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Authors: Anastassios G. Pittas, M.D., Arthur S. Tischler, M.D.

1. Case 1

An 18-year-old woman with a 6-year history of diabetes enters the hospital comatose. Her mother reports that she has not been well for several days due to the "flu." She takes 40 units of Glargine (a long acting insulin analog) at bedtime, but it was not clear whether she took her insulin for the past day or two. On examination, she can be aroused with painful stimuli and she moans, but otherwise cannot communicate. She is clinically volume depleted, breathing at a rate of 32/mm and has a pulse rate of 110. Blood pressure is 100/70. Temperature (rectally) is 100.8 F. No other pertinent findings noted.

Laboratory data include: Hematocrit 50; WBC 12,500 (65% P, 30% B), obvious glucosuria and 3+ "acetonuria," serum "ketones" strongly positive. Serum glucose 642 mg/dl, BUN 43 mg/dl, sodium 135 mEq/L; potassium 3.8 mEq/L; chloride 94 mEq/L; and bicarbonate 9 mEq/L. Blood pH was 7.21. Chest X-ray showed a possible infiltrate in the left lower lobe.

  1. The most likely explanation for her presentation is:
    1. Diabetic ketoacidosis
    2. Hyperglycemic, Hyperosmolar Nonketotic State
    3. Alcohol intoxication
    4. End stage diabetes

      Discuss the pathophysiology of her condition: hyperglycemia, ketone bodies (acetoacetate/hydroxybutyrate), acidosis, and electrolyte loss, precipitating factors.
  2. How should she be managed? How should the response be monitored? What are the possible complications arising during treatment or as a consequence of treatment? Include discussion of bicarbonate, potassium and phosphate in correcting abnormalities.

    After she has recovered, she returns to see you in clinic and she inquires about additional options for management of her diabetes.
  3. Describe some intensive insulin regimens and the types of insulin that are used with them. Discuss the possible role of continuous subcutaneous insulin infusion (CSII) in intensive therapy. What is a potential drawback of intensive therapy?

    The patient is worried that her 13-year old sister may develop the same disease and is asking you to determine her sister's risk of developing this disease.
  4. To better assess her sister, which one of the following would you do?
    1. Measure a glucose level 2 hours after an oral glucose tolerance test
    2. Measure circulating autoantibodies to islet cells.
    3. Measure the sister's Body Mass Index
  5. PATH - What pathological changes would be seen in the patient’s pancreas?

    What changes would have been seen at the onset of her disease 6 years ago?

2. Case 2

A 45-year-old obese woman was referred for newly diagnosed diabetes. She had a past medical history of gestational diabetes with her two children. With her pregnancies she gained a total of 70 lb., which she was unable to lose. Her menses are regular. On physical examination, her weight is 295 lb. with a height of 66 inches (BMI of 47). There is significant abdominal adiposity without striae. She has trace ankle swelling.

Her initial laboratory data revealed:

  • Fasting serum glucose of 184 mg/dl
  • Hemoglobin A1C of 8%
  • Total cholesterol 295 mg/dl
  • HDL cholesterol 29 mg/dl
  • Triglycerides 484 mg/dl.
  • Spot urinary microalbumin ratio (albumin to creatinine) was 0.01 (normal less than 0.03)
  1. According to the NIH Obesity Guidelines, based on the data above, this patient has:
    1. Normal weight
    2. Overweight
    3. Obesity
    4. Severe Obesity
  2. Based on the data above, the patient has
    1. Normal glucose
    2. Impaired fasting glucose
    3. Diabetes
  3. The most significant risk factors for the development of diabetes in this patient is:
    1. Gestational diabetes mellitus
    2. Age
    3. Obesity
    4. Polycystic Ovary Syndrome
  4. The patient most likely has a monogenic cause for her diabetes.
    1. True
    2. False
  5. How would you treat her? What nutritional and activity recommendations would you have for her to help lose weight and what weight loss goal would you set for her initially? What other adjuvant treatments are available that may assist her in weight loss based on her current weight?

