What Is Panhypopituitarism?

Panhypopituitarism is a rare disease in which all the hormones produced by the pituitary gland are reduced. It can affect children and adults. 

Hormones are chemical substances that act like messengers throughout the body. They are released into our bloodstream and carried to organs and tissues in the body where they stimulate certain cells into action. Different hormones affect different cells. They work slowly and impact many different bodily processes like growth, metabolism, and reproduction. 

The pituitary gland 

Hormones are produced and released by endocrine glands. The pituitary gland, hypothalamus, and pineal gland are endocrine glands in the brain. The thyroid gland is located in the neck. The thymus is between the lungs, the adrenals are above the kidneys, and the pancreas is behind the stomach. The ovaries in people assigned female at birth (PAFAB) and the testis in people assigned male at birth (PAMAB) also produce hormones. The pituitary gland is often called the ‘master gland’ because it controls the activity of other glands, like the thyroid, adrenals, ovaries and testes. 

The pituitary is a small gland in the brain that releases hormones. It is split into two lobes - the anterior (front) pituitary and the posterior (back) pituitary.  If the pituitary gland is not producing enough hormones, it’s called hypopituitarism. Panhypopituitarism is a type of hypopituitarism. A deficiency in one or some of the hormones the pituitary gland produces is hypopituitarism. When there’s a deficiency in all the hormones produced by the pituitary gland, it’s called panhypopituitarism (‘pan’ means all and ‘hypo’ means less than normal). 

Hormones produced by the pituitary gland 

The anterior pituitary makes many different hormones.¹ They include:

Growth hormone (GH)

This hormone stimulates the growth of bone and tissue in the body. Its levels rise in childhood and puberty. GH stimulates the production of proteins and increases the breakdown of fat to provide the body with the energy needed for growth. 

Thyroid-stimulating hormone (TSH)

This hormone is produced in the pituitary. TSH tells the thyroid gland in the neck how much thyroid hormone it needs to make. Thyroid hormones affect many organs in the body and are involved in managing metabolism, body temperature, and mood. If you don’t have enough thyroid hormones in your blood, many bodily functions slow down. If you have too much, many bodily functions speed up. If thyroid levels in the blood are too low, the pituitary gland makes more TSH to tell the thyroid gland to make more thyroid hormones. 

Prolactin

This hormone stimulates milk production by the mammary glands after birth. During pregnancy, it contributes to the development of breast tissue. 

Adrenocorticotropic hormone (ACTH)

This hormone stimulates the adrenal glands to release cortisol. Cortisol helps us respond to stress, regulate blood sugar, maintain blood pressure, fight infection, and regulate metabolism. When cortisol levels are low, the pituitary gland produces ACTH in the blood. The adrenal glands detect high levels of ACTH, causing them to release cortisol.

Follicle-stimulating hormone (FSH)

Helps to stimulate egg production and oestrogen by the ovaries and sperm production by the testes. It results in the maturation of the sperm and eggs. FSH also helps to control the menstrual cycle. Levels of FSH vary throughout the menstrual cycle and are highest just before the release of the egg (ovulation). 

Luteinising hormone (LH)

This hormone stimulates the release of an egg (ovulation) in PAFAB and testosterone production in PAMAB. 

Some hormones are produced in the hypothalamus and released into the bloodstream by the pituitary gland.¹ They are secreted by the posterior pituitary and include:

Vasopressin

This hormone is released into the blood to help reabsorb water from the kidneys. This maintains the correct volume of water in and around our cells, allowing them to function properly. It’s also called the antidiuretic hormone.

Oxytocin

This hormone stimulates muscle contraction in the uterus during childbirth. It also increases the production of prostaglandins, which increase uterine contractions. Oxytocin helps milk move from the mammary glands to the ducts in breastfeeding women. It’s also involved in maternal behaviour. 

Causes of panhypopituitarism

Panhypopituitarism can be congenital (from birth) or acquired. It can be caused by damage to the hypothalamus or the pituitary gland.² This damage may be a result of:

• Tumours on or near the pituitary gland — these can compress the gland and interrupt its ability to produce and release hormones
• Surgery 
• Radiation therapy — when used as a treatment for other conditions, radiation therapy may damage the pituitary gland, leading to panhypopituitarism
• Autoimmune reactions — these can cause the immune system to attack its own body, leading to inflammation and damage  
• Brain injury 
• Stroke
• Congenital defects

Sometimes the cause may not be identified.

