Delayed puberty: Etiology, outcome and interactions with growth

Research output: ThesisDoctoral ThesisCollection of Articles

Abstract

During puberty, adolescents achieve reproductive capability and attain adult height. An intact hypothalamic-pituitary-gonadal (HPG) axis is crucial for the normal onset of puberty. Pubertal timing is influenced by genetic and environmental factors, but the exact mechanisms that trigger puberty remain elusive. A finding of a paternally-inherited loss-of-function mutation in makorin ring finger protein 3 (MKRN3) gene in patients who were diagnosed with central precocious puberty suggests that key genes regulate the central restrain on the HPG axis during childhood, and that the loosening of the restrain precedes the onset of puberty. A variety of diseases can delay puberty, but it is particularly important to early identify the patients who suffer from acquired or congenital hypogonadotropic hypogonadism (CHH) which results from the absent or impaired functions of gonadotropin-releasing hormone. This congenital sex steroid deficiency predisposes to long-term consequences, but very little is known about its role in the modulation of growth during early infancy and its impact on health-related quality of life (HRQoL) in adulthood. In the first study, circulating MKRN3 levels were measured in boys with idiopathic short stature before and after the onset of puberty. In boys, serum levels of MKRN3 declined faster before than after the clinical onset of puberty. In the second study, the diagnoses that underlie delayed puberty (DP) were investigated in a large series of patients with delayed puberty examined at the Helsinki University Central Hospital between 2004 and 2014. A multitude of different diagnoses were found to cause DP, albeit constitutional delay of growth puberty (CDGP) was the most common cause in both sexes. Annual growth velocity, a history of prior cryptorchidism, and a positive family history of DP appeared to be useful in the differential diagnosis of DP. The third study consisted of growth charts of 42 patients with CHH, and evaluated the influence of congenital sex steroid deficiency on growth from birth length to adult height. The boys with CHH experienced a length deflection during the first six months of life (i.e. minipuberty), which was likely to result from deficient testosterone surge during the same period. In the fourth study, the HRQoL was measured in men with CHH with the generic 15D questionnaire. The men with CHH experienced an impaired HRQoL, especially in the dimensions of depression and distress. The age of diagnosis correlated negatively with HRQoL scores, which emphasize the timely diagnosis of CHH. In summary, sex steroids modulate growth from early infancy to adulthood. In boys, circulating MKRN3 levels decline before the clinical onset of puberty which supports the current view that MKRN3 is a key regulator of pubertal onset. Many diseases can delay pubertal maturation, but CDGP is the most common cause in Finland. In men, the timely diagnosis of CHH is crucial to avoid the long-term adverse effects of sex steroid deficiency on HRQoL.
Original languageEnglish
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-2838-6
Electronic ISBNs978-951-51-2839-3
Publication statusPublished - 2016
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • 3123 Gynaecology and paediatrics

