Counselling of parents prior to the expected delivery of a preterm infant is a difficult, but important, part of a neonatologist’s workload. In an attempt to provide parents with consistent and up to date information, there is an outline of discussion points and current data that may be helpful to read through prior to the counselling. Of course, every discussion will be different, dependant on gestational age, the expected condition of the baby, the amount of information the mother/parents want and the questions they ask. A clear plan for delivery and care of the baby should be made and documented. This should be reviewed regularly. We are planning to audit parental feedback and assessment of the antenatal counselling. Please complete an audit form for each of the preterm delivery discussions you have with parents. Forms should be put into the folder in the neonatal unit.
Things to consider for discussion with parents prior to an expected preterm delivery
What might happen at the delivery
· Resuscitation (dependant on gestational age)
· Interventions
· Transfer of babies from Kingston <26 weeks/ when full · Comfort/ palliative care for babies not resuscitated (if appropriate) Expected/ possible problems for babies born preterm · Lungs:Ventilation/Surfactant/Oxygen · GI:Feeding / breastfeeding/ NGT/ TPN/NEC · Brain: IVH/ Cranial USS · ROP · Infections/Antibiotics · Haematology: Blood tests/Blood transfusion/Jaundice · Monitoring:monitoring equipment/Leads/incuabator/lines-UAC,UVC The neonatal unit · Visiting · Expected stay Not all parents want information on mortality/ morbidity but these are things that the doctor should be prepared to discuss if the parents request information. Other things to consider in discussion: · Steroid administration · Predicted fetal weight · Multiple pregnancies · Sex · IUGR · Sepsis · Fetal anomaly Parental factors Cultural Religious Medical Past obstetric history
The following information has been taken from ‘The Management of Babies born Extremely Preterm at less than 26 weeks of gestation: A Framework for Clinical Practice at the Time of Birth’ by the British Association of Perinatal Medicine.
Gestation <23 weeks
If the gestation is CERTAIN and less than 23 + 0, it would be considered in the best interests of the baby, and standard practice, for resuscitation not to be carried out. If parents wish, they should have the opportunity to discuss outcomes with a second senior member of the perinatal team.
Gestation 23+0 – 23+6
If gestation is certain at 23+ 0 - 23 + 6 week, and the fetal heart is heard during labour, a professional experienced in resuscitation should be available to attend the birth. In the best interests of the baby a decision not to start resuscitation is an appropriate approach particularly if the parents have expressed this wish. However, if resuscitation is started with lung inflation using a mask, the response of the heart rate will be critical in deciding whether to continue or to stop and sensitively explain to the parents the futility of further interventions.
The EPICure study (1995) reported in 2000 that at 23 weeks 121/241 (50%) of live born babies were admitted for intensive care of whom 105 (80%) died in hospital. 26 babies were discharged home, one died and 14 (54%) have a moderate or severe disability at 6 years.
Early findings in the EPICure 2 study (2006) show that at this gestational age survival has not increased significantly and there has been no change in early major morbidity.
Gestation 24+0 – 24+6
If gestational age is certain at 24 + 0 – 24 + 6 weeks, resuscitation should be commenced unless the parents and clinicians have considered that the baby will be born severely compromised. However the response of the heart rate to lung inflation using a mask will be critical in deciding whether to proceed to intensive care. If the baby is assessed to be more immature than expected, deciding not to start resuscitation may be considered in the best interest of the baby.
In the 1995 study, although 313/382 (78%) of babies born at this gestational age were given intensive care, 198 (66%) died. Half of the survivors (52) have a moderate or severe disability at 6 years. Early findings in the EPICure 2 study (2006) show that at this gestational age, survival has increases significantly by 12%. More babies were treated for retinopathy of prematurity but there is no evidence of any change in other early major morbidity.
23 weeks -- 10 to 35 % survival ----> than 50 % long-term disability
<5% long term disabilities
24 weeks -- 40 to 70 % survival ----- 25 to 50 % long-term disability
25 weeks - 50 to 80 % survival ---- 15 to 25 % long-term disability
26 weeks -- 80-90% survival ----- 10-25% long term disabilities
27-29weeks -- 90+% survival ---- 10% long term disabilities
30-33weeks -- 95+% survival ---- 5% long term disabilities
34-37weeks -- 98% survival <5% long term disabilities
25 Weeks and Greater
When the gestational age is 25 + 0 weeks or more, survival is now considerably greater than in 1995. It is appropriate to resuscitate babies a this gestation and, if the response is encouraging, to start intensive care.
In the 1995 study 389/424 (92%) babies born alive at 25 weeks were admitted for intensive care but 171 (48%) died. 27% of the survivors had no identifiable impairment at 6 years. In 2006 survival had increased significantly from 54% to 67% (by 13%), but there is no evidence or change in early major morbidity.
Audit form for Antenatal Counselling undertaken by Doctors
Please attach mother’s hospital sticker below
Counselled by
Date
Gestation at time of counselling
Time spent (mins)
Place
People present
Were the following areas discussed?
Resuscitation Infections
Lung development/ ventilation Total stay
Cr.USS/ IVH haematology
Feeding/ NGT/ TPN monitoring/lines
Monday 16 March 2009
Sunday 8 March 2009
Postpartum tachycardia
Postpartum tachycardia
1.Anaemia
Secondary to complicated delivery
-PPH
- Instrumental delivery
- Caesarean
- Difficulty in delivering placenta
2.Puerperal sepsis –
- UTI, Episiotomy, Wound infection, Endometritis,, Prolonged SROM, Prolonged labour
3.Pulmonary embolism
-ECG, CXR, Pulse O2, Doppler of lower limbs and pelvis
4.Postpartum thyroditis
- TFTs
5.Postpartum cardiomyopathy
- ECG, ECHO
Investigations
FBC, CRP,TFTs, MSU=C/S, LVS, ECG, CXR, T
Treatment
TEDs, LMWH
1.Anaemia
Secondary to complicated delivery
-PPH
- Instrumental delivery
- Caesarean
- Difficulty in delivering placenta
2.Puerperal sepsis –
- UTI, Episiotomy, Wound infection, Endometritis,, Prolonged SROM, Prolonged labour
3.Pulmonary embolism
-ECG, CXR, Pulse O2, Doppler of lower limbs and pelvis
4.Postpartum thyroditis
- TFTs
5.Postpartum cardiomyopathy
- ECG, ECHO
Investigations
FBC, CRP,TFTs, MSU=C/S, LVS, ECG, CXR, T
Treatment
TEDs, LMWH
ovarian torsion clinical presentation
Our patient is a 34-year-old G0P0 white female who presented with complaints of right lower quadrant pain. The pain began suddenly the morning of admission upon stepping out of the shower. She described it as sharp, constant, nonradiating, and graded it as 10 out of 10 in intensity. Although her pain persisted, she did note episodes of improvement, followed by exacerbation. Her pain was improved with sitting and aggravated with walking and lying supine. She noted associated anorexia, nausea and emesis, and several episodes of watery diarrhea. She denied fever, vaginal discharge, or bleeding from the vagina, bladder, or rectum. Our patient did not recall a similar pain in the past. She was sexually active, but not currently contracepting, and denied prior pelvic infection.
