As kids, we all were in a hurry to grow up. But it is not a very pleasant condition if people keep growing, even in their adulthood. Let us dive into a story of a patient with that peculiar growth disorder, acromegaly.

Case Scenario

Kevin, a 36-year-old man, presented to the outpatient department with headache, tiredness, and coarsening of facial features for two years. He complained about a change in voice, loss of libido, and unusual weight gain for a five-month period. Also, he had breathlessness intermittently.

On examination, his blood pressure was 155/95mmHg. Pulse was regular with normal volume and a rate of 88 beats per minute. Kevin had a respiratory rate of 22 breaths per minute, and there was no evidence of lymphadenopathy. His general appearance looked abnormal. Careful examination revealed prominent supraorbital ridges, widened teeth spaces, macroglossia, and large ears.

He complained that his normal shoes were too tight for him now, and he had spade-like feet and hands. A visual field defect was found in the central nervous system examination. However, Kevin had no symptoms of heart failure.

Basic investigations were normal with normal TSH and free T3/T4 levels. Serum prolactin level was 15ng/ml, which was in the normal range. He had a detectable level of growth hormone (GH) and an impaired oral glucose tolerance test. So, we came to the working diagnosis of acromegaly.

What You Need to Know about Acromegaly

It is a hormonal disorder in adults. ‘Acro’ refers to extremity, and ‘megaly’ means enlargement. So, simply put, in acromegaly, excess GH continues the growth of extremities.

The action of the GH is to stimulate soft tissue and skeletal growth. Before epiphyseal plates fuse in bones, excess GH causes gigantism. After epiphyseal fusion, it causes asymmetrical growth of bones and soft tissues, causing acromegaly.

What is the etiology of acromegaly? Well, in almost all cases, it is due to a GH-secreting pituitary tumor. Very rarely, pituitary hyperplasia due to excess GnRH hormone and non-pituitary GH secreting tumors can cause this.

Pituitary tumors are benign in almost all cases. Symptoms due to some tumors may not arise till later stages as they grow slowly. But in other cases, the rapid growth of the tumor will cause early symptoms. The local effects of the tumor will depend on its size and location.

Acromegaly is a disorder that affects males and females equally. Presentation to medical care can be at any age in adulthood. The overall incidence of this disease is about 3-4million per year.

How can a Patient with Acromegaly Present to You?

The commonest presentation in acromegaly is changes in appearance – hope you remember our patient, Kevin. He had few abnormalities in his appearance. What most people notice in the early stage of the disease is soft tissue swelling of the feet and hands. They will get issues with the sizes of their usual shoes or rings. Gradually, abnormalities in facial features will develop with bony changes due to excess GH.

Some patients will complain about obstructive sleep apnea due to soft tissue swelling in the larynx. In women, the presentation can be due to amenorrhea and oligomenorrhoea. You may also meet patients worried about deep voice, goiter or tingling sensation in hands.

Don’t forget that non-specific features like increased sweating, weight gain, tiredness, breathlessness, muscle weakness, joint pain, or galactorrhea can bring an acromegaly patient to you. Rarely, some patients present with impotence and poor libido due to acromegaly.

As the main reason for acromegaly is a pituitary tumor, we have to look for symptoms of hypopituitarism and local mass effects when an acromegaly patient presents to us. What do you expect to see as effects of hypopituitarism? Tiredness, cold intolerance, dry skin, and slow thinking are common in TSH hormone deficiency. Reduced LH and FSH hormones can lead to amenorrhea, loss of libido, and lack of secondary sexual hair.

Local mass effects due to pituitary tumors on the hypothalamus can lead to obesity, altered appetite, thirst, and somnolence. Ventricular hydrocephalus can cause headaches, while cranial nerve palsies in the third, fourth, and sixth nerves can occur due to compression at the cavernous sinus. About one-fourth of the patients with acromegaly, present with headache or visual field defects. So, always you have to take a comprehensive approach if you suspect acromegaly in your patients.

