AACE ePoster Library

Background: The annual incidence of endogenous Cushing syndrome has been estimated at 13 cases per million individuals. Of these cases, approximately 70% are due to Cushing disease (pituitary ACTH-producing tumor); 15% to ectopic ACTH; and 15% to a primary adrenal tumor. The treatment of choice for endogenous Cushing syndrome is surgical resection of the causative tumor. The spontaneous remission of Cushing’s disease (CD) has been reported and might be a phase of cyclic disease, but could also be explained by an ACTH producing adenoma infarction or hemorrhage
Objective: We present case history of a 53 year old lady who presented with Cushing’s syndrome which later resolved spontaneously without surgery
Case history: The patient was referred initially for minimal galactorrhea and hyperprolactinemia. Galactorrhea was only on expression and the discharge was whitish/cloudy. Apart from hypertension, there was no significant past medical history. The only medication she took was Hydrochlorothiazide for hypertension. She became menopausal at the age of 48. Breast examination was unremarkable. Visual field examination was normal. She did not look Cushingoid.
Prolactin level was 40.6 (3-26 mcg/L). TSH was normal. AM Cortisol was 362 (185-624 nmol/L). MRI scan showed a 1.4 cm pituitary mass undergoing cystic degeneration. The hyperprolactinemia was thought to be due to stalk compression.
As she was post menopausal and since there was no spontaneous and bothersome galactorrhea, no treatment was initiated. The plan was to monitor the pituitary adenoma by serial MR scans.
She didn't look Cushingoid during the initial visit but developed symptoms and signs of Cushing's syndrome 5 months later. She complained of diffuse body swelling, fatigue, weight gain, facial puffiness, bruising of skin, and low mood.
On examination, her face was rounded, red and she had facial hirsutism. There was increased dorsal pad of fat. Blood pressure was high at 160/90 mm Hg. Telangiectasia of the hands and chest were noted. There was no proximal muscle weakness or purple striae over abdominal wall.
The clinical impression was that she had developed Cushing’s disease due to the pituitary adenoma and investigations were initiated.
HbA1c was 7.0% and hypokalemia of 3 mmol/L noted. 24 hour urine cortisol levels were elevated at 1904 and 1311 (<275 nmol/day). AM Cortisol was 798 (170-720 nmol/L). ACTH was 29.7 (0-10.1 pmol/L). Low dose dexamethasone suppression test reduced Cortisol to 774 nmol/L, ACTH remained high at 30.6 pmol/L. With high dose dexamethasone suppression test, Cortisol went down to 659 nmol/L and ACTH to 19.5 pmol/L.
The biochemical tests were suggestive of ectopic ACTH syndrome in this chronic smoker and further investigations were initiated.
Repeat MRI showed considerably smaller pituitary adenoma measuring 7x9 mm in size. As the pituitary adenoma was smaller, inferior petrosal sinus sampling was not done.
As she was symptomatic, Ketoconazole was initiated.
Chest X-ray, CT scan of the chest/abdomen were unremarkable. 24 hour urine 5 HIAA, Octreotide scan, Calcitonin and gastrin levels were normal.
Over the next few months, she showed improvement and Ketoconazole was reduced and eventually stopped.
Off the Ketoconazole, patient continues to show no clinical or biochemical evidence of Cushing's syndrome. MRI pituitary was done again and it showed further stability/slight reduction in the size of adenoma, measuring 5x10 mm in size


Serial MRI scans showing reduction in size of pituitary adenoma

Pictures during and after active Cushing’s syndrome



Discussion: Five months after initial assessment of this postmenopausal patient for hyperprolactinemia and pituitary macroadenoma, she presented with Cushing's syndrome. Initial impression was that she had developed Cushing's disease but biochemically, she behaved like an ectopic ACTH syndrome. The high dose dexamethasone suppression test did not suppress the Cortisol level. ACTH levels were 3 times the upper limit of normal. Work up of ectopic ACTH syndrome did not show any culprit lesion. Although treated with Ketoconazole briefly, patient improved and Ketoconazole was stopped. This correlated with the spontaneous involution of the pituitary adenoma. It is possible that the dexamethasone suppression test did not suppress the cortisol level possibly because the patient did not take the dexamethasone as directed. Inferior petrosal sinus sampling would have helped clarify matters but was not done as by then, patient was improving and there was reduction in size of the pituitary adenoma.
