Dermatitis herpetiformis, primary hypothyroidism and pituitary mass mimicking macroadenoma regression after treatment with thyroxin, corticosteroids and dapsone.

We report a case of 15-year-old girl who was diagnosed as a case of pituitary macroadenoma on computed tomography and magnetic resonance imaging (MRI) scans for her complains of diminished vision in the left eye and headache. On investigation she was found to have optic atrophy of left eye and primary hypothyroidism. She was started on thyroxin therapy in October 2008 and planned for transcranial excision of the tumor. Just before the date for planned surgery she developed mildly itchy vesico-bullous rash and the surgery was postponed. On histopathology and immunoflourescence studies it was confirmed to be the rash of dermatitis herpetiformis (DH) and treatment was started with corticosteroids in the last week of December 2008 and dapsone was added from mid January 2009. The lesions responded dramatically and within 6 weeks of starting treatment, she had become asymptomatic except for persisting diminution of vision. Repeat MRI scans in mid-February 2009 revealed total regression of pituitary mass. The case is being reported for interesting association of primary hypothyroidism, pituitary mass mimicking macroadenoma and DH; its successful outcome with medical management in the form of total regression of pituitary mass, thereby avoiding an unnecessary surgery.

Introduction

Dermatitis herpetiformis (DH) is an autoimmune skin disorder frequently associated with gastrointestinal disease characterized by intensely itchy, chronic papulo-vesicles, distributed symmetrically on extensor surfaces. It has also been found associated with a number of other autoimmune illnesses including autoimmune thyroid disease.[12] Pituitary mass mimicking as pituitary macroadenoma has also been reported in cases of primary hypothyroidism.[3-6] We report here a case which had a combination of primary hypothyroidism, pituitary mass mimicking macroadenoma and DH.

Case Report

A 15-year-old girl, resident of Meerut, Uttar Pradesh, presented with complaints of diminution of vision of left eye since May 2008 and insidious onset, throbbing, progressively increasing headache on the left side since July 2008. Computed tomography of brain in August 2008 revealed a pituitary mass reported as microadenoma. With the advice to get a magnetic resonance imaging (MRI) for the same, she reported to the neurosurgeon in a tertiary care super-specialty hospital in New Delhi in September 2008. Referral to ophthalmologist revealed distant vision of left eye of 6/60 with pale optic disc suggestive of optic atrophy. Hormonal assay revealed level of T3 of 0.3 ng/ml (N 0.52-1.85), T4 3.0 μg/dl (N 4.82-11.60) and thyroid stimulating hormone (TSH) >100 μlU/ml (N 0.39-6.16) suggestive of hypothyroidism. FSH (3.5 U/L), LH (1.2 U/L), GH (O.1 ng/ml) and cortisol (9.3 mcg/dl) levels were found to be normal. Anti-thyroperoxidase (TPO) antibodies were negative. Patient was diagnosed as a case of primary hypothyroidism and started on tablet thyroxin 150 μg/day. MRI of sella revealed well-defined, uniformly enhancing enlargement of the anterior lobe of pituitary gland. Intravenous contrast showed heterogeneous enhancement, the lesion measured 13 (CC) × 7 (ml) × 6 (AP) mm. Laterally the lesion was encroaching the duramater [Figure 1], opined as pituitary macroadenoma. In the meantime patient also had two episodes of projectile vomiting, hence the endocrinologist opined that ideally the patient should be made euthyroid but in view of the signs of raised intracranial tension she can be taken up for surgery.

Figure 1

MRI scan of sella showing pituitary macroadenoma. The intravenous contrast view below showed heterogeneous enhancement with size of the pituitary being 13 (CC) × 7 (ml) × 6 (AP) mm

The child was again reviewed by the neurosurgeon in October and advised admission for transcranial excision of the pituitary adenoma. The patient defaulted and the surgery was rescheduled for 29th December 2008. Ten days prior to her date of surgery, she developed mildly itchy vesicobullous rash on left side of her neck [Figure 2], gradually spread to involve scalp, face, trunk and limbs with sparing of palms and soles. Her surgery was cancelled and she was referred to us.

Figure 2

Tense vesico-bullous rash on erythematous background on left side of the neck

In addition, she had attained her menarche at the age of 13. The periods were regular though painful initially, became irregular since September 2007 and subsequently she developed secondary amenorrhea since January 2008.

