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Ideally a woman who is known to have hyperthyroidism should seek pre-pregnancy advice, although as yet there is no evidence for its benefit. Appropriate education should allay fears that are commonly present in these women. She should be referred for specialist care for frequent checking of her thyroid status, thyroid antibody evaluation and close monitoring of her medication needs. Medical therapy with anti-thyroid medications is the treatment of choice for hyperthyroidism in pregnancy.Methimazole and propylthiouracil (PTU) are effective in preventing pregnancy complications by hyperthyroidism. Surgery is considered for patients who suffer severe adverse reactions to anti-thyroid drugs and this is best performed in the second trimester of pregnancy. Radioactive iodine is absolutely contraindicated in pregnancy and the puerperium. If a woman is already receiving carbimazole, a change to propylthiouracil (PTU) is recommended but this should be changed back to carbimazole after the first trimester. This is because carbimazole can rarely be associated with skin and also mid line defects in the fetus but PTU long term also can cause liver side effects in the adult. Carbimazole and PTU are both secreted in breast milk but evidence suggests that antithyroid drugs are safe during lactation. There are no adverse effects on IQ or psychomotor development in children whose mothers have received antithyroid drugs in pregnancy.
Current guidelines suggest that a pregnant patient should be on PTU during the first trimester of pregnancy due to lower tetragenic effect and then be switched to methimazole during the second and third trimester due to lower liver dysfunction side effects.
Many of the common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety are mediated by increases in beta-adrenergic receptors on cell surfaces. Beta blockers, typically used to treat high blood pressure, are a class of drugs that offset this effect, reducing rapid pulse associated with the sensation of palpitations, and decreasing tremor and anxiety. Thus, a patient suffering from hyperthyroidism can often obtain immediate temporary relief until the hyperthyroidism can be characterized with the Radioiodine test noted above and more permanent treatment take place. Note that these drugs do not treat hyperthyroidism or any of its long-term effects if left untreated, but, rather, they treat or reduce only symptoms of the condition.
Some minimal effect on thyroid hormone production however also comes with Propranolol - which has two roles in the treatment of hyperthyroidism, determined by the different isomers of propranolol. L-propranolol causes beta-blockade, thus treating the symptoms associated with hyperthyroidism such as tremor, palpitations, anxiety, and heat intolerance. D-propranolol inhibits thyroxine deiodinase, thereby blocking the conversion of T to T, providing some though minimal therapeutic effect. Other beta-blockers are used to treat only the symptoms associated with hyperthyroidism. Propranolol in the UK, and metoprolol in the US, are most frequently used to augment treatment for hyperthyroid patients.
Surgery (thyroidectomy to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method, and because there is a risk of also removing the parathyroid glands, and of cutting the recurrent laryngeal nerve, making swallowing difficult, and even simply generalized staphylococcal infection as with any major surgery. Some people with Graves' may opt for surgical intervention. This includes those that cannot tolerate medicines for one reason or another, people that are allergic to iodine, or people that refuse radioiodine.
If people have toxic nodules treatments typically include either removal or injection of the nodule with alcohol.
The main strategies for the management of thyroid storm are reducing production and release of thyroid hormone, reducing the effects of thyroid hormone on tissues, replacing fluid losses, and controlling temperature. Thyroid storm requires prompt treatment and hospitalization. Often, admission to the intensive care unit is needed.
Iodine
Guidelines recommend the administration of inorganic iodide (potassium iodide or Lugol's iodine) to reduce the synthesis and release of thyroid hormone. Iodine reduces the synthesis of thyroid hormone via the Wolf-Chaikoff effect. Some guidelines recommend that iodine be administered after antithyroid medications are started, because iodine is also a substrate for the synthesis of thyroid hormone, and may worsen hyperthyroidism if administered without antithyroid medications.
