Background: Autoimmune thyroid disease (ATD) has been occasionally observed in patients with primary adrenal insufficiency (PAI). In contrast, less than 20 cases of comorbid PAI with ATD have been found in the English literature. One conceivable reason is difficulty in detecting latent PAI. Objective: Information of clinical presentation and diagnostics is sought to facilitate diagnosis of latent PAI. Methods: Latent PAI was pursued in 11 patients among 159 ATD patients. All of them were maintained in a euthyroid state. Except for one patient with nonrheumatic musculoskeletal symptoms, the other patients, who were asymptomatic in their daily lives, presented with recurrent nonspecific gastrointestinal symptoms or fatigue in stress-associated circumstances. Morning cortisol level <303 nmol/l was used as an inclusion criterion. Their basal adrenocorticotropic hormone levels were normal. The adrenal status was examined by a provocation test, either an insulin-induced hypoglycemia test or a 1-μg intravenous corticotrophin test. Eleven patients showed subnormal cortisol response. They were supplemented with hydrocortisone of doses ≤15 mg/day. After a few months of supplementation, PAI was confirmed by another provocation test. Three patients were excluded because of dissociation of two provocation tests. Results: Comorbid latent PAI with ATD was pursued from the symptoms stated above and proven by two provocation tests; it was found in 5% (8/159) of the patients. Conclusion: When patients with ATD are troubled by recurrent stress-associated gastrointestinal or constitutional symptoms or nonrheumatic musculoskeletal symptoms which have remained unrelieved by adjustment of thyroid medication, these symptoms may be a manifestation of comorbid latent PAI. It is worth investigating such patients for latent PAI.

Keywords:
Hypoadrenalism, Gravesߣ disease, Hypothyroidism
1.
Kasperlik-Zaluska A, Czarnocka B, Czech W: High prevalence of thyroid autoimmunity in idiopathic Addison's disease. Autoimmunity 1994;18:213-216.
2.
Erichsen MM, Løvås K, Skinningsrud B,Wolff AB, Undlien DE, Svartberg J, Fougner KJ, Berg TL, Bollerslev J, Carlson JA, Erich H, Husebye ES: Clinical, immunological, and genetic features of autoimmune primary adrenal insufficiency: observations from a Norwegian registry. J Clin Endocrinol Metab 2009;94:4882-4890.
3.
Boelaert K, Newby PR, Simmonds MJ, Holder RL, Carr-Smith JD, Howard JM, Manji N, Allahabadia A, Armitage M, Chatterjee KV, Lazarus JH, Pearce SH, Vaidya B, Gough SC, Franklin JA: Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med 2010;123:183.el-9.
4.
Koshiyama H, Ito M, Yoshinami N, Masaki M, Yorita S, Tanaka M, Mizunoya S, Koh T: Two cases of asymptomatic adrenocortical insufficiency with autoimmune thyroid disease. Endocr J 1994;41:373-378.
5.
Torrejón S, Webb SM, Rodríguez-Espinosa J, Martinez de Osaba MJ, Corcoy R: Long-standing subclinical Addison's disease. Exp Clin Endocrinol Diabetes 2007;115:530-532.
6.
Laureti S, de Bellis A, Muccitelli VI, Calcinaro F, Bizzarro A, Rossi R, Bellastella A, Santeusanio F, Falorni A: Levels of adrenocortical autoantibodies correlate with the degree of adrenal dysfunction in subjects with preclinical Addison's disease. J Clin Endocrinol Metab 1998;83:3507-3511.
7.
Giordano R, Balbo M, Picu A, Bonelli L, Berardelli R, Falorni A, Ghigo E, Arvat E: Corticotrope hypersecretion coupled with cortisol hypo-responsiveness to stimuli is present in patients with autoimmune endocrine diseases: evidence for subclinical hypoadrenalism? Eur J Endocrinol 2006;155:421-428.
8.
Editorial. Hidden adrenal insufficiency. Br Med J 1973;4:5-6.
9.
Betterle C, Lazzarotto F, Presotto F: Autoimmune polyglandular syndrome type 2: the tip of an iceberg? Clin Exp Immunol 2004;137:225-233.