Spontaneous remission of Cushing’s disease is not uncommon and many case reports have been published. This is usually due to an ACTH producing microadenoma infarction or hemorrhage. Our patient did not have the typical symptoms of apoplexy and likely had silent involution of the adenoma. The pituitary adenoma was partly cystic at presentation indicating that it was undergoing cystic degeneration. Resolution of Cushing’s syndrome coincided with spontaneous involution of the pituitary adenoma.
Recurrence of Cushing’s syndrome has been described in the follow-up period of patients who have had spontaneous remission of Cushing’s disease. Cyclical Cushing’s have to be in the differential when dealing with such patients. Our patient has not had a recurrence so far, about 1.5 years after resolution of Cushing’s syndrome.
Conclusions: This case history illustrates the difficulty in sometimes figuring out Cushing's disease versus ectopic ACTH syndrome. It is likely that she had Cushing's disease all along. It is also remarkable to note resolution of Cushing's syndrome non-surgically by spontaneous involution of the pituitary adenoma.
References/Disclosures:
1) Endocrinology Nutrition 2009 Jan;56(1):32-9. doi: 10.1016/S1575-0922(09)70191-3. Epub 2009 Mar 1
2) Cushing Syndrome Treatment & Management Gail K Adler, MD, PhD Associate Professor of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School
3) Endocrine Practice 2003 Mar-Apr;9(2):147-51. Resolution of Cushing's disease followed by secondary adrenal insufficiency after anticoagulant-associated pituitary hemorrhage: report of a case and review of the literature.Taylor HC1, McLean S, Monheim K
4) Endocrine Abstracts (2010) 21 P263 Spontaneous remission of Cushing’s disease: apoplexy of a pituitary microadenoma? Paolo Dalino Ciaramella, Erika Grossrubatscher & Paola Loli
5) Arq Bras Endocrinol Metab. 2013;57/6 Spontaneous remission of hypercortisolism presumed due to asymptomatic tumor apoplexy in ACTH producing pituitary macroadenoma. Marcio Carlos Machado, Patricia Sampaio Gadelha, Marcello Delano Bronstein, Maria Candida Barisson Vilares Fragoso
Disclosures: No conflicts of interest to declare


Background: The annual incidence of endogenous Cushing syndrome has been estimated at 13 cases per million individuals. Of these cases, approximately 70% are due to Cushing disease (pituitary ACTH-producing tumor); 15% to ectopic ACTH; and 15% to a primary adrenal tumor. The treatment of choice for endogenous Cushing syndrome is surgical resection of the causative tumor. The spontaneous remission of Cushing’s disease (CD) has been reported and might be a phase of cyclic disease, but could also be explained by an ACTH producing adenoma infarction or hemorrhage
Objective: We present case history of a 53 year old lady who presented with Cushing’s syndrome which later resolved spontaneously without surgery
Case history: The patient was referred initially for minimal galactorrhea and hyperprolactinemia. Galactorrhea was only on expression and the discharge was whitish/cloudy. Apart from hypertension, there was no significant past medical history. The only medication she took was Hydrochlorothiazide for hypertension. She became menopausal at the age of 48. Breast examination was unremarkable. Visual field examination was normal. She did not look Cushingoid.
Prolactin level was 40.6 (3-26 mcg/L). TSH was normal. AM Cortisol was 362 (185-624 nmol/L). MRI scan showed a 1.4 cm pituitary mass undergoing cystic degeneration. The hyperprolactinemia was thought to be due to stalk compression.