Antithyroid Medications
Antithyroid drugs (propylthiouracil or methimazole) are used to reduce the synthesis and release of thyroid hormone. Propylthiouracil is preferred over methimazole due to its additional effects on reducing peripheral conversion of T4 to T3, however both are commonly used.
Beta Blockers
The administration of beta-1-selective beta blockers (e.g. propranolol) is recommended to reduce the effect of circulating thyroid hormone on end organs. In addition, propanolol at high doses also reduces peripheral conversion of T4 to T3, which is the more active form of thyroid hormone. Although previously unselective beta blockers (e.g., propranolol) have been suggested to be beneficial due to their inhibitory effects on peripheral deiodinases recent research suggests them to be associated with increased mortality. Therefore, cardioselective beta blockers may be favourable.
Corticosteroids
High levels of thyroid hormone result in a hypermetabolic state, which can result in increased breakdown of cortisol, a hormone produced by the adrenal gland. This results in a state of relative adrenal insufficiency, in which the amount of cortisol is not sufficient. Guidelines recommend that corticosteroids (hydrocortisone and dexamethasone are preferred over prednisolone or methylprednisolone) be administered to all patients with thyroid storm. However, doses should be altered for each individual patient to ensure that the relative adrenal insufficiency is adequately treated while minimizing the risk of side effects.
Supportive Measures
In high fever, temperature control is achieved with fever reducers such as paracetamol/acetaminophen and external cooling measures (cool blankets, ice packs). Dehydration, which occurs due to fluid loss from sweating, diarrhea, and vomiting, is treated with frequent fluid replacement. In severe cases, mechanical ventilation may be necessary. Any suspected underlying cause is also addressed.
The goal of newborn screening programs is to detect and start treatment within the first 1–2 weeks of life. Treatment consists of a daily dose of thyroxine, available as a small tablet. The generic name is levothyroxine, and several brands are available. The tablet is crushed and given to the baby with a small amount of water or milk. The most commonly recommended dose range is 10-15 μg/kg daily, typically 12.5 to 37.5 or 44 μg.
Within a few weeks, the T and TSH levels are rechecked to confirm that they are being normalized by treatment. As the child grows up, these levels are checked regularly to maintain the right dose. The dose increases as the child grows.
Hypothyroidism caused by Hashimoto's thyroiditis is treated with thyroid hormone replacement agents such as levothyroxine, triiodothyronine or desiccated thyroid extract. A tablet taken once a day generally keeps the thyroid hormone levels normal. In most cases, the treatment needs to be taken for the rest of the person's life. In the event that hypothyroidism is caused by Hashimoto's thyroiditis, it may be recommended that the TSH levels be kept under 3.0 mIU/L.
Medications to treat hypothyroidism have been found to be safe during pregnancy. Levothyroxine is the treatment of choice for hypothyroidism in pregnancy. Thyroid function should be normalised prior to conception in women with pre-existing thyroid disease. Once pregnancy is confirmed the thyroxine dose should be increased by about 30-50% and subsequent titrations should be guided by thyroid function tests (FT4 and TSH) that should be monitored 4-6 weekly until euthyroidism is achieved. It is recommended that TSH levels are maintained below 2.5 mU/l in the first trimester of pregnancy and below 3 mU/l in later pregnancy. The recommended maintenance dose of thyroxine in pregnancy is about 2.0-2.4 µg/kg daily. Thyroxine requirements may increase in late gestation and return to pre-pregnancy levels in the majority of women on delivery. Pregnant patients with subclinical hypothyroidism (normal FT4 and elevated TSH) should be treated as well, since supplementation with levothyroxine in such cases results in significantly higher delivery rate, with a pooled relative chance of 2.76.
If monitoring reveals failing control of glucose levels with these measures, or if there is evidence of complications like excessive fetal growth, treatment with insulin might be necessary. This is most commonly fast-acting insulin given just before eating to blunt glucose rises after meals. Care needs to be taken to avoid low blood sugar levels due to excessive insulin. Insulin therapy can be normal or very tight; more injections can result in better control but requires more effort, and there is no consensus that it has large benefits. A 2016 Cochrane review concluded that quality evidence is not yet available to determine the best blood sugar range for improving health for pregnant women with GDM and their babies.
