Hypopituitarism

Hypopituitarism is a rare condition where your pituitary gland doesn’t produce enough of the hormones your body needs to function properly. This can affect growth, metabolism, reproduction, and many other vital processes, requiring careful diagnosis and often lifelong treatment.

Table of contents

• What is hypopituitarism?
• Types of hypopituitarism
• Associated anatomy
• Hormones that can be affected
• What causes hypopituitarism?
• Symptoms of hypopituitarism
• How is hypopituitarism diagnosed?
• Treatment options
• Long-term outlook and monitoring

What is hypopituitarism?

Hypopituitarism is a rare medical condition in which the pituitary gland (a small, pea-sized gland located at the base of your brain) does not make enough of one or more of the hormones your body needs.^[1] Hormones are chemical messengers that travel through your bloodstream and tell different parts of your body what to do. The pituitary gland produces several important hormones that control things like growth, metabolism, reproduction, and how your body responds to stress.^[1]

The pituitary gland does not work alone. It works closely with the hypothalamus, a brain structure located just above it. The hypothalamus sends signals to the pituitary gland, telling it when to release specific hormones. It also helps regulate important body functions like blood pressure, heart rate, body temperature, and digestion.^[1] If disease or injury affects either the pituitary gland or the hypothalamus, hypopituitarism can develop.

The condition can happen suddenly after an injury or develop slowly over months or even years.^[1] The incidence rate is estimated at 12 to 42 new patients per million people each year, with a prevalence of 300 to 455 patients per million.^[9] However, the actual numbers may be higher, as many cases go undetected. Between 30% and 70% of patients with brain injury may experience symptoms of reduced hormone secretion from the pituitary gland.^[9]

Types of hypopituitarism

Hypopituitarism can be classified in different ways depending on which hormones are lacking and what causes the condition.^[1]

Based on the number of hormones affected, there are three main types:^[1]

• Isolated pituitary deficiency: Only one pituitary hormone is lacking
• Multiple pituitary hormone deficiency: Two or more pituitary hormones are lacking
• Panhypopituitarism: All pituitary hormones are lacking

Based on the underlying cause, hypopituitarism is divided into:^[1]

• Primary hypopituitarism: Caused by damage to or disorders of the pituitary gland itself
• Secondary hypopituitarism: Caused by damage to or disorders of the hypothalamus
• Idiopathic hypopituitarism: The cause remains unknown

In most cases, three or more hormones are deficient.^[5] The most common problem is insufficient production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which leads to abnormalities in sex hormones.^[5]

Associated anatomy

• Pituitary gland
• Hypothalamus
• Thyroid gland
• Adrenal glands
• Ovaries
• Testes

Hormones that can be affected

The pituitary gland produces several hormones, and hypopituitarism can affect one or more of them. There are six main hormones that may be affected:^[3]

Growth hormone (GH) is needed for growth and development, especially in children and young people. It also plays an important role in metabolism, bone strength, and maintaining general wellbeing throughout life.^[3]

Thyroid-stimulating hormone (TSH) acts on the thyroid gland in your neck and causes it to produce thyroid hormones, which are important for your body’s metabolism.^[3]

Adrenocorticotropic hormone (ACTH) travels through your blood to the adrenal glands, where it causes them to release cortisol. Cortisol is essential for helping your body respond to stress and for regulating blood pressure, blood sugar, and immune responses.^[3]

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are known as gonadotropins. They are needed for the development of sex and reproductive organs. In people assigned female at birth, these hormones cause the ovaries to release estrogen and produce eggs. In people assigned male at birth, they stimulate the testes to produce testosterone and sperm. These hormones are important for fertility.^[3]

Arginine vasopressin (AVP), sometimes called antidiuretic hormone (ADH), regulates water levels in the body by telling the kidneys how much water to remove from the blood and how much to release through urine.^[3]

Prolactin causes the breasts to produce milk. This hormone is produced in large amounts during pregnancy and breastfeeding, but is present at all times in both men and women in small amounts. Having low prolactin levels alone does not always mean someone has hypopituitarism, as many factors like stress or medications can affect prolactin levels.^[3]

What causes hypopituitarism?

