Precocious Puberty

Precocious puberty is an uncommon condition that occurs when puberty begins before the age of eight in girls and before age nine in boys. The signs and symptoms of precocious puberty:

In Girls:

• Development of breasts
  
• Hair development underarm or in public parts
  
• Rapid height growth
  
• Onset of menstruation
  
• Acne
  
• Adult body odor

In Boys:

• Enlargement of testicles
  
• Hair growth in face (usually grows first on the upper lip), public parts /underarm
  
• Rapid height gain
  
• Deepening of voice
  
• Acne
  
• Adult body odor

In some children 'partial' precocious puberty could be seen. Girls may show breast development that later disappears or may persist without any other physical changes of puberty. Such children with partial precocious puberty should be evaluated by a medical professional to rule out any other health problems. By and large such instances do not require any treatment and usually will show the other expected signs of puberty at the right age.

Causes for Precocious Puberty

Abnormalities in ovary and testicles may contribute to precocious puberty. Problems in the ovaries, thyroid gland disorders can also cause the onset of puberty ahead of schedule. Sometimes precocious puberty is the result of a structural problem in the brain such as a tumor, brain injury due to head trauma, infection such as meningitis that triggers puberty to begin early. In a majority of girls there is no underlying medical problem but they simply start puberty too early for no known reason. Certain types of environmental contamination like environmental toxins could play a role in causing precocious puberty.

Central precocious puberty

• Tumor in the brain or spinal cord
  
• Infection such as encephalitis or meningitis
  
• A birth defect in the brain such as hydrocephalus or hamartoma (tumor)
  
• Radiation to brain or spinal cord
  
• Injury to brain or spinal cord
  
• Ischemia
  
• McCune Albright Syndrome - a genetic disease that affects the bones and skin color and causes hormonal problems
  
• A group of inherited disorders known as Congenital adrenal hyperplasia which involves abnormal hormone production by the adrenal glands.
  
• Hypothyroidism

Kallmann Syndrome

A rare hormonal condition characterized by delayed or absence of puberty and an impaired sense of smell is Kallmann syndrome. This belongs to a larger group of conditions known as hypogonadotrophic hypogonadism. This condition is usually characterized by a failure to start or fully complete puberty. However hypogonadotrophic hypogonadism can be treated successfully by means of specialized hormone replacement therapy.

It is estimated that this syndrome affects 1 in 10,000 to 86,000 people and occurs more often in males rather than in females. Kallmann Syndrome 1 is the most common form of this condition. It was Franz Kallmann, an American scientist who first published a paper in 1914 about this syndrome. Therefore this genetic condition is named after him.

Characteristics of Kallmann Syndrome

Males with hypogonadotrophic hypogonadism are born with unusually small penis and undescended testes. Whereas, females affected, usually do not begin menstruating at puberty and have little or no breast development at all. In some women, puberty is either incomplete or delayed. In short, at puberty those affected do not develop secondary sexual characteristics.

In Kallmann syndrome, the sense of smell is particularly diminished or completely absent. This feature indeed distinguishes this syndrome from most other forms of hypogonadotrophic hypogonadism.

The significant aspect here is that most patients are not aware of this inability to detect odors until they are diagnosed. Some points to remember:

Inability to smell strong warning smells such as smoke or gas.

Inability to smell caustic products such as bleach.

Inability to smell rotten/spoilt food.

Personal hygiene, body odor and clothes.

Since the sense of smell is also linked to the sense of taste, some foods will not taste the same as with other people.

Signs and Symptoms

Kallmann Syndrome, even within the same family may vary in its features. Some additional symptoms and signs may include failure of one kidney to develop, a cleft lip with or without an opening in the roof of the mouth or a cleft palate, abnormal eye movements, hearing loss and abnormalities in tooth development.

In some affected persons, the movements of one hand are mirrored by the other hand - Bimanual Synkinesis. This can make it difficult to undertake tasks that require the hands to move separately such as playing a musical instrument. Kallmann syndrome has types designated from 1 through 4 distinguished by their genetic cause. The four types are identified as four forms of Kallmann syndrome, each characterized by an impaired sense of smell. Additional features of cleft palate occur only in types 1 and 2.

