Endocrine (2013) 43:239–241 DOI 10.1007/s12020-012-9759-z
LETTER TO THE EDITOR
Renaissance of acromegaly after bariatric surgery Albert Lecube • Ramon Vilallonga • Giacomo Sturniolo • Gabriel Obiols Jose´ Manuel Fort
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Published online: 26 July 2012 Ó Springer Science+Business Media, LLC 2012
Dear Sir, The discouraging results provided by dietary and behavioural treatments, and the virtually non-existent drug treatments, have led to an exponential increase in use of surgery to treat obesity [1]. An increased prevalence of obesity has also been reported in patients with acromegaly, a rare and severe systemic disease caused by a growth hormone (GH)-secreting pituitary adenoma, compared to the general population [2]. In obesity, GH responses to a wide variety of GH secretion stimulators, as well as 24 h spontaneous GH release are decreased, making difficult acromegaly follow-up. Moreover, insulin-like growth factor-1 (IGF-1), which mediates some of the metabolic actions of GH, is reported to be decreased in obesity and negatively correlated to visceral fat [3]. To the best of our knowledge, we report the first case of a patient with acromegaly who underwent bariatric surgery and we describe the biochemical effects associated with the resolution of obesity and its comorbidities. A 55-year-old Caucasian woman with acromegaly was referred to our Obesity Unit in January 2006. Her history included a long condition of morbid obesity since childhood, with gradual increase of weight from her second pregnancy, holding a weight in recent years around 115 kg.
A. Lecube (&) G. Sturniolo G. Obiols Obesity Unit, Endocrinology and Nutrition Department, Hospital Universitari Vall d’Hebron, Passeig Vall d’Hebron, 119–129, 08035 Barcelona, Spain e-mail:
[email protected] R. Vilallonga J. M. Fort Endocrinology, Bariatric and Metabolic Surgery Unit, Hospital Universitari Vall d’Hebron, Passeig Vall d’Hebron, 119–129, 08035 Barcelona, Spain
She had undergone a selective trans-sphenoidal removal of a pituitary adenoma of 2.3 cm with suprasellar extension, impingement of the optic chiasm, and invasion of the left cavernous sinus at age 35. Postoperatively, she was under treatment first with bromocriptine and after with somatostatine-analogues at stable doses (lanreotide 90 mg once monthly). However, her serum IGF-1 values remained above the adjusted normal range. Her medical history revealed type 2 diabetes (T2D) treated with metformin and insulin without achieving adequate metabolic control, hypertension started on angiotensin-converting enzyme inhibitors with normalization of blood pressure, and sleep apnoea syndrome (SAS) requiring nasal continuous positive airway pressure (nCPAP) mask. In addition, the patient had been treated for degenerative arthritis of the knees, and bilateral carpal tunnel compression syndrome had been surgically resolved few years before. The familial medical history was otherwise unremarkable. Clinical examination showed a female patient with typical clinical signs of acromegaly, including coarse facial features and enlargement of her hands and feet. Her weight, height and body mass index (BMI) were 106.3 kg, 142.0 cm and 52.5 kg/m2, respectively. Laboratory evaluation revealed normal GH level (1.9 ng/ml at 8 a.m. reference value: 0.1–10.0), and an elevated IGF-1 of 297 ng/ml (age-related normal range, 69–252), as well as both increased fasting glucose (199 mg/dl) and glycated haemoglobin (9.1 %). No GH assessment by oral glucose tolerance test was performed because of poorly controlled T2D. In addition, no deficiencies of other pituitary hormones were found. A laparoscopic Roux-en-Y gastric bypass (RYGBP) was undertaken in April 2007. Standard discharge medication included a daily multivitamin during 4 weeks and
