Dr.SreeLekshmy.S, Dr.C.Jayakumar, Dr.Jayasree
Term(37week+1day) old male ba was born to an overt diabetic mother and ba cried immediately after birth with stable vitals.Anterior fontanelle was (1cmx1cm). Systems normal. Total serum bilirubin done at 48hrs of life was above the cut off and was started on double surface phototherapy. No incompatibility.TSH (92.91 uIU/ml) and normal fT4(1.66ng/dl). Repeat TSB levels after 24hrs of phototherapy showed a rising trend with levels above the cutoff (18.12mg/dl) and was started on triple light phototherapy. Sepsis workup was negative. Hemolysis workup done was negative, with normal reticulocyte count (4.25%), normal absolute reticulocyte count (226K/uL), negative direct coombs test, normal peripheral smear. Serum albumin level was normal (3.7g/dl). Serum sodium was normal-136.4mmol/l. Repeat TSB was below the cutoff, phototherapy was changed to double light. As the Repeat and rebound TSB values were well below the cutoffs, phototherapy was stopped
TFT repeated after 24hrs, also showed elevated TSH of 92.35 uIU/ml and normal fT4. Thyroglobulin levels sent to rule out thyroid agenesis was normal(225.40ng/ml).
USG neck done revealed vaguely visualized markedly hypoplastic left lobe of thyroid measuring 3 mm in maximum AP thickness. Right lobe is not convincingly visualized. Rounded hyperechoic solid focus measuring 6 x 4 mm in floor of mouth anteriorly -? ectopic/lingual thyroid.
Ba was diagnosed with Congenital Hypothyroidism due to ectopic thyroid gland and was started on levothyroxine supplementation with12.5mcg/kg, with a plan to repeat TFT after 1month.
Congenital Hypothyroidism
Introduction: Congenital hypothyroidism (CH) is defined as thyroid hormone deficiency present at birth. Congenital hypothyroidism is one of the most common preventable causes of intellectual disability. CH must be diagnosed promptly because delay in treatment can lead to irreversible neurological deficits. Newborn screening (NBS) programs have led to earlier diagnosis and treatment of CH, resulting in improved neurodevelopmental outcomes.
Etiology:
1.Thyroidal (Primary CH) – defect in thyroid gland development (thyroid dysgenesis) or a defect of thyroid hormone biosynthesis (dyshormonogenesis). The majority of CH is due to thyroid dysgenesis (80%), which encompasses a variety of defects, including agenesis, ectopic, or hypoplastic gland.
2.Central CH
3.Transient: Transplacental passage of maternal anti-thyroid medications (methimazole or propylthiouracil), maternal thyroid blocking antibodies (in a mother with autoimmune thyroid disease), or iodine deficiency or excess.
Incidence: 1 in 3,000 to 1 in 4,000 live births. 1.5 or 2 to 1 in females compared with males is affected. Incidence is higher in twin births, multiple births, older mothers and preterm infant
Pathophysiology: The thyroid hormone plays an essential role in energy metabolism, growth, and neurodevelopment. Specifically, the thyroid hormone acts on neuronal differentiation, synapsis development, and myelination in the prenatal and newborn periods, regulating central nervous system development. The thyroid hormones are derived from the amino acid tyrosine and produced the thyroid gland in response to stimulation the thyroid-stimulating hormone (TSH) produced the anterior pituitary. TSH is regulated the thyrotropin-releasing hormone (TRH), which is released from the hypothalamus. This regulation pathway is called the hypothalamic-pituitary-thyroid (HPT) axis. There are two active thyroid hormones, thyroxine (T4) and triiodothyronine (T3).
Both T3 and T4 are secreted the thyroid gland, though the majority of circulating T3 is derived from peripheral tissue deiodination of T4. Deiodination of T4 to T3 is catalyzed a group of enzymes known as iodothyronine deiodinases. T4 and T3 inhibit the secretion of TSH, both directly and indirectly, inhibiting the secretion of TRH. Additional factors that inhibit TSH release are glucocorticoids, somatostatin, and dopamine. Both circulating T4 and T3 are bound tightly to serum proteins, including T4-binding globulin (TBG), and only the tiny fraction of T4 (0.02%) and T3 (0.3%) are unbound, so-called free T4 and free T3, which are biologically active
In infants with primary congenital hypothyroidism (CH), hypofunction of the thyroid gland typically causes low T4 and T3 levels, with elevated TSH and TRH levels due to feedback mechanism to the hypothalamus and pituitary gland. In compensated or subclinical hypothyroidism, serum T4 remains normal, while the TSH level is elevated. Infants with central hypothyroidism have low T4 or free T4, with low or low-normal TSH levels. TSH is the most sensitive indicator of thyroid dysfunction and the HPT axis. Additionally, patients with TBG deficiency present with a low total T4 and normal TSH.