10.
Bleicken B, Hahner S, Ventz M. Quinkler M: Delayed diagnosis of adrenal insufficiency is common: a cross-sectional study in 216 patients. Am J Med Sci 2010;339:525-531.
11.
Labhart A: Chapter 7. Adrenal cortex; in Labhart A (ed): Clinical Endocrinology, Theory and Practice, ed 2. Berlin, Springer, 1986, pp 349-486.
12.
Smith BR, Furmaniak J: Adrenal and gonadal autoimmune diseases. J Clin Endocrinol Metab 1995;80:1502-1505.
13.
Yamamoto T: History of stress-related health changes: a cue to pursue a diagnosis of latent primary adrenal insufficiency. Intern Med 2014;53:183-188.
14.
Japan Thyroid Association: Part 2. Drug treatment; in Nakamura H, Konishi J (eds): Guideline for the Treatment of Graves' Disease 2011. Tokyo, Nankodo, 2011, pp 41-55 (in Japanese).
15.
Oelkers W: Adrenal insufficiency. N Engl J Med 1996;335:1206-1212.
16.
Pura M, Kreze A Jr, Kentos P, Vaňuga P: The low-dose (1 microg) cosyntropin test (LDT) for primary adrenocortical insufficiency: defining the normal cortisol response and report on first patients with Addison's disease confirmed by LDT. Exp Clin Endocrinol Diabetes 2010;118:151-157.
17.
Debono M, Ghobadi C, Rostami-Hodjegan A, Huatan H, Campbell MJ, Newell-Price J, Darzy K, Merke DP, Arlt W, Ross RJ: Modified release hydrocortisone to provide circadian cortisol profiles. J Clin Endocrinol Metab 2009;94:1548-1554.
18.
Betterle C, Dal Pra C, Mantero F, Zanchetta R: Autoimmune adrenal insufficiency and autoimmune polyendocrinopathy syndromes: autoantibodies, autoantigens and their applicability in diagnosis and disease prediction. Endocr Rev 2002;23:327-364.
19.
Boscaro M, Betterle C, Sonino N, Volpato M, Paoletta A, Fallo F: Early adrenal hypofunction in patients with organ-specific autoantibodies and no clinical adrenal insufficiency. J Clin Endocrinol Metab 1994;79:452-455.
20.
Magbool M, Shar ZA, Wani FA, Wahid A, Parveen S, Nazir A: Prevalence of occult adrenal insufficiency and the prognostic value of a short corticotropin stimulation test in patients with septic shock. Indian J Crit Care Med 2009;13:85-91.
21.
Poomthavorn P, Isaradisaikul B, Chuansumrit A, Khlairit P, Sriphrapradang A, Mahachoklertwattana P: High prevalence of ‘biochemical' adrenal insufficiency in thalassemics: is it a matter of different testings or decreased cortisol binding globulin? J Clin Endocrinol Metab 2010;95:4609-4615.
22.
Charmandari E, Nicolaides N, Chrousos GP: Adrenal insufficiency. Lancet 2014;383:2151-2167.
23.
Bancos I, Hahner S, Tomlinson J, Arlt W: Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol 2015;3:216-226.
24.
Dickstein G, Shechner C, Nicholson WE, Rosner I, Shen-Orr Z, Adawi F, Lahav M: Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab 1991;72:773-778.
25.
Tordjman K, Jappe A, Grazas N, Apter C, Stern N: The role of the low dose (1 microgram) adrenocorticotropin test in the evaluation of patients with pituitary diseases. J Clin Endocrinol Metab 1995;80:1301-1305.
26.
Laureti S, Arvat E, Candeloro P, DiVito I, Ghigo E, Santeusanio F, Falorni A: Low dose (1 microg) ACTH test in the evaluation of adrenal dysfunction in pre-clinical Addison's disease. Clin Endocrinol (Oxf) 2000;53:107-115.
27.
Esteban NV, Loughlin T, Yergey AL, Zawadzki JK, Booth JD, Winterer JC, Loriaux DL: Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. J Clin Endocrinol Metab 1991;72:39-45.
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2015
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