There is some evidence that certain medications by mouth might be safe in pregnancy, or at least, are less dangerous to the developing fetus than poorly controlled diabetes. The medication metformin is better than glyburide. If blood glucose cannot be adequately controlled with a single agent, the combination of metformin and insulin may be better than insulin alone. Another review found good short term safety for both the mother and baby with metformin but unclear long term safety.
People may prefer metformin by mouth to insulin injections. Treatment of polycystic ovarian syndrome with metformin during pregnancy has been noted to decrease GDM levels.
Almost half of the women did not reach sufficient control with metformin alone and needed supplemental therapy with insulin; compared to those treated with insulin alone, they required less insulin, and they gained less weight. With no long-term studies into children of women treated with the drug, there remains a possibility of long-term complications from metformin therapy. Babies born to women treated with metformin have been found to develop less visceral fat, making them less prone to insulin resistance in later life.
Women not responding to IV rehydration and medication may require nutritional support. Patients might receive parenteral nutrition (intravenous feeding via a PICC line) or enteral nutrition (via a nasogastric tube or a nasojejunal tube). There is only limited evidence from trials to support the use of vitamin B6 to improve outcome. Hyperalimentation may be necessary in certain cases to help maintain volume requirements and allow weight gain. A physician might also prescribe Vitamin B1 (to prevent Wernicke's encephalopathy) and folic acid supplementation.
Desmopressin will be ineffective in nephrogenic DI which is treated by reversing the underlying cause (if possible) and replacing the free water deficit. The diuretic hydrochlorothiazide (a thiazide diuretic) or indomethacin can be used to create mild hypovolemia which encourages salt and water uptake in proximal tubule and thus improve nephrogenic diabetes insipidus. Amiloride has additional benefit of blocking Na uptake. Thiazide diuretics are sometimes combined with amiloride to prevent hypokalemia. It seems paradoxical to treat an extreme diuresis with a diuretic, and the exact mechanism of action is unknown but the thiazide diuretics will decrease distal convoluted tubule reabsorption of sodium and water, thereby causing diuresis. This decreases plasma volume, thus lowering the glomerular filtration rate and enhancing the absorption of sodium and water in the proximal nephron. Less fluid reaches the distal nephron, so overall fluid conservation is obtained.
Lithium-induced nephrogenic DI may be effectively managed with the administration of amiloride, a potassium-sparing diuretic often used in conjunction with thiazide or loop diuretics. Clinicians have been aware of lithium toxicity for many years, and traditionally have administered thiazide diuretics for lithium-induced polyuria and nephrogenic diabetes insipidus. However, amiloride has recently been shown to be a successful treatment for this condition.
Counselling before pregnancy (for example, about preventive folic acid supplements) and multidisciplinary management are important for good pregnancy outcomes. Most women can manage their GDM with dietary changes and exercise. Self monitoring of blood glucose levels can guide therapy. Some women will need antidiabetic drugs, most commonly insulin therapy.
Any diet needs to provide sufficient calories for pregnancy, typically 2,000 – 2,500 kcal with the exclusion of simple carbohydrates. The main goal of dietary modifications is to avoid peaks in blood sugar levels. This can be done by spreading carbohydrate intake over meals and snacks throughout the day, and using slow-release carbohydrate sources—known as the G.I. Diet. Since insulin resistance is highest in mornings, breakfast carbohydrates need to be restricted more. Ingesting more fiber in foods with whole grains, or fruit and vegetables can also reduce the risk of gestational diabetes.
Regular moderately intense physical exercise is advised, although there is no consensus on the specific structure of exercise programs for GDM.