Differential Diagnoses

I hope you are clear by now that a patient with acromegaly can present with a wide range of symptoms. We have to think about the differential diagnoses for a patient according to that particular presentation. Considering our patient, Kevin, we thought about Marfan’s syndrome, prolactinoma, and hypothyroidism other than acromegaly.

Marfan’s syndrome is a spectrum of symptoms that affects connective tissues. Though it is an inherited disorder, the clinical presentation can happen in adulthood. It can affect different organs in our body, causing a myriad of symptoms.

Prolactinoma is a noncancerous tumor that produces excess prolactin. Major effects of prolactinoma are due to reduced sex hormone levels. Hypothyroidism is a condition where the thyroid gland is not producing sufficient thyroid hormone. As we go on, let us see how we came to the diagnosis of acromegaly excluding others.

On Examination

Considering abnormal facial features, you have to look into prominent supraorbital ridges, inter-dental separations, prognathism, large tongue, and visual field defects. Some of these might not be recognized by patients themselves.

Generally, we have to assess whether patient has thick greasy skin or hirsutism. Also, there will be excess skin as tags over the body. The hands and feet may in spade-like shape. We could find these in Kevin.

Adding insult to injury, acromegaly can lead to many complications. Don’t forget to evaluate the patient for carpal tunnel syndrome as bone and soft tissue overgrowth often trap nerves and cause neurological problems. Bone and cartilage excessive growth also cause arthritis. So, we have to perform a thorough joint examination.

Blood pressure measurement is essential in every patient with acromegaly as they have high blood pressure usually. We also have to look into clinical signs of heart failure like bi-basal crepitation, elevated jugular venous pressure and hepatomegaly.

In central nervous system examination, we have to assess Kevin for cranial nerve palsies and the visual field. In severe cases of acromegaly, the patient may have enlarged body organs, including the heart, kidneys, spleen and liver. So, we have to feel for apex beat and perform abdominal examination carefully.

We can use examination findings to exclude our differential diagnosis. In Marfan’s syndrome, they will have a small jaw and arachnodactyly. Dry skin, puppy face, hair loss, or goiter will lead us towards hypothyroidism. So, we performed a detailed examination of our patient as it is vital to find clues for diagnosis and assess severity and complications.

What Investigations did we Order?

Investigations help us to confirm the diagnosis and get an overall picture of the condition of the patient. What investigations do you think we performed for Kevin? We did a blood GH level, IGF-1 level and oral glucose tolerance test (OGTT) to confirm the diagnosis. We did some other investigations to locate the tumor and assess the complications.

We usually measure the blood GH level after the patient has fasted overnight to decide whether it is elevated. GH is secreted in spurts by the pituitary, and blood GH concentration varies with time. So, a single elevated GH level measurement is not enough in diagnosis. Mr. Kevin had elevated blood GH levels in two consecutive measures.

We can use IGF-1 as a screening test for acromegaly. Elevated GH increases IGF-1 in blood. As IGF-1 blood level is usually stable over the day, it is often a more reliable measure to get an idea about mean GH secretion. Elevated IGF-1 level indicates acromegaly in most cases. But it can be falsely positive in pregnancy, old age, and uncontrolled diabetes mellitus. In about one-fourth of patients with acromegaly, IGF-1 can be normal despite elevated GH secretion. So, we use IGF-1 as a screening test for acromegaly.

OGTT is the diagnostic test for acromegaly. We have to take a series of blood samples for GH and glucose. In acromegaly, there is a failure to suppress GH release by glucose. OGTT can be falsely positive in pregnancy, puberty, hepatic and renal diseases.

To locate the tumor, we have to use imaging methods, like magnetic resonance imaging and computed tomography of the pituitary. This helps to get an idea about the local effects of the tumor also. A lateral skull x-ray may reveal a double floor appearance suggesting a pituitary tumor.

Investigations play a major role in excluding other differentials. We can measure serum prolactin levels to exclude prolactinoma. Thyroid function tests, including TSH and free T3/T4 levels, have to be measured to exclude hypothyroidism.

