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DOI:10.4158/EP12189.CR © 2012 AACE.

Case Report

EP12189.CR

DIABETIC KETOACIDOSIS IN ACROMEGALY: A CASE REPORT Running Title: DKA in Acromegaly Pilaiporn Palakawong MD1; Richard F. Arakaki, MD1

Submitted for publication July 3, 2012 Accepted for publication October 4, 2012 From the 1Department of Medicine, John A. Burns School of Medicine, University of Hawaii-Manoa. Address correspondence to Richard Arakaki, MD, UH Diabetes and Endocrinology, 550 S Beretania Street, Ste 501, Honolulu, Hawaii 96813 E-mail: [email protected] DOI:10.4158/EP12189.CR Endocrine Practice © 2012 AACE. 1

ABSTRACT Objective: To report an uncommon case of diabetic ketoacidosis in a patient with acromegaly, and present the clinical response to treatment. Methods: Patient evaluation and literature review. Results: A 23-year-old Japanese male with no prior medical history, presented with diabetic ketoacidosis (DKA) and found to have acromegaly. His growth hormone (GH) level was 115 ng/ml, serum insulin-like growth factor-1 (IGF-1) was 1118 ng/ml, and cranial MRI showed a non-enhancing 2.4 x 1.7 x 2.0 cm pituitary mass. After transphenoidal hypophysectomy, his GH level decreased but his IGF-1 level remained unchanged, yet he required no anti-hyperglycemic medications and attained near normal A1c level of 5.8%. He subsequently underwent stereotactic radiotherapy, and additional treatment with bromocriptine and octreotide acetate were not effective, but pegvisomant therapy lowered his IGF-1 concentration to targeted levels. Conclusion: The cause of DKA in this patient with acromegaly is most likely due to glucotoxicity and lipotoxicity, which cause severe but partially reversible β-cell dysfunction; possibly categorized within the syndromes of Ketosis-Prone Diabetes Mellitus (KPD). Diabetic ketoacidosis is an uncommon initial presentation of acromegaly. Successful reduction of GH excess appears to control and resolve hyperglycemia.

DOI:10.4158/EP12189.CR Endocrine Practice © 2012 AACE. 2

Abbreviations: ACTH = adrenocorticotropic hormone; Anti-GAD = glutamic acid decarboxylase antibodies; Anti-IA-2 = insulinoma associated-2 antigen antibodies; BMI = body mass index; DM = diabetes mellitus; DKA = diabetic ketoacidosis; FSH = follicle stimulating hormone; GH = growth hormone; IGT = impaired glucose tolerance; IGF-1 = insulin like growth factor-1; KPD = ketosis-prone diabetes mellitus; LH = luteinizing hormone; octreotide-LAR = long acting release; MRI = magnetic resonance imaging; TSH = thyroid stimulating hormone

Keywords: acromegaly, growth hormone, diabetic ketoacidosis, hyperglycemia INTRODUCTION Acromegaly is an acquired disorder caused by growth hormone (GH) hypersecretion from a pituitary adenoma. The clinical manifestations of acromegaly are unique and seen on physical examination with a wide range of endocrine, musculoskeletal, cardiovascular, respiratory, and metabolic morbidities (1). Diabetes mellitus (DM) is more prevalent in patients with acromegaly, a higher rate attributed to increased insulin resistance caused by GH excess (2). Hyperglycemia is typically found in patients with acromegaly on screening laboratory tests, however diabetic ketoacidosis (DKA) is rarely seen, let alone on presentation. There have been case reports of patients who presented with DKA as the initial manifestation of acromegaly (3-12). We report a case of a young patient with acromegaly and DKA, describe changes in glycemia with treatment, and discuss the clinical course of hyperglycemia management in patients with growth hormone-secreting tumor. DOI:10.4158/EP12189.CR Endocrine Practice © 2012 AACE. 3

CASE REPORT A 23-year-old Japanese male in previous good health presented to the Emergency Department in December 2008 with two days of nausea, vomiting after each meal, and generalized weakness. Two weeks prior to his admission, he noted a 5-10 lb weight loss, tingling sensation in hands as well as polydipsia and polyuria. He denied any fever, abdominal pain, diarrhea, constipation, dysuria, or previous history of DM. Initial laboratory data showed random plasma glucose value of 474 mg/dl, serum bicarbonate level of 6 mEq/L, anion gap of 25 with positive serum acetone, and his A1c level was 13.6%. He was diagnosed with DKA and new onset of type 1 diabetes. He was admitted to the intensive care unit and given standard treatment for DKA with vigorous IV fluids and insulin. He improved relatively quickly, and he was discharged on the fourth hospital day in good condition, on multiple daily insulin injections. The past medical and childhood history was noncontributory except that he noted a 45 lb weight gain and increased shoe size over the previous 3 years. The family history was negative for DM, growth disorders or other endocrinopathies. Physical examination revealed an obese young man; 5ft 9in (175.3 cm) tall, weighing 223.5 lb (101.4 kg) with a body mass index (BMI) 33.1 kg/m2. The examination was remarkable for frontal bossing, widened and thickened nose, mandibular overgrowth with prognathism, maxillary widening with tooth separation, broadened extremities, widened thickened and stubby fingers. Ophthalmologic examination with formal visual field testing was unremarkable. The screening laboratory tests performed revealed serum GH of 115 ng/ml (normal range 1

GH level before/after Tx (ng/mL)

Insulin Tx

560/-

Yes

Katz et al (4)

M

40

>1

37.1/2.7

Szeto et al (5) Westphal et al (6)

F

22

1.5x1.7x3

39/5.3

M

37

1.5

27.7/ 1

9.7/-256/-(IGF-1: 935/491)

Time insulin stopped

After surgery 6 weeks after Yes surgery Continue 6 months after Yes surgery 2 weeks after surgery Yes after 2nd Yes and surgery and glibenclamide octreotide 1 week after surgery and octreotide Yes 6 weeks after Yes surgery

N/A 6 months after Yes and surgery, RT and Ali et al (11) M 16 4.2x3.5x3.8 Metformin medications Continue while Mewawala et al on CVVH and (12) octreotide M 54 2.0x1.4x1.3 29.1/7.75 Yes Abbreviations: RT- Radiation Therapy; CVVH: Continuous Venovenous Hemofiltration

DOI:10.4158/EP12189.CR Endocrine Practice © 2012 AACE. 12

Yes

LEGENDS Fig. 1. Longitudinal changes in GH, IGF-I and A1c levels with treatment. Growth Hormone, Insulin-like Growth Factor-1, and A1c changes with various treatments over the course of 3 years since diagnosis. The surgical procedure, Gamma knife radiation, and the initial start of medications including bromocriptine, Octreotide and Pegvisomant are denoted by the arrows. A: GH levels (ng/ml); B: IGF-1 levels (ng/ml); C: A1c levels (%)

DOI:10.4158/EP12189.CR Endocrine Practice © 2012 AACE. 13

Figure 1

A

B

DOI:10.4158/EP12189.CR Endocrine Practice © 2012 AACE. 14

C

DOI:10.4158/EP12189.CR Endocrine Practice © 2012 AACE. 15