**6.2 Evaluation**

Due to its pulsatile nature of secretion, random GH measurement is not preferred. Clinical diagnosis starts by observing the typical manifestations of GH hypersecretion (**Figure 3**). Once it is suspected, early morning GH level and IGF-1 level are measured. It is highly advised to use sex and age adjusted levels of IGF-1 as variations in the levels may result in false negative results. The gold standard test for acromegaly diagnosis confirmation is oral-glucose tolerance test (OGTT).

All patients with confirmed acromegaly should be screened for associated comorbidities which include hypertension, diabetes, cardiomyopathy and ECG, sleep apnea, and colonoscopy if the age above >40 years old. Patients who have acromegaly related comorbidities have two-fold increase in mortality [24]. While clinical manifestation is extremely indicative of the type of pituitary adenoma—lab values for other pituitary hormones are important screening factors for mixed adenomas (e.g. PRL co-secretion is found in 30% of patients). Standard visual field assessment should be offered to all patients who have macroadenomas abutting the visual apparatus on imaging studies.

Pituitary MRI is needed for evaluation of acromegaly of pituitary source. Because of its insidious onset, GH secreting pituitary adenomas present around 4–7 years after onset. At the time of diagnosis, around 75% of acromegaly patients have macroadenoma on MRI. It is important to note the extent of invasion to suprasellar and cavernous sinus compartments (**Figure 4**).

**Figure 3.** *Acromegaly diagnosis algorithm.*

#### **Figure 4.**

*Modified Hardy's classification for sphenoidal sinus and extrasellar extension (A), and Knosp classification of cavernous sinus invasion (B).*

#### **6.3 Management**

The goal of management in GH-secreting adenomas is to normalize GH/IGF-1 levels, remove the mass effect of adenoma from surrounding neurovascular structure, and reverse or control comorbidities that are related to high GH levels. Most of biochemical and structural changes caused by high GH status are reversible (**Table 5**). Treated acromegaly patients with postoperative GH <1 ng/mL have mortality rate that is similar to age-matched general population [27].

Surgical excision through a trans-sphenoidal route is the gold standard. Unless it is contraindicated, all patients should be offered surgical excision of the adenoma. In older reports before the year of 2000, GH normalization rate after surgical management was between 40 and 70% [28]. The most common cause of incomplete tumor excision and failure of GH normalization after surgery is extra-sellar tumor growth, specifically invasion into the cavernous sinus. Adenoma total resection will result in a biochemical cure which is defined as IGF-1 within normal range for age and gender, and suppression of GH to <1 ng/mL following OGTT [29].

Recent studies have found that the rate of medial wall invasion in GH-secreting adenomas between 70 and 89% and resection of the medial wall of the cavernous sinus resulted in higher post-operative GH normalization rate which in recent reports was found to be 67–92% [29–32]. Detection of suprasellar extension or cavernous sinus invasion can be evaluated and graded on pre-operative MRI scans by using Hardy's and Knops' classification systems (**Figure 4**), This system uses CISS and VIPE sequences to evaluate cavernous sinus invasion and optic canal tumor extension [33, 34].

Treatment algorithm is summarized in (**Figure 5**) which is adopted from The Endocrine Society Guidelines released in 2014 [35].

Important points regarding the management of GH-secreting adenomas:

• Surgical debulking should be offered to patients who harbor large adenomas with significant extra-sellar extension as that would increase the response to medical therapy.


*Pituitary Adenomas: Classification, Clinical Evaluation and Management DOI: http://dx.doi.org/10.5772/intechopen.103778*

#### **Table 5.**

*Reversible and irreversible biochemical and structural changes in treated acromegaly patients [22].*


#### **Figure 5.**

*Acromegaly management algorithm. SRL, somatostatin receptors ligands. \*Repeat surgery is recommended for residual and resectable disease. \*\*SRL are the first line of management in patients who are poor surgical candidates, have extensive parasellar invasion, or who had only tumor debulking.*

