Year : 2021 | Volume
: 18 | Issue : 1 | Page : 31--33
Reversible thyrotropin elevation in case of primary Addison's disease
Rajesh Rajput1, Karamvir Yadav2, Surender Kumar2, Suyasha Saini2, Ayush Gupta2,
1 Department of Endocrinology, Pt. B.D, Sharma PGIMS, Rohtak, Haryana, India
2 Department of Medicine, Pt. B.D, Sharma PGIMS, Rohtak, Haryana, India
Dr. Rajesh Rajput
House No. 241, Sector – 2, Huda, Rohtak - 124 001, Haryana
The association of Addison's disease and chronic lymphocytic thyroiditis is a well-known disease complex, historically known as Schmidt disease. Here, we present the case of a patient who presented with primary Addison's disease and on further evaluation was also found to have a subclinical hypothyroidism without a positive marker of autoimmunity. The coexistence of these endocrine disorders simultaneously without thyroid peroxidase antibody positivity and steroid replacement alone in such a case resulting in complete recovery of thyroid function had not described in the literature.
|How to cite this article:|
Rajput R, Yadav K, Kumar S, Saini S, Gupta A. Reversible thyrotropin elevation in case of primary Addison's disease.Thyroid Res Pract 2021;18:31-33
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Rajput R, Yadav K, Kumar S, Saini S, Gupta A. Reversible thyrotropin elevation in case of primary Addison's disease. Thyroid Res Pract [serial online] 2021 [cited 2022 Jan 21 ];18:31-33
Available from: https://www.thetrp.net/text.asp?2021/18/1/31/314047
The coexistence of idiopathic adrenal insufficiency with autoimmune thyroid disease and or Type 1 diabetes mellitus is characteristic of Type II autoimmune polyglandular syndrome. The prevalence of primary hypothyroidism with autoimmune primary adrenal insufficiency is approximately 50%. The diagnosis of hypothyroidism in the presence of Addison's disease is difficult due to similarity in the presenting symptoms including asthenia, fatigue, and debilitation. Rarely, there is presence of clinical hypothyroidism along with idiopathic adrenal insufficiency. Diagnosing their coexistence is clinically important because thyroid therapy before steroid replacement may result in precipitation of adrenal crisis. We report a case where these two endocrine disorders co-presented and hypothyroidism was notably nonimmune mediated in nature.
A 23-year-old male presented with the complaints of weight loss, fatigue, loss of appetite, dizziness, and darkening of the skin in the past 1 year. The complaint of dizziness was more prominent in standing position. There was also a history of significant weight loss (weight decreased from 68 kg to 55 kg) in the last 1 year. The appetite of the patient was so much decreased that he was able to take only one bread per day. There was also a history of hyperpigmentation of sun-exposed areas of the body such as the dorsum of the feet, face, and neck. His history was unremarkable for tuberculosis or chronic illness and any drug addiction. There was no family history of tuberculosis and autoimmune or heritable disorders. On examination, the patient was thin built with a body mass index of 19.48 kg/m and normal body temperature with a pulse rate of 106/min. The blood pressure of the patient was 96/60 mmHg in the supine position and was 64/40 mmHg in the standing position. There was presence of hyperpigmentation over the face, neck, dorsum of the hands, and feet, but hyperpigmentation over the oral mucosa and knuckles was absent. Goiter was not palpable. Examination of the cardiovascular, respiratory, and abdominal system was unremarkable.
Blood investigations revealed a hemoglobin of 12 g% with normal blood indices. Renal function tests and liver function test values were also within normal range. There was presence of hyperkalemia and hyponatremia. Electrocardiogram showed sinus tachycardia with signs of hyperkalemia, and chest X-ray was normal. There was no evidence of suprarenal lesion on ultrasonography (USG) of the abdomen. Contrast-enhanced computed tomography of the abdomen showed that both the adrenal glands are relatively small (R > L), however no abnormal enhancement/calcification or mass lesion was seen. Because of a strong suspicion of adrenal insufficiency, Adrenocorticotropic hormone (ACTH) stimulation test was done with intravenous injection of 250 μg of synthetic ACTH. Two blood samples were taken at 30 min and 60 min after injection Synacthen. The result of the ACTH stimulation test showed that the basal serum cortisol was < 0.05 µg/dL and remained <0.05 µg/dL at 30 min and 60 min poststimulation, respectively. The serum ACTH level was 1000 pg/mL (n: <46 pg/mL). This confirmed the diagnosis of primary adrenal insufficiency. To look for other associated diseases, thyroid profile along with thyroid peroxidase (TPO) antibody was advised. Thyroid-stimulating hormone-sensitive revealed a level of 15.65 µg/mL (0.4–4.2 µg/mL) and serum-free T4 was 1.2 ng/dL (0.3–1.6 ng/dL). The TPO antibody was negative. USG of the neck showed no evidence of thyroiditis.
