Associated Report. th ACTH, PRL, and GH

Transcription

1 Endocrine Journal 1994, 41(3), Severe Dep Deficiency: ression A Case Associated Report wi th ACTH, PRL, and GH KEISUKE KAWAI, HAJIME TAMAI, HIROAKI NISHIKATA, NoBUYUKI KOBAYASHI, AND SUNAO MATSUBAYASHI Department o f Psychosomatic Medicine, Faculty o f Medicine, Kyushu University, Fukuoka 812, Japan Abstract. A 68-year-old man was hospitalized in August, 1990 with general malaise, loss of energy, poor appetite and severe depression. He had experienced depressed moods, markedly diminished interest, feelings of worthlessness, diminished ability to think, general malaise and muscle weakness beginning in November, He was treated for depression at another hospital until his emergent admission to our hospital because of difficulty in walking. Laboratory studies disclosed hyponatremia, low plasma ACTH level (4.2 pmol/l), and a low cortisol level (27.6 nmol/l). Rapid ACTH test elicited an increase in serum cortisol from 75.6 nmol/l to nmol/l at 30 min. Ovine corticotropin releasing hormone (CRH) did not stimulate secretion of either ACTH or cortisol. Human growth hormone releasing hormone (GRH) together with thyrotropin releasing hormone (TRH) elicited a normal response of TSH and low responses of GH and PRL. The patient's serum autoantibodies to anterior pituitary cell membranes using GH3 rat pituitary cells and AtT-20 mouse pituitary cells were positive. On the basis of these data, the diagnosis of selective ACTH, GH and PRL deficiency was made and thought to have been caused by lymphocytic adenohypophysitis. Following cortisol replacement therapy, he quickly regained his appetite and was restored to a normal mental state of being. Key words; Depression, Adrenocorticotropic hormone (ACTH) deficiency, Lymphocytic adenohypophysitis. (Endocrine Journal 41: ,1994) IT HAS BEEN recognized that psychiatric signs and symptoms are common in endocrine disorders [1]. Depressive states have been reported to be associated with Cushing's syndrome and Addison's disease [2]. We herein report a patient with ACTH, PRL, and GH deficiency who had been treated earlier for depression which was characterized by general malaise, loss of energy, depressed mood, diminished interest, feelings of worthlessness, diminished ability to think, headache, nausea, poor appetite Received: October 6, 1993 Accepted: February 9, 1994 Correspondence to: Dr. Hajime TAMAI, Department of Psychosomatic Medicine, Faculty of Medicine, Kyushu University 60, Maidashi, Higashi-ku, Fukuoka 812, Japan and arthralgia of all extremities. Following cortisol replacement therapy, his psychiatric signs and symptoms rapidly improved and ultimately disappeared. The causes of this syndrome and the relationship between the syndrome and the psychiatric symptoms are discussed. Case Report A 68-year-old man was admitted to our hospital in August, 1990, with general malaise, difficulty in walking, weight loss of 6 kg, poor appetite and in a severe depressive state. He had history of pneumonia and atrial flutter 2 years and 8 months, respectively, prior to admission. There was a family history of hypertension in his brother and apo-

