In this patient, the diagnosis of anterior pituitary insufficiency is evident from the constellation of secondary hypothyroidism, secondary amenorrhoea and the clinical manifestations of secondary adrenocortical insufficiency (hypoglycaemia, orthostatic hypotension and marked hyponatremia with low normal K+ levels). Interestingly, her TSH levels were undetectable which is quite rare in panhypopituitarism but has been previously reported . Also noteworthy in this case is the severe hyponatremia which is likely multifactorial. In secondary adrenal insufficiency, one accepted explanation is that hypocortisolism leads to failure of inhibition of vasopressin secretion. In addition severe secondary hypothyroidism, which this patient also had, leads to a syndrome of inappropriate secretion of ADH (SIADH)-like picture [10–12].
Arriving at an etiologic diagnosis is more challenging. The history of post-partum hemorrhage albeit mild, and lactation failure may favor Sheehan’s syndrome (SS) over lymphocytic hypophysitis (LyHy) which is another recognized, but less common cause of post-partum pituitary insufficiency [1, 2]. However in light of a history suggestive of painless post-partum thyroiditis, a physical exam which revealed signs of co-existing autoimmune conditions such as alopecia areata and the elevated ESR, the latter provides a better diagnostic fit [2, 9, 13, 14]. While LyHy often presents with hyperprolactinemia from stalk dysfunction leading to galactorrhoea in a quarter to one-third of cases [1, 6], agalactia has been reported in 11% of patients .
Although, thyroid auto-antibodies could not be tested and her antinuclear antibody and antiphospholipid antibodies were negative, a comprehensive retrospective analysis of 379 patients with lymphocytic hypophysitis (LyHy) by Caturgeli et al found that the prevalence of auto-antibodies for Hashimoto’s and SLE was only 7.4% and 1.3% respectively . Similarly; anti-pituitary antibodies could not be assayed however these are considered of limited sensitivity and specificity in the diagnosis of lymphocytic hypophysitis since they are present in other autoimmune conditions and several non-immune pituitary disorders (including Sheehan’s syndrome) . In the latter, post partum hemorrhage may trigger pituitary autoimmunity by the release of sequestered antigens following necrosis of the gland .
Assessment of visual fields is a simple but very useful diagnostic test. The minor defect in the patient’s temporal visual fields detected bilaterally upon visual perimetry may signify an ischemic process secondary to a mass effect at the optic chiasm – this could indicate a pituitary macroadenoma or an infiltrative process such as LyHy. The normal size sella on skull X-ray and CT scan might argue against a large tumor.
MRI is the imaging study of choice for the pituitary , the lack of which makes it difficult to accurately diagnose pituitary disease in most hospitals in the developing world. In any case, up to 9% of patients suffering from LyHy have normal imaging findings on CT/MRI. More common presentations include symmetric enlargement of sellar content (66%), thickening of the pituitary stalk (56%), homogenous enhancement (51%) and occasionally asymmetry of the enlarged sellar content (18%) . This differs from the imaging findings in Sheehan’s syndrome which almost always results in a partially or completely empty sella that may be normal or reduced in size [18, 19].
A definitive diagnosis usually requires a tissue biopsy often obtained via the endonasal transsphenoidal approach which was not possible in this case. Molitch et al have suggested criteria for making a strong presumptive clinical diagnosis non-invasively. These are as follows: a history of gestational / postpartum hypopituitarism, a contrast-enhancing sellar mass with MRI features characteristic of LyHy, a pattern of endocrine deficiency with early loss of adrenocorticotrophic hormone and thyroid-stimulating hormone unlike that found with macroadenomas and pituitary failure disproportionate to size of the mass .
Of note, livedo reticularis has never been reported before in patients with a clinical or histopathologic diagnosis of lymphocytic hypophysitis and may be unrelated. However, an association is not inconceivable particularly if the patient were to have an underlying co-morbidity such as SLE, since both LyHy and livedo reticularis have independently been documented in lupus [21, 22]. This patient likely meets four (4) of the eleven (11) criteria required for a diagnosis of lupus namely photosensitivity, proteinuria, serositis (pleural and pericardial effusions) and hematologic abnormalities (normocytic anemia) . However her ANA was negative and more specific tests such as anti-ds DNA or anti-Sm antibodies to rule out antinuclear-antibody negative disease were not available.
Finally, does a definitive diagnosis necessarily influence management in post-partum panhypopituitarism? The simple answer is yes - while hormone replacement is often all that is necessary for Sheehan’s syndrome, additional measures may be required for patients with LyHy presenting with symptoms of sellar compression. While surgery or pituitary radiotherapy may eventually be needed, in the absence of urgent visual symptoms it is reasonable to advocate using high dose glucocorticoids as first line therapy for LyHy under imaging surveillance if possible; decrease in volume of the pituitary mass and improving hormone status helps to confirm the diagnosis retrospectively [6, 17]. Methotrexate and azathioprine can be used for poor responders [24–26]. Among the 320 patients with LyHy followed by Caturgeli, 73% required long term hormone replacement therapy, 16% recovered following mass-reduction without need for hormone-replacement, 8% died probably from irreversible adrenal insufficiency and 3% experienced spontaneous resolution without treatment .