There are many possible causes of hypopituitarism. The most common cause is a pituitary tumor, also known as a pituitary adenoma.^[12] These tumors are almost always benign, meaning they are not cancerous. However, a pituitary tumor can put pressure on the remaining normal part of the pituitary gland and limit or even destroy its ability to produce hormones properly.^[12]

Sometimes pituitary tumors produce too much of one hormone while simultaneously causing underproduction of other hormones. In these cases, reduced levels of some hormones can be accompanied by overproduction of others.^[12]

Other causes that can directly affect the pituitary gland include:^[7]

• Poor blood supply to the pituitary gland
• Infections or inflammatory diseases of the brain
• Radiation treatment
• Surgery to remove pituitary tissue
• Autoimmune diseases
• Brain injury or traumatic brain injury
• Genetic diseases and syndromes
• Rare diseases such as sarcoidosis and amyloidosis

Causes that can indirectly affect the pituitary gland through changes in the hypothalamus include:^[7]

• Hypothalamus tumors
• Inflammatory disease or cancer that spreads to the pituitary
• Head injuries
• Surgical damage to the hypothalamus or blood vessels or nerves leading to it
• Certain medicines, such as opioids, that decrease hormone secretion from the hypothalamus

A serious condition called pituitary apoplexy occurs when there is bleeding into the pituitary gland or blood flow to it is blocked. This can cause sudden onset of hypopituitarism and requires immediate medical attention.^[5]

In some cases, severe blood loss during childbirth can lead to hypopituitarism.^[16] Sometimes, no exact cause can be found, and the condition is called idiopathic.^[7]

Symptoms of hypopituitarism

The symptoms of hypopituitarism depend on which pituitary hormones are deficient and vary widely among different people, both in severity and the number of symptoms experienced.^[3] Several factors affect what kind of symptoms a person will experience, including their sex, their age when hypopituitarism begins, the cause of the condition, and how fast the hormone levels decrease.^[1]

The symptoms usually start slowly and get worse over time. They might not be noticed for months or even years. However, for some people, symptoms start suddenly.^[2]

Symptoms related to growth hormone deficiency

In newborns, growth hormone deficiency can cause low blood sugar and an abnormally small penis.^[1]

In children, symptoms include slow or no growth, short height, and missing or delayed sexual development during puberty.^[1]

In adults, growth hormone deficiency causes:^[1]

• Fatigue
• Reduced sense of wellbeing
• Decreased sexual function and interest
• Higher amount of body fat, particularly around the waist
• Sensitivity to heat and cold
• Decreased muscle mass
• Decreased strength and stamina when exercising
• Poor muscle strength causing feelings of weakness
• Low bone mineral density, which can cause weak bones and frequent fractures
• High cholesterol levels in the blood

Symptoms related to thyroid-stimulating hormone deficiency

In newborns, TSH deficiency can cause decreased muscle tone, low body temperature, a bulging belly, and a hoarse cry.^[1]

In children and adults, the symptoms are similar to those of hypothyroidism (an underactive thyroid), because TSH stimulates the thyroid to produce its own hormones. These symptoms include:^[1]

• Fatigue
• Dry skin and thinning hair
• Constipation
• Weight gain
• Muscle weakness
• Sensitivity to cold temperatures
• Depression
• Heavier than normal menstrual periods or irregular periods

Symptoms related to FSH and LH deficiency

In people assigned female at birth, symptoms can include:^[3]

• Less frequent or absent menstrual periods
• Loss of fertility
• Vaginal dryness
• Loss of some female physical characteristics
• Inability to produce breast milk after childbirth

In people assigned male at birth, symptoms include:^[3]

• Problems with fertility
• Sexual dysfunction
• Loss of some male physical characteristics
• Reduced body and facial hair

In children, gonadotropin deficiency means they will not go through puberty.^[7]

Symptoms related to ACTH deficiency

ACTH deficiency is rare but very serious. When ACTH is lacking, it leads to an underactive adrenal gland. Symptoms include:^[7]

• Low blood pressure
• Low blood sugar
• Fatigue
• Feeling easily stressed
• Inability to cope with physical stress or illness

Symptoms related to vasopressin deficiency

A lack of antidiuretic hormone leads to increased urine output and excessive thirst.^[7]

Additional symptoms

Sometimes there are additional symptoms that arise from the underlying cause. For instance, if hypopituitarism is due to a tumor, there may be headaches or visual problems. If the tumor extends to the optic nerve or optic chiasm, there may be visual field defects. In pituitary apoplexy, there can be sudden headaches, rapidly worsening visual loss, and double vision.^[5]

How is hypopituitarism diagnosed?

Diagnosing hypopituitarism involves several steps. Your doctor will ask about your health history and symptoms, and will conduct a careful physical examination that includes checking your blood pressure while lying down, sitting, and standing up, as well as examining your skin and overall appearance.^[7]

Blood tests

Blood tests are the main way to diagnose hypopituitarism. These tests measure the levels of hormones made by the pituitary gland and the levels of hormones made by glands that the pituitary controls, such as the thyroid gland.^[8] Blood tests can show if low hormone levels are due to the pituitary not working as it should.

Hypopituitarism can be easily diagnosed by measuring basic pituitary and target hormone levels for most hormones, except for growth hormone and ACTH deficiency.^[9] For these hormones, special stimulation tests may be needed.

