MAMC Journal of Medical Sciences

: 2015  |  Volume : 1  |  Issue : 3  |  Page : 160--163

Lymphocytic infundibuloneurohypophysitis: A rare case report

Manish Gutch1, Sukriti Kumar2, Syed Razi Mohd1, Keshav Gupta Kumar1, Abhinav Gupta1,  
1 Department of Endocrinology, LLRM Medical College, Meerut, India
2 Department of Radiodiagnosis, SGPGI, Lucknow, Uttar Pradesh, India

Correspondence Address:
Manish Gutch
D.15, LLRM Medical College, Meerut . 250 004, Uttar Pradesh


Lymphocytic hypophysitis is a neuroendocrine disorder characterized by autoimmune infiammation of the pituitary gland with various degrees of pituitary dysfunction. Coexistence of other autoimmune conditions is reported in the vast majority of cases. The clinical presentation varies depending on the pituitary segment that is more severely affected. Early destruction of the ACTH producing cells is a characteristic feature of lymphocytic adenohypophysitis. Other anterior pituitary hormones can also be affected, but posterior pituitary involvement is absent or minimum. Lymphocytic infundibuloneurohypophysitis (LINH) typically presents as acute onset diabetes insipidus (DI) with intracranial mass effect symptoms. A combination of extensive anterior pituitary involvement and DI characterizes lymphocytic infudibulopanhypophysitis. We are presenting a case report of 35-year-old female presenting with insidious onset DI along with a severe headache and found to have LINH, without the involvement of anterior pituitary hormone secretions.

How to cite this article:
Gutch M, Kumar S, Mohd SR, Kumar KG, Gupta A. Lymphocytic infundibuloneurohypophysitis: A rare case report.MAMC J Med Sci 2015;1:160-163

How to cite this URL:
Gutch M, Kumar S, Mohd SR, Kumar KG, Gupta A. Lymphocytic infundibuloneurohypophysitis: A rare case report. MAMC J Med Sci [serial online] 2015 [cited 2019 Oct 20 ];1:160-163
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Full Text


The pituitary gland is occasionally the target of infiammatory response to local infections, neoplasias or autoimmune reactions. Lymphocytic hypophysitis (LYH) is the term commonly used to refer to such processes when an autoimmune origin is considered. This condition is characterized by lymphocytic infiltration and eventual destruction of the pituitary tissue accompanied by various degrees of pituitary dysfunction. As with other autoimmune conditions, LYH is seen more frequently in women. In fact, it was initially considered to be restricted to women in a relationship with pregnancy. With an increasing number of cases in children, postmenopausal women, and men reported in recent years, it is now clear that LYH can occur in children, adults, males, and females.[1] In classical LYH, infiammation is limited to the anterior pituitary or adenohypophysis; therefore, it is often referred in the literature as lymphocytic adenohypophysitis (LAH).[2] In contrast, when diabetes insipidus (DI) is prominent, either as the presenting or dominant symptom, or as permanent sequelae, the term lymphocytic infundibuloneurohypophysitis (LINH) is preferred.[3] Pathologic examination of tissue from patients with LINH has in fact revealed lymphocytic infiammation limited to the infundibulum, the pituitary stalk, and the neurohypophysis.[1] Cases of LINH have been reported with increasing frequency in the last decade.[4] And this condition is now regarded as a LYH variant. LINH is also referred to as stalkitis, infundibulo-stalkitis, neurohypophysis, and necrotizing infundibulo-hypophysitis.[4] Interestingly, LINH seems to occur more often in young men and in children.

 Case Report

A 35-year-old lady presented with insidious onset of polyuria and polydipsia of 6 months duration. She could not sleep well because of nocturnal enuresis and thirst. She did not give any history of trauma, a chronic headache, neurological deficit, or any systemic illness. She did not give any history of diabetes, hypertension, coronary artery disease, or transient ischemic attack in the past. Her personal and family history was noncontributory. On examination, she was conscious and well oriented. She weighed 61 kg and body mass index was 28.3 kg/m 2. Her blood pressure was 130/80 mm of Hg, heart rate 80 beats/min, and respiratory rate 20 breaths/min. All her systems were within normal limits. Her oral intake of fluids was seven liters, and urine output was 8 L/day. Her hemoglobin was 11.8 g%, total leukocyte count 8100/mm 3, platelet count

2.2 lacs/cc, random blood sugar 112 mg%, serum sodium 142 mM/L, serum potassium 3.8 mM/L, serum calcium 9.8 mg/dl, serum creatinine 0.9 mg%, serum uric acid 4 mg%; urine examination: Within normal limits, anti-nuclear antibodies, rheumatoid arthritis, factors negative, thyroid function and adrenal tests were within normal limits. She had a normal X-ray chest, ultrasonography abdomen (no organomegaly and no lymphadenopathy), and electrocardiogram.

