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Thyroid hormone resistance
and attention deficit hyperactivity disorder (ADHD) was described
in a patient by Caetano and co-workers, from Campinas, SP,
Brazil. This patient was a female child from a consanguineous
marriage, aged two years and six months with short stature (2.4
SD below the mean for chronological age). Laboratory tests showed
elevated levels of TSH as well as serum thyroid hormones. Her
mother had Graves’ disease. At examination the child had
attention hyperactivity disorder without goiter. Laboratory
assays revealed a TSH of 10.1 µU/ml (0.4–4.0 ); total T3=
3.67ng/dl (0.8–2.0); free T3= 5.98 pg/ml (2.6–5.1),
total T4=15.3 µg/dl (4.7–13.5); free T4= 1.3 ng/dl
(0.8–1.9); TBG = 35.9 µg/l (13–39). Antithyroid
peroxidase and antithyroglobulin antibodies in serum were absent.
Skeletal bone age was two years. Pituitary CT scan was normal.
These data are compatible with generalized resistance to thyroid
hormone. It is suggested that in a child with ADHD and delayed
bone maturation, resistance to thyroid hormones should be
considered.
Kahaly et al, Mainz, Germany and Cambridge, UK, reported cardiac investigations in patients with resistance to thyroid hormone (RTH). They studied cardiac involvement in 54 patients with RTH (aged 4–63 years, 32 female) and findings of 41/54 adult subjects (>18 yr) with RTH (median age 39 yr, 24 fem) were compared to those of 24 cases (range 23–69 yr, mean 42 yr, 14 fem) with hyperthyroidism (H), 20 cases with hypothyroidism (hypo), (29–59 yr, 46 yr, 10 fem), and 22 healthy controls (C), (26-59 yr, 40 yr, 11 fem). Cardiac volumes were measured using 2-D echocardiography, whereas flow velocities were recorded by continuous and pulse-wave Doppler. Cardiac symptoms (palpitations 32% vs 71%, dyspnoe 3% vs 13%) and signs (sinus tachycardia 29% vs 79%, atrial fibrillation 6% vs 17%) were less frequent in RTH vs H. In patients with RTH, heart rate correlated positively with free T3 (r 0.32, p=0.02), whereas isovolumetric relaxation was negatively correlated both with free T3 (r –0.41, p=0.005) and free T4 (r –0.36, p=0.01). Compared to H, left ventricular ejection and shortening fractions, as well as the preejection period were markedly lower in RTH (82ms vs 42ms, p<0.0004). Stroke volume index (41 l/min/m2 vs 31 l/min/m2, p=0.0007), and cardiac index were strongly increased in RTH and H vs. C and hypo. Deceleration time was shorter in RTH vs C (147 ms vs 176 ms, p=0.02). Maximal flow velocities through the aorta (1.1m/s vs 1.3m/s, p=0.002) and mitral valves were slower in RTH vs H. In summary, in patients with RTH, cardiac investigation revealed an elevated cardiac index as well as a shorter diastolic relaxation in contrast to C and hypo. In comparison to H subjects, Doppler velocities were slower and both indices of contractility as well as systolic cardiac performance were still in the normal range. Thus, an incomplete response of the heart to thyroid hormones is present in RTH. A very interesting case of selective pituitary resistance to thyroid hormone in a patient with a pituitary incidentaloma was reported by Belavenuta et al., Marília, SP, Brazil. The patient was a 43-year-old female with a diagnosis of hyperthyroidism since 1985. Until her first consultation at the endocrine division in 1994, she used antithyroid agents (methimazole or propylthiouracil) in usual doses, but her thyrotoxic symptoms never diminished. At physical examination, the patient had a diffuse goiter (30 g), hyperactivity and tachycardia No other peripheral effects of excessive serum thyroid hormone levels were observed. The initial laboratory findings indicated: TSH = 3.84 µU/ml (normal values = 0.40–4.0); FT4 = 3.45 ng/dl (normal values = 0,95–2.2); total T3 = 3.30 ng/ml (normal values = 0.80–2.0); 24h RAI-U = 53% and serum thyroid autoantibodies were repeatedly absent. The patient was admitted at the University hospital with a tentative diagnosis of TSH-induced hyperthyroidism. A CT-scan and MRI of the sellar region revealed the presence of a pituitary microadenoma (2.9 mm diameter) and a TSH-secreting pituitary adenoma was suspected. Nevertheless, no evidence of pituitary hormone hypersecretion was documented and stimulatory tests with TRH, performed at two different occasions, indicated an exaggerated (immediately after ATD discontinuation) or a normal (using LT3) TSH response. In addition, the TSH-a-subunit serum concentration was normal, confirming the diagnosis of PRTH. Presently, the patient is not using antithyroid drugs and persists with high serum levels of FT4 and a normal TSH concentration. The authors concluded that the most important tests to distinguish between PRTH and TSH-secreting pituitary adenoma were the measurement of serum TSH-a-subunit and the TSH response to TRH. Pituitary resistance to thyroid hormone was also reported by Cercato et al., from the University São Paulo, SP, Brazil. This female child (6y8mo) was first seen with loss of weight, hyperkinesia, ADHD and chronic fatigue. She had a visible and palpable goiter, a moist and warm skin, and finger tremor. The total weight of the thyroid gland (echography) was 16.8g. Total T3 was 435ng/dl, Total T4 = 23.5 µg/dl, Free T4 = 3.6 ng/dl and TSH = 7.3 mU/ml. Thyroid auto-antibodies were repeatedly negative including TRAb. Pituitary glycoprotein hormones subunit alpha was normal and the MRI indicated a normal pituitary. The patient was initially treated with PTU 600 mg/day followed by TRIAC 0.7 mg/day with excellent clinical response (TSH decreased from 49.2 to 2.7 mU/ml). Surprisingly, careful molecular analysis of exons 8, 9 and 10 failed to find a mutation in the TH receptor-beta gene. The possibility is suggested that in this case the mutation might be located in other genes (co-repressors, co-activators) of the complex TH receptor. |
