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

1. Case 1

A 55-year old man is brought to the emergency room by his wife because of confusion and disorientation since the morning. He has been complaining of ‘weakness’ for months. Blood work revealed glucose of 23 mg/dl. The patient was given glucose and his mental status improved but within a few hours he became confused again. A glucose measurement by fingerstick showed "LOW". The nurse was ready to give him more glucose when the 3rd year medical student asked him not to give the patient any glucose until she did further evaluation. The nurse, after checking with the intern, did not give the patient more glucose.

  1. The most appropriate next step should be:
    1. Measure glucose and insulin level
    2. Measure glucose, insulin, C-peptide level
    3. Measure glucose, insulin, C-peptide level, pro-insulin
    4. Measure glucose, insulin, C-peptide level, pro-insulin and sulfonylurea level
    5. Accuse his wife of injecting him with insulin

      After getting the blood tests, the student tells the nurse to continue treating the patient with glucose as required. Results return as follows:

      • Glucose low
      • Insulin level high
      • Proinsulin/Insulin ratio high
      • C-peptide high
      • Sulfonylurea level is undetectable.
  2. Based on these results, the most likely cause for his hypoglycemia is
    1. Insulinoma
    2. Physiologic benign hypercalcemia
    3. Exogenous administration of sulfonylurea
    4. Exogenous administration of insulin

      The patient is placed on intravenous glucose with full recovery of his mental functions and slowly over the next 12 hours, he is weaned off IV glucose. During laparotomy, a small tumor in the tail of the pancreas is found (with the help of intraoperative ultrasound) and it is successfully removed.
  3. PATH – What is the definition of an insulinoma?
  4. PATH – What are the histological features that distinguish insulinoma from other types of pancreatic tumors? What special procedures would differentiate endocrine from non-endocrine tumors in the pancreas? How would a definitive diagnosis of insulinoma be made?
  5. PATH - Immunohistochemical staining of insulinomas will frequently reveal immunoreactivity for additional pancreatic hormones
    1. True
    2. False
  6. PATH –What is the risk of metastasis from insulinoma compared to other types of pancreatic endocrine tumor? What is the prognosis for this patient compared to a patient with metastatic insulinoma?
  7. PATH –Are there any pathology findings that would suggest a need for genetic evaluation of the patient or his family?

2. Case 2

A 50-year-old lawyer was taken to his doctor by his wife because he was unable to remain awake in the evenings. He did not think that he was ill, but on specific questioning he stated he had noted constipation and cold intolerance in the last two years. In addition he had decreased the frequency of shaving to once per week and had noted difficulty in attaining an erection for the last 6 months. He denied headache, visual symptoms, nocturia or polyuria.

On physical examination, pulse was 50, blood pressure was 96/54 and the skin was dry. Visual fields were full to confrontation. The thyroid was not palpable. The testes were soft and symmetric measuring about 3 x 2 cm. The deep tendon reflexes were brisk, but the relaxation phase was delayed.

Laboratory testing revealed:

  • hemoglobin of 11.0 gm (low)
  • T4 was 3.0 mcg/dl (low)
  • TSH of 0.6 mcU/ml ("normal").
  • AM cortisol was 6.0 mcg/dl (“normal”).
  • Testosterone was 200 ng/dl (normal 300-1200 ng/dl)
  • LH of 12 mU/ml ("normal").
  • Prolactin was 296 ng/ml (normal <20 ng/ml).
  1. The patient most likely has a prolactinoma
    1. True
    2. False
  2. Among the following, which is the most appropriate next step?
    1. Cortrosyn (synthetic ACTH) stimulation test
    2. MRI of the adrenals
    3. Pituitary surgery
  3. What would you do next? Why?
    1. MRI of the sella
    2. Replacement with thyroid hormone
    3. Replacement with testosterone

    MRI of the sella revealed a 31 mm heterogeneous mass in the sella with probable invasion of the right cavernous sinus with encasement of the carotid.
  4. Which one of the following is the most appropriate next step? Why?
    1. Pituitary surgery
    2. Referral to an ophthalmologist for visual field testing
    3. Observation
  5. An appointment was made to see an ophthalmologist in 2 weeks. However, one week later, the patient developed severe headache and double vision. The most likely explanation for his symptoms is:
    1. Migraine headache
    2. Pituitary apoplexy
    3. Meningitis
    4. Cerebrospinal Fluid Leak

      The patient is taken to the operating room soon after he develops the above symptoms and during transphenoidal surgery, blood is found in the pituitary fossa which was drained. A pituitary tumor is also found and most of the tumor that was visualized was removed.
  6. PATH - What cell types comprise the normal anterior pituitary?
  7. PATH - How would you describe this lesion? Why is it so fragmented?
  8. PATH What is the differential diagnosis?
  9. PATH What special procedures would be used to establish the diagnosis and characterize the tumor?
  10. Discuss the use of thyroid, adrenal, and testosterone replacement in this patient.
  11. Would he have any benefits with GH replacement therapy?

