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 Table of Contents  
CASE REPORTS
Year : 2021  |  Volume : 12  |  Issue : 1  |  Page : 101-104

A challenge to achieve glycemic control in a patient with diabetes mellitus


1 Department of Endocrinology, AIIMS, Rishikesh, Uttarakhand, India
2 Department of Medicine, Division of Diabetes and Metabolism, AIIMS, Rishikesh, India
3 Department of Medicine, AIIMS, Rishikesh, Uttarakhand, India

Date of Submission17-Mar-2020
Date of Decision25-May-2020
Date of Acceptance20-Jun-2020
Date of Web Publication25-Dec-2020

Correspondence Address:
Dr. Nisha Batra
Department of Endocrinology, AIIMS, Rishikesh, Uttarakhand 249203.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jod.jod_15_20

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  Abstract 

Secondary diabetes mellitus (DM) is a known identity with multiple causes. Acromegaly, a state of growth hormone (GH) excess, is a rare but an established cause of DM. Dysglycemia is present in approximately 50% of patients of acromegaly with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) ranging from 6% to 45% and from 7% to 22%, respectively, and DM has been reported in 16%–56% of patients (Alexopoulou O, Bex M, Kamenicky P, Mvoula AB, Chanson P, Maiter D. Prevalence and risk factors of IGT and DM at diagnosis of acromegaly: A study in 148 patients. Pituitary 2014;17:81-9; Dal J, Feldt-Rasmussen U, Andersen M, Kristensen LØ, Laurberg P, Pedersen L, et al. Acromegaly incidence, prevalence, complications and long-term prognosis: A nationwide cohort study. Eur J Endocrinol 2016;175:181-90). Diabetes in these patients is usually severe and difficult to treat. Glycemic control in these patients is best achieved by treating the underlying GH excess. We report a 60-year-old female patient, case of somatotropinoma, who was referred to diabetic clinic in view of persistent hyperglycemia despite taking multiple antidiabetic medications along with high-dose basal-bolus insulin regimen. Patient had residual pituitary tumor with GH excess and clinically active disease. She was started with somatostatin analogs for the residual disease. Her blood sugar values improved dramatically with episodes of hypoglycemia in between. Patient was shifted to single oral hypoglycemic (OHA) along with low dose insulin. This case highlights the direct association between GH excess and its hyperglycemic effects. Following successful treatment of acromegaly with surgery, irradiation, or medical management, glucose tolerance improves; although complete resolution is rare, OHA/insulin requirement is dramatically reduced.

Keywords: Acromegaly, diabetes mellitus, growth hormone


How to cite this article:
Batra N, Kant R, Sethi P. A challenge to achieve glycemic control in a patient with diabetes mellitus. J Diabetol 2021;12:101-4

How to cite this URL:
Batra N, Kant R, Sethi P. A challenge to achieve glycemic control in a patient with diabetes mellitus. J Diabetol [serial online] 2021 [cited 2021 Jan 28];12:101-4. Available from: https://www.journalofdiabetology.org/text.asp?2021/12/1/101/304347




  Case Summary Top


A 60-year-female was referred to Diabetes Clinic, All India Institute of Medical Science (AIIMS) Rishikesh in view of persistent hyperglycemia. Patient had random plasma glucose of 482 mg/dL. She was a known case of diabetes mellitus (DM) for the last 8 years and was currently taking Tab Gliclazide 60 mg/Tab Voglibose 0.3 mg twice a day/Tab Metformin 1 g twice a day along with regular insulin total of 54 units in divided doses along with basal insulin glargine 38 units. Compliance was ensured. While taking detailed history, patient revealed that she was diagnosed with pituitary macroadenoma (growth hormone [GH] producing) 6 months back for which she underwent trans sphenoidal surgery 3 months back. Her repeat magnetic resonance imaging (MRI) showed persistent residual tumor for which radiotherapy was being planned. Patient still had features of “clinically active” acromegaly in form of persistent headache, arthralgia, and hyperhidrosis.

Possibility of acromegaly leading to worsening glycemic control was kept and she was admitted for the evaluation of the same. On examination, she had moderate built and body mass index (BMI) of 22 kg/m2. Patient was normotensive, had warm, and moist hands with typical acromegalic features in form of bulbous nose, prognathism, thick, and fleshy lips and enlarged hands and feet [Figure 1]. She had hoarse voice with slowness of speech. The findings of the rest of the general examination and systemic examination were normal.
Figure 1: (A) Features of acromegaly: Bullous nose, fleshy lips, and frontal bossing. (B) Features of acromegaly: Macroglossia. (C) Features of acromegaly: enlarged hands. (D) Features of acromegaly: Enlarged feet

