© Borgis - Postępy Nauk Medycznych 12/2015, s. 869-873
Agnieszka Łebek-Szatańska, *Waldemar Misiorowski, Wojciech Zgliczyński
Jatrogenna niedoczynność przytarczyc – nie tylko strumektomia...
Iatrogenic hypoparathyroidism – not only after thyroid surgery...
Department of Endocrinology, Centre of Postgraduate Medical Education, Bielański Hospital, Warszawa
Head of Department: prof. Wojciech Zgliczyński, MD, PhD
Najczęstszą przyczynę niedoczynności przytarczyc stanowi leczenie operacyjne chorób tarczycy lub przytarczyc. Znacznie rzadziej niedoczynność przytarczyc jest wynikiem rozległych zabiegów chirurgicznych z przyczyn onkologicznych, np. z powodu raka krtani czy górnej części przełyku, lub radioterapii szyi, np. w przypadku chłoniaka. W tych szczególnych przypadkach onkologiczny charakter samej choroby skupia na sobie większość uwagi zarówno pacjentów, jak i lekarzy, co często prowadzi do zaniedbywania innych zagrożeń dla zdrowia, zaś potencjalnie złe rokowania i krótki czas przeżycia w tych przypadkach dodatkowo maskują problem. Jednak u poszczególnych pacjentów wyleczonych z raka, nierozpoznana niedoczynność przytarczyc może w dłuższej perspektywie wywierać istotny wpływ na zdrowie i jakość życia. Przedstawiamy dwa takie przypadki. Według naszej wiedzy, przedstawione przez nas przypadki są pierwszymi, rozpoznanymi po tak długim czasie po laryngektomii lub radioterapii. Może to oznaczać, że inni pacjenci poddani takiemu leczeniu mogą być podobnie narażeni na to rzadkie powikłanie, bez względu na okres czasu, który upłynął od terapii. Oznacza to konieczność systematycznego monitorowania kalcemii, jak również wykonywania rozszerzonej diagnostyki w przypadku najmniejszego podejrzenia klinicznego niedoczynności przytarczyc.
The most common causes of hypoparathyroidism are iatrogenic: mostly thyroid or parathyroid surgery. Much less frequently HypoPT is caused by an extensive oncological surgical procedure e.g. because of larynx or upper throat cancer, or external neck radiotherapy, e.g. in the case of lymphoma. In those particular cases, both patients and doctors focus their attention on the oncological nature of the disease itself, which often results in neglect of other health hazards, and potentially poor prognosis, and short survival time in those cases additionally mask the problem. However, in individual patients cured from cancer, unrecognized hypoparathyroidism can significantly affect their health and quality of life. Two such cases are presented. To our knowledge, the cases presented by us are the first cases diagnosed after such a long time after laryngectomy or radiation therapy. This may indicate that other patients undergoing such treatment could be exposed to this rare complication as well, regardless of the time that elapsed after the treatment. This implies the need for systematic monitoring of serum calcium, as well as for enhanced diagnosis in the case of even the slightest clinical suspicion of hypoparathyroidism.
Hypoparathyroidism (HypoPT) is a disease of the endocrine system characterized by low serum calcium and inadequately low PTH level. It is a rare disease, entered on the list of orphan diseases by the European Commission in January 2014 (UE/3/13/1210; http://www.ema.europa.eu/ema/index.jsp?curlZpages/medicines/human/orphans/2014/01/human_orphan_001301.jsp&midZWC0b01ac058001d12b) and the only classical hormonal insufficiency, which is not treated by supplementing the missing hormone (PTH) (1-4). Spontaneous HypoPT may be a disease with autoimmune pathogenesis where the cause is a mutation of the autoimmune regulatory gene (AIRE) (5). In addition, there are many other rare genetic diseases that can cause HypoPT: either as part of a larger complex of diseases (e.g., DiGeorge syndrome), or as a single endocrinopathies (6). However, the most common causes of chronic HypoPT are of iatrogenic origin: surgical treatment of thyroid and parathyroid diseases (7, 8).
