Kaleidoscope: A Man’s Journey through Colors

Hedy Harriet S. Ong, MD and Marivi Grace Mercado-Nerit, MD

We present to you the case of a man’s extraordinary journey of life. Much like a kaleidoscope, the confusing color fragments seen are like the day to day unfolding of his diagnostic workups. It may be perplexing and overwhelming at first but everything would make perfect sense once the wondrous and vibrant tapestry aligns altogether.

This is a case of a 47-year-old male, known diabetic, with no other significant co-morbidities except for a congenital bicuspid aortic valve (without restriction of motion). He was on oral hypoglycemic agents with good glycemic control for over three years but was noted to have increasing sugar levels. In one of his workups, abdominal CT scan with contrast showed an adrenal nodule measuring 1.2 x 0.9 cm, well-defined, low density. Biochemical workup showed a non-functioning adrenal nodule.

In the interim, despite good medication compliance, patient’s blood glucose was persistently increasing and led to hospital admission for diabetic ketoacidosis. This was partly attributed to the ketogenic diet he adopted. He was sent home with Insulin glargine 36 units subcutaneously once daily and Insulin Aspart units subcutaneously three times premeals on top of oral hypoglycemic agents.

In a span of 2 years, he had over 10 kg weight gain associated with coarsening of facial features such as frontal bossing, nose enlargement, macroglossia, acral enlargement and unable to wear his wedding ring. Patient denies headache nor changes in vision. This time period coincided with the COVID-19 pandemic where physician follow up was challenging and changes in facial features were not readily noticeable as patient has been wearing face mask. The constellation of his signs and symptoms at this time led his physician to suspect the presence of a growth hormone-secreting pituitary adenoma. Insulin-like growth factor-1 was 2.8 times elevated, age and gender-matched while all other pituitary hormones were normal1. Pituitary MRI revealed a pituitary macroadenoma measuring 3.7 x 3.1 x 2.2 cm compressing the left optic chiasm and extending to both cavernous sinuses. Patient underwent transsphenoidal excision of pituitary mass and developed transient diabetes insipidus. Histopathology report with immunohistochemical stain showed positive for prolactin and a faint, sparsely positive stain for growth hormone. It stained negative for ACTH, FSH, LH and TSH.

Two months post operative, he was noted to have less frontal creases and subtle reduction in interphalangeal joint sizes of both hands. However blood glucose levels remain erratic with the same preoperative diabetes mellitus regimen.

Repeat cranial MRI 3 months post surgery showed a 35% volume reduction in the pituitary macroadenoma size. He developed panhypopituitarism with decreasing FT4, cortisol and testosterone levels. Deficient hormones were replaced accordingly. The IGF-1 level, however was persistently more than twice elevated. Prolactin dilution test remained low despite a prolactin staining pituitary adenoma. This connotes an aggressive tumor with a more severe IGF-1 elevation and symptoms2. Due to the persistent disease, somatostatin receptor ligand (SRL), Octreotide LAR, was started 4 months post operative. A decreasing blood sugar level was observed upon initiation of Octreotide LAR until the first few weeks of administration requiring an insulin dose reduction of 25-40%. Towards the end of the month prior to the next due SRL dose, an increasing sugar trend was observed. Our patient also had simultaneous radiotherapy sessions with volumetric modulated arc therapy at 180 cGy daily dose for a total of 28 fractions.

Five months post operative, there was significant increase in the appearance of frontal creases. IGF-1 levels further elevated fivefold from the normal level. Our patient was classified as treatment resistant, since there was failure of IGF-1 to decrease by 20% despite pituitary surgery and five doses of SRL and radiotherapy. Predictors associated with treatment resistance include young age, elevated post surgery IGF-1 level, large tumor remnant, cavernous sinus invasion and sparse adenoma granularity on histopathologic findings which are all present in this patient3,4,5. A multidisciplinary approach using multiple modalities of somatostatin receptor ligand, repeat surgery, radiotherapy or second-line medical therapy may be used with consideration of IGF-1 and growth hormone levels, size and invasiveness of tumor, symptoms and comorbidities, and the cost-benefit ratio6. There are limited treatment options available in the country. At present, patient has been compliant with medications except for occasional missed doses due to difficulty in drug procurement overseas. Cabergoline has been added in conjunction with Octreotide LAR.

Medicine is like a kaleidoscope, with a multitude of possibilities. Each fragment representing a different approach to diagnosis and mode of treatment. For this 47-year-old individual with acromegaly, vast treatment options have been explored and utilized. As of now, halting the deleterious effect of an elevated IGF-1 depends on how soon we are able to control the functioning pituitary macroadenoma thru the timely procurement and administration of medications or are we left with the watch and wait game for the radiotherapy effect to set in?


