What kind of disease is this, and how often does it occur?
Acromegaly is a disease of chronic growth hormone (GH) excess. The word “chronic” matters, because every other fact about the disease concerns time: how slowly it starts, how long it goes unnoticed and how much harm accumulates.
It is a very rare condition. The incidence (new cases) is 3–11 per million per year, and the prevalence (all existing cases) is about 60 per million of population. The prevalence is much larger than a year’s worth of new cases because the course is long: people live with the disease for years, so cases accumulate. Acromegaly occurs equally in both genders, and the diagnosis is mostly made at 40–60 years of age.
That age is late in life, and it is consistent with the disease having run unrecognised for years beforehand. So how long has acromegaly been present before anyone notices it?
Why does the diagnosis come so late?
The course of acromegaly is quite elongated, because GH excess develops slowly. Slow change gives the eye and the mind nothing sudden to register. The changes it produces, especially the gradual enlargement of the hands, feet and facial features, are easy to accept as normal: each year looks almost like the last, and family members who see the person every day notice no step. It is likely that this gradual course is why patients, relatives and even physicians overlook the changes.
Patients often adapt to the changes rather than report them, so no new symptom takes them to a doctor. Rarity adds to the problem, since a rare disease whose first signs resemble ordinary ageing or common complaints is seldom the first thing anyone suspects. Some complications of acromegaly also look like common disorders, so a patient may be treated for the problem that is presented rather than for acromegaly. Because of all this, there is usually a lag time of 5–10 years between onset and diagnosis.
Not every case waits this long.
Which cases are found sooner?
Some cases are found earlier. Earlier detection is mostly because a secondary manifestation, such as those caused by hyperprolactinemia (excess prolactin), brings the patient to medical attention sooner. Some adenomas also make prolactin, and its effects are not something a patient accepts as normal. Menstrual irregularity and infertility in women are an example of the kind of problem that sends a patient to a doctor.
Many patients still wait. What does that waiting cost?
What does the delay cost?
While the diagnosis waits, the excess keeps acting on many tissues, so by the time the disease is recognised, many complications are already present. Chronic GH excess is the cause of morbidity and mortality that earlier treatment could prevent. The harm is the sum of exposure over time, so a shorter exposure leaves less accumulated harm. That is why early diagnosis matters, and why the delay is the central problem of the disease.
How does acromegaly affect survival, and can it be changed?
Untreated, or persistently active, acromegaly shortens life expectancy. In pooled data from several studies, the standardized mortality ratio is about 1.7. This ratio compares observed deaths with those expected in the general population, so a value of about 1.7 means about 1.7 times as many deaths as expected.
The excess mortality is driven mainly by cardiovascular, cerebrovascular and respiratory disease rather than by cancer. These are the systems that years of GH excess slowly remodel.
When GH and insulin-like growth factor 1 (IGF-1) are brought under control, mortality falls toward that of the general population. If harm is the sum of exposure, ending the exposure stops further accumulation. Because of this, biochemical control is the aim of treatment.
Which complications make up this burden, beginning with what GH excess does to the body’s tissues over the years?