Weight Gain

Written by: Yumi Lee from Manchester University,

Introduction

Hormone imbalances and weight gain are very closely related. Several endocrine disorders such as hypothyroidism or Cushing’s syndrome may present as unintentional weight gain.  Weight gain occurs when the body is not able to utilize all the energy that is put into it. This could be due to an increased intake of food or a decrease in the body’s ability to metabolize the food consumed. Hormones may play a role in both of these cases.

This article will outline the endocrine conditions associated with weight gain.

Assessing weight gain with BMI

Body mass index or BMI is a way of assessing an individual's body fat calculated from their height and weight (BMI = weight divided by [height squared]). A BMI of 20 to 25 is considered normal, with BMI levels between 25 and 30 considered overweight. A BMI over 30 is considered obese.

However, BMI is not the best measure of obesity as it does not take into account a person’s muscle mass, which can account for a significant amount of certain individuals’ weight – such as in the case of athletes. It also does not account for water weight. The thresholds for BMI vary by ethnic group too. For example, in oriental Asian groups, the BMI value considered obese is lower than for a Caucasian population.

Despite its shortcomings, BMI is often a useful tool for getting a general idea when assessing an individual’s weight.

 

Weight gain history

Questions to consider in a weight gain history:

Nature of weight gain:

  • How much weight have you gained? 
  • How quickly did you gain this weight?

 

Determine if pathological or due to lifestyle change:

  • Have you been eating more? 
  • Have you been less active? 
  • Where have you put on this extra weight?

If central (in abdomen, face and neck), Cushing’s could be a possibility.

 

Enquire about other symptoms relevant to the clinical picture e.g.:

  • Are you feeling tired or unwell in addition to the weight gain? 
  • Are you feeling bloated or oedematous? (Remember to look for oedema on examination.)

 

Consider the past medical history and current medications:

  • Are you currently taking any medications? (Insulin therapy can cause weight gain.)

 

Weight gain examination and investigations

Weight gain and appetite

Hormonal control of hunger and satiety is complex.

Leptin is a hormone that is secreted by adipose tissue. It is thought to activate appetite-suppressing pathways in the body. Leptin receptor deficiency results in an inability to suppress food consumption and results in obesity. Administering leptin can reverse weight gain. In individuals who are neither losing or gaining weight, levels of leptin are positively correlated with BMI values. Paradoxically, the adipose tissue of morbidly obese individuals contains high levels of leptin. When these individuals lose weight, the levels of leptin decrease.  Insulin has similar effects on appetite as leptin.

Ghrelin is a hormone produced by cells in the fundus of the stomach and, in contrast to leptin, is thought to stimulate appetite as its levels in the blood are increased before meals and decreased afterwards. It is inversely related to an individual’s BMI; it decreases with weight gain from overeating and obesity. High levels are correlated with future weight gain.

Hormones secreted from the small intestine such as cholecystokinin (CCK), bombesin, glucagon-like peptide 1 (GLP-1), enterostatin and somatostatin as well as pancreatic hormones such as glucagon and insulin are thought to be involved in the control of satiety.

Treatment for weight gain/ obesity due to increased appetite or the inability to control appetite includes:

  • Dietary (caloric) restriction
  • Behavioural therapy
  • Surgery e.g. Gastric bypass surgery
  • Drugs (which can be centrally or peripherally acting). Orlistat is a peripherally acting drug which reduces the absorption of fat from the diet, causing it to be passed as faces. Side effects including gas, bloating and steatorrhea.

Weight gain and aging

As adults age, their metabolism slows and they put on weight more easily. Although the mechanism behind this phenomenon has not been fully elucidated, loss of muscle cells are thought to play a role in the process. Another likely possibility is the decrease in reproductive hormones with age. There is a negative correlation between age and testosterone in men and age and estrogen in women. 

Rodent studies have suggested that estrogen and testosterone may play a role in the metabolism of the body’s energy stores.

Several genetic hypogonadal conditions, such as Prader-Willi and Bardet-Biedl syndromes are associated with obesity. 

 

Weight gain and hypothyroidism

In hypothyroidism there are low circulating levels of thyroid hormone. Patients may present with fatigue, lethargy, intolerance to cold, constipation, depression, weakness, menorrhagia, hoarse voice and weight gain.

Thyroid hormone acts on all cells in the body, increasing their basal metabolic rate. An increased basal metabolic rate causes more energy to be used. Therefore a decrease in thyroid hormones like that which is seen in hypothyroidism causes a decrease in basal metabolic rate and less energy to be consumed leading to weight gain. The weight gain present in hypothyroidism is not as dramatic as the weight loss seen in hyperthyroidism; typically patients with hypothyroidism put on 5-10 pounds.

Treatment for hypothyroidism:

  • Levothyroxine (replacement of deficient thyroid hormones)

 

Weight gain and Cushing’s syndrome

Cortisol has many functions within the body. These include:

  • Keeping blood glucose levels constant by stimulating gluconeogenesis
  • Aiding in lipid, protein and carbohydrate metabolism

 

It does this by modifying gene activity in target cells (as for all steroid hormones).

In times of stress, there is an increased release of glucocorticoids (cortisol) to help return the body to its original state. It increases the production of glucose from breakdown of fats and carbohydrates to create a quick release of energy to deal with the stress. It also stimulates insulin release to maintain cellular glucose levels. This can cause an increase in appetite. At the onset of stress, fat is broken down for rapid energy. At this time other hormones such as adrenaline are also released. Once the stress has subsided, the levels of these hormones in the blood decrease. However, cortisol remains to re-establish the body’s homeostasis. Subsequently, fat is re-deposited in the abdominal area.

Cushing’s syndrome is a condition in which there is an excess of glucocorticoids regardless of the underlying cause.  Patients with Cushing’s may present with a moon face, skin thinning, limb muscle atrophy, central obesity, buffalo neck hump, supraclavicular fat distribution, osteoporosis, increased blood pressure, hyperglycemia, poor healing, bruises, purple abdominal striae.

The excess cortisol present in individuals with this condition causes loss of muscle and bone, salt and water retention and redistribution of fat to the abdomen and posterior neck.

Treatment for Cushing’s includes:

  • Reducing steroid dose (if cause is iatrogenic)
  • Drugs: cortisol inhibitors
  • Radiotherapy
  • Chemotherapy
  • Surgery (which includes removal of adrenal glands or removal of pituitary gland if it is Cushing's disease)

Insulin and weight gain

An insulinoma is a pancreatic neuroendocrine tumour that secretes insulin. They are generally benign and associated with multiple endocrine neoplasia type1 (MEN 1). They cause hypoglycaemia because the increased levels of insulin cause all the glucose in the blood to be taken up into cells and stored as fat. Therefore, weight gain occurs in 20-40% of patients with insulinomas. The treatment for insulinomas is surgical removal of the tumour.

Patients on insulin therapy for diabetes may experience weight gain as the insulin causes glucose to be taken up into cells and stored as fat.

Insulinomas may present as weight gain and hypoglycaemia relieved by food intake.

If an insulinoma is suspected, blood glucose and insulin levels should be tested, followed by an abdominal CT if any abnormalities are found.

Women with PCOS are considered to be at an increased risk of gaining weight as they are less sensitive to circulating levels of insulin and they also have higher levels of testosterone.