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Cushing's syndrome caused by an adrenal adenoma
Cushing’s Syndrome Caused by an Adrenal Adenoma By M. Zia-ul-Miraj,
G.N.
Usmani,
Lahore,
M.M.
Yaqub,
and
S. Ashraf
Pakistan
A IO-year-old boy presented with features of Cushing’s syndrome. Investigations, including ultrasound scan and computed tomography scans, demonstrated a right adrenal tumor. The tumor was excised and histologically found to be an encapsulated adrenal adenoma. Surgical excision is the treatment of choice for adrenal tumors. However, because it is often difficult to differentiate benign from malignant le-
sions on histopathologic regular long-term follow-up. J Pediatr Surg 33:644-646. ders Company.
A
sone was also given during the operation. Perioperative triple antibiotics (ampicillin, gentamycin, metronidazole) were administered. A laparotomy was performed through an upper transverse incision. No abnormality was detected in the left adrenal gland on palpation. The right hepatic flexure was mobilized and displaced downward. The duodenum was retracted medially after Kocher maneuver and the liver retracted upward. The right adrena gland was found to be replaced by a fleshy, encapsulated tumor measuring 3 X 3 cm. The tumor was excised completely after securing all the blood vessels (Fig 4). The cut surface demonstrated a firm grey tissue with a tiny yellowish area at the periphery. The histopathologic examination result was consistent with the diagnosis of a completely encapsulated adrenal adenoma. Parenteral cortisone was continued until the third postoperative day when it was replaced by oral prednisolone and gradually reduced to 3.5 mgid. The patient made a smooth recovery and was discharged on the 10th postoperative day. Prednisolone was gradually withdrawn over the next 3 months. At 6-month follow-up, the patient remains well.
DRENOCORTICAL TUMORS are rare in children, accounting for 0.6% of all childhood tumors.’ In children, these are functioning tumors and secrete excessive amounts of various normal or abnormal adrenocortical hormones, resulting in a variety of clinical syndromes. Vi&zing tumors are seen in about two thirds of childhood cases resulting in precocious puberty in boys and masculinization in girls.2,3 Cushing’s syndrome is manifested in about one third of cases. Rarely, childhood adrenal tumors may be nonfunctioning or present with symptoms of feminization or hyperaldosteronism.1,2,4 A case of Cushing’s syndrome secondary to an adrenal adenoma is presented here along with a literature review. CASE
Copyright
Cushing’s syndrome, adrenalectomy.
these o
patients 1998 by
adrenal
need W.B.
adenoma,
a
Saun-
ad-
REPORT
A lo-year-old boy presented with a l-year history of obesity. There was no history of any drug intake. Physical examination results showed typical features of Cushing’s syndrome including obesity involving the bunk, face (moon facies; Fig l), supraclavicular areas and upper back (buffalo hump; Fig 2), acne, and striae over the abdomen and thighs. His weight was 41 kg and blood pressure 130/90. Full blood count, triglyceride level, cholesterol level, and lipoprotein level were normal. Blood chemistry showed sodium, 137 mmol/L; potasium, 2.6 mmol/L; chloride, 99 mmol& urea. 8 mg/dL, and creatinine, 0.9 mg/dL. Random serum cortisol levels were 27.7 pg/dL (normal, 5 to 20 pg/dL). X-rays of the skull showed a normal pituitary fossa. Ultrasound scan and computed tomography (CT) scans of the abdomen showed a 2.8- X 2.9-cm soft tissue mass in the right adrenal gland and a normal left adrenal gland (Fig 3). There was no involvement of the kidney, the renal vein, or the inferior vena cava. X-rays of the chest were normal. A diagnosis of an adrenal tumor was made and operation planned. Parenteral cortisone, 75 mg/d (50 mg/m’) in two divided doses, was started 2 days before the operation. Intravenous fluids were started the night before the operation. An additional dose of 100 mg of hydrocort-
