Can immediate postoperative random growth hormone levels predict long-term cure in patients with acromegaly?

BACKGROUND: Growth hormone (GH) levels following oral glucose tolerance test (OGTT) at 12 weeks or later after surgery have been accepted as the most reliable parameter for defining remission and/or cure in patients with acromegaly. However, the role of random GH in predicting remission in the immediate postoperative period using modern criteria is not known. This study was undertaken to evaluate the role of random GH levels in first 5 postoperative days as an early predictive tool for long-term remission of patients with acromegaly following transsphenoidal pituitary surgery (TSS). PATIENTS AND METHODS: Seventy-five consecutive acromegaly patients with at least three postoperative OGTT values at 3, 6, and 12 months of follow-up were included in the study. GH levels were measured just before surgery, in the immediate postoperative period, at 6 h and on day 1 to day 5 after surgery. Remission was defined as normal age-specific insulin-like growth factor-1 and either basal fasting GH <1 ng/ml or a nadir GH following OGTT <0 .4 ng/ml at 3 months of surgery. RESULTS: Of the 75 patients with acromegaly who underwent TSS, long-term remission was achieved in 42 (56%) patients. GH values ≤1.55 ng/ml at 6 h of surgery showed the highest predictive power for long-term remission, with a sensitivity of 81.2% and a specificity of 83.3%. The duration of disease and tumor volume had no effect on the 6 h GH value-related prediction of cure. CONCLUSION: Early postoperative GH values may be used to predict long-term cure. A value of ≤1.5 ng/ml at 6 h following surgery may predict long-term cure in two-thirds of the patients with acromegaly who undergo TSS.

Clinical profile and outcome of patients with acromegaly according to the 2014 consensus guidelines: Impact of a multi-disciplinary team.

AIM: The diagnosis and treatment of acromegaly, a rare and possibly curable disease, has undergone a paradigm shift in the past few decades. Our aim was to study the changing trends in clinical presentation, management and outcome of the disease in the last fifteen years. METHODOLOGY: 271 consecutive patients with acromegaly treated at the Departments of Endocrinology and Neurosurgery, PGIMER, Chandigarh, between 2000 and 2014, were included in the study. Clinical and hormonal profiles, comorbidities, treatment modalities, outcome and mortality data were evaluated. The cure rate was assessed according to the present consensus criteria. RESULTS: The gender distribution was equal with the mean age (±SD) of 37.1 ± 12.3 years at diagnosis. The average lag period to diagnosis was 4.7 ± 4.2 years. The most common presenting manifestations were acral enlargement and headache followed by visual deficits. The overall mortality rate was 5%, with the perioperative mortality being 1.5%. The most prevalent comorbidities in our series were hypertension (17.7%), diabetes mellitus (16.2%), arthropathy (11.8%) and obstructive sleep apnea (10.3%). Overall, 2 patients in our series suffered from extra-pituitary neoplasms and 12 patients had apoplexy as the presenting manifestation. As per the present consensus criteria, cure rate in our series was 28.5%. The cure rate was only 7.9% when many surgeons were operating. It increased to 25.5% when surgeries were being performed by one surgeon exclusively; and, when a sub-specialty clinic exclusively for pituitary diseases was set up, the cure rates improved upto 56%. CONCLUSION: Acromegaly has wide-ranging manifestations from acral enlargement to altered sensorium; incidental diagnosis was not prevalent in our series. Majority of the cases were due to the presence of a pituitary macroadenoma. Better cure rate can be achieved only when a dedicated group of multi-disciplinary team is involved.

Surgery, Octreotide, Temozolomide, Bevacizumab, Radiotherapy, and Pegvisomant Treatment of an AIP Mutation‒Positive Child.

CONTEXT: Inactivating germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are linked to pituitary adenoma predisposition. Here, we present the youngest known patient with AIP-related pituitary adenoma. CASE DESCRIPTION: The patient presented at the age of 4 years with pituitary apoplexy and left ptosis with severe visual loss following a 1-year history of abdominal pain, headaches, and rapid growth. His IGF-1 level was 5× the upper limit of normal, and his random GH level was 1200 ng/mL. MRI showed a 43 × 24 × 35‒mm adenoma with suprasellar extension invading the left cavernous sinus (Knosp grade 4). After transsphenoidal surgery, histology showed a grade 2A sparsely granulated somatotropinoma with negative O6-methylguanine-DNA methyltransferase and positive vascular endothelial growth factor staining. Genetic testing identified a heterozygous germline nonsense AIP mutation (p.Arg81Ter). Exome sequencing of the tumor revealed that it had lost the entire maternal chromosome-11, rendering it hemizygous for chromosome-11 and therefore lacking functional copies of AIP in the tumor. He was started on octreotide, but because the tumor rapidly regrew and IGF-1 levels were unchanged, temozolomide was initiated, and intensity-modulated radiotherapy was administered 5 months after surgery. Two months later, bevacizumab was added, resulting in excellent tumor response. Although these treatments stabilized tumor growth over 4 years, IGF-1 was normalized only after pegvisomant treatment, although access to this medication was intermittent. At 3.5 years of follow-up, gamma knife treatment was administered, and pegvisomant dose increase was indicated. CONCLUSION: Multimodal treatment with surgery, long-acting octreotide, radiotherapy, temozolomide, bevacizumab, and pegvisomant can control genetically driven, aggressive, childhood-onset somatotropinomas.