During physical examination, vital signs included a temperature of 37.3°C, blood pressure of 140/79, pulse of 92 bpm, and respirations of 16/min. She was an obese white female in moderate discomfort. Remarkable findings included marked right lower quadrant tenderness with associated guarding and rebound tenderness. The remainder of her abdomen had generally mild tenderness with palpation. Bowel sounds were present and normal. No gross distension or fluid wave was appreciated.
Laboratory evaluation included a β-hCG assay with negative results, hemoglobin level of 14.8, and white blood cell count of 15,300. Liver function tests and electrolytes levels were within normal range. Her urine contained trace ketones, but no blood, leukocytes, or nitrites were noted. A vaginal smear was obtained and revealed no pathogens or increased leukocytes. Swabs of the endocervix for Neisseria gonorrhoeae and Chlamydia trachomatis were taken.
Radiologic evaluation included a sonogram, which showed an anteverted uterus of normal dimensions with normal myometrium and endometrium. Her right ovary was not seen and her left ovary contained a 3-cm simple cyst.
Based on her examination, the General Surgery service was consulted to evaluate her for possible appendicitis. During their evaluation, a computed tomography scan was obtained. It showed a 10 x 8 x 7 cm cystic structure with septations, either contiguous with or adjacent to the right ovary. The left ovarian simple cyst persisted, and the appendix was deemed normal.
With these findings, our patient was consented for diagnostic laparoscopy to evaluate a probably torsed adnexa. Upon placement of the laparoscope, a large purple cystic mass was seen. Due to its large size, laparotomy was planned to further evaluate the mass.
Upon reaching the pelvis, the enlarged, cyanotic, cystic mass was elevated (See Figure 1). It was identified as the right tube and ovary. Hemorrhage into the fallopian tube had created a cyanotic cyst with fimbria stretched across the cyst surface (Figure 2). Investigation of the vascular supply to these organs revealed torsion (Figure 3). The vascular pedicle was untwisted, but failed to show signs of reperfusion. Right salpingoophorectomy was performed, and the specimen was sent to pathology for further examination (Figure 4).
Discussion:
As noted in Chapter 9, adnexal torsion is more common in the reproductive years, and 70 percent of cases are in women aged 20 to 39 years. In cases of torsion, the tube and ovary are typically involved, although isolated torsion of the tube or ovary may be less commonly found. Classically, pathologic enlargement of an ovary serves to increase ovarian dimension and increase the risk for torsion. Indeed, most cases involve ovarian masses measuring 6 to 10 cm. However, the genesis of torsion in our patient is unclear, as our patient’s involved ovary appeared normal size.
Our patient was classical in her clinical presentation. Her pain waxed and waned, localized to one side, and was associated with nausea and vomiting. In many cases, low-grade fever may point to adnexal necrosis, although our patient was afebrile. However, her elevated WBC of 15,000 resulted from her necrotic tube and ovary.
During surgery, detorsion of the adnexa is reasonable. Previous concerns that untwisting would lead to pulmonary embolism have been refuted. Thus, detorsion of the adnexa is generally recommended to evaluate organ reperfusion and viability. If the adnexa fails to perfuse following untwisting of the vascular pedicle, then removal of the involved structures is recommended.
Hyperthyrodism in pregnancy
Thyrotoxicosis and Pregnancy
Petros Perros
Competing Interests: The author declares that no competing interests exist.
Citation: Perros P (2005) Thyrotoxicosis and Pregnancy. PLoS Med 2(12): e370 doi:10.1371/journal.pmed.0020370
Published: December 27, 2005
Copyright: © 2005 Petros Perros. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abbreviations: 131I, radioiodine; TAO, thyroid-associated ophthalmopathy; TMNG, toxic multinodular goitre; TPO, thyroid peroxidase; TSH, thyroid-stimulating hormone
Petros Perros is in the Endocrine Unit, Freeman Hospital, Newcastle upon Tyne, United Kingdom. E-mail: petros.perros@ncl.ac.uk
The Learning Forum section editors are Susan Lightman and William Lynn.
--------------------------------------------------------------------------------
DESCRIPTION of CASE
A 35-year-old woman became aware of a swelling in her neck about ten weeks before referral. She had been trying to conceive for ten months. She had had a missed abortion five months earlier. Because of the neck swelling, her family doctor arranged thyroid function tests, which were in the thyrotoxic range on two occasions five weeks apart: serum free thyroxine, 26 and 28 pmol/l (normal range, 11–23); serum free tri-iodothyronine, 10.9 and 11 pmol/l (normal range, 3.5–6.5); serum thyroid-stimulating hormone (TSH), <0.05 mU/l (normal range, 0.3–4.1).
Her previous medical history included a partial thyroidectomy for thyrotoxicosis at the age of 24. Other than a goitre, she had no symptoms except increased appetite and a slight tremor, which she had been aware of for about eight weeks. Following the missed abortion, she had two normal menstrual periods. Her only medication was folic acid supplements. She worked part-time and had a two-and-a-half-year-old child.
On examination she was of average weight. Her hands were warm and moist. There was a fine tremor. A previous thyroidectomy scar was noted. The right lobe of the thyroid was palpable and felt smooth. There was a bruit over the right thyroid lobe on auscultation. She had lid retraction and lid lag but no other signs suggestive of thyroid-associated ophthalmopathy (TAO) (Figure 1). Her pulse rate was 100 beats per minute and regular. Her blood pressure was 150/70 mm Hg. The rest of the examination was normal.
Figure 1. The Patient's Appearance at the Time of Presentation with Recurrent Thyrotoxicosis
Note that there are no signs of TAO, but the patient has minimal upper lid retraction (the upper lid should normally be halfway between the limbus and the pupil).