In view of the polyuria, the water deprivation test (WDT) was performed followed by desmopressin injection (DDAVP test). Both test results [Table 1] were compatible with central DI, due to the appearance of urine concentration after a desmopressin injection as shown in the following results:{Table 1}

A magnetic resonance imaging (MRI) of the brain showed a normal sized anterior pituitary with the loss of a normal posterior pituitary bright spot on the T1-weighted image along with thick enchaining infundibulum on post-contrast T1. With the clinical history and investigation results, a diagnosis of central DI was made [Figure 1], [Figure 2], [Figure 3], [Figure 4].{Figure 1}{Figure 2}{Figure 3}{Figure 4}


The patient was treated with high dose of methylprednisolone (120 mg daily for 2 weeks, followed by a tapering dose schedule (80, 60, 40 then 20 mg daily; 1-week per step).


DI is characterized by a spectrum of polyuria and polydipsia, which occurs in various familial and acquired disorders of inadequate secretion of arginine vasopressin (AVP) from the neurohypophysis or AVP response in the renal tubules. Central diabetes insipidus (CDI) is the most common cause of the polyuric and polydipsic disorders occurring due to neurohypophyseal or hypothalamic lesions causing decreased synthesis or release of AVP.[5] Symptoms of DI develop when 80–90% of hypothalamic magnocellular neurons are lost.[5] CDI can occur due to either congenital or acquired causes. Transsphenoidal surgeries and head trauma together constitute the majority of acquired causes.

Autoimmune destruction of neurohypophysis called LINH is an important cause of CDI.[5]

CDI should be differentiated from other cause of polyuria by WDT. Initial tests: Polyuria should be confirmed by 24 h urine volume. Rule out diabetes, urinary tract infection, hypercalcaemia, hypokalemia, renal failure, and thyrotoxicosis. Morning urine osmolality >600 mOsm/kg rules out DI and, therefore, a WDT is not necessary. Preparation: Normal dinner and fluids are allowed the night before the test. No alcohol or caffeine. At 7 a.m light breakfast but NO fluids, tea, coffee, or smoking. Supervision is required throughout to assess compliance and safety. Contraindications: Hypovolaemia or hypernatremia. Procedure: Record results in the table. Please clearly label all blood and urine samples; the TIME of collection is essential. At 8 am: (a) Empty bladder, record the volume, and send urine osmolality (b) take a serum osmolality (c) record the patient's weight. Then for the next 8 h check: Urine osmolality and weight every hour, serum osmolality every 2 h. Stop the test if the patient's weight decreases by more than 5% of body weight or the serum osmolality rises >300 mOsm/kg. If the urine osmolality at 4 p.m. remain <600 mOsm/kg proceed with desmopressin test. Desmopressin 20 µg intranasally or 2 µg intramuscularly. Check hourly urine volume and osmolality.


Urine osmolality > 600 mOsm/kg excludes DI. The test can then be stopped if this is achieved. Urine osmolality <400 mOsm/kg and raised serum osmolality indicates an inability to concentrate urine and in the absence of renal tubular disease this indicates DI. In primary polydipsia, the urine is usually adequately concentrated (osmolality >600 mOsm/kg), and serum osmolality rises only slightly during water deprivation. However, following prolonged primary polydipsia there may be a "washout effect" with a loss of solute from the renal medulla and consequent impairment of concentrating ability (i.e. due to reduced osmolality in the renal medulla and not related to antidiuretic hormone). This may result in a delayed response that is a rise in urine osmolality to above 400 mOsm/kg but <600 mOsm/kg within 8 h of fluid deprivation. The volume of urine passed may give confirmatory information.

