title: Clinical characteristics, etiologies and pathophysiology of patients with severe short stature with severe GH deficiency: questionnaire study on the data registered with the foundation for growth science, Japan.
abstract: In this study, we sent questionnaires to doctors treating severe short stature with severe GH deficiency (GHD) (height SDS (HtSDS) below -4 and all peak GH to provocative stimuli below 2 micro/L) (abbreviated as Severe Case), and obtained effective replies of 51 cases. The clinical characteristics, etiologies, and pathophysiology of these patients were examined. Among the 51 Severe Cases no consanguinity was observed, 44 were IGHD (24 males and 20 females), 3 were GH-1 gene deletion, 2 were Pit-1 gene mutation, and 2 were achondroplasia. HtSDS in these Severe Cases was already remarkably low at 12 (-3.0) and 24 months old (-3.9), while their birth weight and birth length were within normal ranges. Among 44 patients with IGHD, 12 were isolated GHD, and the remaining 32 were combined pituitary hormone deficiency (CPHD). Pituitary MRI was undergone in 25 idiopathic GHD, and abnormal findings (pituitary atrophy, interruption of stalk, and ectopic posterior lobe) were observed in 21 patients with CPHD. More than half of these patients had the history of breech delivery. Three patients with GH-1 gene mutation showed normal pituitary MRI, whereas one of two patients with Pit-1 mutation showed pituitary atrophy and narrowing of pituitary stalk. In conclusion, Severe Cases tended to have CPHD, and the incidence of Severe Case was only 0.6% of total IGHD. Although GHD due to genetic disorders is considered to be extremely rare (0.06% of total IGHD), the incidence reaches high levels (9.8%) among Severe Cases. Growth disorders in these Severe Cases seem to occur soon after delivery. Much earlier diagnosis and hGH treatment are desirable to attain better final height in the Severe Cases. GH-1 and Pit-1 gene analyses are crucial, when genetic abnormalities other than achondroplasia are suspected.
authors.affiliation: Hanew Endocrine Clinic, Sendai, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Hanew
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Tachibana
authors.forename: Susumu
authors.initials: S
authors.lastname: Yokoya
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujieda
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Akira
authors.initials: A
authors.lastname: Shimatsu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Takakuni
authors.initials: T
authors.lastname: Tanizawa
authors.forename: Akira
authors.initials: A
authors.lastname: Teramoto
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nishi
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Hizuka
authors.forename: Takeki
authors.initials: T
authors.lastname: Hirano
authors.forename: Keinosuke
authors.initials: K
authors.lastname: Fujita
mesh_terms: D000130:Achondroplasia / Q000175:diagnosis; D000367:Age Factors; D001827:Body Height; D002648:Child; D003241:Consanguinity; D004393:Dwarfism, Pituitary / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000235:genetics; D020249:Hormone Replacement Therapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010902:Pituitary Gland / Q000002:abnormalities / Q000000981:diagnostic imaging; D010907:Pituitary Hormones / Q000172:deficiency; D011859:Radiography; D011795:Surveys and Questionnaires; D050817:Transcription Factor Pit-1 / Q000235:genetics
chemical_list: D010907:Pituitary Hormones; D050817:Transcription Factor Pit-1; D013006:Growth Hormone