J. Endocrinol. Invest. 13: 677-681, 1990
CASE REPORT
Pituitary granuloma and pyoderma gangrenosum P. Chanson*, J. Timsit*, M. Kujas**, A. Violante*, P.J. Guillausseau*, P. J. Derome***, A. Warnet*, and J. Lubetzki* *Department of Endocrinology, Hopital Lariboisiere, **Department of Pathology, Faculte de Medecine PitieSalpetriere, Paris, and ***Department of Neurosurgery, Hopital Foch, Suresnes, France. ABSTRACT. Pyoderma gangrenosum is a rare chronic and recurrent skin disease characterized by progressing lesions from papulopustules to large necrotic sterile ulcers. Its definite etiology remains unknown. In a 40-year-old woman with typical pyoderma gangrenosum an intrasellar mass with suprasellar extension was diagnosed and removed by transsphenoidal surgery. Histopathological features of the lesion were those of a nonspecific granulomatous hypophysitis. Five months postoperatively the patient experienced visual defects and hypopituitarism demonstrated by endocrine evaluation. Computerized tomography showed the recurrence of the intrasellar expanding
mass. Extensive and repeated evaluation failed to find any evidence of sarcoidosis, tuberculosis or histiocytosis. Corticosteroid therapy was preferred to surgery and 80 mg daily prednisone produced a dramatic shrinkage of the pituitary pseudotumor. Long-term follow-up studies did not disclose any recurrence of the pituitary granulomatous process nor objective evidence of underlying disease even after steroid dosage has been tapered. The hypothesis of a pituitary localization of pyoderma gangrenosum is suggested by the similarity between the histopathologic findings of the two conditions and the excellent response to steroid therapy.
INTRODUCTION Pyoderma gangrenosum is a rare chronic and recurrent skin disease involving typically the lower limbs, the trunk, the abdomen or the perineum. The distribution of the lesions and their aspect are usually very suggestive: they often occur after a minor trauma and rapidly progress from papulopustules to large necrotic sterile ulcers followed by cribriform scars. Several pathogenic hypothesis, including immunological abnormalities, have been proposed, but the definite cause of this affection remains unknown (1,2). Furthermore, pyoderma gangrenosum has been reported to occur in association with various systemic diseases such as ulcerative colitis, arthritis, monoclonal gammapathy or myeloma, malignancies (1, 3). There is no universally admitted
treatment for pyoderma gangrenosum but high-dose steroid therapy is often effective (1, 2). We report here the case of a patient with typical pyoderma gangrenosum in whom a pituitary granuloma was surgically removed. Postoperatively the pituitary lesion rapidly recurred and was then treated by high dose steroid therapy. In this patient, the intrasellar granuloma histopathological features and the effects of steroid therapy strongly suggest a pituitary localization of the pyoderma gangrenosum. To our knowledge, this is the first reported case of a pituitary granulomatous pseudotumor shrinkage by using steroid therapy. CASE REPORT A 40-year-old woman was referred to our department for recurrence of a pituitary tumor six months after previous surgical removal. In 1975, she presented with two skin lesions of the lower limbs, beginning as a pustule, rapidly enlarging and breaking down to form a burrowing, destructive ulcer, irregular in outline with a ragged red over-
Key-words: Pituitary granuloma. pyoderma gangrenosum, corticosteroid therapy. Correspondence.' Philippe Chanson. MD.. Department of Endocrinology. H6pital Lariboisiere. 2, rue A Pare, F - 75475 Paris Cedex 10, France.
Received March 12, 1990; accepted May 24, 1990.