As she was post menopausal and since there was no spontaneous and bothersome galactorrhea, no treatment was initiated. The plan was to monitor the pituitary adenoma by serial MR scans.
She didn't look Cushingoid during the initial visit but developed symptoms and signs of Cushing's syndrome 5 months later. She complained of diffuse body swelling, fatigue, weight gain, facial puffiness, bruising of skin, and low mood.
On examination, her face was rounded, red and she had facial hirsutism. There was increased dorsal pad of fat. Blood pressure was high at 160/90 mm Hg. Telangiectasia of the hands and chest were noted. There was no proximal muscle weakness or purple striae over abdominal wall.
The clinical impression was that she had developed Cushing’s disease due to the pituitary adenoma and investigations were initiated.
HbA1c was 7.0% and hypokalemia of 3 mmol/L noted. 24 hour urine cortisol levels were elevated at 1904 and 1311 (<275 nmol/day). AM Cortisol was 798 (170-720 nmol/L). ACTH was 29.7 (0-10.1 pmol/L). Low dose dexamethasone suppression test reduced Cortisol to 774 nmol/L, ACTH remained high at 30.6 pmol/L. With high dose dexamethasone suppression test, Cortisol went down to 659 nmol/L and ACTH to 19.5 pmol/L.
The biochemical tests were suggestive of ectopic ACTH syndrome in this chronic smoker and further investigations were initiated.
Repeat MRI showed considerably smaller pituitary adenoma measuring 7x9 mm in size. As the pituitary adenoma was smaller, inferior petrosal sinus sampling was not done.
As she was symptomatic, Ketoconazole was initiated.
Chest X-ray, CT scan of the chest/abdomen were unremarkable. 24 hour urine 5 HIAA, Octreotide scan, Calcitonin and gastrin levels were normal.
Over the next few months, she showed improvement and Ketoconazole was reduced and eventually stopped.
Off the Ketoconazole, patient continues to show no clinical or biochemical evidence of Cushing's syndrome. MRI pituitary was done again and it showed further stability/slight reduction in the size of adenoma, measuring 5x10 mm in size
Discussion: Five months after initial assessment of this postmenopausal patient for hyperprolactinemia and pituitary macroadenoma, she presented with Cushing's syndrome. Initial impression was that she had developed Cushing's disease but biochemically, she behaved like an ectopic ACTH syndrome. The high dose dexamethasone suppression test did not suppress the Cortisol level. ACTH levels were 3 times the upper limit of normal. Work up of ectopic ACTH syndrome did not show any culprit lesion. Although treated with Ketoconazole briefly, patient improved and Ketoconazole was stopped. This correlated with the spontaneous involution of the pituitary adenoma. It is possible that the dexamethasone suppression test did not suppress the cortisol level possibly because the patient did not take the dexamethasone as directed. Inferior petrosal sinus sampling would have helped clarify matters but was not done as by then, patient was improving and there was reduction in size of the pituitary adenoma.
Spontaneous remission of Cushing’s disease is not uncommon and many case reports have been published. This is usually due to an ACTH producing microadenoma infarction or hemorrhage. Our patient did not have the typical symptoms of apoplexy and likely had silent involution of the adenoma. The pituitary adenoma was partly cystic at presentation indicating that it was undergoing cystic degeneration. Resolution of Cushing’s syndrome coincided with spontaneous involution of the pituitary adenoma.
Recurrence of Cushing’s syndrome has been described in the follow-up period of patients who have had spontaneous remission of Cushing’s disease. Cyclical Cushing’s have to be in the differential when dealing with such patients. Our patient has not had a recurrence so far, about 1.5 years after resolution of Cushing’s syndrome.