From the Departments of Paediatric Surgery, and Anaesthesia, Shaukat Khanum Memorial Research Centre, Lahore, Pakistan. Address reprint requests to M. Zia-ul-Miraj, Town Extension, Lahore, Pakistan. Copyright 0 1998 by WI. Saunders Company 0022-3468/98/3304-0022$03.00/O 644
INDEX WORDS: renal carcinoma,
grounds,
Paediatric Oncology, Cancer Hospital and FRCS,
86-S,
Model
DISCUSSION
Iatrogenic administration of exogenous steroids is the most common cause of Cushing’s syndrome in childrem Various adrenal lesions responsible for Cushing’s syndrome include bilateral hyperplasia, carcinoma, and adenoma. Tumors are more common in children younger than 7 years, whereas in older children and adults, bilateral adrenal hyperplasia secondary to a pituitary lesion is more frequent. 3,6,7 Cushing’s syndrome is a presenting feature of about one third of childhood adrenocortical tumors and exhibits a strong female over male preponderance. 2,5,6In most cases, a carcinoma is responsible, followed by an adenoma and, rarely, an ectopic adrenocorticotropic hormone (ACTH)-secreting tumor.2 The clinical presentation is a result of abnormally high blood levels of steroid hormones, leading to a characteristic pattern of obesity especially involving the cheeks (moon facies), the tink, the pectoral girdle, and supraclavicular areas (buffalo hump). Other features include a variable degree of virilization, osteoporosis, weakness, acne, seborrhea, growth arrest, hypertension, striae over Journa/
ofPediatric
Surgery,
Vol33,
No 4 (April),
1998: pp 644-646
CUSHING’S
SYNDROME
Fig 3. CT scan tumor (arrow).
of the
abdomen
demonstrates
a right
adrenal
the abdomen and thighs, glycosuria, psychosis, and predisposition to infections.2%3,6 The diagnostic evaluation of Cushing’s syndrome includes three types of investigations: biochemical confirmation of adrenal hyperfunction, search for an etiology, and localization of the lesion. The confirmatory biochemical findings include increased plasma cortisol levels (>20 pg/dL) with loss of diurnal rhythm, increased urinary-free cortisol (UFC) levels, and lack of suppression of plasma cortisol levels after an overnight dexamethasone suppression test. 2,3S,7Various investigations to determine if it is ACTH dependent or ACTH independent include the commonly used high-dose dexamethasone suppression test, the less frequently used radioimmunoassays for ACTH, and, still experimental, ovine corticotropin-releasing hormone (o-CRH) stimulation test.7 Radio-
Fig 1, Fig 2. ing’s syndrome.
Ten-year-old Note “moon
boy presenting with features facies” and “buffalo hump.”
of CushFig 4. Excised specimen cm. Histological examination adenoma.
of right adrenal tumor measuring 3 x 3 confirmed it to be a well-encapsulated
646
ZIA-UL-MIRAJ
graphs of the base of skull and magnetic resonance imaging (MRI) scan are invaluable in detection of an ACTH-secreting pituitary adenoma. Localization of an adrenal tumor can usually be accomplished by ultrasound (US) and CT scans, which usually demonstrate a mass in the suprarenal area on one side and a normal or atrophic adrenal gland on the contralateral side.6.7*8Adenomas are usually solitary and well encapsulated, whereas carcinomas tend to be larger and may infiltrate locally and metastasize to regional lymph nodes as well as to the lungs and liver.3 It is often difficult to differentiate adenoma from carcinoma clinically or radiologically unless a large palpable tumor, vascular invasion, or metastases are evident.6 The treatment of choice for adrenal turnout-s is a complete surgical excision. This can be easily accomplished in case of a well-encapsulated tumor. Even in case of an infiltrating tumor, if a complete excision is not possible, as much tumor as possible should be