Editing Delayed puberty (section)

==Diagnosis==
[[Pediatric endocrinology|Pediatric endocrinologists]] are the physicians with the most training and experience in evaluating delayed puberty. A complete medical history, review of systems, growth pattern, and physical examination, as well as laboratory testing and imaging, will reveal most of the systemic diseases and conditions capable of arresting development or delaying puberty, as well as providing clues to some of the recognizable [[syndrome]]s affecting the reproductive system.<ref name=":0" />

Timely medical assessment is a necessity since as many as half of girls with delayed puberty have an underlying pathology.<ref name=":4">{{Cite book|title=Practical pediatric and adolescent gynecology|last=Adams |first= Paula J. Hillard | name-list-style = vanc |date=2013|publisher=Wiley-Blackwell|isbn=9781118538586|oclc=929718561}}</ref>

=== History and physical ===

==== Constitutional and physiologic delay ====
Children with constitutional delay are reported to be shorter than their peers, lacking a [[growth spurt]], and having an overall smaller build.<ref name=":8" /> Their growth has begun to slow down years before the expected growth spurt secondary to puberty, which helps differentiate a constitutional delay from an HPG-axis related disorder.<ref name=":7" /> A complete family history with the ages at which parents hit the pubertal milestones can also provide a reference point for the expected age of puberty.<ref name=":11" /><ref name=":0" /> Growth measurement parameters in children with suspected constitutional delay include a height, a weight, the rate of growth, and the calculated mid-parental height which represents the expected adult height for the child.<ref name=":1" /><ref name=":11" />

==== Malnutrition or chronic disease ====
Diet and physical activity habits, as well as history of previous serious illnesses and medication history can provide clues as to the cause of delayed puberty.<ref name=":0" /> Delayed growth and puberty can be the first signs of severe chronic illnesses such as metabolic disorders including [[inflammatory bowel disease]] and [[hypothyroidism]].<ref name=":0" /> Symptoms such as fatigue, pain, and abnormal stooling pattern are suggestive of an underlying chronic condition.<ref name=":11" /> Low [[Body mass index|BMI]] can lead a physician to diagnose an eating disorder, [[undernutrition]], child abuse, or chronic gastrointestinal disorders.<ref name=":11" />

==== Primary failure of the ovaries or testes ====
A [[eunuchoid]] body shape where the arm span exceeds the height by more than 5&nbsp;cm suggests a delay in growth plate closure secondary to [[hypogonadism]].<ref name=":0" /> [[Turner syndrome]] has unique diagnostic features including a webbed neck, short stature, shield chest, and low hairline.<ref name=":11" /> [[Klinefelter syndrome]] presents with tall stature as well as small, firm testes.<ref name=":11" />

==== Genetic or acquired defect of the hormonal pathway of puberty ====
Lacking the sense of smell ([[anosmia]]) along with delayed puberty are strong clinical indications for [[Kallmann syndrome]].<ref name=":7" /><ref>Oxford Endocrinology Library. Testosterone Deficiency in Men. 2008. {{ISBN|978-0199545131}} Editor: Hugh Jones. Chapter 9. Puberty & Fertility.</ref><ref name=":14">Male Hypogonadism. Friedrich Jockenhovel. Uni-Med Science. 2004. {{ISBN|3-89599-748-X}}. Chapter 3. Diagnostic work up of hypogonadism.</ref> Deficiencies in GnRH, the signalling hormone produced by the hypothalamus, can cause congenital malformations including cleft lip and scoliosis.<ref name=":0" /> The presence of neurological symptoms including headaches and visual disturbances suggest a brain disorder such as a brain tumor causing [[hypopituitarism]].<ref name=":0" /> The presence of neurological symptoms in addition to [[lactation]] are signs of high prolactin levels and could indicate either a drug side effect or a [[prolactinoma]].<ref name=":11" />

