Optic neuritis as presenting primary hypoparathyroidism

Abstract

Papilloedema and raised intracranial pressure have been frequently reported with hypoparathyroidism, but very rarely optic neuritis. We report a case of a 54-year-old male patient who presented with classical optic neuritis which is believed to be secondary to primary hypoparathyroidism.

Background

Hypoparathyroidism is associated with numerous ocular sequelae, including cataracts,¹ blepharospasm, loss of eyelashes and keratoconjunctivitis.² Papilloedema also has been reported frequently with hypoparathyroidism, which may or may not be associated with raised intracranial pressure.³ However, very rarely, optic neuritis, which is characterised by a marked decrease in visual acuity and relative afferent pupillary defect, has been reported as well.⁴ We report a patient who presented with optic neuritis and was found to have primary hypoparathyroidism after investigations.

Case presentation

A 54-year-old man was referred urgently to the ophthalmology department, after developing an acute marked drop in right visual acuity. On initial assessment in July 2015, his vision on the right side was recorded as 6/60 (6/6 in left eye). The visual fields on the right side showed altitudinal field loss (figures 1 and 2). He had a relative afferent pupillary defect and the fundus on examination looked normal with no papilloedema (figure 3). A diagnosis of optic neuritis was thus made and an urgent MRI scan brain was requested. MRI brain was reported to have atypical white matter changes bilaterally, with the possibility of demyelination and an urgent referral to the neurologist was recommended by the radiologist.

Figure 1.

Visual field: right eye.

Figure 2.

Visual field: left eye.

Figure 3.

Right and left fundus images showing normal retina with no papilloedema.

When the patient was reviewed in the neurology clinic in October 2015, a note was made of additional cognitive symptoms including difficulties in initiating speech, occasional double vision and cramps. Neurological examination revealed normal tone, power and sensation, but with brisk reflexes and slightly broad-based gait. It was considered that his symptoms could be suggestive of an inflammatory demyelinating condition and additional investigations were arranged. Routine blood investigations revealed a very low serum calcium of 1.32 mmol/L (2.20–2.60). This was repeated by the general practitioner in case of laboratory error but remained low. Lumbar puncture revealed opening pressure of 21 cm with no white blood cells, normal protein (0.49 g/L), glucose (3.5 mmol/L), and oligoclonal bands were not detected.

The patient had an emergency admission to Doncaster Royal Infirmary for intravenous calcium replacement and further investigations. The ionised calcium levels on admission were also low at 0.65 mmol/L (reference range 1.1–1.35). His parathyroid hormone levels were undetectable, that is, <0.3 pg/mL (1.6–7.2) and the diagnosis of primary hypoparathyroidism was made. The rest of investigations revealed high phosphate level of 2.2 mmol/L (reference range 0.8–1.5), slightly low magnesium level of 0.61 mmol/L (0.7–1.0) with normal albumin (41 g/L; reference range 35–50) and normal renal functions (creatinine of 85 μmol/L; reference range 64–104). His 24-hour urine calcium levels were undetectable, that is, <2.2 mmol/24 hours (reference range 2.5–7.5), with low 24-hour urine phosphate of 14 mmol/L (reference range 15–50). The rest of endocrine investigations including thyroid function tests, cortisol, adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin levels were normal with normal vitamin D levels of 76 nmol/L (reference range >75). The ultrasound of the renal tract revealed no stones. The patient did not have any relevant family history and low urine calcium levels ruled out autosomal dominant hypocalcaemia. The adrenal antibodies were also negative, and there was no prior history of any neck surgery. Therefore, the hypoparathyroidism was labelled as ‘idiopathic’.

In January 2016, MRI brain images were discussed in neuroradiology multidisciplinary team (MDT) meeting. The diffuse white matter changes, which were initially thought to indicate a central nervous system inflammatory disease, were believed to be consistent with severe hypocalcaemia, and a note was made of the symmetrical increased signal within the corpus striatum and thalamus with the increased T1 signal resulting from primary hypoparathyroidism (figures 4 and 5).

