Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
About 30 cases of primary granulomatous hypophysitis have been reported, one third of them being asymptomatic in terms of sellar disease.1 2 The aetiology is not understood. The adenohypophysis alone or the whole pituitary gland may be involved.2 3 Clinical manifestation of primary granulomatous hypophysitis comprises hypopituitarism and local mass effect. In no symptomatic case reported so far, was the diagnosis suspected before surgery. There is also no experience on preoperative anti-inflammatory high dose corticosteroid therapy for primary granulomatous hypophysitis (PGH).
An otherwise healthy 16 year old girl presented with harmonic dwarfism (body length 1.34 m, body weight 31 kg), pubertas tarda (stage B2P2), and longstanding diabetes insipidus. Dynamic assessment of the adenohypophysis by a combined releasing hormone test and insulin induced hypoglycaemia disclosed somatotrophin and gonadotrophin insufficiency (baseline HGH 2.0 μg/l, stimulated 1.8 μg/l; IGF-1 263 μg/l; oestradiol 15 μg/l; baseline LH 0.5 U/l, stimulated 0.6 U/l; baseline FSH 2.1 U/l, stimulated 2.4 U/l). Central diabetes insipidus was confirmed by increased amounts of urinary excretion (range 2.60–3.85 l/day), low specific urinary densities (< 1005), and increased serum natraemia (range 152–155 E/l) and osmolality (range 316–319 osmol/l). Other laboratory examinations and chest radiography showed no abnormality (in particular no tuberculosis, sarcoidosis, or syphilis). MRI disclosed an atrophic pituitary gland and a grossly enlarged pituitary stalk (figure). The presumed diagnosis was longstanding primary hypophysitis.
Pulsed high dose prednisolone therapy was started with 120 mg/day for four days, then tapered by halving the dose every second week during the next seven weeks. Eight weeks after the start of therapy, repeated endocrinological and MRI evaluation failed to disclose any improvement. Because other diseases could not be definitively ruled out, biopsy of the pituitary stalk through a subfrontal approach was performed. At surgery, the pituitary stalk was thickened but otherwise of normal appearance.
Histology established the diagnosis of PGH with abundant fibrosis. The presence of microorganisms was ruled out by Ziehl-Nielson and periodic acid-Schiff stains.
The endocrinological and neuroradiological findings did not change during a follow up of 1.5 years.
Primary or idiopathic granulomatous hypophysitis has so far been diagnosed by exclusion: the histological criteria have to be fulfilled and any causative agents of granulomatous or other inflammatory disease and tumorous process have to be ruled out.3 4
Its clinical, endocrinological, and neuroradiological features make primary granulomatous hypophysitis indistinguishable from lymphocytic hypophysitis and often hardly distinguishable from secondary granulomatous hypophysitis due to tumorous sellar processes such as pituitary adenoma, Rathke’s cleft cyst, and histiocytosis X.1 2 4 Secondary granulomatous hypophysitis due to tuberculosis, syphilis, sarcoidosis, and other inflammatory disease can be ruled out to a large extent by clinical, laboratory, and radiological investigations.4 In the present case, the longstanding impairment of both adenohypophysial and neurohypophysial function, together with an atrophic sellar content but a strongly enlarged pituitary stalk, in the absence of systemic inflammation, led to the preoperative suspicion of primary hypophysitis. Pulsed high dose prednisolone therapy did not result in any improvement. Bioptic proof was considered necessary. It would seem that the chronic course of the disease with fibrosis of the whole pituitary, rather than an inadequate drug choice or dosage, may explain the failure of corticosteroid therapy. However, eventual non-effectiveness of anti-inflammatory corticosteroid therapy in treating primary granulomatous hypophysitis cannot be generalised from this single case. A case of secondary granulomatous hypophysitis associated with pyoderma gangrenosum was reported to be successfully treated by high dose corticosteroid therapy after surgery and recurrence.5 In two other cases, one with primary granulomatous hypophysitis and the other with secondary granulomatous hypophysitis associated with Crohn’s disease, low dose corticosteroid therapy (adrenal substitution and treatment for Crohn’s disease) was without lasting effect.4 6
Considering the inflammatory nature of primary granulomatous hypophysitis, high dose corticosteroid therapy may represent a therapeutic option in selected cases of this disease. Two conditions have to be fulfilled. Firstly, primary granulomatous hypophysitis has to be suspected from the diagnostic evaluation. Diagnostic hints are a disproportionate severe adenohypophysial dysfunction compared with the pituitary mass,4 diabetes insipidus suggesting neurohypophysial involvement,2 (present case) a usually moderate sellar mass also involving the pituitary stalk, which is homogeneously and markedly contrast enhanced on T1 weighted MRI and hyperintense on T2 weighted MRI,1 (present case) and the absence of any identifiable causative agent such as inflammatory disease or tumour.3 4 Secondly, the suspected primary granulomatous hypophysitis should not cause any pronounced or progressive neurological deficits. None of the above criteria are diagnostic for primary granulomatous hypophysitis and can only suggest it; some uncertainty will always remain. Therefore, during high dose corticosteroid treatment of suspected primary granulomatous hypophysitis, meticulous clinical, endocrinological, and neuroradiological monitoring has to be ensured. In cases that do not fulfill the above mentioned conditions, trans-sphenoidal or, seldom, transcranial surgery, is the therapy of choice. Removal of the usually solid inflammatory process leads to rapid relief of neurological deficits and guarantees accurate histological diagnosis. However, improvement of endocrinological deficits is uncommon.1