2 276 KAWAI et al. plexy in both parents. He began experiencing general malaise and muscle weakness in November, One month later, he was admitted to another hospital because of atrial flutter. At the same time, he became progressively depressed. He had markedly diminished interest and feelings of worthlessness and loss of energy. His ability to think, decreased and he had headaches, nausea, poor appetite and weight loss, and arthralgia of all extremities. These symptoms gradually and progressively worsened. He became emaciated and was treated for malnutrition, but did not improve. He was then treated for depression with anti-depressant drugs for the next three months until his emergent admission to our hospital in August, On admission, his height was cm, weight was 48.6 kg and blood pressure was 168/68 mm Hg. He was lethargic, no hyperpigmentation of the skin or oral cavity was noted, his thyroid was not enlarged and pubic hair was not decreased. Muscle rigidity and pain were present on movement of his neck and extremities, and decreased muscle strength in all extremities was observed. A self-rating depression score (SDS) test [3] revealed a score of 53 (normal < 40). Laboratory tests were as follows: RBC count 3.7 X 1012/L, Hb 115 g/l, hematocrit 0.33, WBC count 4.0 X 109/L, and blood glucose was 3.5 mmol/l. Other laboratory studies disclosed hyponatremia (121 mmol/l), a low plasma ACTH level (4.2 pmol/l) at 0800 h, low serum cortisol level (27.6 nmol/l) at 0800 h and low urinary 17-OHCS (3.0,umol/day) and 17-KS (5.5 pmol/day). Serum T3 was 0.77 nmol/l, free T4, nmol/l and TSH, 1.94 mu/ L (Table 1). Serological tests for antithyroglobulin and antithyroid microsomal antibodies were negative. A 75 g oral glucose test was normal. Rapid adrenocorticotropic hormone (ACTH) test (500 µg) elicited an increase in serum cortisol from 75.6 nmol/l to nmol/l at 30 min. Ovine corticotropin releasing hormone (CRH) did not stimulate secretion of either ACTH or cortisol. A human growth hormone releasing hormone (GRH) stimulation test elicited a low response of serum GH, and a thyrotropin releasing hormone (TRH) stimulation test elicited a normal response of TSH but a low response of prolactin (PRL) (Table 2). Anterior pituitary cell antibodies (PAb-1) were negative using an immunofluorescence method [4], but autoantibodies to anterior pituitary cell membranes (PAb-2) using GH3 rat pituitary cells (GH and PRL secreting cells) and AtT-20 mouse pituitary cells (ACTH secreting cells) were positive using an immunofluorescence method [4]. Serum antipituitary antibody levels were examined by avidin-biotin fluoresent antihuman v-globulin staining in either rat pituitary slice for cell antibodies or in cultured pituitary cells of the AtT20 or GH3 for cell-surface antibodies. The fluorescence positive cell score is the number of fluorescence positive cells relative to 100 cells counted under a microscope. Sera of which scores were >25% and 6% were estimated to be antibodies positive for GH3 and AtT-20 cells, respectively. Magnetic resonance imaging (MM) revealed a small cystic lesion in the pituitary gland Table 1. Basal serum hormone concentrations in a patient with ACTH, deficiency at the time of hospital admission GH and PRL

3 DEPRESSION AND ACTH DEFICIENCY 277 Table 2. Provocative endocrine tests in a patients with ACTH, and after cortisol replacement GH and PRL deficiency before Table 3. Comparison before and cortisol of symptoms and after one month of laboratory treatment data with ment therapy (20 mg/day) was begun. After 3 days of replacement therapy, the patient regained his appetite and mental alertness, and began to feel certain about his recovery. A repeat of the SDS test at that time revealed a score of 32. After 1 week of cortisol treatment, the hyponatremia was improved, and after 1 month of treatment, his low serum T3 level, rigidity of neck and extremities, arthralgia and difficulty in elevating his upper extremities were markedly improved (Table 3). However, the responses of GH and PRL on a human GRH together with TRH stimulation test remained low (Table 2). Discussion that measured 5 mm with a TI enhanced image; there was low intensity, while the lesion changed to high intensity in the late stage when Gadolinium-Diethylene Pentaacetic Acid (Gd-DTPA) was used. On the basis of the above data, the diagnosis of selective ACTH, GH and PRL deficiency syndrome was established, and cortisol replace- We have reported a patient with selective ACTH, GH and PRL deficiency whose primary symptoms were those associated with marked depression. It has been recognized that other psychiatric signs and symptoms e.g., coma, anorexia and weight loss, nausea, headache and seizures [5, 6] are common in ACTH deficiency syndromes as well as in Addison's disease [2]. To our know!-

