Case Discussion A 48-year-old man was sent to the Emergency Department of a teaching hospital on June 4, 2001 because of drowsy consciousness, nausea, vomiting and progressive malaise for 3 days. He began to develop rhinorrhea, cough and sore throat 4 days ago and upper respiratory tract infection was diagnosed at a local hospital. He took some oral medications but his symptoms did not improve. He had an episode of head injury 15 years ago with transient loss of consciousness but without significant neurologic sequelae. He complained of progressive general malaise and decreased libido in recent one year.  On examination, his consciousness was drowsy. The blood pressure was 98/61 mm Hg and pulse rate was 80 per minute. The body temperature was 37.5°C. The breathing sounds were clear and there were no heart murmurs. There were scanty hairs over the axillary and pubic areas, but without hyperpigmentation over the skin.  The chest X-ray was clear (Figure 1) and the urinalysis was within normal limits. The biochemistry data showed hypoglycemia (Glucose: 43 mg/dl) and hyponatremia (Na: 109.6 mmol/L). Under the suspicion of adrenal crisis, glucose water, normal saline and hydrocortisol (100 mg) were administered. His consciousness level improved and was admitted to the Endocrinology Ward. The serum levels of testosterone, LH and FSH were 0.66 ng/ml, 3.3 mIU/ml, and 2.1 mIU/ml, respectively. The brain MRI showed a normal size of the sella turcica but the anterior pituitary lobe was small in size. The signal intensity of the posterior pituitary lobe was well preserved (Figure 2 and Figure 3 ), suggesting the diagnosis of partial empty sella. The TRH and LHRH tests revealed normal response of TSH and LH/FSH. Results of the thyroid function (see lab.) were compatible with hypothyroidism. The titer of antimicrosomal antibody (AMA) was high (1:20480) and the thyroid sonography revealed hypoechogenicity of both lobes. He received replacement therapy of prednisolone, eltroxin, and testosterone enanthate. He was discharged on June 21, 2001 in a stable condition. Laboratory results: 1. CBC/DC:    WBC Hb Hct MCV PLT Seg. Eos. Bas. Mono. Lym.   K/uL g/dL % fL K/uL % % % % % June 04 5.79 9.4 26.3 59.9 256 47.5 4.1 1.2 6.4 40.5 June 19 5.48 9.9 30.0 79.8 168 71.6 1.9 1.0 6.1 19.4 2. Biochemistry and electrolyte:   BUN Cre Na K Ca Cl  P Mg GOT   mg/dl mg/dl mmol/l mmol/l mmol/l mmol/l mg/dl mmol/l U/l June 05 3.3 0.5 120.0 4.4 2.1 85.0 2.8 0.76 94 June 19     133.0 4.2         34 3. U/A: Sp. Gr PH Pro. Glu. Ket. O.B. Urob. RBC WBC Epi. Cast Bac.       mg/dl g/dl     EU/dl /HFL /HFL /HFL /LFL   6/5 1.023 6.0 - - - + 1.0 12-15  5-6 - - - 4. DHEA-SO4 (umol/L): <0.81 (male: 4.6-13.4) 5. hGH (ng/ml): 1.9 (normal: 0.06-5.0) 6. Adrenal function June 05 Cortisol (μg/dl) ACTH (pg/nl) 8 A.M 39.8 <1.0 4 P.M 0.32 18.3 7. Thyroid function June 05 FreeT4 (CIA) hsTSH (CIA) T3 (RIA) T4 (RIA) Normal range ng/dl (0.6-1.75) μIU/ml (0.4-4) ng/dl (80-200) μg/dl (4-12) June 05 0.49 17.5 64.2 3.76 8. LHRH test   0’ 30’ 60’ 120’ LH (mIU/ml) 5.7 27.1 26 20.4 FSH (mIU/ml) 3.3 5.8 6.4 5.9 9. TRH test   0’ 15’ 30’ 60’ 120’ TSH (uIU/ml) 19.7 33.7 36.7 39 34.1 Prolactin (ng/dl) 5.4 29.3 32.1 25.1 13.2 註: Normal range: Cortisol ACTH LH FSH Testosterone μg/dl pg/nl mIU/ml mIU/ml ng/ml 5-25 (8A.M) 2.5-12.5 (4P.M) 10-65 Adult male 1.3-13 Adult male 0.9-15 Adult male 3-10 本病例為急性腎上腺功能不足，以意識不清和噁心嘔吐來表現。