Treatment of hypogonadism is very specific according to the underlying condition. Here is a treatment summary for the conditions mentioned:
|Condition:||Details of treatment:|
|Klinefelter syndrome||small amounts of testosterone replacement prevent atrophy of left temporal lobe (Ref. 6); IVF methods can be used in 40% of patients to father children with normal chromosomes (Ref.5)|
|Bilateral anorchia||replacement therapy of testosterone starting in puberty and slowly increasing over 2 years to adult replacement dosage (injection or trans-dermally); laparoscopic exploration (Ref. 7)|
|Congenital adrenal hyperplasia (CAH)||replacement of glucocorticoid (prednisone or hydrocortisone orally); fludrocortisone given orally to replace aldosterone; in female infants reduction clitoroplasty and creation of vaginal opening|
|Turner syndrome||replacement with female hormones brings on normal puberty; careful check for mosaics with 45,X and 46,XY who require removal of gonadal remnants to prevent gonadal malignancies (Ref.8)|
|Condition:||Details of treatment:|
|Panhypopituitarism||treat underlying pituitary or hypothalamic abnormality; adult males may be treated with gonadotropins (FSH/LH) to induce spermatogenesis (Ref. 10)|
|Kallman syndrome||hCG treatment can treat cryptorchidism and render patients fertile; consider GnRH with portable sc. pump to achieve normal male appearance and fertility|
It is interesting that 40% of patients with Klinefelter syndrome (according to Ref. 5) have sperm in the testicular tubules and 94% of these samples checked out genetically normal!
In the last view years there are several groups throughout the word that reported in vitro fertilization (=IVF) with Klinefelter syndrome sperm resulting in genetically normal babies. There is still a serious fertility problem in this group of patients, but things are not as bleak as they were thought of in the past. High-resolution MRI scan studies with Klinefelter syndrome children in puberty showed that treatment with low dose testosterone lead to more volume of the left temporal gray matter of the brain. This correlated with improved verbal and language skill scores when compared to normal controls and untreated Klinefelter patient controls.
Patients with this condition have to be carefully studied with the hCG test to ensure that there is no other cause for the finding of missing testicles, such as cryptorchidism. If there is even the slightest increase of testosterone on this test from the prior baseline, the authors of Ref. 7 suggest that an examination under a general anesthetic and possible laparoscopy should be done. This study involved more than 900 boys. With early correction of cryptorchidism malignancy and testicular torsion of the testicles will be prevented.
Congenital adrenal hyperplasia (=CAH)
This condition can be present in males or females and the basic primary defect is the same, namely an absence of glucocorticosteroid production in the outer layer of the adrenal glands as well as an inability to produce aldosterone as well. The pediatrician or endocrinologist needs to watch these children as over treatment with prednisone or hydrocortisol leads to Cushing’s disease, but undertreatment leads to ACTH overproduction because of inadequate feedback on the pituitary gland.
This ACTH overproduction leads to an overproduction of androgens (a group of adrenal gland hormones with male attributes), which causes virilization and growth abnormalities. The growth is initially exaggerated, but because of the closing of the growth plates of the long bones under the influence of androgens later leads to permanent short stature. For this reason compliance to the regimen of treatment must be monitored with regular visits to the doctor’s office for weight and height measurements. Growth tables are used to monitor that the growth rate is as close to the normal curve as possible. At the same time blood tests are taken from time to time to ensure normal blood hormone levels. Females affected with CAH often need corrective surgery early on as a baby to do a clitoroplasty and create a vaginal opening. Later in life further corrective surgery might be necessary. Some psychosexual counseling may be required. However, these patients will have normal, fulfilled sexual lives and normal childbearing.
Turner syndrome, as mentioned before consists of a wide spectrum of mosaic Turner syndrome, which is responsible for the wide variation of symptoms. Hormone studies are used to aid in the decision of how much hormone replacement would be necessary. The goal is to mimic normal hormone activity and normal growth. A cardiologist needs to investigate the narrowing at the beginning of the aorta (medically termed “coarctation of the aorta”), and help to decide whether or not surgery is required (Ref. 11).
In severe cases of coarctation the newborn becomes blue and needs immediate intubation and oxygen. Prostaglandin E-1 is given intravenously to reopen the “ductus arteriosus”, which is the artery that during the course of pregnancy bypassed the blood from the lungs. With the first breath when the lungs expand this bypassing artery closes, but the normal circulation depends then on a patent aorta. The first step of defense for a Turner syndrome patient with this malformation of the aorta is to reopen the ductus arteriosus as stated. At age 5 to 7 (Ref. 11) elective removal of the stenotic piece of aorta can then be done by the cardiovascular surgeon. Another area of concern is to spot those patients who are mosaics with a Y-bearing cell line (for instance 45,x and 46,XY). It is this subpopulation who is at a high risk for developing a malignancy of the nonfunctioning gonadal tissue, called “gonadoblastoma”. This tissue is removed prophylactically and then the risk disappears. With hormone replacement and some corrective surgeries, including some plastic surgery regarding the webbing of the neck, Turner syndrome patients will be able to lead a normal life. However, infertility in most patients cannot be avoided.
This condition needs to be treated according to the underlying pathology. If there is an underlying tumor in the hypothalamus or in the pituitary gland, appropriate neurosurgery or radiotherapy may have to be performed . At the same time hormone replacement is given with either hCG injections or GnRH, if the pituitary function is intact. It is interesting to note that endurance athletes, like marathon runners etc., can also have reduced gonadotropin activity, which can lead to low testosterone levels and infertility due to diminished sperm production (Ref. 9). Other acquired cases have also been described (Ref. 10) where the pituitary gland no longer produces enough gonadotropins of its own and replacement hCG by injection has to be given to bring testosterone and sperm levels up to normal.
This condition needs to be treated with hCG to treat cryptorchidism and render the patients fertile. Alternatively, as the pituitary FSH and LH cells are functional, GnRH can be given via a portable pump subcutaneously and programmed in a way how to simulate sporadic release of gonadotropin hormones from the pituitary gland. In this way normal testicular hormone production, normal male appearance and normal fertility will occur.
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