Case report

Michał Graczyk1, Anna Kamińska2, Michał Kamiński3, Roman Junik2, Małgorzata Krajnik1 1Chair and Department of Palliative Care, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Poland 2Clinic of and Diabetology, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Poland 3Endocrinology Outpatient Clinic of Prof. Franciszek Łukaszczyk, Oncology Centre in Bydgoszcz, Poland

Diabetes insipidus in the diagnosis of

Abstract

Diabetes insipidus is a rare condition, whereas polyuria may be a symptom of numerous other ailments. Polyuria intensifies (), which appears to be a natural reaction to an excessive loss of water in the organism. Before diagnosing rare conditions, hypoglycaemia and failure must be excluded. Borderline cases must consult with an endocrinology specialist.

Key words: polyuria, polydipsia, diabetes insipidus

Adv. Pall. Med. 2011; 10, 3–4: 111–114

Introduction — post-operative condition or post-radiotherapy condition (RTH); Diabetes insipidus (DI) is a rare illness caused — ectopic secretion by other malignant tumours; either by deficiency (central diabetes in- — [1, 2]. sipidus, also known as neurohormonal) or by a lack Moreover, neurohormonal diabetes insipidus may of renal canal sensitivity to vasopressin (nephrogenic be idiophatic, either genetically or immunologically diabetes insipidus) [1]. based. The prevalence of diabetes insipidus is one case Nephrogenic diabetes insipidus is caused by a ge- per 25,000 population, with no sex difference. Cen- netic defect in the vasopressin receptors in the kid- tral diabetes insipidus is the result of damage to neys and occurs only in males. It may also occur in the supraoptic nuclei in the , where either acquired neuropathies, such as hypercalcaemia vasopressin is secreted. In such a case, the damage (e.g. hyperactive parathyroid glands) or hyperkalae- leads to permanent DI. In rare cases, for example mia (e.g. primary aldosteronism). when a patient suffers either post-operative in- The clinical picture of diabetes insipidus is influ- fundibulum hypothalamus damage or rear hypotha- enced by the following symptoms: lamus lobe damage (the area which transports and — excessive thirst (polydipsia); stores the neurohormone), the disorder may be — polyuria (passing > 4 litres of urine a day); a passing matter. Neurohormonal diabetes insip- — low specific gravity of the urine (< 1,005; so-called idus is caused in most cases by: diluted urine); — hypothalamus tumours (, — frequent nightly and quenching of invasive pituitary macroadenomas); thirst; — hypothalamic-pituitary area inflammation; — additionally, symptoms of hypothalamic-pituitary — injury; tumour may occur [1].

Address for correspondence: Michał Graczyk Chair and Department of Palliative Care, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Poland e-mail: [email protected] Advances in Palliative Medicine 2011, 10, 111–114 Copyright © 2011 Via Medica, ISSN 1898–3863

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Diagnosis of the disorder is determined by istered, either orally (0.2 mg) or intranasally (20 μg). a two-stage test and a vasopressin test. Only then can the specific gravity, osmolarity and First of all, this allows the exclusion of psychogen- volume of the successive portions of urine be calcu- ic-based polydipsia (psychogenic diabetes insipidus, lated. If the urine concentration increases by at least thirst neurosis), when polyuria is caused by habitual 50% after is administered, this indi- excessive fluid intake. Furthermore, the test ena- cates that we are dealing with central diabetes insip- bles us to determine whether we are dealing with idus. However, a persistent decrease in urine specific neurohormonal diabetes insipidus or nephrogenic gravity and its osmolarity suggests nephrogenic dia- diabetes insipidus (Table 1). The test is carried out betes insipidus. In a case where a magnetic resonance in hospital, prior to excluding polyuria in diabetes. imaging (MRI) of the head has not been performed The dehydration test is a urine concentration on a patient before the test, such a procedure must test which consists of the complete restriction of absolutely be conducted [1]. fluid intake. The test begins in the morning and the The treatment of diabetes insipidus depends upon patient is weighed every 30 minutes. Simultaneously, its cause. In the case that central diabetes insipi- the specific gravity (or osmolarity) of successive sam- dus is a symptom of a large hormonally inactive ples is calculated, as well as the plasma osmolarity. , what appears to treat the cause The test continues as long as the body mass reduc- is a neurosurgical procedure through the transsphe- es by 3% of the initial weight proportion or the con- noidal route. On the other hand, in the symptomatic centration of in the blood serum exceeds the treatment of diabetes insipidus we employ a substi- upper limit of normal. The test usually takes a few tution which involves an individually calculated dose hours and enables the calculation of the vasopressin of a long-acting vasopressin analog (desmopressin). in the blood serum. In central diabetes insipidus the The substance is administered via the intranasal or vasopressin concentration is very low, whereas neph- oral route. The effectiveness of the treatment can be rogenic diabetes insipidus causes high vasopressin evaluated easily: as soon as the clinical symptoms dis- concentration. In central DI neither a urine specific appear, plasma osmolarity returns to normal and the gravity nor urine osmolarity increase is reported (os- sodium in the serum normalizes. If diabetes insipi- molarity < 250 mOsm/kg) with a plasma osmolarity dus results from acquired kidney damage, care of the increase (norm: 275–190 mOsm/kg). On the other underlying illness and symptomatic treatment seem hand, in psychogenic polydipsia, once vasopressin to be essential (with appropriate hydration and fluid is stimulated, increases. deficiency correction). Any symptoms of diabetes in- The vasopressin test appears in the second phase sipidus caused by disturbances disappear of the diagnostic process. It differentiates central as soon as the disturbances are equalized. In diabe- diabetes insipidus from nephrogenic diabetes insip- tes insipidus resulting from genetic defects in the idus. In the dehydration test, as soon as successive vasopressin receptors, what appears to be a basis for urine samples do not reveal significant differences in treatment is an appropriate diet with sodium restric- osmolarity (< 10%), a vasopressin analog is admin- tion and a diuretic. If there is a partial sen-