=== Imaging ===
[[File:X-ray of hand, where bone age is automatically found by BoneXpert software.jpg|thumb|Determination of bone age allows for comparison with chronological age and assessment of future growth potential.]]
Since bone maturation is a good indicator of overall physical maturation, an [[X-ray]] of the left hand and wrist to assess [[bone age]] usually reveals whether the child has reached a stage of physical maturation at which puberty should be occurring.<ref name=":1" /><ref name=":0" /> X-ray displaying a bone age <11 years in girls or <13 years in boys (despite a higher chronological age) is most often consistent with constitutional delay of puberty.<ref name=":0" /><ref name=":9" /> An MRI of the brain should be considered if neurological symptoms are present in addition to delayed puberty, two findings suspicious for pituitary or hypothalamic tumors.<ref name=":1" /><ref name=":7" /> An MRI can also confirm the diagnosis of [[Kallmann syndrome]] due to the absence or abnormal development of the olfactory tract.<ref name=":7" /> However, in the absence of clear neurological symptoms, an MRI may not be the most cost-effective option.<ref name=":7" /> A pelvic ultrasound can detect anatomical abnormalities including undescended testes and [[Müllerian agenesis]].<ref name=":1" /><ref name=":5" />

=== Laboratory evaluation ===
[[File:Delayed Puberty.png|alt=|thumb|Workup for delayed puberty]]
The first step in evaluating children with delayed puberty involves differentiating between the different causes of delayed puberty. Constitutional delay can be evaluated with a thorough history, physical, and bone age.<ref name=":11" /> Malnutrition and chronic diseases can be diagnosed through history and disease-specific testing.<ref name=":1" /> Screening studies include a complete blood count, an [[erythrocyte sedimentation rate]], and thyroid studies.<ref name=":1" /> [[Hypogonadism]] can be differentiated between hyper- and hypo-gonadotropic hypogonadism by measuring serum [[follicle-stimulating hormone]] (FSH) and [[luteinizing hormone]] (LH) ([[gonadotropin]]s to measure pituitary output), and estradiol in girls (to measure gonadal output).<ref name=":0" /><ref name=":5" /> By the age of 10–12, children with failure of the ovaries or testes will have high LH and FSH because the brain is attempting to jump-start puberty, but the gonads are not responsive to these signals.<ref name=":0" /><ref name=":1" />

Stimulating the body by administering an artificial version of [[gonadotropin-releasing hormone]] (GnRH, the hypothalamic hormone) can differentiate between constitutional delay of puberty and a GnRH deficiency in boys, although no studies have been done in girls to prove this.<ref name=":0" /><ref>{{cite journal | vauthors = Jungmann E, Trautermann C | title = [The status of the gonadotropin releasing hormone test in differential diagnosis of delayed puberty in adolescents over 14 years of age] | language = de | journal = Medizinische Klinik | volume = 89 | issue = 10 | pages = 529–33 | date = October 1994 | pmid = 7808353 }}</ref> It is often sufficient to simply measure the baseline gonadotrophin levels to differentiate between the two.<ref name=":7" />

In girls with [[hypogonadotropic hypogonadism]], a serum [[prolactin]] level is measured to identify if they have the pituitary tumor [[prolactinoma]]. High levels of prolactin would warrant further testing with MRI imaging, except if drugs inducing the production of prolactin can be identified.<ref name=":0" /> If the child has any neurological symptoms, it is highly recommended that the physician obtains a head MRI to detect possible brain lesions.<ref name=":0" />

In girls with [[hypergonadotropic hypogonadism]], a [[karyotype]] can identify chromosomal abnormalities, the most common of which is [[Turner syndrome]].<ref name=":0" /> In boys, a karyotype is indicated if the child may have a congenital gonadal defect such as [[Klinefelter syndrome]].<ref name=":1" /> In children with a normal karyotype, defects in the synthesis of the [[Adrenal gland|adrenal]] steroid sex hormones can be identified by measuring [[17-hydroxylase]], an important enzyme involved in the production of sex hormones.<ref name=":0" />