What Is the Cause of Her Thyrotoxicosis?
Thyrotoxicosis is no more than a descriptor for a pattern of biochemical abnormalities. Before considering treatment, it is the clinician's task to define the underlying cause, as an accurate diagnosis is an essential guide to the most appropriate treatment (Box 1).
The most likely causes in this case were Graves disease, thyroiditis, toxic multinodular goitre (TMNG), and toxic adenoma. The hallmark of TMNG or toxic adenoma is the presence of one or more palpable thyroid nodules. In this case the patient had previously undergone a partial thyroidectomy and a vascular thyroid remnant was palpable on the right thyroid lobe. Post-partum thyroiditis occurs within 12 months of childbirth; a variant of this condition occurs after miscarriage. In this patient's case post-partum thyroiditis was unlikely because her previous pregnancy was 2.5 years earlier; however, the miscarriage five months earlier may have been relevant. Viral thyroiditis is usually preceded by an upper respiratory tract infection and the thyroid gland is tender to touch; the absence of these features makes viral thyroiditis unlikely. “Silent” thyroiditis may present in this way and was a possibility here.
Laboratory tests that may help differentiate between the different causes of thyrotoxicosis include a radiolabelled technetium or iodide thyroid scan (Figure 2), and measurement of anti–thyroid peroxidase (TPO) antibodies, TSH receptor antibodies, and inflammatory markers (Table 1). The thyrotoxic phase of thyroiditis is usually followed by spontaneous euthyroidism and in some cases hypothyroidism. Repeating thyroid function tests within a few weeks of the first set may identify cases of thyroiditis.
Figure 2. Technetium 99 Thyroid Uptake Scans
(A) Normal.
(B) Graves disease: diffuse increased uptake in both thyroid lobes.
(C) TMNG: “hot” and “cold” areas of uneven uptake.
(D) Toxic adenoma: increased uptake in a single nodule with suppression of the surrounding thyroid.
(E) Thyroiditis: decreased or absent uptake.
(Image: Giovanni Maki)
Table 1. Diagnostic Tests for Identifying the Cause of Thyrotoxicosis
In this case the prolonged time course of thyrotoxicosis, the presence of a vascular thyroid remnant, the persistently thyrotoxic thyroid function tests, and the elevated serum levels of TSH receptor antibodies (62 U/l; reference range, 0–10) were in favour of a diagnosis of recurrent Graves disease.
What Are the Effects of Thyrotoxicosis on Fertility and Risk of Abortion?
Menstrual irregularities occur in about 20% of thyrotoxic women [1]. Infertility is common in women with thyrotoxicosis even when they maintain ovulatory cycles [1]. Thyrotoxicosis also increases the risk of miscarriage to 26% [2].
How Should This Patient Be Treated?
There are three treatment options for thyrotoxicosis due to Graves disease: radioiodine (131I) therapy, thyroidectomy, and anti-thyroid drugs [3]. 131I therapy is safe and effective, but pregnancy should be deferred for 4–6 months after treatment as there are theoretical risks of fetal abnormalities. Most national regulatory authorities recommend avoidance of close contact with adults for a few days and with children and pregnant women for 2–3 weeks. 131I therapy was not appropriate for this patient because she wished to proceed with pregnancy as soon as possible and she had a two-and-a-half-year-old child, who would be difficult to care for after 131I therapy.
A second thyroidectomy is worthy of consideration, but involves general anaesthesia and a period of recuperation of a few weeks and therefore disruption of family and professional life. The risks of damage to the recurrent laryngeal nerves and parathyroid glands after a second thyroidectomy are considerably greater than after a first operation and are of the order of 5%–10%. Because of these considerations, thyroidectomy was not felt to be a suitable option.
Anti-thyroid drugs (carbimazole, methimazole, and propylthiouracil) restore euthyroidism within a few weeks of initiation of treatment [4]. Minor side effects (such as skin rashes) occur in about 5% of cases. Agranulocytosis is rare (0.4%), but the consequences are life threatening and all patients on anti-thyroid drugs must be made aware of this complication (Box 2). All anti-thyroid drugs have been used and are acceptable in pregnancy.
Congenital anomalies have been reported in association with anti-thyroid drugs, but the increase in risk above background is very marginal. The risks of aplasia cutis and choanal and oesophageal atresia may be slightly lower with propylthiouracil than with other anti-thyroid drugs (choanal and oesophageal atresia, scalp defects, minor facial anomalies, and psychomotor delay compose an embryopathy implicated with methimazole use). But because the evidence is inconclusive and the additional risk minimal, all three drugs are widely used in pregnancy. The lowest dose of anti-thyroid drug that maintains euthyroidism should be used in women who wish to become or are already pregnant, in order to avoid fetal hypothyroidism and fetal goitre formation.
In this case propylthiouracil was used initially, at a dose of 50 mg four times per day. The patient was advised to take contraceptive measures until euthyroidism. Four weeks later her thyroid function tests had improved: serum free thyroxine, 13 pmol/l; serum total tri-iodothyronine, 2.5 nmol/l (normal range, 1.34–2.73); serum TSH, <0.05 mU/l. The dose of propylthiouracil was reduced to 25 mg four times per day, and the patient was advised that she could start trying to conceive.
What Are the Risks of TAO?
TAO is a complication that many patients fear. It can be disfiguring and difficult to treat [3]. If there are no clinical features of TAO at presentation, the risk of developing it in future is approximately 15%. Smoking is an important predisposing factor. As this patient was a non-smoker the probability of developing TAO is less than 10%.
What Monitoring Is Required during Pregnancy?
The dose of anti-thyroid drug usually needs to be decreased during pregnancy, and often Graves disease remits completely and the medication can be withdrawn. This is probably due to the overall immunosuppressive effect of pregnancy.
Monitoring of free thyroid hormone concentrations is of paramount importance during pregnancy and should be performed every 4–6 weeks, or more frequently if thyroid status is changing. The biochemical target is to achieve and maintain maternal serum free thyroxine levels at or slightly above the upper limit of normal, using the lowest dose of anti-thyroid drug possible. TSH receptor antibodies should be measured in the third trimester because positivity is predictive of neonatal thyrotoxicosis [5].
