A case of hypopituitarism associated with antiphospholipid syndrome

K. IKEDA, M. TAKAHAMA, M. MATSUSHITA, S. ANDO, I. SEKIGAWA, N. IIDA and H. HASHIMOTO1

Department of Medicine, Juntendo University, Izu-Nagaoka Hospital, 1129 Nagaoka, Izu-Nagaoka-cho, Tagata-gun, Shizuoka 410–2295,
1 Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113, Japan

SIR, The major clinical features of antiphospholipid syndrome (APS) are thromboses, thrombocytopenia, and recurrent fetal demise. Recent reports have indicated that antiphospholipid antibodies (aPL) are also related to other clinical manifestations, including cardiac valve lesions and haemolytic anaemia with or without underlining autoimmune diseases such as systemic lupus erythematosus (SLE), although the precise mechanism of aPL on the induction of these features is still unclear [1]. We recently encountered a case of multiple hormonal deficiencies in the pituitary gland associated with APS. This patient was a 39-yr-old woman who was admitted to our hospital with the chief complaints of coughing, fever, and clouding of consciousness due to hypoglycaemia (blood sugar level at hospitalization 44 mg/dl). She had been suspected of having Sheehan's syndrome because of her clinical symptoms (fatigue, failure to lactate and to resume menses) and hormonal abnormalities [low levels of adrenocorticotrophic hormone (ACTH) and prolactin (PRL)] after parturition at the age of 33 yr. However, this diagnosis was not confirmed due to discontinuance of clinical care at her own request despite persistence of her symptoms. On hospitalization, her hormonal examination revealed partial pituitary gland dysfunction (ACTH <5 pg/ml, normal = 9–52; PRL <1.0 ng/ml, normal = 1.4–14.6; thyroid stimulating hormone (TSH) 6.4 µU/ml, normal = 0.34–3.5; growth hormone 1.62 ng/ml, normal = 0.66–3.68; luteinizing hormone 1.2 mIU/ml, normal before menopause = 1.0–34.9; follicle stimulating hormone 9.3 mIUml, normal before menopause = 2.0–14.8; antidiuretic hormone 1.4 pg/ml, normal = 0.3–3.5), related adrenocortical insufficiency (cortisol < 1.0 µg/dl, normal = 4.8–18.3), and primary hypothyroidism (TSH 6.4 µU/ml, normal = 0.34–3.5; free triiodothyronine 2.21 pg/ml, normal = 2.47–4.34; free thyroxine 0.57 ng/dl, normal = 0.97–1.79). A magnetic resonance imaging (MRI) examination disclosed ‘empty sella’ of the hypophysis, which is the neuradiological finding of pituitary necrosis [2] (Fig. 1Go). Part of the pituitary hormones was thought to be produced from the remaining pituitary gland. Antipituitary antibodies which are observed in autoimmune hypophysitis [3] were not detected in this patient. Her hypoglycaemic attacks were thought to be caused by this hormonal dysregulation. Even after the return of consciousness by intravenous administration of glucose, she complained of general malaise and clinical examination revealed somnolence and hypomimic face. In addition, thrombocytopenia (platelet count 75 000 /mm3) was observed and aPL was detected in the immunological examination [lupus anticoagulant (LAC) 85.7 s, normal <55.5; anticardiolipin antibodies IgG, 1.2, normal <0.8, IgM 1.4, normal <1.0, ß2-glycoprotein 1, 1.2, normal < 3.5] although proper investigations allowed us to exclude other connective tissue diseases such as SLE. Her thrombocytopenia and positive reactions of aPL were pointed out before hospitalization. Based on these findings, she was diagnosed as having hypopituitarism and primary hypothyroidism associated with APS. After hormonal replacement therapy was started with hydrocortisone 10 mg/day and levothyroxine sodium 100 µ/day, the patient recovered gradually to a satisfactory physical and psychological condition as well as showing improvement of thrombocytopenia.



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FIG. 1. Empty sella (arrow) in the patient's anterior and posterior lobes of hypophysis indicated by MRI examination.

 
Hypopituitarism of the patient had probably occurred after her delivery, so she was thought to have Sheehan's syndrome. In this admission, it seems that her endocrine dysfunction was exacerbated by infections, and that the hormonal replacement therapy by steroid was effective for not only her hormonal disorder but also thrombocytopenia by its action as an immunosuppressive agent. In fact, the titre of aPL was decreased by the treatment. As the pituitary gland is rich with blood vessels, the empty sella of the pituitary gland and related hypopituitarism of our patient may be related to the formation of thrombi caused by aPL. Among risk factors of anterior pituitary insufficiency, vascular damage has been recognized since the first demonstration of ischaemic post-parturient hypophyseal necrosis in 1937 [4]; other vascular causes were reported later, such as sickle cell anaemia, cavernous sinus thrombosis, temporal arteritis, aneurysm of intracranial carotid artery, eclampsia, and pituitary apoplexy [5]. To date, primary and secondary hypopituitarisms, adrenal insufficiencies (Addison's disease), and hyperthyroidisms (Graves' disease) have been reported as endocrine disorders related to cases of APS, besides our patient [5–11]. As far as we know, there are two reported cases of hypopituitarisms related to APS. Primary hypothyroidism was observed in one of them as well as our patient, although the aetiological relationship between hypothyroidisms and APS is unclear. However, there are no reported cases which were suggested to be Sheehan's syndrome and/or in which onsets were related to parturitions [5, 6]. Furthermore, although these reported cases indicated that many such patients showed recurrent multiple thrombotic events affecting veins and arteries, including myocardial infarction and cerebral stroke [5, 6], our patient did not show such symptoms. Our case indicates that the presence of aPL, even if such thrombotic events are not observed, may be one of the risk factors for endocrine diseases, including Sheehan's syndrome, and aPL-related onset of these diseases may be more frequent than is generally appreciated.

Notes

Correspondence to: I. Sekigawa. Back

References

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Accepted 21 October 1999