Self monitoring can be accomplished using a handheld capillary glucose dosage system. Compliance with these glucometer systems can be low. Target ranges advised by the Australasian Diabetes in Pregnancy Society are as follows:
- fasting capillary blood glucose levels <5.5 mmol/L
- 1 hour postprandial capillary blood glucose levels <8.0 mmol/L
- 2 hour postprandial blood glucose levels <6.7 mmol/L
Regular blood samples can be used to determine HbA1c levels, which give an idea of glucose control over a longer time period.
Research suggests a possible benefit of breastfeeding to reduce the risk of diabetes and related risks for both mother and child.
Treatments for this disease depend on the type of thyroiditis that is diagnosed. For the most common type, which is known as Hashimoto's thyroiditis, the treatment is to immediately start hormone replacement. This prevents or corrects the hypothyroidism, and it also generally keeps the gland from getting bigger. However, Hashimoto's thyroiditis can initially present with excessive thyroid hormone being released from the thyroid gland (hyperthyroid). In this case the patient may only need bed rest and non-steroidal anti-inflammatory medications; however, some need steroids to reduce inflammation and to control palpitations. Also, doctors may prescribe beta blockers to lower the heart rate and reduce tremors, until the initial hyperthyroid period has resolved.
A number of antiemetics are effective and safe in pregnancy including: pyridoxine/doxylamine, antihistamines (such as diphenhydramine), and phenothiazines (such as promethazine). With respect to effectiveness, it is unknown if one is superior to another for relieving nausea or vomiting. Limited evidence from published clinical trials suggests the use of medications to treat hyperemesis gravidarum.
While pyridoxine/doxylamine, a combination of vitamin B and doxylamine, is effective in nausea and vomiting of pregnancy, some have questioned its effectiveness in HG.
Ondansetron may be beneficial, however, there are some concerns regarding an association with cleft palate, and there is little high-quality data. Metoclopramide is also used and relatively well tolerated. Evidence for the use of corticosteroids is weak; there is some evidence that corticosteroid use in pregnant women may slightly increase the risk of oral facial clefts in the infant and may suppress fetal adrenal activity. However, hydrocortisone and prednisolone are inactivated in the placenta and may be used in the treatment of hyperemesis gravidarum after 12 weeks.
Acute hypoglycemia is reversed by raising the blood glucose. Glucagon should be injected intramuscularly or intravenously, or dextrose can be infused intravenously to raise the blood glucose. Oral administration of glucose can worsen the outcome, as more insulin is eventually produced. Most people recover fully even from severe hypoglycemia after the blood glucose is restored to normal. Recovery time varies from minutes to hours depending on the severity and duration of the hypoglycemia. Death or permanent brain damage resembling stroke can occur rarely as a result of severe hypoglycemia. See hypoglycemia for more on effects, recovery, and risks.
Further therapy and prevention depends upon the specific cause.
Most hypoglycemia due to excessive insulin occurs in people who take insulin for type 1 diabetes. Management of this hypoglycemia is sugar or starch by mouth (or in severe cases, an injection of glucagon or intravenous dextrose). When the glucose has been restored, recovery is usually complete. Prevention of further episodes consists of maintaining balance between insulin, food, and exercise. Management of hypoglycemia due to treatment of type 2 diabetes is similar, and the dose of the oral hypoglycemic agent may need to be reduced. Reversal and prevention of hypoglycemia is a major aspect of the management of type 1 diabetes.
Hypoglycemia due to drug overdose or effect is supported with extra glucose until the drugs have been metabolized. The drug doses or combination often needs to be altered.
Hypoglycemia due to a tumor of the pancreas or elsewhere is usually curable by surgical removal. Most of these tumors are benign. Streptozotocin is a specific beta cell toxin and has been used to treat insulin-producing pancreatic carcinoma.