其誘發因素可能為上呼吸道感染。其實驗室檢查十分典型，包括低血糖、低血鈉、嗜伊紅性白血球增加、淋巴球增加。因為病人在急診處已先用類固醇治療，因此影響了隔天cortisol, ACTH的判讀。病人有性慾減退的症狀，其testosterone 值很低，而且LH, FSH 的值偏低，因此是低性腺促素性腺功能不足 (hypogonadotropin hypogonadism)。頭部核磁共振發現病人的腦下垂腺前葉較萎縮，但後葉的顯影則正常。所以臨床上的診斷為空鞍症候群合併腦下垂腺功能不足。空鞍 (empty sella) 的形成是由於先天性或後天性蝶鞍膈膜 (diaphrama sellae) 缺損，導致蜘蛛膜下腔的腦脊髓液擴張至蝶鞍中，將腦下垂腺壓扁；或是之前的腦下垂腺腫瘤因血管梗塞而萎縮 (pituitary infarction)。所以空鞍不是完全沒有腦下垂腺組織，而且腦下垂腺柄 (pituitary stalk) 可在核磁共振中清楚顯影 (此稱為infundibulum sign)。空鞍常常是在頭部影像檢查中意外發現，而空鞍症候群則是指臨床上合併頭痛、視野缺陷、腦脊髓液流涕 (CSF rhinorrhea) 或腦垂腺功能不足。空鞍症候群多發生在中年肥胖女性，有的病患可發現良性顱內高壓 (benign intracranial hypertension)。治療上是視腦下垂腺功能不足的程度，以標的器官荷爾蒙來補充，譬如類固醇、甲狀腺素、性荷爾蒙。空鞍和腦下垂腺無發育 (pituitary aplasia) 的鑑別診斷主要是靠腦下垂腺後葉在核磁共振上的顯影來區分。 繼續教育考題 1. (D) Which of the following is NOT commonly observed in adrenal insufficiency? A Hypoglycemia B Hyponatremia C Eosinophilia D Lymphocytopenia 2. (C) Which clinical feature below are is NOT common in acute adrenal crisis？ A hypotension and shock B fever C diarrhea D weakness, apathy 3. (D) Which of the following treatment is the least necessary for adrenal crisis？ A normal saline infusion B glucose water infusion C hydrocortisol infusion D antibiotics 4. (C) Which of the following tests is NOT useful in the diagnosis of adrenal insufficiency？ A ACTH stimulation test B Insulin-induced hypoglycemia test C Dexamethasone suppression test D Metyrapone test 5. (B) Which of the following hormone deficiency will develop FIRST in hypopituitarism？ A TSH B GH C LH D ACTH 6. (C) Which of the following conditions is associated with the most significant response during TRH test？ A Panhypopituitarism B Hyperthyroidism C Primary hypothyroidism D Kallman’s syndrome 7. (A) Which of the following hormones should be replaced FIRST for patients with panhypopituitarism？ A Prednisolone B Eltroxin. C Sex hormone D GH 8. (D) Which of the following conditions is related to the empty sella syndrome？ A Congenital diaphrama sellae defect B Pituitary surgery C Brain irradiation D All of above 9. (A) Which of the following features will distinguish empty sella from pituitary aplasia？ A High signal intensity of posterior pituitary lobe on MRI B Exaggerated response of TRH test C Enlargement of sella turcica on plain X-film D Minimal tissue in sella turcica on CT scan 10. (A) What is the prevalence rate of evident hypopituitarism in primary empty sella？ A < 10% B 25% C 40% D 60%     Case Discussion A 48-year-old man was sent to the Emergency Department of a teaching hospital on June 4, 2001 because of drowsy consciousness, nausea, vomiting and progressive malaise for 3 days. He began to develop rhinorrhea, cough and sore throat 4 days ago and upper respiratory tract infection was diagnosed at a local hospital. He took some oral medications but his symptoms did not improve. He had an episode of head injury 15 years ago with transient loss of consciousness but without significant neurologic sequelae. He complained of progressive general malaise and decreased libido in recent one year.  