pituitary stalk blockade syndrome (PKBS)



OVERVIEW

Definition

Pituitary stalk interruption syndrome (PSIS) is a rare developmental defect caused by an abnormality of the pituitary stalk that “blocks” hormone transportation.

The pituitary gland is an important structure in the brain that secretes a variety of important hormones and transports them throughout the body to maintain normal functioning.

The pituitary stalk is an important “transportation link”, and the absence or thinning of the pituitary stalk can lead to a variety of hormones not being transported normally, and the transportation of hormones to the posterior and anterior pituitary lobes through the pituitary stalk is blocked, which leads to the occurrence of pituitary stalk blockage syndrome [1].

Pituitary stalk blockade syndrome can cause a single growth hormone deficiency, commonly growth hormone deficiency, most often seen in pituitary stalk thinning, or multiple adenopituitary hormone deficiencies, most often seen in pituitary stalk defects [2].

Symptoms of different hormone deficiencies vary in expression, and the main manifestation is anterior pituitary hypopituitarism symptoms, such as backward bone age, short stature, hypoplastic sex organs, and absence of secondary sexual characteristics [3].

Morbidity

The incidence of pituitary stalk blockade syndrome is very low, with approximately 5 new cases per 1 million people per year.

However, there is a high prevalence in patients with combined pituitary hormone deficiency, with 112-630 per 1000 patients developing pituitary stalk block syndrome.

Causes

Pituitary stalk block syndrome can be caused by a variety of factors that can cause structural abnormalities in the pituitary stalk, and sometimes a combination of factors can cause pituitary stalk block syndrome.

Causes

It is believed that pituitary stalk block syndrome is mainly associated with abnormal perinatal delivery, but may also be associated with genetic factors, surgical injuries, or other disease factors [4].

Perinatal abnormalities

These include breech delivery, foot first, transverse delivery, intrauterine or postpartum asphyxia, cesarean section, jaundice, and birth injury.

When the fetus is delivered in breech or full term position, the head is obviously deformed, which is easy to cause pituitary stalk injury or rupture. Hypoxemia or hypoperfusion due to intrauterine hypoxia or postnatal asphyxia can also cause pituitary stalk and pituitary gland damage [5].

Genetic factors

Congenital hypothalamic-pituitary dysplasia is associated with genetics, including mutations, microdeletions, and microduplications.

To date, only 5% of patients are definitively suffering from abnormal embryonic development of the pituitary gland due to genetic mutations [6].

Tumor or surgical injury

For example, craniopharyngioma, pituitary adenoma, and skull base surgery can affect the neurotransmission between the pituitary stalk and the hypothalamus through compression and resection, which can lead to pituitary stalk block syndrome.

Inflammatory diseases

Diseases such as meningitis, encephalitis, and multiple sclerosis can affect neurotransmission through edema and fibrosis resulting from inflammation, leading to pituitary stalk block syndrome.

Vascular diseases

Diseases such as atherosclerosis and hypertension can cause obstruction of blood flow in the hypothalamic-pituitary portal system, resulting in insufficient blood supply to the pituitary stalk, which may lead to the development of pituitary stalk block syndrome.

Symptoms

The clinical manifestations of pituitary stalk disruption syndrome depend on the type and degree of hormone deficiency. Patients with growth hormone deficiency often present with varying degrees of developmental delay, while patients with multiple hormone deficiencies present with symptoms associated with total hypopituitarism [7].

Major Symptoms

Pituitary stalk disruption syndrome often presents with deficiencies of the following hormones causing different symptoms.

Growth hormone deficiency

Symptoms such as hypospadias, cryptorchidism, hypoglycemia, and jaundice may be present in the neonatal period.

Growth hormone deficiency is most commonly seen in childhood, with growth retardation such as short stature, low body weight, and delayed bone age. Usually, these children grow less than 3 centimeters in height per year, and they do not grow taller at puberty.

Sex hormone deficiency

Sex hormone deficiency is characterized by abnormal sexual development.

In males, it is mainly characterized by abnormal development during puberty, such as lack of growth of pubic hair, moustache, laryngeal nodes, and short penis, etc. In females, it is mainly characterized by development of secondary sexual characteristics.

In females, it is mainly characterized by underdevelopment of secondary sexual characteristics, such as absence of pubic hair, axillary hair, underdevelopment of breasts and ovaries, and infantile uterus.

