Neurological manifestation in severe hypothyroidism in pregnancy

Abstract

Neurological manifestations of hypothyroidism include peripheral neuropathy and pituitary hyperplasia. However, these associations are rarely encountered during pregnancy. We report a case of a known hypothyroid with very high thyroid stimulating hormone (TSH) values (512 μIU/mL) in the second trimester. At 24 weeks she developed facial palsy and pituitary hyperplasia which responded to a combination of steroids and thyroxine. She had caesarean delivery at 35 weeks and 3 days gestation in view of pre-eclampsia with severe features and was discharged on oral antihypertensives and thyroxine. On follow-up at 5 months, TSH normalised and pituitary hyperplasia showed a greater than 50% reduction in size. To our knowledge, this is the first reported case of facial palsy and pituitary hyperplasia associated with hypothyroidism during pregnancy.

Background

Hypothyroidism is the second most common endocrinopathy during pregnancy, and its incidence ranges from 2% to 5%¹ worldwide. Studies on Indian pregnant women have shown the incidence of hypothyroidism to range from 9.2% to 13.13%,^2–4 while that of overt hypothyroidism is 2.8%–3.97%.^{5 6}

Overt hypothyroidism during pregnancy is associated with an increased risk of anaemia, cardiac dysfunction, miscarriage, pre-eclampsia, placental abruption, premature birth, low birth weight and postpartum haemorrhage as well as detrimental effects on neurocognitive development of the fetus.⁷ To the best of literature search, this is the first report of the neurological manifestation of hypothyroidism in the mother during pregnancy.

Case presentation

A 32 years old G3P1L1A1, known hypertensive and hypothyroid for 5 years on irregular treatment, presented with a thyroid stimulating hormone (TSH) report of 512 μIU/mL (table 1) in second trimester of pregnancy. She developed superimposed pre-eclampsia at 20 weeks of gestation and was kept on close maternal and fetal surveillance. At 24 weeks, she developed left-sided facial palsy with deviation of angle of the mouth to right side and inability to completely close the left eyelid. In addition, she complained of headache significant enough to disturb her sleep.

Table 1.

Serial monitoring of thyroid function tests

Antepartum- Gestation (weeks)	TSH (μIU/mL) (normal range: 0.35–4)	T3 (ng/mL) (normal range: 0.58–1.59)	T4 (μg/dL) (normal range: 4.87–11.72)	Anti-thyroperoxidase (TPO) antibodies (IU/mL) (normal range: upto 30)
14	512			0.78
18	249
22	83.47
24	61.89	0.58	4.88
28	28.09	1.56	8.18
33	18.30	1.32	11.72
Postpartum
7 days	8.8
5 months	2.3

Investigations

MRI revealed a pituitary mass (figure 1A) with a normal visual perimetry. Repeat TSH was 61.89 μIU/mL and thyroid function tests were repeated serially to monitor and titrate thyroxine supplements (table 1). Foetal anomaly scan and serial growth scans were normal.

Figure 1.

(A) Pituitary mass (arrow pointing) 18×15 mm well-defined lesion. Normal pituitary not seen separately from mass. Sellar expansion present. Suprasellar extension present. Mass not abutting optic chiasma. No cavernous sinus involvement. (B) Greater than 50% reduction in size of pituitary mass (arrow pointing) on follow-up MRI.

Differential diagnosis

A multidisciplinary team comprising of obstetrician, endocrinologist, neurologist, neurosurgeon, radiologist, anaesthetist and neonatologist reviewed and followed the case. A differential diagnosis of either pituitary macroadenoma or reactive pituitary hyperplasia due to uncontrolled hypothyroidism was made.

Treatment

Since no mass effect was seen, as evident by a normal visual perimetry, and a likelihood of reactive pituitary hyperplasia amenable to thyroid hormone replacement therapy, a decision against neurosurgical intervention was made. Her thyroxine supplement dosage was escalated along with addition of oral steroids. Resolution of her symptoms began within a week and steroids were gradually tapered.

