CASE REPORT

Thyroid hormone resistance and pregnancy

Simon Kane, Robert Fox*, Colin Close

Case report

A 31 year old nulliparous woman was seen in the an-

tenatal booking clinic at eight weeks of gestation. She had

developed a large goitre at age 7 and thyroid hormone

resistance had been diagnosed at age 12. Her father was

known to have thyroid hormone resistance. She had been

clinically euthyroid and had required no treatment. The

goitre had, however, gradually increased in size over time;

her neck circumference was 39.5 cm in 1992 and 41.5 cm

in September 1998. Genetic analysis had not yet been

performed on the family.

At eight weeks of gestation, she appeared clinically

euthyroid with a normal pulse rate. Biochemical tests

revealed an elevated concentration of free triiodothyronine

(FT3) at 9.8 pmol/L (normal range 3.5–6.5 pmol/L) and

free thyroxine (FT4) at 44.2 pmol/L (normal range 10.1–

20.9 pmol/L), with normal thyroid stimulating hormone

(TSH) at 0.8 mU/L (normal range 0.5–5.0 mU/L). These

levels were similar to those measured one year earlier

before her pregnancy. She remained well and asympto-

matic during her pregnancy. Thyroid function tests were

performed monthly. From 26 weeks of gestation, the serum

concentrations of FT3 and FT4 both fell and at 34 weeks of

gestation her triiodothyronine concentration was within the

normal range. At term she had a normal labour and vaginal

delivery of her baby son whose Apgar scores were 9 and 10

at 1 and 5 minutes, respectively, and who weighed 3.4 kg.

The infant had no evidence of thyroid enlargement and his

thyroid function tests were normal.

A few weeks after delivery, the goitre enlarged and she

experienced symptoms of obstruction to her airway. Her

neck circumference (measured by the same observer since

1992) was now 44 cm. Pulmonary function analysis (flow

volume loop) showed an inspiratory flow rate half that

recorded two years earlier in October 1988. Her thyroid

hormone concentration had returned to their pre-pregnancy

values: FT3 8.4 pmol/L, FT4 42.0 pmol/L and TSH

1.1 mU/L (Fig. 1). In view of the rapid onset of respiratory

symptoms, she underwent urgent total thyroidectomy. The

gland weighed 328 g (normal 20–25 g) and histological

analysis revealed nodular hyperplasia.

Discussion

Thyroid hormone resistance is a rare condition charac-

terised biochemically by elevated levels of free thyroid

hormones T3 and T4, together with an inappropriately

normal TSH concentration. The condition is usually the

result of a mutation in the T3 binding domain of the thyroid

hormone receptor h (TRh). Most reported cases of thyroid

hormone resistance with a TRh mutation have an autoso-

mal dominant inheritance1, but familial cases without

linkage to TRh have been described2, including one where

both TRh alleles were deleted3.

The TRh mutation leads to partial resistance of the

receptor to T3; usually both the peripheral tissues and the

pituitary thyrotrophs are resistant (generalised resistance),

so the secretion of TSH is uninhibited and its production is

inappropriate for the level of free thyroid hormones. The

TSH is usually in the normal reference range. Although

patients with thyroid hormone resistance have supraphysio-

logical concentrations of FT3 and FT4, most are clinically

euthyroid due to the peripheral tissue resistance. Typically,

the only clinical manifestation of the condition is the

presence of a large smooth goitre, which results from the

Fig. 1. Serum FT4, FT3 and TSH concentrations.

BJOG: an International Journal of Obstetrics and GynaecologyJune 2003, Vol. 110, pp. 633–634

D RCOG 2003 BJOG: an International Journal of Obstetrics and Gynaecology

doi:10.1016/S1470-0328(02)01692-0 www.bjog-elsevier.com

Departments of Obstetrics and Endocrinology/Diabetes,

Taunton & Somerset Hospital, Taunton, UK

* Correspondence: Dr R. Fox, Departments of Obstetrics and

Endocrinology, Taunton & Somerset Hospital, Taunton TA1 5DA, UK.

need for increased thyroid hormone production in order to

overcome the peripheral tissue resistance. However, a

small number of patients exhibit manifestations of hyper-

thyroidism, particularly tachycardia; in these patients the

resistance to T3 is largely confined to the thyrotrophs

(pituitary resistance), with relatively normal peripheral

tissue sensitivity.

