Hypothyroidism Substitution and Adrenal Insufficiency in Diabetic Patients

Czech version

Authors: J. Čáp
Authors‘ workplace: II. interní klinika Lékařské fakulty UK a FN Hradec Králové, přednosta prof. MUDr. Jaroslav Malý, CSc.
Published in: Vnitř Lék 2009; 55(4): 371-374
Category:

Overview

As diabetes mellitus type 1 is part of the polyglandular autoimmune syndrome it is no wonder that autoimmune disorders of the thyroid are in diabetics about five times more common and adrenal insufficiency four times more common than in general population. Manifest hypothyroidism leads to the decrease in insulin sensitivity and increase of glucose stimulated insulin secretion. These changes are reversible by substitution. Even subclinical hypothyroidism increases demand on pancreatic β cell. The glucocorticoid insufficiency causes marked increase of insulin sensitivity, decrease of endogenous glucose production and increase of glucose oxidation. Synthetic thyroxin is optimal for thyroid hormones substitution. Combined substitution with trijodthyronin did not proved to have any beneficial effect. The basis of substitution in adrenal insufficiency is replacement of hydrocortisone in doses that do not have negative metabolic effects. Preparations available today do not allow imitating the nature diurnal rhythm but slow-release tablets are being tested. Androgen substitution is not routinely recommended.

Key words:
diabetes mellitus – hypothyroidism – adrenal insufficiency – Addison’s disease – replacement

Sources

1. de Graaff LC, Smit JW, Radder JK. Prevalence and clinical significance of organ-specific autoantibodies in type 1 diabetes mellitus. Net J Med 2007; 65: 235–247.

2. Dimitriadis GD, Raptis SA. Thyroid hormone excess and glucose intolerance. Exp Clin Endocrinol Diabetes 2001; 109 (Suppl 2): S225–S239.

3. Handisurya A, Pacini G, Tura A et al. Effects of T4 replacement therapy on glucose metabolism in subjects with subclinical (SH) and overt hypothyroidism (OH). Clin Endocrinol (Oxf) 2008; 69: 963–969.

4. Stanicka S, Vondra K, Pelikanova T et al. Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy. Clin Chem Lab Med 2005; 43: 715–720.

5. Rochon C, Tauveron I, Dejax C et al. Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism. Clin Sci (Lond) 2003; 104: 7–15.

6. Owecki M, Nikisch E, Sowiński J. Hypothyroidism has no impact on insulin sensitivity assessed with HOMA-IR in totally thyroidectomized patients. Acta Clin Belg 2006; 61: 69–73.

7. Christiansen JJ, Djurhuus CB, Gravholt CH et al. Effects of cortisol on carbohydrate, lipid, and protein metabolism: studies of acute cortisol withdrawal in adrenocortical failure. J Clin Endocrinol Metab 2007; 92: 3553–3559.

8. Escobar-Morreale HF, del Rey FE, Obregón MJ et al. Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat. Endocrinology 1996; 137: 2490–2502.

9. Bunevicius R, Kazanavicius G, Zalinkevicius R et al. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med 1999; 340: 424–429.

10. Escobar-Morreale HF, Botella-Carretero JI, Gómez-Bueno M et al. Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann Intern Med 2005; 142: 412–424.

11. Appelhof BC, Fliers E, Wekking EM et al. Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial. J Clin Endocrinol Metab 2005; 90: 2666–2674.

12. Walsh JP, Shiels L, Lim EM et al. Combined thyroxine/liothyronine treatment does not improve well‑being, quality of life, or cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism. J Clin Endocrinol Metab 2003; 88: 4543–4550.

13. Rodriguez T, Lavis VR, Meininger JC et al. Substitution of liothyronine at a 1:5 ratio for a portion of levothyroxine: effect on fatigue, symptoms of depression, and working memory versus treatment with levothyroxine alone. Endocr Pract 2005; 11: 223–233.

14. Grozinsky-Glasberg S, Fraser A, Nahshoni E et al. Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta‑analysis of randomized controlled trials. J Clin Endocrinol Metab 2006; 91: 2592–2599.

15. Kraan GP, Dullaart RP, Pratt JJ et al. The daily cortisol production reinvestigated in healthy men. The serum and urinary cortisol production rates are not significantly different. J Clin Endocrinol Metab 1998; 83: 1247–1252.

16. Bergthorsdottir R, Leonsson-Zachrisson M, Odén A et al. Premature mortality in patients with Addison’s disease: a population‑based study. J Clin Endocrinol Metab 2006; 91: 4849–4853.

17. Filipsson H, Monson JP, Koltowska-Häggström M et al. The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients. J Clin Endocrinol Metab 2006; 91: 3954–3961.

18. Løvås K, Thorsen TE, Husebye ES. Saliva cortisol measurement: simple and reliable assessment of the glucocorticoid replacement therapy in Addison’s disease. J Endocrinol Invest 2006; 29: 727–731.

19. Mah PM, Jenkins RC, Rostami-Hodjegan A et al. Weight‑related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency. Clin Endocrinol (Oxf) 2004; 61: 367–375.

20. Arlt W, Rosenthal C, Hahner S et al. Quality of glucocorticoid replacement in adrenal insufficiency: clinical assessment vs. timed serum cortisol measurements. Clin Endocrinol (Oxf) 2006; 64: 384–389.

21. Barbetta L, Dall’Asta C, Re T et al. Comparison of different regimens of glucocorticoid replacement therapy in patients with hypoadrenalism. J Endocrinol Invest 2005; 28: 632–637.

22. Newell‑Price J, Whiteman M, Rostami-Hodjegan A et al. Modified-release hydrocortisone for circadian therapy: a proof-of-principle study in dexamethasone-suppressed normal volunteers. Clin Endocrinol (Oxf) 2008; 68: 130–135.

23. Løvås K, Husebye ES. Replacement therapy for Addison’s disease: recent developments. Expert Opin Investig Drugs 2008; 17: 497–509.

24. Jeffcoate W. Assessment of corticosteroid replacement therapy in adults with adrenal insufficiency. Ann Clin Biochem 1999; 36: 151–157.

25. Cohen N, Gilbert R, Wirth A et al. Atrial natriuretic peptide and plasma renin levels in assessment of mineralocorticoid replacement in Addison’s disease. J Clin Endocrinol Metab 1996; 81: 1411–1415.

26. Hunt PJ, Gurnell EM, Huppert FA et al. Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial. J Clin Endocrinol Metab 2000; 85: 4650–4656.

27. Johannsson G, Burman P, Wirén L et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab 2002; 87: 2046–2052.

28. Løvås K, Gebre‑Medhin G, Trovik TS et al. Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial. J Clin Endocrinol Metab 2003; 88: 1112–1118.

29. Dhatariya K, Bigelow ML, Nair KS. Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in hypoadrenal women. Diabetes 2005; 54: 765–769.

30. Miller KK, Biller BM, Beauregard C et al. Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2006; 91: 1683–1690.

31. Miller KK, Biller BM, Schaub A et al. Effects of testosterone therapy on cardiovascular risk markers in androgen-deficient women with hypopituitarism. J Clin Endocrinol Metab 2007; 92: 2474–2479.

32. Wierman ME, Basson R, Davis SR et al. Androgen therapy in women: an Endocrine Society Clinical Practice guideline. J Clin Endocrinol Metab 2006; 91: 3697–3710.