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Clinical Images

A Growing Resistance to Insulin

Sara Slatkin, MD; Shobha W Stack, MD, PhD; Bryan McColgan, MD

April 20, 2015

A 31 year-old male with no prior past medical history presented with a steadily increasing hemoglobin A1c from 6.1% to 6.9%  over the course of one year. Despite dual therapy with oral hypoglycemic agents, his HbA1c rose to 11.4% over the following seven months.  He presented four months later to an outside hospital with an HbA1c of 18% and was subsequently admitted to initiate insulin therapy. That evening, he developed right eye ptosis and complete extraocular muscle paralysis (Figure 1a). MRI of the brain revealed a multilobulated heterogeneously-enhancing mass located in the sellar and suprasellar region, with extension into the right cavernous sinus (Figure 2).

On review of systems, the patient recalled intermittent headaches for two years. He denied changes in appearance, arthralgia, or hypertension. In addition to the ocular findings above, physical examination was notable for frontal bossing, prominent skin ridges along the hairline, macroglossia, and paresthesia along the right maxillary nerve distribution (Figure 1b).

Laboratory evaluation was remarkable for an elevated serum insulin-like growth factor-1 (IGF-1) level of 579 ng/mL (range 71-241 ng/mL), a random serum growth hormone (GH) level greater than 40 ng/ml, and a serum prolactin level of 1 ng/mL (normal is less than 20 ng/mL). The remainder of his pituitary function was intact.

The patient was transferred to a tertiary hospital where he underwent endoscopic transsphenoidal surgery and anterior cranial fossa craniotomy resulting in excision of approximately 75% of the macroadenoma. Two weeks post-operatively, the patient’s daily insulin requirements decreased from 200 units to 120 units and GH level decreased to 9.9 ng/mL. Pathology confirmed a granulated GH-staining pituitary adenoma that had negative immunostaining for other pituitary hormones.  

Following surgery, the patient had residual disease necessitating adjuvant treatment with medical therapy and radiotherapy.  The goal of non-surgical treatment is to control the GH hypersecretion, improve the co-morbidities, and thus, reduce the risk of premature mortality. Because radiation therapy can take many years for effect, medical therapy is required in the interim until biochemical control is achieved. Somatostatin receptor ligands or the GH receptor antagonist, pegvisomant, are recommended for patients with significant disease (1).

The presentation of acromegaly is usually insidious (2); however, this case was an emergent presentation. In the setting of profound worsening of his type 2 diabetes mellitus, the patient had apoplexy of the tumor invading the right cavernous sinus, which caused his acute neurological deficits. He was subsequently diagnosed with acromegaly based on classic physical stigmata, as well as documentation of IGF-1 and GH hypersecretion.   

A-Growing-Resistance-to-Insulin_Image1_Slatkin.png

 Figure 1

 

A-Growing-Resistance-to-Insulin_Image2_Slatkin.png

Figure 2

A 40 year-old male presents to establish care.  He reports a past medical history of insulin-dependent diabetes, sleep apnea, and four years of progressive polyarthralgia with no contributory family history.  



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References

1. Katznelson, L, Laws, E, Melmed, S, Molitch, M, Murad, M, Utz, A, Wass J. Acromegaly: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014 Nov;99(11):3933-3951. 
2. Nabarro JD. Acromegaly. Clin Endocrinol. 1987; 26:481-512.
3. Rosario PW. Frequency of acromegaly in adults with diabetes or glucose intolerance and estimated prevalence in the general population. Pituitary. 2011 Sep;14(3):217-21. 



Author Biographies

Sara Slatkin, MD: Sara is a first year resident in Internal Medicine at Stanford University Medical Center. She is interested in perusing an academic career in endocrinology. Before attending medical school, she was a research student in a clinical laboratory in Freiburg, Germany. 

Shobha W Stack, MD, PhD:  Shobha is a third year resident in Internal Medicine at Stanford University Medical Center interested in endocrinology and medical education.  Prior to medical school she worked in biomedical device design and has a PhD in mechanical engineering.

Bryan McColgan, MD:  Bryan is a first year endocrinology fellow at Stanford University Medical Center with a research interest in transgender medicine and the intersection of medicine and technology for endocrine care.

 

Acknowledgements

The authors would like to thank Dr. Laurence Katznelson and Dr. Joy Wu, attending Endocrinologists, for their guidance in reviewing this case.

 

 



 

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