What is hypopituitarism, and why does a small gland matter?
Hypopituitarism means deficient production of one or more pituitary hormones. The pituitary sits at the base of the brain and works as a relay: its hormones regulate the thyroid, the adrenal glands and the gonads, and they drive growth. When the relay fails, the glands downstream lose their instructions, so the signs depend on which hormone is missing.
How often does it occur?
If the gland is a relay, partial failure is quiet, and that makes counting difficult. The exact frequency is not well established, for two reasons. Partial deficiency produces few symptoms, so cases may go unrecognised. And much of the evidence comes from a small number of population studies, so the estimates are approximate.
With that caution, the most often quoted incidence is about 1 in 23,000 people per year. Incidence is the number of new cases each year. The most often quoted prevalence is about 1 in 2000 of the population. Prevalence is the number of people affected at a given time.
Who gets it, and from what?
These rates hide a mix of causes that changes with the age of onset, because the processes that damage the gland differ across life: development before birth, tumours and their treatment later.
In adults, a pituitary adenoma is the most common cause. The gland lies in a small bony space, so an adenoma growing there can compress and damage the normal gland around it. Further cases follow treatment of pituitary disease, such as surgery or cranial irradiation, which can itself injure normal gland tissue.
In children, congenital and developmental disorders make up a larger share of cases. A gland that fails to form properly gives a deficiency from birth. Acquired causes such as craniopharyngioma also contribute. Craniopharyngioma lies near the gland and its stalk and is thought to arise from embryonic remnants of Rathke’s pouch.
What does it cost patients?
Beyond how often it occurs and from what, there is the question of what happens to survival. Hypopituitarism is associated with reduced survival. Cohort studies and a systematic review report excess mortality compared with the general population, with standardised mortality ratios broadly around 1.5 to 2. The standardised mortality ratio is the observed deaths divided by the deaths expected in the general population, so a ratio of 1.5 to 2 means more deaths than expected.
The excess mortality falls mainly on cardiovascular and cerebrovascular disease. A hint at why comes from growth hormone deficiency, in which increased cholesterol, central adiposity and a predisposition to atherosclerosis are described. This is consistent with the vascular pattern, though the link is not proven here.
One finding points the same way. Increased cardiovascular mortality persists in patients whose thyroid, gonadal and adrenal axes are replaced but who have no growth hormone. This suggests that unreplaced growth hormone deficiency is an important contributor.
Which deficiency is most dangerous at once?
Most of these deaths are chronic and vascular, but one hormone can fail acutely. The most immediately dangerous deficiency is ACTH, the pituitary hormone that drives cortisol production by the adrenal glands. Without ACTH the adrenal glands are not driven, so there is no cortisol reserve to rise when the body is stressed. An intercurrent illness or a procedure can then progress to adrenal crisis.
Because the problem is a missing reserve, adrenal crisis is preventable when the diagnosis is known and replacement is adjusted for stress.
These figures describe how often the condition occurs and what it costs. Why the pituitary fails depends on the cause, so what actually damages the pituitary, or the hypothalamus above it?