[Primary glucocorticoid resistance syndrome presenting as pseudo-precocious puberty and galactorrhea].
METHODS
Primary glucocorticoid resistance syndrome (PGRS) is a rare condition characterized by hypercortisolism without Cushing's syndrome. This report describes a 7-year-old boy of PGRS with pseudo-precocious puberty and galactorrhea as the main manifestation. His height was 135 cm and body weight was 31 kg. Pigmentation could be seen in the skin, mammary areola and penis. He had hirsutism, low hair line, coarse voice, Tanner stage 3 pubic hair, penis in adult form, accelerated linear growth, and advanced bone age (13 yr.), but normal (for age) testes. Furthermore, he had mammoplasia and galactorrhea. There were no features of glucocorticoid (GC) excess.


RESULTS
Hepatic function was impaired (ALT 1426 IU/L, AST 611 IU/L) with no definite causes. Serum cortisol concentration was 1294 nmol/L, 777 nmol/L, 199.3 nmol/L at 8:00, 16:00 and 24:00 respectively. Plasma adrenocorticotropic hormone (ACTH) was normal or a little higher (43.9-80 ng/L). Urinary-free cortisol (UFC) was normal (55.5-62.4 microg/24 h). Serum estradiol (E2), progesterone (P), testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were normal. Serum dehydroepiandrosterone sulfate (DHEAS, 60 microg/dL) and serum prolactin (PRL, 58.7-183.9 ng/mL) level were high, urinary dehydroepiandrosterone (DHEA) level was also elevated (0.96-3.2 mg/mL). Gonadotrophin hormone-releasing hormone (GnRH) stimulation test was negative. Serum cortisol responded normally to insulin-induced hypoglycemia. However, serum cortisol and plasma ACTH concentration was suppressed to more than 50% by 0.5 mg dexamethasone (DEX). The diagnosis of PGRS was made. TREATMENT AND FOLLOW-UP: The patient received a treatment of 0.75-1.0 mg/d DEX. Because of galactorrhea, bromocriptine was given by 1.25-3.75 mg/d. After 24 months follow-up, the pigmentation was relieved and galactorrhea disappeared. No advanced development of the external genitalia and breast was found. The acceleration of the bone age was also slowed down. But he still had obvious hirsutism. No side effect of DEX was found.


CONCLUSIONS
PGRS may present with pseudo-precocious puberty and galactorrhea. The aim of treatment in glucocorticoid resistance is to suppress the excessive secretion of ACTH and the increased production of adrenal androgens. The administration of synthetic GC with minimal intrinsic mineralocorticoid activity, such as DEX, provides a rational treatment for PGRS. Long-term DEX treatment should be individualized and carefully titrated based on the clinical manifestations and biochemical profile in order to control the clinical manifestations of the disease.
Xiang
Shu-lin
SL
Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.
He
Li-ping
LP
Ran
Xing-wu
XW
Tian
Hao-ming
HM
Li
Xiu-jun
XJ
Liang
Jin-zhong
JZ
D002648:Child; D003480:Cushing Syndrome / Q000175:diagnosis*; D003907:Dexamethasone / Q000627:therapeutic use; D003937:Diagnosis, Differential; D004351:Drug Resistance / Q000235:genetics; D005687:Galactorrhea / Q000175:diagnosis* / Q000209:etiology; D006628:Hirsutism / Q000175:diagnosis*; D006801:Humans; D008297:Male; D011629:Puberty, Precocious / Q000175:diagnosis* / Q000209:etiology; D011965:Receptors, Glucocorticoid / Q000235:genetics; D013577:Syndrome
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone