Introduction

Overview of Frohlich Syndrome

Frohlich syndrome also known as Adiposogenital Dystrophy is a rare condition first described by German physician Hermann Frohlich in 1901. Furthermore, unlike similar diseases such as Prader-Willi syndrome, this disease is not inherited but it is acquired. Frohlich syndrome is characterised by endocrine abnormalities that result in damage to a part of the brain called the hypothalamus.⁵ This part of the brain impacts the regulation of appetite, metabolism and sexual development as it links the nervous system to the endocrine system through the pituitary gland which releases a variety of hormones.⁵

The hallmark of Frohlich syndrome is obesity, usually beginning in childhood or adolescence as a result of increased appetite due to dysregulation of hormones.⁶ Obesity is determined by Body Mass Index or BMI, which is calculated by dividing a person’s weight in kilograms by the square of their height in meters. Furthermore, patients with Frohlich Sydrom might experience delayed growth and/or sexual maturation and reproductive health. 

Importance of Weight Management 

While Frohlich syndrome is an irreversible condition, managing the symptoms holds great significance, in particular, obesity as managing these symptoms can improve overall quality of life. Obesity can be the root cause of many other secondary health problems such as diabetes, joint issues and cardiovascular disease. One of the challenges associated with managing obesity in this population is hormonal imbalance leading to increased appetite and decreased metabolism. Furthermore, dealing with a chronic disease like Frohlich syndrome can result in numerous psychological disorders such that it can have a negative impact on a patient’s motivation to lose weight.

Pathophysiology of Frohlich Syndrome 

Frohlich syndrome is caused by dysfunction of the hypothalamus, resulting in an imbalance of numerous hormones. The main hormones responsible for obesity and this disease are Leptin and Ghrelin. Adipose tissues produce leptin which signals the hypothalamus preventing hunger when the body does not need further caloric intake.³ In other words, leptin is responsible for regulating the balance between food intake and energy use (expenditure). On the other hand, ghrelin, often called hunger hormone, is released when your stomach is empty and your body needs to eat. Ghrelin also promotes fat storage and stimulates your pituitary gland to release growth hormones.² The functions of both Leptin and Ghrelin are vast, however, for the purposes of this article, our focus will remain on obesity and appetite. 

Frohlich syndrome differs from other obesity-related conditions as it is primarily related to dysfunction in the hypothalamus, instead of caloric intake and lifestyle factors. Furthermore, there are other symptoms associated with this disease which is not common in other obesity-related conditions. These symptoms include endocrine disorders, reproductive issues and growth abnormalities.

Approaches to Managing Obesity in Frohlich Syndrome

According to the World Health Organisation (WHO),⁷ obesity is defined as excessive fat accumulation that presents a risk to health. The most useful way to diagnose obesity is Body Mass Index (BMI) which is calculated by dividing your weight in kilogram by the square root of your height in meters. Therefore, a higher BMI indicates higher body fat and if your BMI is 30 or above, you are considered obese. Another diagnosis of obesity is waist circumference which allows screening for possible health problems. If your fat is more around your waist compared to your hip, you have an increased risk of heart disease and type 2 diabetes.¹ There are many ways to manage obesity in Frohlich syndrome:

Diet and physical activity

• Gaining weight happens when you consume more energy than you expend, meaning if your caloric intake exceeds your calories burnt. Therefore, a balanced diet with controlled portion can provide you with the energy that you need without consuming significantly more. In addition, a tailored nutritional guidance, where you can address the unique metabolic and hormonal challenges that occur in Frohlich syndrome could be beneficial in controlling appetite. 
• Implementing physical activity can help you increase the energy you expend both throughout the activity and overall by increasing your metabolic rate. Consistent physical activity is also greatly beneficial for your mental health.

Medical Interventions:

Pharmacological Treatments: 

Pharmacological treatments of obesity influence various physiological pathways to facilitate weight loss. Some examples include:

• GLP-1 agonist - the most common one for Frohlich syndrome which affects the hypothalamus which regulates appetite which leads to suppressed appetite.

Example: Semaglutide, imitates intestinal hormones to increase insulin production 

• Lipase inhibitor - blocks the action of enzymes responsible for fat digestion to reduces the absorption of fats. 

Example: Orlistat, 30% reduction of fat absorption

• Centrally acting agents - influence the central nervous system (CNS) resulting in controlled appetite and increased metabolism. This group of drugs modulate neurotransmitters such as norepinephrine and serotonin

Example: Lorcaserine, activates serotonin receptors. 

• SGLT-2 Inhibitors - increase glucose excretion hence reducing calorie absorption 

Example: Dapagliflozin, primarily used in diabetes 

Hormone Replacement Therapy (HRT) 

Due to the pathophysiology of Frohlich syndrome and the hormonal imbalance, hormone replacement therapy (HRT) is one of the foundational treatments of this disease⁴ as it addresses hormonal deficiencies that result in obesity, some examples are: thyroid hormone, growth hormone, and gonadotropins). This line of treatment is extremely beneficial for you as it addresses the root cause of weight gain, however, close monitoring of hormonal levels is necessary. 

Surgical Interventions - Bariatric surgery

Bariatric surgery is not the first line of treatment for Frohlich syndrome as this disease is caused by hormonal imbalance. Although surgical interventions are options to be carefully considered after numerous attempts to manage obesity. Comprehensive follow-up care is essential after this surgery in addition to lifestyle adjustments. 

FAQs

What causes damage to the hypothalamus? 

The most common cause of Frohlich syndrome and damage to the hypothalamus is tumours as they compress the hypothalamus causing dysfunction. Infection or inflammation from conditions such as meningitis and encephalitis and any other physical trauma to the head can lead to hypothalamus damage.

Does Frohlich syndrome affect both men and women? 

Yes, Frohlich syndrome is a rare disease but it can affect both men and women, however, it is more common in men. 

How is Frohlich syndrome diagnosed? 

To identify hypothalamic or pituitary damage, a combination of clinical evaluation, imaging studies and hormonal levels are used to diagnose patients. Furthermore, given that obesity is the main symptom of this disease, body mass index, body fat percentage and waist circumference are also used. 

Summary

Frohlich syndrome is a disease caused by lesions in the hypothalamus, which controls the release of numerous hormones and therefore can have significant impacts on hunger and appetite. Dysregulation of the leptin and ghrelin hormones in Frehlich syndrome results in increased appetite and eventually causes obesity. Obesity is measured by body mass index (BMI) and can be the root cause of many secondary conditions if not managed. The main two ways to manage obesity in Frohlich syndrome are lifestyle changes such as nutrition and physical activity, and pharmacological intervention. In this syndrome hormone replacement therapy (HRT) is the most common line of treatment as it addresses the hormonal imbalance the root cause of Frohlich syndrome. Furthermore, you also have the option of bariatric surgery, although it is not recommended.