Table 1. of psychogenic diabetes, central diabetes insipidus and nephrogenic diabetes insipidus based on the results of dehydration and vasopressin tests

Thirst neurosis Central diabetes insipidus Nephrogenic (neurohormonal) diabetes insipidus

Dehydration test (urine concentration test)

Urine specific gravity [g/ml] Gradually increases < 1,005 < 1,005

Urine osmolarity Gradually increases < 250 mOsm/kg < 250 mOsm/kg to meet the norm

Vasopressin concentration in the plasma Initially low, increases Low High

Vasopressin test (desmopressin 0.2 mg PO)

Urine specific gravity There is no indication Increases by ≥ 50% Low, does not increase for the test* (200–400%)

*due to satisfactory results of the dehydration test

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sitivity to vasopressin, large doses of hormone seem concentration decrease was reported and the volume appropriate [1]. Prognosis depends upon the cause touched the norm (4.9 Æ 1.1 mg/dl) without ionic of the disorder but is usually auspicious. Even un- disturbances. However, polyuria and excessive thirst treated diabetes insipidus does not pose any threat persisted (up to 5 l/d) and this provided the basis for to a patient’s life, providing the patient drinks plenty maintaining a Foley catheter in the urinary bladder. of fluids. In cases of unconscious patients (such Owing to obstinate astriction, manual removal of an as those with an injury or after brain area surgery) impacted stool was necessary but as soon as intensi- and patients with a thirst disorder, fluid balance fied pharmacological treatment was implemented, should be a particular focus. Substitution treatment bowel evacuation normalized. Badly-managed gly- allows patients to perform normal life activities with- caemy and intense hunger were causes of a dexa- out troublesome symptoms of the illness. methasone dose reduction (to 2–2–0 mg PO). The patient’s medical condition was stabilized. However, Case report sluggishness and malaise appeared and venlafaxine was administered with a morning dosage of 150 mg. On 2 November 2010, a 65-year-old woman pa- Additionally, the thyroid hormone level was tested tient with tumours of both kidneys (potentially and the results revealed the following: TSH 0.79 malignant) was admitted after an incident of gastro- μIU/ml (N: 0.27–4.20), FT3 1.1 pmol/l (N: 3.1–6.8), intestinal bleeding to the ward of the day hospice in FT4 0.7 pmol/l (N: 12–22). Secondary hypothyreo- Bydgoszcz with symptomatic treatment continuation sis was identified and L-thyroxine was administered and further care in mind. Moreover, the patient suf- with an initial dosage of 25 μg/day. Since pituitary fered depressive disorders, bipolar disorder, second- adenoma was diagnosed, the patient was assessed ary anaemia and diabetes mellitus Type 2 treated by an endocrinologist, who confirmed secondary hy- with insulin. Lesions in both kidneys had been de- pothyreosis and increased the L-thyroxine dosage to tected two years before and since then the patient 50 μg/day. The specialist found neither Cushing’s syn- had been closely monitored by urologists at the drome symptoms nor . To determine and Oncology Centre. She did not qualify for an opera- differentiate the causes of the intense thirst and tion. While she was monitored, the doctors observed polyuria, he decided to conduct a further investigation normal creatinine values. On 25 October 2010, when to calculate urine specific gravity. When this turned in the surgical unit of a City Hospital, she underwent out to be low (1,003 g/ml), 0.1 mg of desmopressin a CAT scan on her head, which demonstrated cerebral was implemented, which led to diuresis reduction (to oedema features, and extension to 1.75 l within one day) and the urine specific gravity 13 mm (suspicion of a pituitary gland tumour). increased. Such treatment facilitated catheter removal When the patient was admitted to the unit, her from the urinary bladder, which significantly improved condition was very serious. She was barely con- the quality of the patient’s everyday life. Moreover, scious and illogical. Additionally, she experienced se- we applied rehabilitation, during which the patient vere renal failure (creatinine 4.9 mg/dl) in the polyuria performed both active and passive activities and main- phase with diuresis of 3–5 l/day and erratic BMs. The tained a sitting position. We also attempted a change patient reported dyspnoea and pain in her abdominal from a lying to a standing position. She then tried to cavity. A clinical examination revealed low sensitivity walk with assecuration. The patient was discharged of the abdominal membranes and moderate rest in good condition. dyspnoea, without features of stasis over the lung fields. Owing to the malady and the medical condi- Discussion tion of the patient, we administered the following procedures: subcutaneous hydration in accordance One of the main problems in the aforementioned with fluid balance, diuresis forced by furosemide case was excessive urinating. Polyuria occurs if a pa- (40 mg/day IV), and 2.5 mg of hypodermically injected tient passes more than 2,500 ml of urine a day and morphine in the case of either acute pain or dyspnoea. it may be a symptom of numerous illnesses. In such Omeprazole (20 mg) continued to be administered a case, renal status must be checked, since diuresis may and the steroidotherapy (dexamethasone adminis- result either from uraemia or the polyuria phase of tered intravenously, 8 mg/day) intensified due to the acute renal failure. Moreover, hyperglycaemia should cerebral oedema displayed in the CAT scan images. also be excluded because leads to osmotic Soon, her medical condition improved and this facili- diuresis. Polyuria also accompanies hypercalcaemia tated conscious contact with the patient. A creatinine and psychogenic polydipsia. Finally, polyuria may