On examination, his consciousness was drowsy. The blood pressure was 98/61 mm Hg and pulse rate was 80 per minute. The body temperature was 37.5°C. The breathing sounds were clear and there were no heart murmurs. There were scanty hairs over the axillary and pubic areas, but without hyperpigmentation over the skin.  The chest X-ray was clear (Figure 1) and the urinalysis was within normal limits. The biochemistry data showed hypoglycemia (Glucose: 43 mg/dl) and hyponatremia (Na: 109.6 mmol/L). Under the suspicion of adrenal crisis, glucose water, normal saline and hydrocortisol (100 mg) were administered. His consciousness level improved and was admitted to the Endocrinology Ward. The serum levels of testosterone, LH and FSH were 0.66 ng/ml, 3.3 mIU/ml, and 2.1 mIU/ml, respectively. The brain MRI showed a normal size of the sella turcica but the anterior pituitary lobe was small in size. The signal intensity of the posterior pituitary lobe was well preserved (Figure 2 and Figure 3), suggesting the diagnosis of partial empty sella. The TRH and LHRH tests revealed normal response of TSH and LH/FSH. Results of the thyroid function (see lab.) were compatible with hypothyroidism. The titer of antimicrosomal antibody (AMA) was high (1:20480) and the thyroid sonography revealed hypoechogenicity of both lobes. He received replacement therapy of prednisolone, eltroxin, and testosterone enanthate. He was discharged on June 21, 2001 in a stable condition. Laboratory results: 1. CBC/DC:    WBC Hb Hct MCV PLT Seg. Eos. Bas. Mono. Lym.   K/uL g/dL % fL K/uL % % % % % June 04 5.79 9.4 26.3 59.9 256 47.5 4.1 1.2 6.4 40.5 June 19 5.48 9.9 30.0 79.8 168 71.6 1.9 1.0 6.1 19.4 2. Biochemistry and electrolyte:   BUN Cre Na K Ca Cl  P Mg GOT   mg/dl mg/dl mmol/l mmol/l mmol/l mmol/l mg/dl mmol/l U/l June 05 3.3 0.5 120.0 4.4 2.1 85.0 2.8 0.76 94 June 19     133.0 4.2         34 3. U/A: Sp. Gr PH Pro. Glu. Ket. O.B. Urob. RBC WBC Epi. Cast Bac.       mg/dl g/dl     EU/dl /HFL /HFL /HFL /LFL   6/5 1.023 6.0 - - - + 1.0 12-15  5-6 - - - 4. DHEA-SO4 (umol/L): <0.81 (male: 4.6-13.4) 5. hGH (ng/ml): 1.9 (normal: 0.06-5.0) 6. Adrenal function June 05 Cortisol (μg/dl) ACTH (pg/nl) 8 A.M 39.8 <1.0 4 P.M 0.32 18.3 7. Thyroid function June 05 FreeT4 (CIA) hsTSH (CIA) T3 (RIA) T4 (RIA) Normal range ng/dl (0.6-1.75) μIU/ml (0.4-4) ng/dl (80-200) μg/dl (4-12) June 05 0.49 17.5 64.2 3.76 8. LHRH test   0’ 30’ 60’ 120’ LH (mIU/ml) 5.7 27.1 26 20.4 FSH (mIU/ml) 3.3 5.8 6.4 5.9 9. TRH test   0’ 15’ 30’ 60’ 120’ TSH (uIU/ml) 19.7 33.7 36.7 39 34.1 Prolactin (ng/dl) 5.4 29.3 32.1 25.1 13.2 註: Normal range: Cortisol ACTH LH FSH Testosterone μg/dl pg/nl mIU/ml mIU/ml ng/ml 5-25 (8A.M) 2.5-12.5 (4P.M) 10-65 Adult male 1.3-13 Adult male 0.9-15 Adult male 3-10 本病例為急性腎上腺功能不足，以意識不清和噁心嘔吐來表現。其誘發因素可能為上呼吸道感染。其實驗室檢查十分典型，包括低血糖、低血鈉、嗜伊紅性白血球增加、淋巴球增加。因為病人在急診處已先用類固醇治療，因此影響了隔天cortisol, ACTH的判讀。病人有性慾減退的症狀，其testosterone 值很低，而且LH, FSH 的值偏低，因此是低性腺促素性腺功能不足 (hypogonadotropin hypogonadism)。頭部核磁共振發現病人的腦下垂腺前葉較萎縮，但後葉的顯影則正常。所以臨床上的診斷為空鞍症候群合併腦下垂腺功能不足。