677
P. Chanson, J. Timisit, M. Kujas, et al.
hanging edge. In 1979 she was admitted in another hospital for deterioration of the skin lesions. Multiple extensive and destructive ulcerations involved the two lower limbs. Biopsy specimens demonstrated the usual aspect of pyodermagangrenosum. A complete evaluation was then undertaken. Large bowel barium series, sigmoidoscopy, gastric fibroscopy, tests for rhumatoid factor and antinuclear antibodies, skeletal survey, serum and urine protein immunoelectrophoresis, and marrow examination failed to prove any coexistent disease. Prednisone, 60 mg daily, resulted in a slow improvement of the skin lesions. Prednisone was then gradually reduced to 25 mg daily and various treatments (thalidomide, then minocycline hydrochloride, and, finally, clofazimine) were added because of the persistance of small lesions. In 1981, recurrence of large lesions led to increase the dosage of prednisone to 60 mg daily. From 1982 to 1986, skin lesions remained healed although steroid therapy had been progressively reduced to 10 mg daily and clofazimine discontinued in 1984. During the year prior to admission, the patient experienced a progressive 17 -kg weight gain, amenorrhea, bilateral galactorrhea, weakness, cold intolerance and gradual increase of urinary output and thirst. Routine laboratory studies, chest X-ray, and ECG were normal. Endocrine evaluation only demonstrated a low free urinary cortisol (634 nmol/ day) and a moderate hyperprolactinemia (38.7 jLg/I). A short dehydration test showed no urinary concentration. After parenteral administration of 2jLg desmopressin, diuresis fell from 440 ml/h to 20 ml/h and urinary specific gravity increased from 1,002 to 1,010 confirming ADH deficiency. Visual acuity and visual fields were normal but skull X-ray films demonstrated an enlargement of the sella turcica with demineralized limits. Computerized tomography (CT) evidenced an intrasellar mass with suprasellar extension, enhanced with contrast material. The patient underwent a transsphenoidal procedure and an intrasellar solid mass that occupied the whole sellar cavity was removed. The tumor was gray and firm in consistency, and adhesive to the inner surface of the cavity. Light microscopy of pituitary tissue did not disclose adenomatous cells. The normal architecture of the adenohypophysis was disrupted by a diffuse mononuclear lymphocytic infiltrate. A necrotic area was surrounded by neutrophils and collagen fibers with fibroblasts as a
678
.
... .. .· ~,"~·L"'." .. ,
~
.... .,
Fig. 1 - Anterior pituitary specimen: adenohypophysis cell cords are disrupted by mononuclear infiltrate (Iymphoplasmocytic) and by histocytic cells (magnification, X 160). 1 - Adenohypophysis cell cords 2 - Histiocytic cells 3 - Mononuclear infiltrate 4 - Vascular capillary.
capsule (Fig. 1). Interstitial hemorrhages and cholesterin crystals were also evidenced. Moreover histiocytic and eosinophilic cells were scattered. Immunoperoxydase staining only revealed hyperplasia of lactotrophs. Pathological diagnosis was nonspecific granulomatous hypophysitis. The patient was discharged with hydrocortisone, 30 mg daily and intranasal desmopressin. Over the next 5 months, weight gain, amenorrhea and weakness continued and frontal headaches appeared. Five months postoperatively, visual fields examination disclosed a right scotoma and the patient was admitted in our department. On admission, general examination revealed healed skin lesions. Thyroid gland appeared normal. Multiple pituitary hormones deficiencies but normoprolactinemia (Table 1) were evidenced. CT scan showed an intrasellar mass with suprasellar extension, very similar to the preoperative findings (Fig. 2 A). Thus, relapse of the pituitary granuloma was obvious. In the search of one of the various usual causes of pituitary granuloma, multiple investigations were performed but serum calcium and phosphorus, angiotensin converting enzyme level, chest X-ray, broncho alveolar lavage, pulmonary function studies, skull X-ray, skeletal survey proved to be normal. Because of the recurrence of the pituitary mass and the underlying pyoderma gangrenosum, prednisone was started at a dose of 80 mg daily.
Shrinkage of pituitary pseudotumor with corticosteroids.
matic tumoral shrinkage (Fig . 2 8). Prednisone was gradually reduced to 20 mg daily. Six months after initiation of steroid therapy no tumoral mass could be demonstrated in the sella turcica area (Fig. 2 C). Prednisone was then tapered to 10 mg daily. Long term follow-up (up to 2 yr) with repeated CT scan and magnetic resonance imaging (MRI) (Fig. 2 D) did not disclose any recurrence of the pituitary lesion nor objective evidence of underlying disease. Hypopituitarism and diabetes insipidus remained unchanged.