Hyperinsulinism due to diffuse overactivity of beta cells, such as in many of the forms of congenital hyperinsulinism, and more rarely in adults, can often be treated with diazoxide or a somatostatin analog called octreotide. Diazoxide is given by mouth, octreotide by injection or continuous subcutaneous pump infusion. When congenital hyperinsulinism is due to focal defects of the insulin-secretion mechanism, surgical removal of that part of the pancreas may cure the problem. In more severe cases of persistent congenital hyperinsulinism unresponsive to drugs, a near-total pancreatectomy may be needed to prevent continuing hypoglycemia. Even after pancreatectomy, continuous glucose may be needed in the form of gastric infusion of formula or dextrose.
High dose glucocorticoid is an older treatment used for presumptive transient hyperinsulinism but incurs side effects with prolonged use.
The World Health Organization recommends that women with severe hypertension during pregnancy should receive treatment with anti-hypertensive agents. Severe hypertension is generally considered systolic BP of at least 160 or diastolic BP of at least 110. Evidence does not support the use of one anti-hypertensive over another. The choice of which agent to use should be based on the prescribing clinician's experience with a particular agent, its cost, and its availability. Diuretics are not recommended for prevention of preeclampsia and its complications. Labetolol, Hydralazine and Nifedipine are commonly used antihypertensive agents for hypertension in pregnancy. ACE inhibitors and angiotensin receptor blockers are contraindicated as they affect fetal development.
The goal of treatment of severe hypertension in pregnancy is to prevent cardiovascular, kidney, and cerebrovascular complications. The target blood pressure has been proposed to be 140–160 mmHg systolic and 90–105 mmHg diastolic, although values are variable.
Treatment is beta blockers, ASA, and NSAIDs (or corticosteroids if NSAIDs are ineffective).
The intrapartum and postpartum administration of magnesium sulfate is recommended in severe pre-eclampsia for the prevention of eclampsia. Further, magnesium sulfate is recommended for the treatment of eclampsia over other anticonvulsants. Magnesium sulfate acts by interacting with NMDA receptors.
Several trials investigated a possible therapy for ESS. However, they yielded inconsistent and partly contradictory results. This may be caused by the fact that the investigated populations were too heterogeneous in the lack of a consistent definition of "non-thyroid illness syndrome".
Modern theories regard the TACITUS syndrome as an adaptive and therefore possibly beneficial response of thyroid homeostasis. Their proponents are therefore reserved with respect to substitutive treatment.
Central DI and gestational DI respond to desmopressin which is given as intranasal or oral tablets. Carbamazepine, an anticonvulsive medication, has also had some success in this type of DI. Also, gestational DI tends to abate on its own four to six weeks following labor, though some women may develop it again in subsequent pregnancies. In dipsogenic DI, desmopressin is not usually an option.
90 percent of babies born SGA catch up in growth by the age of 2. However, all SGA babies should be watched for signs of Failure-to-Thrive (FTT), hypoglycemia and other conditions common to SGA babies (see below). Hypoglycemia is common in asymmetrical SGA babies because their larger brains burn calories at a faster rate than their usually limited fat stores hold. Hypoglycemia is treated by frequent feedings and/or additions of cornstarch-based products (such as Duocal powder) to the feedings.
For the 10 percent of those that are SGA without catchup growth by the age of 2, an endocrinologist should be consulted. Some cases warrant growth hormone therapy (GHT).
There are some common conditions and disorders found in many that are SGA (and especially those that are SGA without catchup growth by age 2). They should be treated by the appropriate specialist:
- Gastroenterologist - for gastrointestinal issues such as: reflux (GERD) and/or delayed gastric emptying (DGE)
- Dietitian - to address caloric deficits. Dietitians are usually brought in for cases that include FTT. Also, according to the theory of thrifty phenotype, causes of growth restriction also trigger epigenetic responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment rich in food it may be more prone to metabolic disorders, such as obesity and type II diabetes.
