein R, Kelch R, Jenner M, Kaplan S, Grumbach M . Secretion of unconjugated androgens and estrogens by the normal and abnormal human testis before and after human chorionic gonadotropin. J Clin Invest. 1974; 53(1):1-6. PMC: 301431. DOI: 10.1172/JCI107526. View

Judd H, Parker D, Siler T, Yen S . The nocturnal rise of plasma testosterone in pubertal boys. J Clin Endocrinol Metab. 1974; 38(4):710-3. DOI: 10.1210/jcem-38-4-710. View

Lee P . The relationship of concentrations of serum hormones to pubertal gynecomastia. J Pediatr. 1975; 86(2):212-5. DOI: 10.1016/s0022-3476(75)80470-7. View

Parker D, Judd H, Rossman L, Yen S . Pubertal sleep-wake patterns of episodic LH, FSH and testosterone release in twin boys. J Clin Endocrinol Metab. 1975; 40(6):1099-109. DOI: 10.1210/jcem-40-6-1099. View

Reiter E, Root A, DUCKETT G . The response of pituitary gonadotropes to a constant infusion of luteinizing hormone-releasing hormone (LHRH) in normal prepubertal and pubertal children and in children with abnormalities of sexual development. J Clin Endocrinol Metab. 1976; 43(2):400-11. DOI: 10.1210/jcem-43-2-400. View

Gutai J, Meyer 3rd W, Kowarski A, Migeon C . Twenty-four hour integrated concentrations of progesterone, 17-hydroxyprogesterone and cortisol in normal male subjects. J Clin Endocrinol Metab. 1977; 44(1):116-20. DOI: 10.1210/jcem-44-1-116. View

10.

Hemsell D, Edman C, MARKS J, Siiteri P, MACDONALD P . Massive extranglandular aromatization of plasma androstenedione resulting in feminization of a prepubertal boy. J Clin Invest. 1977; 60(2):455-64. PMC: 372388. DOI: 10.1172/JCI108796. View

11.

Forest M, Lecoq A, Saez J . Kinetics of human chorionic gonadotropin-induced steroidogenic response of the human testis. II. Plasma 17 alpha-hydroxyprogesterone, delta4-androstenedione, estrone, and 17 beta-estradiol: evidence for the action of human chorionic gonadotropin on.... J Clin Endocrinol Metab. 1979; 49(2):284-91. DOI: 10.1210/jcem-49-2-284. View

12.

MACDONALD P, Madden J, Brenner P, Wilson J, Siiteri P . Origin of estrogen in normal men and in women with testicular feminization. J Clin Endocrinol Metab. 1979; 49(6):905-16. DOI: 10.1210/jcem-49-6-905. View

13.

Marynick S, Nisula B, Pita Jr J, Loriaux D . Persistent pubertal macromastia. J Clin Endocrinol Metab. 1980; 50(1):128-30. DOI: 10.1210/jcem-50-1-128. View

14.

Large D, Anderson D . Twenty-four hour profiles of circulating androgens and oestrogens in male puberty with and without gynaecomastia. Clin Endocrinol (Oxf). 1979; 11(5):505-21. DOI: 10.1111/j.1365-2265.1979.tb03103.x. View

15.

Wilson J, Aiman J, MACDONALD P . The pathogenesis of gynecomastia. Adv Intern Med. 1980; 25:1-32. View

16.

Smith D, Picker R, Sinosich M, Saunders D . Assessment of ovulation by ultrasound and estradiol levels during spontaneous and induced cycles. Fertil Steril. 1980; 33(4):387-90. View

17.

George F, Wilson J . pathogenesis of the henny feathering trait in the Sebright bantam chicken. Increased conversion of androgen to estrogen in skin. J Clin Invest. 1980; 66(1):57-65. PMC: 371505. DOI: 10.1172/JCI109835. View

18.

Carlson H . Gynecomastia. N Engl J Med. 1980; 303(14):795-9. DOI: 10.1056/NEJM198010023031405. View

19.

Catt K, Harwood J, Clayton R, Davies T, Chan V, Katikineni M . Regulation of peptide hormone receptors and gonadal steroidogenesis. Recent Prog Horm Res. 1980; 36:557-662. DOI: 10.1016/b978-0-12-571136-4.50021-8. View

20.

Spitz I, Hirsch H, Trestian S . The prolactin response to thyrotropin-releasing hormone differentiates isolated gonadotropin deficiency from delayed puberty. N Engl J Med. 1983; 308(10):575-9. DOI: 10.1056/NEJM198303103081007. View