Cushing’s disease and marked hyperprolactinemia in a patient with a pituitary macroadenoma: effectiveness of bromocriptine treatment

OBJECTIVE: Since Cushing's disease due to large pituitary tumors is rare, we evaluated biochemical characteristics at entry and the results of first surgical approach and of adjuvant therapeutic strategies during a long-term follow-up period. DESIGN: We studied 26 patients (nine male, 17 female; 42.5+/-12.7 years, mean+/-s.e.) with ACTH-secreting pituitary macroadenoma (tumor diameter: 11-40 mm). METHODS: At entry, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were measured in all patients, a high-dose dexamethasone (dexa) suppression test was evaluated in 22 cases and a corticotrophin releasing hormone (CRH) test in 20 cases. Patients were re-evaluated after operation and, when not cured, they underwent second surgery, radiotherapy and/or ketoconazole treatment. The follow-up period was 78+/-10 months. RESULTS: Before surgery, dexa decreased ACTH (>50% of baseline) in only 14/22 patients. The CRH-stimulated ACTH/cortisol response was normal in six patients, impaired in six patients and exaggerated in eight patients. After operation eight patients were cured, nine had normalized cortisol levels and nine were not cured. Pre-surgery, mean ACTH values were significantly higher in the not cured patients than in those normalized (P<0.05) and cured (P<0.01); the ACTH response to CRH was impaired in only six patients of the not cured group. The tumour diameter was significantly less in cured patients (P<0.02) and in normalized patients (P<0.05) than in the not cured ones. Magnetic resonance imaging (MRI) showed invasion of the cavernous sinus in 2/9 normalized, and in 6/9 not cured patients. After surgery, ACTH, cortisol and UFC were significantly lower than at entry in cured and in normalized patients, but not in not cured patients. In the cured group, the disease recurred in one patient who was unsuccessfully treated with ketoconazole. In the normalized group, a relapse occurred in eight patients: radiotherapy and ketoconazole induced cortisol normalization in one case, hypoadrenalism in one case and were ineffective in another one, while five patients were lost at follow-up. In the not cured group, eight patients underwent second surgery, radiotherapy and/or ketoconazole, while one patient was lost at follow-up. These therapies induced cortisol normalization in two patients and hypoadrenalism in one. CONCLUSIONS: (i) A sub-set of patients with ACTH-secreting pituitary macroadenoma showed low sensitivity to high doses of dexamethasone and to CRH, (ii) pituitary surgery cured Cushing's disease in a minority of patients, (iii) high baseline ACTH levels, impaired ACTH response to CRH, increased tumor size or invasion of the cavernous sinus were unfavourable prognostic factors for surgical therapy, and (iv) second surgery, radiotherapy and/or ketaconazole cured or normalized hypercortisolism in half of the patients with recurrence or not cured.

Download Full-text

MON-405 Cushing's Disease: An Oligosymptomatic Patient with ACTH-Secreting Pituitary Macroadenoma

Journal of the Endocrine Society ◽

10.1210/js.2019-mon-405 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Katty Manrique Franco ◽

Diana Liz Urday Ipanaque ◽

Nataly Curo Carrion

Keyword(s):

Cushing’S Disease ◽

Cushing's Disease ◽

Pituitary Macroadenoma ◽

Acth Secreting

Download Full-text

SAT-262 A Case of Pseudotumor Cerebri After Removal and Recurrence of ACTH-Producing Tumor

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1490 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Karla Bermudez Saint Andre ◽

Steven Petak ◽

Laila Tabatabai

Keyword(s):