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result from central diabetes insipidus or nephrogenic concentration test and a thyroid hormones test. diabetes insipidus (discussed above) [3]. Since there were no manifestations of either ac- The patient experienced many ailments which romegaly or Cushing’s , it was decided to could have contributed to the polyuria, and what abandon tests which would calculate the concen- follows to polydipsia. Before the patient was admit- tration of growth hormone, ACTH and cortisol. ted to the hospice, she had gastrointestinal bleed- Moreover, the patient took dexamethasone, which ing which brought about acute renal failure. The impedes a proper interpretation of pituitary-adrenal descending course of such a dysfunction is polyuria. axis hormone concentration test results. The na- Furthermore, the steroid therapy, administered ow- ture of the tumour and the spread of the disease are ing to suspicion of brain metastasis, together with not confirmed (the good clinical status of the patient insulin-treated diabetes, led to poorly-managed and the lack of progression speak against spread); blood sugar which could also have been a cause of it may be an accidentally detected regular pituitary the polyuria and intense thirst. In addition, the CAT adenoma, which would require further diagnos- scan of her head demonstrated pituitary extension tics and perhaps even neurosurgical treatment. Full and implied a tumour which contributed to central evaluation of the hormonal function of the pituitary diabetes insipidus. The reported case does not allow gland and hypothalamic-pituitary area imaging by us to elaborate on features of the tumour. However, means of a scanning procedure may be considered, we are inclined to believe that there was metasta- providing the patient’s condition normalizes, and sis either from the site of disease progression (lack depends upon further progression of the underlying of histopathology examination results) or from the disease. At times, numerous symptoms and treat- hormonally inactive adenoma. Metastases to the ment are reflected in the life span of patients under pituitary gland are not frequent (less than 1% of palliative care. The kind of acute renal failure treat- patients with neurosurgical recommendations and ment the patient was given was neither expensive approximately 5% of autopsied patients diagnosed nor troublesome and once her clinical condition nor- with cancer) and usually manifest disseminated malized and a low-cost test had been recommended, cancer [4]. Tumours which most often give rise to her condition improved considerably. Since then, she metastases for the organ include breast cancer and has reached nearly full capacity after home rehabili- lung cancer [4, 5]. Metastases are usually located in tation, which has enabled her to function normally. the rear lobe of the pituitary gland or in both frontal After a few months, due to the severity of polyuria, and rear lobes (84.6% of 201 cases of metastases); a hospice doctor increased the dose of desmopressin however, frontal metastases comprise 15.4% of all which led to urine output reduction to 1.5 l a day. Full cases [6]. Such locations of metastases make us think diagnostics of the pituitary hormone are planned to that their symptoms cause diabetes insipidus [4, 6]. be conducted at the Endocrinology Outpatient Clinic A diabetes insipidus diagnosis should be pre- at the Oncology Centre in Bydgoszcz. ceded by a dehydration test. In the reported case, the patient was admitted to the hospice in a very bad References condition. She experienced dehydration symptoms, 1. Jarząb B. Choroby układu wewnątrzwydzielniczego. Choroby podwzgórza i przysadki. In: Szczeklik A. (ed.). renal failure and unlevelled diabetes and a dehydra- Choroby wewnętrzne. Medycyna praktyczna, Kraków tion test could have worsened her condition. A urine 2011; 1085–1118. specific gravity calculation seemed a much easier and 2. Jarząb B. Nowotwory gruczołów dokrewnych. In: Krzakowski M. (ed.). Onkologia kliniczna. Wydawnict- more available test. Since there was a diabetes in- wo Medyczne Borgis, Warszawa 2006; 1072–1111. sipidus suspicion, the test was administered. The 3. Kokot F. Choroby nerek i dróg moczowych. Badania virtually immediate and good reaction to vasopressin diagnostyczne. In: Szczeklik A. (ed.). Choroby wewnętrzne. analog treatment confirmed the initial diagnosis. Medycyna praktyczna, Kraków 2011: 1334–1352. 4. 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