Hypothalamic obesity: understanding the pituitary gland

Hypothalamic obesity is a type of obesity caused by damage to the hypothalamus. The hypothalamus is a small structure in the brain (roughly the size of an almond) located just above the brainstem (the part of the brain that connects to the spinal cord). Though small, the hypothalamus plays multiple vital roles, regulating sleep-wake cycles, temperature, and appetite. These processes are regulated through a complex interplay of neurological and hormonal signals.

When a person has hypothalamic obesity, the parts of the hypothalamus that regulate appetite and energy use no longer function normally. Metabolism slows down, causing the body to use fewer calories, both at rest and during activity. The brain cannot interpret signals for fullness (satiety). Many people experience extreme and uncomfortable hunger (polyphagia or hyperphagia). This leads to weight gain, which can occur rapidly and be challenging to treat.

The pituitary gland and hormonal imbalances

Just below the hypothalamus is the pituitary gland. Roughly the size of a pea, the pituitary gland is sometimes called the "master gland," since it produces hormones that send chemical signals to other hormone-producing glands throughout the body, including the thyroid gland (located in the throat), the adrenal glands (located atop each kidney), and the reproductive glands.

The hypothalamus and the pituitary gland are connected by a bundle of blood vessels and nerves called the pituitary stalk (also known as the infundibulum or infundibular stalk). Because the hypothalamus and pituitary gland are closely connected, damage to one usually affects the other. With hypothalamic obesity, damage can occur as a result of tumors, surgery, infection, or an injury to the head.

Problems with the normal functioning of the pituitary gland can disrupt hormone production throughout the body. The resulting hormonal imbalances can create an environment that promotes weight gain and makes weight reduction more difficult:

• Low levels of growth hormone (GH). GH helps maintain muscle mass, bone density, and metabolism (energy consumption). Low levels of GH are associated with a loss of muscle mass, an increase in body fat, and slower metabolism.
• Thyroid hormone deficiency. The thyroid is a butterfly-shaped gland located in the front of the throat. The hormones produced by this gland regulate many functions throughout the body, including weight and metabolism. Low levels of thyroid hormone can contribute to weight gain and make it more difficult to lose weight.
• Cortisol imbalances. Cortisol is a hormone that regulates several processes, including stress response, blood pressure, blood glucose levels, and inflammation. Cortisol is produced by the adrenal glands, but hormonal signals sent from the hypothalamus and pituitary glands tell the adrenal glands how much cortisol to produce. Damage to the pituitary gland can cause high levels of cortisol, which promotes weight gain.

Looking through the above, one can see how damage to the hypothalamus and pituitary gland creates a perfect storm of factors that contribute to weight gain—slower metabolism, appetite dysregulation, and hormonal imbalances that favor weight gain (and interfere with weight loss). Sleep disorders and fatigue are also common, and these can make managing any health condition more difficult.

Treatment for hypothalamic obesity

Hypothalamic obesity is fundamentally different than the more common form of obesity and does not respond to the same treatments. It's recommended that people with hypothalamic obesity work with a multidisciplinary team that includes an endocrinologist, neurologist, primary care provider, diabetes specialists, physiotherapist, and registered dietitian. A treatment plan can include:

• Continuing treatment for the underlying cause of hypothalamic obesity (such as tumor, infection, surgery side effects, or brain injury).
• An eating plan that assists in reducing weight gain and helps manage extreme hunger.
• Medications to manage hormone imbalances related to pituitary gland dysfunction.
• Obesity treatments, like GLP-1 agonists, may be prescribed (though the effects of these medications on hypothalamic obesity are still being studied).
• Working with a counselor or mental health professional is also recommended. Hypothalamic obesity is a distressing condition to live with, and there are healthcare providers who can help a person with hypothalamic obesity and their loved ones manage the emotional and psychological burdens of the condition.

There are new and emerging therapies, including a drug in clinical trials. The drug acts on the melanocortin 4 receptor (MC4R) pathway, an appetite regulation process that occurs in the hypothalamus. The MC4R pathway does not function normally when a person has hypothalamic obesity.

New and emerging treatments are a topic worth discussing with your healthcare provider.