Weight Loss ◽

Cerebrospinal Fluid ◽

Weight Gain ◽

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Pseudotumor Cerebri ◽

Cushing's Syndrome ◽

Cushing's Disease ◽

Pituitary Macroadenoma ◽

Second Surgery

Abstract Introduction: Pseudotumor cerebri also known as idiopathic intracranial hypertension (IIH) is a condition of elevated cerebrospinal fluid pressure which as a result causes headaches and vision problems. Several case reports and studies have reported a relation of IIH with Cushing’s disease (CD) in adults and children, particularly after surgical or medical therapy. We describe a very uncommon presentation of persistent intracranial hypertension (ICH) in a patient with recurrence of cushing’s disease after her initial surgical resection. Case presentation:38-year-old African-American female with a BMI of 45, type 2 diabetes, HTN and history of Cushing’s syndrome from an ACTH-producing pituitary macroadenoma. She initially presented with increasing weight gain and features of Cushing’s syndrome including hypertension, hyperglycemia, truncal obesity and moon facies. Imaging studies showed a 2 cm intrasellar mass with suprasellar extension without compression of the optic chiasm. Hormonal evaluation confirmed Cushing’s syndrome from an ACTH-producing pituitary macroadenoma. Patient underwent initial trans-sphenoidal hypophysectomy (TSR) and was tapered down to physiologic doses of glucocorticoids. Post-operatively she started complaining of significant headaches and transient vision loss. She followed up with neuro-ophthalmology and was diagnosed with papilledema that was not present in the pre-operative examination. An LP (lumbar puncture) was recommended to assess for ICH, however patient declined the procedure. A year after, a second surgery had to be performed for recurrent pituitary adenoma. Unfortunately, a repeat MRI pituitary shortly after her second surgery revealed recurrent pituitary macroadenoma of 2.2 cm. Patient continued with headaches and underwent an LP with an opening pressure of 28 cm H20 (ICH > 26 cm H2O). She underwent a third TSR with follow up MRI showing gross total resection of the previously seen pituitary mass. For her ICH she was started on acetazolamide but was not able to tolerate due to paresthesias and metallic taste. Her symptoms have improved after her last resection and last MRI brain shows no residual tumor. She is currently on furosemide and focusing on weight loss. Conclusion: Our patient’s presentation is an interesting and unusual case because we believe she had both pseudotumor cerebri (IIH) and real tumor cerebri from the complications of her ACTH-secreting macroadenoma. The cause of IIH after treatment of cushing’s disease is believed to be mostly due to steroid withdrawal after surgical resection or medical treatment comprising hormonal control of cerebrospinal fluid production and absorption. In our patient we suppose that the persistent weight gain caused by the recurrence of her CD could also contribute to her IIH. The treatment in general is the same with physiologic doses of corticosteroids, diuretics and weight loss.

Download Full-text

Repeated Remissions of Cushing's Disease Due to Recurrent Infarctions of an ACTH-Producing Pituitary Macroadenoma

Pituitary ◽

10.1007/s11102-005-2961-8 ◽

2005 ◽

Vol 8 (2) ◽

pp. 81-87 ◽

Cited By ~ 15

Author(s):

Abdullah Alarifi ◽

Ali S. Alzahrani ◽

Suzan Abdel Salam ◽

Mohammed Ahmed ◽

Imaduddin Kanaan

Keyword(s):

Cushing’S Disease ◽

Cushing's Disease ◽

Pituitary Macroadenoma

Download Full-text

SAT-279 Crooke’s Cell Adenoma- an Aggressive Form of Cushing’s Disease

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1707 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Natasa Radovanovic ◽

Yuen Alexa ◽

Vafa Tabatabaie

Keyword(s):

Cushing’S Disease ◽

Feedback Inhibition ◽

Hormone Secretion ◽

Interesting Case ◽

Cushing's Disease ◽

Proliferation Index ◽

Pituitary Macroadenoma ◽

Mri Imaging ◽

Cell Adenoma

Abstract Introduction: Cushing’s disease is a condition of cortisol overproduction caused by an ACTH-producing tumor. Corticotroph cells surrounding an ACTH-producing tumor usually undergo Crooke’s hyaline change, where cytokeratin filaments accumulate in the cytoplasm in response to glucocorticoid excess. These changes are thought to be a mechanism of feedback inhibition and thus facilitate a suppression of ACTH. However, in a subtype of ACTH-secreting tumors known as Crooke’s cell adenomas (CCA), the ACTH-producing cells also undergo these hyaline changes. This would be expected to suppress hormone secretion but these cells are still able to release significant amounts of ACTH. Case presentation: A 32-year-old woman presented to the hospital after an episode of syncope. On head MRI, she was found to have a 2 cm sellar mass with optic chiasm compression. Labs showed low TSH, free FT4, T3, FSH, and LH. She was also pre-diabetic with an HgbA1c of 6.2%. Her baseline cortisol of 20.6 µg/dL did not suppress after 1 mg of dexamethasone. After receiving 4 mg of dexamethasone, her cortisol suppressed to 5.2 µg/dL. She was diagnosed with hypopituitarism except for cortisol and a likely ACTH-producing pituitary macroadenoma. She completed a transsphenoidal pituitary resection and pathology revealed Crooke’s hyaline changes with immunohistochemical stains positive for ACTH. The immunostain for the proliferation marker Ki67 showed a relatively low proliferation index. Her course was complicated by diabetes insipidus. She was ultimately discharged on 20 mg hydrocortisone each morning, 10 mg hydrocortisone each afternoon, desmopressin 0.05 µg daily, and levothyroxine 125 µg daily. Two weeks later, the patient was sent to the emergency room by her endocrinologist for hyperglycemia up to 288 mg/dL. She was also found to be newly diabetic with an HgbA1c of 6.5%. A fasting morning cortisol was collected during her admission and showed a cortisol level of <1.0 µg/dL, proving she was cured of Cushing’s disease. However, she will need close endocrinology follow up and MRI imaging of her pituitary for this aggressive type of pituitary adenoma. Discussion: We have come across an interesting case of a young woman who presented for syncope and was found to have a pituitary macroadenoma with pathology consistent with CCA. This type of ACTH-producing tumor is known for aggressive patterns including high rates of recurrence with rates of up to 60% reported in literature, persistent disease after surgery, malignant transformation, and metastases. Despite presentation and symptoms similar to those of other ACTH-producing adenomas, the dangerous pattern of Crooke’s cell adenomas necessitate long-term follow-up in affected patients.

Download Full-text