4 278 KAWAI et al. edge, there are a few reports on the relationship between the depressed state and ACTH deficiency, but they present no detailed information [7, 8]. Depression associated with ACTH deficiency is difficult to detect, because ACTH deficiency is usually partial deficiency, and therefore is less severe than Addison's disease on the basis of the serum cortisol level, and ACTH deficiency does not have characteristic symptoms. Our patient had severe depression which normalized dramatically after glucocorticoid replacement therapy. It had been established that the mechanism of the psychiatric symptoms of Addison's disease can be explained by a decrease in serum glucocorticoids and sodium [2]. The same mechanism applies to ACTH deficiency [7]. Recently the interaction between hypothalamic CRH and locus ceruleus (LC)-norepinephrine (NE)/autonomic systems has been clarified in major depression [9]. As in major depression, CRH might play a role in pituitary ACTH deficiency. If the primary disease (ACTH deficiency) had not been diagnosed and treated appropriately and quickly, it might have resulted in irreversible, chronic, organic brain damage [10]. It should be emphasized that ACTH deficiency should be diagnosed differentially from the diagnosis of depression whenever patients present themselves with symptoms of depression. It has been hypothesized that lymphocytic adenohypophysitis is a possible cause of hypopituitarism with dense infiltrates of lymphocytes and plasma cells with interstitial fibrosis and lymphoid follicles with pale germinal centers in the pituitary glands and positive for anti-pituitary antibodies in sera [11]. And, lymphocytic adenohypophysitis is related to the pathogenicity of ACTH deficiency [12]. Kojima et al. [13] and Richtsmeiter et al. [14] suggest that PAb-2 may contribute to the pathogenicity of the autoimmune mechanism which causes ACTH deficiency. The final diagnosis of lymphocytic adenohypophysitis is reached by histological study, but immunological study of the serum is useful [12]. On CT scanning, many patients with lymphocytic adenohypophysitis show large parasellar masses [15]. Although histopathological examination was not performed on our patient and the size of the mass was too small, he had antipituitary antibodies in his serum. Therefore, the deficiency of ACTH, GH and PRL in this case was thought to result from lymphocytic adenohypophysitis. References 1. Brambilla F, Musettic C, Tacchinic, Petraglia F, Guareschi-Cazzullo A (1992) Psychopathological aspects of neuroendocrine disease: possible parallels with the psychoendocrine aspects of normal aging. Psychoneuroendocrinol 17: Johonshone PAS, Rundell JR, Esposito JR (1990) Mental status changes of Addison's disease. Psychosomatics 31: Zung WWK (1965) A self-rating depressive scale. Arch Gen Psychiatry 12: Sugiura M, Hashimoto A, Shizawa M, Tsukada M, Saito T, Hayami H, Maruyama S, Ishido T (1987) Detection of antibodies to anterior pituitary cell surface membrane with insulin dependent diabetes mellitus and adrenocorticotropic hormone deficiency. Diabetes Research 4: Stacpoole PW, Interlandi JW, Nicholson WE, Rabin D (1982) Isolated ACTH deficiency: a heterogeneous disorder, clinical review and report of four new cases. Medicine 61: Sauter NP, Mclaughlin CD, Dyess EM, Kritzman J, Lechan RM (1990) Isolated adrenocorticotropin deficiency associated with an antibody to a corticotroph antigen that is not adrenocorticotropin or other proopiomelanocortin-derived peptides. J Clin Endocrinol Metab 70: Endo M, Endo J, Notsu K, Note S (1983) Mental status in a patient with isolated ACTH deficiency. Biol Psychiatry 18: Choy EHS, Corkill MM, Gibson T, Hicks BH (1991) Isolated ACTH deficiency presenting with bilateral frozen shoulder. Br J Rheumatol 30: Chrousos GP, Gold PW (1992) The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 267: Bleuler M (1979) Endokrinologische Psychiatrie. In: Hess R (ed) Psychiatrie der Genenwart. Berlin, Springer ed 2, p Guay AT, Agonello V, Tronic BC, Gresham DG, Freidberg SR (1987) Lymphocytic hypophysitis in a man. J Clin Endocrinol Metab 64: Yamamoto T, Fukuyama J, Hasegawa K, Sugiura M (1992) Isolated corticotropin deficiency in adults. Report of 10 cases and review of literature. Arch Intern Med 152:

5 DEPRESSION AND ACTH DEFICIENCY Kojima I, Nejima I, Ogata E (1982) Isolated adrenocorticotropin deficiency associated with polyglandular failure. J Clin Endocrinol Metab 54: Richtsmeier AJ, Henry RA, Bloodworth MB, Ehrlich EN (1980) Lymphoid hypophysitis with selective adrenocorticotropic hormone deficiency. Arch Intern Med 140: Tindall CT, Barrow DL (1986) Pituitary deficiency states. In: Tindall CT, Barrow DL (eds) Disorders of the Pituitary. Mosby, St. Louis,