Pubertal delay can be separated into four categories from most to least common: Constitutional and physiologic delay Children who are healthy but have a slower rate of physical development than average have a constitutional delay with a subsequent delay in puberty. It is the most common cause of<unk>  in girls (30%) and even more so in boys (65%). It is commonly inherited with as much as 80% of the variation in the age of onset of puberty due to genetic factors. These children have a history of shorter stature than their age-matched peers throughout childhood, but their height is appropriate for bone age, meaning that they have<unk>  skeletal maturation with potential for future growth. It is often difficult to establish if it is a true constitutional delay of growth and puberty or if there is an underlying pathology because lab tests are not always discriminatory. In absence of any other symptoms, short stature,<unk>  growth in height and weight, and/or<unk>  may be the only clinical manifestations of certain chronic diseases including coeliac disease. Malnutrition or chronic disease When underweight or sickly children present with pubertal delay, it is warranted to search for illnesses that cause a temporary and reversible delay in puberty. Chronic conditions such as sickle cell disease and thalassemia, cystic fibrosis, HIV/AIDS, hypothyroidism, chronic kidney disease, and chronic gastroenteric disorders (such as coeliac disease and inflammatory bowel disease) cause a<unk>  activation of the hypothalamic region of the brain to send signals to start puberty. Childhood cancer survivors can also present with<unk>  secondary to their cancer treatments, especially males. The type of treatment, amount of exposure/dosage of drugs, and age during treatment determine the level by which the gonads are affected with younger patients at a lower risk of negative reproductive effects. Excessive physical exercise and physical stress, especially in athletes can also delay pubertal onset. Eating disorders such as bulimia nervosa and anorexia nervosa can also impair puberty due to undernutrition. Carbohydrate-restricted diets for weight loss has also been shown to decrease the stimulation of insulin which in turn does not stimulate kisspeptin neurons vital in the release of puberty-starting hormones. This shows that carbohydrate restricted children and children with diabetes mellitus type 1 can have<unk> . Primary failure of the ovaries or testes (hypergonadotropic hypogonadism) Hypothalamic-pituitary-testicular axis and the hormones produced by each part of the axis. The + signs indicate that the organ is stimulated by the hormones released from the previous organ in the chain. Primary failure of the ovaries or testes (gonads) will cause<unk>  due to the lack of hormonal response by the final receptors of the HPG axis. In this scenario, the brain sends a lot of hormonal signals (high gonadotropin), but the gonads are unable to respond to said signals causing hypergonadotropic hypogonadism. Hypergonadotropic hypogonadism can be caused by congenital defects or acquired defects. Congenital disorders Congenital diseases include untreated cryptorchidism where the testicles fail to descend from the abdomen. Other congenital disorders are genetic in nature. In males, there can be deformities in the seminiferous tubule as in Klinefelter syndrome (most common cause in males), defects in the production of testicular steroids, receptor mutations preventing testicular hormones from working, chromosomal abnormalities such as Noonan syndrome, or problems with the cells making up the testes. Females can also have chromosomal abnormalities such as Turner syndrome (most common cause in girls), XX gonadal dysgenesis, and XY gonadal dysgenesis, problems in the ovarian hormone synthesis pathway such as aromatase deficiency or congenital anatomical deformities such as Müllerian agenesis. Acquired disorders Acquired diseases include mumps orchitis, Coxsackievirus B infection, irradiation, chemotherapy, or trauma; all problems causing the gonads to fail. Genetic or acquired defect of the hormonal pathway of puberty (hypogonadotropic hypogonadism) The hypothalamic–pituitary–gonadal axis can also be affected at the level of the brain. The brain does not send its hormonal signals to the gonads (low gonadotropins) causing the gonads to never be activated in the first-place resulting in hypogonadotropic hypogonadism. The HPG axis can be altered in two places, at the hypothalamic or at the pituitary level. CNS disorders such as childhood brain tumors (e.g. craniopharyngioma, prolactinoma, germinoma, glioma) can disrupt the communication between the hypothalamus and the pituitary. Pituitary tumors, especially prolactinomas, can increase the level of dopamine causing an inhibiting effect to the HPG axis. Hypothalamic disorders include Prader-Willi syndrome and Kallmann syndrome, but the most common cause of hypogonadotropic hypogonadism is a functional deficiency in the hormone regulator produced by the hypothalamus, the gonadotropin-releasing hormone or GnRH.
Delayed puberty
Precocious puberty
Late-onset hypogonadism
Prognathism
Oncofertility
Hypogonadotropic hypogonadism
Hyperandrogenism
Male infertility