On examination general and systemic examinations were normal with her weight being 30 kg. Dermatological examination revealed tense vesicles and bullae over neck, face, trunk and extremities. Nickolsky sign and bulla spread sign was negative. Few of the lesions had ruptured spontaneously to form superficial erosions, crusted lesions and few healed with hypopigmentation.

Histopathology of the bulla revealed split at dermoepidermal junction with collection of neutrophils in the cavity [Figure 3]. Immunoflourescence revealed deposits of IgA antibodies in granular pattern at the dermoepidermal junction with accentuation at dermal papilla, consistent with the diagnosis of DH.

Figure 3

Histopathology of bullous lesion showing split at dermoepidermal junction with collection of neutrophils in the bulla fluid (H and E stain, 400×)

Patient was started on tab prednisolone 10 mg thrice daily for 4 weeks and then gradually tapered over next 2 weeks. Tablet dapsone 100 mg daily was added after 2 weeks of steroids and she was continuing on tab thyroxin. By mid February 2009 patient had become totally asymptomatic except for poor vision in the left eye. The skin rash had regressed completely with residual hypopigmentation [Figure 4]. She also restarted her menstrual cycles in February 2009. Repeat MRI scans in mid february revealed total regression of pituitary mass [Figure 5]. T3 (0.6 ng/ml) and T4 (5.0 μg/dl) levels had normalized, although TSH levels were still high (60 μ IU/ml) requiring adjustment of dose of thyroxin by the endocrinologist.

Figure 4

Clearance of skin rash after treatment

Figure 5

MRI scans of the brain showing regression of pituitary mass

Discussion

Idiopathic hypothyroidism, triggered by autoimmunity, most commonly affects women in the age group of 30-70. The trigger or the initiating agent of this autoimmune process is not known. In our case the primary event was primary hypothyroidism with its onset at the age of probably 14 years, when she had started having her menstrual irregularity in september 2007. It was detected only after CD8-mediated damage to the thyroid tissue had destroyed substantial amount of the tissue and it was not able to produce adequate quantities of T3 and T4 hormones. This was inspite of increase stimulation of hypothalamus and anterior lobe of the pituitary gland producing high levels of TSH through the feedback mechanism. Increased secretion of thyrotropin-releasing hormone (TRH) by the hypothalamus led to hyperplasia of the anterior lobe of the pituitary gland to such an extent that it mimicked a macroadenoma. This pituitary mass because of its pressure affect on the optic chiasma causing impaired blood supply led to optic atrophy on the left side, which gave the presenting symptom of diminished vision. Later as the pituitary mass kept increasing in size the symptoms of headache and projectile vomiting appeared. Primary hypothyroidism was detected on routine screening in a case of pituitary macroadenoma by the endocrinologist.

The child was started on thyroxin therapy and endocrinologist gave a go ahead to the neurosurgeon to remove the macroadenoma in view of the signs of increased intracranial tension. The surgery was planned twice and she was lucky both times. On the first occasion she did not report for surgery due to domestic compulsions and second time when she developed bullous rash just prior to the surgery requiring dermatological referral.

Although the patient was put on thyroxin replacement therapy, the autoimmune process was continuing as was manifested by the appearance of rash and demonstration of IgA autoantibodies in the lesions of DH. Autoimmune thyroiditis is a CD8 T-cell-mediated disease and these stimulated T-cells may as well be stimulating B-cells to secrete other autoantibodies including the ones responsible for DH.[7] With the introduction of corticosteroids the autoimmune process was brought under control by decreasing CD8 cell-mediated damage to the thyroid tissueand decrease in autoantibodies by decreased B-cell stimulation, thus both autoimmune thyroiditis and DH improved. This would have led to some increase in endogenous production of thyroid hormones from the salvaged thyroid acini and along with exogenous thyroxin led to decrease levels of TRH from the hypothalamus causing regression of pituitary mass. Thus an unnecessary surgery could be avoided. The eye damage was, however, irreversible.

We, therefore, report this case for its interesting presentation and rewarding outcome. The presence of pituitary mass mimicking macroadenoma in a case of primary hypothyroidism responding to thyroxin therapy has been reported earlier.[3-7] Our case presented with pituitary mass, was found to have primary hypothyroidism and later developed DH, successfully treated with thyroxin, corticosteroids and dapsone. This combination has not been reported in the literature so far.