debulked.5 Preoperative preparation must include careful correction of any electrolyte imbalance, abnormal carbohydrate metabolism, and hypertension. Because the contralateral adrenal is always suppressed by circulating high blood levels of steroids, perioperative administration of cortisone is absolutely essential to avoid postoperative adrenal insufficiency.1v5,8,gVarious surgical approaches include posterior “hockey-stick, ” anterior transabdominal transverse, subcostal, and thoracoabdominal incisions.5,8,gThe transperitoneal anterior approach offers the advantages of allowing exploration of the entire abdomen and the
ET AL
contralateral adrenal, and wide en-block dissection including the ipsilateral kidney in case of an infiltrating tumor.g No single test can differentiate an adrenal carcinoma from an adenoma. It is often difficult to make a differentiation on histological appearance alone because the conventional evidence of malignancy may be absent,6 however, size larger than 5 cm (or 70 g), invasion into veins, extension through the capsule, and distant metastases are indications of ma1ignancy.Q Interestingly, tumors appearing histologically benign have been shown to recur locally, and those appearing malignant may never recur if completely excised.2,6 The prognosis after excision of an adenoma is excellent4,s but the outlook for patients with a carcinoma is less favorable.3J Sabbaga et al lo found age under 2 years, symptoms of less than 6 months duration, and complete tumor excision to be associated with good survival in patients with a carcinoma. In case of a residual or metastatic carcinoma, the antineoplastic drug, mitotane (o,p-DDD), alone or in combination with other chemotherapeutic agents, has been shown to offer effective palliation1-3~5~8J* but does not improve the survival rate.‘O Regardless of the histological diagnosis, regular follow-up is essential, especially if the tumor is more than 5 cm in diameter. In children, the adrenal carcinomas appear to be less aggressive, so a longer period of observation is recommended before labelling the lesion benign.6
REFERENCES 1. Morales L, Rovera J, Rottermann M, et al: Adrenocortical tumors in childhood. J Pediatr Surg 24:276-281, 1989 2. Snyder HM: Genitourinary tumors, in Kelalis PP, King LR, Belman AB (eds): Clinical Pediatric Urology (3rd ed), Philadelphia, PA, Saunders, 1992, pp 1379-1413 3. Di George AM, Levine LS: Cushing syndrome, in Behrman RE, Kliegman RM, Arvin AM (eds): Nelson Textbook of Pediatrics (15th ed), Philadelphia, PA, Saunders, 1996, pp 1623-1624 4. Agarawala S, Mitra DK, Bhatnagar V, et al: Aldosteronoma in childhood: Areview of clinical features and management. J Pediatr Surg 29:1388-1391, 1994 5. Holder TM, Snyder CL: Cushing’s syndrome and adrenal cortical tumours, in Ashcraft KW, Holder TM (eds): Pediatric Surgery (2nd ed) Philadelphia, PA, Saunders, 1993, pp 914-917 6. Bondy PK: Adrenocortical hyperactivity (Gushing’s syndrome), in Wilson JD, Foster DW (eds): Williams Textbook of Endocrinology (17th ed), Philadelphia, PA, Saunders, 1985, pp 858-870
7. Bickler SW, McMahon TJ, Campbell JR, et al: Preoperative diagnostic evaluation of children with Cushing’s syndrome. J Pediatr Surg 29:671-676, 1994 8. Forsham PH: Disorders of the adrenal McAninch JW (eds): Smith’s General Urology Appleton and Lange, 1992, pp 495-503
glands, in Tanagho (13th ed), Norwalk,
EA, CT,
9. Hinman F: Preparation and approaches to adrenal surgery. In Hinman F (ed): Pediatric Urologic Surgery (1st ed) Philadelphia, PA, WB Saunders, 1994, pp 191-197 10. Sabbaga CC, carcinoma in children: 28:841-843, 1993
Avilla SG, Schulz C, et al: Adrenocortical Clinical aspects and prognosis. J Pediatr Surg
11. Tyler DS: Adrenal tumours, in Berger DH, Feig SW, Fuhrman GM (eds): Anderson Surgical Oncology Handbook (1st ed) Boston, MA, Little-Brown, 1995, pp 259-274
G.N.