Stimulation tests

Stimulation tests (also called dynamic testing) measure hormone levels before and after taking medicines that cause the body to make hormones.^[8] These tests are indicated when basic hormone levels are unclear or when testing for growth hormone or ACTH deficiency. A clinic that specializes in hormone conditions typically runs these tests.^[8]

Brain imaging

Brain imaging tests can show a pituitary tumor or other pituitary gland problems. The most common imaging tests include:^[8]

• MRI (Magnetic Resonance Imaging): This is the preferred test. It uses large magnets, radio waves, and a computer to make detailed images of organs and structures inside your body without using X-rays.^[7]
• CT scan (Computed Tomography): This test uses X-rays and computer technology to make detailed images of your body.^[7]

Vision testing

Large pituitary tumors or cysts can affect vision, so vision testing may be part of the diagnostic process.^[7]

Other tests

Additional tests may include:^[17]

• X-rays of the left hand and wrist to estimate bone age in children. With hypopituitarism, bone age is often younger than calendar age.
• Urine tests to measure hormone levels

Treatment options

Treatment for hypopituitarism usually involves replacing the deficient hormones with medication. People with hypopituitarism often need to take medicine for the rest of their lives to manage symptoms.^[2] Your healthcare provider will watch you closely to make sure you get the right treatment.^[1]

Hormone replacement therapy

Hormone replacement medicines are used to bring hormone levels back to normal. Doses are set to match the amount of hormones that the body would make if it didn’t have a pituitary problem.^[8] Hormone replacement is available for all pituitary hormones except prolactin and oxytocin.^[12]

Cortisol replacement: Medicines such as hydrocortisone or prednisone, taken by mouth, replace the adrenal hormones needed because of a lack of ACTH. This is particularly important in cases of sudden collapse due to pituitary apoplexy or acute obstetric hemorrhage with pituitary insufficiency. In such circumstances, treatment should not be delayed while waiting for a definitive diagnosis, as it could be lifesaving.^[11]

Thyroid hormone replacement: Levothyroxine treats low thyroid hormone levels caused by a lack of TSH. Both free thyroxine and TSH measurements are needed to evaluate central hypothyroidism, and people with this condition should be treated with levothyroxine.^[13]

Sex hormone replacement: These include testosterone for men and estrogen and progesterone for women. Testosterone is replaced in men and can be substituted with human chorionic gonadotropin (hCG) injections if the patient desires fertility. In women, estrogen is used with or without progesterone as appropriate.^[11]

Growth hormone replacement: Growth hormone is replaced in children as appropriate. It is not routinely replaced in adults unless the patient has symptoms of growth hormone deficiency after all other pituitary hormones have been replaced. In such cases, a six-month trial of replacement therapy may be considered.^[11]

Vasopressin replacement: Medicines replace the antidiuretic hormone if it is deficient.

Hormone replacement therapy should be individualized according to the specific needs of each patient, taking into account possible interactions between different hormones.^[9]

Treatment of underlying causes

Sometimes, treatment of the condition causing hypopituitarism may restore the body’s ability to make pituitary hormones, either fully or in part.^[8]

Surgical care depends on the underlying cause and clinical state. In pituitary apoplexy, prompt surgical decompression may be lifesaving if imaging reveals a clinically significant tumor mass. Tumors that do not respond to medical therapy or cause significant symptoms may need to be surgically removed.^[11]

If radiation therapy is used to treat pituitary tumors, patients must be monitored carefully, as long-term new-onset hypopituitarism may occur after radiotherapy.^[11]

Special circumstances

Treatment may need to be adjusted in special circumstances such as:^[13]

• Pregnancy care
• Post-surgical care following pituitary or other operations
• Treatment in combination with anti-epilepsy medication
• Care following pituitary apoplexy

Long-term outlook and monitoring

Hypopituitarism is associated with increased mortality risk from cardiovascular and respiratory diseases.^[4] Early detection is imperative given the subtle symptoms that can lead to more severe problems if left untreated.^[4]

Long-term monitoring of patients with hypopituitarism is important to ensure that hormone replacement regimes are working properly and to avoid under-treatment or over-treatment.^[9] It is necessary for physicians to inform their patients that they may require lifetime treatment.^[9]

Several hormone deficiencies associated with hypopituitarism may lead to secondary diseases. For instance, growth hormone deficiency is associated with obesity, raised cholesterol, and metabolic syndrome, while estrogen deficiency may lead to osteoporosis. While effective treatment of the underlying hormone deficiencies may improve these risks, it is often necessary to treat them directly.^[5]

People with hypopituitarism need regular follow-up appointments with their healthcare provider to monitor their condition and adjust treatment as needed. With proper hormone replacement and medical care, many people with hypopituitarism can lead healthy, productive lives.