Cite this

@phdthesis{a9eec0a12e1a4c17a15f5d0f53ac24df,
title = "Delayed puberty: Etiology, outcome and interactions with growth",
abstract = "During puberty, adolescents achieve reproductive capability and attain adult height. An intact hypothalamic-pituitary-gonadal (HPG) axis is crucial for the normal onset of puberty. Pubertal timing is influenced by genetic and environmental factors, but the exact mechanisms that trigger puberty remain elusive. A finding of a paternally-inherited loss-of-function mutation in makorin ring finger protein 3 (MKRN3) gene in patients who were diagnosed with central precocious puberty suggests that key genes regulate the central restrain on the HPG axis during childhood, and that the loosening of the restrain precedes the onset of puberty. A variety of diseases can delay puberty, but it is particularly important to early identify the patients who suffer from acquired or congenital hypogonadotropic hypogonadism (CHH) which results from the absent or impaired functions of gonadotropin-releasing hormone. This congenital sex steroid deficiency predisposes to long-term consequences, but very little is known about its role in the modulation of growth during early infancy and its impact on health-related quality of life (HRQoL) in adulthood. In the first study, circulating MKRN3 levels were measured in boys with idiopathic short stature before and after the onset of puberty. In boys, serum levels of MKRN3 declined faster before than after the clinical onset of puberty. In the second study, the diagnoses that underlie delayed puberty (DP) were investigated in a large series of patients with delayed puberty examined at the Helsinki University Central Hospital between 2004 and 2014. A multitude of different diagnoses were found to cause DP, albeit constitutional delay of growth puberty (CDGP) was the most common cause in both sexes. Annual growth velocity, a history of prior cryptorchidism, and a positive family history of DP appeared to be useful in the differential diagnosis of DP. The third study consisted of growth charts of 42 patients with CHH, and evaluated the influence of congenital sex steroid deficiency on growth from birth length to adult height. The boys with CHH experienced a length deflection during the first six months of life (i.e. minipuberty), which was likely to result from deficient testosterone surge during the same period. In the fourth study, the HRQoL was measured in men with CHH with the generic 15D questionnaire. The men with CHH experienced an impaired HRQoL, especially in the dimensions of depression and distress. The age of diagnosis correlated negatively with HRQoL scores, which emphasize the timely diagnosis of CHH. In summary, sex steroids modulate growth from early infancy to adulthood. In boys, circulating MKRN3 levels decline before the clinical onset of puberty which supports the current view that MKRN3 is a key regulator of pubertal onset. Many diseases can delay pubertal maturation, but CDGP is the most common cause in Finland. In men, the timely diagnosis of CHH is crucial to avoid the long-term adverse effects of sex steroid deficiency on HRQoL.",
keywords = "Adolescent, Child, Child, preschool, Cryptorchidism, Growth, Growth Disorders, +drug therapy, Health Status, Hormone Replacement Therapy, Hypogonadism, +congenital, +diagnosis, +psychology, Hypothalamo-Hypophyseal System, Infant, Inhibins, Kallmann Syndrome, Puberty, Puberty, Delayed, +etiology, Quality of Life, Ribonucleoproteins, Treatment Outcome, 3123 Gynaecology and paediatrics",
author = "Tero Varimo",
note = "M1 - 111 s. Volume: Proceeding volume:",
year = "2016",
language = "English",
isbn = "978-951-51-2838-6",
publisher = "[T. Varimo]",
address = "Finland",

}

Delayed puberty : Etiology, outcome and interactions with growth. / Varimo, Tero.

Helsinki : [T. Varimo], 2016.

Research output: ThesisDoctoral ThesisCollection of Articles

TY - THES

T1 - Delayed puberty

T2 - Etiology, outcome and interactions with growth

AU - Varimo, Tero

N1 - M1 - 111 s. Volume: Proceeding volume:

PY - 2016

Y1 - 2016

N2 - During puberty, adolescents achieve reproductive capability and attain adult height. An intact hypothalamic-pituitary-gonadal (HPG) axis is crucial for the normal onset of puberty. Pubertal timing is influenced by genetic and environmental factors, but the exact mechanisms that trigger puberty remain elusive. A finding of a paternally-inherited loss-of-function mutation in makorin ring finger protein 3 (MKRN3) gene in patients who were diagnosed with central precocious puberty suggests that key genes regulate the central restrain on the HPG axis during childhood, and that the loosening of the restrain precedes the onset of puberty. A variety of diseases can delay puberty, but it is particularly important to early identify the patients who suffer from acquired or congenital hypogonadotropic hypogonadism (CHH) which results from the absent or impaired functions of gonadotropin-releasing hormone. This congenital sex steroid deficiency predisposes to long-term consequences, but very little is known about its role in the modulation of growth during early infancy and its impact on health-related quality of life (HRQoL) in adulthood. In the first study, circulating MKRN3 levels were measured in boys with idiopathic short stature before and after the onset of puberty. In boys, serum levels of MKRN3 declined faster before than after the clinical onset of puberty. In the second study, the diagnoses that underlie delayed puberty (DP) were investigated in a large series of patients with delayed puberty examined at the Helsinki University Central Hospital between 2004 and 2014. A multitude of different diagnoses were found to cause DP, albeit constitutional delay of growth puberty (CDGP) was the most common cause in both sexes. Annual growth velocity, a history of prior cryptorchidism, and a positive family history of DP appeared to be useful in the differential diagnosis of DP. The third study consisted of growth charts of 42 patients with CHH, and evaluated the influence of congenital sex steroid deficiency on growth from birth length to adult height. The boys with CHH experienced a length deflection during the first six months of life (i.e. minipuberty), which was likely to result from deficient testosterone surge during the same period. In the fourth study, the HRQoL was measured in men with CHH with the generic 15D questionnaire. The men with CHH experienced an impaired HRQoL, especially in the dimensions of depression and distress. The age of diagnosis correlated negatively with HRQoL scores, which emphasize the timely diagnosis of CHH. In summary, sex steroids modulate growth from early infancy to adulthood. In boys, circulating MKRN3 levels decline before the clinical onset of puberty which supports the current view that MKRN3 is a key regulator of pubertal onset. Many diseases can delay pubertal maturation, but CDGP is the most common cause in Finland. In men, the timely diagnosis of CHH is crucial to avoid the long-term adverse effects of sex steroid deficiency on HRQoL.

