Sarcoidosis, anterior pituitary failure, and diabetes insipidus

3
BRIEF REPORT SARCOIDOSIS, ANTERIOR PITUITARY FAILURE, AND DIABETES INSIPIDUS Peter Garrett, Claire Langan, Josephine Egan, Elthne Mulloy and John O'Donnell Department of Medicine and Endocrinology, Regional Hospital, Galway. Summary We report a case of sarcoidosis and anterior pituitary failure in which frank diabetes insipidus was unmasked by glucocorticcid replacement therapy. rntroduction Circulating levels of glucocorticoids are known to influence release of antidiuretic hormone (ADH). In clinical practice, this effect may be observl~d as the unmasking of true diabetes insipidus (DI) by commencement of glucocorti- cold replacement therapy in patients with pituit- ary failure. Material and Methods Serum and urine osmolalities were determined by Wescor vapour pressure osmometer after an overnight fast. Free thyroxine was estimated by Thyopac kit (Amersham). Dynamic pituitary function tests were performed by measuring the responses of serum cortisol and growth hormone (GH) to insulin-provoked hypoglycaemic stress; of thyroid-stimulating hor- mone (TSH) and prolactin (Prl) to thyrotrophin releasing hormone (TRH); and of follicle stimu- lating hormone (FSH) and luteinizing hormone (LH) to luteinizing hormone releasing hormone (LHRH). Blood samples for assay of these hor- mones and for plasma glucose estimation were taken before and at intervals after injection of soluble insulin 0.1 unit/kg body weight intraven- ously, TRH 4 mcg/kg body weight intravenously, and LHRH 2 mcg/kg body weight subcutaneously (Table I). Plasma glucose was measured by Beckmann Auto-Analyzer. Serum cortisol, TSH, and Prl were determined by radioimmunoassay using standard Amersham kits (serial numbers IM2021, IM1000, and IM1060 respectively). Serum GH, FSH, and LH were also estimated by radioimmunoassay. Antisera for GH and FSH were supplied by KABI, Stockholm. For LH, anti- serum RHL-5:8/23/72 was used (Skrabanek et a/, 1981). Standard preparations were procured via the National Institute for Biological Standards and Control, London. All assays were performed in the Department of Biochemistry, Galway Regional Hospital, except for GH, FSH, and LH, which wcre carried out in the Endocrine Laboratory, Mater Hospital, Dublin. Case Report A 36-year old woman attended clinic complain- ing of pain, stifness, and swelling of her fingers for the preceding 4 moths. Direct questioning revealed that she had suffered from absent periods, loss of libido, painful sexual intercourse, and infertility since the birth of her third child 5 years previously. Her periods had returned briefly some months after delivery, and she had 3 normal cycles before they stopped altogether. She did not lactate after her confinement, but neither had she following her previous pregnan- cies. There was no history of significant peri- partum haemorrhage. On examination she was a small (height 1.43 m) female who looked older than her stated age. No clinical signs of thyroid failure weFe apparent. Purplish indurated plaques one to four centimeters in diameter were noted on the lateral aspects of both upper arms, the cheeks, the forehead, and the right ear; according to the patient these had been present for the past 7 years. There was no pubic or axillary hair. The breasts were normal; milk could not be expressed from either nipple. Formal testing of the visual fields was normal and there were no clinical features to suggest an expanding lesion in the neighbourhood of the pituitary fossa. Chest radiography demonstrated no abnorm- ality, although a film taken 4 years previously had shown bilateral hilar prominence. Hand X- rays revealed ill-defined irregular erosion of bone. Skull X-ray disclosed a small pituitary fossa and erosions of the bony vault. Standard thyroid function tests were in the hypothyroid range with a free thyroxine index of 48 (normal range 50- 150). Dynamic pituitary function tests demon- strated low baseine levels with inadequate re- sponse to stimulation of all pituitary hormones, including Prl (Table I). Biopsy of one of the skin lesions showed numerous non-caseating epithel- ioid granulomata typical of sarcoidosis. Replacement therapy with hydrocortisone 20 mg in the morning and 10 mg in the evening was commenced. When next seen the patient volun- 136

Transcript of Sarcoidosis, anterior pituitary failure, and diabetes insipidus

BRIEF REPORT

SARCOIDOSIS, ANTERIOR PITUITARY FAILURE, AND DIABETES INSIPIDUS

Peter Garrett, Claire Langan, Josephine Egan, Elthne Mulloy and John O'Donnell

Department of Medicine and Endocrinology, Regional Hospital, Galway.

