ABSTRACT
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic tendency that affects most organ systems in the human body. In this report, we present a review of the endocrinologic manifestations associated with APS by evaluating the medical literature from 1968 to 2009 using MEDLINE and these keywords: APS, antiphospholipid syndrome, antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, anti β-2 glycoprotein I, pituitary, adrenal, thyroid, parathyroid, ovary, testes, diabetes mellitus, and diabetes insipidus. Adrenal insufficiency was found to be the most common endocrine manifestation associated with APS. Autoimmune thyroid disease was associated with increased titers of antiphospholipid antibodies (aPL) without any APS clinical manifestations. In addition, hypopituitarism and Sheehan syndrome are increasingly being reported in association with aPL. Data regarding the prevalence and significance of aPL in diabetic patients remains uncertain. Finally, only a few cases of ovarian and testicular derangements have been reported. APS should be considered in any patient with adrenal insufficiency even in the absence of other thrombotic manifestations. It is also advisable to assess aPL in the sera of patients presenting with pituitary insufficiency. Further studies are needed to clarify the relationship between aPL and thyroid disorders and diabetes mellitus.
KEYWORDS
Antiphospholipid syndrome - adrenal - pituitary - thyroid - diabetes
REFERENCES
-
1
Miyakis S, Lockshin M D, Atsumi T et al.
International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).
J Thromb Haemost.
2006;
4
(2)
295-306
-
2
Thomas R H.
Hypercoagulability syndromes.
Arch Intern Med.
2001;
161
(20)
2433-2439
-
3
Wong R C, Favaloro E J.
Clinical features, diagnosis, and management of the antiphospholipid syndrome.
Semin Thromb Hemost.
2008;
34
(3)
295-304
-
4
Oelkers W.
Adrenal insufficiency.
N Engl J Med.
1996;
335
(16)
1206-1212
-
5
Cervera R, Piette J C, Font J Euro-Phospholipid Project Group et al.
Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients.
Arthritis Rheum.
2002;
46
(4)
1019-1027
-
6
Eichner H L, Schambelan M, Biglieri E G.
Systemic lupus erythematosus with adrenal insufficiency.
Am J Med.
1973;
55
(5)
700-705
-
7
Grottolo A, Ferrari V, Mariano M, Zambruni A, Tincani A, Del Bono R.
Primary adrenal insufficiency, circulating lupus anticoagulant and anticardiolipin antibodies in a patient with multiple abortions and recurrent thrombotic episodes.
Haematologica.
1988;
73
(6)
517-519
-
8
Asherson R A, Hughes G R.
Recurrent deep vein thrombosis and Addison's disease in “primary” antiphospholipid syndrome.
J Rheumatol.
1989;
16
(3)
378-380
-
9
Carette S, Jobin F.
Acute adrenal insufficiency as a manifestation of the anticardiolipin syndrome?.
Ann Rheum Dis.
1989;
48
(5)
430-431
-
10
Asherson R A, Hughes G R.
Hypoadrenalism, Addison's disease and antiphospholipid antibodies.
J Rheumatol.
1991;
18
(1)
1-3
-
11
Espinosa G, Santos E, Cervera R et al.
Adrenal involvement in the antiphospholipid syndrome: clinical and immunologic characteristics of 86 patients.
Medicine (Baltimore).
2003;
82
(2)
106-118
-
12
Presotto F, Fornasini F, Betterle C, Federspil G, Rossato M.
Acute adrenal failure as the heralding symptom of primary antiphospholipid syndrome: report of a case and review of the literature.
Eur J Endocrinol.
2005;
153
(4)
507-514
-
13
Gerner P, Heldmann M, Borusiak P, Bures V, Wirth S.
Adrenal failure followed by status epilepticus and hemolytic anemia in primary antiphospholipid syndrome.
Thromb J.
2005;
3
(1)
6
-
14
Legendre G, Vauthier-Brouzes D, Cornet A et al.
Maternal adrenal necrosis in the third trimester of pregnancy: a rare complication of antiphospholipid syndrome [in French].
Gynecol Obstet Fertil.
2008;
36
(4)
413-416
-
15
Bhattacharya M, Yeh B M, Qayyum A, Coakley F V.
Case 81: antiphospholipid antibody syndrome with adrenal hemorrhage and Budd-Chiari syndrome.
Radiology.
