Case of Cyclic Cushing's Disease With Improvement of Psoriatic Skin Lesions During a Period of Hypercortisolemia

Nobuhiro Nakatake; Fumihiro Hiraoka; Shigetoshi Yano; Takeshi Hara; Sunao Matsubayashi

Disclosures

J Endo Soc. 2021;5(7) 

In This Article

Case Presentation

A 45-year-old man presented to a local neurology clinic with positional vertigo and nausea. A computed tomography (CT) scan of the head incidentally showed a large pituitary tumor. Neurological examination revealed right-sided temporal hemianopsia, and magnetic resonance imaging showed a large pituitary tumor that extended superiorly in the suprasellar cistern and elevated the optic chiasm (Figure 1). He did not report any headache. Almost all of the mass showed contrast enhancement with a partial low-intensity area after injection of gadolinium on T1-weighted images (Figure 1). The tumor diameter was 24 × 20 × 39 mm. At that time, a random serum cortisol level and a plasma adrenocorticotropic hormone (ACTH) level obtained at 3:00 PM were 29.4 μg/dL and 154 pg/mL, respectively. Although the laboratory tests might have been performed under stressful conditions from the patient's point of view, the results indicated an ACTH-producing/secreting pituitary tumor.

Figure 1.

Pre- and post-Gadolinium-enhanced T1-weighted magnetic resonance imaging showing a large pituitary tumor measuring 24 × 20 × 39 mm that extended superiorly in the suprasellar cistern to elevate the optic chiasm. The mass showed contrast enhancement with partially hypointense areas.

The patient was subsequently referred to us for further endocrine evaluation 6 weeks after the previous doctor's visit. According to his medical history, he was visiting a local dermatologist who had prescribed topical glucocorticoids and methotrexate for psoriasis vulgaris and psoriatic arthritis. He had attended annual medical check-ups and there was no other significant medical history such as diabetes mellitus or hypertension. Interestingly, he reported intermittent sensations of "whole-body swelling" that had lasted for 2 to 3 weeks at 2- to 3-month intervals over several years. His story seemed to be reliable, and he also mentioned that his psoriatic skin lesions and arthralgia showed transient but dramatic improvement during the periods of the whole-body swelling sensation even when the medications prescribed by the dermatologist were discontinued.

In addition to the already known psoriatic skin lesions and arthritis, physical examination revealed central obesity with supraclavicular and dorsocervical fat pads and a round face without red cheeks. There was no skin thinning, red-purple striae on the abdomen, or ecchymoses. There was no proximal muscle weakness.

Several endocrine investigations were performed during the patient's hospital stay. On the 1st day of admission, the serum cortisol level measured at 11:00 PM was 5.4 μg/dL. At 8:00 AM on day 2 after admission, the serum cortisol level was 9.3 μg/dL and the 24-hour urinary free cortisol value was 23.0 μg/day (reference range [RR]: 11.2–80.3), indicating normal cortisol secretion. On day 3, after a low-dose (1 mg) overnight dexamethasone suppression test, the serum cortisol level at 8:00 AM was 19.6 μg/dL (normal, <1.8 μg/dL), suggesting hypercortisolemia. During his 14-day hospital stay, cortisol secretion gradually increased and then decreased in an inverted U-shaped manner (Figure 2). The peak serum cortisol level was 75.7 μg/mL (ACTH 585 pg/mL) and the 24-hour urinary free cortisol value was 10 500 μg/day (Figure 2). The serum cortisol level eventually decreased to 20.5 μg/mL on the day of discharge (day 14). Consistent with transient hypercortisolism, there was leukocytosis, a decrease in C-reactive protein suggesting anti-inflammatory activity, and hypokalemia (Figure 2). Furthermore, the patient had low urinary sodium excretion (urine sodium undetectable), indicating sodium retention due to glucocorticoid excess (Figure 2). Even more surprisingly, the rise in cortisol levels coincided with amelioration of his red psoriatic plaques during the hospital stay (Figure 3). These clinical findings were consistent with his reports of periodic whole-body swelling sensations and transient improvement in his skin lesions.

Figure 2.