Summary We report a case of sarcoidosis and anterior

pituitary failure in which frank diabetes insipidus was unmasked by glucocorticcid replacement therapy.

rntroduction Circulating levels of glucocorticoids are known

to influence release of antidiuretic hormone (ADH). In clinical practice, this effect may be observl~d as the unmasking of true diabetes insipidus (DI) by commencement of glucocorti- cold replacement therapy in patients with pituit- ary failure.

Material and Methods Serum and urine osmolalities were determined

by Wescor vapour pressure osmometer after an overnight fast. Free thyroxine was estimated by Thyopac kit (Amersham).

Dynamic pituitary function tests were performed by measuring the responses of serum cortisol and growth hormone (GH) to insulin-provoked hypoglycaemic stress; of thyroid-stimulating hor- mone (TSH) and prolactin (Prl) to thyrotrophin releasing hormone (TRH); and of follicle stimu- lating hormone (FSH) and luteinizing hormone (LH) to luteinizing hormone releasing hormone (LHRH). Blood samples for assay of these hor- mones and for plasma glucose estimation were taken before and at intervals after injection of soluble insulin 0.1 unit/kg body weight intraven- ously, TRH 4 mcg/kg body weight intravenously, and LHRH 2 mcg/kg body weight subcutaneously (Table I).

Plasma glucose was measured by Beckmann Auto-Analyzer. Serum cortisol, TSH, and Prl were determined by radioimmunoassay using standard Amersham kits (serial numbers IM2021, IM1000, and IM1060 respectively).

Serum GH, FSH, and LH were also estimated by radioimmunoassay. Antisera for GH and FSH were supplied by KABI, Stockholm. For LH, anti- serum RHL-5:8/23/72 was used (Skrabanek et a/, 1981). Standard preparations were procured via the National Institute for Biological Standards and Control, London.

All assays were performed in the Department of Biochemistry, Galway Regional Hospital,

except for GH, FSH, and LH, which wcre carried out in the Endocrine Laboratory, Mater Hospital, Dublin.

Case Report A 36-year old woman attended clinic complain-

ing of pain, stifness, and swelling of her fingers for the preceding 4 moths. Direct questioning revealed that she had suffered from absent periods, loss of libido, painful sexual intercourse, and infertility since the birth of her third child 5 years previously. Her periods had returned briefly some months after delivery, and she had 3 normal cycles before they stopped altogether. She did not lactate after her confinement, but neither had she following her previous pregnan- cies. There was no history of significant peri- partum haemorrhage.

On examination she was a small (height 1.43 m) female who looked older than her stated age. No clinical signs of thyroid failure weFe apparent. Purplish indurated plaques one to four centimeters in diameter were noted on the lateral aspects of both upper arms, the cheeks, the forehead, and the right ear; according to the patient these had been present for the past 7 years. There was no pubic or axillary hair. The breasts were normal; milk could not be expressed from either nipple. Formal testing of the visual fields was normal and there were no clinical features to suggest an expanding lesion in the neighbourhood of the pituitary fossa.

Chest radiography demonstrated no abnorm- ality, although a film taken 4 years previously had shown bilateral hilar prominence. Hand X- rays revealed ill-defined irregular erosion of bone. Skull X-ray disclosed a small pituitary fossa and erosions of the bony vault. Standard thyroid function tests were in the hypothyroid range with a free thyroxine index of 48 (normal range 50- 150). Dynamic pituitary function tests demon- strated low baseine levels with inadequate re- sponse to stimulation of all pituitary hormones, including Prl (Table I). Biopsy of one of the skin lesions showed numerous non-caseating epithel- ioid granulomata typical of sarcoidosis.

Replacement therapy with hydrocortisone 20 mg in the morning and 10 mg in the evening was commenced. When next seen the patient volun-

136

SARCOIDOSIS, ANTERIOR PITUITARY FAILURE, AND DIABETES INSIPIDUS 137

TABLE I

Glucose and hormone levels before and after injection of soluble insulin 5 units intravenously, TRH 200 meg intravenously, and LHRH 100 mcg subcutaneously.