2005;
235
(1)
53-55
-
16
Dierking E, Gogoi R, Adamcik S, Greene L W, Curtin J P.
Adrenal insufficiency after laparoscopic hysterectomy in a patient with primary antiphospholipid syndrome.
Obstet Gynecol.
2008;
111
((2 Pt 2))
495-498
-
17
Blanc P L, Forel C, Jay S, Susset V.
Acute adrenal insufficiency during unilateral adrenal hemorrhage secondary to the antiphospholipid syndrome [in French].
Rev Med Interne.
2006;
27
(12)
970-972
-
18
Fujishima N, Komatsuda A, Ohyagi H et al.
Adrenal insufficiency complicated with antiphospholipid syndrome (APS).
Intern Med.
2006;
45
(16)
963-966
-
19
Zhang Z L, Wang Y, Zhou W, Hao Y J.
Addison's disease secondary to connective tissue diseases: a report of six cases.
Rheumatol Int.
2009;
29
(6)
647-650
-
20
Kurtulmus N, Cikrikcioglu M A, Aksoy O, Tukek T.
Primary antiphospholipid syndrome presenting as hyponatremic hypertensive syndrome and acute adrenal insufficiency following it: a rare case.
Rheumatol Int.
2009;
April 14 (Epub ahead of print)
-
21
Starakis I, Mazokopakis E, Siagris D, Liossis S, Karatza C, Antonopoulos A.
Catastrophic antiphospholipid syndrome presented with severe hypertension, adult respiratory distress syndrome and unilateral adrenal haemorrhagic infarction.
Rheumatol Int.
2007;
27
(8)
781-783
-
22
Asherson R A.
Acute respiratory distress syndrome and other unusual manifestations of the catastrophic antiphospholipid (Asherson's) syndrome.
Isr Med Assoc J.
2004;
6
(6)
360-363
-
23
Asherson R A, Cervera R, Piette J C et al.
Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients.
Medicine (Baltimore).
1998;
77
(3)
195-207
-
24
Asherson R A, Cervera R, Piette J C et al.
Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients.
Medicine (Baltimore).
2001;
80
(6)
355-377
-
25
Rao R H, Vagnucci A H, Amico J A.
Bilateral massive adrenal hemorrhage: early recognition and treatment.
Ann Intern Med.
1989;
110
(3)
227-235
-
26
Fox B.
Venous infarction of the adrenal glands.
J Pathol.
1976;
119
(2)
65-89
-
27
Papadopoulos K I, Jönsson A, Berntorp E, Törnquist C, Hulthén U L.
Primary antiphospholipid syndrome associated with postoperative primary adrenal failure.
J Intern Med.
1995;
238
(2)
175-178
-
28
Walz B, Ho Ping Kong H, Silver R.
Adrenal failure and the primary antiphospholipid syndrome.
J Rheumatol.
1990;
17
(6)
836-837
-
29
Arnason J A, Graziano F M.
Adrenal insufficiency in the antiphospholipid antibody syndrome.
Semin Arthritis Rheum.
1995;
25
(2)
109-116
-
30
Berneis K, Buitrago-Téllez C, Müller B, Keller U, Tsakiris D A.
Antiphospholipid syndrome and endocrine damage: why bilateral adrenal thrombosis?.
Eur J Haematol.
2003;
71
(4)
299-302
-
31
Baethge B A, Levine S N, Wolf R E.
Antibodies to nuclear antigens in Graves' disease.
J Clin Endocrinol Metab.
1988;
66
(3)
485-488
-
32
Hofbauer L C, Heufelder A E.
Coagulation disorders in thyroid diseases.
Eur J Endocrinol.
1997;
136
(1)
1-7
-
33
Takahashi A, Tamura A, Ishikawa O.
Antiphospholipid antibody syndrome complicated by Grave's disease.
J Dermatol.
2002;
29
(12)
776-780
-
34
Hofbauer L C, Spitzweg C, Heufelder A E.
Graves' disease associated with the primary antiphospholipid syndrome.
J Rheumatol.
1996;
23
(8)
1435-1437
-
35
Nakayama T, Yamamoto T, Kanmatsuse K, Kokubun S.
Graves' disease associated with anticardiolipin antibody positivity and acquired protein S deficiency.
Rheumatol Int.
2003;
23
(4)
198-200
-
36
Mouelhi L, Chaieb M, Debbeche R et al.