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intramuscular vitamin B (12) administered monthly. Resolution of T2D was achieved in the first 6 months (fasting glucose 5.1 mmol/l, HbA1c 5.4 %) and she was able to discontinue all hypoglycaemic medication at this time. In a similar way, blood pressure, snoring and SAS symptoms markedly improved, and nCPAP was withdrawn. After a follow-up period of 12 months, BMI decreased to a maximum of 36.2 kg/m2. However, after 1 month of follow-up, GH (7.6 ng/ml) and IGF1 (481 ng/ml) levels were marked increased compared to baseline values. These behave to increase lanreotide dose to 120 mg, shortening the time of administration from 4 to 3 weeks that carry to a gradual improvement in IGF-1 levels 6 months and 1 year after bariatric surgery (Fig. 1). A pituitary Magnetic Resonance Imaging performed 12 months after bariatric surgery revealed a residual tumour measuring 9 9 6 mm in the left cavernous sinus. Two years after surgery, GH (8.42 ng/ml) and IGF-1 (376 ng/ml) levels persisted elevated, and treatment with the GH receptor antagonist pegvisomant was initiated (10 mg per day). Her GH and IGF-1 basal plasma levels have maintained, respectively, 9.3–12.8 and 81.5–263 ng/ml. Four years after surgery IGF-1 (81.5 ng/ml) levels were completely normalized as well as GH (12.8 ng/ml) persisted elevated. In relation with glucose homeostasis, fasting plasma glucose was lower than 5.5 mmol/l all over the follow-up period. Finally, no changes in the hormonal function of the pituitary were observed following surgery. The mechanisms responsible for the long-term biochemical GH/IGF-1 axis worsen in our patient are still unclear, but marked weight loss and resolution of both T2D and SAS after bariatric surgery may be implicated [4]. Obesity is probably the greatest confounding factor for evaluating GH secretion in adults, and it has been described that GH secretion decreases by up to 6 % per each unit increase in BMI at a given age [3]. However, this impaired somatotropic function seems to be a potentially reversible state with weight loss, either induced by diet or as a result of surgery. In this way, suppressed serum GH levels in 16 severely obese non-diabetic patients increased to nearnormal 6 months after biliopancreatic diversion, a mainly malabsorptive surgical approach [5]. Hyperinsulinemia, an increased somatostatinergic tone, elevation of plasma free fatty acids, and decreased ghrelin levels have been suggested as pathophysiological mechanisms responsible for this GH impairment secretion [3]. Whether changes in gastric hormone ghrelin levels after bariatric surgery may be another cause of therapy scape in acromegalic patients is not clear. In T2D the GH/IGF-1 axis is grossly disturbed, with increased secretion of GH, reduced plasma levels of IGF-1, and complex tissue-specific changes in IGF binding proteins.
Endocrine (2013) 43:239–241
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Fig. 1 GH and IGF1 levels at baseline, and during and after 48 months follow-up. At baseline, treatment with lanreotide 90 mg every 4 weeks. One month after laparoscopic Roux-en-Y gastric bypass, change to lanreotide 120 mg every 3 weeks. After 24 months follow-up, change to GH receptor antagonist pegvisomant, 10 mg per day
These observations have given rise to the view that GH-IGF1 axis dysfunction, particularly low plasma levels of circulating IGF-1, probably play a significant role in several aspects of the pathophysiology of T2D, including insulin resistance and poor glycemic control, and may also influence the development of microvascular complications. In this way, one longitudinal study has shown that after intensive glycemic control for 1 month, with mean changes in HbA1c of -1.2 %, serum IGF-I was increased with mean changes of 11 ng/ml in Japanese patients with poorly controlled T2D [6]. Finally, SAS is also characterized by a reduction of both spontaneous and stimulated GH secretion coupled with reduced IGF-I concentrations. This impairment in the GH/IGF-1 axis is independent of adiposity and is negatively correlated with polysomnographic parameters. These abnormalities are likely to be due to the effects of hypoxia rather than sleep fragmentation on hormone secretory pattern and are restored by nCPAP treatment before any significant variation in body weight occurs [7]. In conclusion, the GH-IGF-1 axis is down regulated by obesity and its metabolic associated disorders. So, although bariatric surgery has afforded an effective treatment for obesity, T2D and SAS, special attention may be paid when acromegalic patients underwent this kind of surgery.
Endocrine (2013) 43:239–241
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