When the mother (as in this case) has a functioning thyroid gland or remnant in situ, maternal thyroid function mirrors that of the fetus. If there are concerns about fetal thyrotoxicosis (e.g., because maternal hyperthyroidism proves difficult to control), fetal heart rate monitoring should be undertaken. A persistent fetal tachycardia greater than 160 beats per minute is suggestive of fetal thyrotoxicosis. In cases where fetal thyrotoxicosis is diagnosed, monitoring of fetal growth and fetal goitre by ultrasound is imperative. In most cases the fetus can be treated satisfactorily by adjusting the dose of anti-thyroid drug in the mother and by following the fetal response clinically and by ultrasound.
What Are the Risks to the Fetus in a Woman with Graves Disease?
Poor control of maternal hyperthyroidism is associated with significant obstetric complications including miscarriage (26%), low birth weight, prematurity, (pre-)eclampsia, and possibly congenital malformations [6]. After the fetal thyroid matures (from 20 weeks of gestation onwards), maternal TSH receptor antibodies may act on the fetal thyroid to cause fetal thyrotoxicosis and goitre. The risk of fetal thyrotoxicosis is about 1% of all pregnancies in women with Graves disease, and if untreated, fetal mortality may be as high as 24%. Overtreatment may lead to hypothyroidism in the fetus, which is associated with subtle neurocognitive deficits later on in life, particularly if the hypothyroidism occurs in the first trimester [7]. Fetal goitre can develop as a result of fetal thyrotoxicosis or fetal hypothyroidism and in severe cases can obstruct labour.
What Are the Risks of Recurrence of Thyrotoxicosis after Delivery?
The risk of relapse of maternal thyrotoxicosis is high in the post-partum period (up to 80%), and close monitoring is required. Anti-thyroid drugs can be used safely during breastfeeding [8].
Prenatal Counselling of Women with Graves Disease
Pregnancy is a common concern among women of childbearing age who are receiving treatment for Graves disease. Some women may elect to have definitive treatment before pregnancy, which can be either a thyroidectomy or 131I therapy. The advantage of these treatment options is that the risk of maternal thyrotoxicosis during pregnancy is reduced, if not eliminated. Fertility is not affected by 131I therapy for thyrotoxicosis, but pregnancy should be deferred for 4–6 months after 131I therapy, although the basis of this recommendation is largely empirical. The risk of fetal and neonatal thyrotoxicosis is not eliminated by previous thyroidectomy or 131I therapy. The most important advice to women who have a previous history of thyroid dysfunction is to work with their practitioner to ensure that thyroid function tests are normal at the time of conception and throughout pregnancy.
DISCUSSION
Aetiology of Graves Disease
Graves disease is an autoimmune condition and is mediated by stimulatory autoantibodies to the TSH receptor. There is a significant genetic component to the aetiology of Graves disease, although environmental factors and stress also seem to confer risk [3]. Typically, the thyroid gland of patients with Graves disease is diffusely enlarged and vascular.
Toxic Multinodular Goitre
TMNG may also run in families. The pathogenesis is unknown. The disease begins with the formation of a single or few colloid nodules, and over a period of several years these become larger and more numerous. Some nodules are functioning and gradually acquire autonomy. With the passage of time serum TSH declines and may become undetectable until at a later stage serum free thyroid hormones rise. The hyperthyroidism of TMNG is usually mild and tends to occur in middle life or later. Toxic adenomas are benign neoplasms of the thyroid that are autonomous. In some cases they arise because of somatic mutations that lead to constitutive activation of the TSH receptor. As with TMNG, the hyperthyroidism tends to be mild.
Thyroiditis
Thyroiditis is due to an inflammatory process affecting the thyroid epithelium. Unlike other causes of thyrotoxicosis, there is no increased synthesis of thyroid hormones; instead, stored thyroid hormones in colloid are released into the circulation because of the leaky epithelium. The thyrotoxic phase of thyroiditis may be followed by a hypothyroid phase a few weeks later, but as a rule the patient recovers and euthyroidism ensues without any intervention.
Thyroiditis may occur after a viral infection (referred to as subacute or De Quervain thyroiditis), in which case the patient typically has a viral sore throat, the thyroid is tender, and inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) are raised. “Silent” thyroiditis is autoimmune and characterised by positive anti-TPO antibodies.
Investigating the Cause of Thyrotoxicosis
In many cases of thyrotoxicosis the aetiology will be apparent from information that can be obtained from the history and clinical examination. In cases where there is doubt, additional investigations are indicated. Direct measurement of TSH receptor antibody levels is not widely available, but can be very valuable as modern assays are highly sensitive and specific. TSH receptor antibodies can occasionally be positive in post-partum thyroiditis (this seems to be particularly rare in Europe, though reported in North America and Japan), and in cases of doubt a thyroid scan showing no uptake of radioisotope is diagnostic of thyroiditis [9]. TSH receptor antibody measurement is indicated in pregnancy to assess the risks of fetal and neonatal thyrotoxicosis. Anti-TPO antibodies occur in a significant proportion of the normal population, and this limits the use of this test. High concentrations of anti-TPO antibodies are present in silent and post-partum thyroiditis. Radioisotope scans are useful in identifying the cause of thyrotoxicosis (Figure 2), but should be avoided in pregnancy.
Treatment of Thyrotoxicosis
The treatment of thyrotoxicosis depends on the underlying cause. Anti-thyroid drugs are effective in Graves disease, TMNG, and toxic adenoma (Table 2), but not in thyroiditis because the latter is not associated with increased de novo synthesis of thyroid hormones.
Table 2. Response of Common Causes of Thyrotoxicosis to 131I Therapy and Anti-Thyroid Drugs
After a course of anti-thyroid drug treatment, remission may be expected in Graves disease as a result of the immunosuppressive effect of anti-thyroid drugs on synthesis of TSH receptor antibodies, but relapse is the rule in cases of TMNG or toxic adenoma.
131I therapy is effective for Graves disease, TMNG, and toxic adenoma. 131I therapy is ineffective in thyroiditis because iodine uptake is reduced or absent in this condition (Figure 2). Most patients with Graves disease develop permanent hypothyroidism after 131I therapy, whereas most patients with TMNG and toxic adenoma do not. 131I therapy is associated with a small risk of exacerbation of new development of TAO, particularly in smokers.
Thyroiditis may require symptomatic treatment with beta blockers during the thyrotoxic phase.
The type of thyroidectomy (subtotal versus total) for Graves disease as primary treatment has been the subject of controversy for some years. The argument in favour of total thyroidectomy is that the risk of recurrence of the thyrotoxicosis is eliminated, and that if performed by skilled thyroid surgeons the probability of hypoparathyroidism and vocal cord palsy is no greater than for a subtotal thyroidectomy [10]. A subtotal thyroidectomy, on the other hand, provides the best chance of any treatment for Graves disease for long-term euthyroidism without the need for thyroxine or other treatments for thyrotoxicosis.