Table 1. Hormone trends from baseline up to six months post operative.

  Reference Range Preoperative 2 months post-operative 3 months post-operative 6 months post-operative 9 months post operative
IGF-1 71-224 ng/ml 420.50 480.50  ——– 679.60 502.10
Serum Human Growth Hormone 0-0.97 ng/ml ——– ——– 2.32 ——– ——–
TSH 0.27-4.20 uIU/ml 2.1 0.879 0.513 ——– ——–
FT4 12-22 pmol/L 12.73 9.87 11.34 17.77 16.31
FSH 1.50-12.40 mIU/ml 5.34 ——– 3.33 ——– ——–
LH 1.70-8.60 mIU/ml 4.71 ——– 3.02 ——– ——–
Cortisol 172-497 nmol/L 209 353 248 ——– ——–
ACTH 7.20-63.30 pg/ml 26.82 ——– 48.6 ——– ——–
Prolactin 86-324 mIU/L 56.3 59.10 61.1 75 ——–
Prolactin dilution test (1:100) 60-400 uIU/mL ——– ——– ——– 72.3 ——–
Testosterone 1.93-7.4 ng/ml  ——– ——– 0.62 ——– ——–
Free Testosterone 3,6-25,7 pg/ml ——– ——– ——– 2,0 ——–


The corresponding clinical questions for this article are:

  1. What is the correlation of biochemical result to immunostaining result?
  2. Is there a link between Acromegaly and Adrenal Incidentaloma that can change the clinical course of our patient?
  3. Is there a role for extension of radiotherapy session in our patient with significant residual tumor?
  4. What are the potential causes of resistance to standard medical therapy and are there any genetic biomarkers that can predict treatment resistance in acromegaly?
  5. How do we optimize medical therapy and enhance the quality of life of patients with panhypopituitarism and treatment-resistant acromegaly?



  1. Zhu, H., Xu, Y., Gong, F., Shan, G., Yang, H., Xu, K., Zhang, D., Cheng, X., Zhang, Z., Chen, S., Wang, L., & Pan, H. (2017). Reference ranges for serum insulin-like growth factor I (IGF-I) in healthy Chinese adults. PLOS ONE, 12(10). https://doi.org/10.1371/journal.pone.0185561
  2. Rick, J., Jahangiri, A., Flanigan, P. M., Chandra, A., Kunwar, S., Blevins, L., & Aghi, M. K. (2019). Growth hormone and prolactin-staining tumors causing acromegaly: A retrospective review of clinical presentations and surgical outcomes. Journal of Neurosurgery, 131(1), 147–153. https://doi.org/10.3171/2018.4.jns18230
  3. Melmed, S., Bronstein, M. D., Chanson, P., Klibanski, A., Casanueva, F. F., Wass, J. A., Strasburger, C. J., Luger, A., Clemmons, D. R., & Giustina, A. (2018). A consensus statement on Acromegaly Therapeutic Outcomes. Nature Reviews Endocrinology, 14(9), 552–561. https://doi.org/10.1038/s41574-018-0058-5
  4. Asa, S. L., & Ezzat, S. (2021). An update on pituitary neuroendocrine tumors leading to acromegaly and gigantism. Journal of Clinical Medicine, 10(11), 2254. https://doi.org/10.3390/jcm10112254
  5. Besser, G. M., Burman, P., & Daly, A. F. (2005). Predictors and rates of treatment-resistant tumor growth in acromegaly. European Journal of Endocrinology, 153(2), 187–193. https://doi.org/10.1530/eje.1.01968
  6. Coopmans, E. C., van der Lely, A. J., & Neggers, S. J. (2022). Approach to the patient with treatment-resistant acromegaly. The Journal of Clinical Endocrinology & Metabolism, 107(6), 1759–1766. https://doi.org/10.1210/clinem/dgac037



How useful was this article?

Click on a star to rate it!

Average rating 0 / 5. Vote count: 0

No votes so far! Be the first to rate this article.

Since you enjoyed this article

Follow us on social media!

We are sorry that this article was not useful for you!

Let us improve this article!

Tell us how we can improve this article?




What is PCEDM?

The PCEDM is a sub-specialty society of the Philippine College of Physicians, a founding member of the ASEAN Federation of Endocrine Societies, and a member of the International Society of Endocrinology.

Learn More >>