Clinical features: Most newborns with congenital hypothyroidism (CH) have no or few clinical manifestations at birth. The classic clinical features of CH appear gradually over approximately six weeks, but early signs may appear within the first few weeks of life in more severe cases of CH.
Early manifestations: lethargy, hypotonia, large anterior and posterior fontanels, feeding difficulty, prolonged jaundice, poor or hoarse cry, constipation, and hypothermia.
Classic late manifestations: coarse facies with depressed nasal bridge, puffy eyelids, large tongue, coarse hair, thick, dry and cold mottled skin, abdominal distension, umbilical hernia, hyporeflexia, bradycardia, hypotension, and anemia. The respiratory distress may develop due to myxedema of the airway and is characterized noisy breathing, nasal stuffiness, and intermittent perioral cyanosis
Screening: post-delivery TSH surge in response to cold stress after birth. Hence, the ideal time is between 2 and 4 days of life when TSH levels have decreased.
Premature infants may have hypothyroxinemia of prematurity, characterized low free T4 and normal TSH, due to an immature HPT axis. Most patients will have a normal TFT 6 to 10 weeks.
Treatment: Treatment with levothyroxine (L-T4) must be started immediately after the diagnosis of congenital hypothyroidism (CH). NBS programs and early L-T4 treatment initiation (prior to 2 weeks of life) can prevent intellectual deficits and optimize neurodevelopmental outcomes. L-T4 alone is the treatment of choice. The initial dose depends upon the severity of CH. A higher initial L-T4 dose of 10 to 15 micrograms (ug)/kg/day (50 ug/day for full-term infants with severe CH) is recommended, especially for neonates with a very low pretreatment T4 level. A high initial L-T4 dose can normalize serum T4 in 3 days and TSH two weeks of therapy. The majority of full-term infants with severe CH require a short-term high dose L-T4 (50 ug per day) with dose reduction to 37.5 ug per day after TSH is normalized to avoid overtreating.
L-T4 tablets crushed and mixed with a small amount (1 to 2 ml) of water or breast milk may be administered orally via a small spoon or syringe. L-T4 should be given at the same time each day and at a different time of the day from calcium, iron, and soy to avoid interference with the absorption of the L-T4.
The first repeat thyroid function test (TFT), which includes free T4 and TSH, is to be drawn at 1 to 2 weeks after the start of L-T4 therapy with follow-up TFT every two weeks until a complete normalization of TSH. Repeat TFT is recommended every 1 to 3 months until 1 year of age. Children should have follow-up visits with TFT obtained every 2 to 4 months between the ages of 1 to 3 years, and every 3-12 months until growth is completed. More frequent visits and laboratory evaluations may be scheduled for patients with poor adherence or abnormal levels. Any L-T4 dose adjustment or formulation change requires a repeat TFT in 4-6 weeks. The goal of therapy is to maintain the total T4 in the upper half of the age-specific reference range and TSH level within the age-specific reference range
Treatment with L-T4 until at least 36 months of age. At that time, a trial off of L-T4 can be considered to determine the permanency of congenital hypothyroidism. Transient CH is more common in preterm or very low-birthweight infants. L-T4 dose of less than 2.8 mcg/kg/day in the third year of treatment is a predictor of transient CH. Thus, early discontinuation of L-T4 therapy at 2.5 years of age may be possible with careful monitoring of TFT. TFT should be repeated in 2 weeks after a trial time off the therapy. If repeat TFT is abnormal, L-T4 should be restarted. If repeat TFT is normal, TFT may be repeated again in 1 to 2 months to ensure normal thyroid hormone status.
Associated: cardiac malformations, including septal defects, renal abnormalities, and the risk of neurodevelopmental disorders.
Cary home message
Don’t stop investigating and starting treatment in case of T4TSH alteration but we have to do USG neck, look for thyroglobulin level and in some situations even MRI to detect pituitary abnormality and ectopic thyroid gland