Usmani,
Lahore,
M.M.
Yaqub,
and
S. Ashraf
Pakistan
A IO-year-old boy presented with features of Cushing’s syndrome. Investigations, including ultrasound scan and computed tomography scans, demonstrated a right adrenal tumor. The tumor was excised and histologically found to be an encapsulated adrenal adenoma. Surgical excision is the treatment of choice for adrenal tumors. However, because it is often difficult to differentiate benign from malignant le-
sions on histopathologic regular long-term follow-up. J Pediatr Surg 33:644-646. ders Company.
A
sone was also given during the operation. Perioperative triple antibiotics (ampicillin, gentamycin, metronidazole) were administered. A laparotomy was performed through an upper transverse incision. No abnormality was detected in the left adrenal gland on palpation. The right hepatic flexure was mobilized and displaced downward. The duodenum was retracted medially after Kocher maneuver and the liver retracted upward. The right adrena gland was found to be replaced by a fleshy, encapsulated tumor measuring 3 X 3 cm. The tumor was excised completely after securing all the blood vessels (Fig 4). The cut surface demonstrated a firm grey tissue with a tiny yellowish area at the periphery. The histopathologic examination result was consistent with the diagnosis of a completely encapsulated adrenal adenoma. Parenteral cortisone was continued until the third postoperative day when it was replaced by oral prednisolone and gradually reduced to 3.5 mgid. The patient made a smooth recovery and was discharged on the 10th postoperative day. Prednisolone was gradually withdrawn over the next 3 months. At 6-month follow-up, the patient remains well.
DRENOCORTICAL TUMORS are rare in children, accounting for 0.6% of all childhood tumors.’ In children, these are functioning tumors and secrete excessive amounts of various normal or abnormal adrenocortical hormones, resulting in a variety of clinical syndromes. Vi&zing tumors are seen in about two thirds of childhood cases resulting in precocious puberty in boys and masculinization in girls.2,3 Cushing’s syndrome is manifested in about one third of cases. Rarely, childhood adrenal tumors may be nonfunctioning or present with symptoms of feminization or hyperaldosteronism.1,2,4 A case of Cushing’s syndrome secondary to an adrenal adenoma is presented here along with a literature review. CASE
Copyright
Cushing’s syndrome, adrenalectomy.
these o
patients 1998 by
adrenal
need W.B.
adenoma,
a
Saun-
ad-
REPORT
A lo-year-old boy presented with a l-year history of obesity. There was no history of any drug intake. Physical examination results showed typical features of Cushing’s syndrome including obesity involving the bunk, face (moon facies; Fig l), supraclavicular areas and upper back (buffalo hump; Fig 2), acne, and striae over the abdomen and thighs. His weight was 41 kg and blood pressure 130/90. Full blood count, triglyceride level, cholesterol level, and lipoprotein level were normal. Blood chemistry showed sodium, 137 mmol/L; potasium, 2.6 mmol/L; chloride, 99 mmol& urea. 8 mg/dL, and creatinine, 0.9 mg/dL. Random serum cortisol levels were 27.7 pg/dL (normal, 5 to 20 pg/dL). X-rays of the skull showed a normal pituitary fossa. Ultrasound scan and computed tomography (CT) scans of the abdomen showed a 2.8- X 2.9-cm soft tissue mass in the right adrenal gland and a normal left adrenal gland (Fig 3). There was no involvement of the kidney, the renal vein, or the inferior vena cava. X-rays of the chest were normal. A diagnosis of an adrenal tumor was made and operation planned. Parenteral cortisone, 75 mg/d (50 mg/m’) in two divided doses, was started 2 days before the operation. Intravenous fluids were started the night before the operation. An additional dose of 100 mg of hydrocort-
