Acromegaly : A Disease Where Growth Doesn’t Stop

Meet Michael Fig, a 35-year-old software engineer. He noticed that his wedding ring no longer fit and his jaw seemed more pronounced. He also experienced constant fatigue and distressing joint pains. Little did he know that these symptoms would lead to a life-changing diagnosis: acromegaly.

Acromegaly, a rare but serious hormonal disorder, affects approximately 60 individuals per million globally. Despite the seemingly low incidence, the cumulative global impact is substantial. Notably, a Journal of Clinical Endocrinology & Metabolism report indicates an average diagnostic delay of 5 to 10 years, underscoring the imperative to enhance awareness and understanding of this condition.

What Is Acromegaly?

Acromegaly is a hormonal disorder that is caused by excessive production of growth hormone. The most common cause of this condition is a benign tumor in the pituitary gland, which leads to abnormal growth in body tissues, especially in the hands, feet, and face.

Because of the relative rarity of this disorder, delayed diagnosis is relatively common; however, proper management and counteraction of all possible complications require prompt diagnosis and treatment.

Acromegaly Causes

The primary cause of acromegaly is:

1. Tumor in pituitary gland: A benign adenoma of the pituitary gland secretes excessive growth hormone, which has been observed in about 95% of cases.

Other less common causes include the occurrence of other forms of tumors, genetic syndromes, and overproduction of GHRH.

 Acromegaly Symptoms

Acromegaly symptoms arise gradually in the majority of the cases after years. Thus, early diagnosis is extremely difficult in all cases

Adults with acromegaly may experience the following symptoms:

• Enlarged hands or feet.
• Changes in your face shape, including a more prominent jaw and/or forehead.
• Increase in size of your lips, nose and/or tongue.
• Excessive sweating or oily skin.
• Deepening of your voice.

Other symptoms include:

• Headaches.
• Joint pain.
• Vision changes.
• Increase in the number of skin tags.
• Numbness in your hands.
• Sleep apnea.
• Carpal tunnel syndrome or spinal cord issues.

For Michael, it is the gradual changes in appearance with his chronic fatigue that made him go to the emergency room.

Diagnosis of Acromegaly

Diagnosis of acromegaly is step-wise.

1. Medical History and Physical examination: The doctor will ask about medical history and conduct a physical exam.
2. Blood tests: This measures the amount of GH and IGF-1.
3. Oral glucose tolerance test: It is used to measure suppression of GH after glucose ingestion.
4. Imaging studies: MRI scans or CT scans which identify the location and size of the pituitary tumors

Early diagnosis is crucial in ensuring successful therapy and avoidance of complications in the long run.

Treatment of Acromegaly

Treatment aims to reduce excess GH production, relieve the mass effect caused by the pituitary tumor, and control health complications that are already present.

Treatment for acromegaly includes the following:

1. Surgery: Surgical removal of the pituitary tumor (transsphenoidal surgery).
2. Drugs: There are three types of drugs for treating acromegaly – each act by different mechanisms: Somatostatin Analogues, Dopamine Agonist, Pegvisomant 
3. Radiotherapy: Used when drugs and surgery do not help.

Micahel’s history included surgery. Surgical intervention destroyed his pituitary tumor, followed by drug therapy to regulate his hormone levels. With pituitary surgery, he experienced tremendous relief in symptoms and quality of life.

GHRH (Growth Hormone-Releasing Hormone)

GHRH (Growth Hormone-Releasing Hormone) is a hypothalamic hormone that causes the pituitary to secrete GH. It has a central role in the growth and proliferation of cells in humans and other animals. 

IGF-1 is a hormone, a chemical messenger in bloodstream that controls the actions of certain cells or organs. IGF-1 manages the effects of growth hormone (GH) in your body. Together, IGF-1 and GH promote normal growth of bones and tissues.

