Could this be lymphocytic hypophysitis?

I saw a fascinating new consult yesterday.

A 58-year-old man began experiencing excessive thirst and urination approximately nine years ago. When he complained of this to several primary care physicians, they told him to stop drinking so much and the symptoms would disappear. No other work-up was performed or offered. It was suggested that perhaps his symptoms were in his head.

His thirst was so profound, he had to sleep with a cooler of ice water beside his bed. After a few years, he finally saw an astute general internist who confirmed central diabetes insipidus by water deprivation study. The MRI was reportedly negative. There were no other pituitary hormonal abnormalities.

The patient did well on nasal DDAVP (desmopressin acetate) for a few years when he developed fatigue and felt poorly. He missed a few doses of DDAVP and did not have polyuria. He stopped the DDAVP completely. Last year, he saw an endocrinologist who identified hypogonadotropic hypogonadism and central hypothyroidism. A repeat water deprivation test was equivocal. Prolactin and insulin-like growth factor I were normal. An MRI showed a thickened pituitary stalk suggesting an infiltrative process without focal mass. Glucocorticoid deficiency can mask diabetes insipidus but interestingly, the adrenocorticotropic axis appeared intact. His symptoms resolved with testosterone and thyroid hormone replacement therapy.

In spring 2008, he developed sudden renal failure. Renal biopsy showed findings suggestive of lupus nephritis. A rheumatology evaluation failed to identify other features of systemic lupus erythematosus. However, he has had vitiligo for years. He was temporarily on dialysis and subsequently prednisone was begun. Since then, his renal function has improved and he has generally felt much better.

This man’s history and presentation raise the question of autoimmune pituitary disease. There are three forms of primary hypopituitarism: lymphocytic, granulomatous and xanthomatous. Lymphocytic hypophysitis has been further classified based on the region affected: lymphocytic adenohypophysitis, lymphocytic infundibuloneurohypophysitis and lymphocytic panhypophysitis. Although lymphocytic adenohypophysitis is more common in women, especially around the time of pregnancy, lymphocytic infundibuloneurohypophysitis affects males and females equally. The differential diagnosis includes systemic infiltrative disorders such as sarcoidosis, Wegener’s granulomatosis and histiocytosis X.

The presenting hormonal abnormalities depend on the region involved. Lymphocytic adenohypophysitis classically presents with central adrenal insufficiency whereas lymphocytic infundibuloneuro-hypophysitis presents with diabetes insipidus. Sometimes, normal pituitary function returns spontaneously.

Based on history and clinical features, I strongly suspect lymphocytic hypophysitis. Of course, there is no way to confirm the diagnosis without biopsy. Surgery is not recommended unless there is an indication such as mass effect or changes suggesting a neoplastic process. There have been reports of pituitary function improving with the use of glucocorticoid therapy. It will be interesting to see if there is any change in his function with prednisone.

If there are any future developments of interest, I will keep the readers of this blog posted. Cases such as this serve to remind me of why I chose endocrinology as a career in the first place.