Conclusions: This case history illustrates the difficulty in sometimes figuring out Cushing's disease versus ectopic ACTH syndrome. It is likely that she had Cushing's disease all along. It is also remarkable to note resolution of Cushing's syndrome non-surgically by spontaneous involution of the pituitary adenoma.
References/Disclosures:
1) Endocrinology Nutrition 2009 Jan;56(1):32-9. doi: 10.1016/S1575-0922(09)70191-3. Epub 2009 Mar 1
2) Cushing Syndrome Treatment & Management Gail K Adler, MD, PhD Associate Professor of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School
3) Endocrine Practice 2003 Mar-Apr;9(2):147-51. Resolution of Cushing's disease followed by secondary adrenal insufficiency after anticoagulant-associated pituitary hemorrhage: report of a case and review of the literature.Taylor HC1, McLean S, Monheim K
4) Endocrine Abstracts (2010) 21 P263 Spontaneous remission of Cushing’s disease: apoplexy of a pituitary microadenoma? Paolo Dalino Ciaramella, Erika Grossrubatscher & Paola Loli
5) Arq Bras Endocrinol Metab. 2013;57/6 Spontaneous remission of hypercortisolism presumed due to asymptomatic tumor apoplexy in ACTH producing pituitary macroadenoma. Marcio Carlos Machado, Patricia Sampaio Gadelha, Marcello Delano Bronstein, Maria Candida Barisson Vilares Fragoso
Disclosures: No conflicts of interest to declare




Background: The annual incidence of endogenous Cushing syndrome has been estimated at 13 cases per million individuals. Of these cases, approximately 70% are due to Cushing disease (pituitary ACTH-producing tumor); 15% to ectopic ACTH; and 15% to a primary adrenal tumor. The treatment of choice for endogenous Cushing syndrome is surgical resection of the causative tumor. The spontaneous remission of Cushing’s disease (CD) has been reported and might be a phase of cyclic disease, but could also be explained by an ACTH producing adenoma infarction or hemorrhage
Objective: We present case history of a 53 year old lady who presented with Cushing’s syndrome which later resolved spontaneously without surgery
Case history: The patient was referred initially for minimal galactorrhea and hyperprolactinemia. Galactorrhea was only on expression and the discharge was whitish/cloudy. Apart from hypertension, there was no significant past medical history. The only medication she took was Hydrochlorothiazide for hypertension. She became menopausal at the age of 48. Breast examination was unremarkable. Visual field examination was normal. She did not look Cushingoid.
Prolactin level was 40.6 (3-26 mcg/L). TSH was normal. AM Cortisol was 362 (185-624 nmol/L). MRI scan showed a 1.4 cm pituitary mass undergoing cystic degeneration. The hyperprolactinemia was thought to be due to stalk compression.
As she was post menopausal and since there was no spontaneous and bothersome galactorrhea, no treatment was initiated. The plan was to monitor the pituitary adenoma by serial MR scans.
She didn't look Cushingoid during the initial visit but developed symptoms and signs of Cushing's syndrome 5 months later. She complained of diffuse body swelling, fatigue, weight gain, facial puffiness, bruising of skin, and low mood.
On examination, her face was rounded, red and she had facial hirsutism. There was increased dorsal pad of fat. Blood pressure was high at 160/90 mm Hg. Telangiectasia of the hands and chest were noted. There was no proximal muscle weakness or purple striae over abdominal wall.
The clinical impression was that she had developed Cushing’s disease due to the pituitary adenoma and investigations were initiated.
HbA1c was 7.0% and hypokalemia of 3 mmol/L noted. 24 hour urine cortisol levels were elevated at 1904 and 1311 (<275 nmol/day). AM Cortisol was 798 (170-720 nmol/L). ACTH was 29.7 (0-10.1 pmol/L). Low dose dexamethasone suppression test reduced Cortisol to 774 nmol/L, ACTH remained high at 30.6 pmol/L. With high dose dexamethasone suppression test, Cortisol went down to 659 nmol/L and ACTH to 19.5 pmol/L.