Timeline of ACTH and cortisol levels (upper graph) and indicators of the inflammatory response (lower graph). The table at the bottom shows the changes in serum potassium and urine potassium and sodium. Serum cortisol (μg/dL) and plasma ACTH (pg/mL) were collected under fasting conditions in the early morning each day. Dex 1 mg PO, oral administration of dexamethasone 1 mg at 11:00 PM; Dex 8 mg PO, oral administration of dexamethasone 8 mg at 11:00 PM. Abbreviations: ACTH, adrenocorticotropic hormone; CRH, corticotropin-releasing hormone; CRP, C-reactive protein; DDAVP, desmopressin; S-K, serum potassium concentration; UFC, 24-hour urinary free cortisol; U-K, urine potassium concentration; U-Na, urine sodium concentration; WBC, white blood cells.

Figure 3.

Chronological changes in psoriatic skin lesions. Improvement in red psoriatic plaques coincided with the increase in serum cortisol levels.

A corticotropin-releasing hormone (CRH) stimulation test showed a more than 2-fold increase in plasma ACTH from 285 pg/mL to 595 pg/mL after injection of 100 μg of CRH (RR > 50% increase in plasma ACTH), consistent with Cushing's disease due to an ACTH-producing pituitary tumor (Figure 4). There was no increase in the ACTH level after administration of desmopressin 10 μg (Figure 4). A high-dose (8 mg) overnight dexamethasone suppression test resulted in a nearly 40% reduction in the morning serum cortisol level at 8:00 AM from 39.7 μg/mL to 23.6 μg/mL (RR > 50% reduction in serum cortisol), indicating inadequate suppression.

Figure 4.

Results of CRH and DDAVP stimulation tests performed on hospital days 6 and 7, respectively. The CRH test revealed a significant increase in the plasma ACTH level, whereas the DDAVP test found a decrease rather than an increase in ACTH. Abbreviations: ACTH, adrenocorticotropic hormone; CRH, corticotropin-releasing hormone; DDAVP, desmopressin.

Unexpectedly, a thin-slice CT scan of the abdomen did not show bilateral adrenal enlargement due to chronic ACTH stimulation (image not shown). In addition, the large size of the pituitary tumor raised concerns for a malignant primary or metastatic pituitary tumor. A subsequent whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT scan showed only the known pituitary tumor, which had a maximum standardized uptake value of 6.4 to 7.7 (image not shown).

The other pituitary function tests were as follows: thyroid-stimulating hormone (TSH) 3.43 μIU/mL (RR 0.5–5), free T4 0.56 ng/dL (RR 1.0–1.8), growth hormone (GH) 0.03 ng/mL (RR 0–2.47), insulin-like growth factor-1 39 ng/mL (RR 91–253), luteinizing hormone (LH) 0.16 mIU/mL (RR 0.79–5.72), follicle-stimulating hormone (FSH) 0.78 mIU/mL (RR 2.0–8.3), total testosterone < 0.03 ng/mL (RR 1.31–8.71), and prolactin (PRL) 23.0 ng/mL (RR 4.3–13.7). Thyrotropin-releasing hormone (protirelin; Nipro Corporation, Osaka, Japan), GH-releasing peptide-2, and LH releasing-hormone stimulation tests indicated hyposecretion of thyroid, growth, and gonadal hormones due to compression of the normal pituitary tissue by the large pituitary mass (data not shown). The patient had normal serum sodium levels and urine osmolality without polydipsia and polyuria suggestive of diabetes insipidus.

The patient eventually underwent transsphenoidal surgery for his large pituitary tumor. The pathologic findings were consistent with an ACTH-producing pituitary tumor. There was no necrosis in the specimen. Immunohistopathology confirmed pituitary adenoma positive for ACTH and negative for GH, PRL, TSH, FSH, and LH. Only a few cells showed Crooke's degeneration, which was confirmed by low molecular weight keratin (CAM 5.2) staining and a Ki-67/MIB-1 labeling index of less than 1%. The patient's transient whole-body swelling sensations and visual field defect resolved completely after surgery, but he developed postoperative diabetes insipidus. The patient received hydrocortisone, levothyroxine, and desmopressin replacement therapy.

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