Causes

Kallmann syndrome and other related conditions are congenital in nature and are present from birth. Their genetic basis may not be fully understood and this syndrome can be inherited through the generations although it is difficult for the doctor to predict if this will occur.

The genetic factor: Certain mutations in the KAL1, FGFR1, PROKR2, and PROK2 genes cause Kallmann syndrome. Mutations in FGFR1 gene causes syndrome type 2 and mutations in PROKR2 and PROK2 cause Kallmann syndromes types 3 and 4 respectively.

These genes seem to play a role in the development of the brain much before birth. They are involved in the formation and movement of a group of nerve cells that are specialized in olfactory or smell process. The mutations KAL1, FGFR1, PROKR2, and PROK2 genes which play a role in the migration of neurons that produce a hormone called GnRH – Gonodotropin releasing hormone that controls several other hormones that direct sexual development before birth and during puberty. These hormones are necessary for the normal functioning of the ovaries in women and testes in men. These mutations disrupt the olfactory nerve cells and GnRH producing nerve cells in the brain. However these conditions and features vary among individuals and thus additional genetic and environmental factors may be involved.

Treatment

Without proper treatment, the affected female is likely to face infertility and have an increased risk of developing osteoporosis or brittle bones. However, with correct diagnosis and treatment, fertility can be achieved in many cases and risk of osteoporosis decreased.

Following clinical examination, certain biochemical parameters and various imaging tests are done to confirm the diagnosis. As this is a genetic condition, testing for various genetic forms of this disease may also assist in making the diagnosis.

Initially hormone replacement therapy - testosterone in males and estrogen and progesterone in females is used to help induce secondary sexual characteristics.

Once pubertal maturation happens, for fertility either injection of pituitary hormones – gonadotropins, LH and FSH and in some instances therapy with synthetic peptide, GnRH is given. Deficiency of these hormones causes syndromes, and these are required to induce the sex organs to make sperm in males and eggs in females.

In females, the steps taken may vary depending upon individuals and the desired outcome. In premenopausal women, a step-by-step increase in estrogen dosage is given. A bone scan is done to assess the bone age. Without the presence of estrogen, the bone age will be behind that normally seen at that chronological age. The aim is to match the estrogen dosage to the bone age such that the development of bone can be enhanced. The doctor usually monitors the stage of treatment very closely.

Specialist fertility treatments are available and these can induce a certain level of fertility. The aim is to produce hormones by the pituitary and hypothalamus glands and induce natural production of sex hormones. Results can take 6 to 18 months but it is possible to induce fertility in some cases.

There are various drugs available which are usually self-injected twice or thrice a week over a period of at least six weeks. To combat the risk of osteoporosis, it becomes necessary to take tablets that reduce the risk. These tablets help increase the calcium uptake by the bones to strengthen them. However, medication will not eliminate the risk of osteoporosis.

Early diagnosis, education, personal outlook and support from family and friends can help reduce the problems surrounding this syndrome. Kallmann syndrome is usually lifelong in nature and about 10-15% of patients may experience recovery of hormonal system.

Pediatric Endocrinologist

Pediatric endocrinologists specialize in child related developmental problems. Pediatric endocrinologists are specialists in physical and sexual growth developments in children and specialize in childhood diabetes and other endocrine gland disorders. The most commonly faced endocrine problems in children are Type I diabetes, growth hormone treatment, intersexes disorders, hypoglycemia and puberty problems.

After completion of medical school and internship and after a three-year pediatric residency, a period of three years is spent to specialize in pediatric endocrinology. Pediatric endocrinologists help in:

• Problems related to early or delayed puberty
  
• Growth problems such as height related problems
  
• Thyroid problems
  
• Intersex problems
  
• Pituitary, Adrenal gland problems
  
• Ovarian or testicular problems