What Is Frohlich Syndrome?

Introduction

Frohlich Syndrome, also referred to as Babinski-Fröhlich Syndrome, Adiposogenital Dystrophy or Sexual Infantilism, is a relatively rare hormonal disorder that predominantly affects males. 

The condition stems from disruptions in an important brain region called the hypothalamus. Unlike genetic conditions, Frohlich Syndrome is acquired, arising from various factors that can affect the brain at any point in time. The complications of this syndrome require early identification and thorough management due to its diverse consequences, particularly the potential for significant health issues linked to obesity.

Historical context

In the early 1900s, Joseph Babinski and Alfred Fröhlich made a significant breakthrough by identifying the "Frohlich Syndrome", linking obesity and sexual development issues in patients with pituitary tumours. This pivotal discovery marked the inception of Neuroendocrinology. Fröhlich's belief that the syndrome stemmed from pituitary gland problems due to tumour growth was shared by Harvey Cushing. Through surgeries on dogs, Cushing recreated similar features but encountered issues due to anatomical differences. Despite this, Cushing's interpretation gained acceptance due to his influential work on pituitary gland diseases.^1,2

The term "Prader-Willi syndrome" emerged from the doctors Andreas Prader and Heinrich Willi, who introduced it in 1956. Prader-Willi Syndrome is a specific genetic disorder characterized by a loss of gene expression on chromosome 15q11-q13. While Dr. Frohlich's findings were relevant, they were ultimately distinct from Prader and Willi's discoveries. This is why the term "Frohlich Syndrome" is sometimes used to refer to these parallel yet separate conditions.³

Initially, diagnosis relied on specific signs and chromosome studies. However, by the 1990s, more accurate genetic tests emerged, allowing for precise identification. Advancements in recent years, particularly in genetic testing, have deepened our understanding of this condition across all life stages, from infancy to adulthood. This progress aids early recognition, improved care, and a better grasp of its impact on overall health.^3,4

Causes

Froehlich syndrome is a cluster of hormone-related abnormalities that stem from damage to the hypothalamus, a brain region connecting the nervous system and the endocrine system through the pituitary gland. This part of the brain oversees sleep patterns, body temperature, and composition while regulating the pituitary glands to release various hormones governing growth, metabolism, and body maturation. As a result, damage to the hypothalamus can indirectly disrupt several hormonal axes involving the pituitary gland. 

Unlike conditions like Prader-Willi syndrome, Froehlich syndrome is not inherited but rather acquired, usually associated with tumours in the hypothalamus area or their surgical treatment. This leads to increased appetite and reduced gonadotropin secretion. Males are more frequently affected by this syndrome.^3,5

Symptoms

Frohlich syndrome manifests with recognizable symptoms like delayed puberty, short stature, and obesity due to an increased appetite. However, its impact goes beyond these core features. Those affected might also experience issues like nail abnormalities, headaches, sunburn susceptibility, low blood sugar, frequent urination, and low blood pressure. The syndrome disrupts endocrine functions, possibly leading to hormonal imbalances and hypoglycemia. Cardiovascular aspects could result in low blood pressure coupled with excessive thirst. Unusually low body temperatures might occur due to broader regulatory disruptions. 

In children, additional symptoms could involve diabetes, vision problems, and cognitive challenges. This range of symptoms underscores the syndrome's complexity and varied effects on different body systems.^5,6

Complications

The complications of Frolich's Syndrome arise from its severe forms and encompass various challenges. These include obesity due to disrupted metabolism, delayed physical and sexual growth, potential impacts on mental development, and, in rare cases, the development of diabetes mellitus. These complications highlight the syndrome's far-reaching effects on the physical, emotional, and cognitive aspects of an individual's health and underline the need for timely diagnosis and comprehensive management.⁵

Diagnosis

Diagnosing Frohlich Syndrome is challenging due to variations in its presentation. A comprehensive evaluation of patients' developmental history involving physical and cognitive aspects is essential. In male patients, genital examinations are crucial, while pelvic organ assessments are important for females, and hormone assays offer insights into endocrine disruptions. 

Diagnostic tests such as urinalysis often reveal low levels of the hormones excreted by the pituitary glands. Additionally, doctors often order blood tests to assess levels of growth hormone (GH), prolactin, luteinizing hormone (LH), thyroid-stimulating hormone (TSH) and follicle-stimulating hormone (FSH). 

Diagnostic imaging of the brain, like computed tomography (CT) scans or magnetic resonance imaging (MRI), is conducted. These tests allow doctors to examine any growths, lesions, or tumours that may be present in the brain. Distinguishing the syndrome from Prader-Willi syndrome is vital. If hormone levels are within normal ranges, the diagnosis cannot be confirmed.^5,6

Management and treatment

The treatment of Frohlich Syndrome is individualized based on the severity of symptoms. Surgical removal of brain tumours or lesions, often through the paranasal sinuses, is an option. Hormone replacement therapy can restore hormonal balance. Weight management involves diet and exercise programs, and bariatric surgeries like gastric bypass may be considered for obesity control. Personalized care aims to alleviate symptoms and address underlying causes for improved well-being.²

Summary

Froelich's Syndrome, also referred to as Adiposogenital Dystrophy, is a rare acquired disorder with two main causes: tumours near the pituitary gland in the brain or a dysfunctional hypothalamus. This leads to hormonal abnormalities, growth issues, obesity, and vision loss. Treatment involves surgical tumour removal and hormone replacement therapy. The prognosis depends on individual response to treatment and the syndrome's complexities.