The choice of treatment for Graves disease should be tailored to the needs of the individual patient, but also depends on local facilities, surgical expertise, and patient choice.
Box 1. Causes of Thyrotoxicosis
Common causes of thyrotoxicosis in a young female
Graves disease
Thyroiditis
Toxic multinodular goitre
Toxic adenoma
Iodine excess
Other rare causes of thyrotoxicosis
Hyperemesis gravidarum
Choriocarcinoma
TSH-producing pituitary adenoma
Iatrogenic thyrotoxicosis
Factitious thyrotoxicosis
Struma ovarii
Metastatic follicular thyroid cancer
Thyroid hormone resistance syndrome
Box 2. Patient Information Leaflet Used by the Author to Remind Patients Receiving Anti-Thyroid Drugs of the Potential Complication of Agranulocytosis
“You have been started on a drug called Carbimazole/Methimazole/Propylthiouracil to control the activity of your thyroid gland. This is important treatment and Carbimazole/Methimazole/Propylthiouracil is a well established drug that has been used for many years. The great majority of people treated with Carbimazole/Methimazole/Propylthiouracil have no problems whatsoever.
“Some people occasionally develop a rash—if this happens please consult your doctor as soon as possible; you need not discontinue the drug unless he/she tells you to do so.
“More rarely, Carbimazole/Methimazole/Propylthiouracil affects white cells in the blood, in which case you would be likely to develop a very severe sore throat and to feel ill with a fever. If this happens while you are on Carbimazole/Methimazole/Propylthiouracil treatment you must attend either your family doctor or the hospital on the same day, to have your blood count checked. Take no more tablets until the blood count has been checked. If your white blood count is normal you can carry on with the Carbimazole/Methimazole/Propylthiouracil. If your white blood count is abnormal your family doctor or the hospital will need to deal with this problem urgently.
“Please keep this with you in case you need to show it to your doctor.”
Learning Points
Thyrotoxicosis is not a diagnosis, merely a biochemical result. An accurate clinical diagnosis encompassing the aetiology is imperative for optimal management.
The most common cause of thyrotoxicosis in women of childbearing age is Graves disease.
Thyrotoxicosis impairs fertility, and thyroid status should be assessed in women with secondary infertility or recurrent abortions.
Three treatments are available for thyrotoxicosis due to Graves disease: anti-thyroid drugs, 131I therapy, and thyroidectomy. The right treatment is that which suits the patient's individual circumstances best.
131I therapy is an absolute contraindication in pregnancy. Anti-thyroid drugs may be used safely, and the dose should be titrated to the minimum dose that maintains normal maternal thyroid hormone levels.
The hyperthyroidism of Graves disease usually remits after the first trimester, and anti-thyroid drugs can be withdrawn; however, relapse of maternal thyrotoxicosis in the post-partum period is common.
Uncontrolled maternal hyperthyroidism can lead to fetal thyrotoxicosis with devastating effects on the fetus. Fetal thyrotoxicosis can be treated satisfactorily by appropriate manipulation of the maternal dose of anti-thyroid drug and careful fetal monitoring.
Krassas GE, Perros P (2002) Reproductive function in patients with thyroid diseases. Hot Thyroidology 2. Available: http://www.hotthyroidology.com/editorial_83.html. Accessed 12 October 2005.
Abramson J, Stagnaro-Green A (2001) Thyroid antibodies and fetal loss: An evolving story. Thyroid 11:57–63. Find this article online
Weetman AP (2000) Graves' disease. N Engl J Med 26 343:1236–1248. Find this article online
Cooper DS (2005) Antithyroid drugs. N Engl J Med 352:905–917. Find this article online
Laurberg P, Nygaard B, Glinoer D, Grussendorf M, Orgiazzi J (1998) Guidelines for TSH-receptor antibody measurements in pregnancy: Results of an evidence-based symposium organized by the European Thyroid Association. Eur J Endocrinol 139:584–586. Find this article online
Davis LE, Lucas MJ, Hankins GD, Roark ML, Cunningham FG (1989) Thyrotoxicosis complicating pregnancy. Am J Obstet Gynecol 160:63–70. Find this article online
Pop VJ, Vulsma T (2005) Maternal hypothyroxinaemia during (early) gestation. Lancet 365:1604–1606. Find this article online
American Academy of Pediatrics Committee on Drugs. (2001) Transfer of drugs and other chemicals into human milk. Pediatrics 108:776–789. Find this article online
Muller AF, Drexhage HA, Berghout A (2001) Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: Recent insights and consequences for antenatal and postnatal care. Endocr Rev 22:605–630. Find this article online
Palit TK, Miller CC 3rd, Miltenburg DM (2000) The efficacy of thyroidectomy for Graves' disease: A meta-analysis. J Surg Res 90:161–165. Find this article online
Petros Perros
Competing Interests: The author declares that no competing interests exist.
Citation: Perros P (2005) Thyrotoxicosis and Pregnancy. PLoS Med 2(12): e370 doi:10.1371/journal.pmed.0020370
Published: December 27, 2005
Copyright: © 2005 Petros Perros. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abbreviations: 131I, radioiodine; TAO, thyroid-associated ophthalmopathy; TMNG, toxic multinodular goitre; TPO, thyroid peroxidase; TSH, thyroid-stimulating hormone
Petros Perros is in the Endocrine Unit, Freeman Hospital, Newcastle upon Tyne, United Kingdom. E-mail: petros.perros@ncl.ac.uk
The Learning Forum section editors are Susan Lightman and William Lynn.
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DESCRIPTION of CASE
A 35-year-old woman became aware of a swelling in her neck about ten weeks before referral. She had been trying to conceive for ten months. She had had a missed abortion five months earlier. Because of the neck swelling, her family doctor arranged thyroid function tests, which were in the thyrotoxic range on two occasions five weeks apart: serum free thyroxine, 26 and 28 pmol/l (normal range, 11–23); serum free tri-iodothyronine, 10.9 and 11 pmol/l (normal range, 3.5–6.5); serum thyroid-stimulating hormone (TSH), <0.05 mU/l (normal range, 0.3–4.1).