Hypersecretion of GHRH:

Overproduction of GHRH can arise due to various influences, such as a pituitary tumor or disorders in the hypothalamus. Subsequently, the consequence is:

2. Increased secretion of GH: Increased GHRH stimulates the pituitary gland to secrete more growth hormone than usual.
3. Increased levels of IGF-1: Increased GH leads to more IGF-1 production by the liver.
4. Acromegaly: Chronic overproduction of GHRH after attaining adulthood leads to acromegaly, where the growth of hands, feet, and facial features is disproportionately excessive.
5. Gigantism: Overproduction of GHRH in children before closure of the growth plates leads to gigantism, which means excessively increased growth of stature and entire body.

Levels of GH and IGF-1:

Overproduction of GHRH has extreme effects on the levels of GH and IGF-1 in the body:

1. GH levels: The normal range for GH in adults is between 0.4 and 10 ng/mL. In GHRH overproduction, GH levels can rocket to unnatural heights
2. IGF-1 levels: Normal IGF-1 levels will usually be age- and sex-dependent and will range from about 100 to 300 ng/mL in adults. On GHRH overproduction, the IGF-1 level shoots up.
3. Diurnal variation: GH secretion is usually pulsatile and peaks during sleeping, but excessive production of GHRH will disturb this diurnal variation, and the levels of GH become constantly high day long.
4. Feedback mechanism: The physiological mechanisms that feedback to limit hormone production get flattened by the persistent stimulation of GHRH, which in turn keeps levels of GH and IGF-1 high.
5. Metabolic consequences: GH can cause insulin resistance and hyperinsulinemia, which can lead to type 2 diabetes.
6. Long term consequences: Hypersecretion of GH and IGF-1 due to the overproduction of GHRH leads to diverse health complications from cardiovascular diseases to joint pains and also endangering the patient with various types of cancers.

All of these elements play a significant role in the identification and treatment of diseases resulting from oversecretion of growth hormone. Appropriate medical assessment and treatment are essential for effective treatment of conditions associated with overproduction of GHRH.

Acromegaly vs Gigantism

Acromegaly and gigantism both have an excess growth hormone as the causative agent but differ in the time in which they present:

Acromegaly Presents after the closure of the growth plates in adults. Consequently, causes the overgrowth of bones and soft tissues. Gigantism Often starts in childhood or adolescence before the closure of the growth plates. In this situation, there is an abnormal increase in height and the enlargement of internal organs.

Early diagnosis can dramatically improve therapeutic results and quality of life.

Though it is quite rare, acromegaly can manifest in very profound effects on a person’s health and quality of life. Indeed, such is the case with Michael’s story, for it underscores the importance of noticing subtle changes in one’s body and then seeking medical attention if something might seem amiss. With continued research determining more specific information about this condition, new treatment options and diagnostic tools are promising in earlier detection and better management.

The experience of acromegaly varies for everyone, and with proper medical care and support, many people like Michael can successfully manage their condition and become productive members of society. Increased awareness and understanding about this rare but significant hormonal disorder are indispensable steps toward earlier diagnosis and better outcomes for those affected by it.

References :

[1] Lavrentaki A, et al. Epidemiology of acromegaly: review of population studies. Pituitary, 20(1), 4-9.

[2] Broder MS, et al. Delay in diagnosis of acromegaly: A systematic review and meta-analysis. Endocrine Practice, 22(6), 709-720.

[3] Acromegaly. The Pituitary Foundation [Internet].

https://www.pituitary.org.uk/information/acromegaly/. Accessed Oct. 04, 2024.

[4] Acromegaly. Endocrine Society [Internet].

https://www.endocrine.org/patient-engagement/endocrine-library/acromegaly. Accessed Oct. 01, 2024.

[5] Acromegaly: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism [Internet]. 

https://academic.oup.com/jcem/article/99/11/3933/2836347. Accessed Sept. 30, 2024.

[6] Acromegaly. NORD – National Organization for Rare Disorders[Internet]. 

https://rarediseases.org/rare-diseases/acromegaly/. Accessed Sept. 26, 2024.[7] Acromegaly. Orphanet Journal of Rare Diseases [Internet].

https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-3-17. Accessed Oct. 05, 2024