a gnrh deficiency in boys, although no studies have been done in girls to prove this. it is often sufficient to simply measure the baseline gonadotrophin levels to differentiate between the two. 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. if the child has any neurological symptoms, it is highly recommended that the physician obtains a head mri to detect possible brain lesions. in girls with hypergonadotropic hypogonadism, a karyotype can identify chromosomal abnormalities, the most common of which is turner syndrome. in boys, a karyotype is indicated if the child may have a congenital gonadal defect such as klinefelter syndrome. in children with a normal karyotype, defects in the synthesis of the adrenal steroid sex hormones can be identified by measuring 17-hydroxylase, an important enzyme involved in the production of sex hormones. management the goals of short-term hormone therapy are to induce the beginning of sexual development and induce a growth spurt, but should be limited to children with severe distress or anxiety secondary to their delayed puberty. bone age must be monitored frequently to prevent precocious closure of the bone plates, thereby stunting growth. constitutional and physiologic delay if a child is healthy with a constitutional delay of growth and puberty, reassurance and prediction based on the bone age can be provided. no other intervention is usually necessary, but repeat evaluation by measuring serum testosterone or estrogen is recommended. furthermore, the diagnosis of hypogonadism can be excluded once the adolescent has started puberty by age 16–18. boys aged >14 years old whose growth is severely stunted or are experiencing severe distress secondary to their lack of puberty can be started on testosterone to increase their height. testosterone treatment can also be used to stimulate sexual development, but it can close bone plates prematurely stopping growth altogether if not carefully administered. another therapeutic option is the use of aromatase inhibitors to inhibit the conversion of androgens to estrogens as estrogens are responsible for stopping bone growth plate development and thus growth. however, due to side effects, therapy with testosterone alone is most often used. overall, neither growth hormone nor aromatase inhibitors are recommended for constitutional delay to increase growth. girls can be started on estrogen with the same goals as their male counterparts. overall, studies have shown no significant difference in final adult height between adolescents treated with sex steroids and those who were only observed with no treatment. malnutrition or chronic disease if the delay is due to systemic disease or malnutrition, the therapeutic intervention is likely to focus direction on those conditions. in patients with coeliac disease, an early diagnosis and the establishment of a gluten-free diet prevents long-term complications and allows restoration of normal maturation. thyroid hormone therapy will be necessary in the case of hypothyroidism. primary failure of the ovaries or testes (hypergonadotropic hypogonadism) whereas children with constitutional delay will have normal levels of sex hormones post-puberty, gonadotropin deficiency or hypogonadism may require lifelong sex steroid replacement. in girls with primary ovarian failure, estrogen should be started when puberty is supposed to start. progestins are usually added after there is acceptable breast development, about 12 to 24 months after starting estrogen, as starting treatment with progestin too early can negatively affect breast growth. after acceptable breast growth, administering estrogen and progestin in a cyclical manner can help establish regular menses once puberty is started. the goal is to complete sexual maturation over 2 to 3 years. once sexual maturation has been achieved, a trial period with no hormonal therapy can determine whether or not the child will require life-long treatment. girls with congenital gnrh deficiency require enough sex hormone supplementation to maintain body levels in the expected pubertal levels necessary to induce ovulation, especially when fertility is a concern. males with primary failure of the testes will be on lifelong testosterone. pulsatile gnrh, weekly multi-lh, or hcg and fsh can be used to induce fertility in adulthood for both males and females. genetic or acquired defect of the hormonal pathway of puberty (hypogonadotropic hypogonadism) boys aged >12 years old with hypogonadotropic hypogonadism are most often treated with short-term testosterone while males with testicular failure will be on life-long testosterone. choice of formulation (topical vs injection) is dependent on the child's and family's preference as well as on how well they tolerate side effects. although testosterone therapy alone will result in the start of puberty, to increase fertility potential, they may need pulsatile gnrh or hcg with rfsh. hcg can be used by itself in boys with spontaneous onset of puberty from non-permanent forms of hypogonadotropic hypogonadism and rfsh can be added in cases of low sperm count after 6 to 12 months of treatment. if puberty has not started after 1 year of treatment, then permanent hypogonadotropic hypogonadism should be considered. girls with hypogonadotropic hypogonadism are started on the same sex steroid therapy as their counterparts with a constitutional delay, however doses are gradually increased to reach full adult replacement levels. dosage of estrogen is titrated based on the woman's ability to have withdrawal bleeds and to maintain appropriate bone density. induction of fertility must also be done through pulsatile gnrh. others growth hormone is another option that has been described, however it should only be used in proven growth hormone deficiency such as idiopathic short stature. children with a constitutional delay have not been shown to benefit from growth hormone therapy. although serum growth hormone levels are low in constitutional delay of puberty, they increase after treatment with sex hormones and in those cases, growth hormone is not suggested to accelerate growth. subnormal vitamin a intake is one of the etiological factors in delayed pubertal maturation. supplementation of both vitamin a and iron to normal constitutionally delayed children with subnormal vitamin a intake is as efficacious as hormonal therapy in the induction of growth and puberty. more therapies are being developed to target the more discreet modulators of the hpg axis including kisspeptin and neurokinin b. in cases of severe delayed puberty secondary to hypogonadism, evaluation by a psychologist or psychiatrist, as well as counseling and a supportive environment are an important supplemental therapy for the child. transition from pediatric to adult care is also vital as many children are lost during transition of care. outlook constitutional delay of growth and puberty is a variation of normal development with no long-term health consequences, however it can have lasting psychological effects. adolescent boys with delayed puberty have a higher level of anxiety and depression relative to their peers. children with delayed puberty also display decreased academic performance in their adolescent education, but changes in academic achievement in adulthood have not been determined. there is conflicting evidence as to whether or not children with constitutional growth and pubertal delay reach their full height potential. the conventional teaching is that these children catch up on their growth during the pubertal growth spurt and just remain shorter before their delayed puberty starts. however, some studies show that these children fall short of their target height from about 4 to 11 cm. factors that could affect final height include familial short stature and pre-pubertal growth development. pubertal delay can also affect bone mass and subsequent development of osteoporosis. men with delayed puberty often have low to normal bone mineral density unaffected by androgen therapy. women are more likely to have lower bone mineral density and thus an increased risk of fractures as early as even before the onset of puberty. furthermore, delayed puberty is correlated with a higher risk in cardiovascular and metabolic disorders in women only, but also appears to be protective for breast and endometrial in women and testicular cancer in men.