Her previous medical history included a partial thyroidectomy for thyrotoxicosis at the age of 24. Other than a goitre, she had no symptoms except increased appetite and a slight tremor, which she had been aware of for about eight weeks. Following the missed abortion, she had two normal menstrual periods. Her only medication was folic acid supplements. She worked part-time and had a two-and-a-half-year-old child.
On examination she was of average weight. Her hands were warm and moist. There was a fine tremor. A previous thyroidectomy scar was noted. The right lobe of the thyroid was palpable and felt smooth. There was a bruit over the right thyroid lobe on auscultation. She had lid retraction and lid lag but no other signs suggestive of thyroid-associated ophthalmopathy (TAO) (Figure 1). Her pulse rate was 100 beats per minute and regular. Her blood pressure was 150/70 mm Hg. The rest of the examination was normal.
Figure 1. The Patient's Appearance at the Time of Presentation with Recurrent Thyrotoxicosis
Note that there are no signs of TAO, but the patient has minimal upper lid retraction (the upper lid should normally be halfway between the limbus and the pupil).
What Is the Cause of Her Thyrotoxicosis?
Thyrotoxicosis is no more than a descriptor for a pattern of biochemical abnormalities. Before considering treatment, it is the clinician's task to define the underlying cause, as an accurate diagnosis is an essential guide to the most appropriate treatment (Box 1).
The most likely causes in this case were Graves disease, thyroiditis, toxic multinodular goitre (TMNG), and toxic adenoma. The hallmark of TMNG or toxic adenoma is the presence of one or more palpable thyroid nodules. In this case the patient had previously undergone a partial thyroidectomy and a vascular thyroid remnant was palpable on the right thyroid lobe. Post-partum thyroiditis occurs within 12 months of childbirth; a variant of this condition occurs after miscarriage. In this patient's case post-partum thyroiditis was unlikely because her previous pregnancy was 2.5 years earlier; however, the miscarriage five months earlier may have been relevant. Viral thyroiditis is usually preceded by an upper respiratory tract infection and the thyroid gland is tender to touch; the absence of these features makes viral thyroiditis unlikely. “Silent” thyroiditis may present in this way and was a possibility here.
Laboratory tests that may help differentiate between the different causes of thyrotoxicosis include a radiolabelled technetium or iodide thyroid scan (Figure 2), and measurement of anti–thyroid peroxidase (TPO) antibodies, TSH receptor antibodies, and inflammatory markers (Table 1). The thyrotoxic phase of thyroiditis is usually followed by spontaneous euthyroidism and in some cases hypothyroidism. Repeating thyroid function tests within a few weeks of the first set may identify cases of thyroiditis.
Figure 2. Technetium 99 Thyroid Uptake Scans
(A) Normal.
(B) Graves disease: diffuse increased uptake in both thyroid lobes.
(C) TMNG: “hot” and “cold” areas of uneven uptake.
(D) Toxic adenoma: increased uptake in a single nodule with suppression of the surrounding thyroid.
(E) Thyroiditis: decreased or absent uptake.
(Image: Giovanni Maki)
Table 1. Diagnostic Tests for Identifying the Cause of Thyrotoxicosis
In this case the prolonged time course of thyrotoxicosis, the presence of a vascular thyroid remnant, the persistently thyrotoxic thyroid function tests, and the elevated serum levels of TSH receptor antibodies (62 U/l; reference range, 0–10) were in favour of a diagnosis of recurrent Graves disease.
What Are the Effects of Thyrotoxicosis on Fertility and Risk of Abortion?
Menstrual irregularities occur in about 20% of thyrotoxic women [1]. Infertility is common in women with thyrotoxicosis even when they maintain ovulatory cycles [1]. Thyrotoxicosis also increases the risk of miscarriage to 26% [2].
How Should This Patient Be Treated?
There are three treatment options for thyrotoxicosis due to Graves disease: radioiodine (131I) therapy, thyroidectomy, and anti-thyroid drugs [3]. 131I therapy is safe and effective, but pregnancy should be deferred for 4–6 months after treatment as there are theoretical risks of fetal abnormalities. Most national regulatory authorities recommend avoidance of close contact with adults for a few days and with children and pregnant women for 2–3 weeks. 131I therapy was not appropriate for this patient because she wished to proceed with pregnancy as soon as possible and she had a two-and-a-half-year-old child, who would be difficult to care for after 131I therapy.
A second thyroidectomy is worthy of consideration, but involves general anaesthesia and a period of recuperation of a few weeks and therefore disruption of family and professional life. The risks of damage to the recurrent laryngeal nerves and parathyroid glands after a second thyroidectomy are considerably greater than after a first operation and are of the order of 5%–10%. Because of these considerations, thyroidectomy was not felt to be a suitable option.
Anti-thyroid drugs (carbimazole, methimazole, and propylthiouracil) restore euthyroidism within a few weeks of initiation of treatment [4]. Minor side effects (such as skin rashes) occur in about 5% of cases. Agranulocytosis is rare (0.4%), but the consequences are life threatening and all patients on anti-thyroid drugs must be made aware of this complication (Box 2). All anti-thyroid drugs have been used and are acceptable in pregnancy.
Congenital anomalies have been reported in association with anti-thyroid drugs, but the increase in risk above background is very marginal. The risks of aplasia cutis and choanal and oesophageal atresia may be slightly lower with propylthiouracil than with other anti-thyroid drugs (choanal and oesophageal atresia, scalp defects, minor facial anomalies, and psychomotor delay compose an embryopathy implicated with methimazole use). But because the evidence is inconclusive and the additional risk minimal, all three drugs are widely used in pregnancy. The lowest dose of anti-thyroid drug that maintains euthyroidism should be used in women who wish to become or are already pregnant, in order to avoid fetal hypothyroidism and fetal goitre formation.
In this case propylthiouracil was used initially, at a dose of 50 mg four times per day. The patient was advised to take contraceptive measures until euthyroidism. Four weeks later her thyroid function tests had improved: serum free thyroxine, 13 pmol/l; serum total tri-iodothyronine, 2.5 nmol/l (normal range, 1.34–2.73); serum TSH, <0.05 mU/l. The dose of propylthiouracil was reduced to 25 mg four times per day, and the patient was advised that she could start trying to conceive.
What Are the Risks of TAO?
TAO is a complication that many patients fear. It can be disfiguring and difficult to treat [3]. If there are no clinical features of TAO at presentation, the risk of developing it in future is approximately 15%. Smoking is an important predisposing factor. As this patient was a non-smoker the probability of developing TAO is less than 10%.
What Monitoring Is Required during Pregnancy?