Figure 4.

MRI brain showing diffuse white matter changes.

Figure 5.

MRI brain showing increased signal in corpus striatum and thalamus.

Outcome and follow-up

With calcium replacement, the adjusted serum calcium reached and remained in the normal range. However, the visual acuity did not improve to the initial state and the patient is now registered as blind in the right eye. The optical coherence tomography (OCT) scan, performed in August 2015, showed subtle retinal nerve fibre layer (RNFL) thickening in some quadrants with optic disc oedema secondary to optic neuritis. The second OCT scan, performed in May 2016, showed significant RNFL thinning an all quadrants, consistent with optic neuritis (figures 6 and 7).

Figure 6.

Optical coherence tomography of the right eye: August 2015. INF, inferior quadrant; NAS, nasal quadrant; RNFLT, retinal nerve fibre layer thickness; SUP, superior quadrant; TMP, temporal quadrant.

Figure 7.

Optical coherence tomography (OCT) of the right eye: May 2016. INF, inferior quadrant; NAS, nasal quadrant; RNFLT, retinal nerve fibre layer thickness; SUP, superior quadrant; TMP, temporal quadrant.

Discussion

Hypoparathyroidism has been associated with numerous ocular signs including cataracts, keratoconjunctivitis and loss of eyelashes. Papilloedema has been reported several times as well, in association with hypoparathyroidism. Although this was thought to be due to raised intracranial pressure, interestingly, CSF pressures have been found to be normal in some of these cases, raising questions regarding the underlying mechanism. Very rarely, true optic neuritis has been reported as well. After the literature search, we could only find very few published reports of patients, who were thought to have true optic neuritis.

Bajandas and Smith⁴ reported a case of a 61-year-old woman, who was found to have severe hypocalcaemia almost 20 years postsubtotal thyroidectomy. Later on, the patient developed unilateral visual loss. On examination, she was found to have a classic relative afferent pupillary defect, constriction of visual field with dense central scotoma. The optic disc showed blurred margins and was mildly elevated and somewhat pale. The authors at that time considered these findings to be secondary to optic neuritis and raised the possibility of a possible association between optic neuritis and hypoparathyroidism. There are two more reported such cases but unfortunately, despite our best efforts, the details were unavailable.^{5 6}

In contrast to the above cases, our case did not have a history of previous neck surgery and interestingly, hypocalcaemia was only picked up incidentally as the patient was asymptomatic. Because of the established association between optic neuritis and multiple sclerosis,⁷ the diagnosis was initially missed. On further questioning, he did not have any significant family history. It is not clear, how long he had severe hypocalcaemia, but we believe that this could be of long duration considering his adaptation to such low calcium levels.

It is not clear what the exact underlying mechanism for this presentation is. For papilloedema, it has been previously postulated that hypocalcaemia either causes increased cerebrospinal fluid (CSF) production from choroid plexus or decreases its reabsorption, however, since CSF pressure has been found normal in numerous cases, makes the above doubtful. Although we are not sure about the underlying mechanism, we think that severe and chronic hypocalcaemia alters optic nerve function directly which is manifests as papilloedema or rarely optic neuritis.

We do appreciate that it may be possible that it may just be a coincidence that hypoparathyroidism is associated with idiopathic optic neuritis in this cases, however considering the already associated numerous ocular sequelae with hypoparathyroidism, we believe that optic neuritis is also part of the spectrum of hypocalcaemia-related visual changes.

Learning points.

• Primary hypoparathyroidism can be associated with numerous ocular sequelae such as cataracts, keratoconjunctivitis, loss of eyelashes and papilloedema.

• Optic neuritis can also be associated with primary hypoparathyroidism and can also be the first presenting complaint.

• In the cases of unexplained papilloedema or optic neuritis, calcium levels should be checked to rule out hypoparathyroidism.