Association Budd Chiari syndrome, antiphospholipid syndrome and Grave's disease [in French].
Tunis Med.
2009;
87
(2)
164-166
-
37
Mayaudon H, Crozes P, Riveline J P, Boyer B, Simon P, Bauduceau B.
Antiphospholipid antibodies in Basedow disease [in French].
Presse Med.
1994;
23
(32)
1496
-
38
Marongiu F, Conti M, Murtas M L et al.
Anticardiolipin antibodies in Grave's disease: relationship with thrombin activity in vivo.
Thromb Res.
1991;
64
(6)
745-749
-
39
Petri M, Karlson E W, Cooper D S, Ladenson P W.
Autoantibody tests in autoimmune thyroid disease: a case-control study.
J Rheumatol.
1991;
18
(10)
1529-1531
-
40
Díez J J, Doforno R A, Iglesias P, Sastre J, Gómez-Pan A, Borbujo J.
Anticardiolipin antibodies in autoimmune thyroid disease.
J Clin Lab Immunol.
1993;
40
(3)
125-134
-
41
Paggi A, Caccavo D, Ferri G M et al.
Anti-cardiolipin antibodies in autoimmune thyroid diseases.
Clin Endocrinol (Oxf).
1994;
40
(3)
329-333
-
42
Nabriski D, Ellis M, Ness-Abramof R, Shapiro M, Shenkman L.
Autoimmune thyroid disease and antiphospholipid antibodies.
Am J Hematol.
2000;
64
(1)
73-75
-
43
Osundeko O, Hasinski S, Rose L I.
Anticardiolipin antibodies in Hashimoto's disease.
Endocr Pract.
2001;
7
(3)
181-183
-
44
Tektonidou M G, Anapliotou M, Vlachoyiannopoulos P, Moutsopoulos H M.
Presence of systemic autoimmune disorders in patients with autoimmune thyroid diseases.
Ann Rheum Dis.
2004;
63
(9)
1159-1161
-
45
Dagenais P, Urowitz M B, Gladman D D, Norman C S.
A family study of the antiphospholipid syndrome associated with other autoimmune diseases.
J Rheumatol.
1992;
19
(9)
1393-1396
-
46
Innocencio R M, Romaldini J H, Ward L S.
Thyroid autoantibodies in autoimmune diseases.
Medicina (B Aires).
2004;
64
(3)
227-230
-
47
Mavragani C P, Danielides S, Zintzaras E, Vlachoyiannopoulos P G, Moutsopoulos H M.
Antithyroid antibodies in antiphospholipid syndrome: prevalence and clinical associations.
Lupus.
2009;
18
(12)
1096-1099
-
48
Traverse W, Tendler B, Galea C, Lakshminarayan S, Parke A.
Neuroendocrine manifestations of phospholipid antibody disease identified by long-term follow-up study of patients with phospholipid antibodies.
Ann N Y Acad Sci.
2006;
1069
386-390
-
49
Bendon R W, Wilson J, Getahun B, van der Bel-Kahn J.
A maternal death due to thrombotic disease associated with anticardiolipin antibody.
Arch Pathol Lab Med.
1987;
111
(4)
370-372
-
50
Pandolfi C, Gianini A, Fregoni V, Nalli G, Faggi L.
Hypopituitarism and antiphospholipid syndrome.
Minerva Endocrinol.
1997;
22
(4)
103-105
-
51
André M, Aumaître O, Piette J C, Thiéblot P.
Hypopituitarism in a woman with a severe primary antiphospholipid syndrome.
Ann Rheum Dis.
1998;
57
(4)
257-258
-
52
Ikeda K, Matsushita M, Ando S, Sekigawa I, Iida N, Hashimoto H.
A case of hypopituitarism and primary hypothyroidism associated with antiphospholipid syndrome [in Japanese].
Nihon Rinsho Meneki Gakkai Kaishi.
2000;
23
(1)
37-42
-
53
Essaïs O, Ouertani H, Bouzid C, Zidi B.
Hypopituitarism and antiphospholipid syndrome [in French].
Ann Endocrinol (Paris).
2003;
64
(4)
305-308
-
54
Galvin J A, Van Stavern G P.
Ischemic pituitary apoplexy associated with the lupus anticoagulant.
J Neurol Sci.
2004;
221
((1-2))
89-90
-
55
Khochtali I, Kacem M, Kria S, Golli M, Mahjoub S.