The dose of anti-thyroid drug usually needs to be decreased during pregnancy, and often Graves disease remits completely and the medication can be withdrawn. This is probably due to the overall immunosuppressive effect of pregnancy.
Monitoring of free thyroid hormone concentrations is of paramount importance during pregnancy and should be performed every 4–6 weeks, or more frequently if thyroid status is changing. The biochemical target is to achieve and maintain maternal serum free thyroxine levels at or slightly above the upper limit of normal, using the lowest dose of anti-thyroid drug possible. TSH receptor antibodies should be measured in the third trimester because positivity is predictive of neonatal thyrotoxicosis [5].
When the mother (as in this case) has a functioning thyroid gland or remnant in situ, maternal thyroid function mirrors that of the fetus. If there are concerns about fetal thyrotoxicosis (e.g., because maternal hyperthyroidism proves difficult to control), fetal heart rate monitoring should be undertaken. A persistent fetal tachycardia greater than 160 beats per minute is suggestive of fetal thyrotoxicosis. In cases where fetal thyrotoxicosis is diagnosed, monitoring of fetal growth and fetal goitre by ultrasound is imperative. In most cases the fetus can be treated satisfactorily by adjusting the dose of anti-thyroid drug in the mother and by following the fetal response clinically and by ultrasound.
What Are the Risks to the Fetus in a Woman with Graves Disease?
Poor control of maternal hyperthyroidism is associated with significant obstetric complications including miscarriage (26%), low birth weight, prematurity, (pre-)eclampsia, and possibly congenital malformations [6]. After the fetal thyroid matures (from 20 weeks of gestation onwards), maternal TSH receptor antibodies may act on the fetal thyroid to cause fetal thyrotoxicosis and goitre. The risk of fetal thyrotoxicosis is about 1% of all pregnancies in women with Graves disease, and if untreated, fetal mortality may be as high as 24%. Overtreatment may lead to hypothyroidism in the fetus, which is associated with subtle neurocognitive deficits later on in life, particularly if the hypothyroidism occurs in the first trimester [7]. Fetal goitre can develop as a result of fetal thyrotoxicosis or fetal hypothyroidism and in severe cases can obstruct labour.
What Are the Risks of Recurrence of Thyrotoxicosis after Delivery?
The risk of relapse of maternal thyrotoxicosis is high in the post-partum period (up to 80%), and close monitoring is required. Anti-thyroid drugs can be used safely during breastfeeding [8].
Prenatal Counselling of Women with Graves Disease
Pregnancy is a common concern among women of childbearing age who are receiving treatment for Graves disease. Some women may elect to have definitive treatment before pregnancy, which can be either a thyroidectomy or 131I therapy. The advantage of these treatment options is that the risk of maternal thyrotoxicosis during pregnancy is reduced, if not eliminated. Fertility is not affected by 131I therapy for thyrotoxicosis, but pregnancy should be deferred for 4–6 months after 131I therapy, although the basis of this recommendation is largely empirical. The risk of fetal and neonatal thyrotoxicosis is not eliminated by previous thyroidectomy or 131I therapy. The most important advice to women who have a previous history of thyroid dysfunction is to work with their practitioner to ensure that thyroid function tests are normal at the time of conception and throughout pregnancy.
DISCUSSION
Aetiology of Graves Disease
Graves disease is an autoimmune condition and is mediated by stimulatory autoantibodies to the TSH receptor. There is a significant genetic component to the aetiology of Graves disease, although environmental factors and stress also seem to confer risk [3]. Typically, the thyroid gland of patients with Graves disease is diffusely enlarged and vascular.
Toxic Multinodular Goitre
TMNG may also run in families. The pathogenesis is unknown. The disease begins with the formation of a single or few colloid nodules, and over a period of several years these become larger and more numerous. Some nodules are functioning and gradually acquire autonomy. With the passage of time serum TSH declines and may become undetectable until at a later stage serum free thyroid hormones rise. The hyperthyroidism of TMNG is usually mild and tends to occur in middle life or later. Toxic adenomas are benign neoplasms of the thyroid that are autonomous. In some cases they arise because of somatic mutations that lead to constitutive activation of the TSH receptor. As with TMNG, the hyperthyroidism tends to be mild.
Thyroiditis
Thyroiditis is due to an inflammatory process affecting the thyroid epithelium. Unlike other causes of thyrotoxicosis, there is no increased synthesis of thyroid hormones; instead, stored thyroid hormones in colloid are released into the circulation because of the leaky epithelium. The thyrotoxic phase of thyroiditis may be followed by a hypothyroid phase a few weeks later, but as a rule the patient recovers and euthyroidism ensues without any intervention.
Thyroiditis may occur after a viral infection (referred to as subacute or De Quervain thyroiditis), in which case the patient typically has a viral sore throat, the thyroid is tender, and inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) are raised. “Silent” thyroiditis is autoimmune and characterised by positive anti-TPO antibodies.
Investigating the Cause of Thyrotoxicosis
In many cases of thyrotoxicosis the aetiology will be apparent from information that can be obtained from the history and clinical examination. In cases where there is doubt, additional investigations are indicated. Direct measurement of TSH receptor antibody levels is not widely available, but can be very valuable as modern assays are highly sensitive and specific. TSH receptor antibodies can occasionally be positive in post-partum thyroiditis (this seems to be particularly rare in Europe, though reported in North America and Japan), and in cases of doubt a thyroid scan showing no uptake of radioisotope is diagnostic of thyroiditis [9]. TSH receptor antibody measurement is indicated in pregnancy to assess the risks of fetal and neonatal thyrotoxicosis. Anti-TPO antibodies occur in a significant proportion of the normal population, and this limits the use of this test. High concentrations of anti-TPO antibodies are present in silent and post-partum thyroiditis. Radioisotope scans are useful in identifying the cause of thyrotoxicosis (Figure 2), but should be avoided in pregnancy.
Treatment of Thyrotoxicosis
The treatment of thyrotoxicosis depends on the underlying cause. Anti-thyroid drugs are effective in Graves disease, TMNG, and toxic adenoma (Table 2), but not in thyroiditis because the latter is not associated with increased de novo synthesis of thyroid hormones.
Table 2. Response of Common Causes of Thyrotoxicosis to 131I Therapy and Anti-Thyroid Drugs
After a course of anti-thyroid drug treatment, remission may be expected in Graves disease as a result of the immunosuppressive effect of anti-thyroid drugs on synthesis of TSH receptor antibodies, but relapse is the rule in cases of TMNG or toxic adenoma.
