Case Discussion <Case Presentation>           A 32-year-old woman suffered from cough with copious whitish sputum and urine frequency and urgency one week prior to admission. Besides, she gradually turned lethargic and disoriented, with complaints of abdomen discomfort, myalgia, arthralgia, headache, and gingival swelling. One day before admission, she lost consciousness during urination. She was sent to local hospital where hypotension and pyuria were found. The low blood pressure persisted even under intravenous fluid administration and dopamine infusion, so she was transferred to intensive care unit of this hospital for further management.      The patient's family mentioned that she had had massive postpartum hemorrhage during her second childbirth 2 years ago and secondary amenorrhea developed at the age of 30. She recognized to have light-colored areola, sparse pubic hair, and general malaise since then.      She had disturbed consciousness at admission. The temperature was 38.2oC, the pulse was 102 and the respiration was 24. The blood pressure was 100/60 mmHg. General physical examination showed no abnormalities except the pale-looking face, light-colored areola and sparse axillary and pubic hairs, and slightly decrease deep tendon reflexes of elbow and knee. Laboratory tests were performed (Table 1~3).  Table 1. Hematologic laboratory values on admission WBC RBC Hb Hct MCV PLT K/μL M/μL g/dL % fL K/μL 19.74 3.45 10.4 29.1 84.3 107  Table 2. Blood chemical values on admission Alb LDH BUN Cre Na K TG T-Cho LDL-C HDL-C g/dL U/L mg/dL mg/dL M M mg/dL mg/dL mg/dL mg/dL 4.2 1176 47.8 1.3 127 5.4 121 89 28 9  Table 3. Endocrinologic laboratory tests E2 FSH LH Prolactin HGH DHEA-S Free T4 T3 TSH pg/ml mIU/ml mIU/ml ng/ml ng/ml μmol/L ng/dl  ng/dl μIU/ml <20 1.9 0.7 4.2 11 <0.81 0.51 40.9 5.16   Cortisol ACTH   μg/dL pg/ml 0800hr 5.2 61.9 1600hr 3.1 50.6       She was treated with ceftriaxone 1g iv q12h for a total of 7 days. Blood and urine cultures both yielded E.coli. However, profound hypotension did not respond to antibiotic, iv fluid and inotropic agents. Treatment with iv hydrocortisone (100 mg q8h) was begun, under the impression of adrenal insufficiency, which was later proved by laboratory tests. The diagnosis of Sheehan's syndrome was made according to her past history, endocrinologic examinations and imaging studies (Fig. 1&2). Her blood pressure stabilized after steroid use and she regained consciousness gradually. She was maintained on oral prednisolone 7.5 mg per day after discharge from this hospital. Fig. 1. Skull X-ray (lateral view): The sella turcica is intact, No evident destructive bone lesions or fractures are noted. Frontal sinus is prominent. Fig. 2. MRI study without and with enhancement: The anterior pituitary gland was very small in size and the posterior pituitary and stlak was preserved. The sellar fossa was filled with CSF and was compatible with empty sella syndrome or Sheehan's syndrome. <病案分析 >      本案為一腦下垂體前葉功能不足(anterior pituitary insufficiency)，而以腎上腺危症(adrenal crisis)來表現的病例。在處置上, 如果第一線醫師未想到這個診斷, 可能就會失去治療的契機, 造成患者死亡。故而此病雖罕見, 卻非常重要。在鑑別診斷上, 由於患者一開始的表現常只是疲倦、虛弱等等非特異性的症狀,不容易做早期診斷。 但若同時有低血鈉症與休克的表現, 對輸液與升壓劑反應不佳時, 應立刻想到腎上腺危症之診斷, 並進一步抽血測cortisol 與ACTH以實驗室檢查證實。 在實驗室檢查方面, 早晨8:00 之cortisol level若低於3 μg/dL,可直接診斷為adrenal insufficiency; 若高於19 μg/dL, 則可排除此診斷。 但若介於這兩者之間, 則必須依賴ACTH stimulation test做區分: 亦即, 對病人施與250μg之cosyntropin 肌肉注射, 在30及60分鐘後各測一次cortisol level; 若其中有一次到達18μg/dL以上, 就可排除此診斷; 反之, 則可確認病人有adrenal insufficiency。      本案之病人來時是處於所謂adrenal crisis狀態, 此時較為合適的做法, 是抽血測cortisol 及ACTH之後, 立刻給予glucocorticoid replacement。 可考慮使用dexamethasone, 因為若laboratory tests無法確定是adrenal insufficiency時, 可以再做ACTH test證實, 而dexamethasone比較不會干擾cortisol之測定。      此外, 病人的病史詢問及理學檢查也是相當重要的。 Secondary adrenal insufficiency 最常見的原因, 並非本例所見之Sheehan's syndrome, 而是長期使用類固醇抑制本身的hypothalamus-pituitary-adrenal axis, 又因為某些原因停用類固醇時所導致。 此時, 患者外表雖像Cushing's syndrome, 卻有adrenal insufficiency的表現, 病史上也可問到患者過去吃藥的情況。 此外, 過去是否有接受過腦下垂體手術或腦部放射線治療, 也是相當重要的病史; 而其他axes的腦下垂體機能是否有問題, 如是否合併性腺機能低下、 是否有甲狀腺功能過低的表現, 如怕冷、 便秘、 體重增加等等, 都是檢查患者的重點。 