Adrenocorticotropic hormone deficiency

Adrenocorticotropic hormone deficiency can cause adrenal crisis, which involves multiple systems.

Symptoms such as dehydration, hypotension, anorexia, vomiting, dysphoria, and lethargy may be present.

Thyroid hormone deficiency

Symptoms of hypothyroidism predominate. Children show growth retardation, delayed puberty, and mental retardation.

Other hormone deficiencies

Antidiuretic hormone deficiency can cause uremia.

Consultation

Prompt medical attention is recommended when symptoms of suspected pituitary stalk blockade syndrome are present.

Department of Medicine

Endocrinology

Endocrinology should be consulted when there are signs of growth retardation and abnormal sexual development [8].

Pediatrics

Minors may also be referred to the pediatrics department when they have symptoms.

Preparation for medical treatment

Consultation: registration, preparation of information, common problems

Tips for seeking medical treatment

During the visit, you may be required to undergo a full body physical examination and imaging tests, so you should wear loose-fitting clothes and avoid wearing clothes made of metal.

During the visit, the doctor may ask about height and weight growth. If you have any data related to your baby’s growth, please bring it with you.

Preparation Checklist

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

Is the current height and weight significantly lower than those of the same age?

Is the development of pubic hair, armpit hair, laryngeal nodes and menstruation similar to those of the same age?

Is there any loss of appetite, fatigue, poor mental health or other discomfort?

When were the above symptoms noticed?

List of medical history

Were certain hormone deficiencies detected?

Were there any abnormalities during labor, such as breech birth position, intrauterine or postpartum asphyxia?

Is there a history of cranial trauma or surgery?

Are there any allergies to medications, foods or other substances?

Has treatment been given? What measures were used and what were the results?

Checklist

Test results in the last six months, which can be brought to the doctor’s office.

Laboratory tests: blood test, growth hormone, endocrine hormone six tests, etc.

Imaging tests: MRI (Magnetic Resonance Imaging) of the head.

List of medications used

Medications used in the last 3 months, if available, bring the box or package with you to the doctor’s office.

Various hormonal drugs: e.g. growth hormone, estrogen, progesterone, testosterone, androgens, levothyroxine sodium tablets, etc.

Diagnosis

Diagnosis of pituitary stalk blockade syndrome is a complex process that requires MRI of the head and blood hormone tests based on suspicious symptoms and relevant medical history, and also requires attention to differentiate it from other diseases.

Diagnostic basis

Medical History

Patients with this disease may have a history of the following

Abnormal perinatal delivery, such as breech birth position, intrauterine or postpartum asphyxia.

History of craniocerebral injury or surgery.

Clinical manifestations

The main manifestations are short stature, small penis, cryptorchidism, absence of pubic hair, beard, and laryngeal nodes despite having reached puberty, gynecomastia, primary amenorrhea, and infantile vulva.

Laboratory Tests

Growth hormone measurement

Growth hormone stimulation test: including insulin hypoglycemia stimulation test, levodopa stimulation test.

Usually patients with peak growth hormone <10μg/L [9].

Pituitary gonadal axis measurement

Sex hormone measurements: usually patients exhibit deficiencies of luteinizing hormone, follicle-stimulating hormone, estradiol, progesterone, and testosterone.

Human chorionic gonadotropin excitation test: pituitary gland is weakly responsive to hypothalamic hormones and gonadal target organs to pituitary hormones.

Pituitary-adrenocortical axis function measurements: adrenocorticotropic hormone-cortisol rhythm, 24h urinary free cortisol measurements below normal.

Imaging

Cranial MRI is a reliable imaging test for the diagnosis of pituitary stalk blockade syndrome [10].

Cranial MRI shows that the patient’s pituitary stalk is slender or absent, the anterior pituitary lobe is atrophied, and the posterior pituitary lobe is ectopic.

Genetic measurements

Including the determination of genes such as PROKR2, PROK2, HESXl, LHX3, LHX4, OTX2, S0X3, PR0P1, P0U1F1.

Diagnostic criteria

The diagnosis of pituitary stalk disruption syndrome should be based on the combination of medical history, clinical manifestations, and laboratory tests, and the diagnosis can be made if the first 2 criteria are met at the same time.

Cranial MRI shows a triad of pituitary stalk defects or obvious thinning, posterior pituitary ectasia, and anterior pituitary hypoplasia.

There are clinical signs of growth retardation with peak growth hormone <10 μg/L.