We have to perform a pituitary function test to assess the activity of the gland. ECG, echo, chest x-ray, and abdominal x-ray will reveal complications of acromegaly. We can perform usual baseline investigations like full blood count, CRP, and ESR to assess the condition of the patient. It is essential to measure blood sugar levels as they are at a risk of developing type 2 diabetes. But we have to always limit our investigations to necessary and justify their need.

Diagnosis

In a patient presenting with symptoms of acromegaly, we can walk along the pathway of diagnosis with the examination findings and confirm it by investigations. The OGTT test is the primary diagnostic test for acromegaly.

Impaired OGTT test in Kevin was supported by evidence of elevated GH hormone level and IGF-1 level. So, we came to the diagnosis of acromegaly in him. We excluded other differentials by physical examination and investigation findings.

Management

Untreated acromegaly has a markedly high mortality rate. This can be due to coronary artery disease, heart failure, colonic carcinoma, and hypertension-related causes. Therefore, we have to treat all the acromegaly patients except very old with minimal issues. The aim of the treatment is to maintain a mean GH level below 5mU/L.

Treatment options we can use are surgery, pituitary radiotherapy, and medicines. By these methods, we can control tumor size, maintain normal GH and IGF-1 levels, improve symptoms, and prevent complications. The treatment plan will vary from one patient to another, depending on symptom severity, age, tumor size, GH and IGF-I levels, and comorbidities of the patient.

Surgical management

We thought to use a trans-sphenoidal surgery to respect the pituitary tumor in Mr. Kevin. It is done accessing through the sphenoid sinus and nose. This is the first-line therapy in most cases. It has a cure rate of 80% in microadenoma and 40% in macroadenoma. Trans-frontal surgery is a method rarely used.

Complications of the surgery are CSF leakage, bleeding, meningitis, electrolyte imbalance, osmotic imbalance and pituitary insufficiency. But still, surgery is the most successful method to treat acromegaly. Some patients may need additional treatment along with surgery for a full recovery.

Radiotherapy

This is usually used as secondary therapy after a failed surgery or when surgery is contraindicated. Stereotactic is the common radiation type used. Conventional radiotherapy is an alternative method. Often, it is combined with medications as the response to radiotherapy is a slow process.

Medical management

Somatostatin analogs like octreotide and larazotide are the treatment of choice in treating resistant cases. These are usually used for short-term treatment till another modality becomes effective.

Side effects of these drugs are pain at the injection site, abdominal cramp, loose stools, increased risk of gall stones and impaired glucose tolerance.

Prior to definitive therapy, we can give dopamine agonists to shrink the tumor. It will control GH secretion and thus alleviate symptoms. Usually used in combination with somatostatin analogs, these are most effective for mixed GH and prolactin-producing tumors.

GH antagonists can bring IGF-1 to be normal in about 90% of acromegaly patients. But it can’t shrink the tumors or lower GH levels. If other treatment methods are unable to reduce IGF-1 to a safe level, this is a good additive way.

Managing complications

Type 2 diabetes, heart failure, high blood pressure, arthritis, and carpal tunnel syndrome are the common complications seen in acromegaly. We have to examine and investigate patients for these complications. Prevention and early identification of complications is essential to increase the survival of the patient.

Acromegaly can cause turbulence in one’s life. It is essential that we educate Kevin about the disease and make necessary arrangements to monitor his disease progression. Routine clinic visits may be needed for most patients. Some patients will need psychological and social support. So, we have to take a multi-modal approach to give a better outcome to a patient with acromegaly.

Conclusion

Acromegaly is a hormonal disorder that causes overgrowth of bone and soft tissue in adulthood due to excess GH. The main cause of this is pituitary tumors. It is essential to treat acromegaly patients as they have high mortality due to complications. There are different treatments modalities, and we have to arrange the treatment plan according to the individual patient presentation.

References

1. Kumar and Clark’s Clinical Medicine – 9th Edition [Internet]. [cited 2021 Feb 13].  https://www.elsevier.com/books/kumar-and-clarks-clinical-medicine/kumar/978-0-7020-6601-6
2. Acromegaly- NORD

https://rarediseases.org/rare-diseases/acromegaly/

• Acromegaly information

https://www.mountsinai.org/health-library/diseases-conditions/acromegaly