    The patient decided to try a diet with a carbohydrate content of 30% of the total daily caloric requirement. She followed her diet for 3 months, lost weight and her urine no longer showed glucose. Her triglyceride level fell to 235 mg/dl. The patient, however, gradually dropped her diet and regained weight. Polyuria and polydipsia became a problem. When seen 8 months after the initial visit, her fasting plasma glucose was 264 mg/dl and her HbA1c was 10%.
  6. The patient should be treated with
    1. Another trial of lifestyle interventions for another 6 months
    2. Insulin
    3. Sulfonylurea
    4. Metformin
    5. Thiazolidinedione
    6. Sulfonylurea and Metformin combination

      Discuss pharmacologic targets for treatment of Type 2 diabetes.

      She was initially treated with multiple shots of insulin daily until her daily sugar readings were all in the low 100s. Subsequently, she was switched to a combination of glipizide GITS, pioglitazone and NPH insulin at bedtime. Three months later she had a HbA1C of 7.3%, total cholesterol of 210 fasting triglycerides of 220 mg/dl, HDL cholesterol of 38 mg/dl. Her weight increased by 15 lb. on this therapy.
  7. What are goals for lipid profile and blood pressure? What if she has a history of angina or a previous MI?
  8. PATH - How would the patient's pancreas differ histologically from the pancreas of the patient in Case 2?
  9. PATH - What changes would be expected to develop in other organs, and what measures might be taken to retard their development?

3. Case 3

A 50 year old woman who lives in Florida yearlong was found to have the following results on "routine" testing during her annual physical examination.

  • Calcium 12.1 mg/dl (normal = 8.8 to 10.5 mg/dl)
  • Albumin 3.9 mg/dl (low)
  1. The most appropriate next step would be:
    1. Measurement of intact PTH
    2. Parathyroid scan
    3. Age-appropriate screen for malignancy

      Her intact PTH was elevated at 88 pg/ml (normal <10-65 pg/ml), her phosphorus was 2.4 mg/dl (normal 2.5 - 4.5 mg/dl) - and her urine calcium excretion over 24-hours was 390 mg
  2. The most likely cause of her hypercalcemia is
    1. Primary hyperparathyroidism
    2. Familial Hypocalciuric Hypercalcemia
    3. Malignancy-associated hypercalcemia
    4. Pheochromocytoma

      A parathyroid scan was done which showed uptake in the right upper neck area and the patient underwent parathyroid surgery. At surgery, the right upper parathyroid gland measured 1.8 cm in diameter, while the remaining glands were grossly normal. The right upper gland was removed, and a biopsy of the right lower gland was performed
  3. PATH - How would you distinguish parathyroid hyperplasia from parathyroid adenoma?
  4. PATH - Why was the right lower gland biopsied?
  5. PATH - What is the weight of a normal parathyroid gland?
  6. PATH - True or False: The presence of two different-looking cell populations (e.g., chief cells and oxyphil cells) in a parathyroid mass usually rules out a diagnosis of adenoma
    1. True
    2. False

      Three days after discharge, the patient returns to you because of muscle cramps, hand spasms, and a sensation of "pins and needles" around her mouth and at the tip of her fingers. When her blood pressure was taken, muscle spasms in her hand occurred. Laboratory testing reveals: Calcium 6.5 mg/dl (normal 8.5 – 10.5), Phosphorus 4.8 mg/dl (normal 2.5 – 4.5)
  7. Is her condition an emergency?
  8. The most likely cause for her hypercalcemia is:
    1. PTH deficiency
    2. PTH resistance
    3. Vitamin D deficiency
    4. Vitamin D Resistance

Discuss the roles of vitamin D and PTH in regulation of calcium.

Discuss other causes of hypercalcemia. Discuss some mechanisms of hypercalcemia due to malignancy.

4. Case 4

This 18 year old man entered the hospital for evaluation of hypercalcemia and hypo-phosphatemia. Two years before admission, he was found to have hypergastrinemia associated with a pancreatic islet cell tumor which had been completely excised. The patient's father and several aunts and uncles had a history of endocrine tumors. At surgical exploration of the neck, all four parathyroid glands were found to be enlarged and a subtotal parathyroidectomy was performed.

  1. What is the significance of the family history in this case?
  2. What is the underlying molecular abnormality in patients with MEN, Type 1?
  3. PATH - How would you describe the changes in the parathyroid gland?
  4. PATH - What are the large pink cells?
  5. PATH - Can you identify chief cells?
  6. PATH - Does this gland have a compressed rim of atrophic parathyroid tissue?