Big heart, small ring
CASE CONTINUED: LABORATORY VALUES, TREATMENT OPTIONS
Our patient’s repeat fasting plasma glucose is 137 mg/dL; his hemoglobin A1c is 7.3%, consistent with diabetes mellitus secondary to acromegaly. Other laboratory values:
- Morning cortisol level 15 μg/dL (reference range 5.3–22.5),
- Prolactin 23 ng/mL, confirmed with 1:100 dilution (4.0–15.2)
- Total testosterone 59 ng/dL (193–824)
- LH 2.1 mIU/mL (1.8–10.8)
- FSH 3.0 mIU/mL (1.5–12.4)
- TSH 2.5 mIU/L (0.5–4.5)
- Free T4 1.3 ng/dL (0.9–1.7).
The patient is started on metformin 500 mg by mouth twice a day, counseled on a healthy diet, and informed that his diabetes may be a complication of his acromegaly. He is anxious to learn how his acromegaly can be treated.
5. What treatment would you recommend for the patient’s acromegaly?
- Medical treatment first, then transsphenoidal resection of the pituitary macroadenoma if medical treatment fails
- Medical treatment first, radiotherapy if medical treatment fails, and transsphenoidal resection of the pituitary macroadenoma as a last resort
- Transsphenoidal resection of the pituitary macroadenoma first, medical treatment if surgery fails, and radiotherapy if both surgery and medical treatment fail
- Taking a safe, conservative approach, monitoring IGF-1 levels frequently; starting medical treatment if acromegaly does not go into remission in 1 year
The initial treatment of choice for most patients with acromegaly is resection of the pituitary tumor.
A transsphenoidal approach is used for most patients; only rarely is craniotomy necessary. Endoscopic and microsurgical techniques reduce postoperative morbidity.17 Postoperative complications include symptoms related to the transsphenoidal approach (nasal congestion, sinusitis, epistaxis), cerebrospinal fluid leak, hemorrhage, meningitis, stroke, visual impairment, vascular damage, transient or permanent diabetes insipidus, and hypopituitarism. The surgical mortality rate is less than 0.5%.18,19
Successful resection of a pituitary tumor would lead to normalization of the IGF-1 level, a drop of the GH level to below 1 μg/L, and relief of the effect of the tumor pressing against other structures. An IGF-1 level and a random GH level should be obtained 12 weeks after the surgery.14 If the GH level is higher than 1 μg/L, a GH suppression test with a 75-g oral glucose load should be performed.14 MRI of the sella turcica should be done 12 weeks after surgery to visualize residual tumor and adjacent structures.14
A large tumor size, suprasellar extension, and high preoperative levels of IGF-1 and GH are associated with a lack of surgical success; however, surgical debulking should still be considered in patients with a low chance for surgical cure to improve the probability of achieving biochemical remission with postoperative medical and radiologic therapy.20
Medical therapy can be the initial treatment if the patient refuses surgery or if surgery is contraindicated because of severe comorbidities or because structural features of the tumor confer a high surgical risk (eg, if the adenoma encases the cavernous portion of a carotid artery).13 Medical therapy may shrink the tumor in some patients and may thereby make surgical resection easier and more likely to be successful.
Radiotherapy is usually reserved for patients whose tumors recur or persist postoperatively and who are resistant to or intolerant of medical therapy.14 The soft tissue changes caused by acromegaly may regress with treatment to some degree, but they are not likely to resolve completely; the bone changes do not regress.
CASE CONTINUED: MEDICAL TREATMENT
Three months after transsphenoidal resection of his pituitary macroadenoma, our patient’s laboratory values are as follows:
- IGF-1 400 ng/mL
- Morning cortisol 20 μg/dL
- Testosterone 95 ng/dL
- LH 2.1 mU/mL
- FSH 3.7 mU/mL
- Prolactin 12 ng/mL
- TSH 2.3 mIU/L
- Free T4 1.2 ng/dL
- Basic metabolic panel normal.
The patient denies frequent urination or increased thirst. Repeat MRI of the pituitary with contrast shows a residual 1.3-cm adenoma with no suprasellar extension.
6. What is the best next treatment choice for the patient?
- A GH receptor antagonist (pegvisomant)
- A somatostatin receptor ligand (SRL) such as octreotide
- Cabergoline (a dopamine agonist)
- A combination of an SRL and pegvisomant
An SRL such as octreotide would be the best choice for this patient.
The medical options for acromegaly are SRLs, pegvisomant, and cabergoline.21–23 The Endocrine Society guidelines recommend either an SRL or pegvisomant as the initial adjuvant medical therapy in patients with persistent disease after surgery.14 However, pegvisomant is much more expensive than any SRL, so an SRL would be a better choice in this patient. Also, pegvisomant does not suppress tumor growth, in contrast to SRLs, so SRLs are preferred in patients with large tumors abutting the optic chiasm.14
SRLs are used as primary therapy in patients who cannot be cured by surgery, have extensive cavernous sinus invasion, have no chiasmal compression, or are poor surgical candidates.
The medical treatment of acromegaly is summarized in Table 2.14,15 Side effects of the medications used to treat acromegaly are summarized in Table 3.14
