GnRH

Gonadotropin-releasing hormone (GnRH) is a neurohormone consisting of ten amino acids which is produced by the arcuate nuclei of the hypothalamus. It is integral for starting the reproductive hormone cascade.

GnRH is secreted in the hypothalamus which is part of the brain. The hypothalamus is part of the 'Hypothalamus - Pituitary - Gonad' axis which regulates the reproductive system in men and women. Secretion of GnRH by the hypothalamus is delivered through a direct pathway between the hypothalamus and pituitary. GnRH stimulates the synthesis and secretion of two gonadotrophins namely, lutenizing hormone (LH) and follicle stimulating hormone (FSH) by the anterior pituitary gland. Controlled by internal and external factors, GnRH acts in a negative feedback loop. For instance, if there is excess FSH, LH or testosterone, then these hormones will inhibit GnRH production.

Lifestyles can also affect GnRH secretion. Lack of exercise, poor diet, opiad drugs and excessive stress can negatively affect GnRH production. What is so striking in GnRH is that under normal circumstances, GnRH is released at intervals of 90 to 120 minutes. Hence, in patients with GnRH deficiency, the releasing hormone should be administered in pulses. Constant administration of GnRH also suppresses gonadotropin secretion especially in children in puberty stage and in men with prostate cancer.

Why is GnRH treatment used?

This hormone is produced by the hypothalamus and it stimulates the pituitary gland to produce LH and FSH. Lack of GnRH in the hypothalamus can halt testosterone production in the testicles of men. In women, abnormal GnRH levels can be responsible for ovulatory disorders.

This is commonly used when Clomid treatment has not stimulated egg follicles to develop on the ovaries. GnRH works effectively to replace the natural GnRH in women and men who do not produce enough of it. Failure of release of GnRH can result in deficiency that can be partial or complete.

In a woman who is not ovulating because of lack of stimulation from hypothalamus.

In a man who is not producing sperm because his hypothalamus is not stimulating the hormones that trigger sperm production.

The use of GnRH can result in multiple pregnancies.

Some studies report that the pregnancy rate after treatment with GnRH is about 20%.

Side effects

Some side effects include:

• Breathing trouble
  
• Swelling of face, lips, tongue and throat
  
• Itching and redness at the site of the intravenous catheter
  
• Infection at the site of the IV catheter
  
• Ovarian hyper stimulation syndrome - GnRH poses less risk of this syndrome than does human menopausal Gonadotropin and other treatments for ovulation.

The small pump that is used for GnRH may bother some people and treatment requires daily monitoring by a doctor.

Although clinicians and scientists have observed the findings of olfactory disturbances and reproductive dysfunction, the syndrome comprising complete GnRH deficiency and lack of olfactory senses is named Kallmann Syndrome after the American geneticist Kallmann who identified this disorder in 1944.

Treatment

The choice of therapy depends upon the patient's desire to achieve one or more of the following options:

• Secondary sexual characteristics
  
• Fertility
  
• Bone and muscle mass

In males, treatment is decided to provide androgen replacement. The patient's age, potential adverse effects of therapy, patient's desire for fertility are considered. In the prepubertal male, GnRH stimulates penile growth, body and facial hair growth, bone and muscle development and voice changes. Androgens also stimulate growth hormone production, contributing to the adolescent growth spurt. Male androgen deficiency can result in social ridicule and therefore starting androgen therapy around age 14-15 is prudent.

Oral, injectable and transdermal and implantable pellets formulation are available for treatment of males with Kallmann syndrome. Oral androgen preparations should not be used due to their toxic effects on the liver and adverse effects on lipids. Injectable long-acting testosterone are low-cost, relatively safe and effective. The disadvantages include intramuscular injection and non physiologic pattern of testosterone over the dosing interval. There could be wide swings in libido in some men.

Transdermal patches and gel preparation of testosterone are currently available - adverse effect with these formulations include skin reactions at the application. In females as in males, treatment depends upon age and fertility desires. Estrogen replacement is a must to prevent osteoporosis.

Oral preparations, transdermal patches, vaginal cream and rings are available for standard hormone replacement therapy. Transdermally administered 17 beta estradiol has been shown as an effective regimen for preventing bone loss in normal menopausal women.

Women with intact uterus receive a cyclical progestin to accompany estradiol treatment. Optimal hormone therapy depends upon whether the patient has primary or secondary amenorrhea. Gradual dose escalation results in optimal breast development and allows time for young woman to adjust psychologically to her physical maturation.

ACTH Test

ACTH also known as adrenocorticotropic hormone is a hormone produced by the pituitary gland. This hormone in turn regulates the production of another important hormone cortisol, made by adrenal glands. Cortisol, known as a 'stress hormone', controls varied reactions in our body that take place in response to stress. Cortisol regulates blood pressure and blood sugar levels in the body and helps in maintaining immune function and anti-inflammatory processes. ACTH travels through the bloodstream to the adrenal glands and stimulates the adrenals to release cortisol. An ACTH blood test is done to measure the level of the adrenocorticotropic hormone in the blood.

Too much or too little ACTH level reveals problems related to adrenal glands or pituitary glands. High level of ACTH points to problems with adrenal glands and low level of ACTH may imply defective pituitary glands. The results of ACTH test is extremely useful in diagnosing Cushing syndrome and adrenal insufficiency.