Pituitary necrosis and antiphospholipid syndrome [in French].
Ann Endocrinol (Paris).
2009;
70
(2)
126-128
-
56
Kengne F G, Decaux G.
Inappropriate secretion of ADH and central diabetes insipidus are related to antiphospholipid antibodies in SLE—case report and review of the literature.
Nephrol Dial Transplant.
2006;
21
(11)
3311-3315
-
57
Ben Hmida M, Bunker D, Baumelou A, Deray G, Bletry O, Jacobs C.
Inappropriate secretion of antidiuretic hormone (SIADH) in a patient with systemic lupus erythematosus (SLE): a case report.
Clin Nephrol.
1992;
37
(1)
34-35
-
58
Leventhal L J, Kobrin S, Callegari P E.
Systemic lupus erythematosus and the syndrome of inappropriate secretion of antidiuretic hormone.
J Rheumatol.
1991;
18
(4)
613-616
-
59
Elisaf M S, Milionis H J, Drosos A A.
Hyponatremia due to inappropriate secretion of antidiuretic hormone in a patient with systemic lupus erythematosus.
Clin Exp Rheumatol.
1999;
17
(2)
223-226
-
60
Tsai M H, Lu C S, Chen C J, Tsai W P, Liou L B.
Extrapontine myelinolysis in a patient with systemic lupus erythematosus: a case report.
J Formos Med Assoc.
2002;
101
(7)
505-508
-
61
Kajiyama H, Terai C, De Bellis A et al.
Vasopressin cell antibodies and central diabetes insipidus in a patient with systemic lupus erythematosus and dermatomyositis.
J Rheumatol.
2004;
31
(6)
1218-1221
-
62
Sánchez-Román J, Castillo-Palma M J, Ocaña Medina C, Villamil-Fernández F, Wichmann I.
Neurogenic diabetes insipidus in patients with systemic lupus erythematosus.
Ann Rheum Dis.
1998;
57
(4)
261-262
-
63
Tekin N, Kural N, Koçak A K, Köse S.
Diabetes insipidus in a pediatric patient with systemic lupus erythematosus. A case report.
Turk J Pediatr.
1997;
39
(2)
281-284
-
64
Scolari F, Savoldi S, Zubani R, Maiorca R.
Inappropriate ADH secretion: an unusual manifestation of antiphospholipid syndrome?.
Nephrol Dial Transplant.
1993;
8
(4)
382
-
65
Hendra T J, Baguley E, Harris E N et al.
Anticardiolipin antibody levels in diabetic subjects with and without coronary artery disease.
Postgrad Med J.
1989;
65
(761)
140-143
-
66
Triolo G, Giardina E, Scarantino G, Seddio G, Bompiani G.
Detection of anti-phospholipid (cardiolipin, phosphatidylserine) antibodies in the serum of patients with non insulin-dependent (type 2) diabetes mellitus and macroangiopathy. Coexistence of anti-platelet reactivity.
Diabetes Res.
1989;
10
(2)
63-67
-
67
Lorini R, d'Annunzio G, Montecucco C et al.
Anticardiolipin antibodies in children and adolescents with insulin-dependent diabetes mellitus.
Eur J Pediatr.
1995;
154
(2)
105-108
-
68
Vinik A I, Leichter S B, Pittenger G L et al.
Phospholipid and glutamic acid decarboxylase autoantibodies in diabetic neuropathy.
Diabetes Care.
1995;
18
(9)
1225-1232
-
69
Shigeta H, Yamaguchi M, Nakano K et al.
Serum autoantibodies against sulfatide and phospholipid in NIDDM patients with diabetic neuropathy.
Diabetes Care.
1997;
20
(12)
1896-1899
-
70
d'Annunzio G, Caporali R, Montecucco C et al.
Anticardiolipin antibodies in first-degree relatives of type 1, insulin-dependent, diabetic patients.
J Pediatr Endocrinol Metab.
1998;
11
(1)
21-25
-
71
Galtier-Dereure F, Biron C, Vies M, Bourgeois V, Schved J F, Bringer J.
Vascular complications of diabetes mellitus: what role for phospholipid-binding antibodies?.
Lupus.
1998;
7
(7)
469-474
-
72
Gargiulo P, Goldberg J, Romani B et al.
Qualitative and quantitative studies of autoantibodies to phospholipids in diabetes mellitus.
Clin Exp Immunol.