空鞍 (empty sella) 的形成是由於先天性或後天性蝶鞍膈膜 (diaphrama sellae) 缺損，導致蜘蛛膜下腔的腦脊髓液擴張至蝶鞍中，將腦下垂腺壓扁；或是之前的腦下垂腺腫瘤因血管梗塞而萎縮 (pituitary infarction)。所以空鞍不是完全沒有腦下垂腺組織，而且腦下垂腺柄 (pituitary stalk) 可在核磁共振中清楚顯影 (此稱為infundibulum sign)。空鞍常常是在頭部影像檢查中意外發現，而空鞍症候群則是指臨床上合併頭痛、視野缺陷、腦脊髓液流涕 (CSF rhinorrhea) 或腦垂腺功能不足。空鞍症候群多發生在中年肥胖女性，有的病患可發現良性顱內高壓 (benign intracranial hypertension)。治療上是視腦下垂腺功能不足的程度，以標的器官荷爾蒙來補充，譬如類固醇、甲狀腺素、性荷爾蒙。空鞍和腦下垂腺無發育 (pituitary aplasia) 的鑑別診斷主要是靠腦下垂腺後葉在核磁共振上的顯影來區分。 繼續教育考題 1. (D) Which of the following is NOT commonly observed in adrenal insufficiency? A Hypoglycemia B Hyponatremia C Eosinophilia D Lymphocytopenia 2. (C) Which clinical feature below are is NOT common in acute adrenal crisis？ A hypotension and shock B fever C diarrhea D weakness, apathy 3. (D) Which of the following treatment is the least necessary for adrenal crisis？ A normal saline infusion B glucose water infusion C hydrocortisol infusion D antibiotics 4. (C) Which of the following tests is NOT useful in the diagnosis of adrenal insufficiency？ A ACTH stimulation test B Insulin-induced hypoglycemia test C Dexamethasone suppression test D Metyrapone test 5. (B) Which of the following hormone deficiency will develop FIRST in hypopituitarism？ A TSH B GH C LH D ACTH 6. (C) Which of the following conditions is associated with the most significant response during TRH test？ A Panhypopituitarism B Hyperthyroidism C Primary hypothyroidism D Kallman’s syndrome 7. (A) Which of the following hormones should be replaced FIRST for patients with panhypopituitarism？ A Prednisolone B Eltroxin. C Sex hormone D GH 8. (D) Which of the following conditions is related to the empty sella syndrome？ A Congenital diaphrama sellae defect B Pituitary surgery C Brain irradiation D All of above 9. (A) Which of the following features will distinguish empty sella from pituitary aplasia？ A High signal intensity of posterior pituitary lobe on MRI B Exaggerated response of TRH test C Enlargement of sella turcica on plain X-film D Minimal tissue in sella turcica on CT scan 10. (A) What is the prevalence rate of evident hypopituitarism in primary empty sella？ A < 10% B 25% C 40% D 60% 答案解說 (D ) 糖質皮質類固醇會促進肝臟糖質新生作用，並促進肝醣合成，因此腎上腺功能不足會造成低血糖。糖質類固醇可促進腎絲球濾過率，因此次發性腎上腺功能不足時，腎絲球濾過率減少導致水分滯留體內，造成低血鈉。糖質類固醇可促進嗜伊紅性白血球、淋巴球及單核球從循環血中移動出去，所以腎上腺功能不足時會出現嗜伊紅性白血球、淋巴球及單核球增多的現象。 (C) 腎上腺急症常見的表徵包括全身疲憊、意識混亂、水份不足甚至休克、急性腹部症狀、發燒等。其中急性腹部症狀常常是腹痛、噁心、嘔吐，但是較少以腹瀉來表現。 (D) 腎上腺急症的治療以補充水分、鈉鹽、葡萄糖及類固醇為主。類固醇的選擇以hydrocortisol最佳，因為其皮質類固醇與礦物類固醇的效力比為1：1，而且作用時間短效、迅速。抗生素的使用則視有無細菌感染的證據。 (C) 以250 μg ACTH 肌肉注射，可刺激腎上腺產生糖質類固醇。若腎上腺功能不足，則cortisol 的值在刺激後仍小於20 μg/dl。Insulin-induced hypoglycemia test和Metyrapone test 可評估腦下垂腺—腎上腺軸線功能是否有缺陷。Dexamethasone suppression test 是用來診斷庫欣氏症 (Cushing’s syndrome)。 (B) 泛腦下垂腺功能不足時，荷爾蒙缺乏的順序為GH﹐gonadotropin﹐TSH﹐ACTH﹐Prolactin。 (C) 腦下垂腺功能不足時，TRH test 產生的TSH response很低；而甲狀腺功能亢進時，TSH response幾乎沒有。在甲狀腺功能不足時，因為缺乏循環中的甲狀腺素來迴饋抑制，TSH response會增加許多。 (A ) 類固醇的補充必須先於甲狀腺素，因為甲狀腺素會促進身體的代謝，惡化腎上腺功能不足。 (D) 空鞍 (empty sella) 的形成是由於先天性或後天性蝶鞍膈膜 (diaphrama sellae) 缺損，導致蜘蛛膜下腔的腦脊髓液擴張至蝶鞍中，將腦下垂腺壓扁；或是之前的腦垂腺腫瘤因血管梗塞而萎縮 (pituitary infarction)。腦下垂腺手術或是腦部受過放射治療都有可能造成空鞍。 (A ) 空鞍和腦下垂腺無發育的鑑別診斷主要是靠腦下垂腺後葉在核磁共振上的顯影來區分。 (A)原發性空鞍常常是解剖學上的變異構造而已，造成腦下垂腺功能不足的比率不到