Table 1 - Hormonal findings at the time of pituitary granuloma recurrence. Hormones Free thyroxine (pmol/I) Free T3 (pmol / I) Thyrotropin (mU / I) - Basal - Peak after TRHI Growth-Hormone (J.Lg/l) - Basal - Peak after stimulation 2
Normal range
Patient
8.5 - 20.5
4.2
3 - 8.7
3.3
0.1 - 4.5
1A 8A
0.5 - 5
1A 1.8
CASE REPORT
Pituitary granuloma and pyoderma gangrenosum P. Chanson*, J. Timsit*, M. Kujas**, A. Violante*, P.J. Guillausseau*, P. J. Derome***, A. Warnet*, and J. Lubetzki* *Department of Endocrinology, Hopital Lariboisiere, **Department of Pathology, Faculte de Medecine PitieSalpetriere, Paris, and ***Department of Neurosurgery, Hopital Foch, Suresnes, France. ABSTRACT. Pyoderma gangrenosum is a rare chronic and recurrent skin disease characterized by progressing lesions from papulopustules to large necrotic sterile ulcers. Its definite etiology remains unknown. In a 40-year-old woman with typical pyoderma gangrenosum an intrasellar mass with suprasellar extension was diagnosed and removed by transsphenoidal surgery. Histopathological features of the lesion were those of a nonspecific granulomatous hypophysitis. Five months postoperatively the patient experienced visual defects and hypopituitarism demonstrated by endocrine evaluation. Computerized tomography showed the recurrence of the intrasellar expanding
mass. Extensive and repeated evaluation failed to find any evidence of sarcoidosis, tuberculosis or histiocytosis. Corticosteroid therapy was preferred to surgery and 80 mg daily prednisone produced a dramatic shrinkage of the pituitary pseudotumor. Long-term follow-up studies did not disclose any recurrence of the pituitary granulomatous process nor objective evidence of underlying disease even after steroid dosage has been tapered. The hypothesis of a pituitary localization of pyoderma gangrenosum is suggested by the similarity between the histopathologic findings of the two conditions and the excellent response to steroid therapy.
INTRODUCTION Pyoderma gangrenosum is a rare chronic and recurrent skin disease involving typically the lower limbs, the trunk, the abdomen or the perineum. The distribution of the lesions and their aspect are usually very suggestive: they often occur after a minor trauma and rapidly progress from papulopustules to large necrotic sterile ulcers followed by cribriform scars. Several pathogenic hypothesis, including immunological abnormalities, have been proposed, but the definite cause of this affection remains unknown (1,2). Furthermore, pyoderma gangrenosum has been reported to occur in association with various systemic diseases such as ulcerative colitis, arthritis, monoclonal gammapathy or myeloma, malignancies (1, 3). There is no universally admitted
treatment for pyoderma gangrenosum but high-dose steroid therapy is often effective (1, 2). We report here the case of a patient with typical pyoderma gangrenosum in whom a pituitary granuloma was surgically removed. Postoperatively the pituitary lesion rapidly recurred and was then treated by high dose steroid therapy. In this patient, the intrasellar granuloma histopathological features and the effects of steroid therapy strongly suggest a pituitary localization of the pyoderma gangrenosum. To our knowledge, this is the first reported case of a pituitary granulomatous pseudotumor shrinkage by using steroid therapy. CASE REPORT A 40-year-old woman was referred to our department for recurrence of a pituitary tumor six months after previous surgical removal. In 1975, she presented with two skin lesions of the lower limbs, beginning as a pustule, rapidly enlarging and breaking down to form a burrowing, destructive ulcer, irregular in outline with a ragged red over-
Key-words: Pituitary granuloma. pyoderma gangrenosum, corticosteroid therapy. Correspondence.' Philippe Chanson. MD.. Department of Endocrinology. H6pital Lariboisiere. 2, rue A Pare, F - 75475 Paris Cedex 10, France.
Received March 12, 1990; accepted May 24, 1990.