1999;
118
(1)
30-34
-
73
Ciarla M V, Bocciarelli A, Di Gregorio S et al.
Autoantibodies and endothelial dysfunction in well-controlled, uncomplicated insulin-dependent diabetes mellitus patients.
Atherosclerosis.
2001;
158
(1)
241-246
-
74
Alagözlü H, Bakici Z, Gültekin F, Yildirim B, Sezer H.
Anticardiolipin antibody positivity in diabetic patients with and without diabetic foot.
J Diabetes Complications.
2002;
16
(2)
172-175
-
75
Mohamed S M, Abdou M O, Assem H M, Moustafa T M, Soghier L M.
Anticardiolipin antibodies in children with insulin-dependent diabetes mellitus.
Metabolism.
2002;
51
(9)
1148-1152
-
76
Gin H, Vergnot V, Diakou V et al.
Anti-phospholipid antibodies in diabetes mellitus.
Clin Chem Lab Med.
2002;
40
(6)
604-608
-
77
Kalousová M, Fialová L, Skrha J et al.
Oxidative stress, inflammation and autoimmune reaction in type 1 and type 2 diabetes mellitus.
Prague Med Rep.
2004;
105
(1)
21-28
-
78
Tarkun I, Hacihanefioğlu A, Tarkun P, Cetinarslan B, Cantürk Z.
Anticardiolipin and anti-beta2 glycoprotein I antibody concentrations in patients with type 2 diabetes mellitus.
Diabetes Res Clin Pract.
2005;
68
(3)
181-187
-
79
Palomo I G, Mujica V E, Alarcón M L, Pereira J G, Vásquez M R.
Prevalence of antiphospholipid antibodies is not different in Chilean diabetic patients and normal individuals.
J Diabetes Complications.
2005;
19
(3)
133-137
-
80
Laadhar L, Zitouni M, Kallel-Sellami M, Bouguerra R, Chaabouni H, Makni S.
Spectrum of autoantibodies in Tunisian adult type 1 diabetes mellitus.
Ann N Y Acad Sci.
2007;
1107
356-362
-
81
Calvo-Romero J M, Lima-Rodríguez E M.
Anticardiolipin antibodies in patients with type 2 diabetes mellitus.
Clin Med Res.
2009;
7
(3)
93-95
-
82
Benekli M, Savaş M C, Erdem Y et al.
Primary hyperparathyroidism in a patient with systemic lupus erythematosus-antiphospholipid syndrome.
Nephron.
1998;
79
(2)
215-216
-
83
Sefer S, Trotić R, Degoricija V, Vrsalović M, Ratković-Gusić I, Kes P.
Healing of skin necrosis and regression of anticardiolipin antibodies achieved by parathyroidectomy in a dialyzed woman with calcific uremic arteriolopathy.
Croat Med J.
2001;
42
(6)
679-682
-
84
Carbone J, Dulin E, Sarmiento E, Micheloud D, Rodríguez A.
Antiphospholipid syndrome, hyperhomocysteinaemia and normocalcemic hyperparathyroidism.
Thromb Haemost.
2006;
95
(5)
900-901
-
85
Chernyshov V P, Radysh T V, Gura I V, Tatarchuk T P, Khominskaya Z B.
Immune disorders in women with premature ovarian failure in initial period.
Am J Reprod Immunol.
2001;
46
(3)
220-225
-
86
André M, Delèvaux I, Amoura Z et al.
Ovarian vein thrombosis in the antiphospholipid syndrome.
Arthritis Rheum.
2004;
50
(1)
183-186
-
87
Morales-Roselló J, Villa P, Amrani M.
Postpartum ovarian vein thrombosis with positive lupus anticoagulant.
Int J Gynaecol Obstet.
2004;
87
(2)
163-164
-
88
Leder A N, Flansbaum B, Zandman-Goddard G, Asherson R, Shoenfeld Y.
Antiphospholipid syndrome induced by HIV.
Lupus.
2001;
10
(5)
370-374
-
89
Göbel U, Kettritz R, Schneider W, Luft F C.
A particularly private pain.
Nephrol Dial Transplant.
2002;
17
(3)
516-518
Imad W UthmanM.D. M.P.H.
Department of Internal Medicine, American University of Beirut Medical Center
PO Box 11-0236, Riad El-Solh 1107, 2020 Beirut, Lebanon
Email: iuthman@aub.edu.lb
