To the Editor: Mackenzie and Mortimer presented a useful review of the management of thyroid nodules and thyroid cancer.1 In their section on follow-up, they did not mention premature menopause — a clinically relevant side effect of radioactive iodine therapy which seems underinvestigated in the literature and not necessarily considered during post-radioiodine management. Its impact was highlighted by the recent general-practice presentation of a 42-year-old woman with a small thyroid nodule. She had been previously well except for a 5-year history of treated hypothyroidism secondary to Hashimoto’s thyroiditis. Investigation revealed a 2 cm papillary thyroid carcinoma, which was managed by total thyroidectomy and clearance of anterior-compartment cervical lymph nodes. Five of 21 nodes had deposits of papillary carcinoma. The patient was treated with a standard course of radioiodine.

She presented 6 weeks after completing the radioiodine therapy with sudden onset of symptoms of oestrogen deficiency (delayed menstruation, flushes, tiredness and vaginal dryness). Her menstrual cycle had been previously normal, and she had no family history of premature menopause. Investigations confirmed typical menopausal hormone levels (follicle stimulating hormone, 48 IU/L [menopausal range > 30 IU/L]; and oestradiol, < 150 pmol/L [menopausal range, 70–200 pmol/L]). Symptoms resolved after she began hormone replacement therapy.

A recent retrospective cohort study found that radioiodine treatment may predispose to early menopause.2 The patient had not been told of the possibility of this complication, and her surgeon was unaware of the link.

Two clinical lessons arise. The first is that discussion about premature menopause should be a routine part of pre-treatment counselling for women of late reproductive age contemplating thyroid ablation. Secondly, as hospitals and general practitioners are increasingly choosing to share care of patients with cancer,3 all stakeholders should consider the possibility in follow-up strategies.

In reply: As Russell indicates, there are suggestions in the medical literature that radioiodine ablation of thyroid remnants in women with thyroid cancer may be associated with temporary menstrual irregularity or premature menopause. The study he quotes is retrospective and does not take into account the periods of profound hypothyroidism that necessarily precede radioiodine treatment.1

The human oocyte appears to be relatively radioresistant, with an LD50 calculated at < 2 Gy. The ovarian dose from remnant ablation is much lower than this (32–162 mGy for a 4 GBq dose of radioiodine).2 However, it is possible that the ageing ovary is more radiosensitive. The article by Ceccarelli and colleagues,1 quoted by Russell, shows that the proportion of women with amenorrhoea in a group treated with radioiodine for thyroid cancer was identical to the proportion among controls up to the age of 47 years. The proportions then diverged so that, by the age of 51 years, 29% of treated women were still having menstrual cycles, compared with 49% of control women.

It is difficult to be sure that Russell’s 42-year-old patient had radioiodine-induced amenorrhoea. Her amenorrhoea may be temporary, and withdrawal of hormonal treatment may be warranted to investigate this.