The hypothalamus and the pituitary gland 

The hypothalamus is located above the pituitary gland. It’s involved in hormone release. The hypothalamus does this primarily by controlling the pituitary gland. The release of hormones produced by the pituitary gland is controlled by the hypothalamus. It sends signals to the pituitary gland to tell it when to secrete hormones. Vasopressin and oxytocin are produced in the hypothalamus and sent to the posterior pituitary gland which will release them into the bloodstream. 

Symptoms

Symptoms of panhypopituitarism vary between individuals and depend on how much hormone production is reduced. They may include:

• Nausea
• Delayed puberty 
• Sensitivity to cold 
• Poor appetite
• Dizziness
• Unexplained weight loss or weight gain
• Dry skin
• Prolonged jaundice in infants
• Excessive thirst and urination
• Low blood sugar 
• Hair loss
• Depression or anxiety
• Infertility

Diagnosis

A range of tests are used to confirm a diagnosis of panhypopituitarism. Imaging tests like a magnetic resonance imaging (MRI) scan or a computed tomography (CT) scan may be conducted to create detailed images of the brain. These can help identify the cause of panhypopituitarism by determining the presence of pituitary tumours or other issues within the hypothalamus or pituitary gland. 

Hormone tests will also be carried out to check for hormone deficiencies.³ These tests can be carried out in two ways. The first is by measuring basal hormone levels, where blood samples are taken in the morning, and the second is by carrying out stimulation tests. These are when blood samples are taken after a specific injection. Some specific hormone tests may include:⁴

Adrenocorticotropic hormone (ACTH) stimulation test

This test evaluates the adrenal glands’ ability to respond to ACTH. A blood sample is drawn and then an injection of ACTH is administered. Another blood sample is taken after 30-60 minutes and cortisol levels are checked in the samples. 

Blood tests

These are used to measure basal levels of hormones like TSH, LH, FSH, and prolactin. Measuring prolactin levels is important in confirming low levels of LH and FSH because these hormones can be suppressed if prolactin is high. 

Growth hormone (GH) stimulation test

This test measures the body’s ability to produce GH. A blood sample is drawn and then a medicine that stimulates the pituitary gland to release GH is given before another blood sample is taken. 

Treatment and Management 

Treatment of panhypopituitarism depends on the underlying cause of the condition.³ Some treatment options include:

Hormone replacement therapy

Panhypopituitarism can be treated with medicines that increase hormone amounts to healthy levels. People with panhypopituitarism will likely have to take these medications for the rest of their lives. Patients may be given hydrocortisone, which replaces deficient adrenal hormones due to a lack of ACTH. They may also be treated with sex hormones like testosterone, oestrogen, and progesterone. Children with panhypopituitarism can also be treated with GH to help them grow taller. 

Radiation therapy

If a pituitary tumour is causing panhypopituitarism, radiation therapy may be recommended to remove the tumour. 

Surgery

If a pituitary tumour is causing panhypopituitarism, surgery may be recommended to remove the tumour. 

Complications 

Panhypopituitarism can be life-threatening if patients develop complications like adrenal crisis.⁴ Adrenal crisis (acute cortisol insufficiency) is caused by a significant deficiency of ACTH. It is treatable with immediate medical attention. Symptoms of adrenal crisis include:

• Fever
• Weakness
• Confusion 
• Vomiting 
• Diarrhoea 
• Abdominal pain 
• Fast heart rate (tachycardia)
• Low blood pressure (hypotension)
• Low blood sugar (hypoglycaemia)

People with panhypopituitarism can also face an increased risk of developing osteoporosis which is when the bones are weakened and more likely to break.⁵ They can also have an increased risk of developing cardiovascular disease.

Summary 

Panhypopituitarism is a rare condition that affects the production and release of essential hormones from the pituitary gland in the brain. The anterior pituitary gland makes many hormones like LH, GH, TSH and FSH. Whereas the posterior pituitary is responsible for the release of oxytocin and vasopressin. Deficiencies in these hormones can result in symptoms like nausea, hair loss, depression, delayed puberty, low blood sugar, and slow growth. Panhypopituitarism can be congenital (from birth) or acquired as a result of problems in the pituitary gland or the hypothalamus. The condition is diagnosed through blood tests that check your hormone levels and through imaging tests that confirm the presence of pituitary tumours. Panhypopituitarism treatment can involve hormone replacement therapy or surgery. Radiation therapy may be offered if it’s caused by pituitary tumours. Many people with panhypopituitarism are on hormone replacement therapy for the rest of their lives.