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

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

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.

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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.

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-

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

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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.

Table 1 - Hormonal findings at the time of pituitary granuloma recurrence.

Hormones Normal range Patient

Free thyroxine (pmol/I) 8.5 - 20.5 4.2

Free T3 (pmol / I) 3 - 8.7 3.3

Thyrotropin (mU / I) - Basal 0.1 - 4.5 1A - Peak after TRHI 8A

Growth-Hormone (J.Lg/l) - Basal 0.5 - 5 1A - Peak after stimulation2 1.8

Prolactin (J.Lg / l) <20 8.8

FSH (J.Lg / l) - Basal 0.25 - 2.5 OA - Peak after LHRH3 0.9

LH (J.Lg/l) - Basal 0.57 - 4.0 OA - Peak after LH RH 1.0

1 Thyrotropin-releasing hormone (TRH) stimulation test, 200 J.Lg iv. 2 Arginine chlorhydrate stimulation test, 25 9 in 400 ml solution, iv. 3 Luteinizing hormone-releasing hormone ~LHRH) stimulation test, 100 J.Lg iv.

Normalization of visual fields was noticed as soon as the second day of treatment. Headaches disap­peared and CT scan, performed one month after the beginning of prednisone, documented a dra-

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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.

DISCUSSION Nontumoral pituitary lesions are rare. Several in­flammatory or infectious diseases may involve the pituitary, presenting usually as infiltrative lesions, or less commonly as an intrasellar pseudotumoral mass that may extend into the suprasellar region. Lymphocytic hypophysitis has characteristic patho­logical features, namely the presence of lymphoid follicles resembling those Observed in many organ­specific autoimmune diseases and suggesting that autoimmunity may be involved in its pathogenesis (4, 5). Granulomatous hypophysitis can be secon­dary to infectious diseases such as syphilis or tu­berculosis, or to "inflammatory" processes like sar­coidosis (6) or histiocytosis. However in many cases the definite cause can not be assessed and the lesions are called "giant-cell granuloma" because

Fig. 2 - Coronal CT scan showing (Fig. 2A) an intrasellar mass with suprasellar bulging corres­ponding to the recurrence of the pituitary granu­loma. Shrinkage of the pituitary mass one month (Fig. 28) and six months (Fig. 2C) after the begin­ning of steroid therapy. (Fig. 20): MRI of the sellar area after two-year steroid therapy.

P. Chanson, J. Timisit, M. Kujas, et a/.

of nonspecific giant cells in the granulomatous tissue (7). In our patient, the pathological findings ruled out the hypothesis of syphilis or tuberculosis. Lympho­cytic hypophysitis mainly occurs in women. In most cases diagnosis is made either during pregnancy or soon after delivery (4). The lesion often presents as a pituitary pseudotumor and is responsible for pituitary deficiencies. However diabetes insipidus is not an usual feature of this syndrome (4, 5). Neither the case history of our patient nor the patho­logical findings of the removed tissue especially because of the absence of germinal centers were characteristic of lymphocytic hypophysitis. Isolated involvement of hypothalamus has been described in sarcoidosis or histiocytosis and these diagnoses are in our patient impossible to rule out. However, despite extensive and repeated evalua­tion, there was no evidence of sarcoidosis or his­tiocytosis. The hilar lymphadenopathy usually as­sociated with hypothalamic sarcoidosis was absent in our patient, pulmonary function studies, bron­choalveolar lavage and angiotensin converting en­zyme level were normal. Repeated skeletal survey and bone radionuclide scan were normal. Moreover, a 2-yr follow-up did not disclose the emergence of any clinical, biological or radiological symptom sup­porting this hypothesis. In fact, the clinical and mor­phological findings of our patient are consistent with the diagnosis of the so-called "pituitary gran­uloma" comparable to the few cases reported re­cently (8-14). One might however hypothesize that the pituitary lesion was a pituitary localization of her skin disease, pyoderma gangrenosum. Pituitary en­largement had never been previously described in this condition, but in our patient several arguments deserve this hypothesis. First, the pituitary lesion occurred when the patient was treated with a small maintenance dose of prednisone. The skin lesions had recurred in comparable circumstances a few years before, as described in this disease (15), and led to increase steroid dosage. Similarly the pituitary process recurred soon after the postoperative with­drawal of prednisone therapy. Second, histopatho­logic changes of the pituitary mass removed at surgery are very reminiscent of the classical pat­terns of skin biopsies in pyoderma gangrenosum (2). Although neither the depicted lesions of the pituitary nor the classical histopathologic findings of pyoderma gangrenosum are specific, a putative link might be proposed in our patient. Third the

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reactivation of the disease by the trauma due to the surgical procedure, illustrated the principle of pa­thergic reaction, and is also suggestive. Lastly, the complete shrinkage of the lesion with steroid therapy is very similar to the usual response of the skin lesions. Although no definite proof can be provided in this patient, the hypothesis of a pituitary lesion similar to the skin lesion of pyoderma gangrenosum seems likely.

ACKNOWLEDGMENTS We acknowledge Mrs P. Tomi for her excellent secretarial as­sistance.

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