Higher values of ACTH test are associated with one of the following conditions:

• Addison's disease
  
  
• Adrenal Hyperplasia
  
  
• Cushing's disease
  
  
• Tumor in the adrenal glands or pituitary glands
  
  
• Ectopic ACTH, which means ACTH made by a tumor outside the pituitary gland

Lower levels of ACTH could mean adrenal tumor, Exogenous Cushing syndrome or hypopituitarism, a pituitary dysfunction leading to little or no production of hormone.

Preparing for the test

Patient should not eat or drink for 10 hours prior to the test. It is advisable to take a diet low in carbohydrates for two to three days before the test. Exercise and alcohol should be avoided for 12 hours before the test. Few steroid medications result in low levels of ACTH, hence patient should share all the information regarding the current medication with the doctor. Patient should not have undergone any medical test that uses a radioactive tracer for a week before an ACTH test.

ACTH levels do not remain in the same range through the day. The plasma ACTH levels are highest in the morning and start to decline during the waking hours. Therefore, blood is usually collected in the morning hours or multiple blood samples are sought for accurate diagnosis.

The Normal reference range is as follows:

Morning: Less than 80 pg/mL or less than 18 pmol/L

Evening: Less than 50 pg/mL or less than 11 pmol/L

A significant deviation from the normal range could mean defective adrenal glands or pituitary gland and further investigation is ordered for the accurate diagnosis.

Thyroid

Thyroid is a gland in the neck overlying the windpipe that regulates the speed of metabolic processes by producing a hormone with the eponymous name thyroxin. Thyroid is an endocrine gland. The thyroid gland which resembles a butterfly, sits astride the trachea. Its secretion - thyroxin, a hormone that regulates the metabolic activity of the body. Too much thyroxin races the metabolism resulting in weight loss, temperature elevation, nervousness and irritability. On the other hand, too little thyroxin slows down the metabolism rate resulting in deep voice, weight gain and water retention. This can result in retardation in physical growth and mental development in children. Both conditions equally affect hair and skin growth, bowel function and menstrual flow.

The thyroid gland is often enlarged whether it is secreting too much hormone, too little or even when it is functioning normally. The thyroid is controlled by the pituitary gland, which secretes Thyroid Stimulating Hormone (TSH) in response to the amount of thyroxin in the blood. TSH increases the amount of thyroxin secreted by the thyroid and also causes the thyroid gland to grow.

Hyperthyroid Goiter : If the amount of TSH is high, the thyroid will both enlarge and secrete too much thyroxin. The result is termed as Hyperthyroidism with a goiter. Graves' disease is the most common form of this disorder.

Euthyroid goiter : If dietary iodine is insufficient, too little thyroxin will be secreted and the pituitary will sense the deficiency and produce more TSH. The thyroid gland will enlarge enough to make sufficient thyroxin.

Hypothyroid goiter: If dietary iodine is severely low, even an enlarged gland will not be able to make enough thyroxin. The gland may keep growing under the influence of TSH, but it may never make enough thyroxin.

An endocrinologist who specializes in the endocrine system can also be consulted for thyroid problems and diseases. Specialists who deal with thyroid problem are called thyroidologists. Thryoidologist and endocrinologist are specially trained doctors who diagnose and treat diseases affecting the thyroid gland. A thyroid specialist continues specialized education focused on thyroid issues after obtaining a Masters degree in medicine. He is qualified and trained to treat conditions that are complex and involve many systems within the body that may be affected due to thyroid imbalance.

A primary care doctor too often misses the diagnosis of a thyroid disease. Sometimes primary care doctors refer patients to a thyroid specialist when there is problem in the endocrine/ hormone systems. Thyroid specialists treat patients with too much or too little thyroid hormone. The thyroid specialist helps the patients to reach a hormone balance by replacing or blocking thyroid hormone. Thyroid specialists also receive special training to manage patients with thyroid growths or thyroid cancer and enlarged thyroid glands. There are times when the services of a thryoidologist or an endocrinologist become absolutely necessary.

• A thyroid specialist has to be consulted when a patient is suffering from the hyperthyroid autoimmune - Graves' disease. This is a condition which can be treated only by a thyroid specialist and not by a regular GP. Graves's disease and hyperthyroid management involves a number of therapies, anti thyroid drug use, radioactive iodine treatments and even surgery if necessary.
  
• Evaluation and treatment for thyroid nodule can be rendered only by thyroid specialists. Thyroid nodule is evaluated by ultrasound and fine needle biopsy process. This is done to rule out the possibility of thyroid cancer.
  
• Thyroid cancer is rare and less than 15000 new cases are diagnosed every year. An expert thyroid specialist is highly recommended to diagnose, evaluate, treat and help in long term follow up and support management of thyroid cancer.
  
• Thyroid surgery is performed when the gland becomes so large that is cosmetically disfiguring. This is normally done if a thyroid has markedly enlarged for years. Thyroid surgery should be performed by an experienced thyroid surgeon. Only an experienced thyroid surgeon can handle the complications that can arise due to thyroid surgery.
  
• A thyroid specialist can assess hypothyroidism levels. This is done by evaluation of TSH level. S/He considers other options such as symptoms, family history and clinical factors to make a thyroid diagnosis.
  
• After a person has been diagnosed for hypothyroidism, a thyroid specialist treats and manages the patient for other signs and symptoms as well. Such symptoms are weight gain, depression, brain fog, hair loss, shortness of breath, intolerance to heat and cold, muscle aches and joint pains, constipation, carpal tunnel, high cholesterol, infertility, Fibromyalgia and chronic fatigue syndrome.