Outcome and follow-up

Complete resolution of symptoms occurred over 3–4 weeks. She was taken up for delivery by caesarean section at 35 weeks and 3 days in view of pre-eclampsia with severe features and delivered a 2.4 kg male baby with Apgar score of 9/9. Neonate was observed and showed no features of congenital hypothyroidism. She was discharged on oral antihypertensives and thyroxine supplements and her TSH level had fallen to 8 μIU/mL (table 1).

On follow-up after 5 months, the patient and her baby were asymptomatic, maternal TSH had normalised (table 1) and MRI showed a greater than 50% reduction in size of pituitary hyperplasia (figure 1B) confirming a diagnosis of hypothyroidism-induced pituitary hyperplasia.The patient is following up under endocrinology and the infant too has been kept under paediatric follow-up to assess the possible long-term effects on cognitive functions.

Discussion

Pituitary hyperplasia in primary hypothyroidism was recognised for the first time by Bernard Niepce in 1851 and since then been reported several times.^8–11 The incidence varies from 25% to 81%,^{8 9} high incidence (70%) is reported in patients with TSH levels ≥50 μIU/mL.^{9 10} However, this appears to be the first report showing this association during pregnancy.

Thyrotroph hyperplasia results from the lack of negative feedback inhibition due to reduced circulating levels of thyroid hormone causing overstimulation by TRH.⁸

Patients may be asymptomatic while 44% may suffer from headache and about 8% from visual problems.⁸ Distinction between pituitary hyperplasia and pituitary macroadenoma can be very challenging,⁹ more so in pregnancy. A definitive diagnosis can be made after evaluating response to therapy as, unlike adenoma, thyroid replacement therapy results in total or partial regression (62% and 29%, respectively)⁸ of pituitary hyperplasia. Hence, this differential diagnosis must be kept in mind, particularly in known hypothyroid, to avoid unnecessary surgery.⁹

There has been only five reported cases of association of facial palsy with hypothyroidism^12–15 and none to our knowledge during pregnancy. Facial nerve has a long intracranial course and traverses through a narrow bony canal. Hence, it is vulnerable to nerve entrapment due to soft tissue oedema in overt hypothyroidism and myxoedema resulting in facial palsy.^12–15 Hence, hypothyroidism as a cause of facial palsy should be kept as a differential diagnosis, especially in women not responding to steroids alone or those with uncontrolled hypothyroidism and other features of myxoedema.

Patient’s perspective.

(Translated from Hindi)

My thyroid problems were first detected 5 years back and I was advised tablets for it to be taken daily. Due to financial problems my medicine intake had been irregular and since I felt alright, I was not very concerned. When I learnt about my pregnancy, I stopped all medicines as I was unsure of their effects on my baby. When I visited the clinic, the doctor told that my thyroid problem had worsened and I was referred to higher centre where I was started on regular treatment. But my problems were far from over. I started having headache and distortion of my face at 6 months of my pregnancy which left me very scared, and when the doctors informed me that this could be associated with my thyroid problem I regretted not taking my medicines regularly earlier. After my thyroid medications were increased, I started feeling much better and my problems gradually subsided and I felt reassured. Looking back, I feel my whole pregnancy was a roller coaster ride. However, I am grateful that at the end of it all, I have a healthy baby and my health has also greatly improved.

Learning points.

• Management of uncontrolled hypothyroidism and its associated neurological manifestations in pregnancy can pose a significant challenge for obstetrician.

• Knowledge of this rarer association can help in early diagnosis and treatment of such cases, avoiding unnecessary surgery and other complications.

• A multidisciplinary approach is vital in such patients to obtain a favourable maternal and fetal outcome.

• Appropriate preconceptional counselling, early booking and adequate screening of known hypothyroid women can help avoid associated complications.