There may or may not be deficiencies of sex hormones, adrenocorticotropic hormone, thyroid hormone, and other hormones.

Differential Diagnosis

Symptoms such as growth retardation due to pituitary stalk disruption syndrome lack specificity and need to be differentiated from disorders with similar symptoms under medical supervision.

Pituitary dysplasia

Similarities: Growth retardation, short stature, and delayed puberty.

Differences: MRI of pituitary stalk disruption syndrome is dominated by the triad of pituitary stalk agenesis or obvious thinning, posterior pituitary ectasia, and anterior pituitary hypoplasia. It can be differentiated by corresponding cranial MRI.

Growth hormone deficiency

Similarity: Both can cause growth retardation, lack of secondary sexual characteristics, and hypoplasia of sex organs.

Difference: Growth hormone deficiency is caused by the lack of growth hormone, and there is no abnormality in the pituitary stalk as seen in cranial MRI. It can be differentiated by corresponding cranial MRI.

Treatment

Aim of treatment: To improve or eliminate clinical symptoms and control the development of the disease.

Treatment principle: Hormone replacement therapy is the only effective treatment for pituitary stalk blockage syndrome, i.e., to treat the disease by supplementing the lack of hormones.

Hormone replacement therapy

Different types of hormone deficiencies require the use of corresponding hormone replacement therapy, and attention should be paid to the rational use of medication, not excessive use of medication.

Growth hormone deficiency: growth hormone supplementation.

Sex hormone deficiency: supplementation of sex hormones, such as estrogen and progesterone for women and testosterone and androgen for men.

Thyroid hormone deficiency: supplementation of thyroid hormones, such as levothyroxine sodium tablets.

It should be noted that adolescents with growth hormone deficiency combined with sex hormone deficiency are first given growth hormone to solve the height problem, and then given sex hormone replacement therapy after their height reaches the expected height or no longer grows.

Surgery

For those with pituitary stalk blockage syndrome due to tumor-occupying compression, surgical resection should be performed when surgical indications are met.

Prognosis

Pituitary stalk block syndrome may cause different degrees of physical and mental health damage to patients, and active treatment can significantly improve the prognosis.

Cure

Untreated

Pituitary stalk block syndrome cannot be cured on its own and may continue to worsen without treatment.

Treated

Pituitary stalk block syndrome is not curable, but early detection, diagnosis and treatment can lead to a better clinical outcome, and the related symptoms can be significantly improved.

Harmfulness

The risk of pituitary stalk blockade syndrome varies considerably from patient to patient, but overall, it has an impact on both physical and mental health.

Pituitary stalk blockade syndrome can cause growth retardation in children, and in severe cases, it can affect fertility.

The delayed growth and abnormal fertility may lead to psychological problems such as low self-esteem, anxiety, and depression.

In a few patients, adrenal crisis and pituitary crisis may be induced, which can be life-threatening.

Daily

Patients with pituitary stalk blockade syndrome should pay attention to daily management and condition monitoring, and conduct necessary review.

Daily management

Dietary management

There are no special dietary contraindications, and a healthy and balanced diet is sufficient.

Lifestyle management

Moderate physical exercise.

Psychological Support

Establish a scientific concept of coping with the disease, participate in more social activities, and maintain a pleasant and positive mindset.

For patients who have developed low self-esteem, anxiety and depression, they should seek help from a psychiatrist if they cannot be relieved through daily counseling.

Take medication on time and according to dosage

Take medication as prescribed by the doctor, do not reduce or stop the medication arbitrarily, and consult the doctor as soon as any uncomfortable symptoms appear.

Monitoring of illness

Observe changes in height and weight and keep relevant records.

Observe changes in secondary sexual characteristics, such as penis and beard development for men and breast and pubic hair development for women.

Observe changes in psychological mood.

Follow-up and review

During the treatment period, follow the doctor’s instructions for review and medication adjustment.

Blood tests for the hormones mentioned above and MRI of the head may be required, and other necessary tests may be performed in case of new symptoms.

If there is any significant change in signs or if you feel unwell, you should consult your doctor promptly.

Prevention

The following measures will not eliminate the disease, but will reduce its incidence.

Pregnant women should have regular obstetric checkups, follow doctor’s instructions for medication, and take good care of themselves during pregnancy to reduce the incidence of perinatal delivery abnormalities.

Protect the head in daily life to avoid cranial injury.

Actively treat other intracranial pathologies, such as intracranial tumors, meningitis, encephalitis and other diseases.