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Investigations revealed Hb 8.6 g/dL with peripheral blood smear microcytic/hypochromic type and low-iron indices suggestive of iron deficiency. Renal and liver function tests were essentially normal. Insulin-like growth factor-1 (IGF-1) levels were 212 ng/mL (high for age reference values) and random GH levels was 8 ng/mL suggestive of persistent disease. There was evidence of postoperative pituitary damage in form of anterior pituitary insufficiency with secondary hypothyroidism and secondary hypogonadism. Patient had random blood glucose of 503 mg/dL at the time of admission with HbA1c of 11.2%. Her postoperative CEMRI brain (done after 3 months of surgery) showed a well-defined lesion 12mm × 15mm × 15mm seen in sellar region abutting optic chiasma and displaced stalk to left side and lateral extension into cavernous sinuses (Knosp grade 1) suggestive of residual macroadenoma. Considering the residual tumor, she was planned to put on medical management with somatostatin analogues and hence, injection octreotide was started in dose of 100 mcg s/c thrice a day along with insulin, oral hypoglycemic (OHA), and thyroxine replacement therapy. Surprisingly, patient’s blood sugar values dropped within 24h, whereas she was on same diet and treatment and suffered two episodes of hypoglycemia following which OHA were stopped and she was put on titrating doses of insulin therapy [Table 1]. Patient showed a remarkable improvement in headache and arthralgia after 48h of treatment. Her requirement for insulin and OHA doses was reduced to more than half of the previous dose. Patient was further planned to start with long-acting depot preparation of octreotide. All investigation reports of patient are shown in [Table 2].
Table 1: Blood sugar chart of patient during hospital stay

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Table 2: Investigation reports of patient at time of admission

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  Discussion Top


Acromegaly is characterized by chronic GH and IGF-1 excess. IGF-1 has insulin-like effects, whereas GH has insulin-antagonistic properties, and in acromegaly, the effects of GH predominates. GH antagonizes the action of insulin at the liver, skeletal muscle, and adipocytes leading to increased hepatic glucose output due to augmented glycogenolysis and gluconeogenesis, reduced uptake of glucose into muscle, and adipocytes. In addition, it also promotes lipolysis and increases the serum levels of nonesterified fatty acids, resulting in worsening of insulin resistance.[1]

Dysglycemia is present in approximately 50% of patients of acromegaly with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) ranging from 6% to 45% and from 7% to 22%, respectively, and DM has been reported in 16%–56% of patients.[2],[3] It is more prevalent in those with long duration of disease, higher GH levels, and family history of diabetes.[4] Acromegaly patients have been reported to develop DM at younger age as compared to general population. In many patients, the diagnosis of DM may precede that one of acromegaly and in patients with preexistent Diabetes. Acromegaly may worsen glycemic control and aggravate both micro and macrovascular complications.

It is not only disease per se causing DM but various medications used in treatment including somatostatin analogues also impair glucose metabolism. Hyperglycemia associated with acromegaly is frequently severe and difficult to treat. The prevalence of undiagnosed acromegaly in patients with diabetes has been reported to be 0.6%–3%,[5] which is a significant number considering the rising worldwide prevalence of DM in epidemic proportions. Hence, patients with resistant diabetes should be evaluated for acromegaly.

DM is not only a manifestation of acromegaly but also an important predictor of disease activity, mortality, and the presence of DM infers low likelihood of achieving disease control. Studies have even shown increased frequency of malignancies in diabetic acromegaly patients (correlated with high IGF-1 levels)

Glycemic control in these patients is best achieved by treating the underlying state of GH excess. Following successful treatment of acromegaly with surgery, irradiation, or medical management, glucose tolerance improves and OHA/insulin requirement is dramatically reduced but complete resolution is rare. Those with a shorter duration of DM and lower levels of GH are more likely to undergo complete resolution. In case of persistence of DM after successful treatment, hyperglycemia is to be managed as per standard treatment guidelines for patients with type 2 diabetes.

Our case very well shows the direct association between GH levels and glycemic control in a diabetic patient with acromegaly. Patient showed a dramatic improvement in blood sugar levels after initiation of somatostatin analogs. Although it is surprising, somatostatin analogs are known to have deleterious effect on pancreatic beta cells, worsening glycemic profile. Improved glycemic control in our patient strongly reflects the role of excess GH as the main etiological factor in our patient. This association is hence important to recognize so that early treatment can be initiated and complications can be avoided.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Moller N, Jorgensen JO Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. JO Endocr Rev 2009;30:152-77.  Back to cited text no. 1
    
2.
Alexopoulou O, Bex M, Kamenicky P, Mvoula AB, Chanson P, Maiter D Prevalence and risk factors of impaired glucose tolerance and diabetes mellitus at diagnosis of acromegaly: A study in 148 patients. Pituitary 2014;17:81-9.  Back to cited text no. 2
    
3.
Dal J, Feldt-Rasmussen U, Andersen M, Kristensen LØ, Laurberg P, Pedersen L, et al. Acromegaly incidence, prevalence, complications and long-term prognosis: A nationwide cohort study. Eur J Endocrinol 2016;175:181-90.  Back to cited text no. 3
    
4.
Arosio M, Reimondo G, Malchiodi E, Berchialla P, Borraccino A, De Marinis L, et al; Italian Study Group of Acromegaly. Predictors of morbidity and mortality in acromegaly: An Italian survey. Eur J Endocrinol 2012;167:189-98.  Back to cited text no. 4
    
5.
Suda K, Fukuoka H, Iguchi G, Hirota Y, Nishizawa H, Bando H, et al. The prevalence of acromegaly in hospitalized patients with type 2 diabetes. Endocr J 2015;62:53-9.  Back to cited text no. 5
    


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