Because of the primary adrenal insufficiency, the patient was started on tablet hydrocortisone 10 mg at 8 a.m. and 5 mg at 4 p.m. Along with steroids, he was also given tablet DHEAS 50 mg OD and tablet fludrocortisone 0.1 mg OD. The associated subclinical hypothyroidism picture with TSH >10 µg/ml and overlapping symptoms of adrenal insufficiency left us in an uncertain situation whether to treat or not. Finally, no treatment was started for hypothyroidism and decided to follow-up.
Outcome and follow-up
After starting replacement for adrenal insufficiency, his general conditions improved dramatically, and within 3 days of treatment, blood pressure also improved from 96/60 mmHg to 114/74 mmHg in the supine position and from 64/40 mmHg to 106/68 mmHg in the standing position. Hyponatremia and hyperkalemia were corrected within 3 days of hormone replacement therapy. After 1 month of starting the treatment, the patient had 3 kg of weight gain and hyperpigmentation in the sun-exposed parts also decreased. At the end of 1 month, his serum TSH level decreased at 11.37 µg/mL and after 2 months it was 6.0 µg/mL. After 4 months of starting treatment, serum TSH decreased to 3.03 µg/mL; thus, indicating pseudohypothyroidism and not true hypothyroidism.
Adrenal insufficiency can be broadly classified into three categories, namely, primary, central, and relative. Primary adrenal insufficiency is caused by pathological processes that destroy at least 90% of the gland. Adrenal glands are the site of synthesis for corticosteroids, mineralocorticoids, and sex steroids. The clinical manifestations of Addison's disease are due to deficiency of these hormones. Primary adrenal insufficiency is most commonly caused by autoimmune adrenalitis. Isolated autoimmune adrenalitis accounts for 30%–40%, whereas 60%–70% as part of autoimmune polyglandular syndromes. The association of adrenal insufficiency and autoimmune thyroid dysfunction is most common in clinical practice. It is a known fact that high serum cortisol is associated with lowering of immunity of the body and low levels are associated with the induction of autoimmune disease. This statement can be solidified by the findings of Takasu et al. who reported three cases of autoimmune thyroiditis after surgery of adrenocortical adenoma in patients with Cushing syndrome. Hashimoto thyroiditis is a type of autoimmune disorder that is frequently associated with Addison's disease. Nearly 82% of patients with Addison's disease (presumed autoimmune) had lymphocytic infiltration in the thyroid gland. Gharib et al. described for the first time that TSH was falsely elevated in adrenal insufficiency, which usually resolves with the treatment of the primary disease. De Nayer et al. gave the possible explanation for elevated TSH levels in adrenal insufficiency that it could be due to the co-existence of primary hypothyroidism with primary adrenal insufficiency or due to decreased sensitivity of the thyroid gland to TSH and there may be less thyroid hormone production along with the reducing metabolism ability of the body in the hypocortisolemic states. There are many possible explanations for the change in thyroid function and thyrotropin levels during glucocorticoid replacement. Glucocorticoids act on the thyroid axis at both pituitary/hypothalamus and thyroid gland levels. When cortisone is used in both pharmacologic and physiologic doses, it exerts an inhibitory effect on hypophyseal thyrotropin and prolactin secretion. It also controls the thyroid axis by both direct and indirect mechanisms through lipocortin 1 and somatostatin at the level of pituitary gland and hypothalamus. There is also a direct effect of glucocorticoids on the thyroid gland through their anti-inflammatory properties, which result in the resolution of autoimmune thyroid disease. Several case reports on adrenal insufficiency with Hashimoto thyroiditis have shown a beneficial effect on elevated TSH by the above-described mechanisms with glucocorticoid replacement therapy., Only a few cases exhibit primary adrenal insufficiency with nonautoimmune-mediated thyroid dysfunction in literature. The activity of glucocorticoid at the hypothalamus level may explain corticosteroid-dependent changes in thyrotropin levels in patients with chronic adrenal insufficiency not of autoimmune origin and without intrinsic thyroid disease, as present in our case. In general, the TSH elevation is <10 µg/mL with adrenal insufficiency. According to the American Association of Clinical Endocrinologists, an elevated TSH value of <10 µg/mL with normal free T4 can be monitored without initiation of thyroid hormone replacement therapy.
Our case was unique due to having primary adrenal insufficiency with nonautoimmune-mediated thyroid dysfunction in the form of elevated TSH >15 µg/mL. To the best of our knowledge, such high elevated TSH have not been described in past in association with primary adrenal insufficiency, and restoration of TSH to normal range after steroid replacement proves this association.
The present case outlines that in patients with adrenal insufficiency, there should be a search for other associated diseasesAdrenal insufficiency may be primary or relative and the associated thyroid dysfunction could be either autoimmune or nonautoimmune mediatedElevated TSH 10 µg/mL with normal free T4 levels and negative TPO antibody can be monitored without accelerating the initiation of thyroid hormone replacementAlways start glucocorticoid replacement therapy before thyroid hormone replacement in patients having both adrenal insufficiency and thyroid dysfunction.
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The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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