- Speech Language Pathologist (SLP) or Occupational Therapist (OT) - for feeding issues. OTs may also treat sensory issues
- Behaviorist - for feeding issues, a behavioral approach may also be used, but usually for older children (over 2)
- Allergist - to diagnose or rule out food allergies (not necessarily more common in those SGA than the normal population)
- Ear, Nose and Throat doctor (ENT) - to diagnose enlarged adenoids or tonsils (not necessarily more common in those SGA than the normal population)
For IUGR (during pregnancy), possible treatments include the early induction of labor, though this is only done if the condition has been diagnosed and seen as a risk to the health of the fetus.
Most children born with congenital hypothyroidism and correctly treated with thyroxine grow and develop normally in all respects. Even most of those with athyreosis and undetectable T levels at birth develop with normal intelligence, although as a population academic performance tends to be below that of siblings and mild learning problems occur in some.
Congenital hypothyroidism is the most common preventable cause of intellectual disability. Few treatments in the practice of medicine provide as large a benefit for as small an effort.
The developmental quotient (DQ, as per Gesell Developmental Schedules) of children with hypothyroidism at age 24 months that have received treatment within the first 3 weeks of birth is summarised below:
Diabetes mellitus may be effectively managed by appropriate meal planning, increased physical activity and properly-instituted insulin treatment. Some tips for controlling diabetes in pregnancy include:
- Meals – Cut down sweets, eats three small meals and one to three snacks a day, maintain proper mealtimes, and include balanced fiber intake in the form of fruits, vegetables and whole-grains.
- Increased physical activity - walking, swimming/aquaerobics, etc.
- Monitor blood sugar level frequently, doctors may ask to check the blood glucose more often than usual.
- The blood sugar level should be below 95 mg/dl (5.3 mmol/l) on awakening, below 140 mg/dl (7.8 mmol/l) one hour after a meal and below 120 mg/dl (6.7 mmol/l) two hours after a meal.
- Each time when checking the blood sugar level, keep a proper record of the results and present to the health care team for evaluation and modification of the treatment. If blood sugar levels are above targets, a perinatal diabetes management team may suggest ways to achieve targets.
- Many may need extra insulin during pregnancy to reach their blood sugar target. Insulin is not harmful for the baby.
Overt, symptomatic thyroid dysfunction is the most common complication, with about 5% of persons with subclinical hypothyroidism and chronic autoimmune thyroiditis progressing to thyroid failure every year. Transient periods of thyrotoxicosis (over-activity of the thyroid) sometimes occur, and rarely the illness may progress to full hyperthyroid Graves' disease with active orbitopathy (bulging, inflamed eyes). Rare cases of fibrous autoimmune thyroiditis present with severe dyspnea (shortness of breath) and dysphagia (difficulty swallowing), resembling aggressive thyroid tumors – but such symptoms always improve with surgery or corticosteroid therapy. Primary thyroid B cell lymphoma affects fewer than one in a thousand persons, and it is more likely to affect those with long-standing autoimmune thyroiditis.
Blood pressure control can be accomplished before pregnancy. Medications can control blood pressure. Certain medications may not be ideal for blood pressure control during pregnancy such as angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II (AII) receptor antagonists. Controlling weight gain during pregnancy can help reduce the risk of hypertension during pregnancy.
There is no specific treatment, but is monitored closely to rapidly identify pre-eclampsia and its life-threatening complications (HELLP syndrome and eclampsia).
Drug treatment options are limited, as many antihypertensives may negatively affect the fetus. Methyldopa, hydralazine, and labetalol are most commonly used for severe pregnancy hypertension.
The fetus is at increased risk for a variety of life-threatening conditions, including pulmonary hypoplasia (immature lungs). If the dangerous complications appear after the fetus has reached a point of viability, even though still immature, then an early delivery may be warranted to save the lives of both mother and baby. An appropriate plan for labor and delivery includes selection of a hospital with provisions for advanced life support of newborn babies.