Case

A 45-year old soldier presented to emergency room with headache and polyuria for last many weeks. He also gives history of increase in shoe size from 43 to 46 and tightening of ring around his finger along coarsening of facial features with widening of nose and thickening of lips all of which he started to notice for the last one year. He also complained of backache, electric shock like sensation in gloves and stocking distribution as well as excessive sweating. His past medical history is significant for long standing gout, hypertension, multiple lumbosacral disc prolapse, bilateral carpal tunnel syndrome and type 2 diabetes mellitus which was previously controlled but for last 6 months is uncontrolled even on insulin 70/30 combination injection 95 units in the morning and 90 in the evening. His other medications included aspirin, atorvastatin, allopurinol and pantoprazole. His past surgical history includes multiple surgeries for carpal tunnel, trigger fingers, patellar surgery and lumbar disc surgery. His family history is positive for diabetes mellitus in both parents as well as in three of his seven siblings.

On examination the patient had prominent jaw and forehead, wide nose, thick lips and stocky hands and feet. (see figure 1 and 2)

Figure 1

Figure 1: Showing prominent lips and coarse facial features of the patient with acanthosis nigricans over ear lobe

Figure 2

Figure 2: Showing coarse hand features with increased soft tissue and thickened digits

He had excessive soft tissue deposition over his head and neck. (see figure 3). His blood glucose was 16.8 mmol/L and he was normotensive and afebrile in the emergency room. He has acanthosis nigricans over ear lobes, back of neck and bilateral axillae. He had decreased sensation to touch and pain over bilateral feet and hands. Other systemic examination was insignificant for any findings.

Figure 3

Figure 3: X-ray skull showing prominent soft tissue thickening all around the neck and face

Admitting diagnosis of acromegaly was made for this patient and he was booked for MRI pituitary fossa with gadolinium which showed no pituitary mass/adenoma. (see figure 4)

Figure 4

Figure 4: MRI brain showing normal pituitary fossa

His HbA_1C was 11.1 and Insulin like growth factor was normal. A dynamic growth hormone testing was done which was normal while the serum fasting insulin was raised presence of insulin resistance based on HOMA-IR (see table 1). Based on negative MRI and clinical and biochemical features of insulin resistance a diagnosis of pseudoacromeagly was made. The patient was put on pioglitazone and metformin and premeal 20 units regular insulin subcutaneously thrice a day. After 3 months on follow-up the patient blood glucose was much controlled and his HbA_1C had improved _{to around 8.3}

Figure 5

Table 1: SUMMARY OF PERTINENT LABORATORY INVESTIGATIONS

Review Of Literature

Pseudoacromegaly is a rare disorder characterized by tissue overgrowth and acromegaloid features in the absence of growth hormone or IGF-1 oversecretion.¹ it is characterized by very high levels of serum insulin which probably provides the stimulus for abnormal tissue growth. The first case of pseudoacromegaly was described by Flier et al and found resistance to insulin-mediated glucose disposal in the patients cultured fibroblasts.¹ To-date there have been six cases reported with this rare condition.^2-6 it has been postulated that excessive acral growth and changes in the composition of tissues such as fat and muscle are due to supraphysiological insulin levels providing stimulus to growth through an intact mitogenic signaling pathway. One of the studies have shown selective impairment of phosphoinositide-3-kinase activation by insulin in this disorder.² Since the proposed mechanism for pseudoacromegaly in these patients clearly differs from normal mechanism for acromegaly (IGF-1 acting through IGF-1 receptors), such patients mimick the acromegaloid phenotype but usually do not have the classic presentation of acromegaly.

Conclusion

Insulin-mediated pseudoacromegaly is an rare syndrome consisting of insulin resistance associated with acromegaloid phenotype. A selective post receptor defect causes impaired insulin signaling for metabolic effects but there is preservation of mitogenic signaling, resulting in abnormal tissue growth and acromegaly like features in affected patients. Physicians should consider this possibility while evaluating patients with similar clinical and laboratory features.