From the Departments of Paediatric Surgery, and Anaesthesia, Shaukat Khanum Memorial Research Centre, Lahore, Pakistan. Address reprint requests to M. Zia-ul-Miraj, Town Extension, Lahore, Pakistan. Copyright 0 1998 by WI. Saunders Company 0022-3468/98/3304-0022$03.00/O 644
INDEX WORDS: renal carcinoma,
grounds,
Paediatric Oncology, Cancer Hospital and FRCS,
86-S,
Model
DISCUSSION
Iatrogenic administration of exogenous steroids is the most common cause of Cushing’s syndrome in childrem Various adrenal lesions responsible for Cushing’s syndrome include bilateral hyperplasia, carcinoma, and adenoma. Tumors are more common in children younger than 7 years, whereas in older children and adults, bilateral adrenal hyperplasia secondary to a pituitary lesion is more frequent. 3,6,7 Cushing’s syndrome is a presenting feature of about one third of childhood adrenocortical tumors and exhibits a strong female over male preponderance. 2,5,6In most cases, a carcinoma is responsible, followed by an adenoma and, rarely, an ectopic adrenocorticotropic hormone (ACTH)-secreting tumor.2 The clinical presentation is a result of abnormally high blood levels of steroid hormones, leading to a characteristic pattern of obesity especially involving the cheeks (moon facies), the tink, the pectoral girdle, and supraclavicular areas (buffalo hump). Other features include a variable degree of virilization, osteoporosis, weakness, acne, seborrhea, growth arrest, hypertension, striae over Journa/
ofPediatric
Surgery,
Vol33,
No 4 (April),
1998: pp 644-646
CUSHING’S
SYNDROME
Fig 3. CT scan tumor (arrow).
of the
abdomen
demonstrates
a right
adrenal
the abdomen and thighs, glycosuria, psychosis, and predisposition to infections.2%3,6 The diagnostic evaluation of Cushing’s syndrome includes three types of investigations: biochemical confirmation of adrenal hyperfunction, search for an etiology, and localization of the lesion. The confirmatory biochemical findings include increased plasma cortisol levels (>20 pg/dL) with loss of diurnal rhythm, increased urinary-free cortisol (UFC) levels, and lack of suppression of plasma cortisol levels after an overnight dexamethasone suppression test. 2,3S,7Various investigations to determine if it is ACTH dependent or ACTH independent include the commonly used high-dose dexamethasone suppression test, the less frequently used radioimmunoassays for ACTH, and, still experimental, ovine corticotropin-releasing hormone (o-CRH) stimulation test.7 Radio-
Fig 1, Fig 2. ing’s syndrome.
Ten-year-old Note “moon
boy presenting with features facies” and “buffalo hump.”
of CushFig 4. Excised specimen cm. Histological examination adenoma.
of right adrenal tumor measuring 3 x 3 confirmed it to be a well-encapsulated
646
ZIA-UL-MIRAJ
graphs of the base of skull and magnetic resonance imaging (MRI) scan are invaluable in detection of an ACTH-secreting pituitary adenoma. Localization of an adrenal tumor can usually be accomplished by ultrasound (US) and CT scans, which usually demonstrate a mass in the suprarenal area on one side and a normal or atrophic adrenal gland on the contralateral side.6.7*8Adenomas are usually solitary and well encapsulated, whereas carcinomas tend to be larger and may infiltrate locally and metastasize to regional lymph nodes as well as to the lungs and liver.3 It is often difficult to differentiate adenoma from carcinoma clinically or radiologically unless a large palpable tumor, vascular invasion, or metastases are evident.6 The treatment of choice for adrenal turnout-s is a complete surgical excision. This can be easily accomplished in case of a well-encapsulated tumor. Even in case of an infiltrating tumor, if a complete excision is not possible, as much tumor as possible should be debulked.5 Preoperative preparation must include careful