繼續教育考題 1. (C) In the hormone replacement for patients with coexistent thyroid and adrenal failure. A The dose of glucocorticoid must be increased slowly once thyroid replacement has been initiated. B The dose of thyroid hormone must be increased slowly once glucocorticoid replacement has been initiated. C Thyroid replacement must not be initiated until treatment with glucocorticoid has been instituted. D Mineralocorticoid replacement also must be included if combined therapy is required. E Growth hormone replacement also must be included if combined therapy is required. 2. (B) A 36-year-old woman visited your clinics because of absence of menses for 4 months. For confirming the continuing of estrogen production, you should perform which of the following tests? A Plasma estrone and luteinizing hormone levels. B  A short course of progesterone therapy to see if menses will appear. C Plasma prolactin level. D Administering hCG to see if there is an increase in plasma estradiol level. E Whether the patient had hot flashes in physical exam. 3. (E) A previously healthy patient developed Sheehan's syndrome due to a postpartum hemorrhage. Which of the following tests will be abnormal the day after her pituitary ceases to funciton? A Total T3. B ACTH stimulation test. C Total T4. D IGF-1. E Insulin tolerance test. 4. (C) A 60-year-old woman in the intensive care unit is suspected of having panhypopituitarism. She is hypotensive and not responding to antibiotics or pressors. The cortisol level is 4.8 μg/dL, total T3 40 ng/dL, LH 0.2 IU/L, FSH 0.5 IU/L, GH 2 ng/ml. E2 is low. Which of the following is most feasible way to manage this patient? A Start immediately 100 mg hydrocortisone iv q6h wth levothyroxine and estrogen. B Investigate reasons other than hypopituitarism since its not likely the cause. C Give dexamethasone to treat the patient and perform an ACTH stimulation test to see if her adrenal response is intact. D Start thyroid replacement immediately. E Start hydrocortisone iv 100 mg q6h and thyroid hormone concomittently. 5. (A) A 35-year-old woman has secondary amenorrhea for 4 months. A pregnancy test is negative. Serum LH and FSH are elevated and E2 is very low. These findings suggest A Premature menopause. B Bilateral tubal obstruciton. C Exogenous estrogen administration. D Polycystic ovarian disease. E Panhypopituitarism. 6. (B) Which of the following may not be present in patients with secondary adrenal insufficiency? A Hypoglycemia. B Hyperkalemia. C Hyponatremia. D Weight loss. E Hypochloremia. 7. (D) Which of the following is not an etiology of secondary adrenal insufficiency? A Surgical resection or radiation damage. B Pituitary adenoma. C Hemochromatosis. D Ketoconazole. E Tuberculosis. 8. (E) About insulin tolerance test, which of the following is wrong? A The dosage of regular insulin is around 0.05-0.15 U/kg. B In cases of acromegaly and diabetes mellitus, higher dosage of insulin is feasible. C In cases of suspected adrenal insufficiency, the dosage of insulin is lower (0.05 U/kg). D Glucose should be less than 40 mg/dL after insulin injection to induce adequate ACTH and cortisol responses. E In cases of previous coronary heart disease or cerebrovascular disease, the test should be performed with lower doses of insulin. 9. (A) The following conditions/ disorders can result in an increase of prolactin level, except: A Sheehan's syndrome. B Pituitary stalk section. C Psychotropic agents. D Estrogen excess. E Primary hypothyroidism. 10. (E) About steroid replacement in patients with adrenal insufficiency, which of the following is incorrect? A The dose for most adults is 20-30 mg/day of hydrocortisone. B Mineralocorticoids should be replaced if a dose of hydrocortisone is less than 100 mg/day, in patients with primary adrenal insufficiency. C During intercurrent illness, the dose of hydrocortisone should be doubled. D Output of cortisol in normal individuals undergoing proloned major stress is about 10 mg/hr, or 250-300 mg/day. E All of the above are correct.