|Year : 2017 | Volume
| Issue : 4 | Page : 265-267
A case of neonatal graves' Disease in a premature infant with negative thyrotropin stimulating antibodies
Sylvia Robinson1, Stelios Mantis2, Carla Zanatta Minutti2
1 University of Illinois at Chicago; Rush University Medical Center, Chicago, IL 60612, USA
2 Rush University Medical Center, Chicago, IL 60612, USA
|Date of Web Publication||17-Oct-2017|
Carla Zanatta Minutti
Rush University Medical Center, 1725 W. Harrison Street, Suite 710, Chicago, IL 60612
Source of Support: None, Conflict of Interest: None
Neonatal hyperthyroidism is a disorder usually caused by the passage of maternal thyrotropin receptor antibodies. Thyrotropin receptor antibodies can be stimulatory, neutral, or inhibitory. We present a case of neonatal hyperthyroidism in a preterm infant born to a mother with Graves' disease that was thyrotropin receptor stimulating antibody negative. Thyrotropin receptor blocking antibody levels were elevated. Anti-thyroid medication could only be weaned once thyrotropin blocking antibody levels significantly declined. We presume the clinical symptoms of hyperthyroidism in the infant were secondary to the interaction of thyrotropin blocking antibodies with the TSH receptor.
Keywords: Graves, hyperthyroidism, neonatal, thyroid blocking antibodies, thyroid stimulating antibodies
|How to cite this article:|
Robinson S, Mantis S, Minutti CZ. A case of neonatal graves' Disease in a premature infant with negative thyrotropin stimulating antibodies. J Clin Neonatol 2017;6:265-7
|How to cite this URL:|
Robinson S, Mantis S, Minutti CZ. A case of neonatal graves' Disease in a premature infant with negative thyrotropin stimulating antibodies. J Clin Neonatol [serial online] 2017 [cited 2020 Aug 12];6:265-7. Available from: http://www.jcnonweb.com/text.asp?2017/6/4/265/216904
| Introduction|| |
The cause of neonatal hyperthyroidism is almost always transient and related to the passage of maternal thyrotropin stimulating antibodies (TSAbs). Positive levels of TSAbs in the neonate are almost always diagnostic of neonatal Graves' disease.
| Case Report|| |
A 31-year-old G8P5 mother delivered a female infant at 27 4/7 weeks of gestational age weighing 827 g. The mother was diagnosed 2 weeks before delivery with Graves' disease, but medication was not initiated. Due to the maternal history of Graves' disease, the infant's thyroid function tests (TFTs) were obtained on day of life (DOL) 2. Laboratory workup showed a thyroid-stimulating hormone (TSH) of 0.009 uIU/mL and free T4 (FT4) of 1.4 ng/dL. TSAbs were negative. The infant was progressing as expected until DOL 7 when she developed tachycardia with a heart rate in 220 s. Repeat laboratory evaluation showed a TSH of 0.005 uIU/mL, FT4 of 4.3 ng/dL, and total triiodothyronine (T3) of 4.0 ng/dL (0.6–1.6). Methimazole (MMI) (0.4 mg/kg/day) and propranolol (0.5 mg/kg/day) were started. Four days after starting anti-thyroid medication, TSH was still low but FT4 normalized to 1.3 ng/dL and the tachycardia had resolved. By DOL 14, rising liver enzymes led to the discontinuation of MMI. On DOL 18 (4 days off MMI), the tachycardia recurred and FT4 was once again elevated to 4.7 ng/dL. Repeat levels of TSAb were negative with down-trending liver transaminases. MMI and propranolol were restarted at slightly lower doses than before (0.25 mg/kg/day and 0.4 mg/kg/day, respectively). Within 3 days, FT4 normalized to 1.3 ng/dL. Other laboratory studies revealed an elevated thyroglobulin level of 131.9 ng/mL (2.8–40.9), negative anti-thyroglobulin levels, and anti-thyroid peroxidase antibodies positive at 37.4 IU/mL (0.0–5.6). Thyrotropin blocking antibody (TBAb) levels were positive at 40% (normal <17%). Beta-blockers were discontinued, and the patient remained on MMI for approximately 3 weeks. FT4 levels remained normal, and the baby began to thrive. Thyroid levels were checked weekly, and she was allowed to outgrow her MMI dose. By DOL 45, MMI was discontinued. She had repeat TFTs a week later and was found to have a suppressed TSH of 0.013 uIU/mL and a normal FT4 of 1.3 ng/dL. Repeat levels of TBAb were decreased to 20%. She was restarted on MMI at a low dose of 0.1 mg/kg 3 times/week. The baby was then discharged home and seen in an outpatient clinic 1 week later. Repeat TFTs showed an improved TSH of 0.022 uIU/mL and a normal FT4 of 1.1 ng/dL. The MMI dose was then decreased to 0.1 mg/kg twice a week for 2 weeks. Her TSH was 0.225 uIU/mL, FT4 was 0.7 ng/dL, total T3 was 1.1 ng/dL, and TBAb remained at 20%. Her MMI was then discontinued, and she was lost to follow-up.