Asymptomatic patients require no treatment, but those

with features of hyperthyroidism may require treatment

with drugs that inhibit TSH secretion, such as dextrothy-

roxine (D-T4) or 3,5,3V-triiodothyroacetic acid (TRIAC).

There have been two reports of the use of these drugs in

pregnancy4,5. D-T4 was used to assist fertility in one

woman with recurrent miscarriages and mild features of

hyperthyroidism and the drug was stopped after concep-

tion4. Another woman with pituitary thyroid hormone

resistance conceived while receiving TRIAC, discontinued

the drug, only to restart treatment at 20 weeks of gestation

due to a recurrence of hyperthyroidism5. Treatment with

thyroxine is sometimes indicated in children with thyroid

hormone resistance and growth retardation. Although the

goitre is often large, surgery is usually avoided because

thyroidectomy renders the patient hypothyroid and appro-

priate levels of thyroid hormone replacement can then be

difficult to determine.

There have been very few reports of the effect of thyroid

hormone resistance in pregnancy4 – 6 and none in women

with generalised resistance. This case demonstrates that

normal pregnancy and delivery are possible, but we feel it

is important to report the development of severe stridor after

delivery. Although it is not certain that the two events were

causally related, we recommend that women with thyroid

hormone resistance should be monitored for airway obstruc-

tion by analysis of flow–volume curves before and follow-

ing delivery. Serial measurement of thyroid hormone levels

during pregnancy in untreated thyroid hormone resistance

has not previously been reported. The woman in this case

report showed a remarkable reduction in circulating free

thyroid hormone levels during pregnancy. Physiologically,

serum concentrations of FT3 and FT4 rise in early preg-

nancy under the influence of hCG in women with normal

thyroid function, but several studies have reported that

levels of FT3 and TF4 are lower at delivery than in the

non-pregnant state7,8. The profound decrease in FT3 and

FT4 levels in this woman suggests that there may be some

factor increasing T3 receptor sensitivity in pregnancy.

References

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roid hormone. Endocr Rev 1993;14:348 –399.

2. Weiss R, Hayashi Y, Nagaya T, et al. Dominant inheritance of resist-

ance to thyroid hormone not linked to defects in the thyroid hormone

receptor alpha or beta genes may be due to a defective co-factor. J Clin

Endocrinol Metab 1996;81:4196–4223.

3. Takeda K, Sakurai A, DeGroot LJ, Refetoff S. Recessive inheritance

of thyroid hormone resistance caused by complete deletion of the pro-

tein-coding region of the thyroid hormone receptor-beta gene. J Clin

Endocrinol Metab 1992;74:49 –55.

4. Sarkissian G, Dace A, Mesmacque A, et al. A novel resistance to thy-

roid hormone associated with a new mutation (T329N) in the thyroid

hormone receptor h gene. Thyroid 1999;9:165– 171.

5. Asteria C, Rajanayagam O, Collingwood TN, et al. Prenatal diagnosis

of thyroid hormone resistance. J Clin Endocrinol Metab 1999;

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6. Furlanetto TW, Kopp P, Peccin S, Gu W, Jameson JL. A novel muta-

tion (M310L) in the thyroid hormone receptor h causing resistance to

thyroid hormone in a Brazilian kindred and a neonate. Mol Gen Metab

2000;71:520– 526.

7. Ball R, Freedman DB, Holmes JC, Midgley JEM, Sheehan CP.

Low-normal concentrations of free thyroxine in serum in late preg-

nancy: physiological fact, not detected artifact. Clin Chem 1989;

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8. Glinoer D, DeNayer P, Bourdoux P, et al. Regulation of maternal thy-

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Accepted 21 August 2002

CASE REPORT634

D RCOG 2003 Br J Obstet Gynaecol 110, pp. 633–634