Title:
A Case of Impaired Sensitivity to Thyroid Hormones.
Authors:
1. Dr. Lorenzo Gonzales MBBS
2. Professor Surujpal Teelucksingh FRCP(E)
3. Dr. Anjani Sharma MBChB
4. Dr. Michael Omar MBBS
Department & Institution:
Internal Medicine and Endocrinology, Medical Associates Hospital, St Joseph. Trinidad. W.I.
Corresponding Author:
Dr. Lorenzo Gonzales
Medical Associates Hospital, St. Joseph. Trinidad. W. I.
Telephone: 868494-4663 Email: ackoms.razor@gmail.com
Conflict of Interests:
The authors have no conflict of interests to declare.
Article Type: Case Report
Keywords:
Thyroid Hormone Resistance, Reduced Sensitivity to Thyroid Hormones, Impaired Sensitivity to thyroid Hormones.
PRESENTATION
A 43-year-old female presented in January 2017 for evaluation of an abnormal thyroid function test (elevated free T4 and suppressed TSH) which was suggestive of hyperthyroidism. She denied any of the expected symptoms of thyrotoxicosis such as: palpitations, weight loss, anxiousness, diarrhoea, fatigue, and mood disturbance. She was taking bisoprolol for hypertension; and clomiphene citrate, and metformin for subfertility. She admitted to having a Sulphur allergy. There was no history of tobacco or illicit drug use, and she consumed alcohol very occasionally. There was however, a family history of hyperthyroidism affecting her maternal grandmother, and aunt.
Interestingly, the patient was referred to us more than a decade earlier for much the same reason. At that time there was also an elevated free T4 with a suppressed TSH but no symptoms or signs of hyperthyroidism. She was followed over a two-year period and never developed features of hyperthyroidism. She was reassured, and no treatment was deemed necessary.
ASSESSMENT
Like her first presentation, on this occasion too, physical examination was normal. Blood pressure 121/85 mmHg and pulse 65 beats per minute (albeit on concomitant beta-blocker therapy) and regular. Her weight had remained steady in the interval of 13 years between visits, and stood at 76 kg in both instances. There was neither a goitre, thyroid bruit, nor features of thyroid eye disease. There was no tremor or excessive sweating. Her heart sounds were normal, and her jugular venous pressure was not elevated.
A thyroid scintigram showed a normal radioisotope uptake of 1.5% (normal 1-4%). Thyroid
Stimulating Hormone receptor antibody was negative. A Bone Mineral Density scan was requested to ascertain possible effects of long term untreated hyperthyroidism, and this revealed a normal T-score of 3.1. Her complete blood count, liver function, and renal function tests were normal. Triglycerides was 57 mg/dl, total cholesterol 207 mg/dl and her HbA1c was 5.8%.
DIAGNOSIS
The clinical presentations of Impaired Sensitivity to Thyroid Hormones are highly variable, and patients often present with asymptomatic elevation of thyroid hormones found on biochemical testing. Some patients may manifest features of either thyrotoxicosis or hypothyroidism, and sometimes features of both states may be present.1 The classical features of this uncommon condition include: a goiter, high free T4, and a non-suppressed TSH in a completely asymptomatic patient. The presence of intercurrent acute illness or alterations of thyroid hormone binding to serum proteins should be excluded.1,9 Some patients may have hyperactive behavior and a sinus tachycardia. There may also be developmental delay, hearing impairment, and learning disabilities of varying degrees depending on the genetic defect present.1,3 Our patient appears to have peripheral thyroid hormone resistance (high free T4 in the absence of end organ
features of thyrotoxicosis). However, the suppressed pituitary production of TSH would indicate that at least at the pituitary level, there was central sensitivity to thyroid hormones. This biochemical profile (suppressed TSH and elevated thyroid hormones), to the best of our knowledge, is not described in the literature except in cases with the coexistence of Graves’ disease.12 She gives a positive family history of “hyperthyroidism” in her aunt, and grandmother which raises the possibility of a familial form of Impaired Sensitivity to Thyroid Hormones.
Making the diagnosis of Impaired Sensitivity to Thyroid Hormones is important to avoid inappropriate treatment of patients with this group of conditions. The available literature suggests obtaining a detailed history, and physical examination to look for any features of either hyperthyroidism or hypothyroidism. DNA testing to look for an abnormal Thyroid Receptor β gene is recommended, as this is the most common etiology to date. Other approaches include dynamic testing such as the administration of Thyrotropin Releasing Hormone whence a positive response will be an increase in TSH release from the pituitary gland, which will be inappropriate in the setting of elevated thyroid hormones. Similarly, the administration of supplemental T3 at incremental doses can yield a positive result by demonstrating the need for a supraphysiological dose of T3 to achieve suppression of TSH secretion. 8,9 The resources to perform DNA testing to find a culprit gene defect for our patient is not available locally. Dynamic testing as outlined above may not be useful in our patient as she demonstrates central sensitivity to thyroid hormones.
MANAGEMENT
Treatment of this uncommon condition usually involves reassurance, and symptomatic treatment.
When there are concomitant features of both hormone deficiency and excess management can be challenging. In our patient’s case we demonstrated, by detailed history and examination, that she was clinically euthyroid. There was no evidence of cardiac dysfunction, her weight was steady, and her routine blood test were all normal. A thyroid scintigram, and TSH receptor antibodies were within normal limits. In the literature there are examples of patients who were treated inappropriately with either surgery or radioactive iodine.11,13 We were able to reassure our patient that treatment was unnecessary. The follow up care for our patient included education about her diagnosis, and the features of both hyperthyroidism, and hypothyroidism. There was no change in her clinical condition over a thirteen-year gap, so no fixed interval for clinical review seemed justifiable. She was instead given contact details and advised to inform us of any changes or concerns.
References
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