19 year old with<unk>  before diagnosis and treatment Singer Jimmy Scott (r), whose unusual voice was due to<unk>  It is normally difficult to distinguish a case of<unk>  <unk> /hypogonadotropic hypogonadism (HH) from a straightforward constitutional delay of puberty. However, if puberty has not started by either age 14 (girls) or 15 (boys) years and one or more of the non-reproductive features mentioned below is present, then a referral to reproductive endocrinologist might be advisable. The features of<unk>  and other forms of HH can be split into two different categories; "reproductive" and "non-reproductive". Reproductive features * Failure to start or fully complete puberty. * Lack of testicle development in men (size < 4 ml, whereas the normal range is between 12 and 25 ml). * Primary amenorrhoea (failure to start menstruation). * Poorly defined secondary sexual characteristics. * Micropenis in 5-10% of male cases. * Cryptorchidism (undescended testicles) at birth. * Low levels of the gonadotropins LH and FSH. * Hypogonadism due to low levels of testosterone in men or oestrogen/progesterone in women. * Infertility. Non-reproductive features * Total lack of sense of smell (anosmia) or markedly reduced sense of smell (hyposmia). This is the defining feature of<unk> ; it is not seen in other cases of HH. Approximately 50% of HH cases occur with anosmia and can be termed as<unk> . * Cleft palate, cleft lip or other midline cranio-facial defects. * Neural hearing impairment * Absence of one of the kidneys (unilateral renal agenesis) * Skeletal defects including split hand/foot (ectrodactyly), shortened middle finger (metacarpal) or scoliosis * Manual synkinesis (mirror movements of hands) * Missing teeth (hypodontia) * Poor balance or coordination due to cerebral ataxia. * Eye defects such as coloboma or ptosis. * Increased incidence of color-blindness The exact genetic nature of each particular case of<unk> /HH will determine which, if any, of the non-reproductive features will occur. The severity of the symptoms will also vary from case to case. Even family members will not show the same range or severity of symptoms.<unk> /HH is most often present from birth but adult onset versions are found in both males and females. The hypothalamic-pituitary-gonadal axis (HPG axis) functions normally at birth and well into adult life, giving normal puberty and normal reproductive function. The HPG axis then either fails totally or is reduced to a very low level of GnRH release in adult life with no obvious cause (e.g. a pituitary tumour). This will lead to a fall in testosterone or oestrogen levels and infertility. Functional hypothalamic amenorrhoea is seen in females where the HPG axis is suppressed in response to physical or psychological stress or malnutrition but is reversible with the removal of the stressor. Some cases of<unk> /HH appear to reverse during adult life where the HPG axis resumes its normal function and GnRH, LH, and FSH levels return to normal levels. This occurs in an estimated 10 to 22% of people, primarily normosmic CHH cases rather than<unk>  cases and only found in people who have undergone some form of testosterone replacement therapy. It is only normally discovered when testicular volume increases while on testosterone treatment alone and testosterone levels return to normal when treatment is stopped. This type of<unk> /HH rarely occurs in cases where males have had a history of un-descended testes. Affected individuals with<unk>  and other forms of HH are almost invariably born with normal sexual differentiation; i.e., they are physically male or female. This is due to the human chorionic gonadotrophin (hCG) produced by placenta at approximately 12 to 20 weeks gestation (pregnancy) which is normally unaffected by having<unk>  or CHH. People with<unk> /HH lack the surge of GnRH, LH, and FSH that normally occurs between birth and six months of age. This surge is particularly important in infant boys as it helps with testicular descent into the scrotum. The surge of GnRH/LH/FSH in non<unk> /HH children gives detectable levels of testosterone in boys and oestrogen and progesterone in girls. The lack of this surge can sometimes be used as a diagnostic tool if<unk> /HH is suspected in a newborn boy, but is not normally distinct enough for diagnosis in girls. Osteoporosis One possible side effect of having<unk> /CHH is the increased risk of developing secondary osteoporosis or osteopenia. Oestrogen (females) or testosterone (males) is essential for maintaining bone density. Deficiency in either testosterone or oestrogen can increase the rate of bone resorption while at the same time slowing down the rate of bone formation. Overall this can lead to weakened, fragile bones which have a higher tendency to fracture. Even a short time with low oestrogen or testosterone, as in cases of delayed diagnosis of<unk> /CHH can lead to an increased risk of developing osteoporosis but other risk factors, such as smoking are involved so the risk of developing it will vary from person to person. Bone density scans are recommended to monitor the bone mineral density. The bone density scan is known as a dual energy X-ray absorptiometry scan (DEXA or DXA scan). It is a simple test, taking less than 15 minutes to perform. It involves taking a specialised X-ray picture of the spine and hips and measuring the bone mineral density and comparing the result to the average value for a young healthy adult in the general population. Adequate calcium levels and, probably, more importantly, vitamin D levels are essential for healthy bone density. Some people with<unk> /CHH will have their levels checked and may be prescribed extra vitamin D tablets or injections to try to prevent the condition getting worse. The role of vitamin D for general overall health is under close scrutiny at the moment with some researchers claiming vitamin D deficiency is prevalent in many populations and can be linked to other diseases. Some people with severe osteoporosis might be prescribed bisphosphonates to preserve bone mass, in addition to hormone replacement therapy.
Kallmann syndrome
Klinefelter syndrome
Waldmann disease
Turner syndrome
Angelman syndrome
Hanhart syndrome
Parsonage–Turner syndrome
Gerstmann syndrome