131I therapy is effective for Graves disease, TMNG, and toxic adenoma. 131I therapy is ineffective in thyroiditis because iodine uptake is reduced or absent in this condition (Figure 2). Most patients with Graves disease develop permanent hypothyroidism after 131I therapy, whereas most patients with TMNG and toxic adenoma do not. 131I therapy is associated with a small risk of exacerbation of new development of TAO, particularly in smokers.
Thyroiditis may require symptomatic treatment with beta blockers during the thyrotoxic phase.
The type of thyroidectomy (subtotal versus total) for Graves disease as primary treatment has been the subject of controversy for some years. The argument in favour of total thyroidectomy is that the risk of recurrence of the thyrotoxicosis is eliminated, and that if performed by skilled thyroid surgeons the probability of hypoparathyroidism and vocal cord palsy is no greater than for a subtotal thyroidectomy [10]. A subtotal thyroidectomy, on the other hand, provides the best chance of any treatment for Graves disease for long-term euthyroidism without the need for thyroxine or other treatments for thyrotoxicosis.
The choice of treatment for Graves disease should be tailored to the needs of the individual patient, but also depends on local facilities, surgical expertise, and patient choice.
Box 1. Causes of Thyrotoxicosis
Common causes of thyrotoxicosis in a young female
Graves disease
Thyroiditis
Toxic multinodular goitre
Toxic adenoma
Iodine excess
Other rare causes of thyrotoxicosis
Hyperemesis gravidarum
Choriocarcinoma
TSH-producing pituitary adenoma
Iatrogenic thyrotoxicosis
Factitious thyrotoxicosis
Struma ovarii
Metastatic follicular thyroid cancer
Thyroid hormone resistance syndrome
Box 2. Patient Information Leaflet Used by the Author to Remind Patients Receiving Anti-Thyroid Drugs of the Potential Complication of Agranulocytosis
“You have been started on a drug called Carbimazole/Methimazole/Propylthiouracil to control the activity of your thyroid gland. This is important treatment and Carbimazole/Methimazole/Propylthiouracil is a well established drug that has been used for many years. The great majority of people treated with Carbimazole/Methimazole/Propylthiouracil have no problems whatsoever.
“Some people occasionally develop a rash—if this happens please consult your doctor as soon as possible; you need not discontinue the drug unless he/she tells you to do so.
“More rarely, Carbimazole/Methimazole/Propylthiouracil affects white cells in the blood, in which case you would be likely to develop a very severe sore throat and to feel ill with a fever. If this happens while you are on Carbimazole/Methimazole/Propylthiouracil treatment you must attend either your family doctor or the hospital on the same day, to have your blood count checked. Take no more tablets until the blood count has been checked. If your white blood count is normal you can carry on with the Carbimazole/Methimazole/Propylthiouracil. If your white blood count is abnormal your family doctor or the hospital will need to deal with this problem urgently.
“Please keep this with you in case you need to show it to your doctor.”
Learning Points
Thyrotoxicosis is not a diagnosis, merely a biochemical result. An accurate clinical diagnosis encompassing the aetiology is imperative for optimal management.
The most common cause of thyrotoxicosis in women of childbearing age is Graves disease.
Thyrotoxicosis impairs fertility, and thyroid status should be assessed in women with secondary infertility or recurrent abortions.
Three treatments are available for thyrotoxicosis due to Graves disease: anti-thyroid drugs, 131I therapy, and thyroidectomy. The right treatment is that which suits the patient's individual circumstances best.
131I therapy is an absolute contraindication in pregnancy. Anti-thyroid drugs may be used safely, and the dose should be titrated to the minimum dose that maintains normal maternal thyroid hormone levels.
The hyperthyroidism of Graves disease usually remits after the first trimester, and anti-thyroid drugs can be withdrawn; however, relapse of maternal thyrotoxicosis in the post-partum period is common.
Uncontrolled maternal hyperthyroidism can lead to fetal thyrotoxicosis with devastating effects on the fetus. Fetal thyrotoxicosis can be treated satisfactorily by appropriate manipulation of the maternal dose of anti-thyroid drug and careful fetal monitoring.
Krassas GE, Perros P (2002) Reproductive function in patients with thyroid diseases. Hot Thyroidology 2. Available: http://www.hotthyroidology.com/editorial_83.html. Accessed 12 October 2005.
Abramson J, Stagnaro-Green A (2001) Thyroid antibodies and fetal loss: An evolving story. Thyroid 11:57–63. Find this article online
Weetman AP (2000) Graves' disease. N Engl J Med 26 343:1236–1248. Find this article online
Cooper DS (2005) Antithyroid drugs. N Engl J Med 352:905–917. Find this article online
Laurberg P, Nygaard B, Glinoer D, Grussendorf M, Orgiazzi J (1998) Guidelines for TSH-receptor antibody measurements in pregnancy: Results of an evidence-based symposium organized by the European Thyroid Association. Eur J Endocrinol 139:584–586. Find this article online
Davis LE, Lucas MJ, Hankins GD, Roark ML, Cunningham FG (1989) Thyrotoxicosis complicating pregnancy. Am J Obstet Gynecol 160:63–70. Find this article online
Pop VJ, Vulsma T (2005) Maternal hypothyroxinaemia during (early) gestation. Lancet 365:1604–1606. Find this article online
American Academy of Pediatrics Committee on Drugs. (2001) Transfer of drugs and other chemicals into human milk. Pediatrics 108:776–789. Find this article online
Muller AF, Drexhage HA, Berghout A (2001) Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: Recent insights and consequences for antenatal and postnatal care. Endocr Rev 22:605–630. Find this article online
Palit TK, Miller CC 3rd, Miltenburg DM (2000) The efficacy of thyroidectomy for Graves' disease: A meta-analysis. J Surg Res 90:161–165. Find this article online
Wednesday 4 March 2009
Obesity in pregnancy
1. Incision on the skin should not be at the groove of skin, whihc corresponds to pubic symphysis. It should be about 2 cms above or on the top of the prominent bulge.
2. Hands will be slippery becuase of excessive subcut fatty tissue.
3. Try and open the uterine cavity with fingers as the judgment for uterine depth can be misleading.
4. Always close the subcutaneous fat.
2. Hands will be slippery becuase of excessive subcut fatty tissue.
3. Try and open the uterine cavity with fingers as the judgment for uterine depth can be misleading.
4. Always close the subcutaneous fat.
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