Pituitary News, Issue 17 - Autumn 2000.

We know from the letters and phone calls we receive that many of our members have problems with weight gain and have asked Dr Jonathan Pinkney of the Bristol Royal Infirmary to write about the causes of this.

Dr Jonathan Pinkney
Bristol Royal Infirmary

Why do diseases of the Pituitary gland and Hypothalamus lead to weight gain?

The urge to eat is so powerful it is difficult to resist, and can be greatly increased in the presence of pituitary and hypothalamic disease. This explains why diseases of the pituitary gland, particularly when the adjacent part of the brain - the hypothalamus - is affected, may lead to weight gain and sometimes marked obesity. Obesity is often viewed negatively by society, and brings with it various additional health worries including diabetes and heart disease. Thus, obesity is an unwanted and frustrating aspect of pituitary / hypothalamic disease.

Diseases affecting the pituitary gland

Diseases confined to the pituitary alone generally cause only relatively minor weight disturbances. Thus, pituitary tumours, pituitary surgery or Radiotherapy often impair the production of pituitary hormones. Deficiencies of Thyroid stimulating hormone (TSH), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Growth hormone (GH) all have subtle effects on the accumulation of body fat. The severity depends on the mixture of deficiencies, their degree and duration. Deficiencies of TSH, FSH and LH are routinely replaced, and while GH deficiency does not cause obesity it may promote fat deposition and weaken muscle strength. Effects on body weight and strength are most marked in the absence of all the hormones - ie untreated hypopituitarism. In contrast, some with Cushing's disease are prone to develop "pot bellied" obesity from overproduction of the Cortisol, although this resolves with treatment.

Diseases affecting the hypothalamus

In contrast, damage to the hypothalamus often leads to frank obesity. The reason is that the hypothalamus is the centre in the brain controlling appetite. The hypothalamus coordinates signals of "appetite", which we experience as "hunger", and initiates interest in food. We find eating a pleasurable experience, and this is sustained until a second set of signals of "satiety", caused by food ingestion, finally reduce our interest in food. When the hypothalamus is damaged, however, the usual inhibition of appetite is weakened. Overeating ensues, although this may be unnoticed until obesity develops. Occasionally, however, hypothalamic disease leads to a more voracious appetite, constant eating and rapid weight gain. For some individuals, hypothalamic damage also leads to a slowing of metabolism and sleepiness, both of which will exacerbate weight gain.

Is this a problem for me?

A common question asked by patients is whether pituitary / hypothalamic disease has been responsible for unwanted weight gain, or whether weight gain is unrelated to pituitary / hypothalamic disturbances? The answer to this question is usually clear if there is a story of marked weight gain dating from the time of diagnosis and treatment of pituitary / hypothalamic disease. However, any period of physical inactivity related to illness can also contribute to weight gain! Whereas damage to the pituitary alone is unlikely to contribute to severe obesity, this is far more likely in the presence of hypothalamic damage. Hypothalamic damage can sometimes be confirmed by MRI scans of the brain.

What can be done to control obesity in the presence of hypothalamic damage?

Although many find it hard to lose weight, obesity caused by hypothalamic disease is more resistant to weight loss. Despite this, the same principles apply to hypothalamic as to simple obesity. That is, that the food eaten must not exceed the body's requirements if weight gain is to be avoided. Before a treatment plan is devised, it is important to ensure that the levels of pituitary hormones are adequate, otherwise this may impair weight loss.

Since unrestrained eating is the key factor in hypothalamic obesity, treatment usually focuses on this. It is crucial to develop a good relationship with a dietician, and to ensure long term regular follow-up. In addition to eating the right types of food, avoiding grazing on fattening snacks and "junk food", most people with hypothalamic obesity also need to reduce their overall food intake. While the usual "self-help" groups, such as Weight Watchers can do no harm, it is important to remember that hypothalamic obesity is different from ordinary obesity, and that the experiences of hypothalamic patients are likely also to be somewhat different. It is likely that support from other individuals with hypothalamic weight problems might be more helpful. In order to reduce the likelihood of grazing or bingeing, it may be necessary to employ additional "behavioural" measures. These may include minimising the amount of food kept in the house. Occasionally, more extreme measures can be used, such as locking cupboards and refrigerators at night. For those who are able to do so, regular exercise should be performed. Although it may sometimes appear that these measures are not achieving the desired weight loss, it is helpful to remember their value in limiting further weight gain, and that even modest weight loss of 5-10% significantly improves health and wellbeing. Undeniably, however, some individuals with hypothalamic obesity respond poorly to dietary treatment. This is seldom a failing on the part of those individuals, rather an indication of the strength of appetite in the damaged hypothalamus!

Are there any other treatments? A guarded "yes". There are no clinical studies on antiobesity drugs in patients with hypothalamic obesity. However, there is no reason to believe that such drugs might not help some patients. Several new drugs are under development and so the treatment options will increase in the near future. Finally, although stomach surgery has been used in treating obesity, there is little experience in hypothalamic obesity. The concern remains that uncontrollable appetite may render surgery ineffective. More research is certainly required on the use of drugs and surgery to determine what they have to offer patients with hypothalamic obesity.

It has to be acknowledged that the treatment of hypothalamic obesity remains a problem, and that we need further research on this subject.