correction of any electrolyte imbalance, abnormal carbohydrate metabolism, and hypertension. Because the contralateral adrenal is always suppressed by circulating high blood levels of steroids, perioperative administration of cortisone is absolutely essential to avoid postoperative adrenal insufficiency.1v5,8,gVarious surgical approaches include posterior “hockey-stick, ” anterior transabdominal transverse, subcostal, and thoracoabdominal incisions.5,8,gThe transperitoneal anterior approach offers the advantages of allowing exploration of the entire abdomen and the
ET AL
contralateral adrenal, and wide en-block dissection including the ipsilateral kidney in case of an infiltrating tumor.g No single test can differentiate an adrenal carcinoma from an adenoma. It is often difficult to make a differentiation on histological appearance alone because the conventional evidence of malignancy may be absent,6 however, size larger than 5 cm (or 70 g), invasion into veins, extension through the capsule, and distant metastases are indications of ma1ignancy.Q Interestingly, tumors appearing histologically benign have been shown to recur locally, and those appearing malignant may never recur if completely excised.2,6 The prognosis after excision of an adenoma is excellent4,s but the outlook for patients with a carcinoma is less favorable.3J Sabbaga et al lo found age under 2 years, symptoms of less than 6 months duration, and complete tumor excision to be associated with good survival in patients with a carcinoma. In case of a residual or metastatic carcinoma, the antineoplastic drug, mitotane (o,p-DDD), alone or in combination with other chemotherapeutic agents, has been shown to offer effective palliation1-3~5~8J* but does not improve the survival rate.‘O Regardless of the histological diagnosis, regular follow-up is essential, especially if the tumor is more than 5 cm in diameter. In children, the adrenal carcinomas appear to be less aggressive, so a longer period of observation is recommended before labelling the lesion benign.6
REFERENCES 1. Morales L, Rovera J, Rottermann M, et al: Adrenocortical tumors in childhood. J Pediatr Surg 24:276-281, 1989 2. Snyder HM: Genitourinary tumors, in Kelalis PP, King LR, Belman AB (eds): Clinical Pediatric Urology (3rd ed), Philadelphia, PA, Saunders, 1992, pp 1379-1413 3. Di George AM, Levine LS: Cushing syndrome, in Behrman RE, Kliegman RM, Arvin AM (eds): Nelson Textbook of Pediatrics (15th ed), Philadelphia, PA, Saunders, 1996, pp 1623-1624 4. Agarawala S, Mitra DK, Bhatnagar V, et al: Aldosteronoma in childhood: Areview of clinical features and management. J Pediatr Surg 29:1388-1391, 1994 5. Holder TM, Snyder CL: Cushing’s syndrome and adrenal cortical tumours, in Ashcraft KW, Holder TM (eds): Pediatric Surgery (2nd ed) Philadelphia, PA, Saunders, 1993, pp 914-917 6. Bondy PK: Adrenocortical hyperactivity (Gushing’s syndrome), in Wilson JD, Foster DW (eds): Williams Textbook of Endocrinology (17th ed), Philadelphia, PA, Saunders, 1985, pp 858-870
7. Bickler SW, McMahon TJ, Campbell JR, et al: Preoperative diagnostic evaluation of children with Cushing’s syndrome. J Pediatr Surg 29:671-676, 1994 8. Forsham PH: Disorders of the adrenal McAninch JW (eds): Smith’s General Urology Appleton and Lange, 1992, pp 495-503
glands, in Tanagho (13th ed), Norwalk,
EA, CT,
9. Hinman F: Preparation and approaches to adrenal surgery. In Hinman F (ed): Pediatric Urologic Surgery (1st ed) Philadelphia, PA, WB Saunders, 1994, pp 191-197 10. Sabbaga CC, carcinoma in children: 28:841-843, 1993
Avilla SG, Schulz C, et al: Adrenocortical Clinical aspects and prognosis. J Pediatr Surg
11. Tyler DS: Adrenal tumours, in Berger DH, Feig SW, Fuhrman GM (eds): Anderson Surgical Oncology Handbook (1st ed) Boston, MA, Little-Brown, 1995, pp 259-274