Combined pituitary hormone deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Combined pituitary hormone deficiency is a condition that causes a partial or complete loss (deficiency) of two or more hormones that are normally produced by the pituitary gland. The pituitary gland, which is located at the base of the brain, produces hormones that are needed for growth, development, and other critical body functions. A lack of pituitary hormones can affect growth and development.

The signs and symptoms of combined pituitary hormone deficiency depend on the specific hormones involved. The hormones that are produced by the pituitary gland include growth hormone (GH), which is needed for normal growth; follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which play a role in sexual development and the ability to have biological children (fertility); thyroid-stimulating hormone (TSH), which triggers the release of hormones that control how the body uses energy; prolactin, which stimulates the production of breast milk; and adrenocorticotropic hormone (ACTH), which influences how the body responds to stress and helps maintain normal levels of glucose in the blood and blood pressure levels.

Though the features of combined pituitary hormone deficiency can vary, affected individuals often do not grow at the expected rate, and short stature usually becomes apparent in early childhood. Infants with combined pituitary hormone deficiency may have persistent yellowing of the skin and the whites of the eyes (jaundice), low levels of glucose in the blood (hypoglycemia), and genital abnormalities. Features of combined pituitary hormone deficiency include fatigue, changes in weight, delayed or absent puberty, and problems with fertility. Additional signs and symptoms may include abnormal development of the head and face (craniofacial abnormalities), brain abnormalities, recurrent seizures (epilepsy), and developmental delays. Some affected individuals have eye disorders. These include optic nerve hypoplasia, which is a disorder that affects the nerves that carry visual information from the eyes to the brain.

The signs and symptoms of combined pituitary hormone deficiency can resemble those seen in other disorders, which may delay a diagnosis. Because the signs and symptoms of combined pituitary hormone deficiency can vary widely and often overlap with other conditions, some researchers have suggested that combined pituitary hormone deficiency is part of a spectrum of related disorders rather than a single disorder.

Combined pituitary hormone deficiency can be congenital or acquired. Acquired combined pituitary hormone deficiency is caused by factors that occur later in life, such as infections or tumors. When combined pituitary hormone deficiency is not acquired, the condition is called congenital.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in several genes that play important roles in early development have been associated with congenital combined pituitary hormone deficiency. PROP1 gene variants are the most common genetic cause of congenital combined pituitary hormone deficiency and are more common in individuals with ancestors from Eastern Europe or the Iberian Peninsula. Variants in other genes have been identified in a smaller number of affected individuals.

Many of the genes that are associated with congenital combined pituitary hormone deficiency, including PROP1, provide instructions for making proteins called transcription factors, which control the activity of other genes. These proteins are involved in the development of the pituitary gland and the specialization (differentiation) of pituitary gland cells. Changes in these proteins can lead to the abnormal differentiation of pituitary gland cells, which may reduce or prevent the production of several pituitary hormones.

In some cases, combined pituitary hormone deficiency is one of a group of features that occur together and are associated with a specific disease (syndromic). In most cases, the cause of congenital combined pituitary hormone deficiency is unknown.

Acquired combined pituitary hormone deficiency can be caused by damage to the brain, brain tumors, and certain medications. Acquired combined pituitary hormone deficiency can also develop after certain infections or autoimmune disorders.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Congenital combined pituitary hormone deficiency can be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Some cases of this condition are caused by new (de novo) variants in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

Some cases of congenital combined pituitary hormone deficiency are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition. Cases of combined pituitary hormone deficiency that are caused by variants in the PROP1 gene have an autosomal recessive pattern of inheritance.

Congenital combined pituitary hormone deficiency can also be inherited in an X-linked pattern. A condition is considered X-linked if the altered gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), one altered copy of the gene can cause the condition, although the features may be less severe than those seen in individuals with two altered copies, or there may be no signs or symptoms at all.

When combined pituitary hormone deficiency is one of a group of features that are associated with a specific disease, it follows the inheritance pattern of that disease.

Acquired combined pituitary hormone deficiency is not inherited.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The congenital form of combined pituitary hormone deficiency occurs in approximately 1 in 16,000 individuals.

Which doctor should you see?

The suggested department for discussing Combined pituitary hormone deficiency is Endocrinology, with a endocrinologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which hormone or metabolic finding is important in this case?
• How should test timing and current medicines be taken into account?
• What follow-up would show whether the care plan is working?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Combined pituitary hormone deficiency. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.