In normal subjects and primary polydipsia, the urine output should decrease during water deprivation while, in DI relatively large volumes of dilute urine are passed in spite of rising plasma osmolality. If the serum osmolality decreases during the test (and/or the weight increases), it is very likely that the patient has consumed water during the test. Post-DDAVP, in cranial DI, the urine osmolality should rise to above 600 mOsm/kg although, lesser responses are occasionally seen in partial defects. In nephrogenic DI, the urine usually fails to concentrate to 600 mOsm/kg.

LINH is considered as a part of spectrum of LYH which is recently classified as LAH when only adenohypophysis or anterior pituitary are involved, LINH when the pathology is limited to neurohypophysis or posterior pituitary, with CDI as presenting or dominant symptom and lymphocytic infundibuloneurohypophysitis when both anterior and posterior pituitary is involved. LYH is a rare disease with the prevalence of about 5/million and an annual incidence of about 1–7/million accounting for about 0.5% of cases of suspected hypopituitarism with only about 10% of cases having only posterior pituitary involvement comprising LINH.[6] LINH is also referred to as stalkitis, infundibulo-stalkitis, neurohypophysitis, and necrotizing infundibulo-hypophysitis.[4] Like LYH LINH is considered to be having an autoimmune etiology with the association between Adults Still's disease and recurrent optic neuritis. Pathological LINH is characterized by lymphocytic infiltration limited to the infundibulum, the stalk, and the neurohypophysis.[3] In contrast to LAH, which is considered to have female predominance (5–8:1), LINH was considered to be having the equal male-female ratio, with some reports of female predominance.[7] Takahashi et al. reported 70% of the female cases with a mean age 47.3 ± 17.4 years.[8] A headache and impaired vision are the most common complaints and are reported in 50–70% of the cases. A headache is a frequent manifestation of any pituitary conditions and occurs as a consequence of functional or structural changes. It is now clear that even small pituitary lesions, with no apparent dural stretch or cavernous sinus invasion, can cause a headache due to incompletely understood functional disturbances.[4] In LINH, headache tends to occur more frequently than in pituitary adenomas, and it is often the first symptom, typically with a sudden onset. The location is bilateral frontal, retro-orbital, or temporal. Concomitant nausea or vomiting and fatigue are present in 25%, while weakness and anorexia are reported in about 15% of the cases.[4] Anterior pituitary functions are normal, but there can be mild transient involvement most commonly involving growth hormone (GH). Kristof et al.[7] reported that a high dose of methylprednisolone (120 mg daily for 2 weeks, followed by a tapering dose schedule 80, 60, 40 and then 20 mg daily; 1-week/step) improved anterior pituitary function in 4 of 9 patients, and DI in all four patients presenting with this condition. The tentative diagnosis of LINH is entertained when a patient presenting with CDI is having loss of normal posterior pituitary bright spot on T1-weighted MRI along with diffuse stalk thickening, with a diameter > 3.5 mm at the level of median eminence,[8] but the definitive diagnosis requires histopathology. The differential diagnoses which are difficult to rule out are germinoma, Langerhan's histiocytosis, and inflammatory pseudotumors.

The differential diagnosis of LINH includes some rare tumors like germinomas and Langerhans' histiocytosis and can be very difficult. These tumors may present with DI and pituitary stalk thickening. However, the radiological findings are unlikely to regress; instead a rapid progression is seen in most of the cases.[9] Histopathology is essential if such malignancies are considered. LINH can be differentiated from other causes of headache by characteristic symptomatology, and MRI findings (loss of normal posterior pituitary bright spot on T1-weighted MRI along with diffuse stalk thickening, with a diameter >3.5 mm at the level of median eminence) which are absent in other causes of benign headache conditions like cluster headache and complicated migraine.[10]

When LINH occurs in the postpartum period, Sheehan's syndrome needs to be ruled out. The latter is due to apoplexy of the pituitary gland and can present abruptly or insidiously after delivery. Sheehan's syndrome is usually associated with obstetric hemorrhage and a low prolactin with failure to lactate. It will very rarely present with DI, and is not associated with other autoimmune diseases.

In this case, 35-year-old premenopausal woman presented with complaints of headache, polyuria, and polydipsia for 6 months. There was no evidence of any anterior pituitary hormone deficiency and associated autoimmune disease. Patient's MRI showed characteristic findings of LINH and patient responded dramatically to glucocorticoid therapy.

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