3. Case 3

A 30-year-old man was referred by his dentist for prognathism and malocclusion. Shoe size had increased from 8 to 10 in the last four years and the patient complained of excessive sweating, headache, and polyuria, but denied change in sexual activity. He feels tired all the time and he attributes that to waking up often at night because of his snoring. His wife sleeps in another room because his snoring keeps her awake.

On physical examination, the patient had a prominent jaw, spacing of the teeth, thick skin and the thyroid was enlarged 1 1/2 times normal size, and felt firm and finely nodular. The rest of the examination was normal except for large, spade-like hands and feet.

Laboratory evaluation revealed:

  • Fasting AM growth hormone 12 ng/ml
  • Fasting AM glucose was 125 mg/dl
  • A 100-gram oral glucose tolerance test was done with the following results:
    0 min 30 min 60 min 120 min 180 min
    Glucose-mg/dl 125 190 180 160 100
    Growth Hormone - ng/ml 12 8 9 10 7
  1. The most likely diagnosis is
    1. Acromegaly
    2. Gigantism
    3. Physiologic Growth Hormone variation
  2. What other tests would you perform?
  3. How would you explain the glucose intolerance?
  4. What is the etiology of the excessive sweating?
  5. Potential therapy for this patient include all of the following EXCEPT:
    1. Transphenoidal pituitary surgery
    2. Octreotide
    3. Pegvisomant
    4. Radiation
    5. Observation
  6. PATH - How would you describe this lesion?
  7. PATH - What is the differential diagnosis?
  8. PATH - What special procedures would be used to establish the diagnosis and characterize the tumor?
  9. True or False: In Immunohistochemical studies, tumors of this type frequently stain for chromogranin proteins.
    1. True
    2. False

4. Case 4

A 25-year-old woman had noticed, over the last few months weight gain, rounding of her face, difficulty climbing stairs to her second floor apartment, easy bruising with minimal trauma, and wide purple stretch marks over her abdomen. She also noted that she had stopped menstruating about 2 years ago, but she attributed this to her weight gain. She also noticed that she was often upset and was unable to sleep. You suspect that this patient has Cushing's syndrome.

  1. Which one of the following is specific for Cushing's syndrome?
    1. Hypertension
    2. Weight gain
    3. Depression
    4. Wide purple striae

      On physical examination, blood pressure was 180/100. Her face had a moon-like appearance with a red complexion. There were wide (over 1 cm) purple striae over her shoulders and abdomen. There was marked deposition of fat in the abdomen and in the cervical, dorsal and supraclavicular regions. Her arms and legs appeared to be slightly wasted. There were ecchymoses over the extremities.
  2. Cushing's syndrome is suspected on the basis of the history and the physical examination. The most appropriate next step would be: Why?
    1. Measurement of random cortisol level
    2. 1-mg overnight dexamethasone suppression test
    3. MRI of the pituitary and the adrenal glands
    4. Referral to a good surgeon

      Plasma cortisol was 24 mcg/dl at 8 AM and 25 mcg/dl normal < 7.5 mcg/dl) at 9 PM. After 1 mg of dexamethasone taken at 11 PM, plasma cortisol at 8 AM the next morning was 18 mcg/dl (normal < 5 mcg/dl). Her ACTH level was undetectable. A high dose (8 mg) dexamethasone suppression test also failed to suppress the next morning’s cortisol level.
  3. How would you proceed in the evaluation?

    MRI of the sella was normal. CT scan of the adrenals revealed a large mass above the left kidney. At surgery, a 500 gram, partially encapsulated mass was found in the region of the superior pole of the left kidney. Representative microscopic sections were prepared from the mass.
  4. PATH - What changes would you expect to find in the adrenals from patients with Cushing's Syndrome (not due to exogenous glucocorticoids)?
  5. PATH - How would you distinguish nodular hyperplasia of the cortex from a cortical adenoma?
  6. PATH - What gross and microscopic features would permit you to distinguish an adrenal cortical adenoma from a cortical carcinoma?
  7. PATH - How could you distinguish an adrenal cortical carcinoma from a metastasis to the adrenal gland? What tumors commonly metastasize to the adrenals?