The biochemical tests were suggestive of ectopic ACTH syndrome in this chronic smoker and further investigations were initiated.
Repeat MRI showed considerably smaller pituitary adenoma measuring 7x9 mm in size. As the pituitary adenoma was smaller, inferior petrosal sinus sampling was not done.
As she was symptomatic, Ketoconazole was initiated.
Chest X-ray, CT scan of the chest/abdomen were unremarkable. 24 hour urine 5 HIAA, Octreotide scan, Calcitonin and gastrin levels were normal.
Over the next few months, she showed improvement and Ketoconazole was reduced and eventually stopped.
Off the Ketoconazole, patient continues to show no clinical or biochemical evidence of Cushing's syndrome. MRI pituitary was done again and it showed further stability/slight reduction in the size of adenoma, measuring 5x10 mm in size
Discussion: Five months after initial assessment of this postmenopausal patient for hyperprolactinemia and pituitary macroadenoma, she presented with Cushing's syndrome. Initial impression was that she had developed Cushing's disease but biochemically, she behaved like an ectopic ACTH syndrome. The high dose dexamethasone suppression test did not suppress the Cortisol level. ACTH levels were 3 times the upper limit of normal. Work up of ectopic ACTH syndrome did not show any culprit lesion. Although treated with Ketoconazole briefly, patient improved and Ketoconazole was stopped. This correlated with the spontaneous involution of the pituitary adenoma. It is possible that the dexamethasone suppression test did not suppress the cortisol level possibly because the patient did not take the dexamethasone as directed. Inferior petrosal sinus sampling would have helped clarify matters but was not done as by then, patient was improving and there was reduction in size of the pituitary adenoma.
Spontaneous remission of Cushing’s disease is not uncommon and many case reports have been published. This is usually due to an ACTH producing microadenoma infarction or hemorrhage. Our patient did not have the typical symptoms of apoplexy and likely had silent involution of the adenoma. The pituitary adenoma was partly cystic at presentation indicating that it was undergoing cystic degeneration. Resolution of Cushing’s syndrome coincided with spontaneous involution of the pituitary adenoma.
Recurrence of Cushing’s syndrome has been described in the follow-up period of patients who have had spontaneous remission of Cushing’s disease. Cyclical Cushing’s have to be in the differential when dealing with such patients. Our patient has not had a recurrence so far, about 1.5 years after resolution of Cushing’s syndrome.
Conclusions: This case history illustrates the difficulty in sometimes figuring out Cushing's disease versus ectopic ACTH syndrome. It is likely that she had Cushing's disease all along. It is also remarkable to note resolution of Cushing's syndrome non-surgically by spontaneous involution of the pituitary adenoma.
References/Disclosures:
1) Endocrinology Nutrition 2009 Jan;56(1):32-9. doi: 10.1016/S1575-0922(09)70191-3. Epub 2009 Mar 1
2) Cushing Syndrome Treatment & Management Gail K Adler, MD, PhD Associate Professor of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School
3) Endocrine Practice 2003 Mar-Apr;9(2):147-51. Resolution of Cushing's disease followed by secondary adrenal insufficiency after anticoagulant-associated pituitary hemorrhage: report of a case and review of the literature.Taylor HC1, McLean S, Monheim K
4) Endocrine Abstracts (2010) 21 P263 Spontaneous remission of Cushing’s disease: apoplexy of a pituitary microadenoma? Paolo Dalino Ciaramella, Erika Grossrubatscher & Paola Loli
5) Arq Bras Endocrinol Metab. 2013;57/6 Spontaneous remission of hypercortisolism presumed due to asymptomatic tumor apoplexy in ACTH producing pituitary macroadenoma. Marcio Carlos Machado, Patricia Sampaio Gadelha, Marcello Delano Bronstein, Maria Candida Barisson Vilares Fragoso
Disclosures: No conflicts of interest to declare