Time Glucose Cortisol GH TSH Prl LH FSH rains mmol/I nmol/I mU/I mU/I mU/I IU/I IU/I

--15 115 1.0 0 3.4 77 1.0 0.4 0 0 0

15 2.1 106 1.0 0 0

20 0.4 0

30 1.1 168 1.0 2.0 0

45 1.6 218 1.0 2.0 0

60 3.1 185 1.0 0.4 0 0 0

90 2.0 179 1.0

teered that she was feeling much better, but complained spontaneously of being unusually thirsty and passing large quantities of urine. An overnight water deprivation test demonstrated a maximum urine tonicity of only 408 m0sm/kg despite a serum tonicity of 315 m0sm/kg, con- firming a mild degree of DI. Thyroxine replace- ment was subsequently introduced in a dose of 150 mcg daily.

Six months after starting glucocorticoid re- placement therapy the patient states that there has been a great improvement in general well- being with return of libido. The finger pain, stiffness, and swelling have vanished and there has been marked regression of the skin plaques. She no longer complains of thirst or polyuria, although simultaneous measurements of urine and serum tonicity still show poor concentration of the urine, with urine osmolality of 339 m0sm/ kg corresponding to serum osmolality of 300 mOsm/kg.

Discussion

Sarcoidosis is recognized as a cause of both anterior pituitary failure and DI, and seems to be the likeliest aetiology for both syndromes in the case reported here.

Anterior pituitary failure may be either primary or secondary to hypothalamic disease. Primary anterior pituitary disease was demonstrated in this case by the absence of a secretory response to the hypothalamic releasing hormones TRH and LHRH, as well as by low serum Prl levels. On the other hand the presence of continuing DI suggests disease within the hypothalamus, since experimental destruction of the posterior pituitary does not cause permanent DI unless the hypothalamus is also damaged.

The suggestion that the presence of clinical DI requires the anterior pituitary to be at least

partially intact was first made on the basis of autopsy studies (von Harm, 1918). Amelioration of the symptoms of DI with the onset of anterior pituitary disease has since been observed (Leaf e t a l , 1952) The converse observation, that gluco-corticoids may unmask latent DI, is well recognised. However, chronic glucocorticoid de. ficiency is known to cause fluid retention, and it may be that some of the cases quoted as illustrating the unmasking of DI by glucocorticoid replacement are merely examples of diuresis of this excess fluid (Davis and Hipkin, 1977). In fact, our search of the literature has not dis- closed any specific cases in which DI was subsequently confirmed.

In the case under discussion true rather than apparent DI was illustrated by the presence of polydipsia in addition to polyuria and the finding that the urine was not concentrated despite elevation of serum osmolality. Since symptoms of DI did not arise until after the introduction of glucocorticoid replacement a pro-treatment water deprivation test was not carried out, and with- drawal of steroids to determine whether ability to concentrate the urine returned was not con- sidered justifiable.

Fluid retention in chronic glucocorticoid de- ficiency may be due to several possible mechan- isms, including alteration of the osmotic threshold of ADH-secreting cells in the hypothalarnus (Aubrey et at, 1965).

Thyroid failure also causes fluid retention, and thyroxine replacement may theoretically unmask DI. However, in this patient DI was suspected and confirmed before thyroxine replacement was commenced.

We suggest that patients with anterior pituitary failure should be monitored for development of frank DI after starting glucocorticoid replacement therapy.

138 IRISH JOURNAL OF MEDICAL SCIENCE

Our thanks are due to Dr. Helen Grimes, De- partment of Biochemistry, and Dr. Malcolm Little, Department of Histopathology, Galway Regional Hospital; and to Miss OIwyn Lanigan, Endocrine Laboratory, Mater Misericordiae Hospital, Dublin.

References

Aubrey, R. H., Nankin, H. R., Moses, A. M. and Streeten, D. H. P. 1965. Measurement of the osmotic threshold for vasopressin release in human subjects, and its modification by cor- tisol. J. Clin. Endocrinol. 21, 337-365.

Davis, J. C. and Hipkin, J. L. 1977. Cinical Endo- crine Pathology. Blackwell, Oxford, p. 77.

Leaf, A., Mamby, A. R., Rasmussen, H. and Marasco, J. P. 1952. Some hormonal aspects of water excretion in man. J. Clin. Invest. 31, 914-827.

Skrabanek, P., Balfe, A., Webb, M., Maguire, J. and Powell, D. 1981. Electroconvulsive therapy (ECT) increases plasma growth hormone, pro- lactin, luteinizing hormone and follicle-stimu- lating hormone but not thyrotropin or sub- stance P. Psychoneuroendocrinology 6, 261- 267.

Von Hann, F. 1918. Ueber die Bedengtung der Hypophysenver&nderungen bei Diabetes insip- idus. Frankfurt Z. Path. 21, 337-365.