AB - During puberty, adolescents achieve reproductive capability and attain adult height. An intact hypothalamic-pituitary-gonadal (HPG) axis is crucial for the normal onset of puberty. Pubertal timing is influenced by genetic and environmental factors, but the exact mechanisms that trigger puberty remain elusive. A finding of a paternally-inherited loss-of-function mutation in makorin ring finger protein 3 (MKRN3) gene in patients who were diagnosed with central precocious puberty suggests that key genes regulate the central restrain on the HPG axis during childhood, and that the loosening of the restrain precedes the onset of puberty. A variety of diseases can delay puberty, but it is particularly important to early identify the patients who suffer from acquired or congenital hypogonadotropic hypogonadism (CHH) which results from the absent or impaired functions of gonadotropin-releasing hormone. This congenital sex steroid deficiency predisposes to long-term consequences, but very little is known about its role in the modulation of growth during early infancy and its impact on health-related quality of life (HRQoL) in adulthood. In the first study, circulating MKRN3 levels were measured in boys with idiopathic short stature before and after the onset of puberty. In boys, serum levels of MKRN3 declined faster before than after the clinical onset of puberty. In the second study, the diagnoses that underlie delayed puberty (DP) were investigated in a large series of patients with delayed puberty examined at the Helsinki University Central Hospital between 2004 and 2014. A multitude of different diagnoses were found to cause DP, albeit constitutional delay of growth puberty (CDGP) was the most common cause in both sexes. Annual growth velocity, a history of prior cryptorchidism, and a positive family history of DP appeared to be useful in the differential diagnosis of DP. The third study consisted of growth charts of 42 patients with CHH, and evaluated the influence of congenital sex steroid deficiency on growth from birth length to adult height. The boys with CHH experienced a length deflection during the first six months of life (i.e. minipuberty), which was likely to result from deficient testosterone surge during the same period. In the fourth study, the HRQoL was measured in men with CHH with the generic 15D questionnaire. The men with CHH experienced an impaired HRQoL, especially in the dimensions of depression and distress. The age of diagnosis correlated negatively with HRQoL scores, which emphasize the timely diagnosis of CHH. In summary, sex steroids modulate growth from early infancy to adulthood. In boys, circulating MKRN3 levels decline before the clinical onset of puberty which supports the current view that MKRN3 is a key regulator of pubertal onset. Many diseases can delay pubertal maturation, but CDGP is the most common cause in Finland. In men, the timely diagnosis of CHH is crucial to avoid the long-term adverse effects of sex steroid deficiency on HRQoL.

KW - Adolescent

KW - Child

KW - Child, preschool

KW - Cryptorchidism

KW - Growth

KW - Growth Disorders

KW - +drug therapy

KW - Health Status

KW - Hormone Replacement Therapy

KW - Hypogonadism

KW - +congenital

KW - +diagnosis

KW - +psychology

KW - Hypothalamo-Hypophyseal System

KW - Infant

KW - Inhibins

KW - Kallmann Syndrome

KW - Puberty

KW - Puberty, Delayed

KW - +etiology

KW - Quality of Life

KW - Ribonucleoproteins

KW - Treatment Outcome

KW - 3123 Gynaecology and paediatrics

M3 - Doctoral Thesis

SN - 978-951-51-2838-6

PB - [T. Varimo]

CY - Helsinki

ER -