| Discussion|| |
Fetal and/or neonatal hyperthyroidism is a rare condition, and its incidence has been estimated around 1:4000–40000.
The most common causes are active maternal thyroid autoimmune disorders, such as Graves' disease and less frequently hypothyroidism due to Hashimoto's thyroiditis, where there is transplacental passage of TSAbs and/or TBAbs.,
These antibodies may continue to be produced after thyroidectomy, ablation of the thyroid by radioiodine or by the immune mechanisms of Hashimoto's thyroiditis. Therefore, even if mothers have been cured of Graves' disease, they may still transfer these antibodies transplacentally to their babies.
Neonatal Graves' disease tends to resolve spontaneously within 3–12 weeks as maternal thyrotropin receptor (TSHR) stimulating or blocking antibodies are cleared from the circulation.
Rarer nonautoimmune causes include activating mutations of the TSH receptor and activating mutations  of the stimulatory G protein in McCune–Albright syndrome.
TSHR antibodies can stimulate the thyroid receptor causing hyperthyroidism (TSAb) or block thyrotropin action and are occasionally responsible for hypothyroidism (TBAb); these antibodies can also be neutral (TNAb) and neither block or stimulate the receptor.
Unusual patients can switch from TSAb to TBAb (or vice versa) with concomitant thyroid function changes.
Most laboratories used to measure TSHR antibodies use assays that are not able to distinguish between TBAb, TSAb, or TNAb. Bioassays that measure TSAb activity based on cyclic adenosine monophosphate on cultured cells can be useful to distinguish between these antibodies. Our patient had normal TSAb levels measured by anin vitro bioassay. These bioassays have been adapted to detect the antagonistic immunoglobulins with blocking/inhibitory activity and to distinguish between the TBAb and TNAb. She also had positive TBAb measured by a radioreceptor assay.
It is important for the clinician to be aware of the different assays available to measure thyrotropin receptor antibodies, and of the nomenclature used to describe them, as this frequently reflects which assay is being performed by the laboratory.
TBAb to TSAb or TSAb to TBAb switching may occur in patients treated with levothyroxine (LT4), after anti-thyroid drug therapy or during pregnancy, and are well recognized in transient neonatal thyroid dysfunction.
The occurrence of “switching” emphasizes the need for careful patient monitoring and management.
The time course of thyrotoxicosis depends on etiology. Remission by 20 weeks is most common in neonatal Graves' disease; remission by 48 weeks is nearly always seen. A subset of these patients may have persistent disease when there is a strong family history of Graves' disease.
Hyperthyroid neonates may be treated with anti-thyroid drugs, beta-adrenergic receptor blocking agents, iodine or iodinated contrast agents, and at times glucocorticoids and digoxin. Nonremitting causes of neonatal hyperthyroidism require ablative treatments such as thyroidectomy.
A recent article recommends baseline screening for maternal TSH receptor antibodies.
If levels are negative, no specific neonatal follow-up is necessary; if unavailable or positive, the newborn is regarded as “at risk” for the development of hyperthyroidism.
| Conclusion|| |
This was an interesting case of TSAb-negative neonatal Graves' disease who was very sensitive to MMI. Soon after starting medication, her FT4 normalized almost immediately, and once MMI was held early in her course, her FT4 increased threefold in <72 h. We presume that this case of neonatal Graves' disease was caused by the interaction of TBAb with the TSH receptor. It was not until her TBAb levels declined significantly that MMI could be safely weaned off.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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