Much less frequently HypoPT is caused by an extensive oncological surgical procedure e.g. because of larynx or upper throat cancer, or external neck radiotherapy, e.g. in the case of lymphoma. In those particular cases, both patients and doctors focus their attention on the oncological nature of the disease itself, which often results in neglect of other health hazards, and potentially poor prognosis, and short survival time in those cases additionally mask the problem. However, in individual patients cured from cancer, unrecognized hypoparathyroidism can significantly affect their health and quality of life (9). Two such cases are presented.
A 84-year-old male patient with a tracheotomy after surgical treatment of laryngeal cancer 30 years earlier, was admitted to the internal medicine ward diagnosed with pneumonia. Due to the very long period of time that has elapsed since the surgery, detailed information on the carried out procedure could not be obtained. The patient denied to have the history of radiotherapy. The immediate cause of hospitalization was a loss of consciousness for a few minutes while waiting for the medical appointment with the primary care physician. According to the statement of the patient, similar episodes have occurred many times in the past few years, but he did not report this problem to the doctor. The faints occurred mainly in stressful situations, and they were not connected with the changes in body position, without cardiovascular complaints, convulsions, involuntary urination, with no obvious prodromal symptoms. After combating the infection, the doctors started to diagnose the faints. Laboratory tests have shown the profound hypocalcemia: Ca = 1.31 mmol/l, ionized Ca = 0.73 mmol/l, and hypocalciuria Cau = 1.11 mmol/24 h; hyperphosphatemia p = 1.49 mmol/l, and an extremely low concentration of parathyroid hormone intact in the serum (iPTH) = 9.34 pg/ml. Diagnosis: secondary hypoparathyroidism following the laryngectomy. There were no classic signs of tetanic symptoms (Trousseau, Chvostek signs), however there were other clinical features of long hypocalcemia: prolongation of QT interval (QTc = 475 ms) in the electrocardiogram (ECG) and supraventricular and ventricular arrhythmias in 24-hour Holter ECG. A CT scan revealed the presence of massive calcification in the brain and cerebellum (as in Fahr’s disease) (fig. 1), but without clinical neurological disorders or pathologies in the electroencephalographic recordings. The examination showed cataract affecting both eyes. An attempt was made to perform a psychological evaluation, but due to significant difficulties in communication with the patient (hearing loss, speech disorders), as well as the advanced age, it was difficult to objectively assess his cognitive abilities. Treatment consisted in administration of calcium carbonate – 1000 mg three times a day, and alfacalcidol – 1 microgram per day. After two months of treatment a satisfactory improvement in the patient’s condition was achieved, fainting did not reappear, and the patient observed a significantly better efficiency of movement and improvement of mood. Laboratory studies confirmed improvement of serum calcium level (2.13 mmol/l) and normalization of phosphate level (1.11 mmol/l). ECG showed normalization of QT interval (QTc = 435 ms).
Fig. 1. Massive calcification of the brain with hypoparathyroidism.
A 54-year-old male, at the age of 26 treated for non-Hodgkin’s lymphoma with external irradiation of the neck and mediastinum, was repeatedly hospitalized in the last few years due to attacks of breathlessness with wheezing, resembling asthma. Because the provocation tests showed no evident bronchial hyperresponsiveness, the symptoms were classified as psychosomatic ones, especially that the patient connected the occurrence thereof with emotional stress or physical activity. At the same time, the psychological study revealed personality disorders of depressive and hypochondriacal type – with a serious anxiety and significant social dysfunction, especially in the execution phase. Only the accidental serum calcium level test showed severe hypocalcemia Ca = 1.29 mmol/l. The patient was referred to an endocrinologist. The results of the laboratory tests confirmed the diagnosis – it was radiation-induced hypoparathyroidism: Ca = 1.31 mmol/l; Cau = 0.93 mmol/24 h; iP = 1.61 mmol/l; iPTH = 8.1 pg/ml. The patient was also diagnosed with the concomitant hypothyroidism: TSH = 28.6 uIU/ml; FT4 = 8.75 pmol/l. The presence of calcification in the structures of the brain, particularly in the basal ganglia was also demonstrated in this patient. Application of usual therapy (alfacalcidol 1.25 ug/d + CaCO3 6 x 1000 mg + L-thyroxine 100 ug/d) restored normal biochemical balance, and the patient’s condition significantly improved, symptoms of bronchial smooth muscle contraction did not happen again. Also the patient’s mental state and ability to function in society was improved.
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