677
P. Chanson, J. Timisit, M. Kujas, et al.
hanging edge. In 1979 she was admitted in another hospital for deterioration of the skin lesions. Multiple extensive and destructive ulcerations involved the two lower limbs. Biopsy specimens demonstrated the usual aspect of pyodermagangrenosum. A complete evaluation was then undertaken. Large bowel barium series, sigmoidoscopy, gastric fibroscopy, tests for rhumatoid factor and antinuclear antibodies, skeletal survey, serum and urine protein immunoelectrophoresis, and marrow examination failed to prove any coexistent disease. Prednisone, 60 mg daily, resulted in a slow improvement of the skin lesions. Prednisone was then gradually reduced to 25 mg daily and various treatments (thalidomide, then minocycline hydrochloride, and, finally, clofazimine) were added because of the persistance of small lesions. In 1981, recurrence of large lesions led to increase the dosage of prednisone to 60 mg daily. From 1982 to 1986, skin lesions remained healed although steroid therapy had been progressively reduced to 10 mg daily and clofazimine discontinued in 1984. During the year prior to admission, the patient experienced a progressive 17 -kg weight gain, amenorrhea, bilateral galactorrhea, weakness, cold intolerance and gradual increase of urinary output and thirst. Routine laboratory studies, chest X-ray, and ECG were normal. Endocrine evaluation only demonstrated a low free urinary cortisol (634 nmol/ day) and a moderate hyperprolactinemia (38.7 jLg/I). A short dehydration test showed no urinary concentration. After parenteral administration of 2jLg desmopressin, diuresis fell from 440 ml/h to 20 ml/h and urinary specific gravity increased from 1,002 to 1,010 confirming ADH deficiency. Visual acuity and visual fields were normal but skull X-ray films demonstrated an enlargement of the sella turcica with demineralized limits. Computerized tomography (CT) evidenced an intrasellar mass with suprasellar extension, enhanced with contrast material. The patient underwent a transsphenoidal procedure and an intrasellar solid mass that occupied the whole sellar cavity was removed. The tumor was gray and firm in consistency, and adhesive to the inner surface of the cavity. Light microscopy of pituitary tissue did not disclose adenomatous cells. The normal architecture of the adenohypophysis was disrupted by a diffuse mononuclear lymphocytic infiltrate. A necrotic area was surrounded by neutrophils and collagen fibers with fibroblasts as a
678
.
... .. .· ~,"~·L"'." .. ,
~
.... .,
Fig. 1 - Anterior pituitary specimen: adenohypophysis cell cords are disrupted by mononuclear infiltrate (Iymphoplasmocytic) and by histocytic cells (magnification, X 160). 1 - Adenohypophysis cell cords 2 - Histiocytic cells 3 - Mononuclear infiltrate 4 - Vascular capillary.
capsule (Fig. 1). Interstitial hemorrhages and cholesterin crystals were also evidenced. Moreover histiocytic and eosinophilic cells were scattered. Immunoperoxydase staining only revealed hyperplasia of lactotrophs. Pathological diagnosis was nonspecific granulomatous hypophysitis. The patient was discharged with hydrocortisone, 30 mg daily and intranasal desmopressin. Over the next 5 months, weight gain, amenorrhea and weakness continued and frontal headaches appeared. Five months postoperatively, visual fields examination disclosed a right scotoma and the patient was admitted in our department. On admission, general examination revealed healed skin lesions. Thyroid gland appeared normal. Multiple pituitary hormones deficiencies but normoprolactinemia (Table 1) were evidenced. CT scan showed an intrasellar mass with suprasellar extension, very similar to the preoperative findings (Fig. 2 A). Thus, relapse of the pituitary granuloma was obvious. In the search of one of the various usual causes of pituitary granuloma, multiple investigations were performed but serum calcium and phosphorus, angiotensin converting enzyme level, chest X-ray, broncho alveolar lavage, pulmonary function studies, skull X-ray, skeletal survey proved to be normal. Because of the recurrence of the pituitary mass and the underlying pyoderma gangrenosum, prednisone was started at a dose of 80 mg daily.
Shrinkage of pituitary pseudotumor with corticosteroids.
matic tumoral shrinkage (Fig . 2 8). Prednisone was gradually reduced to 20 mg daily. Six months after initiation of steroid therapy no tumoral mass could be demonstrated in the sella turcica area (Fig. 2 C). Prednisone was then tapered to 10 mg daily. Long term follow-up (up to 2 yr) with repeated CT scan and magnetic resonance imaging (MRI) (Fig. 2 D) did not disclose any recurrence of the pituitary lesion nor objective evidence of underlying disease. Hypopituitarism and diabetes insipidus remained unchanged.
Table 1 - Hormonal findings at the time of pituitary granuloma recurrence. Hormones Free thyroxine (pmol/I) Free T3 (pmol / I) Thyrotropin (mU / I) - Basal - Peak after TRHI Growth-Hormone (J.Lg/l) - Basal - Peak after stimulation 2
Normal range
Patient
8.5 - 20.5
4.2
3 - 8.7
3.3
0.1 - 4.5
1A 8A
0.5 - 5
1A 1.8
